USMLE Step 2 CK Eighth Edition TAO LE, MD, MHS Associate Clinical Professor of Medicine and Pediatrics Chief, Section of Allergy and Immunology Department of Medicine University of Louisville VIKAS BHUSHAN, MD Diagnostic Radiologist NATHAN WILLIAM SKELLEY, MD Resident, Department of Orthopaedic Surgery Washington University in St. Louis School of Medicine Barnes-Jewish Hospital St. Louis, Missouri New York Chicago San Francisco Lisbon London Madrid Mexico City Milan New Delhi San Juan Seoul Singapore Sydney Toronto Copyright © 2012, 2010, 2007 by Tao Le. All rights reserved. Except as permitted under the United States Copyright Act of 1976, no part of this publication may be reproduced or distributed in any form or by any means, or stored in a database or retrieval system, without the prior written permission of the publisher. ISBN: 978-0-07-176749-1 MHID: 0-07-176749-5 The material in this eBook also appears in the print version of this title: ISBN: 978-0-07-176137-6, MHID: 0-07-176137-3. All trademarks are trademarks of their respective owners. Rather than put a trademark symbol after every occurrence of a trademarked name, we use names in an editorial fashion only, and to the benefit of the trademark owner, with no intention of infringement of the trademark. Where such designations appear in this book, they have been printed with initial caps. McGraw-Hill eBooks are available at special quantity discounts to use as premiums and sales promotions, or for use in corporate training programs. To contact a representative please e-mail us at bulksales@mcgraw-hill.com. NOTICE Medicine is an ever-changing science. As new research and clinical experience broaden our knowledge, changes in treatment and drug therapy are required. The authors and the publisher of this work have checked with sources believed to be reliable in their efforts to provide information that is complete and generally in accord with the standards accepted at the time of publication. However, in view of the possibility of human error or changes in medical sciences, neither the authors nor the publisher nor any other party who has been involved in the preparation or publication of this work warrants that the information contained herein is in every respect accurate or complete, and they disclaim all responsibility for any errors or omissions or for the results obtained from use of the information contained in this work. Readers are encouraged to confirm the information contained herein with other sources. For example and in particular, readers are advised to check the product information sheet included in the package of each drug they plan to administer to be certain that the information contained in this work is accurate and that changes have not been made in the recommended dose or in the contraindications for administration. This recommendation is of particular importance in connection with new or infrequently used drugs. TERMS OF USE This is a copyrighted work and The McGraw-Hill Companies, Inc. (“McGrawHill”) and its licensors reserve all rights in and to the work. Use of this work is subject to these terms. Except as permitted under the Copyright Act of 1976 and the right to store and retrieve one copy of the work, you may not decompile, disassemble, reverse engineer, reproduce, modify, create derivative works based upon, transmit, distribute, disseminate, sell, publish or sublicense the work or any part of it without McGraw-Hill’s prior consent. You may use the work for your own noncommercial and personal use; any other use of the work is strictly prohibited. Your right to use the work may be terminated if you fail to comply with these terms. THE WORK IS PROVIDED “AS IS.” McGRAW-HILL AND ITS LICENSORS MAKE NO GUARANTEES OR WARRANTIES AS TO THE ACCURACY, ADEQUACY OR COMPLETENESS OF OR RESULTS TO BE OBTAINED FROM USING THE WORK, INCLUDING ANY INFORMATION THAT CAN BE ACCESSED THROUGH THE WORK VIA HYPERLINK OR OTHERWISE, AND EXPRESSLY DISCLAIM ANY WARRANTY, EXPRESS OR IMPLIED, INCLUDING BUT NOT LIMITED TO IMPLIED WARRANTIES OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE. McGraw-Hill and its licensors do not warrant or guarantee that the functions contained in the work will meet your requirements or that its operation will be uninterrupted or error free. Neither McGraw-Hill nor its licensors shall be liable to you or anyone else for any inaccuracy, error or omission, regardless of cause, in the work or for any damages resulting therefrom. McGraw-Hill has no responsibility for the content of any information accessed through the work. Under no circumstances shall McGraw-Hill and/ or its licensors be liable for any indirect, incidental, special, punitive, consequential or similar damages that result from the use of or inability to use the work, even if any of them has been advised of the possibility of such damages. This limitation of liability shall apply to any claim or cause whatsoever whether such claim or cause arises in contract, tort or otherwise. -/ *ÊÓÊ Ê+
8 ,i>ˆÃ̈VÊ1- ÊȓՏ>̈œ˜ LÞÊÌ iÊ,-/Ê
 Ê>ÕÌ œÀà ÊÊÊÊÊ Ê ▲ ÓÈää³Ê ˆ} ‡Þˆi`Ê-Ìi«ÊÓÊ ʵÕiÃ̈œ˜Ã ÜˆÌ Ê`iÌ>ˆi`ÊiÝ«>˜>̈œ˜Ã ▲ Ài>ÌiÊ ˆ} ÞÊVÕÃ̜“ˆâi`ÊÌiÃÌà ▲ -iiVÌʵÕiÃ̈œ˜ÃÊLÞÊ`ˆvvˆVՏÌÞʏiÛi ▲ -ˆ“Տ>ÌiÊ>Ê >v‡`>ÞʜÀÊvՏ‡`>ÞÊiÝ>“ ▲ *>ÃÃÊ}Õ>À>˜Ìiiʇʫ>ÃÃʜÀÊÜiÊ܈ `œÕLiÊޜÕÀÊÃÕLÃVÀˆ«Ìˆœ˜ -iiÊ7iLÊÈÌiÊvœÀÊ/iÀ“ÃÊ>˜`Ê œ˜`ˆÌˆœ˜Ã ÜÜÜ°ÕӏiÀÝ°Vœ“ DEDICATION To our families, friends, and loved ones, who supported and assisted in the task of assembling this guide. and To the contributors to this and future editions, who took time to share their knowledge, insight, and humor for the benefit of students. This page intentionally left blank v Contents Contributing Authors . . . . . . . . . . . . . . . . . . . . . . . . . . vii Image Editor. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vii Web Contributor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vii Faculty Reviewers . . . . . . . . . . . . . . . . . . . . . . . . . . . . vii Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .ix Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . .xi How to Contribute . . . . . . . . . . . . . . . . . . . . . . . . . . . . xiii How to Use This Book. . . . . . . . . . . . . . . . . . . . . . . . . xv SECTION 1: GUIDE TO EFFICIENT EXAM PREPARATION. . . . . . . . . . . . . . . . . . 1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2 USMLE Step 2 CK—Computer-Based Testing Basics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2 Defining Your Goal . . . . . . . . . . . . . . . . . . . . . . . . . . . .7 Study Resources . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 Test-Day Checklist . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 Testing Agencies . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 SECTION 2: DATABASE OF HIGH-YIELD FACTS. . . . . . . . . . . . . . . . . . . . . . . . 15 How to Use the Database. . . . . . . . . . . . . . . . . . . . . 16 Cardiovascular . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 Dermatology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49 Endocrinology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77 Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99 Ethics and Legal Issues . . . . . . . . . . . . . . . . . . . . . . 113 Gastrointestinal . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119 Hematology/Oncology . . . . . . . . . . . . . . . . . . . . . . 151 Infectious Disease . . . . . . . . . . . . . . . . . . . . . . . . . . Musculoskeletal . . . . . . . . . . . . . . . . . . . . . . . . . . . . Neurology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Obstetrics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Gynecology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Pediatrics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Psychiatry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Pulmonary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Renal/Genitourinary . . . . . . . . . . . . . . . . . . . . . . . . Selected Topics in Emergency Medicine . . . . . . . . Rapid Review . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 179 217 241 281 317 353 393 419 439 465 487 SECTION 3: TOP-RATED REVIEW RESOURCES. . . . . . . . . . . . . . . . . . 513 How to Use the Database. . . . . . . . . . . . . . . . . . . . Comprehensive . . . . . . . . . . . . . . . . . . . . . . . . . . . . Question Banks . . . . . . . . . . . . . . . . . . . . . . . . . . . . Internal Medicine . . . . . . . . . . . . . . . . . . . . . . . . . . . Neurology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . OB/GYN . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Pediatrics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Psychiatry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Commercial Review Courses . . . . . . . . . . . . . . . . . 514 516 520 522 527 529 532 535 538 541 Appendix I: Abbreviations and Symbols . . . . . . . . . Appendix II: Common Laboratory Values. . . . . . . . Index. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . About the Authors . . . . . . . . . . . . . . . . . . . . . . . . . . 543 549 551 575 This page intentionally left blank vii CONTRIBUTING AUTHORS Peter DeBartolo, MD Resident, Department of Emergency Medicine Maricopa Medical Center Jessica Schiffman, MD/MPH candidate Harvard School of Public Health Class of 2011 Johns Hopkins University Class of 2012 Whitney Green, MD Resident, Department of Pathology The Johns Hopkins Hospital Jason Solus, MD Resident, Department of Pathology Massachusetts General Hospital Mark Jensen University of Rochester School of Medicine Class of 2012 Sophia Strike, MD Resident, Department of Orthopaedic Surgery The Johns Hopkins Hospital Anisha Khaitan, MD Resident, Department of Pediatrics The Children’s Hospital of Philadelphia Allison Leigh Tsao, MD Resident, Department of Medicine The Johns Hopkins Hospital Richard Pollock, MD Resident, Department of Anesthesiology The Johns Hopkins Hospital IMAGE EDITOR S. Jarrett Wrenn, MD, PhD Resident, Department of Radiology and Biomedical Imaging University of California, San Francisco WEB CONTRIBUTOR Lauren Rothkopf, MD Resident, Department of Internal Medicine Beth Israel Deaconess Medical Center FACULTY REVIEWERS Kia Afshar, MD Fellow, Division of Cardiology Cleveland Clinic Foundation Tina Latimer, MD, MPH Assistant Program Director, Emergency Medicine Residency Johns Hopkins University School of Medicine Eric Darius Balighian, MD Instructor, Department of Pediatrics Saint Agnes and Johns Hopkins Hospital Susan W. Lehmann, MD Faculty, Department of Psychiatry and Behavioral Sciences Johns Hopkins University School of Medicine David Cosgrove, MD Assistant Professor, Department of Medical Oncology Johns Hopkins University School of Medicine Abigail Dennis, MD Assistant Professor, Obstetrics/Gynecology Johns Hopkins Bayview Medical Center Sameer Dhalla, MD Postdoctoral Fellow, Division of Gastroenterology and Hepatology Johns Hopkins University School of Medicine Mark Hughes, MD, MA Assistant Professor, Division of General Internal Medicine Johns Hopkins University School of Medicine Core Faculty, Berman Institute of Bioethics Nancy Hueppchen, MD Assistant Professor, Department of Gynecology/Obstetrics Johns Hopkins University School of Medicine Adrianna Jackson, MD Resident, Department of Dermatology Johns Hopkins University School of Medicine Michael Levy, MD, PhD Assistant Professor, Department of Neurology Johns Hopkins University School of Medicine Murray A. Mittleman, MD, DrPH Director, Cardiovascular Epidemiology Research Unit Beth Israel Deaconess Medical Center Kendall Moseley, MD Instructor, Division of Endocrinology and Metabolism The Johns Hopkins Hospital Adam Spivak, MD Instructor, Department of Medicine Johns Hopkins University School of Medicine R. Scott Stephens, MD Faculty, Division of Pulmonary and Critical Care Medicine Johns Hopkins University School of Medicine Miho J. Tanaka, MD Orthopaedic Fellow, Sports Medicine and Shoulder Service Hospital for Special Surgery Sumeska Thavarajah, MD Assistant Professor, Division of Nephrology Johns Hopkins Bayview Medical Center This page intentionally left blank ix Preface With the eighth edition of First Aid for the USMLE Step 2 CK, we continue our commitment to providing students with the most useful and up-to-date preparation guide for the USMLE Step 2 CK. The eighth edition represents a thorough revision in many ways and includes: n n n n n n n n An all-new color design for better learning. New, innovative flash cards embedded in the margins to reinforce key concepts. Hundreds of new color images and illustrations throughout the text. A revised and updated exam preparation guide for the USMLE Step 2 CK that includes updated study and testtaking strategies for the FRED v2 computer-based testing (CBT) format. Revisions and new material based on student experience with recent administrations of the USMLE Step 2 CK. Concise summaries of more than 1000 heavily tested clinical topics written for fast, high-yield studying. An updated “rapid review” that tests your knowledge of each topic for last-minute cramming. A completely revised, in-depth guide to clinical science review and sample examination books. The eighth edition would not have been possible without the help of the many students and faculty members who contributed their feedback and suggestions. We invite students and faculty to continue sharing their thoughts and ideas to help us improve First Aid for the USMLE Step 2 CK. (See How to Contribute, p. xiii.) Tao Le Louisville Vikas Bhushan Los Angeles Nathan Skelley St. Louis This page intentionally left blank xi Acknowledgments This has been a collaborative project from the start. We gratefully acknowledge the thoughtful comments, corrections, and advice of the many medical students, international medical graduates, and faculty who have supported the authors in the continuing development of First Aid for the USMLE Step 2 CK. For support and encouragement throughout the process, we are grateful to Thao Pham, Selina Franklin, and Louise Petersen. Thanks also to those who supported the authors through the revision process. Thanks to our publisher, McGraw-Hill, for the valuable assistance of their staff. For enthusiasm, support, and commitment to this challenging project, thanks to our editor, Catherine Johnson. For outstanding editorial work, we thank Andrea Fellows. A special thanks to Rainbow Graphics, especially David Hommel, Tina Castle, and Susan Cooper, for remarkable editorial and production work, and to Ravish Amin for creating the web survey. Thanks to Elizabeth Sanders and Ashley Pound for the interior design. For contributions and corrections, we thank Brad Barlow, Pravir Baxi, Carolyn Botros, Sarah Chamberlain, Marla Davis, Jennifer Dias, Christina Dornshuld, Scott Drutman, David Durand, Parastu Emrani, Michael Galabi, Christian Ghattas, Juan Gonzalez, Will Grover, Felipe T. Guillen, Arum Kim, Daniel Kim, Gabriel Kleinman, Nicholas Kotch, Tim LaBonte, David Levy, Christina Li, Michael Lin, Jon Lindquist, Brian J. Manfredi, Edgar Manzanera, David Margolius, Geronimo Mendoza, Karl Migally, Esmy Mohm, Dania Molla-Hosseini, Tareq Nassar, Meg Park, Jennifer Parker, Erin Perko, Kendall Riley, Nelson Royall, Eshan Sapra, Layli Sanaee, Heather Scoffone, Stephen Seedial, Malik Shahid, Joshua Sloan, Versha Srivastasa, Matthew Stewart, Sharon Tsay, Shannon Toohey, Kenneth Visalli, Amanda Weinmann, Melisa Wong, Suzanna Yadgarov, and Dustin Yoon. Thanks to Steve Albrechta, Maureen Ayers Looby, Erika Bernardo, Rachel Burkard, Lindsey Chmielewski, Hector Colon, Erin Conboy, Christine DeSanno, Conor Dolehide, Christina Dornshuld, Travis Dunn, Dan Falvey, William A. Fields, Kristin Gehrking, Marlow Griggs, Michelle Harper, Kristin Huntoon, Benjamin Johnson, Emily Johnson, Gina Johnson, Nicholas Jubert, Dejah Judelson, Landon Karren, Harris Khan, Alexander Kim, Sarah Liebe, Christina Lohbeck, Patrick Looser, Brandon Mauldin, Mitch McKenzie, Michelle Miller, Charles Newlin, Jordan Lee Nordquist, Sara Olmanson, Jonathan James Olson, Andrea Paulson, Monica Pena, Susan Pleasants, Vanessa Raabe, Petra Rahaman, Justin Schulte, Erin Seidel, Michael Silverstein, Rebecca Stepan, Gary Tsai, Lydia I. Turnbull, and Liz Wasson for submitting book reviews. Tao Le Louisville Vikas Bhushan Los Angeles Nathan Skelley St. Louis This page intentionally left blank xiii How to Contribute In our effort to continue to produce a high-yield review source for the Step 2 CK exam, we invite you to submit any suggestions or corrections. We also offer paid internships in medical education and publishing ranging from three months to one year (see below for details). Please send us your suggestions for n n n Study and test-taking strategies for the Step 2 CK exam New facts, mnemonics, diagrams, and illustrations Low-yield topics to remove For each entry incorporated into the next edition, you will receive a $10 gift certificate as well as personal acknowledgment in the next edition. Diagrams, tables, partial entries, updates, corrections, and study hints are also appreciated, and significant contributions will be compensated at the discretion of the authors. Also let us know about material in this edition that you feel is low yield and should be deleted. The preferred way to submit entries, suggestions, or corrections is via our blog: www.firstaidteam.com We are also reachable by e-mail at firstaidteam@yahoo.com. NOTE TO CONTRIBUTORS All entries become property of the authors and are subject to editing and reviewing. Please verify all data and spellings carefully. In the event that similar or duplicate entries are received, only the first entry received will be used. Include a reference to a standard textbook to facilitate verification of the fact. Please follow the style, punctuation, and format of this edition if possible. INTERNSHIP OPPORTUNITIES The author team is pleased to offer part-time and full-time paid internships in medical education and publishing to motivated physicians. Internships may range from three months (eg, a summer) up to a full year. Participants will have an opportunity to author, edit, and earn academic credit on a wide variety of projects, including the popular First Aid series. Writing/editing experience, familiarity with Microsoft Word, and Internet access are desired. For more information, e-mail a résumé or a short description of your experience along with a cover letter to firstaidteam@yahoo.com. This page intentionally left blank xv How to Use This Book We have made many improvements and added several new features to this edition of First Aid for the USMLE Step 2 CK. In particular, we have added more tables, charts, and images throughout the text to facilitate studying. We encourage you to read all aspects of the text to learn the material in context; however, when you get closer to test day, focus on the high-yield bolded text and comments in the margins of each page. These features have many of the “buzzwords” you should be looking for on exam day. Finally, we have included new vignette questions to periodically test your knowledge of key concepts. These questions are located in the lower or upper right corner of certain pages. To prevent peeking at the answers, you’ll find the answer on the back of the same page in the lower or upper left corner. These questions are not always representative of test questions. To simulate the actual test day and to properly judge your true understanding of the material, you can use the USMLERx Step 2 CK Qmax question test bank (www.usmlerx.com), which was developed by the First Aid author team. The test bank and this text are more than enough to allow many students to ace the exam. However, if you are constantly on the move while preparing for this exam or need some extra practice, use the USMLERx Step 2 CK mobile application for mobile devices. To broaden your learning strategy, you can integrate your First Aid study with First Aid Cases for the USMLE Step 2 CK and First Aid Q&A for the USMLE Step 2 CK. Please note that First Aid Q&A draws a portion of its questions from USMLERx. First Aid Cases and First Aid Q&A are organized to match First Aid for the USMLE Step 2 CK chapter for chapter. After reviewing a chapter within First Aid, you can review cases on the same topics and then test your knowledge in the corresponding chapters of First Aid Cases and First Aid Q&A. First Aid Q&A is also available as an iPhone app. Additional materials may also be found in the Review Resources section of this book. Good luck! This page intentionally left blank SECTION 1 GUIDE TO EFFICIENT EXAM PREPARATION Introduction 2 USMLE Step 2 CK—Computer-Based Testing Basics 2 HOW WILL THE CBT BE STRUCTURED? 2 Defining Your Goal WHEN TO TAKE THE EXAM Study Resources 7 10 11 TESTING CONDITIONS: WHAT WILL THE CBT BE LIKE? 3 QUALITY CONSIDERATIONS 11 WHAT DOES THE CBT FORMAT MEAN FOR ME? 3 CLINICAL REVIEW BOOKS 11 HOW DO I REGISTER TO TAKE THE EXAMINATION? 4 TEST BANKS 11 WHAT IF I NEED TO RESCHEDULE THE EXAMINATION? 5 TEXTS AND NOTES 12 WHAT ABOUT TIME? 5 COMMERCIAL COURSES 12 NEW SECURITY MEASURES 5 NBME/USMLE PUBLICATIONS 12 IF I LEAVE DURING THE EXAMINATION, WHAT HAPPENS TO MY SCORE? 6 WHAT TYPES OF QUESTIONS ARE ASKED? 6 HOW LONG WILL I HAVE TO WAIT BEFORE I GET MY SCORES? 7 HOW ARE THE SCORES REPORTED? 7 Test-Day Checklist THINGS TO BRING WITH YOU TO THE EXAM Testing Agencies 13 13 13 1 2 SECTION 1 GUIDE TO EFFICIENT EXAM PREPARATION Introduction The United States Medical Licensing Examination (USMLE) Step 2 allows you to pull together your clinical experience on the wards with the numerous “factoids” and classical disease presentations that you have memorized over the years. Whereas Step 1 stresses basic disease mechanisms and principles, Step 2 places more emphasis on clinical diagnosis and management, disease pathogenesis, and preventive medicine. The Step 2 examination is now composed of two parts: n n The Step 2 Clinical Knowledge examination (Step 2 CK) The Step 2 Clinical Skills examination (Step 2 CS) The USMLE Step 2 CK is the second of three examinations that you must pass in order to become a licensed physician in the United States. The computerized Step 2 CK is a 1-day (9-hour) multiple-choice examination. KEY FACT The goal of the Step 2 CK is to apply your knowledge of medical facts to clinical scenarios you may encounter as a resident. Students are also required to take the Step 2 CS, which is a 1-day live examination in which students examine 12 standardized patients. For more information on this examination, please refer to First Aid for the USMLE Step 2 CS. Information about the Step 2 CS format and about eligibility, registration, and scoring can be found at www.nbme.org. The information found in this section as well as in the remainder of the book will address only the Step 2 CK. USMLE Step 2 CK—Computer-Based Testing Basics HOW WI LL T H E C BT BE S TR U C TU R E D? The Step 2 CK is a computer-based test (CBT) administered by Prometric, Inc. It is a 1-day examination with approximately 352 questions divided into eight 60-minute blocks of 44 questions each, administered in a single 9-hour testing session. The Step 2 CK uses the same FRED v2 software program as that used on the USMLE Step 1 examination. There are three question styles that predominate throughout the examination. The most common format is Single One Best Answer questions. This is the traditional multiple-choice format in which you are tasked with selecting the “most correct” answer. Another common style is Matching Sets. These questions consist of a series of questions related to a similar topic or prompt. Finally, “Sequential Item Sets” have been introduced to the examination. These are sets of multiple-choice questions that are related and must all be answered in order without skipping a question in the set along the way. As you answer questions in a given set, the previous answers become locked and cannot be changed. These are the only questions on the USMLE examination that are locked in such a way. There will be no more than five Sequential Item Sets within each USMLE Step 2 CK examination. During the time allotted for each block on the USMLE Step 2 CK, the examinee can answer test questions in any order as well as review responses and change answers (with the exception of responses within the Sequential Item Sets described above). However, under no circumstances can examinees go back and change answers from previous blocks. Once an examinee finishes a GUIDE TO EFFICIENT EXAM PREPARATION block, he or she must click on a screen icon in order to continue to the next block. Time not used during a testing block will be added to the examinee’s overall break time, but it cannot be used to complete other testing blocks. T ES T I N G C O N D I T I O NS: W H A T WI LL TH E C B T BE LI K E ? 3 SECTION 1 KEY FACT Expect to spend up to 9 hours at the test center. Even if you’re familiar with computer-based testing and the Prometric test centers, FRED v2 is a new testing format that you should access from the USMLE CD-ROM or Web site (www.usmle.org) and try out prior to the examination. If you familiarize yourself with the FRED v2 testing interface ahead of time, you can skip the 15-minute tutorial offered on examination day and add those minutes to your allotted break time of 45 minutes. For security reasons, examinees are not allowed to bring personal electronic equipment into the testing area—which means that watches (even analog), cellular telephones, and electronic paging devices are all prohibited. Food and beverages are prohibited as well. The proctor will assign you a small locker in which you can store your belongings and any food you bring for the day. Examinees will also be given two (8″ × 11″) laminated writing surfaces, pens, and erasers for note taking and for recording their test Candidate Identification Number (CIN). These materials must be returned after the examination. Testing centers are monitored by audio and video surveillance equipment. You should become familiar with a typical question screen. A window to the left displays all the questions in the block and shows you the unanswered questions (marked with an “i”). Some questions will contain figures, color illustrations, audio, or video adjacent to the question. Although the contrast and brightness of the screen can be adjusted, there are no other ways to manipulate the picture (eg, zooming or panning). Larger images are accessed with an “exhibit” button. The examinee can also call up a window displaying normal lab values. You may mark questions to review at a later time by clicking the check mark at the top of the screen. The annotation feature functions like the provided dry erase sheets and allows you to jot down notes during the examination. Play with the highlighting/strike-out and annotation features with the vignettes and multiple answers. You should also do a few practice blocks to determine which tools actually help you process questions more efficiently and accurately. If you find that you are not using the marking, annotation, or highlighting tools, then keyboard shortcuts can save you time over using a mouse. Headphones are provided for listening to audio and blocking outside noise. Alternatively, examinees can bring soft earplugs to block excess noise. These earplugs must be examined by Prometric staff before you are allowed to take them into the testing area. W H A T D O ES T H E C BT F O R M A T ME AN F OR M E ? The CBT format is the same format as that used on the USMLE Step 1. If you are uncomfortable with this testing format, spend some time playing with a Windows-based system and pointing and clicking icons or buttons with a mouse. The USMLE also offers students an opportunity to take a simulated test, or practice session, at a Prometric center. The session is divided into three 1-hour blocks of 50 test items each. The 143 Step 2 CK sample test items that KEY FACT Keyboard shortcuts: n A–E—Letter choices. n Enter or Spacebar—Move to the next question. n Esc—Exit pop-up Lab and Exhibit windows. n Alt-T—Countdown and time-elapsed clocks for current session and overall test. 4 SECTION 1 GUIDE TO EFFICIENT EXAM PREPARATION are available on the CD-ROM or on the USMLE Web site (www.usmle.org) are the same as those used at CBT practice sessions. No new items are presented. The cost is about $52 for U.S. and Canadian students but is higher for international students. Students receive a printed percent-correct score after completing the session. No explanations of questions are provided. You may register for a practice session online at www.usmle.org. The National Board of Medical Examiners (NBME) provides another option for students to assess their Step 2 CK knowledge with the Comprehensive Clinical Science Self-Assessment (CCSSA) test. This test is available on the NBME Web site in several versions for $50 (or $60 for expanded feedback). The content of the CCSSA items resembles that of the USMLE Step 2 CK. Upon completion of the CCSSA, users will be provided with a performance profile indicating their strengths and weaknesses. This feedback is intended for use as a study tool only and is not necessarily an indicator of Step 2 CK performance. For more information on the CCSSA examination, visit the NBME’s Web site at www.nbme.org and click on the link for “NBME Webbased Self-Assessment Service.” HOW DO I RE G I STE R TO TAK E T HE EX AM I NATI ON? Information on Step 2 CK format, content, and registration requirements can be found on the USMLE Web site. To register for the examination in the United States and Canada, apply online at the NBME Web site (www.nbme. org). A printable version of the application is also available on this site. The preliminary registration process for the USMLE Step 2 CK is as follows: n n n n n n n n n Complete a registration form and send your examination fees to the NBME (online). Select a 3-month block in which you wish to be tested (eg, June/July/ August). Attach a passport-type photo to your completed application form. Complete a Certification of Identification and Authorization Form. This form must be signed by an official at your medical school (eg, the registrar’s office) to verify your identity. It is valid for 5 years, allowing you to use only your USMLE identification number for future transactions. Send your certified application form to the NMBE for processing. (Applications may be submitted more than 6 months before the test date, but examinees will not receive their scheduling permits until 6 months prior to the eligibility period.) The NBME will process your application within 4–6 weeks and will send you a slip of paper that will serve as your scheduling permit. Once you have received your scheduling permit, decide when and where you would like to take the examination. For a list of Prometric locations nearest you, visit www.prometric.com. Call Prometric’s toll-free number or visit www.prometric.com to arrange a time to take the examination. The Step 2 CK is offered on a year-round basis except for the first 2 weeks in January. For the most up-to-date information on available testing days at your preferred testing location, refer to www.usmle.org. The scheduling permit you receive from the NBME will contain the following important information: n n Your USMLE identification number. The eligibility period in which you may take the examination. GUIDE TO EFFICIENT EXAM PREPARATION n n Your “scheduling number,” which you will need to make your examination appointment with Prometric. Your CIN, which you must enter at your Prometric workstation in order to access the examination. Prometric has no access to the codes and will not be able to supply these numbers, so do not lose your permit! You will not be allowed to take the Step 2 CK unless you present your permit along with an unexpired, government-issued photo identification that contains your signature (eg, driver’s license, passport). Make sure the name on your photo ID exactly matches the name that appears on your scheduling permit. W H A T I F I N E E D T O R E S CHE D U L E THE E X AM I NATI ON? You can change your date and/or center within your 3-month period without charge by contacting Prometric. If space is available, you may reschedule up to 5 days before your test date. If you need to reschedule outside your initial 3-month period, you can apply for a single 3-month extension (eg, April/May/ June can be extended through July/August/September) after your eligibility period has begun (visit www.nbme.org for more information). This extension currently costs $65. For other rescheduling needs, you must submit a new application along with another application fee. WHAT ABOUT TIME? Time is of special interest on the CBT examination. Here is a breakdown of the examination schedule: Tutorial 60-minute question blocks (44 questions per block) Break time (includes time for lunch) Total test time 15 minutes 8 hours 45 minutes 9 hours The computer will keep track of how much time has elapsed during the examination. However, the computer will show you only how much time you have remaining in a given block. Therefore, it is up to you to determine if you are pacing yourself properly. The computer will not warn you if you are spending more than the 45 minutes allotted for break time. The break time includes not only the usual concept of a break—when you leave the testing area—but also the time it takes for you to make the transition to the next block, such as entering your CIN or even taking a quick stretch. If you do exceed the 45-minute break time, the time to complete the last block of the test will be reduced. However, you can elect not to use all of your break time, or you can gain extra break time either by skipping the tutorial or by finishing a block ahead of the allotted time. N E W S EC U R I T Y M E A SU R ES Smile! In early 2009, the NBME initiated a new check-in/check-out process that includes electronic capture of your fingerprints and photograph. These 5 SECTION 1 KEY FACT Because the Step 2 CK examination is scheduled on a “first-come, firstserved” basis, you should be sure to call Prometric as soon as you receive your scheduling permit. 6 SECTION 1 GUIDE TO EFFICIENT EXAM PREPARATION measures are intended to increase security by preventing fraud, thereby safeguarding the integrity of the examination. The new procedures also decrease the amount of time needed to check in and out of the examination throughout the day, thereby maximizing your break time. However, you still need to sign out and sign in with the Test Center Log when exiting and entering the testing area. I F I LE AVE DU R I NG THE E X AM I NATI ON, W HAT HAP P E N S T O M Y SCO RE? You are considered to have started the examination once you have entered your CIN onto the computer screen. In order to receive an official score, however, you must finish the entire examination. This means that you must start and either finish or run out of time for each block of the examination. If you do not complete all the question blocks, your examination will be documented on your USMLE score transcript as an incomplete attempt, but no actual score will be reported. The examination ends when all blocks have been completed or time has expired. As you leave the testing center, you will receive a written testcompletion notice to document your completion of the examination. W HAT T YP ES O F QU E S TI ONS A R E AS K E D? The Step 2 CK is an integrated examination that tests understanding of normal conditions, disease categories, and physician tasks. Almost all questions on the examination are case based. A substantial amount of extraneous information may be given, or a clinical scenario may be followed by a question that could be answered without actually requiring that you read the case. It is your job to determine which information is superfluous and which is pertinent to the case at hand. Content areas include internal medicine, OB/GYN, pediatrics, preventive services, psychiatry, surgery, and other areas relevant to the provision of care under supervision. Physician tasks are distributed as follows: n n n n Establishing a diagnosis (25–40%) Understanding the mechanisms of disease (20–35%) Applying principles of management (15–25%) Promoting preventive medicine and health maintenance (15–25%) Most questions on the examination have a Single Best Answer format, but some Matching Sets and Sequential Item Sets will be found throughout the examination. Regardless of the question format, the part of the vignette that actually asks the question—the stem—is usually found at the end of the scenario and generally relates to the physician task. From student experience, there are a few stems that are consistently addressed throughout the examination: n n n n n n n What is the most likely diagnosis? (40%) Which of the following is the most appropriate initial step in management? (20%) Which of the following is the most appropriate next step in management? (20%) Which of the following is the most likely cause of . . . ? (5%) Which of the following is the most likely pathogen . . . ? (3%) Which of the following would most likely prevent . . . ? (2%) Other (10%) GUIDE TO EFFICIENT EXAM PREPARATION Additional examination tips are as follows: n n n n Note the age and race of the patient in each clinical scenario. When ethnicity is given, it is often relevant. Know these well (see high-yield facts), especially for more common diagnoses. Be able to recognize key facts that distinguish major diagnoses. Questions often describe clinical findings rather than naming eponyms (eg, they cite “audible hip click” instead of “positive Ortolani’s sign”). Questions about acute patient management (eg, trauma) in an emergency setting are common. The cruel reality of the Step 2 CK is that no matter how much you study, there will still be questions you will not be able to answer with confidence. If you recognize that a question cannot be solved in a reasonable period of time, make an educated guess and move on; you will not be penalized for guessing. Also bear in mind that 10–20% of the USMLE examination questions are “experimental” and will not count toward your score. H O W L O N G W ILL I H A V E T O W A I T BE F OR E I G E T MY S C OR ES ? The USMLE reports scores 3–4 weeks after the examinee’s test date. During peak periods, however, reports may take up to 6 weeks to be scored. Official information concerning the time required for score reporting is posted on the USMLE Web site, www.usmle.org. H O W A R E TH E SCO R ES R E P O R T ED? Like the Step 1 score report, your Step 2 CK report includes your pass/fail status, two numeric scores, and a performance profile organized by discipline and disease process (see Figures 1-1A and 1-1B). The first score is a 3-digit scaled score based on a predefined proficiency standard. In 2010, the required passing score was raised to 189. This score requires answering 60–70% of questions correctly. The second score scale, the 2-digit score, defines 75 as the minimum passing score (equivalent to a score of 189 on the first scale). This score is not a percentile. Any adjustments in the required passing score will be available on the USMLE Web site. Defining Your Goal The first and most important thing to do in your Step 2 CK preparation is define how well you want to do on the exam, as this will ultimately determine the extent of preparation that will be necessary. The amount of time spent in preparation for this examination varies widely among medical students. Possible goals include the following: n n Simply passing. This goal meets the requirements for becoming a licensed physician in the United States. However, if you are taking the Step 2 CK in a time frame in which residency programs will see your score, you should strive to do as well as or better than you did on Step 1. Beating the mean. This signifies an ability to integrate your clinical and factual knowledge to an extent that is superior to that of your peers (between 200 and 220 for recent examination administrations). Others redefine this goal as achieving a score 1 SD above the mean (usually in the range of 220–240). Highly competitive residency programs may SECTION 1 7 8 SECTION 1 GUIDE TO EFFICIENT EXAM PREPARATION Schmoe, Joe T USMLE ID: 1-234-567-8 Anytown, CA 12345 Test Date: August 2011 PASS 200 82 FIGURE 1-1A. n n 189 189 Sample Score Report—Front Page use your Step 1 and Step 2 scores (if available) as a screening tool or as a selection requirement (see Figure 1-2). International medical graduates (IMGs) should aim to beat the mean, as USMLE scores are likely to be a selection factor even for less competitive U.S. residency programs. Acing the exam. Perhaps you are one of those individuals for whom nothing less than the best will do—and for whom excelling on standardized examinations is a source of pride and satisfaction. A high score on the Step 2 CK might also represent a way to strengthen your application and “make up” for a less-than-satisfactory score on Step 1. Evaluating your clinical knowledge. In many ways, this goal should serve as the ultimate rationale for taking the Step 2 CK, as it is technically the reason the examination was initially designed. The case-based nature of GUIDE TO EFFICIENT EXAM PREPARATION FIGURE 1-1B. n Sample Score Report—Back Page the Step 2 CK differs significantly from the more fact-based Step 1 examination in that it more thoroughly assesses your ability to recognize classic clinical presentations, deal with emergent situations, and follow the stepby-step thought processes involved in the treatment of particular diseases. Preparing for internship. Studying for the USMLE Step 2 CK is an excellent way to review and consolidate all of the information you have learned in preparation for internship. Matching statistics, including examination scores related to various specialties, are available at the National Resident Matching Program (NRMP) Web site at www.nrmp.org under “Data and Reports.” SECTION 1 9 GUIDE TO EFFICIENT EXAM PREPARATION Critical Very Important FIGURE 1-2. activities Research grades Preclinica l cores USMLE Step 2 s rades Elective g A hip in AΩ Members cores Step 1 s USMLE Class ran k des rkship gra Other cle lective specialty e Grades in clerkship Important specialty SECTION 1 Grades in 10 Academic Factors Important to Residency Directors W HE N TO TAK E T H E E X AM The second most important thing to do in your examination preparation is to decide when to take the examination. With the CBT, you now have a wide variety of options regarding when to take the Step 2 CK. Here are a few factors to consider: n n n n n n The nature of your objectives, as defined above. The specialty to which you are applying. It is clear that an increasing number of residency programs are viewing the Step 2 CK as an integral part of the residency application process. There are several research publications that demonstrate the increasing importance placed on this examination by residency directors. Some programs are now requiring the Step 2 CK score in order to rank candidates for a residency position. It is therefore in the best interest of candidates to have this examination done in time for scores to be available for the residency application. Taking the examination in June or July ensures that scores will be available for the Match period that begins in September. Some programs, however, will accept scores after the application process starts. Check with programs in your desired specialty to determine when to take the examination. Prerequisite to graduation. If passing the USMLE Step 2 CK is a prerequisite to graduation at your medical school, you will need to take the examination in the fall or winter at the latest. Proximity to clerkships. Many students feel that the core clerkship material is fresher in their minds early in the fourth year, making a good argument for taking the Step 2 CK earlier in the fall. The nature of your schedule. Considerations for MD/PhD students. Some state licensure bodies require that medical licensure occur within 7 years of matriculating into GUIDE TO EFFICIENT EXAM PREPARATION medical school. However, the typical pathway for MD/PhD students consists of 2 years of preclinical work in medical school, 3–4 years of graduate work with research, and finally returning to medical school for clinical work. MD/PhD students typically exceed the 7-year limit. Depending on the state in which licensure is sought, such students may need to petition their licensure body for an exception to this rule. 11 SECTION 1 KEY FACT The Step 2 CK is an opportunity to consolidate your clinical knowledge and prepare for internship. Study Resources Q U A LI T Y CO N SI D E R A T IO N S Although an ever-increasing number of USMLE Step 2 CK review books and software packages are available on the market, the quality of this material is highly variable (see Section 3). Some common problems include the following: n n n n Some review books are too detailed to be reviewed in a reasonable amount of time or cover subtopics that are not emphasized on the examination (eg, a 400-page anesthesiology book). Many sample question books have not been updated to reflect current trends on the Step 2 CK. Many sample question books use poorly written questions, contain factual errors in their explanations, give overly detailed explanations, or offer no explanations at all. Software for boards review is of highly variable quality, may be difficult to install, and may be fraught with bugs. C L IN IC A L R E V I E W B O O K S Many review books are available, so you must decide which ones to buy by carefully evaluating their relative merits. Toward this goal, you should weigh different opinions from other medical students against each other; read the reviews and ratings in Section 3 of this guide; and examine the various books closely in the bookstore. Do not worry about finding the “perfect” book, as many subjects simply do not have one. There are two types of review books: those that are stand-alone titles and those that are part of a series. Books in a series generally have the same style, and you must decide if that style is helpful for you and optimal for a given subject. T ES T B A N KS A test bank can serve multiple functions for examinees, including the following: n n n n n Provide information about strengths and weaknesses in your fund of knowledge. Add variety to your study schedule. Serve as the main form of study. Improve test-taking skills. Familiarize examinees with the style of the USMLE Step 2 CK examination. Students report that many test banks have questions that are, on average, shorter and less clinically oriented than those on the current Step 2 CK. Step KEY FACT The best review book for you reflects the way you like to learn. If a given review book is not working for you, stop using it no matter how highly rated it may be. 12 SECTION 1 GUIDE TO EFFICIENT EXAM PREPARATION 2 CK questions demand fast reading skills and the application of clinical facts in a problem-solving format. Approach sample examinations critically, and do not waste time with low-quality questions until you have exhausted better sources. KEY FACT Use test banks to identify concepts and areas of weakness, not just facts that you missed. After you have taken a practice test, try to identify concepts and areas of weakness, not just the facts that you missed. Use this experience to motivate your study and to prioritize the areas in which you need the most work. Analyze the pattern of your responses to questions to determine if you have made systematic errors in answering questions. Common mistakes include reading too much into the question, second-guessing your initial impression, and misinterpreting the question. TE X TS AND NOTE S Most textbooks are too detailed for high-yield boards review and should be avoided. When using texts or notes, engage in active learning by making tables, diagrams, new mnemonics, and conceptual associations whenever possible. If you already have your own mnemonics, do not bother trying to memorize someone else’s. Textbooks are useful, however, to supplement incomplete or unclear material. C OM M E RC I AL C OU RS ES Commercial preparation courses can be helpful for some students, as they offer an effective way to organize study material. However, multiweek courses are costly and require significant time commitment, leaving limited time for independent study. Also note that some commercial courses are designed for first-time test takers, students who are repeating the examination, or IMGs. NBM E/ U SM LE PU BLI CATI ON S We strongly encourage students to use the free materials provided by the testing agencies and to study the following NBME publications: n n n n USMLE Bulletin of Information. This publication provides you with nuts-and-bolts details about the examination (included on the Web site www.usmle.org; free to all examinees). USMLE Step 2 Computer-Based Content and Sample Test Questions. This is a hardcopy version of the test questions and test content also found on the CD-ROM or at www.usmle.org. NBME Test Delivery Software (FRED) and Tutorial. This includes 143 valuable practice questions. The questions are available on the USMLE CD-ROM and on the USMLE Web site. Make sure you are using the new version of FRED and not the older Prometric version. USMLE Web site (www.usmle.org). In addition to allowing you to become familiar with the CBT format, the sample items on the USMLE Web site provide the only questions that are available directly from the test makers. Student feedback varies as to the similarity of these questions to those on the actual exam, but they are nonetheless worthwhile to know. GUIDE TO EFFICIENT EXAM PREPARATION Test-Day Checklist T HI N GS T O B R IN G WI T H Y O U T O TH E EX AM n n n n Be sure to bring your scheduling permit and a photo ID with signature. (You will not be admitted to the examination if you fail to bring your permit, and Prometric will charge a rescheduling fee.) Remember to bring lunch, snacks (for a little “sugar rush” on breaks), and fluids. Bring clothes to layer to accommodate temperature variations at the testing center. Earplugs will be provided at the Prometric center. Testing Agencies National Board of Medical Examiners (NBME) Department of Licensing Examination Services 3750 Market Street Philadelphia, PA 19104-3102 (215) 590-9500 Fax: (215) 590-9457 www.nbme.org USMLE Secretariat 3750 Market Street Philadelphia, PA 19104-3190 (215) 590-9700 Fax: (215) 590-9457 www.usmle.org Educational Commission for Foreign Medical Graduates (ECFMG) 3624 Market Street Philadelphia, PA 19104-2685 (215) 386-5900 Fax: (215) 386-9196 www.ecfmg.org e-mail: info@ecfmg.org Federation of State Medical Boards (FSMB) 400 Fuller Wiser Road, Suite 300 Euless, TX 76039 (817) 868-4000 Fax: (817) 868-4099 www.fsmb.org e-mail: usmle@fsmb.org SECTION 1 13 14 SECTION 1 GUIDE TO EFFICIENT EXAM PREPARATION NOTES SECTION 2 DATABASE OF HIGH-YIELD FACTS Cardiovascular Neurology Dermatology Obstetrics Endocrinology Gynecology Epidemiology Pediatrics Ethics and Legal Issues Psychiatry Gastrointestinal Pulmonary Hematology/Oncology Renal/Genitourinary Infectious Disease Selected Topics in Emergency Medicine Musculoskeletal Rapid Review 15 16 SECTION 2 DATABASE OF HIGH-YIELD FACTS How to Use the Database The eighth edition of First Aid for the USMLE Step 2 CK contains a revised and expanded database of clinical material that student authors and faculty have identified as high yield for boards review. The facts are organized according to subject matter, whether medical specialty (eg, Cardiovascular, Renal) or high-yield topic (eg, Ethics). Each subject is then divided into smaller subsections of related facts. Individual facts are generally presented in a logical fashion, from basic definitions and epidemiology to History/Physical Exam, Diagnosis, and Treatment. Lists, mnemonics, pull quotes, vignette flash cards, and tables are used when they can help the reader form key associations. In addition, color and black-and-white images are interspersed throughout the text. At the end of Section 2, we also feature a Rapid Review chapter consisting of key facts and classic associations that can be studied a day or two before the exam. The content contained herein is useful primarily for the purpose of reviewing material already learned. The information presented is not ideal for learning complex or highly conceptual material for the first time. The Database of High-Yield Facts is not comprehensive. Use it to complement your core study material, not as your primary study source. The facts and notes have been condensed and edited to emphasize essential material. Work with the material, add your own notes and mnemonics, and recognize that not all memory techniques work for all students. We update Section 2 biannually to keep current with new trends in boards content as well as to expand our database of high-yield information. However, we must note that inevitably many other high-yield entries and topics are not yet included in our database. We actively encourage medical students and faculty to submit entries and mnemonics so that we may enhance the database for future students. We also solicit recommendations of additional study tools that may be useful in preparing for the examination, such as diagrams, charts, and computer-based tutorials (see How to Contribute, p. xiii). DI S C LAI M E R The entries in this section reflect student opinions of what is high yield. Owing to the diverse sources of material, no attempt has been made to trace or reference the origins of entries individually. We have regarded mnemonics as essentially in the public domain. All errors and omissions will gladly be corrected if brought to the attention of the authors, either through the publisher or directly by e-mail. HIGH-YIELD FACTS IN CARDIOVASCULAR Electrocardiogram 18 Acute Coronary Syndromes 32 RATE 18 UNSTABLE ANGINA/NON-ST-ELEVATION MYOCARDIAL INFARCTION 32 RHYTHM 18 ST-ELEVATION MYOCARDIAL INFARCTION 33 AXIS 18 INTERVALS 18 ISCHEMIA/INFARCTION 19 CHAMBER ENLARGEMENT 19 Cardiac Physical Exam 19 Arrhythmias 21 Dyslipidemia 35 Hypertension 36 1° (ESSENTIAL) HYPERTENSION 36 2° HYPERTENSION 37 HYPERTENSIVE CRISES 39 Pericardial Disease 39 BRADYARRHYTHMIAS AND CONDUCTION ABNORMALITIES 21 PERICARDITIS 39 TACHYARRHYTHMIAS 21 CARDIAC TAMPONADE 41 Congestive Heart Failure 21 Valvular Heart Disease 41 SYSTOLIC DYSFUNCTION 21 NONSYSTOLIC DYSFUNCTION 26 Vascular Disease 41 Cardiomyopathy 28 AORTIC ANEURYSM 41 AORTIC DISSECTION 43 DILATED CARDIOMYOPATHY 28 DEEP VENOUS THROMBOSIS 44 HYPERTROPHIC CARDIOMYOPATHY 30 PERIPHERAL ARTERIAL DISEASE 45 RESTRICTIVE CARDIOMYOPATHY 30 LYMPHEDEMA 46 Coronary Artery Disease ANGINA PECTORIS 31 Syncope 47 31 17 18 HIGH-YIELD FACTS IN CARDIOVASCULAR Electrocardiogram (ECG) KEY FACT Estimate heart rate by counting the number of large boxes between 2 consecutive QRS complexes as follows: 300-150-100-75-60-50-43- . . . bpm. Methodically assess the ECG for rate, rhythm, axis, intervals, waveforms, and chamber enlargement (see Figure 2.1-1). RATE n n n The normal heart rate (HR) is 60–100 bpm. HR < 60 bpm is bradycardia. HR > 100 bpm is tachycardia. RHYTHM Look for sinus rhythm (P before every QRS and QRS after every P), irregular rhythms, junctional or ventricular rhythms (no P before a QRS), and ectopic beats. AX I S n n n Normal: An upright (!) QRS in leads I and aVF (0 to +90 degrees). Left-axis deviation: An upright QRS in lead I and a downward (") QRS in lead aVF. Up to –30 degrees is still considered a normal variant. Right-axis deviation: A downward QRS in lead I and an upright QRS in lead aVF (up to +105 degrees is considered a normal variant). I NTE R VALS n n n Normal: PR interval between 120 and 200 msec and QRS < 120 msec. Atrioventricular (AV) block: PR interval > 200 msec, or P with no QRS afterward. Left bundle branch block (LBBB): QRS duration > 120 msec; no R wave in V1; wide, tall R waves in I, V5, and V6 (see Figure 2.1-2). I aVR V1 V4 II aVL V2 V5 III aVF V3 V6 V1 Normal electrocardiogram from a healthy subject. Sinus rhythm is present with a heart rate of 96 bpm. The PR interval is 0.12 sec; the QRS interval (duration) is 0.08 sec; the QT interval is 0.30 sec; QTc is 0.38 sec; and the mean QRS axis is about +60 degrees. The precordial leads show normal R-wave progression with the transition zone (R wave = S wave) between leads V2 and V3. (Adapted with permission from USMLERx.com.) FIGURE 2.1-1. CARDIOVASCULAR n n Right bundle branch block (RBBB): QRS duration > 120 msec; RSR′ complex (“rabbit ears”); qR or R morphology with a wide R wave in V1; QRS pattern with a wide S wave in I, V5, and V6 (see Figure 2.1-3). Long QT syndrome: QTc > 440 msec. An underdiagnosed congenital disorder that predisposes to ventricular tachyarrhythmias. HIGH-YIELD FACTS IN 19 V1 A ISC H E M I A /I N F A R C T I O N n n Ischemia: New inverted T waves; poor R-wave progression in precordial leads; ST-segment changes (elevation or depression). Transmural infarct: Significant Q waves (> 40 msec or more than onethird of the QRS amplitude); ST elevations with T-wave inversions. CH A M B E R EN LA R G E M E N T n n n Atrial enlargement: n Right atrial abnormality (P pulmonale): The P-wave amplitude in lead II is > 2.5 mm. n Left atrial abnormality (P mitrale): The P-wave width in lead II is > 120 msec, or terminal " deflection in V1 is > 1 mm in amplitude and > 40 msec in duration. Notched P waves can frequently be seen in lead II. Left ventricular hypertrophy (LVH; see Figure 2.1-4): n The amplitude of S in V1 + R in V5 or V6 is > 35 mm. n Alternative criteria: The amplitude of R in aVL + S in V3 is > 28 mm in men or > 20 mm in women. Right ventricular hypertrophy (RVH): Right-axis deviation and an R wave in V1 > 7 mm. V6 B F I G U R E 2 . 1 - 3 . RBBB. Characteristic ECG findings are seen in leads V1 (A) and V6 (B). (Adapted with permission from USMLERx.com.) KEY FACT P Pulmonale causes Peaked P waves. P Mitrale causes M-shaped P waves. Cardiac Physical Exam Key examination findings that can narrow the differential include the following: n n n n Jugular venous distention (JVD, > 7 cm above the sternal angle): Suggests right heart failure, pulmonary hypertension, volume overload, tricuspid regurgitation, or pericardial disease. Hepatojugular reflux: Fluid overload; impaired right ventricular compliance. Kussmaul’s sign (↑ in JVP with inspiration): Right ventricular infarction, postoperative cardiac tamponade, tricuspid regurgitation, constrictive pericarditis. Systolic murmurs (see Table 2.1-1 and Figures 2.1-5 and 2.1-6): n Aortic stenosis: A harsh systolic ejection murmur that radiates to the carotids. V1 V2 V5 V6 F I G U R E 2 . 1 - 4 . LVH. Shown are leads V1, V2, V5, and V6. S wave in V1 + R wave in V5 = 45 mm. Note ST changes and T-wave inversion in V5 and V6, suggesting strain. (Reproduced with permission from Gomella LG, Haist SA. Clinician’s Pocket Reference, 11th ed. New York: McGraw-Hill, 2007, Fig. 19-27.) V1 A FIGURE 2.1-2. B V6 LBBB. Characteristic ECG findings are seen in leads V1 (A) and V6 (B). (Adapted with permission from USMLERx.com.) A college-age male “passed out” while playing basketball and had no prodromal symptoms or signs of seizure. His cardiac examination is unremarkable, and an ECG shows a slurred upstroke of the QRS. What are the next best steps? 20 HIGH-YIELD FACTS IN CARDIOVASCULAR TA B L E 2 . 1- 1 . Cardiac Murmurs SYSTOLIC MURMURS DIASTOLIC MURMURS Aortic stenosis Aortic regurgitation Mitral regurgitation Mitral stenosis Mitral valve prolapse A Tricuspid regurgitation P T Mitral regurgitation: A holosystolic murmur that radiates to the axilla or to the carotids. n Mitral valve prolapse: A midsystolic or late systolic murmur with a preceding click. n Flow murmur: Very common, and does not imply cardiac disease. Diastolic murmurs (see Table 2.1-1 and Figures 2.1-5 and 2.1-6): Always abnormal. n Aortic regurgitation: An early decrescendo murmur. n Mitral stenosis: A mid- to late, low-pitched murmur. n M n Auscultation locations. Auscultation sites are shown with FIGURE 2.1-5. associated valves. A = aortic valve, P = pulmonic valve, T = tricuspid valve, M = mitral valve. S1 S2 Mitral/tricuspid regurgitation (MR/TR) Aortic stenosis EC VSD Mitral prolapse MC Aortic regurgitation Mitral stenosis OS PDA This is Wolff-Parkinson-White syndrome (WPW). Advise against vigorous physical activity, initiate β-blockade, and refer for an electrophysiology study. FIGURE 2.1-6. Heart murmurs. Visual representations of common heart murmurs are shown in relation to S1 and S2. EC = ejection click; MC = midsystolic click; OS = opening snap. (Adapted with permission from Le T et al. First Aid for the USMLE Step 1 2009. New York: McGraw-Hill, 2009: 250.) CARDIOVASCULAR n n n Gallops: n S3 gallop: Dilated cardiomyopathy (floppy ventricle), mitral valve disease; often normal in younger patients and in high-output states (eg, pregnancy). n S4 gallop: Hypertension, diastolic dysfunction (stiff ventricle), aortic stenosis; often normal in younger patients and in athletes. Edema: n Pulmonary: Left heart failure (fluid “backs up” into the lungs). n Peripheral: Right heart failure and biventricular failure (fluid “backs up” into the periphery), peripheral venous disease, constrictive pericarditis, tricuspid regurgitation, hepatic disease, lymphedema. Also nephrotic syndrome, hypoalbuminemia, and drugs. Peripheral pulses: n Increased: Compensated aortic regurgitation, coarctation (arms > legs), patent ductus arteriosus. n Decreased: Peripheral arterial disease; late-stage heart failure. n Pulsus paradoxus (↓ systolic BP with inspiration): Pericardial tamponade; also asthma and COPD, tension pneumothorax, and foreign body in airway. n Pulsus alternans (alternating weak and strong pulses): Cardiac tamponade; impaired left ventricular systolic function. Poor prognosis. n Pulsus parvus et tardus (weak and delayed pulse): Aortic stenosis. HIGH-YIELD FACTS IN 21 KEY FACT Heart auscultation locations: All (Aortic) Physicians (Pulmonic) Take (Tricuspid) Money (Mitral). Arrhythmias B RA D Y A R R H Y T H M I A S A ND CO ND U C TI ON A BNOR M ALI TI E S Table 2.1-2 outlines the etiologies, clinical presentation, and treatment of common bradyarrhythmias and conduction abnormalities. T A C H Y A R R H Y T H M IA S Tables 2.1-3 and 2.1-4 outline the etiologies, clinical presentation, and treatment of common supraventricular and ventricular tachyarrhythmias. MNEMONIC Management options for atrial fibrillation— ABCD Anticoagulate β-blockers to control rate Cardiovert/Calcium channel blockers Digoxin Congestive Heart Failure (CHF) A clinical syndrome caused by inability of the heart to pump enough blood to maintain fluid and metabolic homeostasis. Risk factors include CAD, hypertension, cardiomyopathy, valvular heart disease, and diabetes. The American Heart Association/American College of Cardiology guidelines classify heart failure according to clinical syndromes, but alternative classification systems, including that of the New York Heart Association (NYHA), include functional severity, left-sided vs. right-sided failure, and systolic vs. nonsystolic failure (see Tables 2.1-5 through 2.1-7). KEY FACT The most common cause of right-sided heart failure is left-sided heart failure. S Y S T O L IC D Y S F U N C T I O N Defined as a ↓ EF (< 50%) and ↑ left ventricular end-diastolic volumes. It is caused by inadequate left ventricular contractility or ↑ afterload. The heart compensates for ↓ EF and ↑ preload through hypertrophy and ventricular dilation (Frank-Starling law), but the compensation ultimately fails, leading to ↑ myocardial work and worsening systolic function. A man was admitted for a CHF exacerbation with low EF. The patient is now ready for discharge, and his medications include furosemide and metoprolol. What is the next step in management? 22 HIGH-YIELD FACTS IN TA B L E 2 . 1- 2 . CARDIOVASCULAR Bradyarrhythmias and Conduction Abnormalities TYPE Sinus bradycardia First-degree AV block ETIOLOGY SIGNS/SYMPTOMS ECG FINDINGS TREATMENT Normal response May be asymptomatic, Sinus rhythm. None if to cardiovascular but may also present with Ventricular rate < 60 asymptomatic; conditioning; can also lightheadedness, syncope, chest bpm. atropine may be result from sinus node pain, or hypotension. used to ↑ heart dysfunction or from rate. Pacemaker β-blocker or calcium placement is the channel blocker (CCB) definitive treatment excess. in severe cases. Asymptomatic. Can occur in normal individuals; associated PR interval > 200 None necessary. msec. with ↑ vagal tone and with β-blocker or CCB use. Usually asymptomatic. Second-degree AV Drug effects (digoxin, Progressive PR Stop the offending block (Mobitz I/ β-blockers, CCBs) or lengthening until a drug. Atropine as Wenckebach) ↑ vagal tone; right dropped beat occurs; clinically indicated. coronary ischemia or the PR interval then infarction. resets. Second-degree AV Results from fibrotic Occasionally syncope; frequent Unexpected dropped Pacemaker block (Mobitz II) disease of the progression to third-degree AV beat(s) without placement. conduction system or block. a change in PR from acute, subacute, or interval. prior MI. Third-degree No electrical Syncope, dizziness, acute heart No relationship Pacemaker AV block (complete) communication between failure, hypotension, cannon A between P waves placement. the atria and ventricles. waves. and QRS complexes. Sick sinus syndrome/ A heterogeneous 2° to tachycardia or bradycardia; The most common tachycardia-bradycardia disorder that leads may include syncope, palpitations, indication for syndrome to intermittent dyspnea, chest pain, TIA, and pacemaker supraventricular tachy- stroke. placement. and bradyarrhythmias. HISTORY/PE n Add an ACEI to this patient’s current regimen. ACEIs have been shown to have a # mortality benefit when used with β-blockers in NYHA class II–IV heart failure patients. n n n Exertional dyspnea is the earliest and most common presenting symptom and progresses to orthopnea, paroxysmal nocturnal dyspnea (PND), and finally rest dyspnea. Patients may report chronic cough, fatigue, peripheral edema, nocturia, and/or abdominal fullness. Examination reveals parasternal lift, an elevated and sustained left ventricular impulse, an S3/S4 gallop, JVD, and peripheral edema. Look for signs to distinguish left- from right-sided failure (see Table 2.1-6). CARDIOVASCULAR TA B L E 2 . 1- 3 . HIGH-YIELD FACTS IN 23 Supraventricular Tachyarrhythmias TYPE ETIOLOGY SIGNS/SYMPTOMS ECG FINDINGS TREATMENT ATRIAL Sinus tachycardia Palpitations, shortness of breath. Sinus rhythm. Treat the underlying response to fear, Ventricular rate > 100 cause. pain, and exercise. bpm. Normal physiologic Can also be 2° to hyperthyroidism, volume contraction, infection, or pulmonary embolism (PE). Atrial fibrillation (AF) Acute AF— Estimate the risk of Often asymptomatic, but may present No discernible P waves, PIRATES: with shortness of breath, chest pain, with variable and stroke using the Pulmonary or palpitations. Physical examination irregular QRS response. CHADS2 score. disease Anticoagulate if ≥ 2. reveals an irregularly irregular pulse. Anticoagulation if > 48 Ischemia Rheumatic heart hours (to prevent disease CVA); rate control Anemia/Atrial (β-blockers, CCBs, myxoma digoxin). Thyrotoxicosis Initiate cardioversion Ethanol only if new onset Sepsis (< 48 hours) or Chronic AF— transesophageal hypertension, echocardiogram (TEE) CHF. shows no left atrial clot, or after 3–6 weeks of warfarin treatment with a satisfactory INR (2–3). Atrial flutter Circular movement Usually asymptomatic, but can present Regular rhythm; Anticoagulation, of electrical with palpitations, syncope, and “sawtooth” appearance rate control, and activity around the lightheadedness. of P waves can be seen. cardioversion guidelines atrium at a rate of The atrial rate is usually as in AF above. approximately 300 240–320 bpm and the times per minute. ventricular rate ~ 150 bpm. Multifocal atrial Multiple atrial May be asymptomatic. At least 3 Three or more unique Treat the underlying tachycardia pacemakers different P-wave morphologies. P-wave morphologies; disorder; verapamil rate > 100 bpm. or β-blockers for rate or reentrant pathways; COPD, control and suppression hypoxemia. of atrial pacemakers (not very effective). (continues) 24 HIGH-YIELD FACTS IN CARDIOVASCULAR Supraventricular Tachyarrhythmias (continued) TA B L E 2 . 1- 3 . TYPE ETIOLOGY SIGNS/SYMPTOMS ECG FINDINGS TREATMENT AV JUNCTION Atrioventricular A reentry circuit Palpitations, shortness of breath, angina, Rate 150–250 bpm; P Cardiovert if nodal reentry in the AV node syncope, lightheadedness. wave is often buried in hemodynamically tachycardia depolarizes QRS or shortly after. unstable. Carotid (AVNRT) the atrium and massage, Valsalva, or ventricle nearly adenosine can stop simultaneously. the arrhythmia. Atrioventricular An ectopic Palpitations, shortness of breath, angina, A retrograde P wave is Same as that for reciprocating connection syncope, lightheadedness. often seen after a normal AVNRT. tachycardia between the QRS. A preexcitation delta (AVRT) atrium and wave is characteristically ventricle that seen in WPW. causes a reentry circuit. Seen in WPW. Paroxysmal atrial Rapid ectopic Palpitations, shortness of breath, angina, Rate > 100 bpm; P wave Adenosine can be tachycardia pacemaker in the syncope, lightheadedness. with an unusual axis used to unmask before each normal QRS. underlying atrial atrium (not sinus activity. node). DIAGNOSIS n n KEY FACT n n Diuretics and digoxin are for symptomatic relief only and confer no mortality benefit. MNEMONIC Acute CHF management— LMNOP Lasix Morphine Nitrates Oxygen Position (upright) n CHF is a clinical syndrome whose diagnosis is based on signs and symptoms. CXR may show cardiomegaly, cephalization of pulmonary vessels, pleural effusions, vascular congestion, interstitial edema, and prominent hila (see Figure 2.1-7). Echocardiogram will show ↓ EF and ventricular dilation. Lab abnormalities include a BNP > 500 pg/mL, ↑ creatinine (sometimes), and ↓ sodium in later stages. ECG will usually be nondiagnostic but may help pinpoint an underlying cause, such as AF, an old MI, or LVH as a sign of long-standing hypertension. TREATMENT n Acute: n Correct underlying causes such as arrhythmias, myocardial ischemia, and drugs (eg, CCBs, antiarrhythmics, NSAIDs, alcohol, thyroid and valvular disease, high-output states). n Diurese aggressively with loop and thiazide diuretics (see Table 2.1-8). n Give ACEIs to all patients who can tolerate them. Consider an angiotensin receptor blocker (ARB) if the patient cannot tolerate an ACEI. n β-blockers should not be used during decompensated CHF but should be started once the patient is euvolemic. n Treat acute pulmonary congestion with LMNOP (see mnemonic). CARDIOVASCULAR TA B L E 2 . 1- 4 . HIGH-YIELD FACTS IN 25 Ventricular Tachyarrhythmias TYPE ETIOLOGY SIGNS/SYMPTOMS ECG FINDINGS TREATMENT Premature Ectopic beats arise Usually asymptomatic, but may lead to Early, wide QRS Treat the underlying ventricular from ventricular palpitations. not preceded by a cause. If symptomatic, contraction foci. Associated P wave. PVCs are give β-blockers or, (PVC) with hypoxia, usually followed by a occasionally, other electrolyte compensatory pause. antiarrhythmics. abnormalities, and hyperthyroidism. Ventricular Can be associated Nonsustained VT is often asymptomatic; Three or more Cardioversion and tachycardia with CAD, MI, and sustained VT can lead to palpitations, consecutive PVCs; antiarrhythmics (eg, (VT) structural heart hypotension, angina, and syncope. Can wide QRS complexes amiodarone, lidocaine, disease. progress to VF and death. in a regular rapid procainamide). rhythm; may see AV dissociation. Ventricular Associated with Syncope, absence of blood pressure, Totally erratic wide- Immediate electrical fibrillation CAD and structural pulselessness. complex tracing. cardioversion and ACLS (VF) heart disease. protocol. Also associated with cardiac arrest (together with asystole). Torsades Associated with Can present with sudden cardiac death; Polymorphous QRS; VT Give magnesium de pointes long QT syndrome, typically associated with palpitations, dizziness, with rates between 150 initially and cardiovert proarrhythmic and syncope. and 250 bpm. if unstable. Correct response to hypokalemia; withdraw medications, offending drugs. hypokalemia, congenital deafness, and alcoholism. TA B L E 2 . 1- 5 . CLASS NYHA Functional Classification of CHF DESCRIPTION I No limitation of activity; no symptoms with normal activity. II Slight limitation of activity; comfortable at rest or with mild exertion. III Marked limitation of activity; comfortable only at rest. IV Any physical activity brings on discomfort; symptoms present at rest. 26 HIGH-YIELD FACTS IN CARDIOVASCULAR TA B L E 2 . 1- 6 . Left-Sided vs. Right-Sided Heart Failure LEFT-SIDED CHF SYMPTOMS RIGHT-SIDED CHF SYMPTOMS Dyspnea predominates Fluid retention predominates Left-sided S3/S4 gallop Right-sided S3/S4 gallop Bilateral basilar rales JVD Pleural effusions Hepatojugular reflex Pulmonary edema Peripheral edema Orthopnea, paroxysmal Hepatomegaly, ascites nocturnal dyspnea n KEY FACT Loops lose calcium; thiazides take it in. n n Chronic: n Control comorbid conditions and limit dietary sodium and fluid intake. n Long-term β-blockers and ACEIs/ARBs help prevent remodeling of the heart and ↓ mortality for NYHA class II–IV patients. Avoid CCBs. n Daily ASA and a statin are recommended if the underlying cause is a prior MI. n Chronic diuretic therapy (loop diuretics +/− a thiazide) can prevent volume overload. n Low-dose spironolactone ↓ mortality risk in patients with NYHA class III–IV heart failure. n Anticoagulate patients with a history of previous embolic events, AF, or a mobile left ventricular thrombus. Consider an implantable biventricular cardiac defibrillator (ICD) in patients with an EF < 35%. CHF that is unresponsive to maximal medical therapy may require a mechanical left ventricular assist device or cardiac transplantation. NONS YS TOLI C DYS F U NC TI ON Defined by ↓ ventricular compliance with normal systolic function. The ventricle has either impaired active relaxation (2° to ischemia, aging, and/or hypertrophy) or impaired passive filling (scarring from prior MI; restrictive cardiomyopathy). Left ventricular end-diastolic pressure ↑, cardiac output remains essentially normal, and EF is normal or ↑. T A B L E 2 . 1 - 7. Comparison of Systolic and Diastolic Dysfunction VARIABLE SYSTOLIC DYSFUNCTION NONSYSTOLIC DYSFUNCTION Patient age Often < 65 years of age. Often > 65 years of age. Comorbidities Dilated cardiomyopathy, valvular heart disease. Restrictive or hypertrophic cardiomyopathy; renal disease or hypertension. Physical examination Displaced PMI, S3 gallop. Sustained PMI, S4 gallop. CXR Pulmonary congestion, cardiomegaly. Pulmonary congestion, normal heart size. ECG/echocardiography Q waves, ↓ EF (< 40%). LVH, normal EF (> 55%). CARDIOVASCULAR HIGH-YIELD FACTS IN 27 FIGURE 2.1-7. CXR with evidence of CHF. Frontal CXR demonstrates marked cardiomegaly, cephalization of vessels (arrow), interstitial edema (circle), and left-sided pleural effusion that raise concern for CHF. (Reproduced with permission from Tintinalli JE et al. Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 7th ed. New York: McGraw-Hill, 2011, Fig. 57-1.) TA B L E 2 . 1- 8 . Types of Diuretics CLASS Loop diuretics EXAMPLES Furosemide, ethacrynic SITE OF ACTION Loop of Henle MECHANISM OF ACTION SIDE EFFECTS ↓ Na+/K+/2Cl− Ototoxicity, hypokalemia, acid, bumetanide, cotransporter; ↓ urine hypocalcemia, dehydration, torsemide concentration; ↑ Ca gout. 2+ excretion. Thiazide HCTZ, chlorothiazide, diuretics chlorthalidone Early distal tubule ↓ NaCl reabsorption Hypokalemic metabolic leading to ↓ diluting capacity of nephron; ↓ Ca excretion. alkalosis, hyponatremia, 2+ and hyperGLUC (hyperGlycemia, hyperLipidemia, hyperUricemia, hyperCalcemia). K+-sparing Spironolactone, agents triamterene, amiloride Cortical collecting tubule Spironolactone is an Hyperkalemia, aldosterone receptor gynecomastia, sexual antagonist; triamterene dysfunction. and amiloride block Na+ channels. Carbonic Acetazolamide anhydrase Proximal convoluted NaHCO3 diuresis ↓ total Hyperchloremic metabolic tubule body NaHCO3. acidosis, neuropathy, NH3 inhibitors Osmotic agents toxicity, sulfa allergy. Mannitol Proximal tubule Creates ↑ tubular fluid Pulmonary edema, osmolarity, leading to ↑ dehydration. urine flow. Contraindicated in anuria and CHF. 28 HIGH-YIELD FACTS IN CARDIOVASCULAR HISTORY/PE Associated with stable and unstable angina, shortness of breath, dyspnea on exertion, arrhythmias, MI, heart failure, and sudden death. TREATMENT n n n Diuretics are first-line therapy (see Table 2.1-8). Maintain rate and BP control via β-blockers, ACEIs, ARBs, or CCBs. Digoxin is not useful in these patients. Cardiomyopathy Myocardial disease; categorized as dilated, hypertrophic, or restrictive (see Table 2.1-9 and Figure 2.1-8). DI LATE D C AR DI OM YOP ATHY KEY FACT An S3 gallop signifies rapid ventricular filling in the setting of fluid overload and is associated with dilated cardiomyopathy. The most common cardiomyopathy. Left ventricular dilation and ↓ EF must be present for diagnosis. Most cases are idiopathic, but known 2° causes include alcohol, myocarditis, postpartum status, drugs (doxorubicin, AZT, cocaine), endocrinopathies (thyroid dysfunction, acromegaly, pheochromocytoma), infection (coxsackievirus, HIV, Chagas’ disease, parasites), genetic factors, and nutritional disorders (wet beriberi). The most common causes of 2° dilated cardiomyopathy are ischemia and long-standing hypertension. HISTORY/PE n n Often presents with gradual development of CHF symptoms. Examination often reveals displacement of the left ventricular impulse, JVD, an S3/S4 gallop, or mitral/tricuspid regurgitation. TA B L E 2 . 1- 9 . Differential Diagnosis of Cardiomyopathies TYPE VARIABLE DILATED HYPERTROPHIC RESTRICTIVE Major abnormality Impaired contractility Impaired relaxation Impaired elasticity ↑↑ ↓ ↑ ↑↑ ↓↓ ↑ ↓↓ ↑ or ↔ ↓ or ↔ ↓, variable ↑↑ ↑, variable Left ventricular cavity size (end diastole) Left ventricular cavity size (end systole) EF Wall thickness CARDIOVASCULAR A HIGH-YIELD FACTS IN 29 B C FIGURE 2.1-8. Cardiomyopathies. Echocardiogram 4-chamber views of (A) a normal heart, (B) dilated cardiomyopathy, and (C) hypertrophic cardiomyopathy. (Reproduced with permission from Fuster V et al. Hurst’s The Heart, 12th ed. New York: McGraw-Hill, 2008, Figs. 16-17B, 16-108, and 16-109.) DIAGNOSIS n n n Echocardiography is diagnostic. ECG may show nonspecific ST-T changes, a low-voltage QRS, sinus tachycardia, and ectopy. LBBB is common. CXR shows an enlarged, balloon-like heart and pulmonary congestion. TREATMENT n n n n Address the underlying etiology (eg, alcohol use, endocrine disorders). Treat symptoms of CHF with diuretics, ACEIs/ARBs, and β-blockers. Digoxin is a second-line agent; avoid CCBs in heart failure. Consider anticoagulation to ↓ thrombus risk if AF or an intraventricular thrombus is present. Consider an ICD if EF is < 35%. A woman with hypertension and prior MI has an examination notable for a displaced PMI, an S3, a nonelevated JVP, and bibasilar rales. What is the next best step in diagnosis? 30 HIGH-YIELD FACTS IN CARDIOVASCULAR HYP E R TR OP HI C CAR DI OM YOP ATHY KEY FACT HOCM is the most common cause of sudden death in young, healthy athletes in the United States. Defined as impaired left ventricular relaxation and filling (nonsystolic dysfunction) due to thickened ventricular walls. Hypertrophy frequently involves the interventricular septum, leading to left ventricular outflow tract obstruction and impaired ejection of blood. The congenital form, hypertrophic obstructive cardiomyopathy (HOCM), is inherited as an autosomal dominant trait in 50% of HOCM patients and is the most common cause of sudden death in young, healthy athletes in the United States. Other causes of marked hypertrophy include hypertension and aortic stenosis. HISTORY/PE KEY FACT n n An S4 gallop signifies a stiff, noncompliant ventricle and ↑ “atrial kick” and may be associated with hypertrophic cardiomyopathy. Patients may be asymptomatic but may also present with syncope, dyspnea, palpitations, angina, or sudden cardiac death. Examination often reveals a sustained apical impulse, an S4 gallop, and a systolic ejection crescendo-decrescendo murmur that ↑ with ↓ preload (eg, Valsalva maneuver, standing) and ↓ with ↑ preload (eg, passive leg raise). DIAGNOSIS n n n Echocardiography is diagnostic and shows an asymmetrically thickened septum and dynamic obstruction of blood flow. ECG may show signs of LVH. CXR may reveal left atrial enlargement (LAE) 2° to mitral regurgitation. TREATMENT n n n β-blockers are initial therapy for symptomatic relief; CCBs are second-line agents. Surgical options for HOCM include dual-chamber pacing, partial excision or alcohol ablation of the myocardial septum, ICD placement, and mitral valve replacement. Patients should avoid intense athletic competition and training. RE S TR I C TI VE C AR DI OM YOP ATHY Defined as ↓ elasticity of myocardium leading to impaired diastolic filling without significant systolic dysfunction (a normal or near-normal EF). It is caused by infiltrative disease (amyloidosis, sarcoidosis, hemochromatosis) or by scarring and fibrosis (2° to radiation). HISTORY/PE Signs and symptoms of left-sided and right-sided heart failure occur, but symptoms of right-sided heart failure (JVD, peripheral edema) often predominate. DIAGNOSIS n n This patient has evidence of dilated cardiomyopathy. An echocardiogram would be the next best diagnostic step. n Echocardiography is key for diagnosis, with rapid early filling and a nearnormal EF. CXR, MRI, and cardiac catheterization are helpful for characterization (eg, sarcoid, amyloidosis). Cardiac biopsy may reveal fibrosis or evidence of infiltration. ECG frequently shows LBBB; low voltages are seen in amyloidosis. CARDIOVASCULAR HIGH-YIELD FACTS IN 31 TREATMENT Therapeutic options are limited and are generally palliative only. Medical treatment includes cautious use of diuretics for fluid overload and vasodilators to ↓ filling pressure. Coronary Artery Disease (CAD) Clinical manifestations of CAD include stable and unstable angina, shortness of breath, dyspnea on exertion, arrhythmias, MI, heart failure, and sudden death. Risk factors include diabetes mellitus (DM), a family history of premature CAD (males < 55, females < 65), smoking, dyslipidemia, abdominal obesity, hypertension, age (males > 45, females > 55), and male gender. CAD risk equivalents include DM, symptomatic carotid artery disease, peripheral arterial disease, and abdominal aortic aneurysm (AAA). KEY FACT Major risk factors for CAD include age, male gender, ↑ LDL, ↓ HDL, DM, hypertension, a family history, smoking, and peripheral arterial disease. ANG I N A PE C T O R IS Defined as substernal chest pain 2° to myocardial ischemia (O2 supply and demand mismatch). Prinzmetal’s (variant) angina mimics angina pectoris but is caused by vasospasm of coronary vessels. It classically affects young women at rest in the early morning and is associated with ST-segment elevation in the absence of cardiac enzyme elevation. KEY FACT Prinzmetal’s angina doesn’t meddle with enzymes. HISTORY/PE n n n The classic triad consists of substernal chest pain that is usually precipitated by stress or exertion and is relieved by rest or nitrates. Pain can radiate and may be associated with shortness of breath, nausea/ vomiting, diaphoresis, or lightheadedness. Examination of patients experiencing stable angina is generally unremarkable. Look for carotid and peripheral bruits suggesting atherosclerosis and hypertension. DIAGNOSIS n n n Rule out pulmonary, GI, or other cardiac causes of chest pain. Significant ST-segment changes on exercise stress test with ECG monitoring are diagnostic of CAD. Maintain a high index of suspicion in patient populations such as women and diabetics in view of their propensity for “silent” events. KEY FACT Women, diabetics, the elderly, and post–heart transplant patients may have atypical, clinically silent MIs. TREATMENT n n n n Treat acute symptoms with ASA, O2, IV nitroglycerin, and IV morphine, and consider IV β-blockers. The efficacy of nondihydropyridine CCBs (diltiazem, verapamil) and ACEIs has also been validated. Admit to the hospital and monitor until acute MI has been ruled out by serial cardiac enzymes. Treat chronic symptoms with nitrates, ASA, and β-blockers; CCBs are second-line agents for symptomatic control only. Initiate risk factor reduction (eg, smoking, cholesterol, hypertension). Hormone replacement therapy is not protective in postmenopausal women. KEY FACT Only ASA and β-blockers have been shown to have a mortality benefit in the treatment of angina. 32 HIGH-YIELD FACTS IN CARDIOVASCULAR Acute Coronary Syndromes A spectrum of clinical syndromes caused by plaque disruption or vasospasm that leads to acute myocardial ischemia. UNSTABLE ANGINA/NON-ST-ELEVATION MYOCARDIAL INFARCTION (NSTEMI) KEY FACT U Ain’t got enzymes with Unstable Angina. Unstable angina is defined as chest pain that is new onset, is accelerating (ie, occurs with less exertion, lasts longer, or is less responsive to medications), or occurs at rest; it is distinguished from stable angina pectoris by patient history. It signals the presence of possible impending infarction based on plaque instability. In contrast, NSTEMI indicates myocardial necrosis marked by elevations in troponin I and CK-MB without ST-segment elevations seen on ECG. DIAGNOSIS n n n Patients should be risk stratified according to the Thrombolysis in Myocardial Infarction (TIMI) study criteria to determine the likelihood of adverse cardiac events (see Table 2.1-10). Unstable angina is not associated with elevated cardiac markers, but ST changes may be seen on ECG. NSTEMI is diagnosed by serial cardiac enzymes and ECG. TREATMENT n n Acute treatment of symptoms is the same as that for stable angina and consists of clopidogrel, unfractionated heparin, or enoxaparin. Patients with chest pain refractory to medical therapy, a TIMI score of ≥ 3, a troponin elevation, or ST changes > 1 mm should be given IV heparin and scheduled for angiography and possible revascularization (percutaneous coronary intervention [PCI] or CABG). TA B L E 2 . 1- 10 . TIMI Risk Score for Unstable Angina/NSTEMI CHARACTERISTICS POINT History Age ≥ 65 years 1 ≥ 3 CAD risk factors (premature family history, DM, 1 smoking, hypertension, ↑ cholesterol) Known CAD (stenosis > 50%) 1 ASA use in past 7 days 1 Presentation Severe angina (≥ 2 episodes within 24 hours) 1 ST deviation ≥ 0.5 mm 1 + cardiac marker 1 Risk score—total pointsa (0–7) a Higher-risk patients (risk score ≥ 3) benefit more from enoxaparin (vs. unfractionated heparin), glycoprotein IIb/IIIa inhibitors, and early angiography. CARDIOVASCULAR HIGH-YIELD FACTS IN 33 ST - EL E V A T IO N M Y O C A R D I A L I N F AR C TI ON (S TE M I) Defined as ST-segment elevations and cardiac enzyme release 2° to prolonged cardiac ischemia and necrosis. HISTORY/PE n n n n Presents with acute-onset substernal chest pain, commonly described as a pressure or tightness that can radiate to the left arm, neck, or jaw. Associated symptoms may include diaphoresis, shortness of breath, lightheadedness, anxiety, nausea/vomiting, and syncope. Physical examination may reveal arrhythmias, hypotension (cardiogenic shock), and evidence of new CHF. The best predictor of survival is left ventricular EF. DIAGNOSIS n n n n ECG will show ST-segment elevations or new LBBB. ST-segment depressions and dominant R waves in leads V1–V2 can also be reciprocal change indicating posterior wall infarct. Sequence of ECG changes: Peaked T waves → ST-segment elevation → Q waves → T-wave inversion → ST-segment normalization → T-wave normalization over several hours to days. Cardiac enzymes: Troponin I is the most sensitive and specific cardiac enzyme; CK-MB and the CK-MB/total CK ratio (CK index) are also regularly checked. Both troponin I and CK-MB can take up to 6 hours to rise following the onset of chest pain (see Figure 2.1-9). ST-segment abnormalities: n ST-segment elevation in leads II, III, and aVF is consistent with an inferior MI involving the RCA/PDA and LCA (see Figure 2.1-10). Obtain a right-sided ECG to look for ST elevations in the right ventricle. n ST-segment elevation in leads V1–V4 usually indicates an anterior MI involving the LAD and diagonal branches (see Figure 2.1-11). n ST-segment elevation in leads I, aVL, and V5–V6 points to a lateral MI involving the LCA. n ST-segment depression in leads V1–V2 (anterior leads) can be indicative of an acute transmural infarct in the posterior wall. Obtain posterior ECG leads V7–V9 to assess for ST-segment elevations. MONA Morphine Oxygen Nitrogen Aspirin KEY FACT Common causes of chest pain include GERD, angina, esophageal pain, musculoskeletal disorders (costochondritis, trauma), and pneumonia. 50 cTnI 15 10 MLC CK-MB LD1 5 Reference interval 0 FIGURE 2.1-9. 1 2 3 4 5 6 Days after onset of acute MI 7 10 Typical pattern of serum marker elevation after an acute MI. CK-MB = creatine kinase, MB isoenzyme; cTnI = cardiac troponin I; cTnT = cardiac troponin T; LD1 = lactate dehydrogenase isoenzyme 1; MLC = myosin light chain. (Reproduced with permission from Tintinalli JE et al. Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 6th ed. New York: McGraw-Hill, 2004, Fig. 49-1.) When your patient is MOANing from an MI, remember— cTnT Myoglobin Multiples of the upper reference limit 100 MNEMONIC A woman is found with pulseless electrical activity on hospital day 7 after suffering a lateral wall STEMI. The ACLS protocol is initiated. What is the next best step? 34 HIGH-YIELD FACTS IN CARDIOVASCULAR FIGURE 2.1-10. Inferior wall MI. In this patient with acute chest pain, the ECG demonstrated acute ST-segment elevation in leads II, III, and aVF with reciprocal ST-segment depression and T-wave flattening in leads I, aVL, and V4–V6. TREATMENT n n n n This patient has likely suffered a left ventricular free-wall rupture with acute cardiac tamponade. Emergent pericardiocentesis is the next best therapeutic and diagnostic step. Six key medications should be considered: ASA, β-blockers, clopidogrel, morphine, nitrates, and O2. If the patient is in heart failure or in cardiogenic shock, do not give β-blockers; instead, give ACEIs provided that the patient is not hypotensive. Emergent angiography and PCI should be performed; if possible, the patient should undergo PCI for the lesion thought to be responsible for the STEMI. If PCI cannot be performed within 90 minutes, there are no contraindications to thrombolysis (eg, a history of hemorrhagic stroke or recent ischemic stroke, severe heart failure, or cardiogenic shock), and the patient presents within 3 hours of chest pain onset, thrombolysis with tPA, reteplase, or streptokinase should be performed instead of PCI. Anterior wall MI. This patient presented with acute chest pain. The ECG showed acute ST-segment elevation in leads aVL and V1–V6, and hyperacute T waves. FIGURE 2.1-11. CARDIOVASCULAR n n PCI should be attempted immediately for the lesion thought to be responsible for STEMI; the patient is a candidate for CABG afterward. Long-term treatment includes ASA, ACEIs, β-blockers, high-dose statins, and clopidogrel (if PCI was performed). Modify risk factors with dietary changes, exercise, and tobacco cessation. COMPLICATIONS n n n n Arrhythmia is the most common complication following acute MI; lethal arrhythmia is the most frequent cause of death. Less common complications include reinfarction, left ventricular wall rupture, VSD, pericarditis, papillary muscle rupture (with mitral regurgitation), left ventricular aneurysm or pseudoaneurysm, and mural thrombi. Dressler’s syndrome, an autoimmune process occurring 2–10 weeks post-MI, presents with fever, pericarditis, pleural effusion, leukocytosis, and ↑ ESR. A timeline of common post-MI complications is as follows: n First day: Heart failure. n 2–4 days: Arrhythmia, pericarditis. n 5–10 days: Left ventricular wall rupture (acute pericardial tamponade causing electrical alternans, pulseless electrical activity), papillary muscle rupture (severe mitral regurgitation). n Weeks to months: Ventricular aneurysm (CHF, arrhythmia, persistent ST-segment elevation, mitral regurgitation, thrombus formation). HIGH-YIELD FACTS IN MNEMONIC Indications for CABG are UnLimiTeD: Unable to perform PCI (diffuse disease) Left main coronary artery disease Triple-vessel disease Depressed ventricular function Dyslipidemia Defined as a total cholesterol level > 200 mg/dL, LDL > 130 mg/dL, triglycerides > 150 mg/dL, and HDL < 40 mg/dL, all of which are risk factors for CAD. Etiologies include obesity, DM, alcoholism, hypothyroidism, nephrotic syndrome, hepatic disease, Cushing’s syndrome, OCP use, high-dose diuretic use, and familial hypercholesterolemia. HISTORY/PE n n Most patients have no specific signs or symptoms. Patients with extremely high triglyceride or LDL levels may have xanthomas (eruptive nodules in the skin over the tendons), xanthelasmas (yellow fatty deposits in the skin around the eyes), and lipemia retinalis (creamy appearance of retinal vessels). DIAGNOSIS n n n Conduct a fasting lipid profile for patients ≥ 35 years of age or in those ≥ 20 years of age with CAD risk factors, and repeat every 5 years or sooner if lipid levels are elevated. Total serum cholesterol > 200 mg/dL on 2 different occasions is diagnostic of hypercholesterolemia. LDL > 130 mg/dL or HDL < 40 mg/dL is diagnostic of dyslipidemia even if total serum cholesterol is < 200 mg/dL. TREATMENT n n Based on risk stratification (see Table 2.1-11). The first intervention should be a 12-week trial of diet and exercise in a patient with no known atherosclerotic vascular disease. Commonly used lipid-lowering agents are listed in Table 2.1-12. 35 KEY FACT Dyslipidemia: n LDL > 130 mg/dL or n HDL < 40 mg/dL 36 HIGH-YIELD FACTS IN TA B L E 2 . 1- 11 . CARDIOVASCULAR ATP III Guidelines for Risk Stratification of Dyslipidemia LDL TO START LIFESTYLE RISK CATEGORY LDL GOAL MODIFICATION LDL TO CONSIDER DRUG THERAPY < 100 mg/dL (or < 70) ≥ 100 mg/dL ≥ 100 mg/dL 2+ risk factorsb < 130 mg/dL ≥ 130 mg/dL ≥ 130 mg/dL 0–1 risk factorb < 160 mg/dL ≥ 160 mg/dL ≥ 190 mg/dL CAD or CAD risk equivalentsa a CAD risk equivalents include symptomatic carotid artery disease, peripheral arterial disease, AAA, and diabetes. Risk factors include cigarette smoking, hypertension, low HDL (< 40 mg/dL), a family history of premature CAD, and age (men > 45 years; women > 55 years). An HDL > 60 mg/dL counts as a “negative” risk factor and removes 1 risk factor from the total score. b Hypertension Defined as a systolic BP > 140 mm Hg and/or a diastolic BP > 90 mm Hg based on 3 measurements separated in time (see Table 2.1-13). Classified as 1° or 2°. 1 ° ( E S S E NTI AL) HYP E R TE NS I ON Hypertension with no identifiable cause. Represents 95% of cases of hypertension. Risk factors include a family history of hypertension or heart disease, a TA B L E 2 . 1- 12 . Lipid-Lowering Agents CLASS EXAMPLES MECHANISM OF ACTION HMG-CoA reductase Atorvastatin, simvastatin, Inhibit the rate-limiting inhibitors (statins) lovastatin, pravastatin, step in cholesterol rosuvastatin synthesis. Gemfibrozil ↑ lipoprotein lipase, Lipoprotein lipase EFFECT ON LIPID PROFILE ↓ LDL, ↓ triglycerides ↑ LFTs, myositis, warfarin potentiation. ↓ triglycerides, ↑ HDL GI upset, cholelithiasis, myositis, ↑ LFTs. leading to ↑ VLDL and stimulators (fibrates) SIDE EFFECTS triglyceride catabolism. Cholesterol Ezetimibe (Zetia) absorption inhibitors ↓ absorption of ↓ LDL Diarrhea, abdominal pain. Can cause angioedema. cholesterol at the small intestine brush border. Niacin Niaspan ↓ fatty acid release from ↑ HDL, ↓ LDL Skin flushing (can be adipose tissue; ↓ hepatic prevented with ASA), synthesis of LDL. paresthesias, pruritus, GI upset, ↑ LFTs. Bile acid resins ↓ LDL Constipation, GI upset, Cholestyramine, Bind intestinal bile acids, colestipol, colesevelam leading to ↓ bile acid LFT abnormalities, stores and ↑ catabolism myalgias. Can ↓ of LDL from plasma. absorption of other drugs from the small intestine. CARDIOVASCULAR HIGH-YIELD FACTS IN 37 high-sodium diet, smoking, obesity, ethnicity (blacks > whites), and advanced age. HISTORY/PE n n Hypertension is asymptomatic until complications develop. Patients should be evaluated for end-organ damage to the brain (stroke, dementia), eye (cotton-wool exudates, hemorrhage), heart (LVH), and kidney (proteinuria, chronic kidney disease). Renal bruits may signify renal artery stenosis as the cause of hypertension. A 40-year-old male presents for a routine examination. His examination is significant for a BP of 145/75 mm Hg but is otherwise unremarkable, as are his labs. What is the next best step? DIAGNOSIS Obtain a UA, BUN/creatinine, a CBC, and electrolytes to assess the extent of end-organ damage and possible 2° causes. Treatment of hypertension— TREATMENT n n n n n Rule out 2° causes of hypertension, particularly in patients with new-onset hypertension at extremes of age. Begin with lifestyle modifications. Weight loss is the single most effective lifestyle modification. The BP goal in otherwise healthy patients is < 140/< 90 mm Hg. The goal in diabetics or patients with renal disease with proteinuria is < 130/< 80 mm Hg. Diuretics, ACEIs, and β-blockers have been shown to ↓ mortality in uncomplicated hypertension. They are first-line agents unless a comorbid condition requires another medication (see Table 2.1-14). Periodically test for end-organ complications, including renal complications (BUN, creatinine, urine protein-to-creatinine ratio) and cardiac complications (ECG evidence of hypertrophy). 2 ° H Y P E R T E N S IO N Hypertension 2° to an identifiable organic cause. See Table 2.1-15 for the diagnosis and treatment of common causes. TA B L E 2 . 1- 13 . MNEMONIC ABCD ACEIs/ARBs β-blockers CCBs Diuretics MNEMONIC Causes of 2° hypertension— CHAPS Cushing’s syndrome Hyperaldosteronism (Conn’s syndrome) Aortic coarctation Pheochromocytoma Stenosis of renal arteries JNC-7 Classification and Management of Hypertension BP CLASSIFICATION Normal SYSTOLIC BP DIASTOLIC BP LIFESTYLE (mm Hg) (mm Hg) MODIFICATION DRUG THERAPY WITH NO COMORBIDITIES < 120 and < 80 Encourage Prehypertension 120–139 or 80–89 Yes No antihypertensive drug indicated. Stage 1 hypertension 140–159 or 90–99 Yes Thiazide diuretics for most patients; ACEIs, ARBs, β-blockers, CCBs, or a combination may be considered. Stage 2 hypertension ≥ 160 or ≥ 100 Yes Two-drug combination for most patients (usually a thiazide diuretic plus an ACEI, an ARB, a β-blocker, or a CCB). 38 HIGH-YIELD FACTS IN CARDIOVASCULAR TA B L E 2 . 1- 14 . With a single BP recording and no evidence of end-organ damage, the next best step should consist of a repeat BP measurement at the end of the examination with a return visit if BP is still high. TA B L E 2 . 1- 15 . Treatment of 1° Hypertension in Specific Populations POPULATION AGENTS Uncomplicated Diuretics, β-blockers, ACEIs. CHF Diuretics, β-blockers, ACEIs, ARBs, aldosterone antagonists. Diabetes Diuretics, β-blockers, ACEIs, ARBs, CCBs. Post-MI β-blockers, ACEIs, ARBs, aldosterone antagonists. Chronic kidney disease ACEIs, ARBs. BPH Diuretics, α1-adrenergic blockers. Isolated systolic hypertension Diuretics, ACEIs, CCBs (dihydropyridines). Common Causes of 2° Hypertension ETIOLOGY 1° renal disease DESCRIPTION Often unilateral renal parenchymal disease. MANAGEMENT Treat with ACEIs, which slow the progression of renal disease. Renal artery stenosis Especially common in patients < 25 and > 50 years Diagnose with MRA or renal artery Doppler ultrasound. of age with recent-onset hypertension. Etiologies May be treated with angioplasty or stenting. Consider include fibromuscular dysplasia (younger patients) and ACEIs in unilateral disease. (In bilateral disease, atherosclerosis (older patients). ACEIs can accelerate kidney failure by preferential vasodilation of the efferent arteriole.) Open surgery is a second option if angioplasty is not effective or feasible. OCP use Common in women > 35 years of age, obese women, Discontinue OCPs (effect may be delayed). and those with long-standing use. Pheochromocytoma An adrenal gland tumor that secretes epinephrine Diagnose with urinary metanephrines and and norepinephrine, leading to episodic headache, catecholamine levels or plasma metanephrine. sweating, and tachycardia. Surgical removal of tumor after treatment with both α-blockers and β-blockers. Conn’s syndrome Most often 2° to an aldosterone-producing adrenal Metabolic workup with plasma aldosterone and renin (hyperaldosteronism) adenoma. Causes the triad of hypertension, level; ↑ aldosterone and ↓ renin levels suggest 1° unexplained hypokalemia, and metabolic alkalosis. hyperaldosteronism. Surgical removal of tumor. Due to an ACTH-producing pituitary tumor, an ectopic Surgical removal of tumor; removal of exogenous ACTH-secreting tumor, or cortisol secretion by an steroids. Cushing’s syndrome adrenal adenoma or carcinoma. Also due to exogenous steroid exposure. (See the Endocrinology chapter for more details.) Coarctation of the aorta See the Pediatrics chapter. Surgical repair. CARDIOVASCULAR HIGH-YIELD FACTS IN 39 HY PE R T E N S I V E CR IS E S A spectrum of clinical presentations in which elevated BPs lead to end-organ damage. HISTORY/PE Present with end-organ damage revealed by renal disease, chest pain (ischemia or MI), back pain (aortic dissection), or changes in mental status (hypertensive encephalopathy). DIAGNOSIS n n n Hypertensive urgency: Elevated BP with mild to moderate symptoms (headache, chest pain) without end-organ damage. Hypertensive emergency: Elevated BP with signs or symptoms of impending end-organ damage such as acute kidney injury, intracranial hemorrhage, papilledema, or ECG changes suggestive of ischemia or pulmonary edema. Malignant hypertension: Diagnosed on the basis of progressive renal failure and/or encephalopathy with papilledema. KEY FACT Hypertensive crises are diagnosed on the basis of the extent of end-organ damage, not BP measurement. TREATMENT n n Hypertensive urgencies: Can be treated with oral antihypertensives (eg, β-blockers, clonidine, ACEIs) with the goal of gradually lowering BP over 24–48 hours (see Table 2.1-16). Hypertensive emergencies: Treat with IV medications (labetalol, nitroprusside, nicardipine) with the goal of lowering mean arterial pressure by no more than 25% over the first 2 hours to prevent cerebral hypoperfusion or coronary insufficiency. Pericardial Disease Results from acute or chronic pericardial insults; may lead to pericardial effusion. PER I CA R D IT IS Defined as inflammation of the pericardial sac. It can compromise cardiac output via tamponade or constrictive pericarditis. Most commonly idiopathic, although known etiologies include viral infection, TB, SLE, uremia, drugs, radiation, and neoplasms. May also occur after MI (either within days after MI or as a delayed phenomenon, ie, Dressler’s syndrome) or open heart surgery. MNEMONIC Causes of pericarditis— CARDIAC RIND Collagen vascular disease Aortic dissection Radiation Drugs Infections Acute renal failure Cardiac (MI) Rheumatic fever Injury Neoplasms Dressler’s syndrome HISTORY/PE n n n May present with pleuritic chest pain, dyspnea, cough, and fever. Chest pain tends to worsen in the supine position and with inspiration. Examination may reveal a pericardial friction rub. Elevated JVP and pulsus paradoxus (a ↓ in systolic BP > 10 mm Hg on inspiration) can be present with tamponade. DIAGNOSIS n n n CXR, ECG, and echocardiogram to rule out MI and pneumonia. ECG changes include diffuse ST-segment elevation and PR-segment depressions followed by T-wave inversions (see Figure 2.1-12). Pericardial thickening or effusion may be evident on echocardiography. A 20-year-old male presents with an initial BP of 150/85 mm Hg, and repeat measurement yields 147/85 mm Hg. The patient’s potassium level is 3.2 mg/dL. What is the next appropriate diagnostic step? 40 HIGH-YIELD FACTS IN TA B L E 2 . 1- 16 . CARDIOVASCULAR Major Classes of Antihypertensive Agents CLASS Diuretics AGENTS MECHANISM OF ACTION Thiazide, loop, K+ sparing SIDE EFFECTS ↓ extracellular fluid volume and Hypokalemia (not with K+ sparing), thereby ↓ vascular resistance. hyperglycemia, hyperlipidemia, hyperuricemia, azotemia. β-blockers Propranolol, metoprolol, nadolol, ↓ cardiac contractility and renin Bronchospasm (in severe active atenolol, timolol, carvedilol, release. asthma), bradycardia, CHF exacerbation, impotence, fatigue, labetalol depression. ACEIs Captopril, enalapril, fosinopril, Block aldosterone formation, Cough, rashes, leukopenia, benazepril, lisinopril reducing peripheral resistance and hyperkalemia. salt/water retention. ARBs Losartan, valsartan, irbesartan Block aldosterone effects, reducing Rashes, leukopenia, and peripheral resistance and salt/water hyperkalemia but no cough. retention. CCBs Dihydropyridines (nifedipine, ↓ smooth muscle tone and cause felodipine, amlodipine), vasodilation; may also ↓ cardiac nondihydropyridines (diltiazem, output. flushing, peripheral edema. Nondihydropyridines: ↓ contractility. verapamil) Vasodilators Dihydropyridines: Headache, ↓ peripheral resistance by dilating Hydralazine, minoxidil arteries/arterioles. Hydralazine: Headache, lupus-like syndrome. Minoxidil: Orthostasis, hirsutism. α1-adrenergic Prazosin, terazosin, Cause vasodilation by blocking blockers phenoxybenzamine actions of norepinephrine on Orthostatic hypotension. vascular smooth muscle. Centrally acting Methyldopa, clonidine adrenergic agonists Inhibit the sympathetic nervous Somnolence, orthostatic system via central α2-adrenergic hypotension, impotence, rebound receptors. hypertension. I aVR II III V1 V4 aVL V2 V5 aVF V3 V6 PR ST ST PR A hyperaldosteronism workup with serum aldosterone and renin levels is an appropriate next diagnostic step. Acute pericarditis. Diffuse ST-segment elevations in multiple leads not consistent with any discrete coronary vascular territory and PR-segment depressions. (Reproduced FIGURE 2.1-12. with permission from Fauci AS et al. Harrison’s Principles of Internal Medicine, 17th ed. New York: McGraw-Hill, 2008, Fig. 232-1.) CARDIOVASCULAR HIGH-YIELD FACTS IN 41 TREATMENT n n Address the underlying cause (eg, corticosteroids/immunosuppressants for SLE, dialysis for uremia) or symptoms (eg, ASA for post-MI pericarditis, ASA/NSAIDs for viral pericarditis). Avoid corticosteroids within a few days after MI, as they can predispose to ventricular wall rupture. Pericardial effusions without symptoms can be monitored, but evidence of tamponade requires pericardiocentesis with continuous drainage as needed. CA R D I A C T A M PO N A D E Defined as excess fluid in the pericardial sac, leading to compromised ventricular filling and ↓ cardiac output. The rate of fluid formation is more important than the size of the effusion. Risk factors include pericarditis, malignancy, SLE, TB, and trauma (commonly stab wounds medial to the left nipple). HISTORY/PE n n KEY FACT Beck’s triad can diagnose acute cardiac tamponade: n JVD n Hypotension n Distant heart sounds Presents with fatigue, dyspnea, anxiety, tachycardia, and tachypnea that can rapidly progress to shock and death. Examination of a patient with acute tamponade may reveal Beck’s triad (hypotension, distant heart sounds, and JVD), a narrow pulse pressure, pulsus paradoxus, and Kussmaul’s sign (JVD on inspiration). DIAGNOSIS n n n Echocardiogram shows right atrial and right ventricular diastolic collapse. CXR may show an enlarged, globular, water-bottle-shaped heart with a large effusion (see Figure 2.1-13). If present on ECG, electrical alternans is diagnostic of a large pericardial effusion. TREATMENT n n n Aggressive volume expansion with IV fluids. Urgent pericardiocentesis (aspirate will be nonclotting blood). Decompensation may warrant pericardial window. FIGURE 2.1-13. Water-bottleshaped heart seen on CXR with pericardial effusion. (Reproduced with permission from Chen MY et al. Basic Radiology, 2nd ed. New York: McGraw-Hill, 2011, Fig. 3-26.) Valvular Heart Disease Until recently, rheumatic fever (which affects the mitral valve more often than the aortic valve) was the most common cause of valvular heart disease in U.S. adults; the leading cause is now mechanical degeneration. Subtypes are listed in Table 2.1-17 along with their etiologies, presentation, diagnosis, and treatment. Vascular Disease AOR T IC A N E U R Y S M Defined as > 50% dilatation of all 3 layers of the aortic wall. Aortic aneurysms are most commonly associated with atherosclerosis. Most are abdominal, and > 90% originate below the renal arteries. 42 HIGH-YIELD FACTS IN T A B L E 2 . 1 - 1 7. Types of Valvular Heart Disease TYPE Aortic stenosis CARDIOVASCULAR ETIOLOGY HISTORY May be asymptomatic for Most often seen in the elderly. Unicuspid and bicuspid PE: Pulsus parvus et tardus years despite significant (weak, delayed carotid stenosis. upstroke) and a single Once symptomatic, usually valves can lead to EXAM/DIAGNOSIS Aortic valve replacement. or paradoxically split S2 symptoms in childhood progresses from angina to sound; systolic murmur and adolescence. syncope to CHF to death radiating to the carotids. within 5 years. TREATMENT Dx: Echocardiography. Sx (also indications for valve replacements): ACS—Angina, CHF, Syncope. Aortic regurgitation Acute: Rapid onset of Acute: Infective PE: Blowing diastolic Vasodilator therapy endocarditis, aortic pulmonary congestion, murmur at the left sternal (dihydropyridines or dissection, chest trauma. cardiogenic shock, and border, mid-diastolic ACEIs) for isolated severe dyspnea. rumble (Austin Flint aortic regurgitation until murmur), and midsystolic symptoms become severe apical murmur. enough to warrant valve Chronic: Valve malformations, rheumatic Chronic: Slowly progressive fever, connective tissue onset of dyspnea on disorders. exertion, orthopnea, and PND. Widened pulse pressure replacement. causes de Musset’s sign (head bob with heartbeat), Corrigan’s sign (water-hammer pulse), and Duroziez’s sign (femoral bruit). Dx: Echocardiography. Mitral valve The most common etiology Symptoms range from stenosis continues to be rheumatic dyspnea, orthopnea, fever. and PND to infective endocarditis and PE: Opening snap and mid- Antiarrhythmics diastolic murmur at the (β-blockers, digoxin) for apex; pulmonary edema. symptomatic relief; mitral Dx: Echocardiography. balloon valvotomy and valve replacement are arrhythmias. effective for severe cases. Mitral valve Primarily 2° to rheumatic Patients present with regurgitation fever or chordae tendineae dyspnea, orthopnea, and rupture after MI. Infective fatigue. endocarditis. PE: Holosystolic murmur radiating to the axilla. Antiarrhythmics if necessary (AF is common with LAE; Dx: Echocardiography will nitrates and diuretics to demonstrate regurgitant ↓ preload). Valve repair flow; angiography can or replacement for severe assess the severity of cases. disease. HISTORY/PE n n Usually asymptomatic and discovered incidentally on examination or radiologic study. Risk factors include hypertension, high cholesterol, other vascular disease, a # family history, smoking, gender (males > females), and age. CARDIOVASCULAR Examination demonstrates a pulsatile abdominal mass or abdominal bruits. Ruptured aneurysm leads to hypotension and severe, tearing abdominal pain that radiates to the back. n n DIAGNOSIS All men 65–75 years of age with a history of smoking should be screened once by ultrasound for AAA (see Figure 2.1-14). Abdominal ultrasound is used for diagnosis or to follow an aneurysm over time. CT with contrast may be useful to determine the precise anatomy. n n n HIGH-YIELD FACTS IN 43 A 70-year-old male with hypertension presents for a routine appointment. He quit smoking 20 years ago but has a 20-pack-year history. What screening, if any, is indicated? TREATMENT In asymptomatic patients, monitoring is appropriate for lesions < 5 cm. Surgical repair is indicated if the lesion is > 5.5 cm (abdominal), > 6 cm (thoracic), or smaller but rapidly enlarging. Emergent surgery for symptomatic or ruptured aneurysms. n n n AOR T IC D IS S E C T I O N KEY FACT Defined as a transverse tear in the intima of a vessel that results in blood entering the media, creating a false lumen and leading to a hematoma that propagates longitudinally. Most commonly 2° to hypertension. The most common sites of origin are above the aortic valve and distal to the left subclavian artery. Most often occurs at 40–60 years of age, with a greater frequency in males than in females. Aortic aneurysm is most often associated with atherosclerosis, whereas aortic dissection is commonly linked to hypertension. HISTORY/PE n n Presents with sudden tearing/ripping pain in the anterior chest (ascending) or back (descending). Patients are typically hypertensive. If a patient is hypotensive, consider pericardial tamponade, hypovolemia from blood loss, or other cardiopulmonary etiologies. Ao A B FIGURE 2.1-14. Abdominal aortic aneurysm. (A) Ultrasound image of an AAA (Ao = aorta). (B) Transaxial image from a contrastenhanced CT showing an aneurysm with extensive mural thrombus (arrowhead). (Image A reproduced with permission from Tintinalli JE et al. Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 6th ed. New York: McGraw-Hill, 2004, Fig. 58-2. Image B reproduced with permission from Doherty GM. Current Diagnosis & Treatment: Surgery, 13th ed. New York: McGraw-Hill, 2010, Fig. 34-16.) 44 HIGH-YIELD FACTS IN CARDIOVASCULAR n n The United States Preventive Services Task Force (USPSTF) guidelines recommend one-time screening for AAA by ultrasound in males ages 65–75 who have ever smoked. n n Signs of pericarditis or pericardial tamponade may be seen. Asymmetric pulses and BP measurements are indicative of aortic dissection. A murmur of aortic regurgitation may be heard if the aortic valve is involved with a proximal dissection. Neurologic deficits may be seen if the aortic arch or spinal arteries are involved. DIAGNOSIS n KEY FACT Ascending aortic dissections are surgical emergencies; descending dissections are still emergencies but can often be treated medically. n n CT angiography is the gold standard of imaging. MRA can be used if contrast CT is contraindicated. TEE can provide details of the thoracic aorta, the proximal coronary arteries, the origins of arch vessels, the presence of a pericardial effusion, and aortic valve integrity. The Stanford system classifies any dissection proximal to the left subclavian artery as type A and all others as type B (see Figure 2.1-15). TREATMENT n n Monitor and medically manage BP and heart rate as necessary. Avoid thrombolytics. Begin β-blockade before starting vasodilators to prevent reflex tachycardia. If the dissection involves the ascending aorta, it is a surgical emergency; descending dissections can often be managed with BP and heart rate control. KEY FACT Virchow’s triad: (1) hemostasis, (2) trauma (endothelial damage), (3) hypercoagulability. DE E P VE NOU S THR OM BOS I S ( DVT) Clot formation in the large veins of the extremities or pelvis. The classic Virchow’s triad of risk factors includes venous stasis (eg, from plane flights, bed rest, or incompetent venous valves in the lower extremities), endothelial A B Aortic dissection. Stanford classification of aortic dissections. Shown are (A) proximal or ascending types and (B) descending type. (Reproduced with permission from Doherty GM. FIGURE 2.1-15. Current Diagnosis & Treatment: Surgery, 13th ed. New York: McGraw-Hill, 2010, Fig. 19-16.) CARDIOVASCULAR HIGH-YIELD FACTS IN 45 Suspect DVT or PE Assess clinical likelihood DVT PE Not low Low D-dimer Not high High D-dimer Normal High Normal High No DVT Imaging test needed No PE Imaging test needed FIGURE 2.1-16. Algorithm for diagnostic imaging of DVT and PE. (Reproduced with permission from Fauci AS et al. Harrison’s Principles of Internal Medicine, 17th ed. New York: McGraw-Hill, 2008, Fig. 256-1.) trauma (eg, surgery, injury to the lower extremities), and hypercoagulable states (eg, malignancy, pregnancy, OCP use). HISTORY/PE n n Presents with unilateral lower extremity pain and swelling. Homans’ sign is calf tenderness with passive foot dorsiflexion (poor sensitivity and specificity for DVT). DIAGNOSIS Doppler ultrasound; a spiral CT or V/Q scan may be used to evaluate for PE (see Figure 2.1-16). TREATMENT n n n Anticoagulate with IV unfractionated heparin or SQ low-molecular-weight heparin (LMWH) followed by PO warfarin for a total of 3–6 months. In patients with contraindications for anticoagulation, IVC filters should be placed. Hospitalized patients should receive DVT prophylaxis consisting of exercise as tolerated, anti-thromboembolic stockings, and SQ unfractionated heparin or LMWH. PER I PH E R A L A R T E R IA L D IS E A S E Defined as a restriction of the blood supply to the extremities by atherosclerotic plaque. The lower extremities are most commonly affected. Clinical manifestations depend on the vessels involved, the extent and rate of obstruction, and the presence of collateral blood flow. HISTORY/PE n Presents with intermittent claudication (reproducible leg pain that occurs with walking and is relieved with rest). As the disease progresses, pain occurs at rest and affects the distal extremities. Dorsal foot ulcerations may develop 2° to poor perfusion. A painful, cold, numb foot is characteristic of critical limb ischemia. KEY FACT A " D-dimer test can be used to rule out the possibility of PE in low-risk patients. 46 HIGH-YIELD FACTS IN MNEMONIC The 6 P’s of acute ischemia: Pain Pallor Paralysis Pulse deficit Paresthesias Poikilothermia CARDIOVASCULAR n n n n KEY FACT Aortoiliac disease: Buttock claudication, ↓ femoral pulses, male impotence (Leriche’s syndrome). Femoropopliteal disease: Calf claudication; ↓ pulses below the femoral artery. Acute ischemia: n Most often caused by embolization from the heart; acute occlusions commonly occur at bifurcations distal to the last palpable pulse (see mnemonic). n May also be 2° to cholesterol atheroembolism (“blue toe syndrome”). Chronic ischemia: Lack of blood perfusion leads to muscle atrophy, pallor, cyanosis, hair loss, and gangrene/necrosis. DIAGNOSIS n ABI = Pleg / Parm. ABI < 0.4 with rest pain. n n Measurement of ankle and brachial systolic BP (ankle-brachial index, or ABI) can provide objective evidence of atherosclerosis (rest pain usually occurs with an ABI < 0.4). A very high ABI can indicate calcification of the arteries. Doppler ultrasound helps identify stenosis and occlusion. Normal ankle Doppler readings are > 90% of brachial readings. Arteriography and digital subtraction angiography are necessary for surgical evaluation. TREATMENT n n n n Control underlying conditions (DM, tobacco) and institute careful hygiene and foot care. Exercise helps develop collateral circulation. ASA, cilostazol, and thromboxane inhibitors may improve symptoms; anticoagulants may prevent clot formation. Angioplasty and stenting have a variable success rate that is dependent on the area of occlusion. Surgery (arterial bypass) or amputation can be employed when conservative treatment fails. LYM P HEDE M A A disruption of the lymphatic circulation that results in peripheral edema and chronic infection of the extremities. It is often a complication of surgery involving lymph node dissection. In underdeveloped countries, parasitic infection can lead to lymphatic obstruction. Congenital malformations of the lymphatic system (eg, Milroy’s disease) can present with lymphedema in childhood. HISTORY/PE n n n Postmastectomy patients present with unexplained swelling of the upper extremity. Immigrants present with progressive swelling of the lower extremities bilaterally with no cardiac abnormalities (ie, filariasis). Children present with progressive, bilateral swelling of the extremities. DIAGNOSIS Diagnosis is clinical. Rule out other causes of edema, such as cardiac and metabolic disorders. TREATMENT n Directed at symptom management, including exercise, massage therapy, and pressure garments to mobilize and limit fluid accumulation. CARDIOVASCULAR n n HIGH-YIELD FACTS IN 47 Diuretics are ineffective and relatively contraindicated. Maintain vigilance for cellulitis with prompt gram-# antibiotic coverage for infection. Syncope A sudden, temporary loss of consciousness and postural tone 2° to cerebral hypoperfusion. Etiologies are either cardiac or noncardiac: n n Cardiac: Valvular lesions, arrhythmias, PE, cardiac tamponade, aortic dissection. Noncardiac: Orthostatic/hypovolemic hypotension, neurologic (TIA, stroke), metabolic abnormalities, neurocardiogenic syndromes (eg, vasovagal/micturition syncope), psychiatric. HISTORY/PE n n Triggers, prodromal symptoms, and associated symptoms should be investigated. Cardiac causes of syncope are typically associated with very brief or absent prodromal symptoms, a history of exertion, lack of association with changes in position, and/or a history of cardiac disease. DIAGNOSIS Depending on the suspected etiology, Holter monitors or event recorders (arrhythmias), echocardiograms (structural abnormalities), stress tests (ischemia), and tilt-table testing (neurally mediated syncope) can be useful. TREATMENT Tailored to the etiology; commonly β-blockers for rate control. KEY FACT Cardiac syncope is associated with 1-year sudden cardiac death rates of up to 40%. 48 HIGH-YIELD FACTS IN CARDIOVASCULAR NOTES HIGH-YIELD FACTS IN DERMATOLOGY Layers of the Skin 50 Common Terminology 50 Allergic and Immune-Mediated Disorders HYPERSENSITIVITY REACTIONS 50 50 Ischemic Disorders 70 DECUBITUS ULCERS 70 GANGRENE 70 Miscellaneous Skin Disorders 71 ATOPIC DERMATITIS (ECZEMA) 50 ACANTHOSIS NIGRICANS CONTACT DERMATITIS 53 LICHEN PLANUS 71 SEBORRHEIC DERMATITIS 54 ROSACEA 71 PSORIASIS 55 PITYRIASIS ROSEA 71 VITILIGO 72 Neoplasms 72 URTICARIA (HIVES) 56 71 DRUG ERUPTION 57 ERYTHEMA MULTIFORME 57 SEBORRHEIC KERATOSIS STEVENS-JOHNSON SYNDROME/TOXIC EPIDERMAL NECROLYSIS 58 ACTINIC KERATOSIS 73 ERYTHEMA NODOSUM 59 SQUAMOUS CELL CARCINOMA 73 BULLOUS PEMPHIGOID/PEMPHIGUS VULGARIS 59 BASAL CELL CARCINOMA 74 59 MELANOMA 74 59 KAPOSI’S SARCOMA 75 63 MYCOSIS FUNGOIDES (CUTANEOUS T-CELL LYMPHOMA) 75 Infectious Disease Manifestations VIRAL DISEASES BACTERIAL INFECTIONS FUNGAL INFECTIONS 67 PARASITIC INFECTIONS 69 72 49 50 HIGH-YIELD FACTS IN DERMATOLOGY Layers of the Skin The skin consists of 3 layers: the epidermis, the dermis, and subcutaneous tissue (see Figure 2.2-1). Common Terminology Table 2.2-1 outlines terms frequently used to describe common manifestations of dermatologic disease. Allergic and Immune-Mediated Disorders HYP E R S E NS I TI VI TY R E AC TI ONS Table 2.2-2 outlines the types and mechanisms of hypersensitivity reactions. ATOP I C DE R M ATI TI S ( EC ZE M A) A relapsing inflammatory skin disorder that is common in infancy and presents differently in different age groups. It is characterized by pruritus leading to lichenification (see Figure 2.2-2). HISTORY/PE n n Patients are at ↑ risk of 2° bacterial (S aureus) and viral (HSV or molluscum) infection. Triggers include climate, food, contact with allergens or physical or chemical irritants, and emotional factors. Epidermis Dermal papillae Dermis Arrector pili Sebaceous gland Sweat gland Hair follicle Hair bulb FIGURE 2.2-1. Vein Artery Nerve Subcutaneous tissue Layers of the skin. (Adapted with permission from Hardman JG et al. Goodman and Gilman’s The Pharmacological Basis of Therapeutics, 10th ed. New York: McGraw-Hill, 2001: 1805.) DERMATOLOGY TA B L E 2 . 2 - 1 . HIGH-YIELD FACTS IN 51 Common Terms Used to Describe Skin Lesions TERM DEFINITION Macule A flat lesion that differs in color from surrounding skin (< 1 cm in diameter). Papule An elevated solid lesion that is generally small (< 5 mm in diameter). Patch A small, circumscribed area differing in color from the surrounding surface APPEARANCE See Macule above. (> 1 cm in diameter). Plaque An elevated solid lesion (> 5 mm in diameter). Cyst An epithelial-lined sac containing fluid or semisolid material. Vesicle A fluid-filled, very small (< 5 mm), elevated lesion. Bulla A large vesicle (> 5 mm). Wheal (or hive) An area of localized edema that follows vascular leakage and usually See Papule above. See Vesicle above. disappears within hours. Erosion A circumscribed, superficial depression resulting from the loss of some or all of the epidermis. (continues) 52 HIGH-YIELD FACTS IN TA B L E 2 . 2 - 1 . DERMATOLOGY Common Terms Used to Describe Skin Lesions (continued) TERM Ulcer DEFINITION APPEARANCE A deeper depression resulting from destruction of the epidermis and upper dermis. Scale Abnormal shedding or accumulation of stratum corneum in flakes. Crust A hardened deposit of dried serum, blood, or purulent exudates. Lichenification Thickening and hardening of the skin with accentuation of normal skin markings. Scar A healing defect of the dermis (the epidermis alone heals without a scar). (Images adapted with permission from LeBlond RF et al. DeGowin’s Diagnostic Examination, 9th ed. New York: McGraw-Hill, 2009, Figs. 6-5 through 6-11.) KEY FACT n Atopic dermatitis is commonly associated with asthma and allergic rhinitis. KEY FACT Erythema toxicum neonatorum typically begins 1–3 days after delivery and resembles eczema, presenting with red papules, pustules, and/or vesicles with surrounding erythematous halos. ↑ eosinophils are present in the pustules or vesicles. This benign rash usually resolves in 1–2 weeks with no treatment. Clinical manifestations by age group are as follows: n Infants: Erythematous, edematous, weeping, pruritic papules and plaques on the face, scalp, and extensor surfaces of the extremities. The diaper area is often spared. n Children: Dry, scaly, pruritic, excoriated papules and plaques in the flexural areas and neck. n Adults: Lichenification and dry, fissured skin in a flexural distribution. Often there is hand or eyelid involvement. DIAGNOSIS Diagnosis is clinical. Patients may have mild eosinophilia and ↑ IgE. TREATMENT n n n Prophylactic measures include use of nondrying soaps, application of moisturizers, and avoidance of known triggers. Topical corticosteroids are the first-line therapy. Topical immunomodulators (eg, tacrolimus, pimecrolimus) are useful for moderate to severe eczema if the patient is > 2 years of age. Topical corticosteroids should not be used for longer than 2–3 weeks to avoid decreasing the integrity of the skin. DERMATOLOGY TA B L E 2 . 2 - 2 . HIGH-YIELD FACTS IN 53 Types and Mechanisms of Hypersensitivity Reactions DESCRIPTION MECHANISM COMMENTS EXAMPLES TYPE I Anaphylactic and Antigen cross-links IgE on First and Fast (like anaphylaxis). Anaphylaxis, asthma, urticarial atopic presensitized mast cells and Types I, II, and III are all antibody drug reactions, local wheal and basophils, triggering the release of mediated. flare. vasoactive amines like histamine. Reaction develops rapidly as a result of preformed antibody. TYPE II Cytotoxic IgM and IgG bind to antigen on Cy-2-toxic. Autoimmune hemolytic an “enemy” cell, leading to lysis by Antibody and complement lead to anemia, erythroblastosis fetalis, complement or phagocytosis. membrane attack complex (MAC). Goodpasture’s syndrome, rheumatic fever. TYPE III Immune complex Antigen-antibody complexes activate complement, which attracts PMNs; PMNs release lysosomal enzymes. Imagine an immune complex as 3 Polyarteritis nodosa, immune things stuck together: antigen- complex glomerulonephritis, SLE, antibody-complement. rheumatoid arthritis. Includes many glomerulonephritides and vasculitides. Serum sickness Antibodies to the foreign proteins Most serum sickness is now caused are produced in ~ 5 days. Immune by drugs (not serum). Fever, complexes form and are deposited urticaria, arthralgias, proteinuria, in membranes, where they lead to and lymphadenopathy occur 5–10 tissue damage by fixing complement. Drug reaction. days after antigen exposure. More common than Arthus reaction. Arthus reaction A local reaction to antigen by Arthus reaction occurs rarely 4–12 preformed antibodies characterized hours after vaccination. Hypersensitivity pneumonitis. by vascular necrosis and thrombosis. TYPE IV Delayed (cell- Sensitized T lymphocytes 4th and last—delayed. Cell TB skin tests, transplant rejection, mediated) type encounter antigen and then release mediated, not antibody mediated; contact dermatitis. lymphokines (leading to macrophage therefore, it is not transferable by activation). serum. CO N T A CT D E R M A T IT IS A type IV hypersensitivity reaction that results from contact with an allergen to which the patient has previously been exposed and sensitized. More common in adults than in children. An infant with a history of eczema treated with corticosteroids is brought in for a new-onset rash and fever. Physical examination reveals grouped vesicles involving eczematous areas of the infant’s extremities and face. What is the appropriate therapy? 54 HIGH-YIELD FACTS IN DERMATOLOGY Atopic dermatitis. Lichenification, excoriations, and ill-defined, scaling erythema are characteristic. (Reproduced with permission from Tintinalli JE et al. Tintinalli’s Emergency Medicine: A FIGURE 2.2-2. Comprehensive Study Guide, 7th ed. New York: McGraw-Hill, 2011, Fig. 249-10.) HISTORY/PE n n n n FIGURE 2.2-3. Contact dermatitis. Shown are erythematous papules and vesicles with serous weeping localized to areas of contact with the offending agent. (Reproduced with permission from Hurwitz RM. Pathology of the Skin: Atlas of Clinical-Pathological Commonly presents with pruritus and rash, but can also present with edema, fever, and lymphadenopathy. Frequently implicated allergens include poison ivy, poison oak, nickel, soaps, detergents, cosmetics, and rubber products containing latex (eg, gloves and elastic bands in clothing). The overall shape of the rash often mimics that of the exposing object (see Figure 2.2-3), and characteristic distributions of involvement are often seen where makeup, clothing, perfume, nickel jewelry, and plants come into contact with the skin. The rash can spread over the body via transfer of allergen by the hands or via circulating T lymphocytes. Patients are at ↑ risk of 2° infection. DIAGNOSIS Diagnosed by clinical impression. Patch testing can be used to establish the causative allergen after the acute-phase rash has been treated. TREATMENT Correlation, 2nd ed. Stamford, CT: Appleton & Lange, n 1998: 3.) n Prophylaxis consists of avoidance of the offending allergen. Treat with topical or systemic corticosteroids as needed and with cool, wet compresses to soothe crusted lesions of the skin. SE BOR R HE I C DE R M ATI TI S This infant has eczema herpeticum, a medical emergency that is due to the propensity for HSV infection to spread systemically, potentially affecting the brain. IV acyclovir must be started immediately! A common disease that may be caused by Pityrosporum ovale, a generally harmless yeast found in sebum and hair follicles. It has a predilection for areas with oily skin. DERMATOLOGY HIGH-YIELD FACTS IN 55 FIGURE 2.2-4. Seborrheic dermatitis (cradle cap) in an infant. Note the yellow, scaly crust present on the infant’s scalp with an area of erosion. (Reproduced with permission from Tintinalli JE et al. Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 7th ed. New York: McGraw-Hill, 2011, Fig. 134-25.) HISTORY/PE n n The appearance of the rash varies with age: n Infants: Presents as a severe, red diaper rash with yellow scale, erosions, and blisters. A thick crust (“cradle cap”) may be seen on the scalp (see Figure 2.2-4). n Children/adults: Red, scaly patches are seen around the ears, eyebrows, nasolabial fold, midchest, and scalp. The rash is more localized and less dramatic than that seen in infants. Patients with HIV/AIDS and Parkinson’s disease can develop severe seborrheic dermatitis. DIAGNOSIS Diagnosed by clinical impression. Rule out contact dermatitis and psoriasis. TREATMENT Treatment consists of selenium sulfide or zinc pyrithione shampoos for the scalp, and topical antifungals and/or topical corticosteroids for other areas in adults. Cradle cap often resolves with routine bathing and application of emollients in infants. PSO R I A S I S A T-cell-mediated inflammatory dermatosis characterized by erythematous plaques with silvery scales (see Figure 2.2-5A) due to dermal inflammation and epidermal hyperplasia. The condition usually starts in puberty or young adulthood. HISTORY/PE n n Lesions are classically found on the extensor surfaces, including the elbows, knees, scalp, and lumbosacral regions. Lesions may initially appear very small but may become confluent. The patient’s nails are frequently affected as well; psoriatic nails feature pitting, “oil spots,” and onycholysis, or lifting of the nail plate (see Figure 2.2-5B). A 23-year-old female is seen for an itchy, linear rash on her right leg. She returned from a camping trip 4 days ago and denies using any new makeup, clothing, or jewelry. What features of this presentation favor a contact dermatitis? 56 HIGH-YIELD FACTS IN DERMATOLOGY A B FIGURE 2.2-5. Psoriasis. (A) Skin changes. The classic sharply demarcated plaques with silvery scales are commonly located on the extensor surfaces (eg, elbows, knees). (B) Nail changes. Note the pitting, onycholysis, and “oil spots.” (Reproduced with permission from Hurwitz RM. Pathology of the Skin: Atlas of Clinical-Pathological Correlation, 2nd ed. Stamford, CT: Appleton & Lange, 1998: 15, 18.) KEY FACT A rash commonly involving the extensor surfaces? Think psoriasis. A rash commonly involving the flexor surfaces? Think atopic dermatitis. n DIAGNOSIS n n KEY FACT Five percent of patients with psoriasis also have a seronegative arthritis. Psoriatic lesions can be provoked by local irritation or by trauma (Koebner’s phenomenon). Some medications, such as β-blockers, lithium, and ACEIs, can also induce psoriasis. Classically presents with the Auspitz sign (bleeding when scale is scraped). Biopsy can be useful. Histology classically shows a thickened epidermis, elongated rete ridges, an absent granular cell layer, preservation of nuclei in the stratum corneum (parakeratosis), and a sterile neutrophilic infiltrate in the stratum corneum (Munro’s microabscess). TREATMENT Treat with topical steroids combined with keratolytic agents, tar, or anthralin along with UV therapy. Methotrexate may be used for severe cases. Retinoids (vitamin A derivatives) and vitamin D3 analogs may also be used. U R TI C AR I A ( HI VE S ) Urticaria is characterized by superficial, intense erythema and edema in a localized area. It is usually acute but can also be chronic (lasting > 6 weeks). The condition results from the release of histamine and prostaglandins from mast cells in a type I hypersensitivity response. HISTORY/PE n n The asymmetric involvement of the rash, its linear arrangement (possibly from contact with a plant during the camping trip), and the time from exposure to rash presentation all point to contact dermatitis. n The typical lesion is an elevated papule or plaque that is reddish or white and variable in size. Lesions are widespread and last a few hours. In severe allergic reactions, extracutaneous manifestations can include tongue swelling, angioedema (deeper, more diffuse swelling), asthma, GI symptoms, joint swelling, and fever. Acute urticaria is a response to a trigger that may be a food, drug, virus, insect bite, or physical stimulus. Chronic urticaria is usually idiopathic. DIAGNOSIS Diagnosed by clinical impression and patient report. It can often be difficult to determine the cause. DERMATOLOGY HIGH-YIELD FACTS IN 57 TREATMENT Treat urticaria with systemic antihistamines; anaphylaxis requires epinephrine IM, antihistamines, IV fluids, and airway maintenance. D R UG ER U P T I O N Maintain a high suspicion for a cutaneous drug reaction in patients who are hospitalized and develop rashes. Such reactions can take many forms. Drugs can cause all 4 types of hypersensitivity reactions, and sometimes the same drug may cause different types of reactions in different patients. HISTORY/PE n n n Eruptions usually occur 7–14 days after exposure, so if a patient reacts within 1–2 days of starting a new drug, that drug is probably not the causative agent. Eruptions are generally widespread, relatively symmetrical, and pruritic. Most are relatively short-lived, disappearing within 1–2 weeks following removal of the offending agent. Extreme complications of drug eruptions include erythroderma, StevensJohnson syndrome (SJS), and toxic epidermal necrolysis (TEN). DIAGNOSIS Diagnosed by clinical impression. KEY FACT Patients with drug eruptions often have eosinophilia and eosinophils on histopathology. TREATMENT Discontinue the offending agent; treat symptoms with antihistamines and topical steroids to relieve pruritus. E R Y TH E M A M UL T I F O R M E ( E M ) A cutaneous reaction pattern with classic targetoid lesions (see Figure 2.2-6) that has many triggers and is often recurrent. KEY FACT EM is often triggered by recurrent HSV infection of the lip. Other common triggers are drugs and mycoplasmal infections. HISTORY/PE n n n The disease can occur on mucous membranes, where erosions are seen. Typically, lesions start as erythematous macules that become centrally clear and then develop a blister. The palms and soles are often affected. May be associated with systemic symptoms, including fever, myalgias, headache, and arthralgias. In its minor form, the disease is uncomplicated and localized to the skin. However, EM major can lead to TEN or SJS. DIAGNOSIS Diagnosed by clinical impression. TREATMENT n n Symptomatic treatment is all that is necessary; systemic corticosteroids are of no benefit. Minor cases can be treated with antipruritics; major cases should be treated as burns. Erythema multiforme. Evolving erythematous plaques FIGURE 2.2-6. and papules are seen with a target appearance consisting of a dull red center, a pale zone, and a darker outer ring. (Reproduced with permission from Hurwitz RM. Pathology of the Skin: Atlas of Clinical-Pathological Correlation, 2nd ed. Stamford, CT: Appleton & Lange, 1998: 24.) 58 HIGH-YIELD FACTS IN DERMATOLOGY STE VE NS -JO HNS ON S YNDR OM E ( SJ S) / T OX I C E P ID E R M AL N ECRO L Y SIS (TEN ) SJS and TEN constitute 2 different points on the spectrum of life-threatening exfoliative mucocutaneous diseases that are often caused by a drug-induced immunologic reaction. The epidermal separation of SJS involves < 10% of body surface area (BSA), whereas TEN involves > 30% of BSA. HISTORY/PE n n KEY FACT Always include SJS and TEN in your differential diagnosis if a ! Nikolsky’s sign is present. n n May be preceded by EM, a flulike prodrome, skin tenderness, a maculopapular drug rash, or painful mouth lesions. Often associated with a history of exposure to new drugs, such as sulfonamides, penicillin, seizure medications (eg, phenytoin, carbamazepine), quinolones, cephalosporins, allopurinol, corticosteroids, or NSAIDs. Examination reveals severe mucosal erosions with widespread erythematous, dusky red or purpuric macules or atypical targetoid lesions (see Figure 2.2-7). The epidermal lesions often become confluent and show a ! Nikolsky’s sign (separation of the superficial skin layers with slight rubbing) and epidermal detachment. The mucous membranes of the eyes, mouth, and genitals often become eroded and hemorrhagic as well. DIAGNOSIS KEY FACT n n Don’t confuse SJS and TEN with SSSS. SSSS is usually seen in children < 6 years of age and has an infectious etiology. SJS/TEN is generally seen in adults and is usually caused by a drug reaction. n SJS: Biopsy shows degeneration of the basal layer of the epidermis. TEN: Biopsy shows full-thickness eosinophilic epidermal necrosis. The differential also includes staphylococcal scalded-skin syndrome (SSSS), graft-versus-host reaction (usually after bone marrow transplant), radiation therapy, and burns. TREATMENT n Patients have the same complications as burn victims, including thermoregulatory difficulties, electrolyte disturbances, and 2° infections. Toxic epidermal necrolysis. Note the diffuse erythematous bullae and areas of sloughing 2° to the full-thickness necrosis of the epidermis. (Reproduced with permission FIGURE 2.2-7. from Tintinalli JE et al. Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 7th ed. New York: McGraw-Hill, 2011, Fig. 245-5.) DERMATOLOGY n HIGH-YIELD FACTS IN 59 Treatment includes skin coverage and maintenance of fluid and electrolyte balance. Pharmacologic therapy includes systemic corticosteroids in the early stages of SJS/ TEN and IVIG. There is a high risk of mortality. E R Y TH E M A NO D O SU M A panniculitis (or an inflammatory process of the subcutaneous adipose tissue) whose triggers include infection (eg, Streptococcus, Coccidioides, Yersinia, TB), drug reactions (eg, sulfonamides, various antibiotics, OCPs), and chronic inflammatory diseases (eg, sarcoidosis, Crohn’s disease, ulcerative colitis, Behçet’s disease). HISTORY/PE n n Painful, erythematous nodules appear on the patient’s lower legs (see Figure 2.2-8) and slowly spread, turning brown or gray. Patients may present with fever and joint pain. Patients with erythema nodosum may have a false-! VDRL (as in SLE). DIAGNOSIS n n Diagnosed by clinical impression. Workup can include an ASO titer, a PPD test in high-risk patients, a CXR to rule out sarcoidosis, or a small bowel series to rule out IBD based on the patient’s complaints. TREATMENT FIGURE 2.2-8. Erythema nodosum. Erythematous plaques and nodules are commonly located on pretibial areas. Lesions are painful and indurated but heal spontaneously without ulceration. (Reproduced with permission from Hurwitz RM. Pathology of the Skin: Atlas of Clinical-Pathological Correlation, 2nd ed. Stamford, CT: Appleton & Lange, 1998: 132.) Remove the triggering factor and treat the underlying disease where possible. NSAIDs can be used. B U LLO U S PE M P H IG O ID / PE M PH IG U S VU LG AR I S Table 2.2-3 contrasts the clinical features of bullous pemphigoid with those of pemphigus vulgaris. Infectious Disease Manifestations VIRAL DISEASES Herpes Simplex A painful, recurrent vesicular eruption of the mucocutaneous surfaces due to infection with HSV. HSV-1 usually produces oral-labial lesions, whereas HSV-2 usually causes genital lesions. The virus spreads through epidermal cells, causing them to fuse into giant cells. The local host inflammatory response leads to erythema and swelling. KEY FACT Dermatitis herpetiformis (DH) looks like herpes but is not caused by HSV. DH consists of pruritic papules and vesicles on the elbows, knees, buttocks, neck, and scalp, and it is associated with celiac disease (15–25%). Treat with dapsone and a gluten-free diet. HISTORY/PE n n The initial infection is passed by direct contact, after which the herpesvirus remains dormant in local nerve ganglia. 1° episodes are generally longer and more severe than recurrences. Onset is preceded by prodromal tingling, burning, or pain but can also present with lymphadenopathy, fever, discomfort, malaise, and edema of involved tissue. A 28-year-old African American female is seen by her physician for a new-onset, painful rash. She noticed the erythematous nodules on both lower legs 3 days ago. She has a history of uveitis. What is the next best step to identify the underlying cause of this rash? 60 HIGH-YIELD FACTS IN DERMATOLOGY Acquired, Autoimmune Blistering Dermatoses TA B L E 2 . 2 - 3 . VARIABLE BULLOUS PEMPHIGOID PEMPHIGUS VULGARIS Anatomic location of blisters Basement membrane zone. Intraepidermal. Autoantibodies Anti–bullous pemphigoid antigen. Anti-desmoglein; desmoglein is responsible for keratinocyte adhesion. Blister appearance Firm, stable blisters; may be preceded by Erosions are more common than intact urticaria (see Figure 2.2-9). blisters owing to the lack of keratinocyte adherence (see Figure 2.2-10). Nikolsky’s sign " ! Mucosal involvement Rare. Common. Patient age Usually > 60 years of age. Usually 40–60 years of age. Associated medication triggers Generally idiopathic. ACEIs, penicillamine, phenobarbital, penicillin. Mortality Rare and milder course. Possible. Diagnosis Clinical features, skin biopsy with Same as that for bullous pemphigoid. immunofluorescence, and/or ELISA. Treatment Steroids (prednisone). High-dose steroids (prednisone) + immunomodulatory therapy (IVIG, MMF, rituximab). n KEY FACT No multinucleated giant cells on Tzanck smear? Tzanck goodness it’s not herpes! Recurrences are limited to mucocutaneous areas innervated by the involved nerve. n Recurrent oral herpes (HSV-1): Typically consists of the common “cold sore,” which presents as a cluster of crusted vesicles on an erythematous base (see Figure 2.2-11A). It is often triggered by sun and fever. n Recurrent genital herpes (HSV-2): Unilateral and characterized by a cluster of blisters on an erythematous base, but with less pain and systemic involvement than the 1° infection. DIAGNOSIS Diagnosed primarily by the clinical picture. Multinucleated giant cells on Tzanck smear (see Figure 2.2-11B) yield a presumptive diagnosis. TREATMENT n A CXR to look for bilateral hilar adenopathy, which is suggestive of sarcoidosis. Erythema nodosum is the most common nonspecific cutaneous manifestation of sarcoidosis, after cutaneous sarcoidosis. n Oral or IV acyclovir (IV for severe cases or for immunocompromised patients) ↓ both the frequency and the severity of recurrences. Daily acyclovir, valacyclovir, or famciclovir suppressive therapy may be used in patients with > 6 outbreaks per year or for those with EM. Acyclovir ointment is somewhat effective in reducing the duration of viral shedding but does not prevent recurrence. DERMATOLOGY FIGURE 2.2-9. Bullous pemphigoid. Multiple tense vesicles and bullae can be seen. (Re- produced with permission from Wolff K, Johnson RA. Fitzpatrick’s Color Atlas & Synopsis of Clinical Dermatology, 6th ed. New York: McGraw-Hill, 2009, Fig. 6-13.) n In AIDS patients, HSV can persist, with ulcers remaining resistant to antiviral therapy. Symptomatic HSV infection lasting > 1 month can be considered an AIDS-defining illness. Varicella-Zoster Virus (VZV) VZV causes 2 different diseases, varicella and herpes zoster—with transmission occurring via respiratory droplet or by direct contact. VZV has an incubation period of 10–20 days, with contagion beginning 24 hours before the eruption appears and lasting until lesions have crusted. Pemphigus vulgaris. Note the confluent, flaccid blisters and erosions, which are extremely painful. Mucous involvement is common. (Reproduced with permission from Wolff FIGURE 2.2-10. K, Johnson RA. Fitzpatrick’s Color Atlas & Synopsis of Clinical Dermatology, 6th ed. New York: McGraw-Hill, 2009, Fig. 6-10.) HIGH-YIELD FACTS IN 61 62 HIGH-YIELD FACTS IN DERMATOLOGY A B FIGURE 2.2-11. Herpes simplex. (A) 1° infection. Grouped vesicles on an erythematous base on the patient’s lips and oral mucosa may progress to pustules before resolving. (B) Tzanck smear. The multinucleated giant cells from vesicular fluid provide a presumptive diagnosis of HSV infection. The Tzanck smear cannot distinguish between HSV and VZV infection. (Reproduced with permission from Hurwitz RM. Pathology of the Skin: Atlas of Clinical-Pathological Correlation, 2nd ed. Stamford, CT: Appleton & Lange, 1998: 145.) KEY FACT HISTORY/PE n Immunocompromised patients, cancer patients (especially those undergoing chemotherapy), the elderly, and severely stressed individuals are more susceptible to zoster infection. n FIGURE 2.2-12. Varicella zoster. The unilateral dermatomal distribution of the grouped vesicles on an erythematous base is characteristic. (Reproduced with permission from Wolff K et al. Fitzpatrick’s Color Atlas DIAGNOSIS Diagnosed by the clinical picture. TREATMENT & Synopsis of Clinical Dermatology, 5th ed. New York, n McGraw-Hill, 2005: 823.) n KEY FACT If you see giant molluscum contagiosum, think HIV or ↓ cellular immunity. Varicella: n A prodrome consisting of malaise, fever, headache, and myalgia occurs 24 hours before the onset of the rash. n Pruritic lesions appear in crops over a period of 2–3 days, evolving from red macules to vesicles that then crust over. n At any given time, patients have all stages of lesions over their entire body. The trunk, face, scalp, and mucous membranes are involved, but the palms and soles are spared. n In adults, chickenpox is often more severe, with systemic complications such as pneumonia and encephalitis. Zoster: n Herpes zoster, also called shingles, represents the recurrence of VZV in a specific nerve, with lesions cropping up along the nerve’s dermatomal distribution. Outbreaks are usually preceded by intense local pain and then arise as grouped blisters on an erythematous base (see Figure 2.2-12). n Older patients with severe zoster may develop postherpetic neuralgia. Varicella is self-limited in healthy children. A vaccine is available. Adults should be treated with systemic acyclovir. Although acyclovir may speed the cutaneous course of zoster, pain control is most important for patients with this disease. Molluscum Contagiosum A poxvirus infection that is most common in young children and in AIDS patients. It is spread by physical contact. DERMATOLOGY HIGH-YIELD FACTS IN 63 HISTORY/PE n n The rash is composed of tiny waxy papules, frequently with central umbilication. In children, lesions are found on the trunk, extremities, or face (see Figure 2.2-13). In adults, they are commonly found on the genitalia and in the perineal region. Lesions are asymptomatic unless they become inflamed or irritated. DIAGNOSIS Diagnosed by the clinical picture, and confirmed by expressing and staining the contents of the papules for large inclusion or molluscum bodies. TREATMENT Any local destructive method is effective, including curetting, freezing, or applying trichloroacetic acid to the lesions. Lesions resolve spontaneously over months to years and are often left untreated in children. FIGURE 2.2-13. Molluscum contagiosum. The dome-shaped, fleshy, umbilicated papule on the child’s eyelid is characteristic. (Reproduced with permission from Hurwitz RM. Pathology of the Skin: Atlas of Verrucae (Warts) Warts are caused by many different types of HPV and can occur on skin, mucous membranes, and other epithelia. Although usually benign, some subtypes of HPV (especially 16 and 18) lead to squamous malignancies. Spread is by direct contact. Clinical-Pathological Correlation, 2nd ed. Stamford, CT: Appleton & Lange, 1998: 149.) HISTORY/PE n n Common warts are the most prevalent HPV infection. Although most often seen on the hands, they can occur anywhere. The classic genital wart is a cauliflower-like papule or nodule appearing on the glans penis, the vulva, or the perianal region. Warts on mucous membranes are generally velvety and white. Mothers with genital HPV can transmit laryngeal warts to the infant by aspiration during delivery. DIAGNOSIS n n Diagnosed by the clinical picture. Acetowhitening can be helpful in visualizing mucosal lesions. There is a long latency period, with children sometimes acquiring HPV at birth and not manifesting any lesions until years later. TREATMENT Genital warts are treated locally with cryotherapy, podophyllin, trichloroacetic acid, imiquimod, or 5-FU. HPV lesions on the cervix must be monitored cytologically and histologically for evidence of malignancy. FIGURE 2.2-14. Impetigo. Dried pustules with a superficial golden-brown crust are most commonly found around the nose and mouth. (Reproduced with permission from Bondi EE. Dermatology: Diagnosis and Therapy, 1st ed. Stamford, CT: Appleton & Lange, B A C T E R IA L I N F E CT IO N S 1991: 390.) Impetigo A superficial, weeping local infection that primarily occurs in children and is caused by both group A streptococcal and staphylococcal organisms. It is transmitted by direct contact. Streptococcal impetigo can be complicated by acute streptococcal glomerulonephritis. HISTORY/PE n Common type: Characterized by pustules and honey-colored crusts on an erythematous base; generally appears on the face (see Figure 2.2-14). A 7-year-old female presents with fever, sore throat, and a facial rash. Physical examination reveals an erythematous pharynx without exudates and a red, painful patch on the child’s cheek that the mother notes has been expanding. What is the appropriate therapy? 64 HIGH-YIELD FACTS IN KEY FACT n n Scarlet fever: “Sunburn with goosebumps” appearance; strawberry tongue. Caused by Streptococcus pyogenes. Treat with penicillin. Salmonella typhi: Small pink papules on the trunk (“rose spots”) in groups of 10–20 plus fever and GI involvement. Treat with fluoroquinolones and thirdgeneration cephalosporins. Consider cholecystectomy for chronic carrier state. KEY FACT Ludwig’s angina is a bilateral cellulitis of the submental, submaxillary, and sublingual spaces that usually results from an infected tooth. It presents with dysphagia, drooling, fever, and a red, warm mouth and can lead to death from asphyxiation. DERMATOLOGY n Bullous type: Characterized by large stable blisters that frequently involve the acral surfaces. Bullous impetigo is almost always caused by S aureus and can evolve into SSSS. DIAGNOSIS Diagnosed by the clinical picture. TREATMENT Treat with antibiotics with antistaphylococcal activity. Topical antibiotics are often sufficient, but systemic agents can hasten recovery and prevent spread to other patients. Cellulitis A deep, local infection involving the connective tissue, subcutaneous tissue, or muscle in addition to the skin. It is commonly caused by staphylococci or group A streptococci originating from an area of damaged skin or from a systemic source of infection. Community-acquired MRSA is an increasingly common cause. Risk factors include diabetes, IV drug use, venous stasis, and immune compromise. HISTORY/PE Presents with red, hot, swollen, tender skin. Fever and chills are also common. DIAGNOSIS n n Diagnosed by the clinical picture; wound culture may aid in diagnosis and help determine antibiotic sensitivities for treatment. Blood cultures should be obtained when bacteremia is suspected. Culture and sensitivities are important in ruling out MRSA. Rule out abscess, osteomyelitis, and necrotizing fasciitis. TREATMENT Treat with 7–10 days of oral antibiotics for mild cases or with IV antibiotics if there is evidence of systemic toxicity, comorbid conditions, diabetes mellitus (DM), extremes of age, hand or orbital involvement, or other concerns. Necrotizing Fasciitis Deep infection along a fascial plane causing severe pain followed by anesthesia. Infection is caused by S pyogenes (10% of cases) or, commonly, by a mixed infection of anaerobic and aerobic bacteria that includes S aureus, E coli, and Clostridium perfringens. A history of trauma or a recent surgery to the affected area is often but not always elicited. HISTORY/PE n This child has erysipelas, a rash commonly caused by group A streptococcus. It can present as a small red patch on the cheek or extremities that turns into a painful, shiny red plaque. Patients often have a history of chronic cutaneous ulcers, lymphedema, or pharyngitis. Treat with penicillin. n n Presents with sudden onset of pain and swelling at the site of trauma or recent surgery. Pain often progresses to anesthesia. An area of erythema quickly spreads over the course of hours to days. Margins move out into normal skin, and skin becomes dusky or purplish near the site of insult, ultimately leading to necrosis. Necrosis can initially have the appearance of undermining of the skin and subcutaneous layer; if the skin is open, gloved fingers can easily pass DERMATOLOGY n between the 2 layers to reveal yellow-green necrotic fascia (infection spreads quickly in deep fascia). The most important signs are tissue necrosis, a putrid discharge, bullae, severe pain, gas production, rapid burrowing through fascial planes, lack of classical tissue inflammatory signs, and intravascular volume loss. HIGH-YIELD FACTS IN 65 KEY FACT Fournier gangrene is a form of necrotizing fasciitis that is localized to the genital and perineal area. DIAGNOSIS Local radiographs or CT scans show air in tissue. Biopsy from the edge of the lesion can be diagnostic. TREATMENT n n A surgical emergency. Early and aggressive surgical debridement is critical. If Streptococcus is the principal organism involved, penicillin G is the drug of choice. Clindamycin is second line. For anaerobic coverage, give metronidazole or a third-generation cephalosporin. In most cases, broadspectrum coverage is necessary. Folliculitis Inflammation of the hair follicle. Although typically caused by infection with Staphylococcus, Streptococcus, and gram-" bacteria, folliculitis may occasionally be caused by yeast such as Candida albicans, or it may arise from ingrown hairs. HISTORY/PE n n Presents as a tiny pustule that appears at the opening of a hair follicle and usually has a hair penetrating it. When the infection is deeper, a furuncle, or hair follicle abscess, develops. Furuncles may disseminate to adjacent follicles to form a carbuncle. Patients with diabetes or immunosuppression are at ↑ risk. Folliculitis can also be a critical problem in AIDS patients, in whom the disease is intensely pruritic and resistant to therapy. DIAGNOSIS Diagnosed by the clinical picture. TREATMENT Topical antibiotics can be used to treat mild disease, but severe cases require systemic antibiotics. Large lesions must be incised, drained, and cultured to rule out MRSA. Acne Vulgaris An endogenous skin disease that is common among adolescents. The pathogenesis involves hormonal activation of sebaceous glands, the development of the comedo or plugged sebaceous follicle, and involvement of Propionibacterium acnes in the follicle, causing inflammation. Acne lesions may be caused by medications (eg, lithium, corticosteroids) or by topical occlusion (eg, cosmetics). HISTORY/PE n There are 3 stages of acne lesions: n Comedo: May be open (“blackheads”) or closed (“whiteheads”); present in large quantities but with little inflammation. n Inflammatory: The comedo ruptures, creating a pustule that can be large and nodular. KEY FACT Folliculitis → furuncle → carbuncle. KEY FACT Pseudomonas aeruginosa leads to “hot tub folliculitis.” 1 A 42-year-old male is admitted for cellulitis after injuring his leg while swimming. He is febrile and has a well-demarcated area of erythema on the anterior aspect of his right knee. Antibiotics are started. Six hours later, the patient is in excruciating pain. The erythema has spread circumferentially around the knee, and the anterior aspect of the knee now has a purplish hue. What is the next best step? 2 A 17-year-old female has been followed by a dermatologist for severe cystic acne that has been refractory to both topical and systemic antibiotics. She inquires about isotretinoin (Accutane). Given this drug’s potentially hazardous side effects, what laboratory tests would have to be performed monthly if this patient were to be placed on isotretinoin? 66 HIGH-YIELD FACTS IN DERMATOLOGY Scar: As the inflammation heals, scars may develop. Picking at papules exacerbates scarring. Acne first develops at puberty and typically persists for several years. Males are more likely to have severe cystic acne than are females. Women in their 20s tend to have a variant that flares cyclically with menstruation, featuring fewer comedones and more painful lesions on the chin. Androgenic stimulation may contribute to these lesions. n KEY FACT n Ironically, erythromycin does not cause erythema with sun exposure. It is tetracycline and doxycycline that can cause serious photosensitivity! DIAGNOSIS Diagnosed by the clinical picture. TREATMENT n n n KEY FACT Antibiotics are not needed for pilonidal cysts unless cellulitis is present; if antibiotics are prescribed, both aerobic and anaerobic coverage is required. 1 Emergent surgical consult for debridement given the clinical suspicion for necrotizing fasciitis, a surgical emergency. Comedonal acne: Topical tretinoin (Retin-A) and benzoyl peroxide. Pustulocystic, or inflammatory, acne: Benzoyl peroxide plus topical antibiotics (eg, erythromycin, clindamycin). Systemic antibiotics (eg, tetracycline, erythromycin) are used for acne refractory to topical antibiotics. Severe cystic acne: Isotretinoin (Accutane) leads to marked improvement in > 90% of acne patients. n Isotretinoin is, however, a teratogen and may cause transient elevations in cholesterol, triglycerides, and LFTs, and it may also be associated with depression. n Patients on isotretinoin thus require monthly blood tests to check quantitative serum β-hCG (to rule out pregnancy), LFTs, cholesterol, and triglycerides. Monthly refills are contingent on the completion of blood testing and evaluation by a dermatologist. Pilonidal Cysts Abscesses in the sacrococcygeal region that usually occur near the top of the natal cleft. Their name may not be appropriate, as not all contain hair or are true cysts. Repetitive trauma to the region plays a role. The condition is thought to start as a folliculitis that becomes an abscess complicated by perineal microbes, especially Bacteroides. It most commonly occurs between the ages of 20 and 40, affecting males more often than females. HISTORY/PE n n Patients present with an abscess at the natal cleft that can be tender, fluctuant, warm, and indurated and is sometimes associated with purulent drainage or cellulitis. Systemic symptoms are uncommon, but cysts may develop into perianal fistulas. Risk factors include deep and hairy natal clefts, obesity, and a sedentary lifestyle. DIAGNOSIS Diagnosed by the clinical picture. Rule out perirectal and anal abscess. 2 Serum β-hCG (to rule out pregnancy), LFTs, cholesterol, and triglycerides. TREATMENT n n Treatment consists of incision and drainage of the abscess under local anesthesia followed by sterile packing of the wound. Good local hygiene and shaving of the sacrococcygeal skin can help prevent recurrence. Patients should follow up with a surgeon. DERMATOLOGY HIGH-YIELD FACTS IN 67 FU N G A L I N F E C T I O N S Tinea Versicolor Caused by Malassezia furfur, a yeast that is part of the normal skin flora. It is unclear what leads the organism to become a pathogen, but humid and sweaty conditions as well as host factors such as oily skin can contribute. Cushing’s syndrome and immunosuppression are also risk factors. HISTORY/PE n n Patients present with small, scaly patches of varying color, usually on the chest or back (see Figure 2.2-15A). Lesions may be hypopigmented as a result of interference with melanin production, or they may be hyperpigmented by virtue of thickened scale. DIAGNOSIS Diagnosed by clinical impression, and confirmed by KOH preparation of scale that reveals a “spaghetti and meatballs” pattern of hyphae and spores (see Figure 2.2-15B). TREATMENT Treat lesions with topical ketoconazole or selenium sulfide. Candidiasis Commonly called “yeast infection” or “thrush,” candidiasis can be caused by any Candida species but is most commonly caused by C albicans. In immune-competent patients, it typically presents as a superficial infection of the skin or mucous membranes in moist areas such as skin folds, armpits, the vagina, and below the breasts. Oral thrush is not uncommon among children, but in adults it is often a sign of a weakened immune system. A B FIGURE 2.2-15. Tinea versicolor. (A) Note the discrete, hypopigmented patches extensively involving the patient’s back. Tinea versicolor may also present as hyperpigmented macules or patches in some individuals. (B) KOH preparation shows the characteristic “spaghetti and meatballs” pattern. (Image A reproduced with permission from Tintinalli JE et al. Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 7th ed. New York: McGraw-Hill, 2011, Fig. 249-8. Image B reproduced with permission from Wolff K et al. Fitzpatrick’s Dermatology in General Medicine, 7th ed. New York: McGraw-Hill, 2008, Fig. 189-11.) 68 HIGH-YIELD FACTS IN DERMATOLOGY HISTORY/PE n n n Patients often have a history of antibiotic use, steroid use, or diabetes. Oral candidiasis: Presents with painless white plaques that cannot easily be scraped off. Candidiasis of the skin: Presents as markedly erythematous patches with occasional erosions and smaller satellite lesions seen nearby, often in skin folds. In infants, infection can often be seen in the diaper area and along the inguinal folds. DIAGNOSIS Diagnosed by the clinical picture; confirmed by KOH preparation of a scraping or swab of the affected area. KOH dissolves the skin cells but leaves the Candida untouched such that candidal hyphae and pseudospores become visible. TREATMENT n n n Oral candidiasis: Oral fluconazole; nystatin swish and swallow. Superficial (skin) candidiasis: Topical antifungals; keep skin clean and dry. Diaper rash: Topical nystatin. Dermatophyte Infections Dermatophytes live only in tissues with keratin (ie, the skin, nails, and hair) and are a common cause of infection. Causative organisms include Microsporum, Trichophyton, and Epidermophyton. Trichophyton rubrum is the most common dermatophyte worldwide. Risk factors include diabetes, ↓ peripheral circulation, immune compromise, and chronic maceration of skin (eg, from athletic activities). HISTORY/PE Presentation varies according to subtype: n n n n Tinea corporis: Presents as a scaly, pruritic eruption with a sharp, irregular border, often with central clearing (see Figure 2.2-16). May be seen in immunocompromised patients or in children following contact with infected pets. Tinea pedis/manuum: Presents as chronic interdigital scaling with erosions between the toes (“athlete’s foot”) or as a thickened, scaly skin on the soles and interdigital web spaces. Asymmetric involvement of the hands is typical. Tinea cruris (“jock itch”): A chronic infection of the groin (typically sparing the scrotum) that is usually associated with tinea pedis. Tinea capitis: A diffuse, scaly scalp eruption similar to seborrheic dermatitis. DIAGNOSIS FIGURE 2.2-16. Tinea corporis. Note the “ringworm-like” rash with a scaly, erythematous, distinct border and central clearing. (Reproduced with permission from Wolff K et al. Fitzpatrick’s Dermatology in General Medicine, 7th ed. New York: McGraw-Hill, 2008, Fig. 188-11.) Diagnosed by the clinical picture; confirmed by scales prepared in KOH showing hyphae. TREATMENT Patients can be treated with topical or systemic antifungals. Tinea capitis must be treated with systemic drugs; systemic treatment should also be considered in immunocompromised patients. DERMATOLOGY HIGH-YIELD FACTS IN PA R A S I T I C IN F E CT IO N S Lice Lice live off blood and on specific parts of the body, depending on their species (head lice, body lice, pubic lice). Lice are spread through body contact or by the sharing of bedclothes and other garments or hair accessories. They secrete local toxins that lead to pruritus. HISTORY/PE n n Patients with lice often experience severe pruritus, and 2° bacterial infection of the excoriations is a risk. Classroom epidemics of head lice are common. Body lice are seen in people with inadequate hygiene or in those with crowded living conditions. Pubic lice (called “crabs” because of their squat, crablike body shape) contain anticoagulant in their saliva, so their bites often turn blue. DIAGNOSIS Lice can be seen on hairs or in clothes. TREATMENT n n n Head lice: Treat with OTC pyrethrin (RID), benzyl alcohol, and mechanical removal of nits. Body lice: Wash body, clothes, and bedding thoroughly. Treating the body with topical permethrin or pyrethrin may also be required. Pubic lice: Treat with RID. Scabies Caused by Sarcoptes scabiei. The burrowing of this arthropod into the epidermis leads to pruritus that ↑ in intensity once an allergy to the mite or its products develops. Scabies mites are spread through close contact. HISTORY/PE n n n Patients present with intense pruritus, especially at night and after hot showers, and erythematous, pimple-like papules with linear tracks, representing the burrows of the mite. The most commonly affected sites are the hands (often includes the spaces between knuckles), axillae, and genitals. 2° bacterial infection is common. DIAGNOSIS A history of pruritus in several family members is suggestive. The mite may be identifiable by scraping an intact tunnel and looking under the microscope. TREATMENT n n Patients should be treated overnight with 1–2 applications of 5% permethrin from the neck down, and their contacts should be treated as well. Oral ivermectin is also effective. Pruritus may persist for 2 weeks after treatment, so symptomatic treatment should be provided. KEY FACT Get rid of lice with RID. 69 70 HIGH-YIELD FACTS IN DERMATOLOGY Ischemic Disorders DE C U BI TU S U LC E R S Result from ischemic necrosis following continuous pressure on an area of skin that restricts microcirculation to the area. HISTORY/PE Ulcers are most commonly seen in bedridden patients who lie in the same spot for too long. An underlying bony prominence or lack of fat ↑ the likelihood of ulcer formation. Patients who lack mobility or cutaneous sensation are also at ↑ risk. Incontinence of urine or stool may macerate the skin, facilitating ulceration. DIAGNOSIS Diagnosed by the history and clinical appearance. TREATMENT n n Prevention is key and involves routinely moving bedridden patients and using special beds that distribute pressure. Once an ulcer has developed, low-grade lesions can be treated with routine wound care, including hydrocolloid dressings. High-grade lesions require surgical debridement. GANG R E NE Defined as necrosis of body tissue. There are 3 subtypes: dry, wet, and gas. Etiologies are as follows: n n n Dry gangrene: Due to insufficient blood flow to tissue, typically from atherosclerosis. Wet gangrene: Involves bacterial infection, usually with skin flora. Gas gangrene: Due to C perfringens infection. HISTORY/PE n n n Dry gangrene: Early signs are a dull ache, cold, and pallor of the flesh. As necrosis sets in, the tissue (usually a toe) becomes bluish-black, dry, and shriveled. Diabetes, vasculopathy, and smoking are risk factors. Wet gangrene: The tissue appears bruised, swollen, or blistered with pus. Gas gangrene: Typically occurs at a site of recent injury or surgery, presenting with swelling around the injury and with skin that turns pale and then dark red. Bacteria are rapidly destructive of tissue, producing gas that separates healthy tissue and exposes it to infection. A medical emergency. DIAGNOSIS Diagnosed by clinical impression. TREATMENT n n Surgical debridement, with amputation if necessary, is the mainstay of treatment. Antibiotics alone do not suffice by virtue of inadequate blood flow, but they should be given as an adjuvant to surgery. Gas gangrene can be treated with hyperbaric oxygen, which is toxic to the anaerobic C perfringens. Susceptible patients should maintain careful foot care and should avoid trauma. DERMATOLOGY HIGH-YIELD FACTS IN 71 Miscellaneous Skin Disorders AC A N T H O S IS N I G R I CA N S n n n A condition in which the skin in the intertriginous zones (genital and axillary regions, and especially the nape of the neck) is hyperkeratotic and hyperpigmented with a velvety appearance (see Figure 2.2-17). Associated with DM, Cushing’s disease, polycystic ovarian syndrome, and obesity. May also be a paraneoplastic sign of underlying adenocarcinoma (usually GI). Tx: Typically not treated. Patients should be encouraged to lose weight. LI C HE N PL A N US n n n A chronic inflammatory dermatosis involving the skin and mucous membranes. The condition is intensely pruritic, can be induced by drugs, and can be associated with HCV infection. Hx/PE: Presents with violaceous, flat-topped, polygonal papules (see Figure 2.2-18). Lesions may have prominent Koebner’s phenomena (lesions that appear at the site of trauma). The initial lesions often appear on the genitalia, where they are erosive. Tx: Mild cases are treated with topical corticosteroids. For severe disease, systemic corticosteroids and phototherapy may be used. FIGURE 2.2-17. Acanthosis nigricans. Velvety, dark brown epidermal thickening of the armpit is seen with prominent skin fold and feathered edges. (Reproduced with permission from Wolff K, Johnson RA. Fitzpatrick’s Color Atlas & Synopsis of Clinical Dermatology, 6th ed. New York: McGraw-Hill, 2009, RO S A C E A n n n A chronic disorder of pilosebaceous units whose etiology is unclear. Early in the disease, central facial erythema is seen with telangiectasias. Later, papules and pustules may develop. Hx/PE: n Patients are generally middle-aged persons with fair skin and often have an abnormal flushing response to various substances. There is a female predominance. n Rosacea can be confused with acne but is not follicular in origin and involves an older age group. Tx: Treat with topical metronidazole. For more severe disease, systemic antibiotics may be used. Fig. 5-1.) KEY FACT Lichen planus is the “P” disease: Planar, Purple, Pruritic, Persistent, Polygonal, Penile, Perioral, Puzzling, and Koebner’s Phenomenon. PI TY R I A S I S R O S E A n n n An acute dermatitis whose etiology is unknown but has been hypothesized to represent a reaction to a viral infection with human herpesvirus (HHV) 6 or 7 because it tends to occur in mini-epidemics among young adults. Hx/PE: n The initial lesion is a herald patch that is erythematous with a peripheral scale. n Days to weeks later, a 2° exanthem appears, presenting with multiple tiny, symmetric papules with a fine “cigarette paper” scale (see Figure 2.2-19). Papules are arranged along skin lines, giving a classic “Christmas tree” pattern on the patient’s back. Dx: Diagnosed by clinical impression and confirmed by KOH exam to rule out fungus (the herald patch may be mistaken for tinea corporis). Syphilis should also be ruled out with RPR. FIGURE 2.2-18. Lichen planus. Flat-topped, polygonal, sharply defined papules of violaceous color are grouped and confluent. The surface is shiny and reveals fine white lines (Wickham’s striae). (Reproduced with permission from Wolff K et al. Fitzpatrick’s Dermatology in General Medicine, 7th ed. New York: McGraw-Hill, 2008, Fig. 26-1.) 72 HIGH-YIELD FACTS IN DERMATOLOGY FIGURE 2.2-19. Pityriasis rosea. The round to oval erythematous plaques are often covered with a fine white scale (“cigarette paper”) and are often found on the trunk and proximal extremities. Plaques are often preceded by a larger herald patch (inset). (Reproduced with permission from Tintinalli JE et al. Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 7th ed. New York: McGraw-Hill, 2011, Fig. 249-6.) n Tx: Patients usually heal without treatment in 6–8 weeks, but skin lubrication, topical antipruritics, and systemic antihistamines are supportive therapies. V I TI LI G O n n n n A disease of depigmentation 2° to the absence of functional melanocytes. Its pathogenesis is unknown. Hx/PE: Patients develop small, sharply demarcated, depigmented macules or patches on otherwise normal skin, often on the hands, face, or genitalia. These spots then expand to include large segments of skin. The disease is usually chronic and progressive, with some patients becoming completely depigmented. Dx: Many patients have serologic markers of autoimmune disease (eg, antithyroid antibodies, DM, pernicious anemia) but seldom present with these diseases. Tx: Topical or systemic psoralens and exposure to sunlight or PUVA may be helpful. Patients must wear sunscreen because depigmented skin lacks inherent sun protection. Dyes and makeup may be used to color the skin, or the skin may be chemically bleached to produce a uniformly white color. Neoplasms SE BOR R HE I C K E R ATOS I S A very common skin tumor that appears in almost all patients after age 40. The etiology is unknown. Lesions have no malignant potential but may be a cosmetic problem (see Figure 2.2-20). DERMATOLOGY HIGH-YIELD FACTS IN 73 HISTORY/PE n n Present as exophytic, waxy brown papules and plaques with prominent follicle openings (see Figure 2.2-20). Lesions often appear in great numbers and have a “stuck-on” appearance. Lesions may become irritated either spontaneously or by external trauma, especially in the groin, breast, or axillae. DIAGNOSIS Diagnosed by the clinical picture. TREATMENT Cryotherapy or curettage is curative. AC T IN I C K E R A T O S I S A precursor of squamous cell carcinoma in situ. Lesions are caused by exposure to sunlight. HISTORY/PE Lesions appear on sun-exposed areas (especially the face and arms) and primarily affect older patients, who rarely have a solitary lesion. They are erythematous with a light scale that can become thick and crusted (see Figure 2.2-21). FIGURE 2.2-21. Actinic keratosis. The discrete patch above has an erythematous base and a rough white scale. (Reproduced with permission from Hurwitz RM. Pathology of the Skin: Atlas of Clinical-Pathological Correlation, 2nd ed. Stamford, CT: Appleton & Lange, 1998: 359.) DIAGNOSIS Diagnosed by clinical impression. TREATMENT Cryosurgery, topical 5-FU, or topical imiquimod can be used to destroy the lesion. If carcinoma is suspected, biopsy followed by excision or curettage is appropriate. Patients should be advised to use sun protection. S Q UA M O US C E LL CA R C IN O M A (S C C) The second most common skin cancer, with locally destructive effects as well as the potential for metastasis and death. UV light is the most common causative factor, but exposure to chemical carcinogens, prior radiation therapy, and sites of chronic trauma (as in draining infectious sinuses in osteomyelitis) also predispose patients to developing SCC. Most SCCs occur in older adults with sun-damaged skin, arising from actinic keratoses. Arsenic exposure is a well-defined cause of multiple SCCs in a palmoplantar distribution. HISTORY/PE n n SCCs have a variety of forms, and a single patient will often have multiple variants (see Figure 2.2-22). Bowen’s disease is a form of SCC in situ. SCCs that arise from actinic keratoses rarely metastasize, but those that arise on the lips and on ulcers are more likely to do so. SCC occurs on the lip far more commonly than does basal cell carcinoma (BCC). DIAGNOSIS Diagnosed by clinical suspicion and confirmed by biopsy, which is necessary for accurate diagnosis and appropriate therapeutic planning. FIGURE 2.2-22. Squamous cell carcinoma. Note the crusting and ul- ceration of this erythematous plaque. Most lesions are exophytic nodules with erosion or ulceration. (Reproduced with permis- sion from Hurwitz RM. Pathology of the Skin: Atlas of Clinical-Pathological Correlation, 2nd ed. Stamford, CT: Appleton & Lange, 1998: 360.) A 72-year-old male presents to a new internist after moving to Florida. The internist notes a chronic wound on the patient’s right lower leg. The patient states that the wound followed an episode of cellulitis and has been present for 3 years. What is the next best step? 74 HIGH-YIELD FACTS IN DERMATOLOGY TREATMENT Surgical excision or Mohs’ surgery (microscopic surgery for close excision and identification of clear tumor margins). Lesions with high metastatic potential may require additional radiation or chemotherapy. B AS AL C E LL C AR C I NOM A ( BC C) The most common malignant skin cancer, BCC is slow growing and locally destructive but has virtually no metastatic potential. Chronic UV light exposure is the main risk factor. Multiple lesions on non-sun-exposed areas are suggestive of inherited basal cell nevus syndrome. Most lesions appear on the face and on other sun-exposed areas. HISTORY/PE There are many types of BCC with varying degrees of pigmentation, ulceration, and depth of growth (see Figure 2.2-23). DIAGNOSIS Diagnosed by clinical impression. FIGURE 2.2-23. Nodular basal cell carcinoma. A smooth, pearly nodule with telangiectasias. (Reproduced with permission from Wolff K et al. Fitzpatrick’s Color Atlas & Synopsis of Clinical Dermatology, 5th ed. New York: McGraw-Hill, 2005: 283.) TREATMENT Options include excision, curettage and electrodesiccation/cautery, deep cryotherapy, superficial radiation therapy, and Mohs’ surgery. ME LANOM A The most common life-threatening dermatologic disease. Risk factors include fair skin and a tendency to burn; intense bursts of sun exposure (especially in childhood and with intermittent exposure); and the presence of large congenital melanocytic nevi, an ↑ number of nevi, or dysplastic nevi. Immunosuppression also ↑ risk. Some patients inherit a predisposition to melanoma with the familial atypical mole and melanoma (FAM-M) syndrome. There are several subtypes (see Table 2.2-4). MNEMONIC The ABCDEs of melanoma: Asymmetric Irregular Border Irregular Color Diameter > 6 mm Evolution: changing or new lesions HISTORY/PE n n Malignant melanomas usually begin in the epidermal basal layer, where melanocytes are normally found. Malignant melanomas may metastasize, and 3–5% of patients with metastatic melanoma have no known 1° lesion. DIAGNOSIS n n Biopsy the lesion to rule out SCC. n Early recognition and treatment are essential. All adults should be examined for lesions that are suspicious for melanoma according to the ABCDE criteria, which identify dysplastic nevi and superficial spreading melanoma (see mnemonic and Figure 2.2-24). The onset of pruritus is also an early sign of malignant change. An excisional biopsy should be performed on any suspicious lesion. Malignancy is determined histologically. Malignant melanomas are staged by Breslow’s thickness (depth of invasion measured in millimeters) and by tumor-node-metastasis (TNM) staging. Ulceration is a poor prognostic sign. DERMATOLOGY HIGH-YIELD FACTS IN 75 TREATMENT n n Lesions confined to the skin are treated by excision with margins. Sentinel lymph node biopsy is useful for staging but does not ↑ survival. Chemotherapy (including interferon) and radiation therapy may be used but are not likely to be successful. Malignant melanoma has the potential to relapse after several years and is known for its tendency to bleed; patients with early melanoma are at low risk for relapse but are at high risk for the development of subsequent melanomas. Patient surveillance is thus essential. K A P O S I ’ S S A R CO M A (K S) A vascular proliferative disease that has been attributed to a herpesvirus, HHV-8, which is also called Kaposi’s sarcoma–associated herpesvirus (KSHV). HISTORY/PE n n Patients present with multiple red to violaceous macules, papules, or nodules that can progress to plaques on the lower limbs, back, face, mouth, and genitalia (see Figure 2.2-25). Epidemic HIV-associated KS is an aggressive form of the disease, and although less common since the advent of HAART, it remains the most common HIV-associated malignancy. KEY FACT Bacillary angiomatosis, caused by Bartonella henselae and Bartonella quintana, can mimic KS and should be excluded in suspected KS patients; erythromycin is the treatment of choice. DIAGNOSIS Diagnosed by history, clinical impression, and histology. TREATMENT Treatment is technically palliative. Local lesions may be treated with radiation or cryotherapy; surgery is not recommended. Widespread or internal disease is treated with systemic chemotherapy (anthracyclines, paclitaxil, or IFN-α). MYCO S I S F UN G O I DE S (CU T A N E OU S T -CE LL LYM P HOM A) Not a fungus, but rather a slow, progressive neoplastic proliferation of T cells. The disease is chronic and is more common in males than in females. HISTORY/PE n n n The early lesion is a nonspecific, psoriatic-appearing plaque that is palpable and often pruritic with a predilection for the buttocks. A later lesion is characterized by limited or generalized skin involvement with palpable lymph nodes or 1 or more skin tumors with multicentric, often confluent reddish-brown nodules (see Figure 2.2-26). Patients may have dermatopathic lymphadenopathy without actual tumor involvement of the node. However, the internal organs can be involved, including the lymph nodes, liver, and spleen. Sézary’s syndrome is the leukemic phase of cutaneous T-cell lymphoma and is characterized by circulating Sézary cells in the peripheral blood, erythroderma, and lymphadenopathy. FIGURE 2.2-25. Kaposi’s sarcoma. Note the multiple violaceous papules on the neck, back, and face. (Reproduced with permission from Wolff K et al. Fitzpatrick’s Color Atlas & Synopsis of Clinical Dermatology, 5th ed. New York: McGraw-Hill, 2005, Fig. 1e-HIV7.) 76 HIGH-YIELD FACTS IN DERMATOLOGY TA B L E 2 . 2 - 4 . Types of Melanoma TYPE PRESENTATION Lentigo maligna Arises in a lentigo. Usually found on sun-damaged skin of the face. Superficial spreading Typically affects younger adults, presenting on the trunk in men and on the legs in women. A relatively prolonged horizontal growth phase helps identify the disease early, when it is still confined to the epidermis. Nodular Lesions have a rapid vertical growth phase and appear as a rapidly growing reddish-brown nodule with ulceration or hemorrhage. Acral lentiginous Begins on the hands and feet as a slowly spreading, pigmented patch. Most commonly seen in Asians and African Americans. Amelanotic Presents as a lesion without clinical pigmentation. Extremely difficult to identify. This variant of melanoma can be further classified into any of the above types. DIAGNOSIS n n FIGURE 2.2-26. Mycosis fungoides. Massive nodular infiltration of the face leads to a leonine facies. (Repro- duced with permission from Wolff K et al. Fitzpatrick’s Dermatology in General Medicine, 7th ed. New York: McGraw-Hill, 2008, Fig. 146-7.) Diagnosed by clinical features and histology, with immunologic characterization and electron microscopy showing the typical Sézary or Lutzner cells (cerebriform lymphocytes). The early lesion is clinically indistinguishable from dermatitis, so histologic diagnosis is indicated for any dermatitis that is chronic and resistant to treatment. TREATMENT Phototherapy is the mainstay of treatment for many patients. For more extensive or advanced disease, radiation therapy is an effective option. Treatment modalities, including steroids, chemotherapy, retinoids, monoclonal antibodies, and interferon, are often combined. HIGH-YIELD FACTS IN ENDOCRINOLOGY Disorders of Glucose Metabolism 78 Pituitary and Hypothalamic Disorders 91 TYPE 1 DIABETES MELLITUS (TYPE 1 DM) 78 CUSHING’S SYNDROME 91 TYPE 2 DIABETES MELLITUS (TYPE 2 DM) 79 ACROMEGALY 92 METABOLIC SYNDROME 81 HYPERPROLACTINEMIA 92 83 DIABETES INSIPIDUS 93 TESTING OF THYROID FUNCTION 83 SIADH 94 HYPERTHYROIDISM 83 Adrenal Gland Disorders HYPOTHYROIDISM 84 ADRENAL INSUFFICIENCY 94 THYROIDITIS 86 PHEOCHROMOCYTOMA 95 THYROID NEOPLASMS 86 HYPERALDOSTERONISM 96 87 CONGENITAL ADRENAL HYPERPLASIA 96 OSTEOPOROSIS 87 Multiple Endocrine Neoplasias 97 PAGET’S DISEASE 89 HYPERPARATHYROIDISM 89 Thyroid Disorders Bone and Mineral Disorders 94 77 78 HIGH-YIELD FACTS IN ENDOCRINOLOGY Disorders of Glucose Metabolism TYP E 1 DI ABE TE S M E LLITU S ( TYP E 1 DM ) Due to autoimmune pancreatic β-cell destruction, leading to insulin deficiency and abnormal glucose metabolism. HISTORY/PE n n n n Classically presents with polyuria, polydipsia, polyphagia, and rapid, unexplained weight loss. Patients may also present with ketoacidosis (see Table 2.3-1). Usually affects nonobese children or young adults. Associated with HLA-DR3 and -DR4. Type I DM in adults is known as latent autoimmune diabetes of adults (LADA). DIAGNOSIS n n At disease onset, anti–islet cell and anti–glutamic acid decarboxylase (anti-GAD) antibodies may be present in serum. At least 1 of the following is required to make the diagnosis: n A fasting (> 8-hour) plasma glucose level ≥ 126 mg/dL on 2 separate occasions. n A random plasma glucose level ≥ 200 mg/dL plus symptoms. n A 2-hour postprandial glucose level ≥ 200 mg/dL following an oral glucose tolerance test on 2 separate occasions if the results of initial testing are equivocal. n Hemoglobin A1c (HbA1c) > 6.5%. TREATMENT n n Insulin injections (see Table 2.3-1 and Figure 2.3-1) to maintain blood glucose in the normal range (80–120 mg/dL). Higher blood glucose levels (≥ 200 mg/dL) can be tolerated, particularly in the very young, in light of the ↑ risk of hypoglycemia. Consider the use of an insulin pump, which provides continuous, shortacting insulin infusion. TA B L E 2 . 3 - 1 . Types of Insulin INSULINa ONSET PEAK EFFECT DURATION Regular 30–60 minutes 2–4 hours 5–8 hours Short acting (lispro, aspart, 5–20 minutes 0.5–3.0 hours 3–8 hours NPH 2–4 hours 6–10 hours 18–28 hours Long acting (detemir, glargine) 1–3 hours No discernible 20–24 hours glulisine) peak a Combination preparations mix longer-acting and shorter-acting types of insulin together to provide immediate and extended coverage in the same injection (eg, 70 NPH/30 regular = 70% NPH + 30% regular). ENDOCRINOLOGY HIGH-YIELD FACTS IN 79 Aspart, lispro, glulisine Regular Insulin level NPH Detemir Glargine 0 5 10 15 20 25 Time (hours) FIGURE 2.3-1. n Pharmacokinetics of insulin preparations. Encourage routine HbA1c testing every 3 months (with a goal HbA1c < 8% in children and < 7% in adults), frequent BP checks, a cardiac review of systems in adults at each clinic visit, monofilament foot exams, annual dilated-eye exams, annual urine microalbuminuria screening, and a fasting lipid profile every 2–5 years. COMPLICATIONS Table 2.3-2 outlines the acute, chronic, and treatment-related complications of DM. T Y P E 2 D IA B ET E S M E LLIT U S ( T YP E 2 DM ) A dysfunction in glucose metabolism due to varying degrees of insulin resistance in peripheral tissues that may ultimately lead to β-cell failure and complete insulin dependence. HISTORY/PE n n n n n Patients typically present with symptoms of hyperglycemia (polyuria, polydipsia, polyphagia, blurred vision, fatigue). Onset is more insidious than that of type 1 DM, and patients often present with complications. Nonketotic hyperosmolar hyperglycemia may be seen in the setting of poor glycemic control. Usually occurs in older adults with obesity (often truncal) and has a strong genetic predisposition; diagnosed increasingly in obese children. Risk factors include obesity, rapid weight gain, a ! family history, a sedentary lifestyle, increasing age, and other components of metabolic syndrome (see below). DIAGNOSIS n n Diagnostic criteria are the same as those for type 1 DM. Anti–islet cell and anti-GAD antibodies will be ". KEY FACT Microalbuminuria cannot be detected on routine UA protein dipstick. 80 HIGH-YIELD FACTS IN TA B L E 2 . 3 - 2 . ENDOCRINOLOGY Complications of DM COMPLICATION DESCRIPTION TREATMENT COMPLICATIONS Dawn phenomenon Morning hyperglycemia due to the normal nocturnal release of counterregulatory hormones (eg, glucagon, epinephrine, cortisol), which ↑ insulin resistance and blood glucose levels (see Figure 2.3-2). ↑ P.M. NPH insulin. Somogyi effect Rebound hyperglycemia. Results from excess exogenous insulin, which causes hypoglycemia overnight and stimulates the release of counterregulatory hormones that in turn ↑ blood glucose levels (see Figure 2.3-2). ↓ P.M. NPH insulin. ACUTE COMPLICATIONS DKA Hyperglycemia-induced crisis that most commonly occurs in type 1 DM. Often precipitated by stress (including infections, MI, trauma, or alcohol) or by noncompliance with insulin therapy. May present with abdominal pain, vomiting, Kussmaul respirations, and a fruity, acetone breath odor. Patients are severely dehydrated with electrolyte abnormalities and may also develop mental status changes. Treatment includes fluids, potassium, insulin, bicarbonate (if pH is < 7), and treatment of the initiating event or underlying disease process. Hyperosmolar hyperglycemic state Presents with profound dehydration, mental status changes, hyperosmolarity, and extremely high plasma glucose (> 600 mg/dL) without acidosis and with small or absent ketones. Occurs in type 2 DM; precipitated by acute stress (dehydration, infections) and can often be fatal. Treatment includes aggressive fluid, electrolyte replacement, and insulin. Treat the initiating event. CHRONIC COMPLICATIONS Retinopathy Appears when diabetes has been present for at least 3–5 years (see Figure 2.3-3). Preventive measures include (nonproliferative, control of hyperglycemia and hypertension, annual eye exams, and laser photocoagulation therapy for retinal proliferative) neovascularization. Diabetic nephropathy Characterized by glomerular hyperfiltration followed by microalbuminuria. Preventive measures include ACEIs or angiotensin receptor blockers (ARBs) and BP/glucose control. Neuropathy Peripheral, symmetric sensorimotor neuropathy leading to burning pain, foot trauma, infections, and diabetic ulcers. Treat with preventive foot care and analgesics. Late complications due to autonomic dysfunction include delayed gastric emptying, esophageal dysmotility, impotence, and orthostatic hypotension. Macrovascular Cardiovascular, cerebrovascular, and peripheral vascular disease. Cardiovascular disease is the most common complications cause of death in diabetic patients. The goal BP is < 130/< 80 mm Hg; ↓ LDL to < 100 mg/dL and ↓ triglycerides to < 150 mg/dL. Patients should also be started on low-dose ASA. n Screening recommendations: n Patients with no risk factors: Test HbA1c at age 45; retest every 3 years if HbA1c is < 5.7% and no other risk factors develop. n Patients with impaired fasting glucose (> 110 mg/dL but < 126 mg/ dL) or impaired glucose tolerance: Follow up with frequent retesting. TREATMENT The goal of treatment is tight glucose control (see Table 2.3-3)—ie, blood glucose levels ranging from 80 to 120 mg/dL and HbA1c levels < 7%. Treatment measures are outlined in Table 2.3-3. ENDOCRINOLOGY Blood glucose Blood glucose Epinephrine, cortisol Time A B F I G U R E 2 . 3 - 2 . Mechanisms of morning hyperglycemia in diabetes. (B) Dawn phenomenon. GH Time (A) Somogyi effect. COMPLICATIONS See Table 2.3-2 for an outline of the complications of DM. M E TA B O LI C S Y N D R O ME Also known as insulin resistance syndrome or syndrome X. Associated with an ↑ risk of CAD and mortality from a cardiovascular event. HISTORY/PE Presents with abdominal obesity, high BP, impaired glycemic control, and dyslipidemia. DIAGNOSIS Three out of five of the following criteria must be met: n n n n n Abdominal obesity (↑ waist girth): > 40 inches in men and > 35 inches in women. Triglycerides ≥ 150 mg/dL. HDL < 40 mg/dL in men and < 50 mg/dL in women. BP ≥ 130/85 mm Hg or a requirement for antihypertensive drugs. Fasting glucose ≥ 100 mg/dL. A B Diabetic retinopathy. (A) Nonproliferative retinopathy presents with exudates, dot-blot hemorrhages, and microaneurysms. (B) Proliferative retinopathy presents with macular edema, vitreous traction, and neovascularization of the retinal vasculature. (Repro- FIGURE 2.3-3. duced with permission from USMLERx.com.) HIGH-YIELD FACTS IN 81 82 HIGH-YIELD FACTS IN TA B L E 2 . 3 - 3 . ENDOCRINOLOGY Treatment of Type 2 DM TREATMENT DESCRIPTION LIFESTYLE MODIFICATIONS Diet Low-fat, moderate-carbohydrate, low-calorie personalized diet. Weight loss Goal: 5–10% body weight loss with a combination of diet and exercise. Exercise Moderate-intensity exercise for 30 minutes 5 days per week. PHARMACOTHERAPY (MONOTHERAPY OR COMBINATION THERAPY IF POOR GLYCEMIC CONTROL) Sulfonylureas (glipizide, glyburide, ↑ endogenous insulin secretion. Side effects include hypoglycemia and weight gain. glimepiride) Metformin Inhibits hepatic gluconeogenesis and ↑ peripheral sensitivity to insulin. Side effects include weight loss, GI upset, and, rarely, lactic acidosis. Contraindicated in the elderly (> 80 years of age) and in renal insufficiency, hepatic failure, or heart failure. Thiazolidinediones (rosiglitazone, ↑ insulin sensitivity. Side effects include weight gain, edema, hepatotoxicity, and bone loss. pioglitazone)a Contraindicated in patients with heart failure. α-glucosidase inhibitors ↓ intestinal absorption of carbohydrates. Side effects include flatulence and hypoglycemia. DPP-4 inhibitors (sitagliptin) Inhibit the degradation of glucagon-like peptide 1 (GLP-1). Incretins (exenatide) GLP-1 agonists. Injected subcutaneously. Delay absorption of food; ↑ insulin secretion and ↓ glucagon secretion. Side effects include nausea and, rarely, pancreatitis. Insulin Given alone or in conjunction with oral agents. GENERAL HEALTH MAINTENANCE Cardiovascular risk modification The presence of diabetes is equivalent to the highest risk for cardiovascular disease regardless of all other risk factors. ASA for patients at risk of cardiovascular disease or for those > 40 years of age. Statins for hypercholesterolemia (goal LDL < 100 mg/dL; optimal goal LDL < 70 mg/dL for persons with cardiac disease). BP management Strict BP control to < 130/80 mm Hg; ACEIs/ARBs are first-line agents. Screening exams Annual physical examination to screen for cardiovascular disease, nephropathy, retinopathy, and neuropathy. a In September 2010, the FDA restricted access to rosiglitazone because of concern for ↑ cardiovascular risks. The drug is still available but is restricted to patients currently on the medication who acknowledge that they understand the risks and to patients who cannot achieve adequate glycemic control with other medications. TREATMENT Intensive weight loss, aggressive cholesterol management, and BP control. Metformin has been shown to slow the onset of diabetes in this high-risk population. ENDOCRINOLOGY TA B L E 2 . 3 - 4 . HIGH-YIELD FACTS IN 83 TFTs in Thyroid Disease DIAGNOSIS 1° hyperthyroidism TSH T4 T3 ↓ ↑ ↑ CAUSES Graves’ disease, toxic multinodular goiter, toxic adenoma, amiodarone, postpartum thyrotoxicosis, postviral thyroiditis. 1° hypothyroidism ↑ ↓ ↓ Hashimoto’s thyroiditis, iatrogenic (radioactive ablation, excision), drugs (lithium, amiodarone). Thyroid Disorders T ES TIN G O F T H Y R O ID F U N CT IO N Thyroid function tests (TFTs) include the following (see also Table 2.3-4): n n n n TSH measurement: The single best test for the screening of thyroid disease and for the assessment of thyroid function. High TSH levels are associated with 1° hypothyroidism; low TSH levels are associated with hyperthyroidism. Radioactive iodine uptake (RAI) and scan: Determines the level and distribution of iodine uptake by the thyroid. Useful for the differentiation of hyperthyroid states, but has a limited role in determining malignancy. Total T4 measurement: Not an adequate screening test. Ninety-nine percent of circulating T4 is bound to thyroxine-binding globulin (TBG). Total T4 levels can be altered by changes in levels of binding proteins. Free T4 measurement: The preferred screening test for thyroid hormone levels. HY PE RT H Y R O I DI S M A state involving ↑ levels of T3/T4. Most commonly due to Graves’ disease, but can also result from other causes (see Table 2.3-4). n n n Graves’ disease: The autoimmune form of hyperthyroidism. Thyroidstimulating antibodies ↑ T3/T4. RAI percent uptake will be high, and RAI scan will show diffuse iodine uptake. Toxic adenoma/toxic multinodular goiter: Result in hyperthyroidism due to autonomous hyperactive thyroid nodules. RAI percent uptake will be normal to high, and RAI scan will show nodules/regions of ↑ uptake only. Thyroiditis (postpartum, postviral, subacute): Due to transient inflammation of the thyroid gland with release of previously synthesized thyroid hormone; causes a temporary ↑ in circulating T3/T4. RAI percent uptake will be low, and RAI scan will show low iodine uptake. A hypothyroid phase may follow the hyperthyroid phase (see below). HISTORY/PE n Presents with weight loss, heat intolerance, anxiety, palpitations, ↑ bowel frequency, insomnia, and menstrual abnormalities. KEY FACT ↑ TBG can be found in pregnancy, estrogen administration, infection, nephritic syndrome, and anabolic steroid use. You do not need to treat. KEY FACT In 1° endocrine disturbances, the gland itself is abnormal. In 2° endocrine disturbances, the pituitary gland is the source. In 3° endocrine disturbances, the hypothalamus malfunctions (see Figure 2.3-4). KEY FACT Exophthalmos, pretibial myxedema, and thyroid bruits are specific for Graves’ disease. A 10-year-old male presents to the ER with 2 weeks of polyuria and polydipsia together with new-onset lethargy. Physical examination reveals signs of severe dehydration, and labs reveal a blood glucose level of 800 mg/dL. The diagnosis of diabetic ketoacidosis (DKA) is made, and the patient is started on insulin and IV fluids. What is the next best step in management? 84 HIGH-YIELD FACTS IN ENDOCRINOLOGY Hypothalamus TRH (-) Dopamine Somatostatin Glucocorticoids (-) Pituitary (-) TSH T4 T3 Thyroid FIGURE 2.3-4. The hypothalamic-pituitary-thyroid axis. (Reproduced with permission from Molina PE. Endocrine Physiology, 3rd ed. New York: McGraw-Hill, 2009, Fig. 4-1.) n KEY FACT TSH receptor-stimulating antibodies are found in patients with Graves’ disease. KEY FACT Examination reveals warm, moist skin, goiter, sinus tachycardia or atrial fibrillation (AF), fine tremor, lid lag, and hyperactive reflexes. Exophthalmos, pretibial myxedema, and thyroid bruits are seen only in Graves’ disease (see Figure 2.3-5). DIAGNOSIS The initial test of choice is a serum TSH level, followed by T4 levels and, rarely, T3 (unless TSH is low and free T4 is not elevated). See Table 2.3-4. TREATMENT Thyroid storm is an acute, lifethreatening form of thyrotoxicosis that may present with AF, fever, and delirium. Administer IV propranolol and steroids, and admit to the ICU. n n n n Symptomatic treatment: Propranolol to manage adrenergic symptoms. Pharmacologic treatment: Antithyroid drugs (methimazole or propylthiouracil). Definitive treatment: Radioactive 131I thyroid ablation or total thyroidectomy (less common in the United States). Administer levothyroxine (oral T4 replacement) to prevent hypothyroidism in patients who have undergone ablation or surgery. COMPLICATIONS Add 5% dextrose to the IV fluids. In the management of DKA, it is important to start IV fluids and insulin immediately. Initially, the goal is to rehydrate the patient and lower blood glucose, but as blood glucose reaches 250–300 mg/dL, it is important to add 5% dextrose to ↓ the risk of hypoglycemia. Thyroid storm, an acute, life-threatening form of thyrotoxicosis. Treat urgently with IV propranolol, propylthiouracil, and corticosteroids. High-dose potassium iodide (SSKI) is also effective. HYP OTHYR OID I S M A state involving ↓ levels of T3/T4. Most commonly due to Hashimoto’s thyroiditis, but can result from other causes (see Table 2.3-4). ENDOCRINOLOGY A B Physical signs of Graves’ disease. (A) Graves’ ophthalmopathy. (B) Pretibial myxedema. (Reproduced with permission from USMLERx.com.) FIGURE 2.3-5. n n Hashimoto’s thyroiditis (autoimmune hypothyroidism): Associated with ! antithyroglobulin and antimicrosomal (anti-TPO) antibodies that precipitate thyroid destruction. Thyroiditis (postpartum, postviral, subacute): Can have a hypothyroid phase that follows the hyperthyroid phase. Hypothyroidism can be permanent. HISTORY/PE n n Presents with weakness, fatigue, cold intolerance, constipation, weight gain, depression, hair loss, menstrual irregularities, and hoarseness. Examination reveals dry, cold, puffy skin accompanied by edema, bradycardia, and delayed relaxation of DTRs. DIAGNOSIS The initial test of choice is serum TSH level, followed by free T4 levels. See Table 2.3-4. TREATMENT For uncomplicated hypothyroidism (eg, Hashimoto’s disease), administer levothyroxine. COMPLICATIONS Myxedema coma: severe hypothyroidism with ↓ mental status, hypothermia, and other parasympathetic symptoms. Mortality is 30–60%. Admit to the ICU and treat urgently with IV levothyroxine and IV hydrocortisone (if adrenal insufficiency has not been excluded). HIGH-YIELD FACTS IN 85 86 HIGH-YIELD FACTS IN ENDOCRINOLOGY THYR OI DI TI S KEY FACT Subacute thyroiditis is not a “cute” thyroiditis—it is painful! Inflammation of the thyroid gland. Common subtypes include subacute granulomatous, radiation-induced, autoimmune, postpartum, and drug-induced (eg, amiodarone) thyroiditis. HISTORY/PE n n The subacute form presents with a tender thyroid, malaise, and URI symptoms. All other forms are associated with painless goiter. DIAGNOSIS Thyroid dysfunction (typically thyrotoxicosis followed by hypothyroidism), with ↓ uptake on RAI and scan during the hyperthyroid phase. TREATMENT n n β-blockers for hyperthyroidism; levothyroxine for hypothyroidism. Subacute thyroiditis is usually self-limited; for severe cases, treat with NSAIDs or with oral corticosteroids. THYR OI D NE OP LAS MS Thyroid nodules are very common and show an ↑ incidence with age. Most (~ 95%) are benign. MNEMONIC HISTORY/PE n Thyroid neoplasms— The most Popular is Papillary Papillae (branching) Palpable lymph nodes “Pupil” nuclei (“Orphan Annie” nuclei) Psammoma bodies within lesion (often) Also has a Positive Prognosis n n n n KEY FACT Check calcitonin levels if medullary cancer is suspected. n DIAGNOSIS n KEY FACT Hyperfunctioning thyroid nodules are not malignant. Usually asymptomatic on initial presentation; discovered incidentally with imaging for other purposes (eg, carotid ultrasound) or on examination. Hyperfunctioning nodules present with hyperthyroidism. Large nodules adjacent to the trachea/esophagus present with local symptoms (dysphagia, dyspnea, cough, choking sensation) and are associated with a ! family history (especially medullary thyroid cancer). An ↑ risk of malignancy is associated with a history of childhood neck irradiation, “cold” nodules (minimal uptake on RAI scan), male sex, age < 20 or > 70, firm and fixed solitary nodules, a ! family history (especially medullary thyroid cancer), and rapidly growing nodules with hoarseness. Check for anterior cervical lymphadenopathy. Carcinoma (see Table 2.3-5) may be firm and fixed. Medullary thyroid carcinoma is associated with multiple endocrine neoplasia (MEN) type 2. n n TFTs to detect hyperfunctioning nodules, followed by RAI scan, which will show a “hot” nodule. Hot nodules are not cancerous and should not be biopsied. Ultrasound to determine if the nodule is solid or cystic. Cystic nodules are more likely to be benign. The best method to assess a nodule for malignancy is fine-needle aspiration (FNA), which has high sensitivity and moderate specificity. “Cold” nodules on RAI scan should be biopsied. ENDOCRINOLOGY TA B L E 2 . 3 - 5 . Types of Thyroid Carcinoma TYPEa Papillary Follicular CHARACTERISTICS PROGNOSIS Represents 75–80% of thyroid Ninety percent of patients survive cancers. The female-to-male ratio is 10 years or more after diagnosis; 3:1. Slow growing; found in thyroid the prognosis is worse in elderly hormone–producing follicular cells. patients or those with large tumors. Accounts for 17% of thyroid Same as above. cancers; found in thyroid hormone– producing follicular cells. Medullary Responsible for 6–8% of thyroid Eighty percent of patients survive cancers. Found in calcitonin- at least 10 years after surgery. producing C cells; the prognosis Consider MEN 2A or 2B based on is related to degree of vascular family history. invasion. Anaplastic Accounts for < 2% of thyroid Ten percent of patients survive for cancers; rapidly enlarges and > 3 years. metastasizes. a Tumors may contain mixed papillary and follicular pathologies. TREATMENT n n n Benign FNA: Follow with physical examination/ultrasound to assess for continued nodule growth or for the development of suspicious characteristics (eg, calcification, ↑ vascular flow). Malignant FNA: Surgical resection with hemi- or total thyroidectomy is first-line treatment; adjunctive radioiodine ablation following excision is appropriate for some follicular lesions. Indeterminate FNA: Watchful waiting vs. hemithyroidectomy (10–30% chance of malignancy). If resected, await final pathology to guide further treatment. Bone and Mineral Disorders O ST E O PO R O S IS A common metabolic bone disease characterized by low bone mass and microarchitectural disruption, with bone mineral density (BMD) < 2.5 SDs from normal peak bone mass (at 30 years of age). It most often affects thin, postmenopausal women (17%), especially Caucasians and Asians, with risk doubling after age 65. Males are also at risk for osteoporosis, but the diagnosis is often overlooked. HISTORY/PE n n Commonly asymptomatic even in the presence of a vertebral fracture. Examination may reveal hip fractures, vertebral compression fractures (loss of height and progressive thoracic kyphosis), and/or distal radius fractures (Colles’ fracture) following minimal trauma (see Figure 2.3-6). HIGH-YIELD FACTS IN 87 88 HIGH-YIELD FACTS IN ENDOCRINOLOGY Radiographic findings in osteoporosis. Lateral thoracic spine radiograph shows osteoporosis and an anterior wedge deformity of a lower thoracic vertebral body with associated kyphosis. This is a typical insufficiency fracture in osteoporotic patients. (Reproduced with FIGURE 2.3-6. permission from Fauci AS et al. Harrison’s Principles of Internal Medicine, 17th ed. New York: McGraw-Hill, 2008, Fig. 348-2.) KEY FACT n n Osteoporosis is the most common cause of pathologic fractures in thin, elderly women and men. Bone pain (especially anterior tibial pain) unrelated to fracture is most likely osteomalacia, a mineralization defect, rather than osteoporosis. Smoking, age, excessive caffeine or alcohol intake, a history of estrogendepleting conditions in women (eg, amenorrhea, eating disorders) or hypogonadism in men, uncontrolled hyperthyroidism, chronic inflammatory disease, and corticosteroid use are all associated with an ↑ risk. DIAGNOSIS n n n Dual-energy x-ray absorptiometry (DEXA): The standard imaging technique for diagnosing osteoporosis; reveals BMD < 2.5 SDs from the normal peak level, with sites reported including the vertebral bodies, proximal femur, and distal radius. Labs: Rule out 2° causes with TFTs, CMP, 24-hour urine calcium, serum 25-hydroxyvitamin D, CBC, testosterone (in men), and SPEP/UPEP (to rule out multiple myeloma). X-rays: Global demineralization is apparent only after > 30% of bone density is lost. TREATMENT n n n Prevention and treatment with calcium and vitamin D supplementation. Smoking cessation and weight-bearing exercises help maintain and even restore some bone density. Antiresorptive agents that can prevent further bone loss include bisphosphonates (eg, alendronate, risedronate, ibandronate, zoledronic acid), selective estrogen receptor modulators (eg, raloxifene), intranasal calcitonin, and denosumab (a monoclonal antibody to RANK-L). COMPLICATIONS Fracture is the most devastating consequence of low BMD/osteoporosis, carrying a 50% chance of mortality in the year following hip fracture. ENDOCRINOLOGY HIGH-YIELD FACTS IN 89 PA G E T’ S D IS E A S E Characterized by an ↑ rate of bone turnover with both excessive resorption and formation of bone, leading to a “mosaic” lamellar bone pattern on x-ray. Suspected to be due to the effects of a latent viral infection in genetically susceptible individuals. Occurs in roughly 4% of men and women > 40 years of age. Associated with 1° hyperparathyroidism in up to one-fifth of patients. HISTORY/PE n n Usually asymptomatic, but may present with aching bone or joint pain, headaches (if the skull is involved), bony deformities, fracture at a pagetoid site, or nerve entrapment (leads to loss of hearing in 30–40% of cases involving the skull). The disease can affect 1 (monostotic) or many (polyostotic) bones, with the skull, vertebral bodies, pelvis, and long bones most commonly affected. DIAGNOSIS Based on clinical history, characteristic radiographic changes (see Figure 2.3-7), and lab findings. n n Labs: Abnormalities include ↑ serum alkaline phosphatase with normal calcium and phosphate levels. Must be distinguished from metastatic bone disease. Imaging: Radionuclide bone scan is the most sensitive test in early Paget’s disease, but plain films are critical to diagnosis. TREATMENT n n Most patients are asymptomatic and require no treatment. There is no cure for Paget’s disease. In the setting of severe pain, involvement of a vulnerable site (femoral neck), or fracture, bisphosphonates and calcitonin can be used to slow osteoclastic bone resorption; NSAIDs and acetaminophen can be given for pain management. FIGURE 2.3-7. Radiographic findings in Paget’s disease. Pelvic radio- graph demonstrates a thickened cortex (arrow), thickened trabeculae (arrowhead), and expansion of the right femoral head, classic signs of Paget’s disease. COMPLICATIONS (Reproduced with permission from Fauci AS et al. Har- Pathologic fractures, high-output cardiac failure, osteosarcoma (up to 1%). York: McGraw-Hill, 2008, Fig. 349-3.) rison’s Principles of Internal Medicine, 17th ed. New HY PE R PA R A T H Y R O I D I S M The parathyroid glands make parathyroid hormone (PTH) and are responsible for calcium and phosphate regulation in the body. Hyperparathyroidism is defined as an ↑ serum PTH level with variable effects on calcium and phosphate, depending on the specific cause. n n n 1° hyperparathyroidism: Most cases (80%) are due to a single hyperfunctioning adenoma, with the rest (15%) resulting from parathyroid hyperplasia and, rarely (5%), parathyroid carcinoma. 2° hyperparathyroidism: A physiologic ↑ of PTH in response to renal insufficiency, calcium deficiency, or vitamin D deficiency. 3° hyperparathyroidism: Seen in dialysis patients with long-standing 2° hyperparathyroidism that leads to hyperplasia of the parathyroid glands. When 1 or more of the glands become autonomous, 3° hyperparathyroidism results. An asymptomatic 36-year-old male presents for his annual physical. The patient has no past medical history and takes no medications. His physical examination is unremarkable. Routine labs reveal a serum calcium level of 11.3 mg/dL. He returns in 2 weeks, and his serum calcium level remains persistently elevated. Further workup is initiated, and additional studies show a normal serum PTH level and a low 24-hour urinary calcium level. What is the most likely diagnosis? 90 HIGH-YIELD FACTS IN KEY FACT Hypercalcemia is associated with “stones, bones, moans, groans, and psychiatric overtones.” Administer IV fluids and then loop diuretics. ENDOCRINOLOGY HISTORY/PE Most cases of 1° hyperparathyroidism are asymptomatic, but signs and symptoms of hypercalcemia may be mild and include stones (nephrolithiasis), bones (bone pain, myalgias, arthralgias, fractures), abdominal groans (abdominal pain, nausea, vomiting, PUD, pancreatitis), and psychiatric overtones (fatigue, depression, anxiety, sleep disturbances). DIAGNOSIS n Hypothalamus n n Labs in 1° hyperparathyroidism reveal hypercalcemia, hypophosphatemia, and hypercalciuria. Intact PTH is inappropriately ↑ relative to total and ionized calcium (see Table 2.3-6). DEXA may reveal low bone density or frank osteoporosis in the distal radius or other sites. A 99mTc sestamibi scan, in conjunction with thyroid ultrasound, can help localize a solitary adenoma. TREATMENT n n n n Target organ FIGURE 2.3-8. The hypothalamic- pituitary axis. Parathyroidectomy if the patient is symptomatic or if certain criteria are met. In the case of a solitary adenoma, 1 gland may be removed. In the setting of hyperplasia, 3.5 glands must be removed. For acute hypercalcemia, give IV fluids, loop diuretics, and an IV bisphosphonate. In patients with renal insufficiency, administer oral phosphate binders (aluminum hydroxide, calcium salts, sevelamer hydrochloride, and lanthanum carbonate) and restrict dietary phosphate intake to prevent 2° hyperparathyroidism. Cinacalcet is a calcimimetic that acts to lower serum PTH levels and is approved for use in hyperparathyroidism due to renal failure. COMPLICATIONS Hypercalcemia is the most severe complication of 1° hyperparathyroidism, presenting acutely with coma or altered mental status, bone disease, nephrolithiasis, and abdominal pain with nausea and vomiting. TA B L E 2 . 3 - 6 . Familial hypocalciuric hypercalcemia (FHH), an inherited disorder due to mutations in a calcium-sensing receptor present in the parathyroid and kidney, presents with elevated serum calcium levels. Unlike patients with 1° hyperparathyroidism, these patients are asymptomatic and have low urinary calcium levels. No treatment is required. Lab Values in Hyperparathyroidism PTH CALCIUM PO4 1° ↑ ↑ ↓ 2° ↑ Nl/↓ ↑ 3° ↑ Nl/↓ ↑ Ectopic PTHrP a ↓ ↑ ↓ a PTH-releasing peptide (PTHrP) is a member of the PTH family and acts on the same PTH receptors. Some tumors (eg, breast, lung) produce PTHrP, causing hypercalcemia of malignancy. ENDOCRINOLOGY HIGH-YIELD FACTS IN 91 Pituitary and Hypothalamic Disorders Figure 2.3-8 illustrates the hypothalamic-pituitary axis. The sections that follow outline the manner in which the components of this axis interact with target organs in various pathologic states. CU S H IN G ’ S S Y N D R O M E The result of elevated serum cortisol levels, Cushing’s syndrome is most frequently iatrogenic, resulting from prolonged treatment with exogenous corticosteroids. The most common endogenous cause is hypersecretion of ACTH from a pituitary adenoma (known as Cushing’s disease; see Figure 2.3-9). Other endogenous causes include excess adrenal secretion of cortisol (eg, bilateral adrenal hyperplasia, adenoma, adrenal cancer) and ectopic ACTH production from an occult neoplasm (eg, carcinoid tumor, medullary thyroid cancer, small cell lung cancer). KEY FACT Cushing’s syndrome = too much cortisol. Cushing’s disease = too much cortisol from an ACTH-producing pituitary adenoma. HISTORY/PE n n n Presents with hypertension, type 2 DM, depression, weight gain, muscle weakness, easy bruisability, ↑ susceptibility to infection, psychological disturbances, oligomenorrhea, and hirsutism. Examination reveals central obesity, growth retardation, proximal muscle wasting and weakness, acne, excessive hair growth, wide purple striae, moon facies, and supraclavicular or retrocervical fat pads (“buffalo hump”). Headache or cranial nerve deficits (bitemporal hemianopsia, impaired extraocular movements) can occur with increasing size of the pituitary mass. KEY FACT In Cushing’s disease, cortisol secretion remains elevated with the low-dose dexamethasone test but is suppressed with the high-dose dexamethasone test. Hypothalamus DIAGNOSIS Diagnosis is as follows (see also Table 2.3-7): n n n n n Begin with a screen: Pick 2 of 3 tests: (1) an elevated 24-hour free urine cortisol; (2) an elevated midnight salivary cortisol level on 2 separate nights; or (3) a 1-mg dexamethasone suppression test (! if A.M. cortisol is persistently elevated the morning after administration of dexamethasone). Distinguish ACTH-dependent (pituitary/ectopic) from ACTH-independent causes (adrenal): Measure morning (8:00 A.M.) cortisol and ACTH levels. If ACTH is elevated, Cushing’s disease or ectopic ACTH is likely. A pituitary MRI should be ordered only if laboratory testing suggests Cushing’s disease (associated with a high risk of pituitary incidentalomas). Adrenal imaging should be ordered only if the workup suggests an ACTHindependent etiology (associated with a high risk of adrenal incidentalomas). Hyperglycemia, glycosuria, and hypokalemia may also be present. TREATMENT n n n Surgical resection of the source (pituitary, adrenal, neoplasm). Inhibitors of adrenal steroidogenesis (eg, spironolactone, eplerenone) are helpful in cases of bilateral adrenal hyperplasia. Permanent hormone replacement therapy to correct deficiencies after treatment of the 1° lesion. CRH CRH CRH CRH ACTH ACTH ACTH ACTH ACTH Cortisol FIGURE 2.3-9. The hypothalamicpituitary axis: Cushing’s disease. 92 HIGH-YIELD FACTS IN T A B L E 2 . 3 - 7. ENDOCRINOLOGY Laboratory Findings in Cushing’s Syndrome CUSHING’S DISEASE EXOGENOUS ECTOPIC ACTH ADRENAL CORTISOL (PITUITARY HYPERSECRETION) STEROID USE SECRETION HYPERSECRETION 24-hour urinary free cortisol ↑ ↑ ↑ ↑ Salivary cortisol ↑ ↑ ↑ ↑ ACTH ↑ ↓ ↑ ↓ Low dose ↑ ↑ ↑ ↑ High dose ↓ ↑ ↑ N/Aa Dexamethasone suppression test morning cortisol level: a A high-dose dexamethasone suppression test is not required once the diagnosis of ACTH-independent Cushing’s syndrome is made. AC R OM E G ALY Hypothalamus GHRH GHRH GHRH GHRH Elevated growth hormone (GH) levels in adults, most commonly due to a benign pituitary GH-secreting adenoma (see Figure 2.3-10). Children with excess GH production present with gigantism. HISTORY/PE n n n Presents with enlargement of the skull, hands, and feet and coarsening of facial features. Associated with an ↑ risk of carpal tunnel syndrome, obstructive sleep apnea, type 2 DM, heart disease (diastolic dysfunction), hypertension, and arthritis. Bitemporal hemianopsia may result from compression of the optic chiasm by a pituitary adenoma. Excess GH may also lead to glucose intolerance or diabetes. DIAGNOSIS n GH GH GH GH GH n Labs: Measure insulin-like growth factor 1 (IGF-1) levels (↑ with acromegaly); confirm the diagnosis with an oral glucose suppression test (GH levels will remain elevated despite glucose administration). Baseline GH is not a reliable test. Imaging: MRI shows a sellar lesion. TREATMENT n Target tissues IGF-1 The hypothalamic-pituitary axis: acromegaly. FIGURE 2.3-10. n Transsphenoidal surgical resection or external beam radiation of the tumor. Octreotide (a somatostatin analog) can be used to suppress GH secretion; pegvisomant (a GH receptor antagonist) can be used to block the peripheral actions of GH. HYP E R P R OLACTI NE M I A Elevated prolactin levels, most commonly due to a pituitary adenoma (see Figure 2.3-11). Prolactinoma is the most common functioning pituitary tumor. Other causes include pituitary stalk compression from other masses (eg, craniopharyngioma, meningioma), drugs (eg, dopamine antagonists), renal failure, and cirrhosis. ENDOCRINOLOGY HIGH-YIELD FACTS IN Hypothalamus GnRH GnRH GnRH GnRH LH/FSH LH/FSH LH/FSH TSH FIGURE 2.3-11. Prolactin Prolactin Prolactin Prolactin The hypothalamic-pituitary axis: prolactinoma. HISTORY/PE Elevated prolactin inhibits GnRH secretion and consequently lowers LH and FSH secretion, manifesting as infertility, galactorrhea, and amenorrhea. Bitemporal hemianopsia may also be present. DIAGNOSIS n n The serum prolactin level is typically > 200 mg/mL. MRI shows a sellar lesion. KEY FACT Rule out pregnancy in all cases of hyperprolactinemia. Hypothalamus TREATMENT n n First line: Dopamine agonists (eg, cabergoline, bromocriptine). Surgery: Indicated in adenomas refractory to medical management or with compressive effects (eg, visual loss). D I A B E T E S I N S IP ID U S ( DI ) Inability to produce concentrated urine as a result of ADH dysfunction. The 2 subtypes are as follows: n n Central DI (ADH deficiency): The posterior pituitary fails to secrete ADH. Causes include tumor, ischemia (Sheehan’s syndrome), pituitary hemorrhage, traumatic brain injury, infection, metastatic disease, and autoimmune disorders (see Figure 2.3-12). Nephrogenic DI (ADH resistance): The kidneys fail to respond to circulating ADH. Causes include renal disease and drugs (eg, lithium, demeclocycline). ADH ADH ADH ADH HISTORY/PE n n Presents with polydipsia, polyuria, and persistent thirst with dilute urine. Most cases are normonatremic. If access to water is limited (eg, in the institutionalized or elderly), patients may present with dehydration and severe hypernatremia leading to altered mental status, lethargy, seizures, and coma. ↑ Plasma osmolality The hypothalamic-pituitary axis: DI. FIGURE 2.3-12. 93 94 HIGH-YIELD FACTS IN KEY FACT ENDOCRINOLOGY DIAGNOSIS n For unknown reasons, patients with DI prefer ice-cold beverages. n Hypothalamus n Water deprivation test: In central and nephrogenic DI, patients excrete a high volume of inappropriately dilute urine. Desmopressin acetate (DDAVP, a synthetic analog of ADH) replacement test: n Central DI: ↓ urine output and ↑ urine osmolarity. n Nephrogenic DI: No effect is seen on urine output or urine osmolarity. MRI may show a pituitary or hypothalamic mass in central DI. TREATMENT n n n Treat the underlying cause. Central DI: Administer DDAVP intranasally or orally. Nephrogenic DI: First-line treatment consists of salt restriction and water intake. Thiazide diuretics can be used to promote mild volume depletion and to stimulate ↑ water reabsorption. S I ADH A common cause of euvolemic hyponatremia that results from persistent ADH release independent of serum osmolality (see Figure 2.3-13). ADH ADH ADH ADH HISTORY/PE Associated with CNS disease (eg, head injury, tumor), pulmonary disease (eg, sarcoid, COPD, pneumonia), ectopic tumor production/paraneoplastic syndrome (eg, small cell lung carcinoma), and drugs (eg, antipsychotics, antidepressants). DIAGNOSIS ↓ Plasma osmolality The hypothalamic-pituitary axis: SIADH. n FIGURE 2.3-13. KEY FACT n n Urine osmolality is > 50–100 mOsm/kg in the setting of serum hypoosmolarity without a physiologic reason for ↑ ADH (eg, CHF, cirrhosis, hypovolemia). A urinary sodium level ≥ 20 mEq/L demonstrates that the patient is not hypovolemic. Serum uric acid is < 4 mg/dL. TREATMENT Fluid restriction is the cornerstone of SIADH treatment. KEY FACT Correct hyponatremia slowly to prevent central pontine myelinolysis. n n n Restrict fluid and address the underlying cause. If hyponatremia is severe (< 110 mEq/L) or if the patient is significantly symptomatic (eg, comatose, seizing), cautiously give hypertonic saline. Patients must be monitored in the ICU to prevent central pontine myelinolysis. Demeclocycline, an ADH receptor antagonist, can help normalize serum sodium. Adrenal Gland Disorders KEY FACT 1° AI, but not 2°, is associated with ↑ skin pigmentation. AD R E NAL I NS U F F I C I E NC Y (AI ) Inadequate production of adrenal hormones, including glucocorticoids and/ or mineralocorticoids. May be 1° or 2°/3°. Etiologies are as follows: ENDOCRINOLOGY n n 1°: In the United States, most commonly due to autoimmune adrenal cortical destruction (Addison’s disease), leading to deficiencies of mineralocorticoids and glucocorticoids. Other causes include congenital enzyme deficiencies, adrenal hemorrhage, and infections (Neisseria meningitidis, HIV, histoplasmosis, TB). TB is the most common cause of AI worldwide. 2°/3°: Caused by ↓ ACTH production by the pituitary; most often due to cessation of long-term glucocorticoid treatment. HISTORY/PE n n n Most symptoms are nonspecific. Weakness, fatigue, and anorexia with weight loss are common. GI manifestations, hypoglycemia, hypotension, and salt craving are also seen. Hyperpigmentation (due to ↑ ACTH secretion) is seen in Addison’s disease, especially in areas of sun exposure or friction. HIGH-YIELD FACTS IN 95 MNEMONIC The 4 S’s of adrenal crisis management: Salt: 0.9% saline Steroids: IV hydrocortisone 100 mg q 8 h Support Search for the underlying illness KEY FACT Do not delay the administration of steroids in a patient with suspected AI. DIAGNOSIS n n n n Labs show hyponatremia and eosinophilia (1° or 2°). Hyperkalemia is specific to 1° AI. Hypercalcemia is seen in up to one-third of cases. Confirm with 8 A.M. plasma cortisol levels and a synthetic ACTH stimulation test: n An 8 A.M. plasma cortisol level < 3 µg/dL in the absence of exogenous glucocorticoid administration is diagnostic of AI. n Failure of cortisol to rise > 18 µg/dL following ACTH administration confirms the diagnosis. n A random plasma cortisol level > 18 µg/dL excludes the diagnosis. MNEMONIC Pheochromocytoma rule of 10’s: 10% extra-adrenal 10% bilateral 10% malignant 10% occur in children 10% familial TREATMENT n n n n n 1°: Glucocorticoid and mineralocorticoid replacement. 2°/3°: Only glucocorticoid replacement is necessary (mineralocorticoid production is not ACTH dependent). In adrenal crisis, provide IV steroids; correct electrolyte abnormalities as needed; provide 50% dextrose to correct hypoglycemia; and initiate aggressive volume resuscitation. ↑ steroids during periods of stress (eg, major surgery, trauma, infection). In patients on chronic steroid therapy, taper slowly to prevent 2°/3° AI. PH E O C H R OM O C Y T OM A A tumor of chromaffin tissue that secretes catecholamines and is found either in the adrenal medulla or in extra-adrenal sites. Most commonly associated with MEN 2A and 2B. HISTORY/PE n n Presents with paroxysmal tachycardia, palpitations, chest pain, diaphoresis, hypertension, headache, tremor, and anxiety. It is important to obtain a family history in order to rule out genetic causes of pheochromocytoma (eg, MEN 2A/2B, von Hippel–Lindau disease, neurofibromatosis). DIAGNOSIS n CT and MRI are both sensitive for pheochromocytomas. A nuclear MIBG scan can localize extra-adrenal lesions and metastatic disease. 1 A 23-year-old male with a history of schizophrenia presents with complaints of fatigue, weakness, cramps, and headache for the past several days. He denies any other symptoms, although he had to urinate several times while in the office. Routine labs reveal hyponatremia. With water deprivation, his urine osmolality ↑. What is the most likely diagnosis? 2 An asymptomatic 36-year-old female presents with a 2-cm thyroid mass. TFTs are unremarkable, but FNA reveals medullary carcinoma. Total thyroidectomy with thyroid hormone replacement is recommended. What is the most important screening test to perform prior to surgery? 96 HIGH-YIELD FACTS IN MNEMONIC The 5 P’s of pheochromocytoma: Pressure (BP) Pain (headache) Perspiration Palpitations Pallor ENDOCRINOLOGY n TREATMENT n n Surgical resection. Preoperatively, use α-adrenergic blockade first to control hypertension, followed by β-blockade to control tachycardia. Never give β-blockade first, as unopposed α-adrenergic stimulation will lead to refractory hypertension. HYP E R ALD OS TE R ONI SM KEY FACT In pheochromocytoma, administer α-blockers before β-blockers to prevent hypertensive crisis. Look for elevated plasma-free metanephrines (metanephrine and normetanephrine) or 24-hour urine metanephrines and catecholamines. Results from excessive secretion of aldosterone from the zona glomerulosa of the adrenal cortex. It is usually due to adrenocortical hyperplasia (70%) but can also result from unilateral adrenal adenoma (Conn’s syndrome). HISTORY/PE n n n Presents with hypertension, headache, polyuria, and muscle weakness. Tetany, paresthesias, and peripheral edema are seen in severe cases. Consider hyperaldosteronism in younger adults who are diagnosed with hypertension without risk factors or a family history of hypertension. DIAGNOSIS n n n 1 1° (psychogenic) polydipsia, a condition in which patients consume large volumes of fluid, resulting in polyuria. It most often occurs in patients with psychiatric disorders. Patients present with symptoms similar to DI, but following a water deprivation test, urine osmolality ↑ (vs. DI, in which urine remains dilute). 2 VMA and metanephrines. Medullary carcinoma of the thyroid is associated with MEN type 2A/2B, an autosomal dominant condition that predisposes patients not only to medullary carcinoma but also to parathyroid adenomas and pheochromocytomas. Screening for pheochromocytoma with urine VMA and metanephrines prior to surgery can prevent potentially life-threatening hypertensive crises during thyroidectomy. Patients have diastolic hypertension without edema. Labs show hypokalemia, mild hypernatremia, metabolic alkalosis, hypomagnesemia, hyperaldosteronism, and an ↑ aldosterone/plasma renin activity ratio (usually > 30). CT or MRI may reveal an adrenal mass. Adrenal venous sampling may be needed to localize the adenoma or to confirm bilateral adrenal hyperplasia. TREATMENT n n Surgical resection for adrenal tumors (after correction of BP and potassium). Treat bilateral hyperplasia with spironolactone, an aldosterone receptor antagonist. CONG E NI TAL ADR E NAL HYP E R P LAS I A ( C AH) A condition of adrenal insufficiency due to a variety of inherited enzyme deficiencies that impair cortisol synthesis and result in the accumulation of cortisol precursors. Without the " feedback of cortisol on the hypothalamus and pituitary, ACTH secretion ↑, leading to the overproduction of adrenal androgens. Most cases are due to 21-hydroxylase deficiency (95%, autosomal recessive), but other causes include 11- and 17-hydroxylase deficiencies. CAH can manifest either in a salt-losing form or in a non-salt-losing form. HISTORY/PE Presentation varies with gender: n n Females: In both forms, presents at birth with ambiguous genitalia. Males: Presents at birth with adrenal crisis in the salt-losing form, but presents with precocious puberty in the non-salt-losing form. ENDOCRINOLOGY HIGH-YIELD FACTS IN DIAGNOSIS n n Electrolyte abnormalities include hyponatremia, hyperkalemia, and metabolic acidosis. In severe cases, mineralocorticoid deficiency may lead to life-threatening salt wasting. An elevated serum 17-hydroxyprogesterone level is diagnostic. TREATMENT n n n Medical: Immediate fluid resuscitation and salt repletion. Administer cortisol to ↓ ACTH and adrenal androgens. Fludrocortisone is appropriate for severe 21-hydroxylase deficiency. Surgical: Correct ambiguous genitalia in female infants. Refer to the Gynecology chapter for information on the diagnosis and treatment of late-onset CAH. Multiple Endocrine Neoplasias (MEN) A family of tumor syndromes with autosomal dominant inheritance. n n n MEN type 1 (Wermer’s syndrome): Pancreatic islet cell tumors (eg, gastrinomas [Zollinger-Ellison syndrome], insulinomas, VIPomas), parathyroid hyperplasia, and pituitary adenomas. MEN type 2A (Sipple’s syndrome): Medullary carcinoma of the thyroid, pheochromocytoma or adrenal hyperplasia, parathyroid gland hyperplasia. Due to mutations in the RET proto-oncogene. MEN type 2B: Medullary carcinoma of the thyroid, pheochromocytoma, oral and intestinal ganglioneuromatosis (mucosal neuromas), marfanoid habitus. Due to mutations in the RET proto-oncogene. MNEMONIC MEN 1 affects “P” organs: Pancreas Pituitary Parathyroid 97 98 HIGH-YIELD FACTS IN ENDOCRINOLOGY NOTES HIGH-YIELD FACTS IN EPIDEMIOLOGY Assessment of Disease Frequency CROSS-SECTIONAL STUDIES Assessment of Diagnostic Studies 100 100 100 SENSITIVITY AND SPECIFICITY 100 POSITIVE AND NEGATIVE PREDICTIVE VALUES 101 Treatment 104 RANDOMIZED CONTROLLED TRIALS 104 BIAS 105 CHANCE 106 Prevention 107 LIKELIHOOD RATIO 101 VACCINATION 107 COHORT STUDIES 102 BEHAVIORAL COUNSELING 108 CASE-CONTROL STUDIES 102 Screening Recommendations 109 Measures of Effect 103 Causes of Death 111 Survival Curves 103 Reportable Diseases 111 99 100 HIGH-YIELD FACTS IN EPIDEMIOLOGY Assessment of Disease Frequency KEY FACT Incidence can be measured in a cohort study; prevalence can be measured in a cross-sectional study. KEY FACT As the mortality of a disease ↓, the prevalence of that disease ↑ (eg, HIV infection) because the duration of disease has lengthened. Remember: P = I × D. n Prevalence = n total number of cases in the population at 1 point in time total population Prevalence depends on incidence and duration: Prevalence (P) = incidence (I) × average duration of disease (D) n The incidence of a disease is the number of new cases in the disease-free population that develop over a period of time. Incidence = n number of new cases in the population over a given time period total population at risk during the specified time period Remember to subtract the number of new cases of disease (numerator) from the total population at risk (denominator) because these individuals are no longer at risk. C R OS S -SE C TI ONAL STU DI E S KEY FACT Another name for a prevalence study is a cross-sectional study. The prevalence of a disease is the number of existing cases in the population at a specific moment in time. A cross-sectional study that is undertaken to estimate prevalence is called a prevalence study. In a prevalence study, people in a population are examined for the presence of a disease of interest at a given point in time. n n The advantages of prevalence studies are as follows: n They provide an efficient means of examining a population, allowing cases and noncases to be assessed all at once. n They can be used as a basis for diagnostic testing. n They can be used to plan which health services to offer and where. Their disadvantages include the following: n One cannot determine causal relationships because information is obtained only at a single point in time. n The risk or incidence of disease cannot be directly measured. Assessment of Diagnostic Studies SE NS I TI VI TY AND S P EC I F IC I TY Physicians often use tests to try to ascertain a diagnosis, but because no test is perfect, a given result may be falsely ! or " (see Figure 2.4-1). When deciding whether to administer a test, one should thus consider both its sensitivity and its specificity. Disease Present No Disease Positive test a b PPV = a / (a + b) Negative test c d NPV = d / (c + d) Sensitivity = a / (a + c) Specificity = d / (b + d) FIGURE 2.4-1. Sensitivity, specificity, PPV, and NPV. EPIDEMIOLOGY n Sensitivity: The probability that a patient with a disease will have a ! test result. A sensitive test will rarely miss people with the disease and is therefore good at RULING OUT those who do not have the disease. False-" ratio = 1 − sensitivity n Specificity: The probability that a patient without a disease will have a " test result. A specific test will rarely determine that someone has the disease when in fact they do not and is therefore good at RULING IN those who have the disease. HIGH-YIELD FACTS IN 101 KEY FACT SNOUT: SeNsitive tests rule OUT disease. SPIN: SPecific tests rule IN disease. False-! ratio = 1 − specificity n The ideal test is both sensitive and specific, but a trade-off must often be made between sensitivity and specificity. When sensitivity ↑, specificity ↓ (and vice versa). n High sensitivity is particularly desirable when there is a significant penalty for missing a disease. It is also desirable early in a diagnostic workup or screening test, when it is necessary to reduce a broad differential. Example: An initial ELISA test for HIV infection. n High specificity is useful for confirming a likely diagnosis or for situations in which false-! results may prove harmful. Example: A Western blot confirmatory HIV test. PO S IT IV E A N D NE G A T IV E P R E D ICTI VE V ALU E S Once a test has been administered and a patient’s result has been made available, that result must be interpreted through use of predictive values (or posttest probabilities): n n Positive predictive value (PPV): The probability that a patient with a ! test result truly has the disease. The more specific a test, the higher its PPV. The higher the disease prevalence, the higher the PPV of the test for that disease. Negative predictive value (NPV): The probability that a patient with a " test result truly does not have the disease. The more sensitive a test, the higher its NPV. The lower the disease prevalence, the higher the NPV of the test for that disease. KEY FACT Because the predictive value of a test is affected by disease prevalence, it is advantageous to apply diagnostic tests to patients with an ↑ likelihood of having the disease being sought (ie, an at-risk population). 1 LI K E L IH O O D R A T IO ( L R ) Another way to describe the performance of a diagnostic test involves the use of likelihood ratios (LRs), which express how much more or less likely a given test result is in diseased as opposed to nondiseased people: n n ! LR = diseased people with a ! test result sensitivity = nondiseased people with a ! test result 1 − specificity " LR = diseased people with a " test result 1 − sensitivity = nondiseased people with a " test result specificity The ! LR represents the fraction of patients with a disease who have a ! test divided by the fraction of patients without a disease who have a ! test. In other words, the ! LR answers the following question: What is the proportion of patients with a target disorder who have a ! test compared with the proportion of healthy patients who have a ! test? The " LR represents the fraction of patients with a disease who have a " test divided by the fraction of patients without a disease who have a " test. A local child-care center that was built before the 1950s was found to have elevated lead levels in its paint. A student organization at your medical school is hosting a lead-screening event to test all the children at the center. Which initial screening test would be more appropriate: a test that has high sensitivity or one that has high specificity? 2 What happens to the PPV and NPV when prevalence ↓? 102 HIGH-YIELD FACTS IN EPIDEMIOLOGY n n In other words, the " LR answers the following question: What is the proportion of patients with a target disorder who have a " test compared with the proportion of healthy patients who have a " test? The ! LR shows how much the odds (or probability) of disease are ↑ if the test result is !. The " LR shows how much the odds (or probability) of disease are ↓ if the test result is ". Posttest odds = pretest odds × LR C OHOR T S TUDIES KEY FACT If you see a set of COworkers being followed over time, think COhort study. KEY FACT In a cohort study, a group of people is assembled, none of whom has the outcome of interest (ie, the disease), but all of whom could potentially experience that outcome. For each possible risk factor, the members of the cohort are classified as either exposed or unexposed. All the cohort members are then followed over time, and the incidence of outcome events is compared in the 2 exposure groups. n Cohort studies are also known as longitudinal studies or incidence studies. KEY FACT In cohort studies, the researcher determines whether the participants are exposed or unexposed and follows them over time for disease development. The relative risk ratio can be calculated directly. 1 A test with high sensitivity such as a fingerstick lead test (capillary blood) is preferred for initial screening because it can ensure that no children who might have the disease—and who might therefore benefit from further testing and treatment—will be missed. The children with a ! fingerstick test should subsequently have a serum blood level drawn (higher specificity). n Cohort studies may be either prospective, in which a cohort is assembled in the present and followed into the future, or retrospective, in which a cohort is identified from past records and is followed to the present. CAS E -C ONTR OL S TU DI E S Case-control studies can be thought of as an efficient way to study a population. A series of cases are identified and a set of controls are sampled from the underlying population to estimate the frequency of exposure in the population at risk of the outcome. In such studies, a researcher compares the frequency of exposure to a possible risk factor in the 2 groups. n n 2 PPV ↓ and NPV ↑. Remember that if prevalence is low, even a test with high sensitivity or specificity will have a low PPV. Advantages of cohort studies are as follows: n They follow the same logic as the clinical question (if people are exposed, will they get the disease?). n They are the only way to directly determine incidence (because they follow a cohort over time to assess disease development). n They can be used to assess the relationship of a given exposure to many diseases. n In prospective studies, exposure is elicited without bias from a known outcome. Disadvantages of cohort studies include the following: n They can be time consuming and expensive. n Studies assess only the relationship of the disease to the few exposure factors recorded at the start of the study. n They require many subjects, which makes it difficult to study rare diseases. n The validity of a case-control study depends on appropriate selection of cases and controls, the manner in which exposure is measured, and the manner in which extraneous variables (confounders) are dealt with. Cases and controls should be comparable in terms of opportunity for exposure (ie, they should be members of the same base population with an equal opportunity of risk factor exposure). “Matching” in case-control studies occurs when the researcher chooses controls that match cases on a particular characteristic. For example, if matching on gender, female cases would be matched to female controls and male cases would be matched to male controls. The purpose of matching, followed by the appropriate analysis, is to ↓ confounding. EPIDEMIOLOGY n n Advantages of case-control studies are as follows: n They use smaller groups than cohorts, thereby reducing cost. n They can be used to study rare diseases and can easily examine multiple risk factors. Disadvantages include the following: n Studies cannot calculate disease prevalence or incidence or directly estimate the relative risk because the numbers of subjects with and without a disease are determined artificially by the investigator rather than by nature; however, an odds ratio can be used to estimate a measure of relative risk (rate ratio). n Retrospective data may be inaccurate owing to recall or survivorship biases. Measures of Effect There are several ways to express and compare risk. These include the following: n n HIGH-YIELD FACTS IN 103 KEY FACT If alcohol intake among individuals with breast cancer is compared with that of individuals without breast cancer, think case-control study. KEY FACT In case-control studies, the researcher determines whether the participants have the disease or not and determines if they were exposed or unexposed. The odds ratio is calculated as an estimate of relative risk because it can’t be calculated directly. Absolute risk: Defined as the incidence of disease. Attributable risk (or risk difference): The difference in risk between the exposed and unexposed groups. Attributable risk = incidence of disease in exposed − incidence in unexposed n Relative risk (or risk ratio): Expresses how much more likely an exposed person is to get the disease in comparison to an unexposed person. This indicates the relative strength of the association between exposure and disease, making it useful when one is considering disease etiology. Relative risk = incidence in exposed incidence in unexposed n Odds ratio: An estimate of relative risk that is used in case-control studies. The odds ratio tells how much more likely it is that a person with a disease has been exposed to a risk factor than someone without the disease. The lower the disease incidence, the more closely it approximates relative risk. In case-control studies, the odds ratio also describes how many times more likely an exposed individual is to have disease compared to an unexposed individual (see Figure 2.4-2). Odds ratio = KEY FACT Odds = probability of event 1 − probability of event Probability = odds 1 + odds odds that a diseased person is exposed odds that a nondiseased person is exposed Survival Curves Once a diagnosis has been established, it is important to be able to describe the associated prognosis. Survival analysis is used to summarize the aver- Assume that the data below are from a hypothetical case-control study. Calculate and interpret the odds ratio (OR). Disease Develops No Disease Exposure a b a / (a + b) RR = c / (c + d) No exposure c d OR = ad / bc FIGURE 2.4-2. Relative risk (RR) vs. odds ratio (OR). EXPOSED NOT EXPOSED Cases 734 433 Controls 563 538 104 HIGH-YIELD FACTS IN EPIDEMIOLOGY age time from 1 event (eg, presentation, diagnosis, or start of treatment) to any outcome that can occur only once during follow-up (eg, death or recurrence of cancer). The usual method is with a Kaplan-Meier curve (see Figure 2.4-3) describing the survival (or time-to-event if the measured outcome is not death) in a cohort of patients, with the probability of survival decreasing over time as patients die or drop out (are censored) from the study. Treatment Studies are typically used to compare treatments for a disease. Although the gold standard for such evaluation is a randomized, double-blinded controlled trial, other types of studies may be used as well (eg, an observational study, in which the exposure in question is a therapeutic intervention). In descending order of quality, published studies regarding treatment options include randomized controlled trials, observational studies, and case series/ case reports. Meta-analyses are often used to systematically synthesize information across studies to help summarize the totality of the evidence. RANDOM I ZE D C ONTR OLLE D TR I ALS (R C T s) KEY FACT Randomization minimizes bias and confounding; double-blinded studies prevent observation bias. An RCT is defined as an experimental, prospective study in which subjects are randomly assigned to a treatment or control group. Random assignment helps ensure that the 2 groups are truly comparable. The control group may be treated with a placebo or with the accepted standard of care. The study may be masked in 1 of 2 ways: single blinded, in which patients do not know which treatment group they are in, or double blinded, in which neither the patients nor their physicians know who is in which group. Double-blinded studies are the gold standard for studying treatment effects. n n Advantages of RCTs are as follows (see also Table 2.4-1): n They minimize bias. n They have the potential to demonstrate causal relationships because exposure is assigned randomly, which minimizes confounding. Disadvantages include the following: n They are costly and time intensive. n Some interventions (eg, surgery) are not amenable to masking. 100 OR = ad / bc = (734 × 538) / (433 × 563) = 1.62. Interpretation: The exposed group had 1.62 times the odds of having disease compared to the unexposed group. Survival (%) Chemotherapy plus radiation 50 Radiation alone 0 5 FIGURE 2.4-3. 10 Years Example of a Kaplan-Meier curve. 15 EPIDEMIOLOGY TA B L E 2 . 4 - 1 . Comparison of Study Designs VARIABLE Purpose Outcomes HIGH-YIELD FACTS IN 105 RCT COHORT CROSS-SECTIONAL CASE CONTROL Tests causality through Tests association over a Determines prevalence in Tests association (usually random assignment of specified period of time to a snapshot of time. retrospectively). exposure; randomization capture the development removes confounding. of disease. Any outcomes that are Relative risk, odds ratio, Prevalence Odds ratio. reported represent causal incidence, prevalence. (not incidence). Subjects are not assigned Determines disease Identifies cases (disease) prevalence at 1 point in and controls (no disease) relationships. Design Subjects are randomly assigned to be in to groups. exposed (treatment A) or Determines if subjects time; cannot determine groups first and then goes nonexposed (treatment B) are in exposed or the directionality of backward to determine if groups. nonexposed groups and association between they are exposed or not follows them until they exposure and outcome. (the opposite of RCT and cohort studies). develop the disease (or do not). Advantages Disadvantages Can determine causality; Temporality can be Less time consuming and Predetermined number of minimizes bias and determined; incidence can costly. cases; less time consuming confounding. be determined. RCT is not possible when: Follows large groups over long time periods. n The treatment has an n The outcome is very rare. retrospective cohort n The treatment is in studies. adverse outcome. Selection bias in and costly. Recall bias, selection bias. Directionality of association cannot be determined. Incidence cannot be determined. widespread use or represents the best option (because it is unethical to withhold treatment). BIAS Defined as any process that causes results to systematically differ from the truth. Common types of bias include the following: n n n Selection bias: Occurs when samples or participants are selected that differ from other groups in additional determinants of outcome. Example: Individuals concerned about a family history of breast cancer may be more likely to self-select in entering a mammography program, giving the impression of a prevalence that is higher than it is in reality. Measurement bias: Occurs when measurement or data-gathering methods differ between groups. Example: One group is assessed by CT while another group is assessed by MRI. Confounding bias: Occurs when a third variable is either positively or negatively associated with both the exposure and outcome variables, inducing an incorrect association. Example: Fishermen in an area may KEY FACT Studies that are masked and randomized are better protected from the effects of bias, whereas observational studies are particularly susceptible to bias. 106 HIGH-YIELD FACTS IN EPIDEMIOLOGY KEY FACT Confounding variables reduce the internal validity of a study. n n n experience a higher incidence of lung cancer than that found in the general population. However, if smokers are more likely to become fishermen and are also more likely to develop lung cancer than nonsmokers, becoming a fisherman will not in itself lead to lung cancer. Rather, it is the smoking to which those fishermen are exposed that causes the association. Recall bias: Results from a difference between 2 groups in the retrospective recall of past factors or outcomes. Example: A patient with cancer may be more motivated than would a healthy individual to recall past episodes of chemical exposure. Lead-time bias: Results from earlier detection of disease, giving an appearance of prolonged survival when in fact the natural course is not altered. Example: A new and widely used screening test that detects cancer 5 years earlier may yield the impression that patients are living longer with the disease. Length bias: Occurs when screening tests detect a disproportionate number of slowly progressive diseases but miss rapidly progressive ones, leading to overestimation of the benefit of the screen. Example: A better prognosis for patients with cancer is celebrated following the implementation of a new screening program. However, this test disproportionately detects slowgrowing tumors, which generally tend to be less aggressive. C HAN CE Even with bias reduction, unsystematic random error is unavoidable owing to chance variation in studied data. Types of errors are as follows: n n Type I (α) error: n Defined as the probability of concluding that there is a difference in treatment effects between groups when in fact there is not (ie, a false-! conclusion)—in other words, rejecting the null hypothesis (of no effect) when it should not be rejected. n The p-value is an estimate of the probability that differences in treatment effects in a study could have happened by chance alone if no true association exists. Often, differences associated with a p < 0.05 are statistically significant. A p-value alone does not give any information about the direction or size of the effect. Type II (β) error: n Defined as the probability of concluding that there is no difference in treatment effects when in fact a difference exists (ie, a false-" conclusion)—in other words, not rejecting the null hypothesis (of no effect) when it should be rejected. n Power is the probability that a study will find a statistically significant difference when one is truly there. Increasing the number of subjects in a study ↑ the power. Power (β) = 1 – type II error n The confidence interval (CI) is a way of expressing statistical significance (p-value) that shows the size of the effect and the statistical power (the narrower the CI, the greater the statistical power). CIs are interpreted as follows: n If one is using a 95% CI, there is a 95% chance that the interval contains the true value. By definition, the 95% CI contains the point estimate 100% of the time (in other words, if the calculated OR is 2.4, then the CI will always contain that value by definition). n Example: You would like to estimate the percentage of women with a specific disease. A 10% result from a sample of 3000 women would provide a 95% CI of 9–11%, whereas a 10% finding from a sample of EPIDEMIOLOGY n HIGH-YIELD FACTS IN 30 women would yield a CI of −1% of 21%. The first case has more power because the sample size is larger, producing a narrow interval. In the latter case, you cannot state with 95% certainty that women in general even have the disease because the interval contains 0%, which is the null value. If the CI includes the null value (relative risk or odds ratio of 1.0 or 0%), the results are not statistically significant. Prevention n n KEY FACT There are 3 levels of prevention: n 1° prevention: Includes preventive measures to ↓ the incidence of disease. n 2° prevention: Focuses on identifying the disease early, when it is asymptomatic or mild, and implementing measures that can halt or slow disease progression. Includes screening tests that are designed to identify subclinical disease. n 3° prevention: Includes measures that ↓ morbidity or mortality resulting from the presence of disease. Prevention may be accomplished by a combination of immunization, chemoprevention, behavioral counseling, and screening. A good screening test has the following characteristics: n It has high sensitivity and specificity (usually more important to have high sensitivity to rule out those that don’t have the disease). n It has a high PPV. n It is inexpensive, easy to administer, and safe. n Treatment after screening is more effective than subsequent treatment without screening. V AC C I N A T IO N n n 107 Vaccines work by mimicking infections and triggering an immune response in which memory cells are formed to recognize and fight any future infection. There are several different vaccine formulations, as indicated in Table 2.4-2. Recommended vaccination schedules for children and adults are outlined in Figures 2.4-4 through 2.4-6. TA B L E 2 . 4 - 2 . Types of Vaccinations VACCINE TYPE Live attenuated TARGETED DISEASES Measles, mumps, rubella, polio (Sabin), yellow fever, influenza (nasal spray). Inactivated (killed) Cholera, influenza, HAV, polio (Salk), rabies, influenza (injection). Toxoid Diphtheria, tetanus. Subunit HBV, pertussis, Streptococcus pneumoniae, HPV, meningococcus. Conjugate Hib, S pneumoniae. n n n 1° prevention: A woman reduces dietary intake of fat or alcohol to reduce her risk of developing breast cancer. 2° prevention: A woman obtains a mammogram to screen for breast cancer. 3° prevention: A woman undergoes adjuvant therapy with tamoxifen for breast cancer. 108 HIGH-YIELD FACTS IN Vaccine ▼ Age ► Birth HepB Hepatitis B EPIDEMIOLOGY 1 month 2 4 6 12 15 18 19–23 months months months months months months months HepB RV RV RV DTaP DTaP Hib Hib Hib Hib Pneumococcal PCV PCV PCV PCV Inactivated Poliovirus IPV IPV Diphtheria, Tetanus, Pertussis type b DTaP Varicella DTaP IPV MMR MMR Varicella Varicella HepA (2 doses) Hepatitis A Range of recommended ages for all children PPSV IPV Measles, Mumps, Rubella Range of recommended ages for certain high-risk groups HepA Series MCV4 Meningococcal FIGURE 2.4-4. 4–6 years HepB DTaP Rotavirus 2–3 years Recommended vaccinations for children 0–6 years of age. (Reproduced with permission from the Centers for Disease Control and Preven- tion, Atlanta, GA, www.cdc.gov/vaccines/recs/schedules/child-schedule.htm. Data from 2011.) n Live vaccines should not be administered to immunosuppressed patients. They are also contraindicated in pregnant women owing to a theoretical risk of maternal-fetal transmission. A possible exception to this rule can be some asymptomatic HIV/AIDS patients who may be candidates for the MMR vaccine. B E HAVI OR AL C OU NS E LI NG In offering counsel, physicians should tailor their education and suggestions to the individual patient as well as to his or her stage of change (see Table 2.4-3). Vaccine ▼ Age ► 7–10 years Tetanus, Diphtheria, Pertussis Human Papillomavirus MCV4 Meningococcal 11–12 years 13–18 years Tdap Tdap HPV (3 doses)(females) HPV Series MCV4 MCV4 Range of recommended ages for all children Influenza Pneumococcal Pneumococcal Hepatitis A HepA Series Hepatitis B Hep B Series Inactivated Poliovirus IPV Series Measles, Mumps, Rubella MMR Series Varicella Series Varicella FIGURE 2.4-5. Range of recommended ages for catch-up immunization Range of recommended ages for certain high-risk groups Recommended vaccinations for children 7–18 years of age. (Reproduced with permission from the Centers for Disease Control and Preven- tion, Atlanta, GA, www.cdc.gov/vaccines/recs/schedules/child-schedule.htm. Data from 2011.) EPIDEMIOLOGY AGE GROUP VACCINE 19–26 years 27–49 years 50–59 years Influenza * HIGH-YIELD FACTS IN 109 60–64 years > 65 years 1 dose annually Tetanus, diphtheria, pertussis (Td/Tdap)* Substitute 1-time dose of Tdap for Td booster; then boost with Td every 10 yrs Varicella* Td booster every 10 yrs 2 doses Human papillomavirus (HPV)* 3 doses (females) 1 dose Zoster Measles, mumps, rubella (MMR)* 1 or 2 doses 1 dose 1 dose 1 or 2 doses Pneumococcal (polysaccharide) Meningococcal* 1 or more doses Hepatitis A* 2 doses Hepatitis B* 3 doses *Covered by the Vaccine Injury Compensation Program. For all persons in this category who meet the age requirements and who lack evidence of immunity (eg, lack documentation of vaccination or have no evidence of previous infection) Recommended if some other risk factor is present (eg, based on medical, occupational, lifestyle, or other indications) No recommendation Recommended vaccinations for adults. (Reproduced with permission from the Centers for Disease Control and Prevention, Atlanta, GA, www.cdc. FIGURE 2.4-6. gov/vaccines/recs/schedules/adult-schedule.htm. Data from 2011.) Screening Recommendations Tables 2.4-4 and 2.4-5 outline recommended health care screening measures by gender and age. TA B L E 2 . 4 - 3 . Stages of Change in Behavioral Counseling STAGE OF CHANGE CHARACTERIZATION EXAMPLE Precontemplation Denial or ignorance of the problem. A 51-year-old smoker has not even thought about cessation. Contemplation Ambivalence or conflicted emotions; A 43-year-old crack cocaine addict considers treatment for her assessing benefits and barriers to change. addiction. Experimenting with small changes; A 28-year-old heroin addict visits his doctor to ask questions about collecting information about change. quitting. Taking direct action toward achieving a goal. A 33-year-old enters a rehabilitation facility for treatment of addiction Preparation Action to prescription narcotics. Maintenance Maintaining a new behavior; avoiding A 41-year-old continues to visit Alcoholics Anonymous meetings to temptation. gain support and reinforcement against relapse. 110 HIGH-YIELD FACTS IN TA B L E 2 . 4 - 4 . EPIDEMIOLOGY Health Screening Recommendations for Women by Age RECOMMENDATION AGE 19–39 CARDIOVASCULAR BP screening at least once every 2 years. Cholesterol screening starting at age 20. BREAST/REPRODUCTIVE Discuss clinical breast examination with OTHER N/A physician or nurse. Pap test every 2 years starting at age 21; then every 3 years for women ≥ 30. Pelvic exam yearly starting at age 21; chlamydia test yearly until age 24 if sexually active. Women ≥ 25 should be tested only if there is an ↑ risk. HIV test at least once to ascertain status. 40–49 BP screening at least once every 2 years. Discuss cholesterol screening with physician or nurse. Mammogram once every 1–2 years. Diabetes: Blood glucose or HbA1c Discuss clinical breast examination with screening starting at age 45 and then physician or nurse. every 3 years. Pap test every 3 years. Pelvic examination yearly; chlamydia test if the patient has new or multiple partners. HIV test at least once to ascertain status. 50–64 BP screening at least once every 2 years. Discuss cholesterol screening with physician or nurse. Mammogram once every 1–2 years. Discuss clinical breast examination with physician or nurse. Pap test every 3 years. Pelvic exam yearly; chlamydia test if the patient has new or multiple partners. Diabetes: Blood glucose or HbA1c screening every 3 years. Bone: Discuss bone mineral density (BMD) test with physician or nurse. Colorectal: Discuss which test is best with physician or nurse. HIV test at least once to ascertain status. ≥ 65 BP screening at least once every 2 years. Discuss cholesterol screening with physician or nurse. Mammogram once every 1–2 years. Discuss clinical breast examination with physician or nurse. Discuss Pap test with physician or nurse. Pelvic examination yearly; chlamydia test if the patient has new or multiple partners. Discuss HIV test with physician or nurse. (Adapted with permission from the U.S. Department of Health and Human Services, Washington, DC, www.womenshealth.gov/pub/women.cfm.) Diabetes: Blood glucose or HbA1c screening every 3 years. Bone: BMD test at least once. Colorectal: Discuss which test is best with physician or nurse. EPIDEMIOLOGY TA B L E 2 . 4 - 5 . HIGH-YIELD FACTS IN 111 Health Screening Recommendations for Men by Age RECOMMENDATION AGE 19–39 CARDIOVASCULAR BP screening at least once every 2 years. Cholesterol screening starting at age 20. REPRODUCTIVE Discuss testicular examination with OTHER N/A physician or nurse. Both partners should be tested for STDs, including HIV, before initiating sexual intercourse. 40–49 BP screening at least once every 2 years. Discuss cholesterol screening with physician or nurse. Discuss DRE and PSA with physician or nurse. Diabetes: Blood glucose or HbA1c screening starting at age 45 and then every 3 years. Discuss testicular examination with physician or nurse. HIV test at least once to ascertain status. 50–64 BP screening at least once every 2 years. Discuss cholesterol screening with physician or nurse. Discuss DRE and PSA with physician or nurse. Discuss testicular examination with physician or nurse. HIV test at least once to ascertain Diabetes: Blood glucose or HbA1c screening every 3 years. Colorectal: Fecal occult blood test (FOBT) yearly; flexible sigmoidoscopy every 5 years or colonoscopy every 10 years. status. ≥ 65 BP screening at least once every 2 years. Discuss cholesterol screening with physician or nurse. Discuss DRE and PSA with physician or nurse. Discuss testicular examination with physician or nurse. Discuss HIV test with physician. Diabetes: Blood glucose or HbA1c screening every 3 years. Colorectal: FOBT yearly (patients > 75 should discuss with physician); flexible sigmoidoscopy every 5 years or colonoscopy every 10 years (patients > 75 should discuss with physician). (Adapted with permission from the U.S. Department of Health and Human Services, Washington, DC, www.womenshealth.gov/pub/women.cfm.) Causes of Death The leading cause of cancer mortality in the United States is lung cancer. Prostate and breast cancers are the most prevalent cancers in men and women, respectively, with lung and colorectal cancers ranking second and third most common in both sexes. Table 2.4-6 lists the principal causes of death in the United States by age group. Reportable Diseases By law, disease reporting is mandated at the state level, and the list of diseases that must be reported to public health authorities varies slightly by state. The CDC has a list of nationally notifiable diseases that states voluntarily report to the CDC. These diseases include but are not limited to those listed in Table 2.4-7. A hypothetical study finds a ! association between poor sleep habits and the risk of Parkinson’s disease. The relative risk is 10 and the p-value is 0.4. How do you interpret these results? 112 HIGH-YIELD FACTS IN EPIDEMIOLOGY TA B L E 2 . 4 - 6 . Leading Causes of Death by Gender RANK MEN WOMEN 1 Heart disease (26.3%) Heart disease (25.8%) 2 Cancer (24.1%) Cancer (22%) 3 Unintentional injuries (6.6%) Stroke (6.7%) 4 Chronic lower respiratory diseases Chronic lower respiratory diseases (4.9%) (5.3%) 5 Stroke (4.5%) Alzheimer’s disease (4.2%) 6 Diabetes (3%) Unintentional injuries (3.5%) 7 Suicide (2.2%) Diabetes (3%) 8 Influenza and pneumonia (2.1%) Influenza and pneumonia (2.5%) 9 Kidney disease (1.8%) Kidney disease (1.9%) 10 Alzheimer’s disease (1.8%) Septicemia (1.5%) (Adapted with permission from the Centers for Disease Control and Prevention, Atlanta, GA, www.cdc.gov/men/lcod/ and www.cdc.gov/women/lcod/. Data from 2006.) T A B L E 2 . 4 - 7. Common Reportable Diseases DISEASE CATEGORY EXAMPLES STDs HIV, AIDS, syphilis, gonorrhea, chlamydia, chancroid, HCV. Tick-borne Lyme disease, ehrlichiosis, Rocky Mountain spotted fever. disease Potential Anthrax, smallpox, plague. bioweapons Vaccine- Diphtheria, tetanus, pertussis, measles, mumps, rubella, polio, varicella, preventable HAV, HBV, H influenzae (invasive), meningococcal disease. disease There is not sufficient evidence to reject the null hypothesis, and therefore there is insufficient evidence to support an association between poor sleep habits and the risk of Parkinson’s disease. Remember that the null hypothesis always assumes that there is no association between the exposure and outcome variables. If the p-value is > 0.05, then you cannot reject the null hypothesis. Water-/food- Cholera, giardiasis, Legionella, listeriosis, botulism, shigellosis, shiga borne disease toxin–producing E coli, salmonellosis, trichinellosis, typhoid. Zoonoses Tularemia, psittacosis, brucellosis, rabies. Miscellaneous TB, leprosy, toxic shock syndrome, SARS, West Nile virus, vancomycinresistant S aureus (VRSA), coccidioidomycosis, cryptosporidiosis. Methicillin-resistant S aureus (MRSA) is reportable in several states. HIGH-YIELD FACTS IN ETHICS AND LEGAL ISSUES General Principles 114 Informed Consent 114 Minors 114 Competence and Decision-Making Capacity 115 End-of-Life Issues 115 WRITTEN ADVANCE DIRECTIVES 115 WITHDRAWAL OF CARE 116 EUTHANASIA AND PHYSICIAN-ASSISTED SUICIDE 116 FUTILE TREATMENT 116 Disclosure 116 FULL DISCLOSURE 116 MEDICAL ERRORS 117 CLINICAL RESEARCH 117 Confidentiality 117 Conflict of Interest 118 Malpractice 118 113 114 HIGH-YIELD FACTS IN ETHICS AND LEGAL ISSUES General Principles n n n n Respect for autonomy: Clinicians are obligated to respect patients as individuals and to honor their preferences. Example: A surgeon presents the risks and benefits of tumor resection to her patient before consent is given to proceed with the procedure. Beneficence: Physicians have a responsibility to act in the patient’s best interest. As a fiduciary, the physician stands in a special relationship of trust and responsibility to patients. Respect for patient autonomy may conflict with beneficence. Example: An elderly woman is adamant that she does not want to go to a rehabilitation facility and thus refuses amputation of a potentially gangrenous foot. The procedure is necessary to prevent life-threatening complications. The physician has a responsibility to recommend what is in the patient’s best interest. Nonmaleficence: “Do no harm.” All medical interventions involve benefits and risks, and the physician should avoid recommending treatments where the risks are high and the benefits are negligible, remote, or improbable. Sometimes harm cannot be averted, but the benefits of an intervention outweigh the harms and risks. Example: A surgeon declines to perform a procedure because she thinks the patient will die intraoperatively. Justice: With regard to individual patients, fairness is expressed as the notion that similar persons should be treated similarly. Health care is an important resource, and access to quality health care gives individuals a greater chance for a healthy and productive life. Fair distribution of this resource is an ongoing challenge for health policy and in the clinical arena. Informed Consent n n MNEMONIC n BRAIN of informed consent: Benefits Risks Alternatives Indications Nature KEY FACT In general, it is ethically acceptable for a physician to honor a pregnant woman’s refusal of treatment directed toward the fetus if the treatment poses a significant risk of harm to the woman. Physicians should not harm one patient in order to benefit another. Defined as willing and voluntary acceptance of a medical intervention by a patient after adequate discussion with a physician about the nature of the intervention along with its indications, risks, benefits, and potential alternatives (including no treatment). Patients may change their minds at any time. Informed consent is required for significant procedures unless: n Emergency treatment is required. Examples: An unconscious patient presents with cerebral edema after a motor vehicle collision, or a patient without previously indicated DNR/DNI status undergoes cardiac arrest. n Patients lack decision-making capacity (consent is still required but must be obtained from a surrogate decision maker). When possible, assent should be obtained from the patient lacking capacity. Examples: Patients may present with dementia or significant psychiatric disturbances. Minors generally require surrogate decision makers until they demonstrate adequate decision-making capacity or are of legal age. Minors In general, minors (persons < 18 years of age) cannot consent for their own medical treatment and require parents or guardians to consent on their behalf, except in the following situations: n n Life-threatening emergencies when parents cannot be contacted. Legal emancipation: Emancipated minors do not require parental consent for medical care. Minors are emancipated if they are married, are in ETHICS AND LEGAL ISSUES n n the armed services, or are financially independent of their parents and have sought legal emancipation. Sexually transmitted infections and substance abuse treatment: Rules concerning contraception, pregnancy, and abortion services and treatment for drug and alcohol dependency vary across the United States. Some states leave the decision of informing parents about adolescent use of confidential services to the physician based on the best interest of the patient; other states limit disclosure. Refusal of treatment: A parent has the right to refuse treatment for his/her child as long as those decisions do not pose a serious threat to the child’s well-being (eg, refusing immunizations is not considered a serious threat). If a parental decision is not in the best interest of the child, a physician may provide treatment against parental wishes. In emergent situations, if withholding treatment jeopardizes the child’s safety, treatment can be initiated on the basis of legal precedent. Example: A physician provides blood transfusion to save the life of a 6-year-old child seriously injured in a motor vehicle collision despite parental requests to withhold such a measure. Competence and Decision-Making Capacity n n n n n n Competence: Refers to a person’s global and legal capacity to make decisions and be held accountable in a court of law. Competence is assessed by the courts and is distinct from the term decision-making capacity. Decision-making capacity: A medical term that refers to the ability of a patient to understand relevant information, appreciate the severity of the medical situation and its consequences, communicate a choice, and deliberate rationally about one’s values in relation to the decision being made. This can be assessed by the physician. Decision-making capacity is best understood as varying with the complexity of the decision involved. Example: The level of capacity needed for a decision about liver transplantation is different from that needed to choose between 2 types of pain medication for fracture-related pain. Incompetent patients, as assessed by the courts, or temporarily incapacitated patients may still be able to provide assent or dissent for treatment. However, the need to treat supersedes the dissent of an incapacitated patient in emergency situations. Example: An extremely hypertensive patient with altered mental status who refuses treatment must receive antihypertensive therapy, as this constitutes a medical emergency. In general, patients who have decision-making capacity have the right to refuse or discontinue treatment. Example: Jehovah’s Witnesses can refuse blood products. A patient’s decision to refuse treatment can be overruled if the choice endangers the health and welfare of others. Example: A patient with active TB must undergo antibiotic treatment because not treating would pose a public health threat. End-of-Life Issues W R IT T E N A D VA N C E DI R E C T I V E S n Living will: Addresses a patient’s wishes to maintain, withhold, or withdraw life-sustaining treatment in the event of terminal disease or a persistent vegetative state. DNR (do not resuscitate) and DNI (do not intubate) orders are based on patient preferences regarding CPR and intubation only. HIGH-YIELD FACTS IN 115 KEY FACT Patients with psychiatric illness can still give consent if their decision-making capacity is intact. KEY FACT In the absence of a living will or DPOAHC, the Spouse CHIPS in For the patient: Spouse, CHIldren, Parent, Sibling, Friend. 1 A 47-year-old male is diagnosed with pancreatic cancer. His diagnosis and treatment options are discussed, but the patient refuses any intervention. He states that he would like to go home to his wife and children to die peacefully. What is the most appropriate next step in management? 2 A 5-year-old girl with hydrocephalus needs another revision of her ventriculoperitoneal shunt. There are no satisfactory alternative options available to relieve her symptoms. Her father consents but her mother refuses, arguing that she has been through enough procedures in her young life. What is the most appropriate next step in management? 3 A 51-year-old male is brought to the ER after he was struck by a motor vehicle. He is unresponsive and in need of emergent surgery. His wife and children cannot be reached. What is the most appropriate next step in treatment? 116 HIGH-YIELD FACTS IN KEY FACT DNR/DNI orders do not mean “do not treat.” ETHICS AND LEGAL ISSUES n n KEY FACT In general, physicians do not have to comply with requests for futile treatment. W I THDR AW AL OF C AR E n n n 1 Respectfully ask the patient about his reasons for not wanting to pursue treatment. Patients often need clarification and reassurance. If he continues to decline treatment, you should abide by his decision. n 2 Euthanasia is the administration of a lethal agent with the intent to end life. n It is opposed by the AMA Code of Medical Ethics and is illegal in all states. n Patients who request euthanasia should be evaluated for inadequate pain control and comorbid depression. Physician-assisted suicide (also known as physician aid-in-dying) is prescribing a lethal agent to a patient who will self-administer it to end his/ her own life. This is currently illegal except in the states of Oregon, Washington, and Montana. FU TI LE T R E ATM E NT Physicians are not ethically obligated to provide treatment and may refuse a patient’s or family member’s request for further intervention on the grounds of futility under any of the following circumstances: n n n n 3 Proceed with the surgery. A physician may give emergent treatment in the absence of informed consent when immediate intervention is necessary to prevent serious harm or death. Patients and their decision makers have the right to forego or withdraw life-sustaining treatment. Nevertheless, physicians should seek to understand patients and their reasons for refusing beneficial treatments. No ethical distinction is made between withholding a treatment and withdrawing a treatment because a patient may choose to refuse an intervention either before or after it is initiated. This may include ventilation, fluids, nutrition, and medications such as antibiotics. If the intent is to relieve suffering and medications administered are titrated for that purpose, it is considered ethical to provide palliative treatment to relieve pain and suffering even if it may hasten a patient’s death. Example: A physician may prescribe an ↑ dose of an opioid analgesic to a patient who is expected to die within a day, even though it may suppress respiration and hasten death. EU TH ANAS I A AND P HYS I C I AN-AS S I S TE D SU I C I DE n Proceed with the shunt revision. The consent of 1 parent is sufficient to proceed with the treatment of a minor, particularly when it is unequivocally clear that the decision is in the child’s best interest. Durable power of attorney for health care (DPOAHC): Legally designates a surrogate health care decision maker if a patient lacks decisionmaking capacity. More flexible than a living will. Surrogates should make decisions consistent with the person’s stated wishes. If no living will or DPOAHC exists, decisions should be made by close family members (spouse, adult children, parents, and adult siblings) or friends, in that order. There is no evidence or pathophysiologic rationale for the treatment. The intervention has already failed. Maximal intervention is currently failing. Treatment will not achieve the goals of care. Disclosure FU LL DI S C LOS U R E n Patients have a right to know about their medical status, prognosis, and treatment options (full disclosure). They have the legal right to obtain copies of their medical records. ETHICS AND LEGAL ISSUES n n A patient’s family cannot require that a physician withhold information from the patient without the knowledge and consent of the patient. A physician may withhold information only if the patient requests not to be told, or perhaps in the rare and controversial case in which a physician determines that disclosure would cause severe and immediate harm to the patient (therapeutic privilege). MED IC AL E R R O R S n n Physicians are obligated to inform patients of mistakes made in their medical treatment. If the cause of a specific error or series of errors is not known, the physician should communicate this with the family promptly and maintain contact with the patient as investigations reveal more facts. CL I N IC AL R E S EA R CH n n Physicians are obligated to inform patients considering involvement in a clinical research protocol about the purpose of the research study and the entire study design as it will affect the patient’s treatment. This includes the possible risks, benefits, and alternatives to the research protocol. An informed consent form approved by the overseeing research institutional review board (IRB) must be completed for participation in any clinical research protocol, describing the possible risks and benefits of involvement in the research study. Confidentiality n n n Information disclosed by a patient to his/her physician and information about a patient’s medical condition are confidential and cannot be divulged to anyone not directly involved in the patient’s care without expressed patient consent, with few exceptions (described below). A patient may waive the obligation of the physician to protect confidentiality (eg, with insurance companies), preferably by way of written consent. It is ethically and legally necessary to override confidentiality in the following situations: n Patient intent to commit a violent crime (Tarasoff decision): Physicians have a duty to protect the intended victim through reasonable means (eg, warn the victim, notify police). n Suicidal patients. n Child abuse/neglect and elder mistreatment. n Reportable infectious diseases (duty to warn public officials and identifiable people at risk). It is normally best to encourage patients themselves to inform loved ones who are at risk for contracting the illness. n Gunshot and knife wounds (duty to notify the police). n Impaired automobile drivers. Currently, only 6 states have mandatory physician reporting laws. Example: A patient begins to drive 1 week after hospitalization for seizures, although the department of motor vehicles in his state requires that licensed drivers be without seizures for at least 3 months. HIGH-YIELD FACTS IN 117 KEY FACT Physicians cannot report isolated intimate-partner violence without the consent of the patient, but they can and should document the encounter in detail. KEY FACT Potential signs of elder mistreatment: n Cuts, bruises, pressure ulcers, burns n Uncommon fractures n Malnutrition or dehydration n Anogenital injury or infection n Evidence of poor caretaking KEY FACT Signs of suspected child abuse: n History given is not consistent with injury n Subdural hematomas n Retinal hemorrhages n Spiral, bucket-handle, or rib fractures n Injuries in different stages of healing n Unusual child or parental behavior MNEMONIC Overriding confidentiality— WAIT a SEC before letting a dangerous patient go! Wounds Automobile-driving impairment Infectious disease Tarasoff—violent crimes Suicide Elder mistreatment Child abuse A 35-year-old female visits a primary care physician after hurting her wrist. Physical examination reveals circumferential bruises of her wrist, neck, and arms. The patient admits that the injuries were inflicted by her husband. What is the most appropriate next step in management? 118 HIGH-YIELD FACTS IN ETHICS AND LEGAL ISSUES KEY FACT Guiding principles for overriding confidentiality: n There is an identifiable third party at risk for harm. n The harm is significant and probable. n Disclosure will help prevent or mitigate the harm. n Other measures, such as convincing the patient to self-disclose, have failed. Conflict of Interest n n Malpractice n KEY FACT A physician should never engage in a romantic or sexual relationship with a patient. MNEMONIC The 4 D’s of malpractice: Duty Dereliction Damage Direct cause Offer support and acknowledge the courage it takes to discuss abuse. Assess the safety of the woman and of any children involved, introduce the concept of an emergency plan, and encourage the use of community resources. Occurs when physicians find themselves having a personal interest in a given situation that influences their professional obligations. Example: A physician may own stock in a pharmaceutical company (financial interest) that produces a drug he is prescribing to his patient (patient care interest). Physicians should disclose existing conflicts of interest to affected parties (eg, patients, institutions, audiences of journal articles or scientific meetings). n The essential elements of a civil suit under negligence include the 4 D’s: n The physician has a Duty to the patient. n Dereliction of duty occurs. n There is Damage to the patient. n Dereliction is the Direct cause of damage. Unlike a criminal suit, in which the burden of proof is “beyond a reasonable doubt,” the burden of proof in a malpractice suit is “a preponderance of the evidence.” HIGH-YIELD FACTS IN GASTROINTESTINAL Esophageal Disease 120 LARGE BOWEL OBSTRUCTION DYSPHAGIA/ODYNOPHAGIA 120 COLORECTAL CANCER 133 INFECTIOUS ESOPHAGITIS 120 ISCHEMIC COLITIS 135 DIFFUSE ESOPHAGEAL SPASM 120 ACHALASIA 120 ESOPHAGEAL DIVERTICULA 121 ESOPHAGEAL CANCER 132 Gastrointestinal Bleeding 135 Inflammatory Bowel Disease 136 121 Inguinal Hernias 136 GASTROESOPHAGEAL REFLUX DISEASE 122 Biliary Disease 136 HIATAL HERNIA 123 CHOLELITHIASIS AND BILIARY COLIC 136 124 ACUTE CHOLECYSTITIS 137 124 CHOLEDOCHOLITHIASIS 139 GASTRIC CANCER 124 ASCENDING CHOLANGITIS 139 PEPTIC ULCER DISEASE 125 GALLSTONE ILEUS 141 ZOLLINGER-ELLISON SYNDROME 126 PRIMARY SCLEROSING CHOLANGITIS 141 Disorders of the Small Bowel 126 Disorders of the Stomach and Duodenum GASTRITIS Liver Disease 141 DIARRHEA 126 ABNORMAL LIVER FUNCTION TESTS 141 MALABSORPTION/MALDIGESTION 128 HEPATITIS 141 LACTOSE INTOLERANCE 128 CIRRHOSIS 144 CARCINOID SYNDROME 128 PRIMARY BILIARY CIRRHOSIS 146 IRRITABLE BOWEL SYNDROME 129 HEPATOCELLULAR CARCINOMA 146 SMALL BOWEL OBSTRUCTION 129 HEMOCHROMATOSIS 147 WILSON’S DISEASE (HEPATOLENTICULAR DEGENERATION) 148 ILEUS 130 MESENTERIC ISCHEMIA 131 APPENDICITIS 132 PANCREATITIS 148 132 PANCREATIC CANCER 148 Disorders of the Large Bowel DIVERTICULAR DISEASE Pancreatic Disease 148 132 119 120 HIGH-YIELD FACTS IN GASTROINTESTINAL Esophageal Disease DYS P HAG I A/ ODYNO P HAG I A Difficulty swallowing (dysphagia) or pain with swallowing (odynophagia) due to abnormalities of the oropharynx or esophagus. HISTORY/PE n KEY FACT Esophageal webs are associated with iron deficiency anemia and glossitis (Plummer-Vinson syndrome). n The presentation of dysphagia varies according to location: n Oropharyngeal dysphagia: Usually involves aspiration of food into the lungs (liquids more than solids), leading to coughing or choking. Causes can be neurologic or muscular and include stroke, Parkinson’s disease, myasthenia gravis, prolonged intubation, and Zenker’s diverticula. n Esophageal dysphagia: If due to obstruction, usually involves solids more than liquids (strictures, Schatzki rings, webs, carcinoma) and is progressive. If due to a motility disorder (achalasia, scleroderma, esophageal spasm), usually presents with both liquid and solid dysphagia. Examine for masses (eg, goiter, tumor) and anatomic defects. DIAGNOSIS n n n Oropharyngeal dysphagia: Video fluoroscopy. Esophageal dysphagia: Barium swallow (aka esophagram) followed by endoscopy, manometry, and/or pH monitoring. If an obstructive lesion is suspected, proceed directly to endoscopy with biopsy. Odynophagia: Upper endoscopy. TREATMENT Etiology dependent. I NF E C TIOU S E SOP HAG I TI S KEY FACT Candidal esophagitis is an AIDS-defining illness. Table 2.6-1 outlines the etiology, diagnosis, and treatment of infectious esophagitis. DI F F U S E ES OP HAG E AL S P AS M n KEY FACT n The musculature of the upper third of the esophagus is skeletal, whereas that of the lower two-thirds is smooth muscle. n n A motility disorder in which normal peristalsis is periodically interrupted by high-amplitude nonperistaltic contractions. Also known as nutcracker esophagus (see Figure 2.6-2A). Hx/PE: Presents with chest pain, dysphagia, and odynophagia. Often precipitated by ingestion of hot or cold liquids; relieved by nitroglycerin. Dx: Barium swallow may show a corkscrew-shaped esophagus. Esophageal manometry reveals high-amplitude, simultaneous contractions. Tx: Nitrates and calcium channel blockers (CCBs) for symptomatic relief; surgery (esophageal myotomy) for severe, incapacitating symptoms. AC HALAS I A n A motility disorder of the esophagus characterized by impaired relaxation of the lower esophageal sphincter (LES) and loss of peristalsis in the distal two-thirds of the esophagus. Results from degeneration of the inhibitory neurons in the myenteric (Auerbach’s) plexus. GASTROINTESTINAL TA B L E 2 . 6 - 1 . Causes of Infectious Esophagitis ETIOLOGIC AGENT Candida albicans HSV HIGH-YIELD FACTS IN 121 EXAM FINDINGS UPPER ENDOSCOPY TREATMENT Oral thrush (see Yellow-white Nystatin oral Figure 2.6-1). plaques adherent to suspension or the mucosa. fluconazole PO. Small, deep Acyclovir IV. Oral ulcers. ulcerations; multinucleated giant cells with Oropharyngeal candidiasis. Multiple thick, yellowish-white FIGURE 2.6-1. intranuclear inclusions on biopsy plaques are seen on the palate and buccal mucosa. (Reproduced with permission from + Tzanck smear. Kantarjian HM et al. MD Anderson Manual of Medical CMV Retinitis, colitis. Large, superficial Ganciclovir IV. ulcerations; Oncology, 1st ed. New York: McGraw-Hill, 2006, Fig. 37-1.) intranuclear and intracytoplasmic inclusions on biopsy. n n n Hx/PE: Common symptoms include progressive dysphagia, chest pain, regurgitation of undigested food, weight loss, and nocturnal cough. Dx: n Barium swallow reveals esophageal dilation with a “bird’s beak” tapering of the distal esophagus (see Figure 2.6-2B). n Manometry shows ↑ resting LES pressure, incomplete LES relaxation upon swallowing, and ↓ peristalsis in the body of the esophagus. n Endoscopy is indicated to rule out mechanical causes of obstruction. Tx: Nitrates, CCBs, or endoscopic injection of botulinum toxin into the LES may provide short-term relief of symptoms. Pneumatic balloon dilation and surgical (Heller) myotomy are definitive treatment options. KEY FACT Beware: malignancy may mimic achalasia (pseudoachalasia). E SO PH A G E A L D IV E R T I CU LA n n n n Diverticula can be present in any location. Zenker’s diverticulum is defined as cervical outpouching through the cricopharyngeus muscle. Hx/PE: Presents with chest pain, dysphagia, halitosis, and regurgitation of undigested food. Dx: Barium swallow will demonstrate outpouchings. Tx: If symptomatic, treat with surgical excision of the diverticulum. For Zenker’s diverticulum, myotomy of the cricopharyngeus is required to relieve the high-pressure zone. E SO PH A G E A L C A N C E R n n Squamous cell carcinoma (SCC) is the most common type of esophageal cancer worldwide, whereas adenocarcinoma is most prevalent in the United States, Europe, and Australia. Risk factors include the following: n SCC: Alcohol and tobacco use. n Adenocarcinoma: Barrett’s esophagus (columnar metaplasia of the distal esophagus 2° to chronic GERD). KEY FACT Squamous cell esophageal cancer is associated with tobacco and alcohol use. 122 HIGH-YIELD FACTS IN GASTROINTESTINAL A B C D Esophageal disease on barium esophagram. (A) Esophageal spasm. (B) Achalasia. Note the dilated esophagus tapering to a “bird’s beak” narrowing (arrows) at the LES. (C) Barrett’s esophagus with adenocarcinoma. Note the nodular mucosa of Barrett’s esophagus (arrow) and the raised filling defect (arrowhead) representing adenocarcinoma in this patient. (D) Peptic stricture (arrows) 2° to GERD above a hiatal hernia (right). (Image A reproduced with permis- FIGURE 2.6-2. sion from USMLERx.com. Image B reproduced with permission from Doherty GM. Current Diagnosis & Treatment: Surgery, 13th ed. New York: McGraw-Hill, 2010, Fig. 20-5. Images C and D reproduced with permission from Chen MY et al. Basic Radiology, 1st ed. New York: McGraw-Hill, 2004, Figs. 10-19 and 10-14.) KEY FACT Esophageal cancer metastasizes early because the esophagus lacks a serosa. n n n KEY FACT SCC of the esophagus tends to occur in the upper and middle thirds of the esophagus, whereas adenocarcinoma occurs in the lower third. KEY FACT GAS TR O E SOP HAG E AL RE F LU X DI S E AS E (G E RD) Symptomatic reflux of gastric contents into the esophagus, most commonly from transient LES relaxation. Can also result from an incompetent LES, gastroparesis, or hiatal hernia. HISTORY/PE n GERD can mimic cough-variant asthma. n KEY FACT Patients with GERD should avoid caffeine, alcohol, chocolate, garlic, onions, mints, and nicotine. Hx/PE: Progressive dysphagia, initially to solids and later to liquids, is common. Weight loss, odynophagia, GERD, GI bleeding, and vomiting are also seen. Dx: Barium study shows narrowing of the esophagus with an irregular border protruding into the lumen (see Figure 2.6-2C). EGD with biopsy confirms the diagnosis. CT and endoscopic ultrasound are used for staging. Tx: Chemoradiation and surgical resection are first-line treatment. Resection is also indicated in cases of high-grade Barrett’s dysplasia. Has a poor prognosis. n Patients present with heartburn that commonly occurs 30–90 minutes after a meal, worsens with reclining, and often improves with antacids, sitting, or standing. Sour taste (“water brash”), a globus sensation (a sensation of a lump in the throat), unexplained cough, and morning hoarseness are also common. Examination is usually normal unless a systemic disease (eg, scleroderma) is present. DIAGNOSIS n n n Primarily a clinical diagnosis. An empiric trial of lifestyle modification and medical treatment is often attempted first. Studies may include barium swallow (to look for hiatal hernia and demonstrate reflux; see Figure 2.6-2D), esophageal manometry, and 24-hour pH monitoring. EGD with biopsies should be performed in patients whose symptoms are unresponsive to initial empiric therapy, long standing (to rule out Barrett’s GASTROINTESTINAL HIGH-YIELD FACTS IN 123 esophagus and adenocarcinoma; see Figure 2.6-3), or associated with alarm symptoms (eg, blood in the stool, weight loss, dysphagia/odynophagia). TREATMENT n n n Lifestyle: Weight loss, head-of-bed elevation, small but frequent meals, and avoidance of nocturnal meals and substances that ↓ LES tone. Pharmacologic: Start with antacids in patients with mild, intermittent symptoms; use H2 receptor antagonists (cimetidine, ranitidine) or PPIs (omeprazole, lansoprazole) in patients with chronic and frequent symptoms. PPIs are preferred for severe or erosive disease. Surgical: Nissen fundoplication may offer significant relief for refractory or severe disease. COMPLICATIONS Erosive esophagitis, esophageal peptic stricture, aspiration pneumonia, upper GI bleeding, Barrett’s esophagus. Barrett’s esophagus on upper endoscopy. Shown is an irreg- FIGURE 2.6-3. ular Z line (squamocolumnar junction between the esophagus and stomach) due to columnar metaplasia of the lower esophagus. (Reproduced with permission from Fauci AS et al. Harrison’s Principles of Internal Medicine, 17th ed. New York: McGraw-Hill, 2008, Fig. 285-3A.) HI A T A L H E R N IA n n n n Herniation of the stomach upward into the chest through the diaphragm. There are 3 common types: n Sliding hiatal hernia (95%): The gastroesophageal junction and a portion of the stomach are displaced above the diaphragm (see Figure 2.6-4A). n Paraesophageal hiatal hernia (5%): The gastroesophageal junction remains below the diaphragm, while the fundus herniates into the thorax (see Figure 2.6-4B). n Mixed hiatal hernias (rare). Hx/PE: May be asymptomatic. Patients with sliding hernias may present with GERD. Dx: Commonly an incidental finding on CXR; also frequently diagnosed by barium swallow or EGD. Tx: n Sliding hernias: Medical therapy and lifestyle modifications to ↓ GERD symptoms. Esophagus Esophagus Cardioesophageal junction Peritoneal reflection Diaphragm Peritoneal reflection Cardioesophageal junction Herniated portion of stomach Diaphragm Phrenoesophageal ligament Phrenoesophageal ligament Diaphragm Peritoneal reflection Phrenoesophageal ligament Diaphragm Intra-abdominal portion of stomach A FIGURE 2.6-4. Herniated portion of stomach Intra-abdominal portion of stomach B Hiatal hernia. (A) Sliding hiatal hernia. (B) Paraesophageal hiatal hernia. (Reproduced with permission from Doherty GM. Current Diagnosis & Treatment: Surgery, 13th ed. New York: McGraw-Hill, 2010, Figs. 20-9 and 20-11.) 124 HIGH-YIELD FACTS IN GASTROINTESTINAL n Paraesophageal hernias: Surgical gastropexy (attachment of the stomach to the rectus sheath and closure of the hiatus) is recommended to prevent gastric volvulus. Disorders of the Stomach and Duodenum GAS TR I TI S Inflammation of the gastric mucosa. Subtypes are as follows: KEY FACT Type A gastritis is associated with pernicious anemia due to lack of intrinsic factor necessary for the absorption of vitamin B12. n n KEY FACT Stress ulcers include Curling ulcers, which are associated with burn injuries, and Cushing ulcers, which are associated with traumatic brain injury. Acute gastritis: Rapidly developing, superficial lesions that are often due to NSAID use, alcohol, H pylori infection, and stress from severe illness (eg, burns, CNS injury). Chronic gastritis: n Type A (10%): Occurs in the fundus and is due to autoantibodies to parietal cells. Causes pernicious anemia and is associated with other autoimmune disorders. Associated with an ↑ risk of gastric adenocarcinoma and carcinoid tumors. n Type B (90%): Occurs in the antrum and may be caused by NSAID use or H pylori infection. Often asymptomatic, but associated with an ↑ risk of PUD and gastric cancer. HISTORY/PE Patients may be asymptomatic or may complain of epigastric pain, nausea, vomiting, hematemesis, or melena. DIAGNOSIS n KEY FACT H pylori antibodies stay ! even when the infection is cleared. Use the urease breath test or a repeat stool antigen as a test of cure. n TREATMENT n n KEY FACT A gastric adenocarcinoma that metastasizes to the ovary is called a Krukenberg tumor. Upper endoscopy to visualize the gastric mucosa. A double-contrast upper GI series can also be used but is less sensitive than EGD. H pylori infection can be detected by the urease breath test, serum IgG antibodies (which point to a history of exposure, not current infection), H pylori stool antigen (indicates current infection), or endoscopic biopsy. n ↓ intake of exacerbating agents. Antacids, sucralfate, H2 blockers, and/or PPIs may help. Administer triple therapy (amoxicillin, clarithromycin, omeprazole) to treat H pylori infection unless the patient is penicillin allergic, in which case metronidazole should be substituted for amoxicillin. Give prophylactic PPIs to patients at risk for stress ulcers (eg, ICU patients). GAS TR I C C ANC E R KEY FACT MALT (mucosa-associated lymphoid tissue) lymphoma is a rare gastric tumor that presents in patients with chronic H pylori infection. It is the only malignancy that can be cured with antibiotics. Treat with triple therapy. n A malignant tumor with a poor prognosis that is particularly common in Korea and Japan. Most are adenocarcinomas, which exhibit 2 morphologic types: n Intestinal type: Differentiated cancer that originates from the intestinal metaplasia of gastric mucosal cells. Risk factors include a diet high in nitrites and salt and low in fresh vegetables (antioxidants), H pylori colonization, and chronic gastritis. n Diffuse type: Undifferentiated cancer not associated with H pylori infection or chronic gastritis. Risk factors are unknown; signet ring cells on biopsy are characteristic. GASTROINTESTINAL n n n Hx/PE: Early-stage disease is usually asymptomatic but may be associated with indigestion and loss of appetite. Late-stage disease presents with abdominal pain, weight loss, and upper GI bleeding. Dx: Upper endoscopy with biopsy is necessary to rule out other etiologies and confirm the diagnosis. Tx: If detected early, treatment is surgical resection. Most patients present with late-stage, incurable disease. Five-year survival is < 10% for advanced disease. HIGH-YIELD FACTS IN 125 KEY FACT Gastric cancer may present with Virchow’s node (an enlarged left supraclavicular lymph node). PEP T IC U LC E R D I S E A S E (P U D ) Although commonly thought to result from stress, PUD is now known to result from damage to the gastric or duodenal mucosa caused by impaired mucosal defense and/or ↑ acidic gastric contents. H pylori is the causative factor in > 90% of duodenal ulcers and 70% of gastric ulcers. Other risk factors include corticosteroid, NSAID, alcohol, and tobacco use. Males are affected more often than females. KEY FACT Stress is not a risk factor for PUD. HISTORY/PE n n n n Presents with chronic or periodic dull, burning epigastric pain that is often related to meals and can radiate to the back. Patients may also complain of nausea, hematemesis (“coffee-ground” emesis), or blood in the stool. Examination is usually normal but may reveal epigastric tenderness and ! stool guaiac. Acute perforation presents with a rigid abdomen, rebound tenderness, and/or guarding. DIAGNOSIS n n n n Rule out perforation: n Gastric ulcers: AXR reveals free air under the diaphragm (see Figure 2.6-5). n Duodenal ulcers: CT scan with contrast shows air in the retroperitoneal space. Order a CBC to detect GI bleeding. Upper endoscopy with biopsy to confirm and to rule out active bleeding or gastric adenocarcinoma (10% of gastric ulcers). H pylori testing. In recurrent or refractory cases, check serum gastrin levels to screen for Zollinger-Ellison syndrome. KEY FACT After a meal, pain from a Gastric ulcer is Greater, whereas Duodenal pain Decreases. KEY FACT All gastric ulcers must be biopsied to rule out malignancy. TREATMENT n n Acute management: n If perforation is suspected, CT with IV contrast is indicated. If the diagnosis is confirmed, surgical laparotomy will likely be required. Carefully monitor BP. n Rule out active bleeding with rectal vault examination, NG lavage, and serial hematocrits. Monitor BP and treat with IV hydration, blood transfusion, and IV PPIs. Urgent EGD should be performed to control suspected bleeding. Long-term management: n Medical therapy is indicated to protect the mucosa, ↓ acid production, and eradicate H pylori infection. n For mild disease, treat with antacids, PPIs, or H2 blockers. n Patients with H pylori infection should receive triple therapy. n Discontinue use of exacerbating agents. FIGURE 2.6-5. Pneumoperitoneum. Upright CXR reveals free air under the diaphragm. (Reproduced with permission from USMLERx.com.) 126 HIGH-YIELD FACTS IN GASTROINTESTINAL n KEY FACT n Misoprostol can help patients with PUD who require NSAID therapy (eg, for arthritis). Endoscopy with targeted biopsy is indicated in patients with symptoms refractory to medical therapy to rule out gastric cancer. Surgical therapy (eg, partial cell vagotomy) is indicated in severe cases. COMPLICATIONS Hemorrhage (posterior ulcers that erode into the gastroduodenal artery), gastric outlet obstruction, perforation, intractable pain. ZO LLI NG E R -ELLI SO N SYNDR O M E n n n n n n A rare condition characterized by gastrin-producing tumors in the duodenum and/or pancreas that lead to oversecretion of gastrin. Oversecretion of gastrin ↑ gastric acid production, leading to recurrent or intractable ulcers in the stomach and duodenum (may occur more distally). In 20% of cases, gastrinomas are associated with multiple endocrine neoplasia (MEN) type 1. Hx/PE: Patients may present with unresponsive, recurrent gnawing, burning abdominal pain as well as with diarrhea, nausea, vomiting, fatigue, weakness, weight loss, and GI bleeding. Dx: ↑ fasting serum gastrin levels and ↑ gastrin with the administration of secretin are diagnostic; CT is indicated to characterize and stage disease. Tx: n Moderate- to high-dose PPIs often control symptoms. n Surgical resection of the gastrinoma after localization by CT or octreotide scan to identify suspected carcinoid tumors. Disorders of the Small Bowel D I AR R HE A KEY FACT Cryptosporidium and Isospora are associated with chronic diarrhea in patients with HIV/AIDS. Defined as the production of > 200 g of feces per day along with ↑ frequency or ↓ consistency of stool. The most common mechanisms are malabsorption/ maldigestive/osmotic, secretory, inflammatory/infectious, and ↑ motility (see also Table 2.6-2). HISTORY/PE n KEY FACT Organisms that cause bloody diarrhea include Salmonella, Shigella, E coli (EHEC), and Campylobacter. n Acute diarrhea: Acute onset with a duration of < 2 weeks; usually infectious and self-limited. n Multiple pathogens may be responsible (see Table 2.6-2). n One of the most common causes of pediatric diarrhea is rotavirus infection. Chronic diarrhea: Insidious onset with a duration of > 4 weeks. n Secretory: Carcinoid tumors, VIPomas. n Malabsorption/maldigestive/osmotic: Bacterial overgrowth, pancreatic insufficiency, mucosal damage, lactose intolerance, celiac disease, laxative abuse, postsurgical short bowel syndrome. n Inflammatory/infectious: IBD. n Increased motility: IBS. DIAGNOSIS n For acute diarrhea, no further studies are indicated unless the patient has a high fever, bloody diarrhea, or diarrhea lasting > 4–5 days. GASTROINTESTINAL TA B L E 2 . 6 - 2 . HIGH-YIELD FACTS IN 127 Causes of Infectious Diarrhea INFECTIOUS AGENT Campylobacter HISTORY The most common etiology of bacterial diarrhea. Caused by ingestion of EXAM COMMENTS Fecal RBCs and WBCs. Rule out appendicitis and Frequently presents with IBD. TREATMENT Erythromycin. bloody diarrhea. contaminated food or water. Affects young children and young adults; generally lasts 7–10 days. Clostridium difficile Associated with recent treatment with antibiotics (penicillins, quinolones, clindamycin). Presents with fever, abdominal pain, and possible systemic toxicity. Fecal RBCs and WBCs. Most commonly causes colitis, but can involve the small bowel. Identify C difficile toxin in the stool. Affects hospitalized adult patients. Watch for toxic megacolon. Cessation of the inciting antibiotic. Treat with PO metronidazole or vancomycin; give Sigmoidoscopy shows IV metronidazole if pseudomembranes. the patient cannot tolerate PO. Entamoeba histolytica Caused by ingestion of Presents with severe contaminated food or abdominal pain and water; look for a history fever. of travel in developing Fecal RBCs and WBCs. countries. Endoscopy shows “flask- The incubation period can Chronic amebic colitis mimics IBD. Steroids can lead to fatal perforation. Treat with metronidazole. shaped” ulcers. last up to 3 months. E coli O157:H7 Caused by ingestion of Presents with severe It is important to rule out Avoid antibiotic or contaminated food (raw abdominal pain, low- GI bleed and ischemic antidiarrheal therapy, meat). grade fever, and vomiting. colitis. which ↑ HUS risk. Affects children and the Fecal RBCs and WBCs. Hemolytic-uremic syndrome elderly; generally lasts (HUS) is a potential 5–10 days. complication, primarily in children. Salmonella Caused by ingestion of contaminated poultry or eggs. Affects young children and Presents with a prodromal headache, fever, myalgia, and abdominal pain. Fecal WBCs. Sepsis is a concern, as Treat bacteremia or 5–10% of patients at-risk patients (eg, become bacteremic. sickle cell patients) Sickle cell patients are with oral quinolone the elderly; generally lasts susceptible to invasive 2–5 days. disease leading to or TMP-SMX. osteomyelitis. Shigella Extremely contagious; transmitted between people by the fecal-oral route. Affects young children and institutionalized patients. Fecal RBCs and WBCs. May lead to severe dehydration. Can also cause febrile seizures in the very young. Treat with TMP-SMX to ↓ person-to-person spread. 128 HIGH-YIELD FACTS IN KEY FACT Organisms that cause watery diarrhea include Vibrio cholerae, rotavirus, E coli (ETEC), Cryptosporidium, and Giardia. GASTROINTESTINAL n For chronic diarrhea, the history and physical examination are critical to narrowing the differential diagnosis. Additional studies include the following: n Stool analysis: Leukocytes, culture, C difficile toxin, and O&P. n Sigmoidoscopy: In patients with bloody diarrhea. TREATMENT n KEY FACT Diarrhea after ingestion of raw eggs or dairy: think Salmonella. n Acute diarrhea: n The most important treatment is oral rehydration. n Antibiotics do not shorten the course of illness and thus are not indicated (except in C difficile infection). n Symptomatic treatment includes antidiarrheal agents (eg, loperamide, bismuth salicylate). Avoid if the patient has high fever or bloody stools. Chronic diarrhea: Treatment is etiology specific. MALABS O R P TION/ MAL D I G E S TION n n FIGURE 2.6-6. Dermatitis her- petiformis. Grouped, papulovesicular, pruritic skin lesions are shown. Lesions tend to be symmetrically located on the extensor surfaces of the elbows, knees, buttocks, and posterior scalp and are associated with celiac disease. (Reproduced n Inability to absorb macro- and/or micronutrients. Common etiologies include the following: n Mucosal abnormalities: Celiac disease (associated with dermatitis herpetiformis; see Figure 2.6-6), Whipple’s disease, tropical sprue. n Bile salt deficiency: Bacterial overgrowth, ileal disease. n Other: Pancreatic insufficiency, short bowel syndrome. Hx/PE: Presents with frequent, loose, watery stools (carbohydrate malabsorption) and/or pale, foul-smelling, bulky stools (steatorrhea of fat maldigestion) associated with abdominal pain, flatus, bloating, weight loss, nutritional deficiencies, and fatigue. Tx: Etiology dependent. In severe cases, patients may require TPN, immunosuppressants, and anti-inflammatory medications. with permission from Fauci AS et al. Harrison’s Princi- LAC TOS E I NT OLE R ANC E ples of Internal Medicine, 17th ed. New York: McGrawHill, 2008, Fig. 52-8.) n n n n n KEY FACT The classic presentation of pellagra is the 4 D’s: diarrhea, dementia, dermatitis, and death. n CAR C I NOI D S YNDR OM E n KEY FACT n Carcinoid tumors must metastasize to the liver in order to manifest with carcinoid syndrome. Results from a deficiency of lactase, a brush-border enzyme that hydrolyzes lactose into glucose and galactose. Common among populations of African, Asian, and Native American descent. Transient lactose intolerance can occur after an acute episode of gastroenteritis. Hx/PE: Presents with abdominal bloating, flatulence, cramping, and watery diarrhea following milk ingestion. Dx: An empiric lactose-free diet that improves symptoms is highly suggestive of the diagnosis. Hydrogen breath test reveals ↑ hydrogen following the ingestion of lactose. Tx: Avoidance of dairy products; oral lactase enzyme replacement. n n Due to the metastasis of carcinoid tumors, which most commonly arise from the ileum and appendix and produce serotonin. Prior to metastasis, most secreted hormones undergo first-pass metabolism by the liver and do not reach systemic circulation. Hx/PE: Cutaneous flushing, diarrhea, abdominal cramps, wheezing, and right-sided cardiac valvular lesions are the most common manifestations. Dx: High urine levels of the serotonin metabolite 5-HIAA are diagnostic. CT and In-111 octreotide scans are used to localize the tumor. Tx: Treatment includes octreotide and surgical resection. GASTROINTESTINAL HIGH-YIELD FACTS IN 129 IR R IT A B LE B O W E L SY N D RO M E (I BS) An idiopathic functional disorder characterized by chronic, intermittent abdominal pain and changes in bowel habits. It is commonly diagnosed in women in their 20s to 30s but affects men and women of all ages. Half of all IBS patients who seek medical care have comorbid psychiatric disorders (eg, depression, anxiety, fibromyalgia). HISTORY/PE n n n Patients present with abdominal pain that is relieved by bowel movements, diarrhea and/or constipation, abdominal distention, and mucous stools. Symptoms often worsen with stress. IBS rarely awakens patients from sleep; vomiting, significant weight loss, and constitutional symptoms are uncommon. Examination is usually unremarkable. DIAGNOSIS n n Exclude organic disorders such as IBD. The Rome III diagnostic criteria for IBS involve at least 3 months of episodic abdominal discomfort that is (1) relieved by defecation and (2) associated with a change in stool frequency or consistency. Tests to exclude other etiologies include CBC, TSH, electrolytes, stool cultures, abdominal films, barium contrast studies, and, rarely, colonoscopy with biopsy. TREATMENT n n n Psychosocial: Patients benefit from a strong patient-physician relationship. Physicians should offer reassurance and should not dismiss the symptoms. Diet: Fiber supplements (psyllium); exclude gas-producing foods. Pharmacologic: Symptomatic treatment with antispasmodics. Long-term medical therapy is usually not indicated. S M A LL B O WE L O B S T R U CT IO N (SBO) Defined as blocked passage of bowel contents through the small bowel. Common etiologies include adhesions from prior abdominal surgery (60% of cases), hernias (10–20%), neoplasms (10–20%), intussusception, gallstone ileus, stricture due to IBD, and volvulus. The obstruction can be complete or partial: n n KEY FACT The leading cause of SBO in children is hernia. The leading cause of SBO in adults is adhesions. Partial SBO: Continued passage of flatus, but no stool. Complete SBO: No passage of flatus or stool (obstipation). HISTORY/PE n n n n n Patients experience crampy abdominal pain at 4- to 5-minute intervals. Vomiting typically follows the pain. In proximal obstruction, emesis is early, bilious, and nonfeculent; in distal obstruction, it is late and feculent. Abdominal examination often reveals distention, tenderness, prior surgical scars, or hernias. Hyperactive bowel sounds are characterized by high-pitched tinkles and peristaltic rushes. In prolonged obstruction, ischemic necrosis and bowel rupture are concerns. Patients present with peritonitis manifested by fever, hypotension, rebound tenderness, and tachycardia. A 53-year-old woman with a history of carcinoid tumor of the appendix (status post resection) presents to a local clinic with symmetric, dry, hyperpigmented skin lesions and persistent diarrhea. Her husband expresses concern that the patient does not seem to be herself anymore; he reports that she has been irritable, confused, and forgetful. What is the most likely diagnosis? 130 HIGH-YIELD FACTS IN GASTROINTESTINAL DIAGNOSIS Abdominal films demonstrate a stepladder pattern of dilated small-bowel loops, air-fluid levels (see Figure 2.6-7), and a paucity of gas in the colon. CBC may demonstrate leukocytosis if there is ischemia or necrosis of bowel. Labs often reveal dehydration and metabolic alkalosis. Lactic acidosis is a prognostic sign, as it suggests necrotic bowel. n n n KEY FACT TREATMENT Initial management involves fluid resuscitation. For partial obstruction, supportive care alone may be sufficient and should include NPO status, NG suction, IV hydration, correction of electrolyte abnormalities, and Foley catheterization to monitor fluid status. Exploratory laparotomy is indicated in cases of complete SBO, ischemic necrosis, or partial SBO symptoms lasting > 3 days without resolution. n Gallstone ileus is a form of SBO that occurs when a gallstone erodes through the intestinal wall into the lumen and lodges at the ileocecal valve. n n I LE U S Loss of peristalsis without structural obstruction. Risk factors include recent surgery/GI procedures, severe medical illness, immobility, hypokalemia or other electrolyte imbalances, hypothyroidism, diabetes mellitus (DM), and medications that slow GI motility (eg, anticholinergics, opioids). HISTORY/PE Patients present with diffuse, constant abdominal discomfort, nausea and vomiting, and an absence of flatus or bowel movements. Examination may reveal diffuse tenderness, abdominal distention, and ↓ or absent bowel sounds. A rectal examination is required to rule out fecal impaction in elderly patients. n n n Pellagra, a deficiency of vitamin B3 (niacin), 2° to a recurrent carcinoid tumor. Carcinoid tumors produce serotonin, which is a derivative of tryptophan. However, tryptophan is also the precursor of niacin. In patients with carcinoid tumors, the tumor can be so active that most tryptophan is used for serotonin production, resulting in niacin deficiency. A B Small bowel obstruction. (A) Supine abdominal radiograph shows dilated air-filled small bowel loops with relatively little gas in the colon. (B) Left lateral decubitus radiograph on the same patient demonstrates multiple air-fluid levels (arrows) at different levels. These are typical plain film findings of complete SBO. (Reproduced with permission from Doherty GM. CurFIGURE 2.6-7. rent Diagnosis & Treatment: Surgery, 13th ed. New York: McGraw-Hill, 2010, Fig. 29-5.) GASTROINTESTINAL DIAGNOSIS n n The clinical history must be considered in diagnosis. Abdominal films show distended loops of small and large bowel, with air seen throughout the colon and rectum (SBO has no air distal to the obstruction). TREATMENT n n n n ↓ or discontinue the use of narcotics and any other drugs that reduce bowel motility. Temporarily ↓ or discontinue oral feeds. Initiate NG suction/parenteral feeds as necessary. Replete electrolytes as needed; hydrate with IV fluids. MES E N T E R I C I S C H E M IA Insufficient blood supply to the small intestine, resulting in ischemia and, potentially, necrosis. The 2 most common causes are as follows: n n Acute arterial occlusion from thrombosis: Most commonly occurs in the proximal SMA. The 1° risk factor is atherosclerosis. Embolism: Emboli most commonly originate in the heart. Risk factors include atrial fibrillation and stasis from a ↓ ejection fraction. Other causes include nonocclusive arterial disease (low cardiac output, arteriolar vasospasm, atherosclerosis of mesenteric vessels) and venous thrombosis (due to hypercoagulable states). HISTORY/PE n n n n Patients present with severe abdominal pain out of proportion to the examination. Patients may have a history of prior episodes of abdominal pain after eating (“intestinal angina”). If severe, this can lead to fear of eating and weight loss. Other symptoms may include nausea, vomiting, diarrhea, and bloody stools. Abdominal examination is often unremarkable until late in the disease course. DIAGNOSIS n n n Lab tests may show leukocytosis, metabolic acidosis with ↑ lactate, ↑ amylase, ↑ LDH, and ↑ CK. AXR and CT may reveal bowel wall edema (“thumbprinting”) and air within the bowel wall (pneumatosis intestinalis). Mesenteric angiography is the gold standard for the diagnosis of arterial occlusive disease. TREATMENT n n n n n Volume resuscitation; broad-spectrum antibiotics. For acute arterial thrombosis or embolism, treat with anticoagulation and either laparotomy or angioplasty. For venous thrombosis, treat with anticoagulation. For all other etiologies, address the underlying cause. Surgical resection of infarcted bowel. HIGH-YIELD FACTS IN 131 KEY FACT In ileus, there is air present throughout the small and large bowel on AXR. 132 HIGH-YIELD FACTS IN GASTROINTESTINAL COMPLICATIONS Sepsis/septic shock, multisystem organ failure, death. AP P E NDI C I TI S See the Emergency Medicine chapter. Disorders of the Large Bowel DI VE R TI C U LAR DI S E AS E KEY FACT Diverticulosis is the most common cause of acute lower GI bleeding in patients > 40 years of age. KEY FACT Following resolution of an acute episode of lower GI bleeding, all patients must have a colonoscopy to rule out colon cancer if they have not been screened within the last 5–10 years. KEY FACT Outpouchings of mucosa and submucosa (false diverticula) that herniate through the colonic muscle layers in areas of high intraluminal pressure; most commonly found in the sigmoid colon. Diverticulosis is the most common cause of acute lower GI bleeding in patients > 40 years of age. Risk factors include a low-fiber and high-fat diet, advanced age (65% occur in those > 80 years of age), and connective tissue disorders. Diverticulitis is inflammation and, potentially, perforation of a diverticulum 2° to fecalith impaction. HISTORY/PE n n n DIAGNOSIS n Sigmoidoscopy should be avoided in the initial stages of diverticulitis in light of the risk of perforation. L S GB n n n n n UB n Acute diverticulitis. Coronal reconstruction from a contrastenhanced CT demonstrates sigmoid diverticula with perisigmoid inflammatory “fat stranding.” The area of abnormality is circled in red. L = liver; S = stomach; GB = gallbladder; UB = urinary bladder. (Reproduced with permission from USMLERx.com.) Clinical history is important to diagnosis. CBC may show leukocytosis or anemia. In diverticulitis, CT scan may reveal inflammation or abscess (see Figure 2.6-8). Colonoscopy provides the definitive diagnosis in diverticular disease. Avoid sigmoidoscopy/colonoscopy in patients with early diverticulitis in view of the risk of perforation. TREATMENT n FIGURE 2.6-8. Diverticulosis is often asymptomatic. When symptomatic, patients present with sudden, intermittent, painless bleeding. If severe, patients may present with symptoms of anemia (fatigue, lightheadedness, dyspnea on exertion). Diverticulitis presents with LLQ abdominal pain, fever, nausea, and vomiting. Perforation is a serious complication that presents with peritonitis and shock. Uncomplicated diverticulosis: Routine follow-up. Encourage a high-fiber diet or fiber supplements. Diverticular bleeding: Bleeding usually stops spontaneously; transfuse and hydrate as needed. If bleeding does not stop, hemostasis by colonoscopy, angiography with embolization, or surgery is indicated. Diverticulitis: Treat with bowel rest (NPO), NG tube placement, and broad-spectrum antibiotics (metronidazole and a fluoroquinolone or a second- or third-generation cephalosporin). For perforation, perform immediate surgical resection of diseased bowel via a Hartmann’s procedure with a temporary colostomy. LAR G E BOW E L OBS TR U C TION ( LBO) Table 2.6-3 describes features that distinguish SBO from LBO. Figure 2.6-9 demonstrates the classic radiographic findings of LBO. GASTROINTESTINAL TA B L E 2 . 6 - 3 . Characteristics of Small and Large Bowel Obstruction VARIABLE History Exam SBO Constipation/obstipation, deep and cramping abdominal Cramping pain with distal SBO. pain (less intense than SBO), nausea/vomiting (less than Fever, signs of dehydration, and hypotension may be seen. that of SBO, but more commonly feculent). Abdominal distention (distal SBO), abdominal tenderness, Significant distention, tympany, and tenderness; examine Look for surgical scars/hernias; perform a rectal exam. High-pitched “tinkly” bowel sounds; later, absence of bowel sounds. Adhesions (postsurgery), hernias, neoplasm, volvulus, intussusception, gallstone ileus, foreign body, Crohn’s Differential LBO Moderate to severe acute abdominal pain; copious emesis. visible peristaltic waves, fever, hypovolemia. Etiologies HIGH-YIELD FACTS IN 133 for peritoneal irritation or mass. Fever or signs of shock suggest perforation/peritonitis or ischemia/necrosis. High-pitched “tinkly” bowel sounds; later, absence of bowel sounds. Colon cancer, diverticulitis, volvulus, fecal impaction, benign tumors. disease, cystic fibrosis (CF), stricture, hematoma. Assume colon cancer until proven otherwise. LBO, paralytic ileus, gastroenteritis. SBO, paralytic ileus, appendicitis, IBD, Ogilvie’s syndrome (pseudo-obstruction). Diagnosis Treatment CBC, electrolytes, lactic acid, AXR (see Figure 2.6-7); CBC, electrolytes, lactic acid, AXR (see Figure 2.6-9), CT contrast studies (determine if it is partial or complete), scan; water contrast enema (if perforation is suspected); CT scan. sigmoidoscopy/colonoscopy if stable. Hospitalize. Partial SBO can be treated conservatively with Hospitalize. Obstruction can be relieved with a Gastrografin NG decompression and NPO status. Patients with complete SBO should be managed aggressively with NPO status, NG decompression, IV fluids, electrolyte replacement, and surgical correction. enema, colonoscopy, or a rectal tube; however, surgery is usually required. Ischemic colon usually requires partial colectomy with a diverting colostomy. Treat the underlying cause (eg, neoplasm). C OLO R E CT A L C A N CE R The second leading cause of cancer mortality in the United States. There is an ↑ incidence with age, with a peak incidence at 70–80 years. Risk factors and screening recommendations are summarized in Tables 2.6-4 and 2.6-5. KEY FACT Iron deficiency anemia in an elderly patient is colorectal cancer until proven otherwise. HISTORY/PE Most patients are asymptomatic. When they are symptomatic, symptoms depend on the location of the lesion: n n n Right-sided lesions: Often bulky, ulcerating masses that lead to anemia from chronic occult blood loss. Patients may complain of weight loss, anorexia, diarrhea, weakness, or vague abdominal pain. Obstruction is rare. Left-sided lesions: Typically “apple-core” obstructing masses (see Figure 2.6-10). Patients complain of a change in bowel habits (eg, ↓ stool caliber, constipation, obstipation) and/or blood-streaked stools. Obstruction is common. Rectal lesions: Usually present with bright red blood per rectum, often with tenesmus and/or rectal pain. Rectal cancer must be ruled out in all patients with rectal bleeding. A 60-year-old male with no past medical history presents with fever, dyspnea, and orthopnea of 2 weeks’ duration. Physical examination reveals splinter hemorrhages and a new IV/VI diastolic decrescendo murmur. Echocardiogram confirms aortic valve endocarditis, and IV antibiotics are started. Blood cultures are ! for Streptococcus bovis. What is the next diagnostic step? 134 HIGH-YIELD FACTS IN GASTROINTESTINAL TA B L E 2 . 6 - 4 . Risk Factors for Colorectal Cancer RISK FACTOR COMMENTS Risk ↑ with age; peak incidence is at 70–80 Age years. Hereditary polyposis syndromes Familial adenomatous polyposis (FAP; 100% risk by age 40); hereditary nonpolyposis colorectal cancer (HNPCC). ! family history — IBD Ulcerative colitis > Crohn’s disease. Adenomatous polyps Villous > tubular; sessile > pedunculated. High-fat, low-fiber diet — Large bowel obstruction. AP radiograph from a barium FIGURE 2.6-9. enema in a patient with an LBO reveals a massively dilated sigmoid colon (arrow) and a “bird’s beak” appearance of the barium column at the site of volvulus (circle). (Reproduced with permission from Doherty DIAGNOSIS n n n GM. Current Diagnosis & Treatment: Surgery, 13th ed. New York: McGraw-Hill, 2010, Fig. 30-16.) Colonoscopy with biopsy can yield a definitive diagnosis. Order a CXR, LFTs, and an abdominal/pelvic CT to evaluate for metastases. Staging is based on the depth of tumor penetration into the bowel wall and the presence of lymph node involvement and distant metastases. TREATMENT n n n Surgical resection of the tumor is first-line treatment. Adjuvant chemotherapy is appropriate in cases with ! lymph nodes. Follow with serial CEA levels to detect recurrence, colonoscopy, LFTs, CXR, and abdominal CT to screen for metastases. TA B L E 2 . 6 - 5 . Screening Recommendations for Colorectal Cancer RISK CATEGORY No past medical or family history First-degree relative with colon cancer RECOMMENDATIONS Starting at age 50: n DRE and stool guaiac annually and n Colonoscopy every 10 years or n Sigmoidoscopy every 5 years. Colonoscopy every 10 years starting at age 40 or Colonoscopy every 10 years starting 10 Colonoscopy. Although the mechanism of association has yet to be determined, there is a wellestablished association between S bovis and colon cancer. years prior to the age of the affected family member at the time of diagnosis (whichever comes first). Ulcerative colitis Colonoscopy every 1–2 years starting 8–10 years after diagnosis. GASTROINTESTINAL HIGH-YIELD FACTS IN 135 ISC H E M I C CO LI T I S n n n n n Insufficient blood supply to the colon that results in ischemia and, potentially, necrosis. Most commonly affects the left colon, particularly the “watershed area” at the splenic flexure. Hx/PE: Presents with crampy lower abdominal pain and bloody diarrhea. Fever and peritoneal signs suggest bowel necrosis. Dx: n CT scan with contrast may show thickened bowel wall. n Colonoscopy reveals pale mucosa with petechial bleeding. Tx: n Supportive therapy with bowel rest, IV fluids, and broad-spectrum antibiotics. n Surgical bowel resection is indicated for infarction, fulminant colitis, or obstruction. Surgical Diagnosis & Treatment, 10th ed. Stamford, CT: Appleton & Lange, 1994: 658.) Bleeding from the GI tract may present as hematemesis, hematochezia, and/ or melena. Upper GI tract bleeding is defined as bleeding from lesions proximal to the ligament of Treitz (the anatomic boundary between the duodenum and jejunum). Table 2.6-6 presents the features of upper and lower GI bleeding. KEY FACT One unit of packed RBCs should ↑ hemoglobin by 1 g/dL and hematocrit by 3–4 units. Features of Upper and Lower GI Bleeding VARIABLE History/exam Colon carcinoma. (Reproduced with permission from Way LW. Current Gastrointestinal Bleeding TA B L E 2 . 6 - 6 . FIGURE 2.6-10. The encircling carcinoma appears as an “apple-core” filling defect in the descending colon on barium enema x-ray. UPPER GI BLEEDING Hematemesis (“coffee-ground” emesis), melena LOWER GI BLEEDING Hematochezia > melena, but can be either. > hematochezia, hypovolemia (eg, tachycardia, lightheadedness, hypotension). Diagnosis NG tube and lavage; if stable, endoscopy. Rule out upper GI bleed with NG lavage if brisk. Anoscopy/sigmoidoscopy for patients < 45 years of age with small-volume bleeding. Colonoscopy if stable; arteriography or exploratory laparotomy if unstable. PUD, esophagitis/gastritis, Mallory-Weiss tear, esophageal Diverticulosis (60%), angiodysplasia, IBD, hemorrhoids/ varices. fissures, neoplasm, AVM. Initial Protect the airway (intubation may be needed). Stabilize Similar to that of upper GI bleed. management the patient with IV fluids and packed RBCs (hematocrit Etiologies may be normal early in acute blood loss). Long-term Endoscopy followed by therapy directed at the underlying Depends on the underlying etiology. Endoscopic therapy management cause. (eg, epinephrine injection), intra-arterial vasopressin infusion or embolization, or surgery for diverticular disease or angiodysplasia. 136 HIGH-YIELD FACTS IN GASTROINTESTINAL Inflammatory Bowel Disease (IBD) Includes Crohn’s disease (see Figure 2.6-11) and ulcerative colitis (see Figure 2.6-12). Most common in Caucasians and Ashkenazi Jews, with onset most frequently occurring in the teens to early 30s or in the 50s. Table 2.6-7 summarizes the features of IBD. Inguinal Hernias Protrusions of abdominal contents (usually the small intestine) into the inguinal region through a weakness or defect in the abdominal wall. Classified as either direct or indirect: Indirect: Herniation of abdominal contents through the internal and external inguinal rings (see Figure 2.6-13A). n The most common hernia in both genders. n Due to a congenital patent processus vaginalis. n Protrudes lateral to the inferior epigastric vessels. Direct: Herniation of abdominal contents through the floor of Hesselbach’s triangle (see Figure 2.6-13B). n Protrudes medial to the epigastric vessels. n Due to an acquired defect in the transversalis fascia from mechanical breakdown that occurs with age. n KEY FACT Hesselbach’s triangle is an area bounded by the inguinal ligament, the inferior epigastric artery, and the rectus abdominis. n TREATMENT Because of the risk of incarceration and strangulation, surgical correction is indicated. Biliary Disease CH OLE LI THI AS I S AN D BI LI AR Y C OLI C Colic results from transient cystic duct blockage from impacted stones. Although risk factors include the 4 F’s—Female, Fat, Fertile, and Forty— the disorder is common and can occur in any patient. Additional risk factors A B C Crohn’s disease. (A) Small bowel follow-through (SBFT) barium study shows skip areas of narrowed small bowel with nodular mucosa (arrows) and ulceration. Compare with normal small bowel (arrowhead). (B) Spot compression image from SBFT shows “string sign” narrowing (arrow) due to stricture. (C) Deep ulcers in the colon of a patient with Crohn’s disease, seen at colonoscopy. (Image A reproduced with permission from Chen MY et al. Basic Radiology, FIGURE 2.6-11. 1st ed. New York: McGraw-Hill, 2004, Fig. 10-30. Image B reproduced with permission from USMLERx.com. Image C reproduced with permission from Fauci AS et al. Harrison’s Principles of Internal Medicine, 17th ed. New York: McGraw-Hill, 2008, Fig. 285-48). GASTROINTESTINAL A B HIGH-YIELD FACTS IN 137 C Ulcerative colitis. (A) Radiograph from a barium enema showing a featureless (“lead pipe”) colon with small mucosal ulcerations (arrow). Compare with normal haustral markings in (B). (C) Diffuse mucosal ulcerations and exudates at colonoscopy in chronic ulcerative colitis. (Image A reproduced with permission from Doherty GM. Current Diagnosis & Treatment: FIGURE 2.6-12. Surgery, 13th ed. New York: McGraw-Hill, 2010, Fig. 30-17. Image B reproduced with permission from Chen MY et al. Basic Radiology, 1st ed. New York: McGraw-Hill, 2004, Fig. 10-10A. Image C reproduced with permission from Fauci AS et al. Harrison’s Principles of Internal Medicine, 17th ed. New York: McGraw-Hill, 2008, Fig 285-4A.) include OCP use, rapid weight loss, chronic hemolysis (pigment stones in sickle cell disease), small bowel resection (loss of enterohepatically circulated bile), and TPN. HISTORY/PE n n n Patients present with postprandial abdominal pain (usually in the RUQ) that radiates to the right subscapular area or the epigastrium. Pain is often associated with nausea and vomiting, dyspepsia, and flatulence. Gallstones may be asymptomatic in up to 80% of patients. Examination may reveal RUQ tenderness and a palpable gallbladder. DIAGNOSIS n n n Plain x-rays are rarely diagnostic; only 10–15% of stones are radiopaque. RUQ ultrasound is the imaging modality of choice (see Figure 2.6-14). Table 2.6-8 contrasts lab findings with those of other forms of biliary disease. KEY FACT Pigmented gallstones result from hemolysis (black) or infection (brown). KEY FACT Most gallstones are precipitations of cholesterol and are not radiopaque. TREATMENT Cholecystectomy is curative and recommended for patients with symptomatic gallstones. Asymptomatic gallstones do not require treatment. AC U T E CHO L E CY S T IT IS Prolonged blockage of the cystic duct by a gallstone that leads to progressive distention, inflammation, and superinfection. Acalculous cholecystitis occurs in the absence of cholelithiasis in patients who are chronically debilitated or critically ill. HISTORY/PE n n Patients present with RUQ pain, nausea, vomiting, and fever. Look for a history notable for RUQ pain and nausea. Examination may reveal RUQ tenderness, inspiratory arrest with deep palpation of the RUQ (Murphy’s sign), and low-grade fever. A 35-year-old male with a 12-year history of ulcerative colitis presents to a clinic for annual follow-up. He has no current complaints. What is the most important screening test he should undergo? 138 HIGH-YIELD FACTS IN T A B L E 2 . 6 - 7. Features of Ulcerative Colitis and Crohn’s Disease VARIABLE Site of involvement GASTROINTESTINAL ULCERATIVE COLITIS The rectum is always involved. May extend proximally in CROHN’S DISEASE May involve any portion of the GI tract, particularly the ileocecal region, in a discontinuous pattern (“skip a continuous fashion. Inflammation and ulceration are limited to the mucosa lesions”). The rectum is often spared. Transmural inflammation is seen, sometimes leading to and submucosa. fistulas to other organs. History/exam Bloody diarrhea, lower abdominal cramps, tenesmus, Abdominal pain, abdominal mass, low-grade fever, weight loss, watery diarrhea. urgency. Examination may reveal orthostatic hypotension, Examination may reveal fever, abdominal tenderness tachycardia, abdominal tenderness, frank blood on or mass, perianal fissures or tags, fistulas, and rectal examination, and extraintestinal manifestations. extraintestinal manifestations. Extraintestinal Aphthous stomatitis, episcleritis/uveitis, arthritis, primary The same as ulcerative colitis in addition to fistulas to the manifestations sclerosing cholangitis, erythema nodosum, and skin, to the bladder, or between bowel loops. pyoderma gangrenosum. Diagnosis CBC, AXR, stool cultures, O&P, stool assay for C difficile. Colonoscopy can show diffuse and continuous rectal involvement, friability, edema, and pseudopolyps. Definitive diagnosis can be made with biopsy. The same lab workup as that of ulcerative colitis. Upper GI series with small bowel follow-through. Colonoscopy may show aphthoid, linear, or stellate ulcers, strictures, “cobblestoning,” and “skip lesions.” “Creeping fat” may also be present during laparotomy. Definitive diagnosis can be made with biopsy. Treatment 5-ASA agents (eg, sulfasalazine, mesalamine), topical or oral; corticosteroids and immunomodulating agents (eg, azathioprine) for refractory disease. Total proctocolectomy can be curative for long- 5-ASA agents; corticosteroids and immunomodulating agents (eg, azathioprine, infliximab) are indicated if no improvement is seen. Surgical resection may be necessary for suspected standing or fulminant colitis or toxic megacolon; also perforation, stricture, fistula, or abscess; may recur ↓ cancer risk. anywhere in the GI tract. Incidence of There is a markedly ↑ risk of colorectal cancer in long- The incidence of 2° malignancy is lower than that of cancer standing cases (monitor with frequent fecal occult blood ulcerative colitis but is greater than that of the general screening and yearly colonoscopy with multiple biopsies population. after 8 years of disease). DIAGNOSIS n n n Colonoscopy. Patients with ulcerative colitis are at significantly ↑ risk of colon cancer. Thus, colonoscopies are recommended for such patients every 1–2 years beginning 8–10 years after diagnosis. If dysplasia is present on random biopsy, total colectomy is recommended. Fever is sometimes present, and CBC shows leukocytosis (see Table 2.6-8). Ultrasound may demonstrate stones, bile sludge, pericholecystic fluid, a thickened gallbladder wall, gas in the gallbladder, and/or an ultrasonic Murphy’s sign (see Figure 2.6-14). When ultrasound is equivocal, obtain a HIDA scan. In this nuclear medicine scan, which uses a radiotracer excreted through the biliary system, nonvisualization of the gallbladder suggests acute cholecystitis. TREATMENT n n Give broad-spectrum IV antibiotics and IV fluids; replete electrolytes. Nonemergent cholecystectomy is indicated. GASTROINTESTINAL Transversus abdominis Internal oblique External oblique HIGH-YIELD FACTS IN 139 Inferior epigastric vessels Internal inguinal ring External inguinal ring Transversus aponeurosis Aponeurosis of external oblique Persistent processus vaginalis A Transversalis fascia Transversus abdominis Internal oblique Obliterated processus vaginalis Inferior epigastric vessels Neck of hernia Transversus aponeurosis Aponeurosis of external oblique External oblique External inguinal ring Testis B FIGURE 2.6-13. Indirect (A) and direct (B) inguinal hernias. (Reproduced with permission from Tintinalli JE et al. Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 7th ed. New York: McGraw-Hill, 2010, Figs. 87-4 and 87-3.) CH O LE D O CH O L IT H I A S I S n n n n Gallstones in the common bile duct. Symptoms vary according to the degree of obstruction, the duration of the obstruction, and the extent of bacterial infection. Hx/PE: Presents with biliary colic, jaundice, fever, and/or pancreatitis. Dx: The hallmark is ↑ alkaline phosphatase and total and direct bilirubin (see Table 2.6-8). Tx: Management consists of ERCP with sphincterotomy followed by cholecystectomy. AS C E N D I N G C H OL A N G I T I S An acute bacterial infection of the biliary tree that commonly occurs 2° to obstruction, usually from gallstones (choledocholithiasis). Other etiologies include bile duct stricture, primary sclerosing cholangitis, and malignancy. Gram-" enterics are commonly identified pathogens. A 43-year-old female presents to the ER with nausea, vomiting, and epigastric pain. She has complained of intermittent RUQ pain for the past several months. Physical examination reveals marked epigastric tenderness. Labs show leukocytosis, ↑ AST and ALT, and ↑ lipase. AXR is unremarkable. What is the most likely diagnosis? 140 HIGH-YIELD FACTS IN GASTROINTESTINAL L L A B F I G U R E 2 . 6 - 1 4 . Gallstone disease. (A) Cholelithiasis. Ultrasound image of the gallbladder shows a gallstone (arrow) with posterior shadowing. (B) Acute cholecystitis. Ultrasound image shows a gallstone (red arrow), a thickened gallbladder wall (arrowheads), and pericholecystic fluid (white arrow). L = liver. (Reproduced with permission from USMLERx.com.) KEY FACT HISTORY/PE n Charcot’s triad consists of RUQ pain, jaundice, and fever/chills. Reynolds’ pentad consists of RUQ pain, jaundice, fever/chills, shock, and altered mental status. n Charcot’s triad—RUQ pain, jaundice, and fever/chills—is classic. Reynolds’ pentad—Charcot’s triad plus septic shock and altered mental status—may be present in acute suppurative cholangitis and suggests sepsis. DIAGNOSIS n n n Labs reveal leukocytosis, ↑ bilirubin, and ↑ alkaline phosphatase (see Table 2.6-8). Obtain blood cultures to rule out sepsis. ERCP is both diagnostic and therapeutic. TREATMENT n n Patients often require ICU admission for monitoring, hydration, BP support, and broad-spectrum IV antibiotic treatment. Patients with acute suppurative cholangitis require emergent bile duct decompression via ERCP/sphincterotomy, percutaneous transhepatic drainage, or open decompression. TA B L E 2 . 6 - 8 . Differential Diagnosis of Biliary Disease ELEVATED TOTAL BILIRUBIN/ Gallstone pancreatitis results from a gallstone that travels through the common bile duct and lodges at the ampulla of Vater, which obstructs the flow of both pancreatic exocrine enzymes and bile. It most commonly occurs in women, who often report a history of biliary colic. Treatment involves management of the pancreatitis with supportive care and elective cholecystectomy. FEVER/ELEVATED ALKALINE ELEVATED SERUM WBC COUNT PHOSPHATASE AMYLASE Cholelithiasis (colic) − − − Acute cholecystitis + − − Choledocholithiasis/ + + − + + + ascending cholangitis Gallstone pancreatitis GASTROINTESTINAL HIGH-YIELD FACTS IN 141 GA L L S TO N E I L E U S n n n n A mechanical obstruction resulting from the passage of a large (> 2.5-cm) stone into the bowel through a cholecystoduodenal fistula. Obstruction is often at the ileocecal valve. Hx/PE: The classic presentation is a subacute SBO in an elderly woman. Patients may have no history of biliary colic. Dx: AXR with characteristics of SBO and pneumobilia (gas in the biliary tree) confirms the diagnosis. Upper GI barium contrast images will demonstrate no contrast in the colon. Tx: Laparotomy with stone extraction; closure of the fistula and cholecystectomy. PR I M A R Y SCLE R OS IN G CH OL A N G I TI S n n n n An idiopathic disorder characterized by progressive inflammation and fibrosis accompanied by strictures of extra- and intrahepatic bile ducts. The disease usually presents in young males with ulcerative colitis. Patients are at ↑ risk for cholangiocarcinoma. Hx/PE: Presents with progressive jaundice, pruritus, and fatigue. Dx: n Laboratory findings include ↑ alkaline phosphatase and ↑ bilirubin. n MRCP/ERCP show multiple bile duct strictures and dilatations (“beading”). n Liver biopsy reveals periductal sclerosis (“onion skinning”). Tx: High-dose ursodiol; ERCP with dilation and stenting of strictures. Liver transplantation is the definitive treatment. KEY FACT Primary sclerosing cholangitis is strongly associated with ulcerative colitis. Liver Disease AB N OR M A L L I V E R F U N C T I O N T E S TS Liver diseases can be divided into several patterns based on LFT results: n n n Hepatocellular injury: ↑ AST and ALT. Cholestasis: ↑ alkaline phosphatase and bilirubin. Isolated hyperbilirubinemia: ↑ bilirubin. Jaundice is a clinical sign that occurs when bilirubin levels exceed 2.5 mg/dL. Figures 2.6-15 and 2.6-16 summarize the clinical approaches toward cholestasis and isolated hyperbilirubinemia. KEY FACT HCV is Chronic; 60–70% of patients with HCV infection will develop chronic hepatitis. HE P A T IT IS Inflammation of the liver leading to cell injury and necrosis. Hepatitis can be either acute or chronic. n n n n Acute: The most common causes are viruses (HAV, HBV, HCV, HDV, HEV) and drugs (alcohol, acetaminophen, INH, methyldopa). Chronic: The most common causes are chronic viral infection, alcohol, autoimmune hepatitis, and metabolic syndromes (Wilson’s disease, hemochromatosis, α1-antitrypsin deficiency). HAV and HEV are transmitted by the fecal-oral route. HBV and HCV are transmitted by body fluids, although the risk of acquiring HCV sexually is very low. A 21-year-old male college student in the midst of final exams presents to a local clinic with “yellow eyes.” His physical examination is unremarkable except for scleral icterus, and a CBC and blood smear show no abnormalities. A comprehensive metabolic profile reveals a normal AST and ALT but elevated unconjugated bilirubin. What is the most likely diagnosis? 142 HIGH-YIELD FACTS IN GASTROINTESTINAL Cholestasis (↑↑ alkaline phosphatase and bilirubin) Ductal dilation? FIGURE 2.6-15. No Yes Intrahepatic cholestasis Biliary obstruction Medications Postop Sepsis Stone Stricture Cancer Approach to cholestasis. HISTORY/PE n n KEY FACT An AST/ALT ratio > 2 suggests alcohol hepatitis: you’re toASTed. Acute hepatitis: n Often begins with a nonspecific viral prodrome (malaise, fever, joint pain, fatigue, URI symptoms, nausea, vomiting, changes in bowel habits) followed by jaundice and RUQ tenderness. Examination often reveals jaundice, scleral icterus, and tender hepatomegaly. n HAV and HEV have only a self-limited acute phase; HBV and HCV may feature a mild acute phase or none at all. Acetaminophen toxicity can cause a life-threatening hepatitis. Chronic hepatitis: Usually presents with symptoms only when the liver scars to the point of cirrhosis (jaundice, fatigue, ascites). At least 80% of those infected with HCV and 10% of those with HBV will develop persistent infection with chronic active hepatitis. DIAGNOSIS n n n Acute hepatitis: Labs reveal markedly ↑ ALT and AST and ↑ bilirubin/ alkaline phosphatase. Chronic hepatitis: ALT and AST are persistently elevated for > 3–6 months. The diagnosis of viral hepatitis is made by hepatitis serology (see Table 2.6-9 and Figure 2.6-17 for a description and timing of serologic markers) and by liver biopsy in chronic or severe cases. Isolated hyperbilirubinemia (↑↑ bilirubin) Unconjugated Gilbert’s syndrome is an autosomal recessive disorder of bilirubin glucuronidation due to ↓ activity of the enzyme glucuronyl transferase. Patients present with unconjugated hyperbilirubinemia but have a normal CBC, blood smear, and LFTs. The condition is benign, and no treatment is indicated. Overproduction Hemolytic anemia FIGURE 2.6-16. Conjugated Defective conjugation Defective excretion Gilbert’s syndrome (< 5 mg/dL) Crigler-Najjar syndrome Dubin-Johnson syndrome Rotor’s syndrome Approach to isolated hyperbilirubinemia. GASTROINTESTINAL TA B L E 2 . 6 - 9 . Key Hepatitis Serologic Markers SEROLOGIC MARKER DESCRIPTION IgM HAVAb IgM antibody to HAV; the best test to detect acute HAV. HBsAg Antigen found on the surface of HBV; continued presence indicates carrier state. HBsAb Antibody to HBsAg; indicates immunity to HBV. HBcAg Antigen associated with core of HBV. Not measured in clinical practice. Antibody to HBcAg; IgM ! during the window period. IgG HBcAb is HBcAb an indicator of prior or current infection. HBeAg A different antigenic determinant in the HBV core. An important indicator of transmissibility (BEware!). HBeAb n Antibody to e antigen; indicates low transmissibility. Other diagnostic studies include the following: n Autoimmune hepatitis: ! anti–smooth muscle antibodies. n Hemochromatosis: High ferritin and transferrin saturation > 50%. n Wilson’s disease: Low ceruloplasmin, high urine copper. Important diagnostic tests Convalescence Incubation Prodrome, period acute disease HBsAg (anti-HBc) HBsAg 0 1 2 3 4 5 Early Late AntiHBc Anti-HBs (anti-HBc) 6 7 8 DNA polymerase HBV particles Titer Anti-HBc HBsAg Window period Anti-HBs HBeAg Anti-HBe Level of detection 0 FIGURE 2.6-17. 1 2 3 4 5 6 7 Months after exposure 8 Time course of hepatitis B with serologic markers. HIGH-YIELD FACTS IN 143 144 HIGH-YIELD FACTS IN KEY FACT GASTROINTESTINAL TREATMENT n The sequelae of chronic hepatitis include cirrhosis, liver failure, and hepatocellular carcinoma. n n Acute hepatitis: Supportive care. Chronic hepatitis: Treatment is etiology specific. n Chronic HBV infection: Interferon and lamivudine (3TC) or adefovir. n Chronic HCV infection: Interferon and ribavirin. Liver transplantation is the definitive treatment for patients with endstage liver failure. Emergent transplantation is indicated in cases of fulminant hepatic failure. COMPLICATIONS Cirrhosis, liver failure, hepatocellular carcinoma (3–5%). CI R R HOS I S Defined as fibrosis and nodular regeneration resulting from chronic hepatic injury. Etiologies can be intra- or extrahepatic: n n Intrahepatic: All causes of chronic hepatitis. Extrahepatic: n Biliary tract disease (primary biliary cirrhosis, primary sclerosing cholangitis). n Posthepatic causes include right-sided heart failure, constrictive pericarditis, and Budd-Chiari syndrome (hepatic vein thrombosis 2° to hypercoagulability). HISTORY/PE KEY FACT Spontaneous bacterial peritonitis is diagnosed by > 250 PMNs/mL in the ascitic fluid. n n Presents with jaundice, ascites, spontaneous bacterial peritonitis, hepatic encephalopathy (asterixis, altered mental status), gastroesophageal varices, coagulopathy, and renal dysfunction. Ascites can be complicated by spontaneous bacterial peritonitis. Examination may reveal an enlarged, palpable, or firm liver and other signs of portal hypertension and liver failure (see Figures 2.6-18 and 2.619). Effects of portal hypertension s %SOPHAGEAL VARICES (EMATEMESIS 0EPTIC ULCER s -ELENA s 3PLENOMEGALY s #APUT MEDUSAE s !SCITES s (EMORRHOIDS FIGURE 2.6-18. Effects of liver cell failure s #OMA s 3CLERAL ICTERUS s &ETOR HEPATICUS BREATH SMELLS LIKE A FRESHLY OPENED CORPSE s 3PIDER NEVI s 'YNECOMASTIA s *AUNDICE s ,OSS OF SEXUAL HAIR s ,IVER FLAP  ASTERIXIS COARSE HAND TREMOR s "LEEDING TENDENCY DECREASED PROTHROMBIN s !NEMIA s 4ESTICULAR ATROPHY s !NKLE EDEMA Presentation of cirrhosis/portal hypertension. (Adapted with permission from Chandrasoma P, Taylor CE. Concise Pathology, 3rd ed. Stamford, CT: Appleton & Lange, 1998: 654.) GASTROINTESTINAL HIGH-YIELD FACTS IN 145 1 Gastroesophageal vv. L. gastric v. Portal v. Splenic v. 4 Gastrorenalsplenorenal vv. Paraumbilical v. 3 5 Retroperitoneal paravertebral v v. IVC Superior mesenteric v. 2 Superiormiddle/inferior rectal vv. Systemic venous Portal venous F I G U R E 2 . 6 - 1 9 . Portosystemic anastomoses. 1. Left gastric–azygos → esophageal varices. 2. Superior–middle/inferior rectal → hemorrhoids. 3. Paraumbilical–inferior epigastric → caput medusae (navel). 4. Gastrorenal-splenorenal. 5. Retroperitoneal paravertebral. DIAGNOSIS n n n n Lab studies show ↓ albumin, ↑ PT/INR, and ↑ bilirubin. Anemia or thrombocytopenia (2° to hypersplenism and bone marrow suppression) may also be seen. Other studies, including hepatitis serologies, serum ferritin, ceruloplasmin, and α1-antitrypsin, will identify other causes, such as infection, hemochromatosis, Wilson’s disease, and α1-antitrypsin deficiency, respectively. If ascites is present, the etiology of ascites can be determined by the serum-ascites albumin gradient (SAAG = serum albumin – ascites albumin); see Table 2.6-10. Liver biopsy will show bridging fibrosis and nodular regeneration. TREATMENT The goal is to slow the progression of cirrhosis and prevent associated complications (see Table 2.6-11). TA B L E 2 . 6 - 10 . Etiologies of Cirrhosis by SAAG SAAG > 1.1 Related to portal hypertension: n Presinusoidal: Splenic or portal vein thrombosis, schistosomiasis n Sinusoidal: Cirrhosis n Postsinusoidal: Right heart failure, constrictive pericarditis, Budd-Chiari syndrome SAAG < 1.1 Not related to portal hypertension: n Nephrotic syndrome n TB n Malignancy with peritoneal carcinomatosis (eg, ovarian cancer) A 36-year-old woman with a past medical history of hypercholesterolemia and type 2 DM presents with intermittent dull RUQ discomfort. The patient does not drink alcohol. Her physical examination is unremarkable. Lab studies show elevated AST and ALT but are otherwise normal. Hepatitis serologies are #. What is the most likely diagnosis? 146 HIGH-YIELD FACTS IN TA B L E 2 . 6 - 11 . GASTROINTESTINAL Complications of Cirrhosis COMPLICATION MECHANISM/HISTORY ↑ portal hypertension results in transudative Ascites effusion. Physical examination reveals abdominal MANAGEMENT Sodium restriction and diuretics (furosemide, spironolactone); large-volume paracentesis. Treat underlying liver disease if possible. distention, fluid wave, and shifting dullness to percussion. Spontaneous bacterial peritonitis Presents with fever, abdominal pain, chills, nausea, and vomiting. Diagnostic paracentesis reveals > 250 PMNs/mL IV antibiotics acutely (third-generation cephalosporin), IV albumin; prophylaxis with a fluoroquinolone to prevent recurrence. and a ! Gram stain. Hepatorenal syndrome Acute prerenal failure in the setting of advanced Difficult to treat; often requires dialysis. The only cirrhosis. A diagnosis of exclusion. Urinary cure is liver transplantation. sodium is < 10 mEq/L. Hepatic encephalopathy Esophageal varices ↓ clearance of ammonia; often precipitated by Protein restriction, lactulose, and/or rifaximin. dehydration, infection, electrolyte abnormalities, Correct underlying triggers (eg, replete and GI bleeding. potassium). Portal hypertension leads to ↑ flow through Endoscopic surveillance in all patients with portosystemic anastomoses. cirrhosis; medical prophylaxis with β-blockers to prevent bleeding. For acute bleeding, endoscopy with band ligation or sclerotherapy is indicated. Coagulopathy Impaired synthesis of all clotting factors (except For acute bleeding, administer fresh VIII). frozen plasma. Vitamin K will not correct coagulopathy. PR I M AR Y BI LI AR Y CI R R HOS I S KEY FACT Primary biliary cirrhosis is an autoimmune disease that presents with jaundice and pruritus in middle-aged women. n n n n Nonalcoholic fatty liver disease, a condition that is associated with insulin resistance and metabolic syndrome. In its earliest stage, the condition can be reversed with weight loss and a fat-restricted diet. Later, however, it can progress to irreversible nonalcoholic steatohepatitis and cirrhosis. An autoimmune disorder characterized by destruction of intrahepatic bile ducts. Most commonly presents in middle-aged women with other autoimmune conditions. Hx/PE: Presents with progressive jaundice, pruritus, and fat-soluble vitamin deficiencies (A, D, E, K). Dx: Laboratory findings include ↑ alkaline phosphatase, ↑ bilirubin, ! antimitochondrial antibody, and ↑ cholesterol. Tx: Ursodeoxycholic acid (slows progression of disease); cholestyramine for pruritus; liver transplantation. HE P ATO C E LLU LAR CAR C I NO M A One of the most common cancers worldwide despite its relatively low incidence in the United States. 1° risk factors for the development of hepatocellular carcinoma in the United States are cirrhosis from alcohol and chronic hepatitis (HCV). In developing countries, aflatoxins (in various food sources) and HBV infection are major risk factors. GASTROINTESTINAL HISTORY/PE n n Patients commonly present with RUQ tenderness, abdominal distention, and signs of chronic liver disease such as jaundice, easy bruisability, and coagulopathy. Examination may reveal tender enlargement of the liver. DIAGNOSIS Often suggested by the presence of a mass on ultrasound or CT as well as by abnormal LFTs and significantly elevated α-fetoprotein (AFP) levels. TREATMENT n n n Surgical: Partial hepatectomy for single lesions < 5 cm with no cirrhosis; orthotopic liver transplantation in patients with cirrhosis. Nonsurgical: Transarterial chemoembolization (TACE) and/or sorafenib for advanced disease. Monitor AFP levels to screen for recurrence. HE M O C H RO M A T O S I S A state of iron overload in which hemosiderin accumulates in the liver, pancreas (islet cells), heart, adrenals, testes, pituitary, and kidneys. n n 1° hemochromatosis: An autosomal recessive disease characterized by mutations in the HFE gene that result in excessive absorption of dietary iron. 2° hemochromatosis: Occurs in patients receiving chronic transfusion therapy (eg, α-thalassemia). HISTORY/PE n n n Patients may present with abdominal pain, DM, hypogonadism, arthropathy of the MCP joints, heart failure, or cirrhosis. Examination may reveal bronze skin pigmentation, cardiac dysfunction (CHF), hepatomegaly, and testicular atrophy. Labs may reveal evidence of DM. Hemochromatosis does not affect the lung, kidney, or eye. DIAGNOSIS n n n n ↑ serum iron, percent saturation of iron, and ferritin with ↓ serum transferrin. A transferrin saturation (serum iron divided by TIBC) > 45% is highly suggestive of iron overload. In severe cases, patients may be report being repeatedly interrogated at airport security because they can accumulate so much iron that it activates metal detectors. Perform a liver biopsy (to determine hepatic iron index), MRI, or HFE gene mutation screen. TREATMENT n n Weekly phlebotomy to normalize serum iron levels, and then maintenance phlebotomy every 2–4 months. Deferoxamine can be used for maintenance therapy. COMPLICATIONS Cirrhosis, hepatocellular carcinoma, restrictive cardiomyopathy, arrhythmias, DM, impotence, arthropathy, hypopituitarism. HIGH-YIELD FACTS IN 147 148 HIGH-YIELD FACTS IN GASTROINTESTINAL W I LSON’S DI S E AS E ( HE P AT OLE NTI C U LAR DE G E NE R ATI ON) n n F I G U R E 2 . 6 - 2 0 . Kayser-Fleischer ring. Note the brown ring encircling the iris. This is a result of copper deposition in Descemet’s membrane and is a classic finding in Wilson’s disease. (Reproduced with permission from USMLERx.com.) n n n An autosomal recessive disorder that results in defective copper transport and subsequent accumulation and deposition of copper in the liver and brain. Usually occurs in patients < 30 years of age; 50% are symptomatic by age 15. Hx: Patients present with hepatitis/cirrhosis, neurologic dysfunction (ataxia, tremor), and psychiatric abnormalities (psychosis, anxiety, mania, depression). PE: May reveal Kayser-Fleischer rings (green-to-brown deposits of copper in Descemet’s membrane; see Figure 2.6-20) as well as jaundice, hepatomegaly, asterixis, choreiform movements, and rigidity. Dx: ↓ serum ceruloplasmin; ↑ urinary copper excretion. Tx: Dietary copper restriction (avoid shellfish, liver, legumes), penicillamine (a copper chelator that ↑ urinary copper excretion), and zinc (↑ fecal excretion). Pancreatic Disease PANC R E ATI TI S Table 2.6-12 outlines the features of acute and chronic pancreatitis. Table 2.6-13 lists Ranson’s criteria for predicting mortality in acute pancreatitis. PANC R E ATI C CANC E R Most (75%) are adenocarcinomas in the head of the pancreas. Risk factors include smoking, chronic pancreatitis, and a first-degree relative with pancreatic cancer. Incidence ↑ after age 45; slightly more common in males. HISTORY/PE n n n KEY FACT The hallmark finding in pancreatic cancer is a nontender, palpable gallbladder. Presents with abdominal pain radiating toward the back as well as with obstructive jaundice, loss of appetite, nausea, vomiting, weight loss, weakness, fatigue, and indigestion. Often asymptomatic, and thus presents late in the disease course. Examination may reveal a palpable, nontender gallbladder (Courvoisier’s sign) or migratory thrombophlebitis (Trousseau’s sign). DIAGNOSIS n n n CT scan with contrast to localize the tumor and assess the extent of local invasion and distant metastases. If a mass is not visualized on CT, use endoscopic ultrasound +/– ERCP. CA-19-9 is often elevated but is neither sensitive nor specific. TREATMENT n n n Most patients present with locally advanced or metastatic disease, so treatment is palliative. Patients with small tumors in the pancreatic head with no metastasis or major vessel involvement are eligible for surgical resection using the Whipple procedure (pancreaticoduodenectomy). Chemotherapy with 5-FU and gemcitabine may improve short-term survival, but long-term prognosis is poor (5–10% 5-year survival). GASTROINTESTINAL TA B L E 2 . 6 - 12 . VARIABLE Pathophysiology HIGH-YIELD FACTS IN 149 Features of Acute and Chronic Pancreatitis ACUTE PANCREATITIS CHRONIC PANCREATITIS Leakage of pancreatic enzymes into pancreatic and Irreversible parenchymal destruction leading to peripancreatic tissue. pancreatic dysfunction and insufficiency. Time course Abrupt onset of severe pain. Persistent, recurrent episodes of severe pain. Risk factors Gallstones, alcohol abuse, hypercalcemia, Alcohol abuse (90%), gallstones, CF, smoking, hypertriglyceridemia, trauma, drug side effects (thiazide pancreatic divisum, family history. diuretics), viral infections, post-ERCP, scorpion bites. History/exam Severe epigastric pain (radiating to the back); nausea, vomiting, weakness, fever, shock. Flank discoloration (Grey Turner’s sign) and Recurrent episodes of persistent epigastric pain; anorexia, nausea, constipation, flatulence, steatorrhea, weight loss, DM. periumbilical discoloration (Cullen’s sign) may be evident on examination. Diagnosis ↑ amylase, ↑ lipase, ↓ calcium if severe; “sentinel loop” or “colon cutoff sign” on AXR. Abdominal ultrasound or CT may show an enlarged ↑ to normal amylase and lipase, ↓ stool elastase, pancreatic calcifications (see Figure 2.6-21B), and mild ileus on AXR and CT (“chain of lakes”). pancreas with stranding, abscess, hemorrhage, necrosis, or pseudocyst (see Figure 2.6-21A). Treatment Removal of the offending agent if possible. Analgesia, pancreatic enzyme replacement, avoidance of Supportive care, including IV fluids/electrolyte causative agents (EtOH), celiac nerve block; surgery for replacement, analgesia, bowel rest, NG suction, intractable pain or structural causes. nutritional support, and O2. Treat severe necrotizing pancreatitis with IV antibiotics, respiratory support, and surgical debridement. Prognosis Roughly 85–90% are mild and self-limited; 10–15% are Patients can have chronic pain and pancreatic severe, requiring ICU admission. Mortality may approach dysfunction. 50% in severe cases. Complications Pancreatic pseudocyst, fistula formation, hypocalcemia, renal failure, pleural effusion, chronic pancreatitis, sepsis. Mortality 2° to acute pancreatitis can be predicted with Ranson’s criteria (see Table 2.6-13). Chronic pain, opiate addiction, malnutrition/weight loss, pancreatic cancer. 150 HIGH-YIELD FACTS IN GASTROINTESTINAL P A B F I G U R E 2 . 6 - 2 1 . Pancreatitis. (A) Uncomplicated acute pancreatitis. Peripancreatic fluid and fat stranding can be seen (arrows). P = pancreas. (B) Chronic pancreatitis. Note the dilated pancreatic duct (arrowhead) and pancreatic calcifications (arrow). (Reproduced with permission from USMLERx.com.) TA B L E 2 . 6 - 13 . Ranson’s Criteria for Acute Pancreatitisa ON ADMISSION WITHIN 48 HOURS “GA LAW”: “C HOBBS”: Glucose > 200 mg/dL Ca2+ < 8.0 mg/dL Age > 55 years Hematocrit ↓ by > 10% LDH > 350 IU/L PaO2 < 60 mm Hg AST > 250 IU/dL Base deficit > 4 mEq/L WBC > 16,000/mL BUN ↑ by > 5 mg/dL Sequestered fluid > 6 L a The risk of mortality is 20% with 3–4 signs, 40% with 5–6 signs, and 100% with ≥ 7 signs. HIGH-YIELD FACTS IN HEMATOLOGY/ONCOLOGY Coagulation Disorders 152 White Blood Cell Disorders 166 COAGULATION CASCADE 152 LEUKEMIAS 166 HEMOPHILIA 153 LYMPHOMAS 170 154 Plasma Cell Disorders 172 HYPERCOAGULABLE STATES 155 MULTIPLE MYELOMA 172 DISSEMINATED INTRAVASCULAR COAGULATION 156 WALDENSTRÖM’S MACROGLOBULINEMIA 173 THROMBOTIC THROMBOCYTOPENIC PURPURA 156 AMYLOIDOSIS 174 IDIOPATHIC THROMBOCYTOPENIC PURPURA 157 VON WILLEBRAND’S DISEASE Blood Cell Differentiation 158 Red Blood Cell Disorders 159 ANEMIAS 159 THALASSEMIAS 164 POLYCYTHEMIAS 165 TRANSFUSION REACTIONS 165 PORPHYRIA 165 Neutropenia 175 Eosinophilia 175 Transplant Medicine 176 Diseases Associated With Neoplasms 177 151 152 HIGH-YIELD FACTS IN HEMATOLOGY/ONCOLOGY Coagulation Disorders C OAG U LATI ON C AS C ADE Hemostasis requires the interaction of blood vessels, platelets, monocytes, and coagulation factors. This activates the clotting cascade, as shown in Figure 2.7-1. n n n Heparin: ↑ PTT, activates antithrombin III and affects the intrinsic pathway, and ↓ fibrinogen levels. Protamine sulfate is the antidote. Warfarin: ↑ PT, inhibits vitamin K and affects the extrinsic pathway (factors II, VII, IX, and X and protein C and S), and is teratogenic, as its small size allows it to cross the placenta. Vitamin K is the antidote. The goal INR is 2.0–3.0 (2.5–3.5 in patients with mechanical valves). Enoxaparin (low-molecular-weight heparin, or LMWH): Inhibits factor Xa and does not have to be monitored in most situations; dosing is once or twice daily. Intrinsic pathway—measured by PTT (initiated by exposure of collagen following vascular trauma) XII XIIa Extrinsic pathway—measured by PT (initiated by endotheliumproduced tissue factor) XIa XI VII* IX* Hemophilia B is characterized by factor IX deficiency. IXa X* III VIII VIIIa VIIa Hemophilia A is characterized by factor VIII deficiency. Xa V Va Thrombin is inactivated by antithrombin III. The rate of inactivation increases in the presence of heparin. Fibrinogen F (Thrombin) IIa (Prothrombin) II* Fibrin XIII XIIIa X-linked fibrin * Vitamin K–dependent clotting factors (II, VII, IX, X). Their synthesis is inhibited by warfarin. FIGURE 2.7-1. Coagulation cascade. HEMATOLOGY/ONCOLOGY Heparin-to-warfarin conversion is necessary because warfarin inhibits proteins C and S before other vitamin K–dependent factors (II, VII, IX, and X), leading to a transient period of paradoxical hypercoagulability before proper anticoagulation. H EM O P H I L IA A deficiency of a clotting factor that leads to a bleeding diathesis. Subtypes are distinguished on the basis of which factor is lacking (see Table 2.7-1). The condition is usually hereditary but may be acquired through the development of an antibody to a clotting factor. This may occur with autoimmune or lymphoproliferative disease, postpartum, or following a blood transfusion. Patients are nearly always male and may have a ! family history. HISTORY/PE n n n Presents with spontaneous hemorrhage into the tissues and joints that, if left untreated, can lead to arthropathy and joint destruction. Spontaneous intracerebral hemorrhages as well as renal, retroperitoneal, and GI bleeding may also be seen. Mild cases may have major hemorrhage after surgery or trauma but are otherwise asymptomatic. DIAGNOSIS n n n Order labs: n PT: Usually normal, but isolated elevations are seen in congenital factor VII deficiency. n aPTT: Prolonged (the more prolonged, the more severe the hemophilia). n Thrombin time, fibrinogen, bleeding time: Usually normal. Conduct a mixing study: Mix the patient’s plasma with normal plasma; if this corrects the aPTT, a factor deficiency is likely. If the aPTT does not correct, the patient may have a clotting factor inhibitor. Obtain factor assays: Specific factor assays should then be performed for factors VII, VIII, IX, XI, and XII. Hemophilia is characterized according to factor level as follows: n Mild: > 5% of normal. n Moderate: 1–3% of normal. n Severe: ≤ 1% of normal. TA B L E 2 . 7- 1 . Types of Hemophilia SUBTYPE/INCIDENCE Hemophilia A (factor VIII deficiency) (90%) PATHOGENESIS X-linked inheritance; the most common severe congenital clotting deficiency. Hemophilia B (factor IX deficiency) (9%) X-linked inheritance. Hemophilia C (factor XI deficiency) (< 1%) Most common in Ashkenazi Jews. Factor VII deficiency (< 1%) Presents in a milder, likely heterozygous form. HIGH-YIELD FACTS IN 153 KEY FACT Bleeding disorders due to platelet dysfunction usually manifest as petechiae, whereas disorders of coagulation factors cause other symptoms, such as hemarthroses. KEY FACT The classic case of hemophilia is the boy (X-linked) from the Imperial Russian family (Recessive) who presents with hemarthroses following minimal or no trauma. 154 HIGH-YIELD FACTS IN HEMATOLOGY/ONCOLOGY TREATMENT KEY FACT n Cryoprecipitate consists mainly of factor VIII and fibrinogen, with smaller concentrations of factor XIII, vWF, and fibronectin. It is a more concentrated source of factor VIII and fibrinogen than fresh frozen plasma (FFP). n n n KEY FACT Treat bleeding episodes with immediate transfusion of clotting factors (or cryoprecipitate) to at least 40% of normal concentration. The length of treatment varies with the lesion, extending up to several weeks after orthopedic surgery. Mild hemophilia may be treated with desmopressin (DDAVP); if so, patients should be fluid restricted to prevent the side effect of hyponatremia. Depending on the degree of blood loss, it may be necessary to transfuse RBCs. V ON W I LLE BR AND’S DI S E AS E ( v WD) DDAVP helps the body release extra factor VIII. An autosomal dominant condition in which patients have deficient or defective von Willebrand’s factor (vWF) with low levels of factor VIII, which is carried by vWF (see Figure 2.7-2). Symptoms are due to platelet dysfunction and to deficient factor VIII. The disease is milder than hemophilia. vWD is the most common inherited bleeding disorder (1% of the population is affected). HISTORY/PE Presents with easy bruising, mucosal bleeding (eg, epistaxis, oral bleeding), menorrhagia, and postincisional bleeding. Platelet dysfunction is not severe enough to produce petechiae. Symptoms worsen with ASA use. DIAGNOSIS KEY FACT n Ristocetin cofactor assay measures the ability of vWF to agglutinate platelets in vitro in the presence of ristocetin. n n Look for a family history of bleeding disorders. Platelet count and PT are normal, but a prolonged aPTT and prolonged bleeding time may be seen as a result of factor VIII deficiency. A ristocetin cofactor assay of patient plasma can measure the capacity of vWF to agglutinate platelets. Irreversibly blocked by clopidogrel and ticlopidine Platelet Inside platelets Fibrinogen ADP receptor FIGURE 2.7-2. GpIb vWF Thrombogenesis deficiencies. Platelet phospholipid Deficiency: Glanzmann’s thrombasthenia Protein C GpIIb/IIIa insertion Subendothelial collagen (fibrinogen) Arachidonic COX TxA 2 acid GpIIb/IIIa Deficiency: BernardSoulier syndrome (vWF) Deficiency: von Willebrand’s disease Thrombomodulin Activated protein C Vascular endothelial cells Inside endothelial cells (vWF) thromboplastin tPA, PGI2 HEMATOLOGY/ONCOLOGY TREATMENT n n Bleeding episodes can be treated with DDAVP; menorrhagia can be controlled with OCPs. Avoid ASA and other inhibitors of platelet function. HIGH-YIELD FACTS IN 155 KEY FACT ASA ↑ the risk of bleeding in patients with vWD. H Y P E RC O A G U LA B L E ST A T E S Also called thrombophilias or prothrombotic states, hypercoagulable states is an all-inclusive term describing conditions that ↑ a patient’s risk of developing thromboembolic disease. Causes are multiple and may be genetic, acquired, or physiologic (see Table 2.7-2). Inherited causes are collectively called hereditary thrombotic disease, of which factor V Leiden (a polymorphism in factor V, rendering it resistant to inactivity by activated protein C, or APC) is the most common. HISTORY/PE n n KEY FACT Presents with recurrent thrombotic complications, including DVT, pulmonary embolism (PE), arterial thrombosis, MI, and stroke. Women may have recurrent miscarriages. Although patients may have no recognizable predisposing factors, they usually have 1 or more of the causative factors outlined in Table 2.7-2. They may also have a ! family history. Suspect PE in a patient with rapid onset of dyspnea, pleuritic chest pain, hypoxia, tachycardia, and an ↑ alveolararterial oxygen gradient without another obvious explanation. DIAGNOSIS n n Under ideal circumstances, patients should be diagnosed before they are symptomatic, but this rarely occurs. Before a workup is conducted for hereditary causes (see Table 2.7-2), acquired causes of abnormal coagulation values should be ruled out. Confirmation of a hereditary abnormality requires 2 abnormal values that are obtained while the patient is asymptomatic and untreated, with similar values obtained in 2 other family members. TREATMENT n n Treatment should address the type of thrombotic event as well as the area of thrombosis. Treat DVT and PE with heparin (unfractionated or LMWH) followed by 3–6 months of oral warfarin anticoagulation for the first event, 6–12 months for the second, and lifelong anticoagulation for subsequent events. TA B L E 2 . 7- 2 . Causes of Hypercoagulable States GENETIC ACQUIRED PHYSIOLOGIC Antithrombin III deficiency Surgery Age Protein C deficiency Trauma Pregnancy Protein S deficiency Malignancy Factor V Leiden Immobilization Hyperhomocysteinemia Smoking Dysfibrinogenemia Obesity Plasminogen deficiency Antiphospholipid syndrome Prothrombin G20210A Nephrotic syndrome mutation MTHFR gene mutation OCPs/hormone replacement therapy A 33-year-old female was admitted to the hospital for anticoagulation after a PE. On day 4 of her stay, her platelet level ↓ from 100,000 to 60,000/ mm3 and her INR remains < 2. What is the next best step, and what complications can result from this condition? 156 HIGH-YIELD FACTS IN HEMATOLOGY/ONCOLOGY n An IVC filter is the best means of preventing PE in DVT patients who have contraindications to anticoagulation (eg, recent trauma, hemorrhage, severe hypertension) and is also recommended for patients who have recurrent DVTs on anticoagulation. DI S S E M I NATE D INTR A VAS CU LAR C OAG U LATI ON ( DI C ) A common disorder among hospitalized patients, second only to liver disease as a cause of acquired coagulopathy. It is caused by deposition of fibrin in small blood vessels, leading to thrombosis and end-organ damage. Depletion of clotting factors and platelets leads to a bleeding diathesis. It may be associated with almost any severe illness. HISTORY/PE n KEY FACT n DIC is characterized by both thrombosis and hemorrhage. Disorders commonly associated with DIC include obstetric complications, infections with septicemia, neoplasms, acute promyelocytic leukemia, pancreatitis, intravascular hemolysis, vascular disorders (eg, aortic aneurysm), massive tissue injury and trauma, drug reactions, acidosis, and ARDS. Clinical presentation is as follows: n Acute: Presents with generalized bleeding from venipuncture sites and into organs, with ecchymoses and petechiae. n Chronic: Presents with bruising and mucosal bleeding, thrombophlebitis, renal dysfunction, and transient neurologic syndromes. DIAGNOSIS n n Diagnosed as outlined in Table 2.7-3. DIC may be confused with severe liver disease, but unlike liver disease, factor VIII is depressed. TREATMENT Reverse the underlying cause; RBC transfusion, platelet transfusion, and shock management. THR OM BOTI C TH R OM BOCYTOP E NI C P U R P U R A (TTP ) A bleeding disorder due to platelet microthrombi that block off small blood vessels, leading to end-organ ischemia and dysfunction. RBCs are fragTA B L E 2 . 7- 3 . DIC and TTP Features VARIABLE This patient is experiencing heparininduced thrombocytopenia (HIT), which occurs 2° to the formation of antibodies that activate platelets. Because HIT can lead to a hypercoagulable state, heparin must be stopped immediately, and the patient must be switched to lepirudin, danaparoid, or argatroban. DIC TTP Clotting factors ↓ Normal PT and aPTT ↑ Normal Platelets ↓ ↓ D-dimer ↑ Normal ↓ Normal Present Present and fibrin degradation products Fibrinogen level Microangiopathic hemolytic anemia HEMATOLOGY/ONCOLOGY mented by contact with the microthrombi, leading to hemolysis (microangiopathic hemolytic anemia). The cause of initial microthrombus formation is unknown but may be infectious (bacterial toxins), drug related, autoimmune, or idiopathic. HISTORY/PE n n A clinical syndrome characterized by 5 signs/symptoms: n Low platelet count n Microangiopathic hemolytic anemia n Neurologic changes (delirium, seizure, stroke) n Impaired renal function n Fever Maintain high clinical suspicion for TTP if 3 of 5 of these symptoms are present. DIAGNOSIS n n n Diagnosis is largely clinical (see Table 2.7-3). It is rare for all signs to be present, but the presence of schistocytes (broken RBCs) on peripheral smear (see Figure 2.7-3) with low platelets and rising creatinine is highly suggestive. Nucleated RBCs are also often seen in the peripheral smear. Part of a spectrum of diseases that includes hemolytic-uremic syndrome (HUS) and HELLP syndrome (see the Obstetrics chapter). n HUS: Characterized by renal failure, hemolytic anemia, and low platelets. Severe elevations in creatinine levels are more typical of HUS than of TTP. n HELLP syndrome: Affects pregnant women, often occurring in conjunction with preeclampsia. HIGH-YIELD FACTS IN 157 An 8-year-old girl presents to the ER with 2 days of fever, vomiting, bloody diarrhea, and irritability. She began feeling unwell after attending a classmate’s birthday party. Her labs reveal thrombocytopenia and an ↑ creatinine level. What is the best antibiotic therapy? KEY FACT The 3 causes of microangiopathic hemolytic anemia are HUS, TTP, and DIC. KEY FACT Remember: DICk’s HoUSe got TPed because he caused microangiopathic hemolytic anemia. TREATMENT Steroids to ↓ microthrombus formation; plasma replacement and plasmapheresis for severe cases. Platelet transfusion is contraindicated, as it often worsens the patient’s condition 2° to added platelet aggregation and microvascular thrombosis. ID I O P A T HI C T H R O M B O C Y T O PE NIC PU R P U R A (I TP) A relatively common cause of thrombocytopenia. IgG antibodies are formed against the patient’s platelets. Bone marrow production of platelets is ↑, with ↑ megakaryocytes in the marrow. The most common immunologic disorder in women of childbearing age. May be acute or chronic. HISTORY/PE n n Patients often feel well and present with no systemic symptoms. They may have minor bleeding, easy bruising, petechiae, hematuria, hematemesis, or melena. Bleeding is mucocutaneous. Generally there is no splenomegaly. ITP is associated with a range of conditions, including lymphoma, leukemia, SLE, HIV, and HCV. Presentation is as follows: n Acute: Abrupt onset of hemorrhagic complications following a viral illness. Commonly affects children 2–6 years of age, with males and females affected equally. n Chronic: Insidious onset that is unrelated to infection. Most often affects adults 20–40 years of age; females are 3 times more likely to be affected than males. FIGURE 2.7-3. Schistocytes. These fragmented RBCs may be seen in microangiopathic hemolytic anemia and in mechanical hemolysis. (Courtesy of Peter McPhedran, MD, Yale Department of Hematology.) 158 HIGH-YIELD FACTS IN HEMATOLOGY/ONCOLOGY DIAGNOSIS n HUS is the most common cause of acute renal failure in children. Supportive therapy includes IV fluids, BP control, blood transfusion, and, if necessary, dialysis. Antibiotics are not indicated, as they are thought to ↓ expulsion of the toxin and may ↑ toxin from the destruction of bacteria. n n TREATMENT n MNEMONIC Differential diagnosis of thrombocytopenia— n n n HIT SHOC HIT or HUS ITP TTP or Treatment (meds) Splenomegaly Hereditary (eg, Wiskott-Aldrich syndrome) Other causes (eg, malignancy) Chemotherapy A diagnosis of exclusion, as the test for platelet-associated antibodies is a poor one. Once other causes of thrombocytopenia have been ruled out, a diagnosis can be made on the basis of the history and physical, a CBC, and a peripheral blood smear showing normal RBC morphology. Most patients do not require bone marrow biopsy, which would show ↑ megakaryocytes as the only abnormality. n Most patients with acute childhood ITP spontaneously remit, but this is rarely the case with chronic ITP. Treatment is reserved for patients with symptomatic bleeding. Those with platelet counts > 20,000/mm3 are generally asymptomatic. Platelet transfusions are of no benefit, as patients’ IgG levels will lead to destruction of platelets. The main therapies are corticosteroids, high-dose gamma globulin (IVIG), and splenectomy. Most patients respond to corticosteroids, but if they cannot be tapered after 3–6 months, splenectomy should be considered. In pregnant patients, severe thrombocytopenia may occur in the fetus. Blood Cell Differentiation Figure 2.7-4 illustrates the various blood cell categories and lineages. KEY FACT Anti-D (Rh) immunoglobulin and rituximab are second-line therapies for ITP. Pluripotent hematopoietic stem cell Proerythroblast Lymphoblast Myeloblast Monoblast Megakaryoblast Neutrophil Eosinophil Basophil KEY FACT Anti-D (Rh) immunoglobulin and IVIG act as “decoys” so that WBCs will recognize them instead of IgG on platelets. Reticulocyte B cell T cell Promyelocyte Erythrocyte Plasma cell Active T cell Myelocyte Metamyelocyte Band Neutrophil Eosinophil Basophil FIGURE 2.7-4. Blood cell differentiation. Megakaryocyte Monocyte Platelets HEMATOLOGY/ONCOLOGY HIGH-YIELD FACTS IN 159 Red Blood Cell (RBC) Disorders ANE M IA S Anemia is a disorder of low hematocrit and hemoglobin. There are several subtypes, which are classified according to RBC morphology and reticulocyte count (see Figure 2.7-5). Once anemia has been diagnosed by a low hemoglobin/hematocrit, the approach starts with the mean corpuscular volume (MCV): n n n < 80 fL: Microcytic anemia. 80–100 fL: Normocytic anemia. > 100 fL: Macrocytic anemia. KEY FACT Iron Deficiency Anemia (a Microcytic Anemia) A condition in which iron loss exceeds intake. May occur when dietary intake is insufficient for the patient’s needs (eg, when needs are ↑ by growth or pregnancy) or in the setting of chronic blood loss, usually 2° to menstruation or GI bleeding. Toddlers, adolescent girls, and women of childbearing age are most commonly affected. Anemia #"# RETICULOCYTe COUNT 2ETIC  5 2ETIC  5 2ED CELl MORPHOLOGY (EMOLYSIs/ hemorrhage Blood loss .ORMOCYTIC NORMOCHROMIC -ICRO OR MACROCYTIC (YPOPROLIFERATIVE -ATURATION DISORDEr )NTRAVASCULAR HEMOLYSIs -ETABOLIC DEFECt Marrow damage s )nfiltration /fibrosis s Aplasia )RON DEFICIENCY 3TIMULATION s )nflammation s -ETABOLIC DEFECT s 2enal disease FIGURE 2.7-5. #YTOPLASMIC DEFECTS s )RON DEFICIENCY s 4halassemla s 3IDEROBLASTIC anemia .UCLEAR DEFECTS s &OLATE DEFICIENCY s 6itamin B DEFICIENCY s $RUG TOXICITY s 2EFRACTORY ANEMIa Anemia algorithm. Membrane abnormaliTY HemoglobinopathY !UTOIMMUNE DEFECt &RAGMENTATIOn HEMOLYSIs Iron deficiency anemia in an elderly patient may be due to colorectal cancer and must therefore be evaluated to rule out malignancy. 160 HIGH-YIELD FACTS IN MNEMONIC Causes of microcytic anemia— TICS Thalassemia Iron deficiency Chronic disease Sideroblastic anemia HEMATOLOGY/ONCOLOGY HISTORY/PE n n Symptoms include fatigue, weakness, brittle nails, and pica. If the anemia develops slowly, patients are generally asymptomatic. Physical findings include glossitis, angular cheilitis, and koilonychia (“spoon nails”). DIAGNOSIS n n n n n Bone marrow biopsy looking for evidence of iron stores is the gold standard but is seldom performed. Iron deficiency is often confused with anemia of chronic disease, in which iron use by the body is impaired. Labs can help differentiate these conditions (see Table 2.7-4). Peripheral blood smear shows hypochromic and microcytic RBCs (see Figure 2.7-6) with a low reticulocyte count. Low serum ferritin reflects low body stores of iron and confirms the diagnosis. However, ferritin is also an acute-phase reactant and may thus obscure evidence of iron deficiency. Red cell distribution width (RDW) elevation is a highly specific test for iron deficiency anemia. TREATMENT n FIGURE 2.7-6. Iron deficiency ane- mia. Note the microcytic, hypochromic RBCs (“doughnut cells”) with enlarged areas of central pallor. (Courtesy of Peter n McPhedran, MD, Yale Department of Hematology.) KEY FACT Most macrocytic anemias are caused by processes that interfere with normal DNA synthesis and replication. Treat with replacement iron for 4–6 months. Oral iron sulfate may lead to nausea, constipation, diarrhea, and abdominal pain. Antacids may interfere with iron absorption. If necessary, IV iron dextran can be administered but is associated with a 10% risk of serious side effects, including anaphylaxis. Other parenteral preparations are available with less allergic risk, such as iron sucrose. Megaloblastic Anemia (a Macrocytic Anemia) Vitamin B12 (cobalamin) and folate deficiency interfere with DNA synthesis, leading to a delay in blood cell maturation. Cobalamin deficiency is due to intestinal malabsorption, traditionally from pernicious anemia (destruction of parietal cells, which produce the intrinsic factor needed for cobalamin absorption), although this is a rare disorder. Folate deficiency results from insufficient dietary folate, malabsorption, alcoholism, or use of certain drugs. Drugs that interfere with DNA synthesis, including many chemotherapeutic agents, may lead to megaloblastic anemia. HISTORY/PE n n Presents with fatigue, pallor, diarrhea, loss of appetite, and headaches. Cobalamin deficiency affects the nervous system, so patients lacking that vitamin may develop a demyelinating disorder and may present with TA B L E 2 . 7- 4 . Iron Deficiency Anemia vs. Anemia of Chronic Disease IRON DEFICIENCY CHRONIC DISEASE BOTH Serum iron ↓ ↓ ↓ TIBC or transferrin ↑ ↓ Normal/↑ Ferritin ↓ ↑ Normal/↓ Serum transferrin receptor ↑ Normal Normal/↑ HEMATOLOGY/ONCOLOGY HIGH-YIELD FACTS IN symptoms of motor, sensory, autonomic, and/or neuropsychiatric dysfunction, known as subacute combined degeneration of the cord. DIAGNOSIS n n n n Peripheral smear shows RBCs with an elevated MCV. Hypersegmented (> 5) granulocytes can also be seen (see Figure 2.7-7). Bone marrow sample reveals giant neutrophils and hypersegmented mature granulocytes. The Schilling test (ingestion of radiolabeled cobalamin both with and without added intrinsic factor) is classic for measuring the absorption of cobalamin. Although this test is rarely performed, its interpretation is frequently tested. The patient is first given unlabeled B12 IM to saturate B12 receptors in the liver, followed by an oral challenge of radiolabeled B12. The radiolabeled B12 will pass into the urine if it is properly absorbed, as the liver’s B12 receptors will be saturated from the IM dose. n Radiolabeled B12 in urine: Dietary B12 deficiency. n No radiolabeled B12 in urine: Consider pernicious anemia, bacterial overgrowth, or pancreatic enzyme deficiency; test the hypothesis with the addition of intrinsic factor, antibiotics, or pancreatic enzymes to radiolabeled B12. Serum vitamin levels are poorly diagnostic of deficiencies and are thus used with adjunctive tests, including red cell folate levels and methylmalonic acid (MMA) and homocysteine levels: n B12 deficiency: Elevated MMA and homocysteine. n Folate deficiency: Normal MMA; elevated homocysteine. 161 KEY FACT B12 deficiency can be due to infection by a tapeworm, Diphyllobothrium latum. FIGURE 2.7-7. Hypersegmentation. The nucleus of this hypersegmented neutrophil has 6 lobes (6 or more nuclear lobes are required). This is a characteristic finding of megaloblastic anemia. (Courtesy of Peter McPhedran, MD, Yale Department of Hematology.) TREATMENT Address the cause of the anemia, and correct the underlying cause. Hemolytic Anemia (a Normocytic Anemia) Occurs when bone marrow production is unable to compensate for ↑ destruction of circulating blood cells. Etiologies include the following: n n n n n n n n G6PD deficiency: An X-linked recessive disease that ↑ RBC sensitivity to oxidative stress. Paroxysmal nocturnal hemoglobinuria: A disorder in which blood cell sensitivity to complement activation is ↑. Patients are prone to thrombotic events. Hereditary spherocytosis: An abnormality of the RBC membrane. Diagnose with a peripheral smear (see Figure 2.7-8) and an osmotic fragility test. Autoimmune RBC destruction: Occurs 2° to EBV infection, mycoplasmal infection, CLL, rheumatoid disease, or medications. Sickle cell disease: A recessive β-globin mutation (see the following section). Microangiopathic hemolytic anemia: TTP, HUS, DIC. Mechanical hemolysis: Associated with mechanical heart valves. Other: Malaria, hypersplenism. HISTORY/PE n n Presents with pallor, fatigue, tachycardia, and tachypnea. Patients are typically jaundiced, with low haptoglobin and elevated indirect bilirubin and LDH. Urine is dark with hemoglobinuria, and there is ↑ excretion of urinary and fecal urobilinogen. Reticulocyte count is elevated. S S S Spherocytes. These RBCs (S) lack areas of central pallor. Spherocytes are seen in autoimmune hemolysis and in hereditary spherocytosis. FIGURE 2.7-8. (Courtesy of Peter McPhedran, MD, Yale Department of Hematology.) KEY FACT The classic case of G6PD deficiency is an African American male soldier in Vietnam who took quinine. 162 HIGH-YIELD FACTS IN KEY FACT Causes of oxidative stress in G6PD deficiency include infection, metabolic acidosis, fava beans, antimalarials, dapsone, sulfonamides, and nitrofurantoin. KEY FACT Patients with Fanconi’s anemia may be identified on physical examination by café au lait spots, short stature, and radial/thumb hypoplasia/aplasia. KEY FACT The indirect Coombs’ test detects antibodies to RBCs in the patient’s serum. The direct Coombs’ test detects sensitized erythrocytes. HEMATOLOGY/ONCOLOGY DIAGNOSIS Diagnosed by the history and clinical presentation. High LDH, elevated indirect bilirubin, and ↓ haptoglobin levels are consistent with a diagnosis of hemolytic anemia. Also obtain a reticulocyte count. A Coombs’ test (see Figure 2.7-9) is used to detect autoimmune hemolysis. TREATMENT Treatment varies with the cause of hemolysis but typically includes corticosteroids to address immunologic causes and iron supplementation to replace urinary losses. Splenectomy may be helpful, and transfusion may be necessary to treat severe anemia. Aplastic Anemia A rare condition caused by failure of blood cell production due to destruction of bone marrow cells. It may be hereditary, as in Fanconi’s anemia; may have an autoimmune or a viral etiology (eg, HIV, parvovirus B19); or may result from exposure to toxins (eg, drugs, cleaning solvents) or radiation. HISTORY/PE Patients are typically pancytopenic, with symptoms resulting from a lack of RBCs, WBCs, and platelets—eg, pallor, weakness, a tendency to infection, petechiae, bruising, and bleeding. DIAGNOSIS Diagnosed by clinical presentation and CBC; verified by a bone marrow biopsy revealing hypocellularity and space occupied by fat. Antihuman antibodies (Coombs’ reagent) are added. Patient’s RBCs are washed to remove anyy unbound b d antib antibodies. antiib bod die ies es. A Donor RBCs are added to patient’s antibodies. Patient’s serum containing antibodies is obtained. Positive test result when RBCs agglutinate, demonstrating the presence of bound antibodies to RBC antigens. Antihuman antibodies (Coombs’ reagent) are added. Donor’s RBCs are bound by patient’s antibodies if RBC antigens are present. B FIGURE 2.7-9. Direct (A) and indirect (B) Coombs’ tests. Positive test result when RBCs agglutinate, demonstrating the presence of bound antibodies to RBC antigens. HEMATOLOGY/ONCOLOGY HIGH-YIELD FACTS IN 163 TREATMENT Blood transfusion and stem cell transplantation to replace absent cells; immunosuppression with cyclosporin A and antithymocyte globulin to prevent autoimmune destruction of marrow. Infections are a major cause of mortality and should be treated aggressively. Sickle Cell Disease (SCD) An autosomal recessive disorder most commonly caused by a mutation of adult hemoglobin (the β chain has glu replaced by val). Signs and symptoms are due to ↓ RBC survival and a tendency of sickled cells to lead to vaso-occlusion. KEY FACT SCD represents a qualitative defect in the β-globin chain. HISTORY/PE n n n Asymptomatic during the first 1–2 years of life; may first present with dactylitis in childhood. Later, hemolysis results in anemia, jaundice, cholelithiasis, ↑ cardiac output (murmur and cardiomegaly), and delayed growth. Vaso-occlusion leads to ischemic organ damage, especially splenic infarction, which predisposes to pneumococcal sepsis and acute chest syndrome (pneumonia and/or pulmonary infarction; see Figure 2.7-10). Patients also experience painful crises of unknown etiology. Common triggers for a vaso-occlusive crisis (VOC) include cold temperatures, dehydration, and infection. Other potential complications include splenic sequestration, which occurs in patients who have not infarcted their spleens, and aplastic crisis, which is usually 2° to infection with parvovirus B19. These complications both present with ↓ hematocrit but are distinguished clinically by ↓ platelets in aplastic crisis (2° to bone marrow involvement) and normal to ↑ platelets in splenic sequestration. DIAGNOSIS The sickle cell screen is based on a blood smear with sickle cells and target cells (see Figure 2.7-11). The gold standard is quantitative hemoglobin electrophoresis. Acute chest syndrome. Frontal CXR of a 19-year-old female with sickle cell disease and acute chest pain. Note the bilateral lower and midlung opacities and mild cardiomegaly. (Reproduced with permission from USMLERx.com.) FIGURE 2.7-10. KEY FACT The most common cause of osteomyelitis in SCD patients is S aureus. However, SCD patients are especially prone to Salmonella infections causing osteomyelitis. They are also at ↑ risk for AVN of the hip. 164 HIGH-YIELD FACTS IN HEMATOLOGY/ONCOLOGY TREATMENT n n S FIGURE 2.7-11. Sickle cell dis- ease. Sickle-shaped RBCs (S) are almost always seen on blood smear, regardless of whether the patient is having a sickle cell crisis. Anisocytosis, poikilocytosis, target cells, and nucleated RBCs can also be seen. (Courtesy of Peter McPhedran, MD, Yale Depart- n n n ment of Hematology.) Treat with hydroxyurea, which stimulates the production of fetal hemoglobin (hydroxyurea is teratogenic, so it is contraindicated in pregnancy). If hydroxyurea does not prove effective, chronic transfusion therapy, which carries the risk of iron overload, can be tried. Health maintenance includes treating cholelithiasis with cholecystectomy, chronic folate supplementation, pneumococcal vaccination, and, when the patient is < 5 years of age, penicillin BID. VOCs must be treated with adequate pain management, O2 therapy, IV fluid rehydration, and antibiotics (if infection is suspected to be the trigger). To prevent VOCs from progressing to acute chest syndrome, initiate aggressive hydration and incentive spirometry, and keep the sickle variant < 40%. This can be done with simple transfusions or, if necessary, exchange transfusion in an ICU setting. T HALAS S E M I AS Hereditary disorders involving ↓ or absent production of normal globin chains of hemoglobin. α-thalassemia is caused by a mutation of 1 or more of the 4 genes for α-hemoglobin; β-thalassemia results from a mutation of 1 or both of the 2 genes for β-hemoglobin. HISTORY/PE Thalassemia is most common among people of African, Middle Eastern, and Asian descent. Disease presentation and prognosis vary with the number of genes missing (see Table 2.7-5). DIAGNOSIS Diagnosed by hemoglobin electrophoresis evaluation (but note that this is normal in α-thalassemia) and DNA studies. TA B L E 2 . 7- 5 . Differential Diagnosis of Thalassemias SUBTYPE β-thalassemia major NUMBER OF GENES PRESENT 0/2 β CLINICAL FEATURES Patients develop severe microcytic anemia in the first year of life and need chronic transfusions or marrow transplant to survive. β-thalassemia minor 1/2 β Patients are asymptomatic, but their cells are microcytic and hypochromic on peripheral smear. Hydrops fetalis 0/4 α Patients die in utero. Hemoglobin H disease 1/4 α Patients have severe hypochromic, microcytic anemia with chronic hemolysis, splenomegaly, jaundice, and cholelithiasis. The reticulocyte count elevates to compensate, and one-third of patients have skeletal changes due to expanded erythropoiesis. α-thalassemia trait 2/4 α Patients have low MCV but are usually asymptomatic. Silent carrier 3/4 α Patients have no signs or symptoms of disease. HEMATOLOGY/ONCOLOGY HIGH-YIELD FACTS IN 165 TREATMENT Most patients do not require treatment, but those with β-thalassemia major and hemoglobin H disease are commonly transfusion dependent and should be given iron chelators (deferoxamine) to prevent overload. PO L Y C Y T HE M I A S Erythrocytosis (an abnormal elevation of hematocrit) may be either 1° (due to ↑ RBC production) or 2° (due to ↓ plasma volume and hemoconcentration). HISTORY/PE n n n n Characterized by ↑ hematocrit, ↓ tissue blood flow and oxygenation, and ↑ cardiac work. Patients present with “hyperviscosity syndrome,” which consists of easy bleeding/bruising, blurred vision, neurologic abnormalities, plethora, pruritus (especially after a warm bath), hepatomegaly, splenomegaly, and CHF. 1° erythrocytosis is associated with hypoxia (from lung disease, smoking, high altitudes, or a poor intrauterine environment), neoplasia (erythropoietin-producing tumors), or polycythemia vera (PCV). n PCV results from clonal proliferation of a pluripotent marrow stem cell due to a JAK2 mutation. Although all marrow cell lines ↑, RBCs are most significantly affected. n This blood disorder primarily affects the elderly. 2° erythrocytosis is associated with excessive diuresis, severe gastroenteritis, and burns. KEY FACT Premedication with acetaminophen and diphenhydramine is sometimes used to prevent transfusion reactions. DIAGNOSIS n n Erythrocytosis is diagnosed clinically and by cell counts, with ABGs used to assess hypoxia or imaging to demonstrate neoplasia. Patients with PCV have excess RBCs, WBCs, and platelets. Levels of erythropoietin may be useful in distinguishing PCV, in which levels are low, from other causes of polycythemia. JAK2 mutation tests often confirm the diagnosis. KEY FACT Hemoglobinuria in hemolytic transfusion reaction may lead to acute tubular necrosis and subsequent renal failure. TREATMENT n n Phlebotomy relieves symptoms of erythrocytosis, but treatment should also address the underlying cause. PCV can be treated with cytoreductive drugs such as hydroxyurea or interferon. Because PCV is prothrombotic, ASA should also be used. With treatment, survival is 7–10 years. KEY FACT Heme is necessary for the production of hemoglobin, myoglobin, and cytochrome molecules. T R A N S F U S I O N R E A CT I O N S Blood transfusion is generally safe but may result in a variety of adverse reactions (see Table 2.7-6). Nonhemolytic febrile reactions and minor allergic reactions are the most common, each occurring in 3–4% of all transfusions. PO R P HY R IA The porphyrias are a group of inherited disorders that include acute intermittent porphyria, porphyria cutanea tarda, and erythropoietic porphyria. Some porphyrias are autosomal dominant (eg, acute intermittent porphyria) and A 15-year-old female sees her pediatrician after being diagnosed with mononucleosis. Her WBC count returns at 56,000/mm3. The physician orders a leukocyte alkaline phosphatase (LAP) to distinguish between a leukemoid reaction and a hematologic malignancy. What is the expected result in a leukemoid reaction? 166 HIGH-YIELD FACTS IN TA B L E 2 . 7- 6 . VARIABLE Mechanism HEMATOLOGY/ONCOLOGY Transfusion Reactions NONHEMOLYTIC FEBRILE REACTION MINOR ALLERGIC REACTION HEMOLYTIC TRANSFUSION REACTION Cytokine formation during storage of Antibody formation against donor Antibody formation against donor blood. proteins, usually after receiving erythrocytes, resulting either from plasma-containing product. ABO incompatibility or from minor antigen mismatch. Presentation Fever, chills, rigors, and malaise 1–6 Prominent urticaria. hours after transfusion. Fevers, chills, nausea, flushing, burning at the IV site, tachycardia, hypotension during or shortly after the transfusion. Treatment Stop the transfusion and give Give antihistamines. If the reaction is Stop the transfusion immediately! acetaminophen. severe, it may be necessary to stop Give vigorous IV fluids and maintain the transfusion and give epinephrine. good urine output. KEY FACT The telltale sign of porphyria is pink urine. The classic case involves a college student who consumes alcohol and barbiturates at a party and then has an acute episode of abdominal pain and brown urine the next day. others autosomal recessive (eg, erythropoietic porphyria). All involve abnormalities of heme production that lead to an accumulation of porphyrins. HISTORY/PE n n n Signs and symptoms vary with the type of porphyria. In general, however, porphyrias are characterized by a combination of photodermatitis, neuropsychiatric complaints, and visceral complaints that typically take the form of colicky abdominal pain and seizures. Physical examination reveals tachycardia, skin erythema and blisters, areflexia, and a nonspecific abdominal examination. Patients with the erythropoietic form present with hemolytic anemia. Acute attacks are associated with stimulants of ↑ heme synthesis such as fasting or chemical exposures; well-known triggers are alcohol, barbiturates, and OCPs. Urine may appear red, pink, or brown after an acute attack. Patients may have a ! family history. DIAGNOSIS Diagnosed by a combination of the history and physical along with labs showing elevated blood, urine, and stool porphyrins. Enzyme assays may also be helpful. TREATMENT n n LAP would be elevated. Hematologic malignancies, in contrast, have low LAP values. Avoidance of triggers and symptomatic treatment during acute attacks. High doses of glucose may be administered to ↓ heme synthesis during attacks (provides " feedback to the heme synthetic pathway). White Blood Cell (WBC) Disorders LE U K E M I AS Malignant proliferations of hematopoietic cells, categorized by the type of cell involved and their level of differentiation. HEMATOLOGY/ONCOLOGY HIGH-YIELD FACTS IN 167 Acute Leukemias Acute myelogenous and lymphocytic leukemias are clonal disorders of early hematopoietic stem cells. They are characterized by rapid growth of immature blood cells (blasts) that overwhelms the ability of bone marrow to produce normal cells. HISTORY/PE n n n Acute myelogenous leukemia (AML) and acute lymphocytic leukemia (ALL) affect children as well as adults. ALL is the most common childhood malignancy. Disease onset and progression are rapid; patients present with signs and symptoms of anemia (pallor, fatigue) and thrombocytopenia (petechiae, purpura, bleeding). Medullary expansion and periosteal involvement may lead to bone pain (common in ALL). On examination, patients may have hepatosplenomegaly and swollen/ bleeding gums from leukemic infiltration and ↓ platelets. Leukemic cells also infiltrate the skin and CNS. A 41-year-old male is diagnosed with acute myelogenous leukemia (AML). Fluorescence in situ hybridization (FISH) analysis reveals that he has acute promyelocytic leukemia (APL), FAB subtype M3. What is the preferred therapy for this subtype of AML? KEY FACT A characteristic sign for AML type M3 (APL) is the Auer rod (see Figure 2.713), although Auer rods can be seen in other AML subtypes as well. DIAGNOSIS n n n Based on examination of the patient’s bone marrow, obtained by biopsy and aspiration, or peripheral blood if circulating blasts are present. Marrow that is infiltrated with blast cells (> 20–30%) is consistent with a leukemic process. In AML, the leukemic cells are myeloblasts; in ALL they are lymphoblasts. These cells may be distinguished by examination of morphology (see Figure 2.7-12), cytogenetics, cytochemistry, and immunophenotyping (see Table 2.7-7). The WBC count is usually elevated, but the cells are dysfunctional, and patients may be neutropenic with a history of frequent infection. If the WBC count is very high (> 100,000/mm3), there is a risk of leukostasis (blasts occluding the microcirculation, leading to pulmonary edema, CNS symptoms, ischemic injury, and DIC). The type of acute leukemia is further classified according to the FAB system (ALL: L1–L3; AML: M0–M7) and karyotype analysis. Prognosis varies with leukemic cytogenetics. A FIGURE 2.7-13. Auer rod in AML. The red rod-shaped structure (arrow) in the cytoplasm of the myeloblast is pathognomonic. (Courtesy of Peter McPhedran, MD, Yale Department of Hematology.) B AML vs. ALL on peripheral smear. (A) AML. Large, uniform myeloblasts with round or kidney-shaped nuclei and prominent nucleoli are characteristic. (B) ALL. Peripheral blood smear reveals numerous large, uniform lymphoblasts, which are large cells with a high nuclear-to-cytoplasmic ratio. Some lymphoblasts have visible clefts in their nuclei. (Courtesy of Peter McPhedran, MD, Yale Department of Hema- FIGURE 2.7-12. tology.) 168 HIGH-YIELD FACTS IN HEMATOLOGY/ONCOLOGY T A B L E 2 . 7 - 7. Myeloblasts vs. Lymphoblasts VARIABLE APL has a good prognosis because it is responsive to all-trans-retinoic acid (ATRA) therapy. This AML subtype is also associated with an ↑ incidence of DIC and a chromosomal translocation involving chromosomes 15 and 17. MYELOBLAST LYMPHOBLAST Size Larger (2–4 times RBC) Smaller (1.5–3.0 times RBC) Amount of cytoplasm More Less Nucleoli Conspicuous Inconspicuous Granules Common, fine Uncommon, coarse Auer rods Present in 50% of cases (see Absent Figure 2.7-13) Myeloperoxidase ! " TREATMENT n n KEY FACT n n Eighty-five percent of children with ALL achieve complete remission with chemotherapy. ALL and AML are treated primarily with chemotherapeutic agents, although transfusions, antibiotics, and colony-stimulating factors are also used. Patients with unfavorable genetics or those who do not achieve remission may be candidates for bone marrow transplantation. Prior to therapy, patients should be well hydrated; if their WBC counts are high, they may be started on allopurinol to prevent hyperuricemia and renal insufficiency resulting from blast lysis (tumor lysis syndrome). Leukostasis syndrome may be treated with hydroxyurea +/− leukapheresis to rapidly ↓ WBC count. Indicators of a poor prognosis are as follows: n ALL: Age < 1 year or > 10 years; an ↑ in WBC count to > 50,000/mm3; the presence of the Philadelphia chromosome t(9,22) (associated with B-cell cancer); CNS involvement at diagnosis. n AML: Age > 60 years; elevated LDH; poor-risk or complex karyotype. Chronic Lymphocytic Leukemia (CLL) A malignant, clonal proliferation of functionally incompetent lymphocytes that accumulate in the bone marrow, peripheral blood, lymph nodes, spleen, and liver. The most common type of leukemia. Almost all cases involve welldifferentiated B lymphocytes. Primarily affects older adults (median age 65); the male-to-female ratio is 2:1. HISTORY/PE Often asymptomatic, but many patients present with fatigue, malaise, and infection. Common physical findings are lymphadenopathy and splenomegaly. DIAGNOSIS n KEY FACT n Look for smudge cells to point you toward CLL. Smudge cells result from the coverslip crushing the fragile leukemia cells. Diagnosed by the clinical picture; may be confirmed by flow cytometry demonstrating the presence of CD5—normally found only on T cells—on leukemic cells with the characteristic B-cell antigens CD20 and CD21. CBC shows lymphocytosis (lymphocyte count > 5000/mm3) with an abundance of small, normal-appearing lymphocytes and ruptured smudge cells on peripheral smear (see Figure 2.7-14). Granulocytopenia, anemia, and thrombocytopenia are common owing to marrow infiltration with leukemic cells. Abnormal function by the leukemic cells leads to hypogammaglobulinemia. HEMATOLOGY/ONCOLOGY n HIGH-YIELD FACTS IN 169 Bone marrow biopsy is rarely required for diagnosis or staging but may provide prognostic information and may help assess response to therapy. S TREATMENT n n n n The clinical stage correlates with expected survival. Treatment is palliative. The degree of peripheral lymphocytosis does not correlate with prognosis, nor does it dictate when treatment should be initiated. Treatment is often withheld until patients are symptomatic—eg, when they present with recurrent infection, severe lymphadenopathy or splenomegaly, anemia, and thrombocytopenia. Treatment consists primarily of chemotherapy, although radiation may be useful for localized lymphadenopathy. Although CLL is not curable, long disease-free intervals may be achieved with adequate treatment of symptoms. Chronic Myelogenous Leukemia (CML) Involves clonal expansion of myeloid progenitor cells, leading to leukocytosis with excess granulocytes and basophils and sometimes ↑ erythrocytes and platelets as well. To truly be CML, the BCR-ABL translocation must be present. In > 90% of patients, this is reflected by the Philadelphia chromosome t(9,22). CML primarily affects middle-aged patients. S FIGURE 2.7-14. CLL with characteristic smudge cells. The numerous small, mature lymphocytes and smudge cells (S; fragile malignant lymphocytes are disrupted during blood smear preparation) are characteristic. (Courtesy of Peter McPhedran, Yale Department of Hematology.) HISTORY/PE n n n With routine blood testing, many patients are diagnosed while asymptomatic. However, typical signs and symptoms are those of anemia. Patients frequently have splenomegaly with LUQ pain and early satiety. Hepatomegaly may be present as well. The constitutional symptoms of weight loss, anorexia, fever, and chills may also be seen. Patients with CML go through 3 disease phases: n Chronic: Without treatment, typically lasts 3.5–5.0 years. Signs and symptoms are as described above. Infection and bleeding complications are rare. n Accelerated: A transition toward blast crisis, with an ↑ in peripheral and bone marrow blood counts. Should be suspected when the differential shows an abrupt ↑ in basophils and thrombocytopenia (platelet count < 100,000/mm3). n Blast crisis: Resembles acute leukemia; survival is 3–6 months. DIAGNOSIS n n n Diagnosed by the clinical picture, including labs; cytogenetic analysis usually reveals the Philadelphia chromosome. CBC shows a very high WBC count—often > 100,000/mm3 at diagnosis, and sometimes reaching > 500,000/mm3. The differential shows granulocytes in all stages of maturation. Rarely, the WBC count will be so elevated as to cause a hyperviscosity syndrome. LAP is low; LDH, uric acid, and B12 levels are elevated. TREATMENT Varies with disease phase and is undergoing rapid change, particularly since the introduction of targeted therapies. n Chronic: Treated with imatinib. Younger patients can be treated with allogeneic stem cell transplantation if a suitable matched sibling donor is available. KEY FACT Likely diagnosis based on age at presentation: n ALL: < 13 years (but can present in any age group) n AML: 13–40 years (but can present in any age group) n CML: 40–60 years n CLL: > 60 years A 71-year-old male seeks care for marked lethargy and constipation that are worsening. He also notes a dull back pain that is present at most times, even at night. His lab studies have been normal with the exception of an ↑ creatinine level. What is most likely responsible for the patient’s worsening renal function? 170 HIGH-YIELD FACTS IN KEY FACT Imatinib (Gleevec) is a selective inhibitor of the BCR-ABL tyrosine kinase, the product of the t(9,22) translocation, or Philadelphia chromosome. HEMATOLOGY/ONCOLOGY n Blast: Treatment is the same as that for acute leukemia, or it may involve dasatinib plus hematopoietic stem cell transplantation or a clinical trial. Hairy Cell Leukemia (HCL) A malignant disorder of well-differentiated B lymphocytes with an unclear cause. HCL is a rare disease that accounts for 2% of adult leukemia cases and most commonly affects older males. HISTORY/PE n n Typically presents with pancytopenia, bone marrow infiltration, and splenomegaly. Patients complain of weakness, fatigue, petechiae and bruising, infection (especially with atypical mycobacteria such as Mycobacterium avium– intracellulare), abdominal pain, early satiety, and weight loss. Symptoms are similar to those of CLL except that patients rarely have lymphadenopathy. DIAGNOSIS n n FIGURE 2.7-15. Hairy cell leukemia. Note the hairlike cytoplasmic n projections from neoplastic lymphocytes. Villous lymphoma can also have this appearance. (Courtesy of Peter McPhedran, MD, Yale Department of Hematology.) Diagnosed by the history, physical examination, and labs; confirmed through the identification of hairy cells in the blood, marrow, or spleen (see Figure 2.7-15). Tartrate-resistant acid phosphatase (TRAP) staining of hairy cells, electron microscopy, and flow cytometry are helpful in distinguishing the pathognomonic hairy cells. CBC usually demonstrates leukopenia (making the name leukemia a misnomer); roughly 85% of the time a peripheral smear shows hairy cells, or mononuclear cells with abundant pale cytoplasm and cytoplasmic projections. TREATMENT n n Ten percent of patients have a benign course and never require therapy, but the remainder develop progressive pancytopenia and splenomegaly, requiring therapy. Nucleoside analogs (the first-line therapy is cladribine) are currently the initial treatment of choice and effectively induce remission. Other treatment options include splenectomy and IFN-α. The median survival without treatment is 5 years. LYM P HOM AS Malignant transformations of lymphoid cells residing primarily in lymphoid tissues, especially the lymph nodes. Classically organized into Hodgkin’s and non-Hodgkin’s varieties. Non-Hodgkin’s Lymphoma (NHL) Patients with multiple myeloma frequently have renal dysfunction 2° to urinary immunoglobulins, also known as Bence Jones protein, that have the ability to form casts, leading to cast nephropathy. NHL represents a diverse group of diseases characterized by a progressive clonal expansion of B cells, T cells, and/or natural killer (NK) cells stimulated by chromosomal translocations, most commonly t(14,18); by the inactivation of tumor suppressor genes; or by the introduction of exogenous genes by oncogenic viruses (eg, EBV, HTLV-1, HCV). There is a strong association between H pylori infection and MALT gastric lymphoma. Most NHLs (almost 85%) are of B-cell origin. NHL is the most common hematopoietic neoplasm and is 5 times more common than Hodgkin’s lymphoma. HEMATOLOGY/ONCOLOGY HIGH-YIELD FACTS IN 171 HISTORY/PE The median patient age is > 50 years, but NHL may also be found in children, who tend to have more aggressive, higher-grade disease. Patient presentation varies with disease grade (see Table 2.7-8). DIAGNOSIS n n Excisional lymph node biopsy is necessary for diagnosis; the disease may first present at an extranodal site, which should be biopsied for diagnosis as well. A CSF examination should be done in patients with HIV, neurologic signs or symptoms, or 1° CNS lymphoma. Disease staging (Ann Arbor classification) is based on the number of nodes and on whether the disease involves sites on both sides of the diaphragm. TREATMENT n n Treatment is based on histopathologic classification rather than on stage. Symptomatic patients are treated with radiation and chemotherapy. The rule of thumb is for low-grade, indolent NHL to be treated with palliative intent in symptomatic patients and for high-grade, aggressive NHL to be treated aggressively with a curative approach. Hodgkin’s Disease (HD) A predominantly B-cell malignancy with an unclear etiology. There is a possible association with EBV. HD has a bimodal age distribution, peaking first in the third decade (primarily the nodular sclerosing type) and then in the elderly at around age 60 (mainly the lymphocyte-depleted type). It has a male predominance in childhood. HISTORY/PE n HD commonly presents above the diaphragm (classically as cervical adenopathy; see Figure 2.7-16), with infradiaphragmatic involvement suggesting more widely disseminated disease. TA B L E 2 . 7- 8 . Presentation of Non-Hodgkin’s Lymphoma GRADE Low HISTORY PHYSICAL Painless peripheral adenopathy. Peripheral adenopathy, Cytopenia from bone marrow splenomegaly, hepatomegaly. involvement; fatigue and weakness. Intermediate Adenopathy. to high Extranodal disease (GI, GU, skin, thyroid, CNS). B symptoms (temperature > 38.5°C [101.3°F], night sweats, weight loss). Mass formation (eg, abdominal mass with bowel obstruction in Burkitt’s lymphoma; mediastinal mass and SVC syndrome in lymphoblastic lymphoma). Bulky adenopathy, splenomegaly, hepatomegaly. Masses (abdominal, testicular, mediastinal). Skin findings. KEY FACT The treatment of high-grade NHL may be complicated by tumor lysis syndrome, in which rapid cell death releases intracellular contents and leads to hyperkalemia, hyperphosphatemia, hyperuricemia, and hypocalcemia. 172 HIGH-YIELD FACTS IN HEMATOLOGY/ONCOLOGY A B Hodgkin’s lymphoma. (A) CXR of a 27-year-old male presenting with several weeks of fevers and night sweats shows bulky bilateral hilar (arrows) and right paratracheal (arrowhead) lymphadenopathy. (B) Lymph node sampling shows a mixed inflammatory infiltrate and a classic binucleate Reed-Sternberg cell (circle) consistent with Hodgkin’s lymphoma. (Reproduced with permission from USMLERx.com.) FIGURE 2.7-16. n Patients also have systemic B symptoms (see Table 2.7-8), pruritus, and hepatosplenomegaly. Pel-Ebstein fevers (1–2 weeks of high fever alternating with 1–2 afebrile weeks) and alcohol-induced pain at nodal sites are rare signs that are specific for HD. DIAGNOSIS n n KEY FACT Chemotherapy and radiation can lead to 2° neoplasms such as AML, NHL, breast cancer, and thyroid cancer. Preventive measures such as mammography are warranted. Fine-needle biopsy is usually nondiagnostic, so diagnosis is typically made by excisional lymph node biopsy, which is examined for the classic ReedSternberg cells (giant abnormal B cells with bilobar nuclei and huge, eosinophilic nucleoli, which create an “owl’s-eye” appearance; see Figure 2.7-16) and for abnormal nodal morphology. Staging is based on the number of nodes, the presence of B symptoms, and whether the disease involves sites on both sides of the diaphragm; staging laparotomy is not recommended. TREATMENT n n Treatment is stage dependent, involving chemotherapy and/or radiation. Five-year survival rates are very good and are 90% for stage I and II disease (nodal disease limited to 1 side of the diaphragm), 84% for stage III, and 65% for stage IV. Lymphocyte-predominant HD has the best prognosis. Plasma Cell Disorders MU LTI P LE MYE LOM A KEY FACT The triad of anemia, renal failure, and bone pain must always raise suspicion for multiple myeloma. Clonal proliferation of malignant plasma cells at varying stages of differentiation, with excessive production of monoclonal immunoglobulins (typically IgA or IgG) or immunoglobulin fragments (kappa/lambda light chains). It is commonly believed to be a disease of the elderly, with a peak incidence in the seventh decade. Risk factors for disease development include radiation; monoclonal gammopathy of undetermined significance (MGUS); and, possibly, petroleum, pesticides, and other chemicals. HEMATOLOGY/ONCOLOGY HISTORY/PE Patients present with anemia, plasmacytosis of the bone marrow, lytic bone lesions, hypercalcemia, and renal abnormalities. They are prone to infection and have elevated monoclonal (M) proteins in the serum and/or urine. HIGH-YIELD FACTS IN 173 KEY FACT Bone pain at rest should raise concern for malignancy. DIAGNOSIS The classic triad of diagnostic criteria are > 10% plasma cells in the bone marrow and/or histologically proven plasma cell infiltration, M protein in serum or urine, and evidence of lytic bone lesions. The presence of M proteins alone is insufficient for the diagnosis of multiple myeloma; MGUS is relatively common. Other lymphoproliferative diseases may also result in M proteins, including CLL, lymphoma, Waldenström’s macroglobulinemia, and amyloidosis. Patients should be evaluated with a skeletal survey (see Figure 2.7-17), a bone marrow biopsy, serum and urine protein electrophoresis, and CBC. n n n TREATMENT Treat with chemotherapy. Common initial treatment involves a combination of melphalan (an oral alkylating agent), prednisone, and other agents. n n W A LD E N S T R Ö M ’ S M A CR O G LO B U LI NE M I A A clonal disorder of B cells that leads to a malignant monoclonal gammopathy. Elevated levels of IgM result in hyperviscosity syndrome, coagulation abnormalities, cryoglobulinemia, cold agglutinin disease (leading to autoimmune hemolytic anemia), and amyloidosis. Tissue is infiltrated by IgM and neoplastic plasma cells. A chronic, indolent disease of the elderly. A B Multiple myeloma skeletal survey. Characteristic lytic bony lesions of multiple myeloma involving the tibia and fibula (A) and the skull (B) are seen. (Image A reproduced with per- FIGURE 2.7-17. mission from Lichtman MA et al. Williams Hematology, 8th ed. New York: McGraw-Hill, 2010, Fig. 109-13A. Image B reproduced with permission from Kantarjian HM. MD Anderson Manual of Medical Oncology, 1st ed. New York: McGraw-Hill, 2006, Fig. 8-1.) KEY FACT Hypercalcemia manifests in symptoms of polyuria, constipation, confusion, nausea, vomiting, and lethargy. KEY FACT Because multiple myeloma is an osteoclastic process, a bone scan, which detects osteoblastic activity, may be ". 174 HIGH-YIELD FACTS IN KEY FACT HEMATOLOGY/ONCOLOGY HISTORY/PE n Cryoglobulinemia and cold agglutinins are different disorders caused by IgM antibodies. Cryoglobulinemia is most often seen in HCV and has systemic signs such as joint pain and renal involvement. Cold agglutinins cause numbness upon cold exposure and are seen with EBV, mycoplasmal infection, and Waldenström’s macroglobulinemia. n Presents with nonspecific symptoms of lethargy and weight loss along with Raynaud’s phenomenon from cryoglobulinemia. Patients complain of neurologic problems ranging from mental status changes to sensorimotor peripheral neuropathy and blurry vision. Organomegaly and organ dysfunction affecting the skin, GI tract, kidneys, and lungs are also seen. As with multiple myeloma, MGUS is a precursor to disease. DIAGNOSIS n n Labs show elevated ESR, uric acid, LDH, and alkaline phosphatase. Bone marrow biopsy and aspirate are required to establish the diagnosis. Marrow shows abnormal plasma cells, classically with Dutcher bodies (PAS-! IgM deposits around the nucleus). Serum and urine protein electrophoresis and immunofixation are also used. TREATMENT Excess immunoglobulin is removed with plasmapheresis; underlying lymphoma is treated with chemotherapy. AM YLOI DOS I S A generic term referring to extracellular deposition of protein fibrils. There are many different kinds of amyloidosis (see Table 2.7-9). Classically a disease of the elderly. HISTORY/PE n n The clinical presentation depends on the type of precursor protein, tissue distribution, and the amount of amyloid deposition. In the 2 most common forms of systemic amyloidosis, 1° (AL) and 2° (AA), the major sites of clinically important amyloid deposition are in the kidneys, heart, and liver. In some disorders, clinically important amyloid deposition is limited to 1 organ (eg, the brain in Alzheimer’s disease). TA B L E 2 . 7- 9 . Types of Amyloidosis AMYLOID AL CAUSE A plasma cell dyscrasia with deposition of monoclonal lightchain fragments. Associated with multiple myeloma and Waldenström's macroglobulinemia. AA Deposition of the acute-phase reactant serum amyloid A. Associated with chronic inflammatory diseases (eg, rheumatoid arthritis), infections, and neoplasms. Dialysis related Deposition of β2 microglobulin, which accumulates in patients on long-term dialysis. Heritable Deposition of abnormal gene products (eg, transthyretin, aka prealbumin). A heterogeneous group of disorders. Senile-systemic Deposition of otherwise normal transthyretin. HEMATOLOGY/ONCOLOGY HIGH-YIELD FACTS IN DIAGNOSIS Diagnosed by the clinical picture; confirmed by tissue biopsy with Congo red staining showing apple-green birefringence under polarized light. TREATMENT 1° amyloidosis is treated with experimental chemotherapy to reduce protein burden; in 2° amyloidosis, the underlying condition should be addressed. Transplantation is also used. Neutropenia An absolute neutrophil count (ANC) < 1500/mm3, where ANC = (WBC count) × (% bands + % segmented neutrophils). Neutropenia may be due to a combination of ↓ production, sequestration to marginated or tissue pools, and ↑ destruction or utilization. It may be acquired or intrinsic. HISTORY/PE n n n Patients are at ↑ risk of infection, with the risk varying inversely with neutrophil count. Acute neutropenia: Associated with S aureus, Pseudomonas, E coli, Proteus, and Klebsiella sepsis. Chronic and autoimmune neutropenia: Presents with recurrent sinusitis, stomatitis, gingivitis, and perirectal infections rather than sepsis. Some chronic neutropenias are accompanied by splenomegaly (eg, Felty’s syndrome, Gaucher’s disease, sarcoidosis). DIAGNOSIS n n n The history (recent drug exposure or infection) and laboratory data are the cornerstones of diagnosis. A CBC with ANC may be used to follow neutropenia. If thrombocytopenia or anemia is present, bone marrow biopsy and aspirate should be performed. Serum immunologic evaluation, ANA levels, and a workup for collagen vascular disease may be merited. TREATMENT n n n Infection management is most important, as patients may not be able to mount an inflammatory response to infection owing to their lack of neutrophils. Fever in the context of neutropenia should be treated immediately with broad-spectrum antibiotics such as cefepime. Suspected fungal infections should be treated appropriately as well. Hematopoietic stem cell factors such as G-CSF can be used to shorten the duration of neutropenia. In some instances, IVIG and allogeneic bone marrow transplantation may be used. Eosinophilia An absolute eosinophil count > 350/mm. Eosinophilia can be triggered by the overproduction of cytokines (IL-3, IL-5, and GM-CSF) or by chemokines KEY FACT Hypothermia can be caused by fungemia. 175 176 HIGH-YIELD FACTS IN MNEMONIC Causes of 2° eosinophilia— NAACP Neoplasm Allergies Asthma Collagen vascular disease Parasites HEMATOLOGY/ONCOLOGY that stimulate the migration of eosinophils into peripheral blood and tissues. Eosinophilia may be a 1° disorder but is usually 2° to another cause. HISTORY/PE n n A travel, medication, atopic, and diet history should be elicited along with a history of symptoms relating to lymphoma/leukemia. Physical examination findings vary. Patients with hypereosinophilic syndrome (HES) may present with fever, anemia, and prominent cardiac findings (emboli from mural thrombi, abnormal ECGs, CHF, murmurs). Other affected organs include the lung, liver, spleen, skin, and nervous system (due to eosinophilic infiltration). DIAGNOSIS n n In addition to a history and physical, a CBC and differential should be obtained, and CSF should be analyzed for eosinophilia, which is suggestive of a drug reaction or infection with coccidioidomycosis or a helminth. Hematuria with eosinophilia may be a sign of schistosomiasis. TREATMENT Medication should be tailored to the cause of the eosinophilia. HES is treated with corticosteroid and cytotoxic agents to ↓ the eosinophilia. Transplant Medicine n n n Tissue transplantation is increasingly used to treat a variety of diseases. Types of transplantation include the following: n Autologous: Transplantation from the patient to him/herself. n Allogeneic: Transplantation from a donor to a genetically different patient. n Syngeneic: Transplantation between identical twins (ie, from a donor to a genetically identical patient). With allogeneic donation, efforts are made to ABO and HLA match the donor and recipient. Even with antigenic matching and immunosuppression, however, transplants may be rejected. There are 3 types of rejection: hyperacute, acute, and chronic (see Table 2.7-10). Graft-versus-host disease (GVHD) is a complication specific to allogeneic bone marrow transplantation in which donated T cells attack host tissues, especially the skin, liver, and GI tract. It may be acute (occurring < 100 days posttransplant) or chronic (occurring > 100 days afterward). n Minor histocompatibility antigens are thought to be responsible for GVHD, which typically presents with skin changes, cholestatic liver dysfunction, obstructive lung disease, or GI problems. n Patients are treated with high-dose corticosteroids. HEMATOLOGY/ONCOLOGY TA B L E 2 . 7- 10 . HIGH-YIELD FACTS IN 177 Types of Transplant Rejection VARIABLE HYPERACUTE ACUTE CHRONIC Timing after transplant Within minutes. Five days to 3 months. Months to years. Pathomechanism Preformed antibodies. T-cell mediated. Chronic immune reaction causing fibrosis. Tissue findings Vascular thrombi; tissue Laboratory evidence of tissue ischemia. destruction such as ↑ GGT, Gradual loss of organ function. alkaline phosphatase, LDH, BUN, or creatinine. Prevention Check ABO compatibility. N/A N/A Treatment Cytotoxic agents. Confirm with sampling of No treatment; biopsy to rule out transplanted tissue; treat with treatable acute reaction. corticosteroids, antilymphocyte antibodies (OKT3), tacrolimus, or MMF. n n The typical regimen after transplant can include these commonly used drugs: prednisone, mycophenolate mofetil (MMF), FK506 (tacrolimus) to suppress immune-mediated rejection, TMP-SMX, ganciclovir, and ketoconazole to prevent subsequent infection in the immunosuppressed host. A variant of GVHD is the graft-versus-leukemia effect, in which leukemia patients who are treated with an allogeneic bone marrow transplant have significantly lower relapse rates than those treated with an autologous transplant. This difference is thought to be due to a reaction of donated T cells against leukemic cells. Diseases Associated With Neoplasms Table 2.7-11 outlines conditions that are commonly associated with neoplasms. 178 HIGH-YIELD FACTS IN TA B L E 2 . 7- 11 . HEMATOLOGY/ONCOLOGY Disorders Associated with Neoplasms CONDITION NEOPLASM Down syndrome ALL (“We will ALL go Down together”). Xeroderma pigmentosum Squamous cell and basal cell carcinomas of the skin. Chronic atrophic gastritis, pernicious anemia, postsurgical gastric Gastric adenocarcinoma. remnants Tuberous sclerosis (facial angiofibroma, seizures, mental Astrocytoma and cardiac rhabdomyoma. retardation) Actinic keratosis Squamous cell carcinoma of the skin. Barrett’s esophagus (chronic GI reflux) Esophageal adenocarcinoma. Plummer-Vinson syndrome (atrophic glossitis, esophageal webs, Squamous cell carcinoma of the esophagus. anemia; all due to iron deficiency) Cirrhosis (alcoholic, HBV or HCV) Hepatocellular carcinoma. Ulcerative colitis Colonic adenocarcinoma. Paget’s disease of bone 2° osteosarcoma and fibrosarcoma. Immunodeficiency states Malignant lymphomas. AIDS Aggressive malignant NHLs and Kaposi’s sarcoma. Autoimmune diseases (eg, myasthenia gravis) Benign and malignant thymomas. Acanthosis nigricans (hyperpigmentation and epidermal Visceral malignancy (stomach, lung, breast, uterus). thickening) Multiple dysplastic nevi Malignant melanoma. HIGH-YIELD FACTS IN INFECTIOUS DISEASE Respiratory Infections 180 Genitourinary Infections 203 PNEUMONIA 180 URINARY TRACT INFECTIONS 203 TUBERCULOSIS 181 PYELONEPHRITIS 203 ACUTE PHARYNGITIS 184 SINUSITIS 185 SEPSIS COCCIDIOIDOMYCOSIS 186 MALARIA 205 INFLUENZA 187 INFECTIOUS MONONUCLEOSIS 206 CNS Infections 188 MENINGITIS 188 ENCEPHALITIS 189 BRAIN ABSCESS 190 Human Immunodeficiency Virus 192 Opportunistic Infections 194 OROPHARYNGEAL CANDIDIASIS (THRUSH) 194 CRYPTOCOCCAL MENINGITIS 195 HISTOPLASMOSIS Hematologic Infections Fever 204 204 207 FEVER OF UNKNOWN ORIGIN 207 NEUTROPENIC FEVER 208 Tick-Borne Infections 208 LYME DISEASE 208 ROCKY MOUNTAIN SPOTTED FEVER 209 Infections of the Eyes and Ears 209 INFECTIOUS CONJUNCTIVITIS 209 195 ORBITAL CELLULITIS 210 PNEUMOCYSTIS JIROVECI PNEUMONIA 196 OTITIS EXTERNA 210 CYTOMEGALOVIRUS 196 MYCOBACTERIUM AVIUM COMPLEX 198 TOXOPLASMOSIS 198 Sexually Transmitted Diseases 199 CHLAMYDIA 199 GONORRHEA 200 SYPHILIS 200 GENITAL LESIONS 202 Miscellaneous Infections 211 INFECTIVE ENDOCARDITIS 211 ANTHRAX 213 OSTEOMYELITIS 214 179 180 HIGH-YIELD FACTS IN INFECTIOUS DISEASE Respiratory Infections P NE U M ONI A Some common causes of pneumonia are outlined in Tables 2.8-1 and 2.8-2. HISTORY/PE n n n KEY FACT An adequate sputum Gram stain sample has many PMNs (> 25 cells/ hpf) and few epithelial cells (< 10 cells/ hpf). May present classically or atypically. n Classic symptoms: Sudden onset, fever, productive cough (purulent yellow-green sputum or hemoptysis), dyspnea, night sweats, pleuritic chest pain. n Atypical symptoms: Gradual onset, dry cough, headaches, myalgias, sore throat, GI symptoms. Lung examination may show ↓ or bronchial breath sounds, rales, wheezing, dullness to percussion, egophony, and/or tactile fremitus. Elderly patients as well as those with COPD, diabetes, or immune compromise may have minimal or atypical signs on physical examination. DIAGNOSIS n n n Diagnosis requires 2 or more symptoms of acute respiratory infection plus a new infiltrate on CXR or CT. Workup includes physical examination, CXR (see Figure 2.8-1), CBC, sputum Gram stain and culture (see Figure 2.8-2), nasopharyngeal aspirate, blood culture, and ABG. Tests for specific pathogens include the following: n Legionella: Urine Legionella antigen test (detects only serogroup 1), sputum staining with direct fluorescent antibody (DFA), culture. n Chlamydia pneumoniae: Serologic testing, culture, PCR. n Mycoplasma: Usually clinical. Serum cold agglutinins and serum Mycoplasma antigen may also be used. n Streptococcus pneumoniae: Urine pneumococcal antigen test, culture. n Viral: Nasopharyngeal aspirate, rapid tests for pathogens (eg, influenza, RSV), DFA, viral culture. TREATMENT n n Table 2.8-3 summarizes the recommended initial treatment for pneumonia. Outpatient treatment with oral antibiotics is recommended in uncomplicated cases. TA B L E 2 . 8 - 1 . Common Causes of Pneumonia by Age CHILDREN ADULTS ADULTS (6 WEEKS–18 YEARS) (18–40 YEARS) (40–65 YEARS) ELDERLY Viruses (RSV) Mycoplasma S pneumoniae S pneumoniae Mycoplasma C pneumoniae H influenzae Viruses C pneumoniae S pneumoniae Anaerobes Anaerobes Viruses H influenzae Mycoplasma Gram-! rods S pneumoniae (GNRs) INFECTIOUS DISEASE TA B L E 2 . 8 - 2 . HIGH-YIELD FACTS IN 181 Causes of Pneumonia by Category CATEGORY ETIOLOGY Atypical Mycoplasma, Legionella, Chlamydia. Nosocomial (hospital acquired) GNRs, Staphylococcus, anaerobes. Immunocompromised Staphylococcus, gram-" rods, fungi, viruses, Pneumocystis jiroveci (with HIV), mycobacteria. Aspiration Anaerobes. Alcoholics/IV drug users S pneumoniae, Klebsiella, Staphylococcus. Cystic fibrosis (CF) Pseudomonas, Burkholderia, S aureus, mycobacteria. COPD H influenzae, Moraxella catarrhalis, S pneumoniae. Postviral S pneumoniae, Staphylococcus, H influenzae. Neonates Group B streptococci (GBS), E coli. Recurrent Obstruction, bronchogenic carcinoma, lymphoma, Wegener’s granulomatosis, immunodeficiency, unusual organisms (eg, Nocardia, Coxiella burnetii, Aspergillus, Pseudomonas). n n In-hospital treatment with IV antibiotics is recommended for patients > 65 years of age and for those with comorbidities (alcoholism, COPD, diabetes, malnutrition), immunosuppression, malignancy, unstable vitals or signs of respiratory failure, altered mental status, and/or multilobar involvement. For patients with obstructive diseases (eg, CF or bronchiectasis), consider adding pseudomonal, staphylococcal, or anaerobic coverage. COMPLICATIONS Pleural effusion, empyema, lung abscess, necrotizing pneumonia, bacteremia. T U B E R C U L O S IS (TB) Infection due to Mycobacterium tuberculosis. Roughly 2 billion people worldwide are infected with TB. Initial infection usually leads to latent TB infection (LTBI) that is asymptomatic. Most symptomatic cases (ie, active disease) are due to reactivation of latent infection rather than to 1° exposure. Pulmonary TB is most common, but disseminated or extrapulmonary TB can occur as well. TB can infect almost any organ system, including the lungs, CNS, GU tract, bone, and GI tract. Risk factors include the following: n Risk factors for active disease (ie, reactivation): Immunosuppression (HIV), alcoholism, preexisting lung disease, diabetes, advancing age. A 70-year-old male presents to the ER with 5 days of fever, productive cough, and altered mental status. He is also found to be hypotensive and tachypneic. Broad-spectrum antibiotics and fluid resuscitation are promptly administered, but the patient continues to be hypotensive. What is the next best step in treatment? 182 HIGH-YIELD FACTS IN INFECTIOUS DISEASE A B Lobar pneumonia. PA (A) and lateral (B) CXRs of a 41-year-old male with cough and shortness of breath show a left lower lobe opacity consistent with lobar pneumonia. S pneumoniae was confirmed by sputum Gram stain and culture. (Reproduced with permission from FIGURE 2.8-1. USMLERx.com.) n Risk factors for TB exposure in the United States: Homelessness and crowded living conditions (eg, prisons), emigration/travel from developing nations, employment in a health profession, interaction with known TB contacts. HISTORY/PE KEY FACT TB almost always presents with an extended duration (> 3 weeks) of symptoms. Administration of vasopressors and ICU admission. This patient is in septic shock, likely 2° to pneumonia. Patients with pneumonia who require vasopressors or mechanical ventilation warrant admission to an ICU. n n n Presents with cough, hemoptysis, dyspnea, weight loss, fatigue, night sweats, fever, cachexia, hypoxia, tachycardia, lymphadenopathy, an abnormal lung examination, and a prolonged (> 3-week) symptom duration. TB is a common cause of fever of unknown origin. HIV patients can present with atypical signs and symptoms and have higher rates of extrapulmonary TB. A B Common pathogens causing pneumonia. (A) S aureus. These clusters of gram-" cocci were isolated from the sputum of a patient who developed pneumonia while hospitalized. (B) S pneumoniae. Sputum sample from a patient with pneumonia. Note the characteristic lancet-shaped gram-" diplococci. FIGURE 2.8-2. INFECTIOUS DISEASE TA B L E 2 . 8 - 3 . HIGH-YIELD FACTS IN 183 Treatment of Pneumonia PATIENT TYPE SUSPECTED PATHOGENS Outpatient community-acquired S pneumoniae, Mycoplasma pneumoniae, pneumonia, ≤ 65 years, otherwise healthy, C pneumoniae, H influenzae, viral. EMPIRIC COVERAGE Macrolide or doxycycline. no antimicrobials within 3 months > 65 years or comorbidity (COPD, heart S pneumoniae, H influenzae, aerobic GNRs failure, renal failure, diabetes, liver disease, (E coli, Enterobacter, Klebsiella), S aureus, EtOH abuse) or antimicrobial use within 3 Legionella, viruses. Fluoroquinolone or β-lactam + macrolide. months Community-acquired pneumonia requiring S pneumoniae, H influenzae, anaerobes, Fluoroquinolone or antipneumococcal hospitalization aerobic GNRs, Legionella, Chlamydia. β-lactam + macrolide. Community-acquired pneumonia requiring S pneumoniae, Legionella, H influenzae, Antipneumococcal β-lactam + either ICU care anaerobes, aerobic GNRs, Mycoplasma, azithromycin or fluoroquinolone. Pseudomonas. Institution-/hospital-acquired pneumonia— GNRs (including Pseudomonas and hospitalized > 48 hours or in a long-term Acinetobacter), S aureus, Legionella, mixed care facility > 14 days; ventilator-associated flora. Extended-spectrum cephalosporin or carbapenem with antipseudomonal activity. Add an aminoglycoside or a fluoroquinolone pneumonia for coverage of resistant organisms (Pseudomonas) until lab sensitivities identify the best single agent. Critically ill or worsening over 24–48 hours MRSA. on initial antibiotic therapy Add vancomycin or linezolid; broader gram-! coverage. DIAGNOSIS n n Active disease: Mycobacterial culture of sputum (or blood/tissue for extrapulmonary disease) is the gold standard but can take weeks to obtain. A sputum acid-fast stain (see Figure 2.8-3) can yield rapid preliminary results but lacks sensitivity. n The most common finding among typical hosts is a cavitary infiltrate in the upper lobe on CXR (see Figure 2.8-4). n HIV patients or those with 1° TB may show lower lobe infiltrates with or without cavitation. n Multiple fine nodular densities distributed throughout both lungs are typical of miliary TB, which represents hematologic or lymphatic dissemination. Latent disease (asymptomatic and previous exposure): Diagnose with a " PPD test (see Figure 2.8-5). n Immunocompromised individuals with LTBI may have a " PPD (anergy). n All patients with a " PPD should be evaluated with a CXR to rule out active disease. Tuberculosis. Note the red color (“red snappers”) of tubercle bacilli on acid-fast staining. (Reproduced with FIGURE 2.8-3. permission from Milikowski C. Color Atlas of Basic Histopathology, 1st ed. Stamford, CT: Appleton & Lange, 1997: 193.) 184 HIGH-YIELD FACTS IN INFECTIOUS DISEASE A B Pulmonary TB. (A) Right apical opacity with areas of cavitation (arrow) is seen in an elderly man with reactivation TB. (B) Coned-in view of a CXR in a young male with miliary TB shows innumerable 1- to 2-mm pulmonary nodules. (Image A reproduced with permis- FIGURE 2.8-4. sion from Halter JB et al. Hazzard’s Geriatric Medicine and Gerontology, 6th ed. New York: McGraw-Hill, 2009, Fig. 126-7. Image B reproduced with permission from USMLERx.com.) KEY FACT Rifampin turns body fluids orange (including tears); ethambutol can cause optic neuritis. INH causes peripheral neuropathy and hepatitis. TREATMENT All cases (both latent and active) must be reported to local and state health departments. Respiratory isolation should be instituted if active TB is suspected. Treatment measures are as follows: n MNEMONIC n Patients with TB are RIPE for treatment: Rifampin INH Pyrazinamide Ethambutol Active disease: n Directly observed multidrug therapy with a 4-drug regimen (INH, pyrazinamide, rifampin, ethambutol) × 2 months followed by INH and rifampin × 4 months. n Administer vitamin B6 (pyridoxine) with INH to prevent peripheral neuritis. Latent disease: For a " PPD without signs or symptoms of active disease, treat with INH × 9 months. Alternative regimens include INH × 6 months or rifampin × 4 months. AC UTE P HAR YNG I T I S Viral causes are more common (90% in adults), but it is important to identify streptococcal pharyngitis (group A β-hemolytic Streptococcus pyogenes). Etiologies are as follows: n n KEY FACT Early antibiotic treatment of streptococcal pharyngitis can prevent rheumatic fever but not glomerulonephritis. Bacterial: Group A streptococci (GAS), Neisseria gonorrhoeae, Corynebacterium diphtheriae, M pneumoniae. Viral: Rhinovirus, coronavirus, adenovirus, HSV, EBV, CMV, influenza virus, coxsackievirus, acute HIV infection. HISTORY/PE n n Typical of streptococcal pharyngitis: Fever, sore throat, pharyngeal erythema, tonsillar exudate, cervical lymphadenopathy, soft palate petechiae, headache, vomiting, scarlatiniform rash (indicates scarlet fever). Atypical of streptococcal pharyngitis: Coryza, hoarseness, rhinorrhea, cough, conjunctivitis, anterior stomatitis, ulcerative lesions, GI symptoms. INFECTIOUS DISEASE HIGH-YIELD FACTS IN 185 PPD is injected intradermally on the volar surface of the forearm. The diameter of induration is measured at 48–72 hours. BCG vaccination typically renders a patient PPD but should not preclude prophylaxis as recommended for unvaccinated individuals. The size of induration that indicates a test is interpreted as follows: ≥ 5 mm: HIV or risk factors, close TB contacts, CXR evidence of TB. ≥ 10 mm: Indigent/homeless, residents of developing nations, IV drug use, chronic illness, residents of health and correctional institutions, and health care workers. ≥ 15 mm: Everyone else, including those with no known risk factors. A reaction with controls implies anergy from immunosuppression, old age, or malnutrition and thus does not rule out TB. FIGURE 2.8-5. PPD interpretation. DIAGNOSIS Diagnosed by clinical evaluation, rapid GAS antigen detection, and throat culture. With 3 out of 4 of the Centor criteria, the sensitivity of rapid antigen testing is > 90%. TREATMENT If GAS is suspected, begin empiric antibiotic therapy with penicillin × 10 days. Cephalosporins, amoxicillin, and azithromycin are alternative options. Symptom relief can be attained with fluids, rest, antipyretics, and salt-water gargles. KEY FACT The Centor criteria for identifying streptococcal pharyngitis are fever, tonsillar exudate, tender anterior cervical lymphadenopathy, and lack of cough (3 of 4 are required). COMPLICATIONS n n n Nonsuppurative: Acute rheumatic fever (see the Cardiovascular chapter), poststreptococcal glomerulonephritis. Suppurative: Cervical lymphadenitis, mastoiditis, sinusitis, otitis media, retropharyngeal or peritonsillar abscess, and, rarely, thrombophlebitis of the jugular vein (Lemierre’s syndrome) due to Fusobacterium, an oral anaerobe. Peritonsillar abscess may present with odynophagia, trismus (“lockjaw”), a muffled voice, unilateral tonsillar enlargement, and erythema, with the uvula and soft palate deviated away from the affected side. Culture abscess fluid and localize the abscess via intraoral ultrasound or CT. Treat with antibiotics and surgical drainage. SI N U S IT IS Refers to inflammation of the paranasal sinuses. The maxillary sinuses are most commonly affected. Subtypes include the following: n n Acute sinusitis (symptoms lasting < 1 month): Most commonly associated with viruses, S pneumoniae, H influenzae, and M catarrhalis. Bacterial causes are rare and characterized by purulent nasal discharge, facial or tooth tenderness, and symptoms lasting > 7 days. Chronic sinusitis (symptoms persisting > 3 months): A chronic inflammatory process often due to obstruction of sinus drainage and ongoing low-grade anaerobic infections. In patients with hematologic malignancy or poorly controlled diabetes mellitus (DM), mucormycosis should be considered. KEY FACT Always consider occult sinusitis in febrile ICU patients. KEY FACT Potential complications of sinusitis include meningitis, frontal bone osteomyelitis, cavernous sinus thrombosis, and abscess formation. 186 HIGH-YIELD FACTS IN KEY FACT INFECTIOUS DISEASE HISTORY/PE n Beware of invasive and life-threatening fungal sinusitis (caused by Mucor and Rhizopus) in patients with poorly controlled DM or immune compromise. n Presents with fever, facial pain/pressure, headache, nasal congestion, and discharge. Examination may reveal tenderness, erythema, and swelling over the affected area. High fever, leukocytosis, and a purulent nasal discharge are suggestive of acute bacterial sinusitis. DIAGNOSIS n n n A clinical diagnosis. Culture and radiography are generally not required for acute sinusitis but may guide the management of chronic cases. Transillumination shows opacification of the sinuses (low sensitivity). CT is the test of choice for sinus imaging (see Figure 2.8-6) but is usually necessary only if symptoms persist after treatment. TREATMENT n n FIGURE 2.8-6. Sinusitis. Coronal CT image shows an opacified left maxillary sinus and marked associated bony thickening, consistent with chronic maxillary sinusitis. (Reproduced with permission from n Lalwani AK. Current Diagnosis & Treatment in Otolaryngology—Head and Neck Surgery, 2nd ed. New York: McGraw-Hill, 2008, Fig. 14-2.) COC C I DI OI DOM YC OS I S KEY FACT Consider coccidioidomycosis in an HIV-", Filipino, African American, or pregnant patient from the southwestern United States who presents with respiratory infection. Most cases of acute sinusitis are viral and/or self-limited and are treated with symptomatic therapy (decongestants, antihistamines, nasal saline lavage, pain relief). Acute bacterial sinusitis: Consider amoxicillin/clavulanate 500 mg PO TID × 10 days or clarithromycin, azithromycin, TMP-SMX, a fluoroquinolone, or a second-generation cephalosporin × 10 days. Chronic sinusitis: n Antibiotics are similar to those used for acute disease, although a longer course (3–6 weeks) may be necessary. n Adjuvant therapy with intranasal corticosteroids, decongestants, and antihistamines may be useful in combating the allergic/inflammatory component of the disease. Surgical intervention may be required. A pulmonary fungal infection endemic to the southwestern United States (see Figure 2.8-7). Can present as an acute or subacute pneumonia or as a flulike illness, and may involve extrapulmonary sites, including bone, CNS, and skin. The incubation period is 1–4 weeks after exposure. Filipino, African American, pregnant, and HIV-" patients are at ↑ risk for disseminated disease. HISTORY/PE Patients present with fever, anorexia, headache, chest pain, cough, dyspnea, arthralgias, and night sweats. Disseminated infection can present with meningitis, bone lesions, and soft tissue abscesses. DIAGNOSIS n n n n n Obtain bronchoalveolar lavage (BAL) as well as fungal cultures of sputum, wound exudate, or other affected tissue. Serum anti-coccidioidal antibodies are specific but not sensitive and lag behind clinical illness by weeks or months. Identify Coccidioides immitis spherules on H&E or other special sputum or tissue stains. CXR findings may be normal or may show infiltrates, nodules, cavities, mediastinal or hilar adenopathy, or pleural effusion. Consider bronchoscopy, fine-needle biopsy, open lung biopsy, or pleural biopsy if serology is indeterminate. INFECTIOUS DISEASE HIGH-YIELD FACTS IN 187 Blastomycosis Histoplasmosis Coccidioidomycosis Geographic distribution of systemic fungal infection in the United States. (Reproduced with permission from Ryan KJ, Ray CG. Sherris Medical Microbiology, 5th ed. New York: McGraw-Hill, FIGURE 2.8-7. 2010, Fig. 46-4.) TREATMENT n n Acute: PO fluconazole or itraconazole may be used for mild infection or continuation therapy once the patient is stable. IV therapy is rarely necessary; however, consider IV amphotericin B for severe or protracted 1° pulmonary infection and disseminated disease. Chronic: No treatment is needed for asymptomatic chronic pulmonary nodules or cavities. Progressive cavitary or symptomatic disease usually requires surgery plus long-term azole therapy for 8–12 months. IN F LU E N Z A A highly contagious orthomyxovirus transmitted by droplet nuclei. There are 3 types of influenza: A, B, and C. Subtypes of influenza A (eg, H5N1, H1N1) are classified on the basis of glycoproteins (hemagglutinin and neuraminidase). Relevant terms are as follows: n n Antigenic drift: Refers to small, gradual changes in surface proteins through point mutations. These small changes are sufficient to allow the virus to escape immune recognition, accounting for the fact that individuals can be infected with influenza multiple times. Antigenic shift: Describes an acute, major change in the influenza A subtype (significant genetic reassortment) circulating among humans; leads to pandemics. In the United States, the typical influenza season begins in November and lasts until March. Vaccination with inactivated influenza virus is currently recommended for all patients ≥ 6 months of age. Children 6 months to 9 years of age require 2 doses of the seasonal vaccine if they are receiving the vaccine for the first time. A high-dose flu vaccine is available for people ≥ 65 years of age. HISTORY/PE Patients typically present with abrupt onset of fevers, myalgias, chills, cough, coryza, and weakness. Elderly patients may have atypical presentations characterized only by confusion. A 70-year-old male presents to the ER in February with a high fever and a productive cough. One week ago he was treated for influenza, and his symptoms improved until 3 days ago, when they returned with greater severity. Examination now reveals cyanosis, tactile fremitus, and dullness to percussion over the left lower lobe. Against what organism should antibiotic therapy be directed? 188 HIGH-YIELD FACTS IN INFECTIOUS DISEASE DIAGNOSIS KEY FACT A live attenuated, nasally delivered influenza vaccine is available for healthy people 2–49 years of age who are not pregnant or severely immunocompromised. Leukopenia is a common finding. Rapid influenza tests of viral antigens from nasopharyngeal swabs are available. More definitive diagnosis can be made with DFA tests, viral culture, or PCR assays. TREATMENT n n Symptomatic care with analgesics and cough medicine. Antivirals such as oseltamivir or zanamivir are most effective when used within 2 days of onset and may shorten the duration of infection by 1–2 days. COMPLICATIONS n n Severe 1° viral pneumonia, 2° bacterial pneumonia (see “Postviral” in Table 2.8-2), sinusitis, bronchitis, and exacerbation of COPD and asthma can occur. Reye’s syndrome, or fatty liver encephalopathy, has been associated with ASA use in children with viral infections, including influenza. CNS Infections ME NI NG IT I S Acute bacterial meningitis is a life-threatening emergency. Viral (also called “aseptic”) meningitis is more common and clinically less morbid. Risk factors for meningitis include recent ear infection, sinusitis, immunodeficiencies, recent neurosurgical procedures, and sick contacts. Causes by age group are listed in Table 2.8-4. HISTORY/PE Patients present with fever, malaise, headache, neck stiffness, photophobia, altered mental status, nausea/vomiting, seizures, or signs of meningeal irritation (" Kernig’s and Brudzinski’s signs). TA B L E 2 . 8 - 4 . Causes of Meningitis by Age Groupa,b NEWBORN CHILDREN (0–6 MONTHS) (6 MONTHS–6 YEARS) 60 YEARS + GBS S pneumoniae N meningitidis S pneumoniae E coli/GNRs Neisseria Enteroviruses GNRs S pneumoniae Listeria HSV N meningitidis Listeria (see Figure 2.8-8) S aureus. Postviral pneumonia is an important complication of influenza, especially in the elderly. Staphylococcus is the most common organism responsible for early bacterial superinfection, presenting just days after the onset of influenza. 6–60 YEARS meningitidis H influenzae serotype b Enteroviruses a Causes in HIV include Cryptococcus, CMV, HSV, VZV, TB, toxoplasmosis (brain abscess), and JC virus (PML). b The incidence of H influenzae meningitis has greatly ↓ over the past 10–15 years as a result of the H influenzae vaccine. INFECTIOUS DISEASE DIAGNOSIS n n n Order an LP for CSF Gram stain and culture; obtain glucose, protein, WBC count plus differential, RBC count, and opening pressure (in the absence of papilledema or focal neurologic deficits). Viral PCRs (eg, HSV); cryptococcal antigen (for HIV patients). CT or MRI to rule out other diagnoses. Obtain blood cultures. CBC may reveal leukocytosis; CSF findings vary (see Table 2.8-5). TREATMENT n n n n Antibiotics should be administered rapidly (see Table 2.8-6) and may be given empirically up to 2 hours before an LP. Some cases of viral meningitis can be treated with supportive care and close follow-up. Close contacts of patients with meningococcal meningitis should receive rifampin. Second-line prophylactic regimens include ciprofloxacin, ceftriaxone, or azithromycin. Dexamethasone may be beneficial in bacterial meningitis, especially S pneumoniae or H influenzae, if given 15–20 minutes before antibiotics. HIGH-YIELD FACTS IN 189 KEY FACT Acute bacterial meningitis is a lifethreatening emergency. Antibiotics should be started as soon as possible. KEY FACT Although other medications may be used, rifampin is the frequently tested prophylaxis of choice for close contacts of patients with meningococcal meningitis. COMPLICATIONS n n n n n n n Cerebral edema: Visible on CT/MRI. Presents with loss of oculocephalic reflex. Treat with IV mannitol. Subdural effusions: May be seen on CT scan. Occur in 50% of infants with H influenzae meningitis. No treatment is necessary. Ventriculitis/hydrocephalus: Presents as a worsening clinical picture with improved CSF findings. Requires ventriculostomy and possibly intraventricular antibiotics. Seizures: Treat with benzodiazepines and phenytoin. Hyponatremia: Assess intravascular volume status; if low, administer fluids to prevent ischemic stroke. Closely monitor sodium concentration and fluid intake/output. Subdural empyema: Presents with intractable seizures. Requires surgical evacuation. Other: Cranial nerve palsies, sensorineural hearing loss, coma, death. E N C EP H A LI T I S HSV and arboviruses are the most common causes of encephalitis. Rarer etiologies include CMV, toxoplasmosis, West Nile virus, VZV, Borrelia, Rickettsia, Legionella, enterovirus, Mycoplasma, and cerebral malaria. Children and the elderly are the most vulnerable. FIGURE 2.8-8. Listeria. These numerous rod-shaped bacilli were isolated from the blood of a patient with Listeria meningitis. KEY FACT The presence of RBCs in CSF without a history of trauma is highly suggestive of HSV encephalitis. HISTORY/PE n n Presents with altered consciousness, headache, fever, and seizures. Lethargy, confusion, coma, and focal neurologic deficits (cranial nerve deficits, accentuated DTRs) may also be present. The differential includes brain abscess, malignancy, toxic-metabolic encephalopathy, subdural hematoma, and SAH. DIAGNOSIS n n CSF shows lymphocytic pleocytosis and moderately ↑ protein. RBCs without evidence of trauma suggest HSV encephalitis. The glucose level is low in tuberculous, fungal, bacterial, and amebic infections. Obtain a CSF Gram stain (bacteria), acid-fast stain (mycobacteria), India ink stain (Cryptococcus), a wet preparation (free-living amebae), and a A 19-year-old college student is brought to the ER from her dorm room, where she was found by her roommate in a confused state. She complains of fever, nausea, vomiting, and pain in her neck and head. She has a petechial rash on her legs. CSF examination reveals a glucose level of 22 mg/dL, a protein level of 140 mg/dL, and a WBC count of 1400/mm3. What is the most likely organism responsible for her condition? 190 HIGH-YIELD FACTS IN INFECTIOUS DISEASE CSF Profiles TA B L E 2 . 8 - 5 . OPENING RBCS WBCS GLUCOSE PROTEIN PRESSURE (per mm3) (per mm3) (mg/dL) (mg/dL) (cm H2O) < 10 <5 ∼ 2/3 of 15–45 10–20 ↓ ↑ ↑ Cloudy/purulent ↔ or ↑ ↔ ↔ or ↑ ↔ or ↑ Most often clear ↔ or ↑ Normal GAMMA GLOBULIN APPEARANCE Clear (% PROTEIN) 3–12 serum Bacterial meningitis ↔ ↑ (> 1000 PMNs) Viral meningitis ↔ ↑ (monos/ lymphs) Aseptic meningitis ↔ ↑ ↔ ↔ or ↑ ↔ SAH ↑↑ ↑ ↔ ↑ ↔ or ↑ Guillain-Barré ↔ ↔ ↔ or ↑ ↑↑ ↔ Clear Yellow/red Clear or yellow ↔ ↔ or ↑ ↔ (high protein) syndrome MS ↔ ↔ or ↑ ↔ ↔ ↔ Clear ↑↑ Pseudotumor ↔ ↔ ↔ ↔ ↑↑↑ Clear ↔ cerebri KEY FACT n HSV encephalitis is associated with high morbidity. PCR is highly sensitive and specific. IV acyclovir should be started ASAP if this diagnosis is suspected. Giemsa stain (trypanosomes). Order a PCR for HSV, CMV, EBV, VZV, and enterovirus. MRI may demonstrate characteristic temporal lobe signal abnormalities in HSV encephalitis (see Figure 2.8-9). TREATMENT n n n HSV encephalitis: Requires immediate IV acyclovir. CMV encephalitis: Treat with IV ganciclovir +/− foscarnet. Give doxycycline for suspected Rocky Mountain spotted fever, Lyme disease, or ehrlichiosis. B R AI N A BS C E S S Neisseria meningitidis. Suspect meningococcal meningitis in a very ill patient with fever, headache, altered mental status, a petechial rash in the lower extremities, and a CSF profile indicative of bacterial meningitis. A focal, suppurative infection of the brain parenchyma, usually with a “ringenhancing” appearance due to fibrous capsule. The most common pathogens are streptococci, staphylococci, and anaerobes; multiple organisms are often implicated (80–90% are polymicrobial). Nonbacterial causes include Toxoplasma, Aspergillus, and Candida; zygomycosis should be considered in immunocompromised hosts, and neurocysticercosis should be considered in relevant epidemiologic settings. Modes of transmission include the following: n n Direct spread: Due to paranasal sinusitis (10% of cases; frequently affects young males, and often due to Streptococcus milleri), otitis media or mastoiditis (33%), or dental infection (2%). Direct inoculation: Affects patients with a history of head trauma or neurosurgical procedures. INFECTIOUS DISEASE TA B L E 2 . 8 - 6 . HIGH-YIELD FACTS IN 191 Empiric Treatment of Bacterial Meningitis AGE < 1 month CAUSATIVE ORGANISM GBS, E coli/GNRs, Listeria. TREATMENT Ampicillin + cefotaxime or gentamicin. 1–3 months 3 months – adulthood Pneumococci, meningococci, H Vancomycin IV + ceftriaxone influenzae. or cefotaxime. Pneumococci, meningococci. Vancomycin IV + ceftriaxone or cefotaxime. n > 60 years/alcoholism/ Pneumococci, gram-! bacilli, Ampicillin + vancomycin + chronic illness Listeria, meningococci. cefotaxime or ceftriaxone. Hematogenous spread (25% of cases): Often shows an MCA distribution with multiple abscesses that are poorly encapsulated and located at the gray-white junction. HISTORY/PE n n Headache, drowsiness, inattention, confusion, and seizures are early symptoms, followed by signs of increasing ICP and then a focal neurologic deficit. Headache is the most common symptom and is often dull, constant, and refractory to treatment. ↑ ICP leads to CN III and CN VI deficits. DIAGNOSIS n n n CT scan will show a ring-enhancing lesion with a low-density core. MRI has higher sensitivity for early abscesses and posterior fossa lesions. CSF analysis is not necessary and may precipitate brainstem herniation. Lab values may show peripheral leukocytosis, ↑ ESR, and ↑ CRP. FIGURE 2.8-9. HSV encephalitis. Coronal FLAIR image of a young male with HSV encephalitis shows the characteristic MRI pattern within the cortex of the right temporal lobe (circle). The left temporal lobe is also involved (arrow), but to a lesser extent. (Reproduced with permission from Fauci AS et al. Harrison’s Principles of Internal Medicine, 17th ed. New York: McGraw-Hill, 2008, Fig. 376-3.) KEY FACT The classic clinical triad of headache, fever, and a focal neurologic deficit is present in 50% of cases of brain abscess. KEY FACT When fever is absent, 1° and metastatic brain tumors should be considered in the differential diagnoses. 192 HIGH-YIELD FACTS IN KEY FACT INFECTIOUS DISEASE TREATMENT n In general, do not LP a patient with a mass lesion in the brain in light of the risk of uncal herniation. n n Initiate broad-spectrum IV antibiotics and surgical drainage (aspiration or excision) if necessary for diagnostic and/or therapeutic purposes. Lesions < 2 cm can often be treated medically. Administer a third-generation cephalosporin + metronidazole +/− vancomycin; give IV therapy for 6–8 weeks. Obtain serial CT/MRIs to follow resolution. Dexamethasone with taper may be used in severe cases to ↓ cerebral edema; IV mannitol may be used to ↓ ICP. Give prophylactic anticonvulsants. Human Immunodeficiency Virus (HIV) A retrovirus that targets and destroys CD4+ T lymphocytes. Infection is characterized by a high rate of viral replication that leads to a progressive decline in CD4+ count (see Figure 2.8-10). n n CD4+ count: Indicates the degree of immunosuppression; guides therapy and prophylaxis and helps determine prognosis. Viral load: May predict the rate of disease progression; provides indications for treatment and gauges response to antiretroviral therapy. HISTORY/PE n n In acute HIV (acute infection/seroconversion, acute retroviral syndrome), the initial infection is often asymptomatic, but patients may also present with mononucleosis-like or flulike symptoms (eg, fever, lymphadenopathy, maculopapular rash, pharyngitis, diarrhea, nausea/vomiting, weight loss, headache). HIV may later present as night sweats, weight loss, thrush, recurrent infections, or opportunistic infections. Complications are inversely correlated with CD4+ count (see Figure 2.8-11). ACUTE LATENT IMMUNODEFICIENCY CD4 lymphocytes Virus, p24 antigen 0 1 2 3 Months 4 5 6 3 – ≥10 Years Time course of HIV infection. Note that the level of CD4 lymphocytes (red curve) remains normal for many years but then declines, resulting in the immunodeficiency stage, which is characterized by opportunistic infections and malignancies. FIGURE 2.8-10. INFECTIOUS DISEASE 1270 HIGH-YIELD FACTS IN 193 CMDT 2011 Absolute CD4 lymphocyte count (/µL) 500 Bacterial infections Tuberculosis Herpes simplex Herpes zoster Vaginal candidiasis Hairy leukoplakia Kaposi’s sarcoma 200 Pneumocystosis Toxoplasmosis Cryptococcosis Coccidioidomycosis Cryptosporidiosis 50 Disseminated MAC infection Histoplasmosis CMV retinitis CNS lymphoma FIGURE 2.8-11. Relationship of CD4+ count to development of opportunistic infections. (Reproduced with permission from McPhee SJ et al. Current Medical Diagnosis & Treatment 2011. New York: McGrawHill, 2011, Fig. 31-1.) DIAGNOSIS n n n n n ELISA test (high sensitivity, moderate specificity): Detects anti-HIV antibodies in the bloodstream (can take up to 6 months to appear after exposure). Western blot (low sensitivity, high specificity): Confirmatory. Rapid HIV tests are now available. Baseline evaluation should include HIV RNA PCR (viral load), CD4+ cell count, CXR, PPD skin test, Pap smear, mental status exam, VDRL/ RPR, and serologies for CMV, viral hepatitis, toxoplasmosis, and VZV. Evaluation for acute retroviral syndrome (acute HIV) should include HIV RNA PCR (viral load); ELISA may be !. TREATMENT n n n Initiate antiretroviral therapy for (1) symptomatic patients (those with AIDS-defining illness) regardless of CD4+ count or viral load; (2) patients with a CD4+ count < 350/mm3; (3) pregnant patients; and (4) those with specific HIV-related conditions (eg, HIV-associated nephropathy, neurocognitive deficits). The initial regimen should generally consist of a combination of 2 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) plus either 1 nonnucleoside RTI (NNRTI) or 1 protease inhibitor. The most important principle is to select multiple medications (usually at least 3) in order to achieve a durable treatment response and limit the emergence of resistance. The goal of therapy is complete viral suppression (< 50 copies). After therapy is started, CD4+ count and viral load should be monitored monthly until suppression is achieved and every 3–6 months afterward. KEY FACT Common AIDS-defining illnesses: n Esophageal candidiasis n CMV retinitis n Kaposi’s sarcoma n CNS lymphoma, toxoplasmosis, PML n P jiroveci pneumonia or recurrent bacterial pneumonia n HIV encephalopathy n Disseminated mycobacterial or fungal infection n Invasive cervical cancer KEY FACT If a pregnant HIV-" patient is not on antiretroviral therapy at the time of delivery, she should be treated with zidovudine (AZT) intrapartum. Infants should receive AZT for 6 weeks after birth. 194 HIGH-YIELD FACTS IN INFECTIOUS DISEASE n KEY FACT MMR is the only live vaccine that should be given to HIV patients. Do not give oral polio vaccine to HIV-" patients or their contacts. n n MNEMONIC An HIV genotype should be obtained before the initiation of therapy and when resistance is suspected, as such testing can provide mutation information and identify resistance to specific antiretrovirals. The recommended prophylaxis for HIV exposure varies according to the severity of the source infection and the exposure. In the setting of a percutaneous injury, mucous membrane exposure, or nonintact skin exposure with an HIV-" source, begin antiretroviral therapy as soon as possible with a basic 2-drug regimen or an expanded regimen of 3 or more drugs for 4 weeks, depending on the severity of the source infection. Table 2.8-7 outlines prophylactic measures against opportunistic infections. AIDS pathogens— The Major Pathogens Concerning Complete T-Cell Collapse Toxoplasma gondii Mycobacterium avium-intracellulare Pneumocystis jiroveci Candida albicans Cryptococcus neoformans Tuberculosis CMV Cryptosporidium parvum T A B L E 2 . 8 - 7. Opportunistic Infections Figure 2.8-12 illustrates the microscopic appearance of some common opportunistic organisms. OR OP HAR YNG E AL C ANDI DI AS I S ( THR U S H) n Risk factors include xerostomia, antibiotic use, denture use, and immunosuppression (eg, HIV, leukemias, lymphomas, cancer, diabetes, corticosteroid inhaler use, immunosuppressive treatment). Prophylaxis for HIV-Related Opportunistic Infections PATHOGEN INDICATION FOR PROPHYLAXIS P jiroveci CD4+ < 200/mm3, prior P jiroveci pneumonia infection, unexplained fever × TREATMENT Single-strength TMP-SMX. NOTES Discontinue prophylaxis when CD4+ is > 200/mm3 for ≥ 3 months. 2 weeks, or HIV-related oral candidiasis. Mycobacterium CD4+ < 50–100/mm3. Weekly azithromycin. Discontinue prophylaxis when CD4+ is > 100/mm3 for > 6 months. avium complex (MAC) Toxoplasma gondii CD4+ < 100/mm3 + " IgG Double-strength TMP-SMX. — PPD > 5 mm or “high risk” (see TB INH × 9 months (+ pyridoxine) or Include pyridoxine with INH- section). rifampin × 4 months. containing regimens. Multiple recurrences. Esophagitis: Fluconazole. — serologies. M tuberculosis Candida Oral: Nystatin swish and swallow. HSV Multiple recurrences. Daily suppressive acyclovir, — famciclovir, or valacyclovir. S pneumoniae All patients. Pneumovax. Give every 5 years provided that CD4+ is > 200/mm3. Influenza All patients. Influenza vaccine annually. — INFECTIOUS DISEASE Pseudohyphae + budding yeasts 4 5° ang a gl gle 45° angle bra an a nc n cchi hing g branching sep se ept ptate tate e septate hyyyp h ph hae ae e hyphae Rare Rar R Ra arre a r fruiting fr rrui uitttin ui ng b bodies odie od dies d 5–10 µm yeasts with wide capsular halo Narrow-based unequal equa budding budd g unequal HIGH-YIELD FACTS IN 195 Irregular gular broad (empty-looking) pty-looking) no nonseptate onsep ptate hyphae, hyph hae, hae e, wide-angle wiide-a ang gle branching b chin branc ng Germ tubes at 37°C Aspergillu A Asp ergillu erg gillu uss u Aspergillus Candida FIGURE 2.8-12. n n n Cryptococcus ryptococcus Mucor Common opportunistic organisms. Hx/PE: Presents with soft white plaques that can be rubbed off, with an erythematous base and possible mucosal burning. The differential includes oral hairy leukoplakia (affects the lateral borders of the tongue; not easily rubbed off). Odynophagia is characteristic of candidal esophagitis. Dx: Usually clinical. KOH or Gram stain shows budding yeast and/or pseudohyphae. Tx: Treat thrush with local therapy (eg, nystatin suspension, clotrimazole tablets, or a PO azole such as fluconazole). Treat candidal esophagitis with PO azole therapy. CR Y PT O CO C CA L M E N I N G IT I S n n n n Risk factors include AIDS and exposure to pigeon droppings. Hx/PE: Presents with headache, fever, impaired mentation, and absent meningeal signs. The differential includes toxoplasmosis, lymphoma, TB meningitis, AIDS dementia complex, PML, HSV encephalitis, and other fungal disease. Dx: LP (↓ CSF glucose; ↑ protein; ↑ leukocyte count with monocytic predominance, ↑↑ opening pressure); " cryptococcal antigen testing in CSF and/or blood, CSF India ink stain, and fungal culture. Tx: n IV amphotericin B + flucytosine × 2 weeks; then fluconazole × 8 weeks. Lifelong maintenance therapy should be administered with fluconazole until symptoms resolve and CD4+ is > 100/mm3 for > 1 year. n ↑ opening pressure may require serial LPs or a ventriculoperitoneal shunt for management. HI ST O P L A S M O S IS Risk factors include HIV/AIDS, spelunking, and exposure to bird or bat excrement, especially in the Ohio and Mississippi river valleys (see Figure 2.8-7). HISTORY/PE n n n 1° exposure is often asymptomatic or causes a flulike illness. Presentation may range from no symptoms to fulminant disease with pulmonary and/or extrapulmonary manifestations. Fever, weight loss, hepatosplenomegaly, lymphadenopathy, a nonproductive cough, palatal ulcers, and pancytopenia indicate disseminated infection (most often within 14 days). KEY FACT The CSF antigen test for cryptococcal meningitis is highly sensitive and specific. A 35-year-old HIV-infected man from Ohio presents to his primary care provider with low-grade fever, dry cough, malaise, and a 5-lb weight loss over the past month. He is compliant with his HIV medications. Physical examination shows hepatosplenomegaly and palatal ulcers. His CBC reveals pancytopenia, and a CXR shows hilar lymphadenopathy. What is the next most appropriate step in management? 196 HIGH-YIELD FACTS IN INFECTIOUS DISEASE n The differential includes atypical bacterial pneumonia, blastomycosis, coccidioidomycosis, TB, sarcoidosis, pneumoconiosis, and lymphoma. DIAGNOSIS n n n CXR shows diffuse nodular densities, focal infiltrate, cavity, or hilar lymphadenopathy (chronic infection is usually cavitary). The urine and serum polysaccharide antigen test is the most sensitive test for making the initial diagnosis of disseminated disease, monitoring response to therapy, and diagnosing relapse. Culture is also diagnostic (blood, sputum, bone marrow, CSF). The yeast form is seen with special stains on biopsy (bone marrow, lymph node, liver) or BAL. TREATMENT Depends on the severity of disease and the host: n n n Mild pulmonary disease or stable nodules: Treat supportively in the immunocompromised host. Consider itraconazole. Chronic cavitary lesions: Give itraconazole for > 1 year. Severe acute pulmonary disease or disseminated disease: Liposomal amphotericin B or amphotericin B × 14 days followed by itraconazole × 1 year or longer. Lifelong maintenance therapy with daily itraconazole may be necessary. P NE U MOC YSTI S JI R OVE C I P NE U M ONI A Formerly known as Pneumocystis carinii pneumonia, or PCP. Risk factors include impaired cellular immunity and AIDS. HISTORY/PE KEY FACT Suspect P jiroveci pneumonia in any HIV patient who presents with a nonproductive cough and dyspnea. n n n Presents with dyspnea on exertion, fever, a nonproductive cough, tachypnea, weight loss, fatigue, and impaired oxygenation. Typically, symptoms have been present for weeks. Can also present as disseminated disease or as local disease in other organ systems. The differential includes TB, histoplasmosis, and coccidioidomycosis. DIAGNOSIS n n Liposomal amphotericin B followed by itraconazole. The patient has clinical features of disseminated histoplasmosis (fever, malaise, weight loss, pancytopenia, hepatosplenomegaly, palatal ulcers). Diagnosed by cytology of induced sputum or bronchoscopy specimen with silver stain and immunofluorescence (see Figure 2.8-13A). Obtain an ABG to check PaO2. CXR may show diffuse, bilateral interstitial infiltrates with a ground-glass appearance (see Figure 2.8-13B), but any presentation is possible. TREATMENT n n Treat with high-dose TMP-SMX × 21 days. A prednisone taper should be used in patients with moderate to severe hypoxemia (PaO2 < 70 mm Hg or an arterial-alveolar oxygen gradient > 35). CYT OM E G ALOVI R U S (C M V) Seventy percent of adults in the United States have been infected with CMV, and most are asymptomatic; reactivation generally occurs in immunocompromised patients. INFECTIOUS DISEASE A HIGH-YIELD FACTS IN 197 B FIGURE 2.8-13. Pneumocystis pneumonia. (A) Lung tissue stained with silver uncovers folded cysts containing comma-shaped spores. (B) Frontal CXR shows diffuse “ground-glass” lung opacities characteristic of PCP in this patient with AIDS and a CD4+ count of 26. (Image A reproduced with permission from Ryan KJ, Ray CG. Sherris Medical Microbiology, 5th ed. New York: McGraw-Hill, 2010, Fig. 459. Image B reproduced with permission from USMLERx.com.) n n Transmission occurs via sexual contact, breast milk, respiratory droplets in nursery or day care facilities, and blood transfusions. Risk factors for reactivation include the first 100 days status post tissue or bone marrow transplant and HIV/AIDS (CD4+ < 100/mm3 or viral load > 10,000). HISTORY/PE n n Systemic infection may resemble EBV mononucleosis (see the discussion of infectious mononucleosis). Specific manifestations include the following: n CMV retinitis: Associated with retinal detachment (“pizza pie” retinopathy); presents with floaters and visual field changes (CD4+ < 50/ mm3). n GI and hepatobiliary involvement: Can present with multiple nonspecific GI symptoms, including bloody diarrhea. CMV, microsporidia, and cryptosporidia have been implicated in the development of AIDS cholangiopathy. n CMV pneumonitis: Presents with cough, fever, and sparse sputum production; associated with a high mortality rate. Much more common in patients with hematologic malignancies and transplant patients than in those with AIDS. n CNS involvement: Can include polyradiculopathy, transverse myelitis, and subacute encephalitis (CD4+ < 50/mm3; periventricular calcifications). DIAGNOSIS Virus isolation, culture, tissue histopathology, serum PCR. TREATMENT Treat with ganciclovir or foscarnet. Treat underlying disease if the patient is immunocompromised. KEY FACT Treat CMV infection with ganciclovir. 198 HIGH-YIELD FACTS IN INFECTIOUS DISEASE MYC OBAC TE R I U M AVI U M COM PLE X (M AC ) Ubiquitous organisms causing pulmonary and disseminated infection in several demographic groups. The 1° pulmonary form occurs in apparently healthy nonsmokers (Lady Windermere syndrome); a 2° pulmonary form affects patients with preexisting pulmonary disease such as COPD, TB, or CF. Disseminated infection occurs in AIDS patients with a CD4+ < 50/mm3. HISTORY/PE n n n Disseminated M avium infection in AIDS is associated with fever, weakness, and weight loss in patients who are not on HAART or chemoprophylaxis for MAC. Hepatosplenomegaly and lymphadenopathy are occasionally seen. Adrenal insufficiency is possible in the setting of adrenal infiltration. DIAGNOSIS n n n Obtain mycobacterial blood cultures (" in 2–3 weeks). Labs show anemia, hypoalbuminemia, and ↑ serum alkaline phosphatase and LDH. Biopsy of bone marrow, intestine, or liver reveals foamy macrophages with acid-fast bacilli. Typical granulomas may be absent in immunocompromised patients. TREATMENT Treat with clarithromycin and consider HAART if drug-naïve. Ethambutol +/− rifabutin is second line. Continue for > 12 months and until CD4+ is > 100/mm3 for > 6 months. PREVENTION Weekly azithromycin for those with a CD4+ < 50/mm3 or AIDS-defining opportunistic infection. TOX OP LAS M OS I S Risk factors include ingesting raw or undercooked meat and changing cat litter. HISTORY/PE n n n KEY FACT Ring-enhancing lesions in patients with AIDS should always prompt consideration of toxoplasmosis and CNS lymphoma. 1° infection is usually asymptomatic. Reactivated toxoplasmosis occurs in immunosuppressed patients and may present in specific organs (brain, lung, and eye > heart, skin, GI tract, and liver). Encephalitis is common in seropositive AIDS patients. Classically, CNS lesions present with fever, headache, altered mental status, seizures, and focal neurologic deficits. DIAGNOSIS n n Serology, PCR (indicates exposure and risk for reactivation); tissue examination for histology, isolation of the organism in mice, or tissue culture. In the setting of CNS involvement, obtain a CT scan (look for multiple isodense or hypodense ring-enhancing mass lesions) or an MRI (has a predilection for the basal ganglia; more sensitive). INFECTIOUS DISEASE HIGH-YIELD FACTS IN 199 TREATMENT n n Induction with high-dose PO pyrimethamine + sulfadiazine and leucovorin (a folic acid analog to prevent hematologic toxicity) × 4–8 weeks; maintenance with a low-dose regimen until the disease has resolved clinically and radiographically. TMP-SMX (Bactrim DS) or pyrimethamine + dapsone can be used for prophylaxis in patients with a CD4+ count < 100/mm3 and a " toxoplasmosis IgG. Sexually Transmitted Diseases (STDs) CH LA M Y D IA The most common bacterial STD in the United States. Caused by Chlamydia trachomatis, which can infect the genital tract, urethra, anus, and eye. Risk factors include unprotected sexual intercourse and new or multiple partners. Often coexists with or mimics N gonorrhoeae infection (known as nongonococcal urethritis when gonorrhea is absent). LGV serovars of Chlamydia cause lymphogranuloma venereum, an emerging cause of proctocolitis. KEY FACT Chlamydia infection is a common cause of nongonococcal urethritis in men. HISTORY/PE n n n n Infection is often asymptomatic in men and may present with urethritis, mucopurulent cervicitis, or PID. Examination may reveal cervical/adnexal tenderness in women or penile discharge and testicular tenderness in men. The differential includes gonorrhea, endometriosis, PID, orchitis, vaginitis, and UTI. Lymphogranuloma venereum presents in its 1° form as a painless, transient papule or shallow ulcer. In its 2° form, it presents as painful swelling of the inguinal nodes, and in its 3° form it can present as an “anogenital syndrome” (anal pruritus with discharge, rectal strictures, rectovaginal fistula, and elephantiasis). KEY FACT Chlamydia species cause arthritis, neonatal conjunctivitis, pneumonia, nongonococcal urethritis/PID, and lymphogranuloma venereum. DIAGNOSIS n n n Diagnosis is usually clinical; culture is the gold standard. Urine tests (nucleic acid amplification tests) are a rapid means of detection, whereas DNA probes and immunofluorescence (for gonorrhea/chlamydia) take 48–72 hours. Gram stain of urethral or genital discharge may show PMNs but no bacteria (intracellular). TREATMENT n n Doxycycline × 7 days or azithromycin once. Use azithromycin or amoxicillin in pregnant patients. Treat sexual partners, and maintain a low threshold to treat for N gonorrhoeae. LGV serovars require prolonged therapy for 21 days. COMPLICATIONS n Chronic infection and pelvic pain, Reiter’s syndrome (urethritis, conjunctivitis, arthritis), Fitz-Hugh–Curtis syndrome (perihepatic inflammation and fibrosis). A 27-year-old male with HIV presents to his primary care physician with fever, night sweats, weight loss, and diarrhea. Today his CD4+ count is 25 cells/mm3. A CBC is performed and is significant for anemia (a hemoglobin level of 8 mg/dL). Other labs show hypoalbuminemia and elevated alkaline phosphatase. What could have prevented this patient’s condition? 200 HIGH-YIELD FACTS IN INFECTIOUS DISEASE n Ectopic pregnancy/infertility can result from PID (in women) and epididymitis (in men). G ONOR R HE A A gram-! intracellular diplococcus that can infect almost any site in the female reproductive tract. Infection in men tends to be limited to the urethra. HISTORY/PE n n Presents with a greenish-yellow discharge, pelvic or adnexal pain, and swollen Bartholin’s glands. Men experience a purulent urethral discharge, dysuria, and erythema of the urethral meatus. The differential includes chlamydia, endometriosis, pharyngitis, PID, vaginitis, UTI, salpingitis, and tubo-ovarian abscess. DIAGNOSIS n n KEY FACT Gram stain and culture is the gold standard for any site (pharynx, cervix, urethra, or anus). Nucleic acid amplification tests can be sent on penile/ vaginal tissue or from urine. Disseminated disease may present with monoarticular septic arthritis, rash, and/or tenosynovitis. TREATMENT n Treat for both gonorrhea and chlamydia in light of the high prevalence of coinfection. n Ceftriaxone IM or cefixime PO. Also treat for presumptive chlamydia coinfection with doxycycline or a macrolide. Condoms are effective prophylaxis. Treat the sexual partner or partners if possible. Fluoroquinolones should not be used because of emerging resistance. Disseminated disease requires IV ceftriaxone for at least 24 hours. COMPLICATIONS Persistent infection with pain; infertility; tubo-ovarian abscess with rupture; disseminated gonococcal infection (see Figure 2.8-14). SYP HI LI S Caused by Treponema pallidum, a spirochete. AIDS can accelerate the course of disease progression. HISTORY/PE n n Azithromycin. The patient has signs and symptoms of disseminated Mycobacterium avium complex. HIV-infected patients with CD4+ counts < 50 cells/mm3 should receive prophylaxis against MAC with azithromycin once a week. n 1° (10–90 days after infection): Presents with a painless ulcer (chancre; see Figure 2.8-15). 2° (4–8 weeks after chancre): Presents with low-grade fever, headache, malaise, and generalized lymphadenopathy with a diffuse, symmetric, asymptomatic (nonpruritic) maculopapular rash on the soles and palms. Highly infective 2° eruptions include mucous patches or condylomata lata (see Figure 2.8-16). Meningitis, hepatitis, nephropathy, and eye involvement may also be seen. n Early latent (period from resolution of 1° or 2° syphilis to the end of the first year of infection): No symptoms; " serology. n Late latent (period of asymptomatic infection beyond the first year): No symptoms; " or ! serology. One-third of cases progress to 3° syphilis. 3° (late manifestations appearing 1–20 years after initial infection): Presents with destructive, granulomatous gummas. Neurosyphilis includes INFECTIOUS DISEASE FIGURE 2.8-14. Disseminated gonococcal infection. Hemorrhagic, painful pustules are seen on erythematous bases. (Reproduced with permission from Wolff K et al. Fitzpatrick’s Dermatology in General Medicine, 7th ed. New York: McGraw-Hill, 2008, Fig. 205-4.) HIGH-YIELD FACTS IN 201 FIGURE 2.8-15. 1° syphilis. The chancre is an ulcerated papule with a smooth, clean base; raised, indurated borders; and scant discharge. (Reproduced with permission from Bondi EE. Dermatology: Diagnosis and Therapy, 1st ed. Stamford, CT: Appleton & tabes dorsalis (posterior column degeneration), meningitis, and Argyll Robertson pupil (constricts with accommodation but not reactive to light). Cardiovascular findings include dilated aortic root, aortitis, aortic root aneurysms, and aortic regurgitation. DIAGNOSIS n n n Table 2.8-8 summarizes relevant diagnostic tests. VDRL false "s are seen with Viruses (mononucleosis, HSV, HIV, hepatitis), Drugs/IV drug use, Rheumatic fever/Rheumatoid arthritis, and SLE/ Leprosy. Neurosyphilis should be suspected and ruled out in patients with AIDS, neurologic symptoms, and a " RPR. TREATMENT n n n 1°/2°: Benzathine penicillin IM × 1 day. Tetracycline or doxycycline × 14 days may be used for patients with penicillin allergies. Pregnant patients who are penicillin allergic and have " antibody titers must be desensitized and treated with penicillin. Latent infection: Treat with benzathine penicillin. Give 1 dose for early latent infection; give a weekly dose × 3 weeks for late latent infection or for asymptomatic infection of unknown duration. Neurosyphilis: Treat with penicillin IV × 10–14 days; penicillin-allergic patients should be desensitized prior to therapy. TA B L E 2 . 8 - 8 . Lange, 1991: 394.) KEY FACT Syphilis is the “great imitator” because its dermatologic findings resemble those of many other diseases. KEY FACT Remember that treatment of syphilis can result in an acute flulike illness known as the Jarisch-Herxheimer reaction. Diagnostic Tests for Syphilis TEST COMMENTS Dark-field microscopy Identifies motile spirochetes (only 1° and 2° lesions). VDRL/RPR Nontreponemal tests. Rapid and cheap, but sensitivity is only 75–85% in 1° disease. Many false "s. Used for screening and quantitative measurement. FTA-ABS, TP-PA, MHA-TP, Treponemal tests. Sensitive and specific. Used as TP-EIA confirmatory tests. FIGURE 2.8-16. Condylomata lata. Typical appearance of the verrucous, heaped-up lesions of condylomata lata. (Reproduced with permission from Tintinalli JE et al. Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 7th ed. New York: McGraw-Hill, 2011, Fig. 248-7.) 202 HIGH-YIELD FACTS IN INFECTIOUS DISEASE GE NI T AL LE S I ONS See Table 2.8-9 for a description of common sexually transmitted genital lesions along with an outline of their diagnosis and treatment. TA B L E 2 . 8 - 9 . Sexually Transmitted Genital Lesions KLEBSIELLA GRANULOMATISa VARIABLE Lesion (GRANULOMA HAEMOPHILUS DUCREYI HSV-1 OR INGUINALE) (CHANCROID) HSV-2b HPVc Papule becomes a Papule or pustule Vesicle (3–7 days Papule (condylomata beefy-red ulcer with (chancroid; see postexposure). acuminata; warts). a characteristic rolled Figure 2.8-17). TREPONEMA PALLIDUM Papule (chancre). edge of granulation tissue. Appearance Raised red lesions Irregular, deep, well Regular, red, shallow Irregular, pink Regular, red, round, with a white border. demarcated, necrotic. ulcer. or white, raised; raised. cauliflower. Number 1 or multiple 1–3 Multiple Multiple Single Size 5–10 mm 10–20 mm 1–3 mm 1–5 mm 1 cm Pain No Yes Yes No No Concurrent Granulomatous Inguinal Malaise, myalgias, Pruritus. Regional signs and ulcers. lymphadenopathy. and fever with vulvar burning and pruritus. symptoms Diagnosis adenopathy. Clinical exam, biopsy Difficult to culture; Tzanck smear shows Clinical exam; biopsy Spirochetes seen (Donovan bodies). diagnosis is made on multinucleated giant for confirmation. under dark-field clinical grounds. cells; viral cultures; microscopy; DFA or serology. T pallidum identified by serum antibody test. Treatmentd Doxycycline or Azithromycin or Acyclovir, famciclovir, Cryotherapy, laser, azithromycin. ceftriaxone. or valacyclovir for 1° or excision; topical infection. agents such as podophyllotoxin, imiquimod, or trichloroacetic acid. a Previously known as Calymmatobacterium granulomatis. b Some 85% of genital herpes lesions are caused by HSV-2. c HPV serotypes 6 and 11 are associated with genital warts; types 16, 18, and 31 are associated with cervical cancer. d For all, treat sexual partners. Penicillin IM. INFECTIOUS DISEASE HIGH-YIELD FACTS IN 203 Genitourinary Infections URI N A R Y T R A C T I N F E CT IO N S (U TI s) Affect females more frequently than males, and " E coli cultures are obtained in 80% of cases. See the mnemonic SEEKS PP for other pathogens. Risk factors include the presence of catheters or other urologic instrumentation, anatomic abnormalities (eg, BPH, vesicoureteral reflux), previous UTIs or pyelonephritis, DM, recent antibiotic use, immunosuppression, and pregnancy. HISTORY/PE n n n Present with dysuria, urgency, frequency, suprapubic pain, and hematuria. Children may present with bedwetting, poor feeding, recurrent fevers, and foul-smelling urine. The differential includes vaginitis, STDs, urethritis or acute urethral syndrome, and prostatitis. Chancroid. Multiple, painful ulcers are seen. (Reproduced FIGURE 2.8-17. with permission from Wolff K, Johnson RA. Fitzpatrick’s Color Atlas & Synopsis of Clinical Dermatology, 6th ed. DIAGNOSIS n n n n Diagnosed by clinical symptoms. In the absence of symptoms, treatment is warranted only for children, patients with anatomical GU tract anomalies, pregnant women, those with instrumented urinary tracts, patients scheduled for GU surgery, and renal transplant patients. Urine dipstick/UA: ↑ leukocyte esterase (a marker of WBCs) is 75% sensitive and up to 95% specific. ↑ nitrites (a marker of bacteria), ↑ urine pH (Proteus infections), and hematuria (seen with cystitis) are also commonly seen. Microscopic analysis: Pyuria (> 5 WBCs/hpf) and bacteriuria (1 organism/hpf = 106 organisms/mL) are suggestive. Urine culture: The gold standard is > 105 CFU/mL. TREATMENT n n n n n Uncomplicated UTI: Treat on an outpatient basis with PO TMP-SMX or a fluoroquinolone × 3 days, or nitrofurantoin × 5 days. The use of fluoroquinolones should be reserved for severe symptoms in light of resistance and MRSA selection. Complicated UTI (urinary obstruction, men, renal transplant, catheters, instrumentation): Administer the same antibiotics as above, but for 7–14 days. Pregnant patients: Treat asymptomatic bacteruria or symptomatic UTI with nitrofurantoin or amoxicillin × 3–7 days. Avoid fluoroquinolones. Confirm clearance with a posttreatment urine culture. Urosepsis: Patients with urosepsis should be hospitalized and initially treated with IV antibiotics. Consider broader coverage to include resistant GNRs or enterococcus. Prophylactic antibiotics may be given to women with uncomplicated recurrent UTIs. Check for prostatitis in men. P Y E LO N EPH R I T IS Nearly 85% of community-acquired cases of pyelonephritis result from the same pathogens that cause cystitis. Cystitis and pyelonephritis have similar risk factors. New York: McGraw-Hill, 2009, Fig. 30-28.) MNEMONIC Common UTI bugs— SEEKS PP Serratia E coli Enterobacter Klebsiella pneumoniae Staphylococcus saprophyticus Pseudomonas Proteus mirabilis A 45-year-old woman presents to the ER with fever, chills, nausea, vomiting, and severe flank pain. She has a history of multiple UTIs and was recently hospitalized for pyelonephritis. UA reveals pyuria and bacteriuria. Ultrasound performed in the ER shows what appears to be a perinephric abscess. What is the next most appropriate step in management? 204 HIGH-YIELD FACTS IN KEY FACT INFECTIOUS DISEASE HISTORY/PE n Pyelonephritis is the most common serious medical complication of pregnancy. Twenty to thirty percent of patients with untreated bacteriuria will develop pyelonephritis. n Signs and symptoms are similar to those of cystitis but show evidence of upper urinary tract disease. Symptoms include flank pain, fever/chills, and nausea/vomiting. Dysuria, frequency, and urgency are also possible. DIAGNOSIS n n n UA and culture: Results are similar to those of cystitis, but with WBC casts. Send blood cultures to rule out urosepsis. CBC: Reveals leukocytosis. Imaging: In general, imaging is not necessary. Patients who relapse or do not respond to therapy within 48–72 hours should be evaluated by ultrasound or CT for obstruction, abscess, and other complications of pyelonephritis. TREATMENT n KEY FACT n When in doubt, admit a patient with pyelonephritis and administer IV antibiotics. For mild cases, patients may be treated on an outpatient basis for 7–14 days. Fluoroquinolones are first-line therapy. Encourage ↑ PO fluids and monitor closely. Admit and administer IV antibiotics to patients who have serious medical complications or systemic symptoms, are pregnant, present with severe nausea and vomiting, or have suspected bacteremia. Fluoroquinolones, third- or fourth-generation cephalosporins, β-lactam/β-lactamase inhibitors, and carbapenem may be used depending on disease severity. Hematologic Infections SE P S I S KEY FACT Urosepsis should be considered in any elderly patient with altered mental status. Defined as the presence of systemic inflammatory response syndrome (SIRS) with a documented infection induced by microbial invasion or toxins in the bloodstream. Severe sepsis refers to sepsis with end-organ dysfunction due to poor perfusion. Septic shock refers to sepsis with hypotension and organ dysfunction from vasodilation. Examples include the following: n n n n n n Admit the patient for empiric broadspectrum antibiotics. This patient has complicated pyelonephritis and therefore needs to be initially managed as an inpatient. Antibiotic therapy can subsequently be narrowed and converted to PO as patient circumstances permit. n Gram-" shock (eg, staphylococci and streptococci) 2° to fluid loss caused by exotoxins. Gram-! shock (eg, E coli, Klebsiella, Proteus, and Pseudomonas) 2° to vasodilation caused by endotoxins (lipopolysaccharide). Neonates: GBS, E coli, Listeria monocytogenes, H influenzae. Children: H influenzae, pneumococcus, meningococcus. Adults: Gram-" cocci, aerobic gram-! bacilli, anaerobes (dependent on the presumed site of infection). IV drug users/indwelling lines: S aureus, coagulase-! Staphylococcus species. Asplenic patients: Pneumococcus, H influenzae, meningococcus (encapsulated organisms). HISTORY/PE n Presents with abrupt onset of fever and chills, altered mental status, tachycardia, and tachypnea. Severe sepsis may lead to end-organ dysfunction such as renal or hepatic failure. Hypotension occurs in cases of septic shock. INFECTIOUS DISEASE n n Septic shock is typically a warm shock with warm skin and extremities. This contrasts with cardiogenic shock, which typically presents with cool skin and extremities. Petechiae, ecchymoses, or abnormal coagulation tests suggest DIC (2–3% of cases). DIAGNOSIS n n n n A clinical diagnosis. Labs show leukocytosis or leukopenia with ↑ bands, thrombocytopenia (50% of cases), evidence of ↓ tissue perfusion (↑ creatinine, ↑ LFTs, ↑ lactate), and abnormal coagulation studies (↑ INR). It is critical to obtain cultures of all appropriate sites (eg, blood, sputum, CSF, wound, urine). Imaging (CXR, CT) may aid in establishing the etiology or site of infection. HIGH-YIELD FACTS IN 205 KEY FACT SIRS = 2 or more of the following: 1. Temperature: Either < 35°C or > 38.5°C (ie, hypothermia or fever). 2. Tachypnea: > 20 breaths per minute or PaCO2 < 32 mm Hg on ABG. 3. Tachycardia: Heart rate > 90 bpm. 4. Leukocytosis/leukopenia: WBC count < 4000 cells/mm3 or > 12,000 cells/mm3. TREATMENT n n n ICU admission may be required. Treat aggressively with IV fluids, empiric antibiotics (based on the likely source of infection), and vasopressors. Treat underlying factors (eg, remove Foley catheter or infected lines). The 1° goal is to maintain BP and perfuse end organs. MA LA R I A A protozoal disease caused by 4 strains of the genus Plasmodium (P falciparum, vivax, ovale, malariae) and transmitted by the bite of an infected female Anopheles mosquito. P falciparum has the highest morbidity and mortality, occasionally within 24 hours of symptom onset. Travelers to endemic areas should take chemoprophylaxis and use mosquito repellent and bed nets to minimize exposure. KEY FACT Consider malaria in the differential for any patient who has emigrated from or recently traveled to tropical locations and presents with fever. HISTORY/PE n n n Patients have a history of exposure in a malaria-endemic area, with periodic attacks of sequential chills, fever (> 41°C, or > 105.8°F), and diaphoresis occurring over 4–6 hours. Splenomegaly often appears 4 or more days after symptom onset. Patients are often asymptomatic between attacks, which recur every 2–3 days depending on the Plasmodium strain. Severely ill patients may present with hyperpyrexia, prostration, impaired consciousness, agitation, hyperventilation, and bleeding. The presence of rash, skin ulcer, eosinophilia, lymphadenopathy, neck stiffness, or photophobia suggests a different or additional diagnosis. DIAGNOSIS n n n n Timely diagnosis of the correct strain is essential because P falciparum can be fatal and is often resistant to standard chloroquine treatment. Giemsa- or Wright-stained thick and thin blood films should be sent for expert microscopic evaluation to determine the species as well as the degree of parasitemia (see Figure 2.8-18). CBC usually demonstrates normochromic, normocytic anemia with reticulocytosis. If resources allow, more sensitive serologic tests are available, including rapid antigen detection methods, fluorescent antibody methods, and PCR. KEY FACT P vivax, P ovale, and P malariae can all cause symptoms months to years after the initial infection. KEY FACT Obtain a fingerstick in a patient with malaria and mental status changes to rule out hypoglycemia. KEY FACT Nearly all malaria-endemic countries now have chloroquine-resistant malaria. 206 HIGH-YIELD FACTS IN INFECTIOUS DISEASE TREATMENT n n n FIGURE 2.8-18. Plasmodium falciparum hyperparasitemia in the thin smear of a patient with cerebral malaria. (Courtesy of Dr. S. Glenn, Public Health Image Library, Centers for Disease Control and Prevention, Atlanta, GA, as published in Levinson W. Review of Medical Microbiology and Immunology, 11th ed. New York: McGraw-Hill, 2010, Fig. 52-2.) n COMPLICATIONS Cerebral malaria, severe hemolytic anemia, renal impairment, noncardiogenic pulmonary edema, hypoglycemia, lactic acidosis, acute hepatopathy, gram-! bacteremia. I NF E CTI OU S M ONONU C LE OS I S KEY FACT Cerebral malaria presents with headache, a change in mental status, neurologic signs, retinal hemorrhages, convulsions, and delirium. If left untreated, it may rapidly progress to coma and death. KEY FACT A young adult who presents with the triad of fever, sore throat, and lymphadenopathy may have infectious mononucleosis. KEY FACT Most commonly occurs in young adult patients; usually due to acute EBV infection. Transmission most often occurs through exchange of body fluids, most commonly saliva. HISTORY/PE n n n n Presents with fever and pharyngitis. Fatigue invariably accompanies initial illness and may persist for 3–6 months. Examination may reveal lowgrade fever, generalized lymphadenopathy (especially posterior cervical), tonsillar exudate and enlargement, palatal petechiae, a generalized maculopapular rash, splenomegaly, and bilateral upper eyelid edema. Patients who present with pharyngitis as their 1° symptom may be misdiagnosed with streptococcal pharyngitis (30% of patients with infectious mononucleosis are asymptomatic carriers of GAS in their oropharynx). The differential also includes CMV, toxoplasmosis, HIV, HHV-6, other causes of viral hepatitis, and lymphoma. Most patients with mononucleosis who are given ampicillin for suspected streptococcal pharyngitis develop a prolonged, pruritic maculopapular rash. DIAGNOSIS n The lymphocytosis in EBV infection is predominantly due to B-cell proliferation, but the atypical cells are T lymphocytes. Uncomplicated malarial infection can be treated orally. Chloroquine has been the standard antimalarial medication, but increasing resistance often necessitates the use of other medications. In cases of P vivax, P ovale, or an unknown strain, primaquine is added to eradicate the hypnozoites in the liver. Severe infections can be treated with parenteral antimalarial medications (IV quinidine) with transition to oral regimens as tolerated. Symptoms can be treated with supportive care. Mefloquine is the first-line chemoprophylaxis against chloroquine-resistant malaria. n n n Diagnosed by the heterophil antibody (Monospot) test (may be ! in the first few weeks after symptoms begin). EBV-specific antibodies can be ordered in patients with suspected mononucleosis and a ! Monospot test. Infectious mononucleosis syndromes that are Monospot ! and EBV-antibody ! are most often due to CMV infection. Acute HIV and other viral etiologies should be considered. CBC with differential often reveals mild thrombocytopenia with relative lymphocytosis and > 10% atypical T lymphocytes. CMP usually reveals mildly elevated transaminases, alkaline phosphatase, and total bilirubin. TREATMENT Treatment is mostly supportive, as there is no effective antiviral therapy. Corticosteroids are indicated for airway compromise due to tonsillar enlargement, severe thrombocytopenia, or severe autoimmune hemolytic anemia. INFECTIOUS DISEASE HIGH-YIELD FACTS IN 207 COMPLICATIONS n n n n n n CNS infection: Can present as aseptic meningitis, encephalitis, meningoencephalitis, cranial nerve palsies (particularly CN VII), optic and peripheral neuritis, transverse myelitis, or Guillain-Barré syndrome. Splenic rupture: Occurs in < 0.5% of cases. More common in males, and presents with abdominal pain, referred shoulder pain, or hemodynamic compromise. Upper airway obstruction: Treat with steroids. Bacterial superinfection: Many patients develop a 2° streptococcal pharyngitis. Fulminant hepatic necrosis: More common in males; the most common cause of death in affected males. Autoimmune hemolytic anemia: Occurs in 2% of patients during the first 2 weeks. Coombs ". Mild anemia lasts 1–2 months. Treat with corticosteroids if severe. KEY FACT Many patients with infectious mononucleosis have coexisting streptococcal pharyngitis that requires treatment. Fever F EV E R O F UN K N O WN O R IG I N ( F U O) A temperature of > 38.3°C (> 100.9°F) of at least 3 weeks’ duration that remains undiagnosed following 3 outpatient visits or 3 days of hospitalization. HISTORY/PE Presents with fever, headache, myalgia, and malaise. The differential includes the following: n n n n n Infectious: TB, endocarditis (eg, HACEK organisms; see the discussion of infective endocarditis), occult abscess, osteomyelitis, catheter infections. In HIV patients, consider MAC, histoplasmosis, CMV, or lymphoma. Neoplastic: Lymphomas, leukemias, hepatic and renal cell carcinomas. Autoimmune: Still’s disease, SLE, cryoglobulinemia, polyarteritis nodosa, connective tissue disease, granulomatous disease (including sarcoidosis). Miscellaneous: Pulmonary emboli, alcoholic hepatitis, drug fever, familial Mediterranean fever, factitious fever. Undiagnosed (10–15%). DIAGNOSIS n n n Confirm the presence of fever and take a detailed history, including family, social, sexual, occupational, dietary, exposures (pets/animals), and travel. Labs: Obtain a CBC with differential, ESR, serum protein electrophoresis, multiple blood cultures, sputum Gram stain and culture, UA and culture, and PPD. Specific tests (ANA, RF, CK, viral cultures, viral serologies/antigen tests) can be obtained if an infectious or autoimmune etiology is suspected. Imaging: Obtain a CXR. CT of the chest, abdomen, and pelvis should be done early in the workup of a true FUO. Invasive testing (marrow/liver biopsy) is generally low yield. Laparoscopy and colonoscopy are higher yield as second-line tests (after CT). TREATMENT Stop unnecessary medications. Patients with FUO and a completely ! workup have a good prognosis, with fevers resolving over months to years. KEY FACT Overall, infections and cancer account for the majority of cases of FUO (> 60%). Autoimmune diseases account for ~ 15%. In the elderly, rheumatic diseases account for onethird of cases. KEY FACT FUO patients without other symptoms do not require empiric antibiotic therapy. A 17-year-old male presents with 1 week of fever, sore throat, and progressive fatigue. Physical examination reveals palatal petechiae, large tonsils with whitish exudates, splenomegaly, and cervical and axillary lymphadenopathy. The patient says that he has been too tired to attend football practices and is concerned that he may lose his spot on the starting roster. What is the most appropriate advice to be given regarding his participation in athletics? 208 HIGH-YIELD FACTS IN INFECTIOUS DISEASE NE UT R OP E NI C F E VE R n n n n Defined as a single oral temperature of ≥ 38.3°C (≥ 101°F) or a temperature of ≥ 38.0°C (≥ 100.4°F) for ≥ 1 hour in a neutropenic patient (ie, an absolute neutrophil count < 500 cells/mm3). Hx/PE: Common in cancer patients undergoing chemotherapy (neutropenic nadir 7–10 days postchemotherapy). Inflammation may be minimal or absent. Dx: n Conduct a thorough physical examination, but avoid a rectal examination in light of the bleeding risk if the patient is thrombocytopenic. n Obtain a CBC with differential, serum creatinine, BUN, and transaminases; send blood, urine, lesion, sputum, and stool cultures. Consider testing for viruses, fungi, and mycobacteria. n CXR for patients with respiratory symptoms; CT scan to evaluate for abscesses or other occult infection. Tx: Empiric antibiotic therapy. Admission and IV antibiotics are warranted for high-risk patients (eg, hematologic malignancy, chemotherapy, neutropenia > 14 days). Routine use of colony-stimulating factors is not indicated. If fevers persist after 72 hours despite antibiotic therapy, start antifungal treatment. Tick-Borne Infections LYM E D I S E AS E KEY FACT n Lyme disease is the most common vector-borne disease in North America. n KEY FACT Lyme arthritis can be very subtle and minimally inflammatory, and it can wax and wane. n Tell the patient to refrain from contact sports until his physical examination normalizes. Splenomegaly 2° to infectious mononucleosis puts him at ↑ risk for splenic rupture. KEY FACT Lyme arthritis can be very subtle and minimally inflammatory, and it can wax and wane. n A tick-borne disease caused by the spirochete Borrelia burgdorferi. Usually seen during the summer months, and carried by Ixodes ticks on whitetailed deer and white-footed mice. Endemic to the Northeast, northern Midwest, and Pacific coast. Hx/PE: Presents with the onset of rash with fever, malaise, fatigue, headache, myalgias, and/or arthralgias. Infection usually occurs after a tick feeds for > 18 hours. n 1° (early localized disease): Erythema migrans begins as a small erythematous macule or papule that is found at the tick-feeding site and expands slowly over days to weeks. The border may be macular or raised, often with central clearing (“bull’s eye”; see Figure 2.8-19). n 2° (early disseminated disease): Presents with migratory polyarthropathies, neurologic phenomena (eg, Bell’s palsy), meningitis and/or myocarditis, and conduction abnormalities (third-degree heart block). n 3° (late disease): Arthritis and subacute encephalitis (memory loss and mood change). Dx: n ELISA and Western blot: Use the Western blot to confirm a " or indeterminate ELISA. A " ELISA denotes exposure but is not specific for active disease. Western blots sent without ELISA have high false-" rates. n Tissue culture/PCR: Extremely difficult to obtain; not routinely done. Tx: n Treat early disease with doxycycline (or amoxicillin in children < 8 years of age and in pregnant patients); more advanced disease (eg, CNS or arthritic disease) should be treated with ceftriaxone. n Consider empiric therapy for patients with the characteristic rash, arthralgias, or a tick bite acquired in an endemic area. Prevent with tick bite avoidance. INFECTIOUS DISEASE HIGH-YIELD FACTS IN 209 Erythema chronicum migrans seen in Lyme disease. Note the classic “bull’s eye” lesion, which consists of an outer ring where the spirochetes are found, an inner ring of clearing, and central erythema due to an allergic response at the site of the tick bite. FIGURE 2.8-19. (Courtesy of James Gathany, Public Health Image Library, Centers for Disease Control and Prevention, Atlanta, GA, as published in McPhee SJ et al. Current Medical Diagnosis & Treatment 2010. New York: McGraw-Hill, 2010, Plate 32.) RO CK Y M O U N T A I N S P OT T E D F E VE R n n n n A disease caused by Rickettsia rickettsii and carried by the American dog tick (Dermacentor variabilis). The organism invades the endothelial lining of capillaries and causes small vessel vasculitis. Hx/PE: Presents with headache, fever, malaise, and rash. The characteristic rash is initially macular (beginning on the wrists and ankles) but becomes petechial/purpuric as it spreads centrally (see Figure 2.8-20). Altered mental status or DIC may develop in severe cases. Dx: Clinical diagnosis should be confirmed with biopsy and indirect immunofluorescence of the skin lesion. Tx: Doxycycline or chloramphenicol (for pregnant women). The condition can be rapidly fatal if left untreated. If clinical suspicion is high, begin treatment while awaiting testing. Prevent by avoiding tick bites. MNEMONIC With fever and rash, think— Tiny GERMS Typhoid fever Gonococcemia Endocarditis Rocky Mountain spotted fever Meningococcemia Sepsis (bacterial) KEY FACT Rocky Mountain spotted fever starts on the wrists and ankles and then spreads centrally. Infections of the Eyes and Ears IN F E C T I O U S C O N JU N CTI V I T IS A common complaint in the ER setting, inflammation of the conjunctiva is most often bacterial or viral but can also be fungal, parasitic, allergic, or chemical. It is essential to differentiate potentially vision-threatening infectious etiologies from allergic or other causes of conjunctivitis, as well as to identify other vision-threatening conditions that may mimic conjunctivitis. Table 2.8-10 lists the common etiologies of infectious conjunctivitis. A 70-year-old female with a history of hypertension and lymphoma presents with nausea, vomiting, and fever for the past 2 days. She just underwent her second cycle of high-dose chemotherapy. She has a temperature of 38.5°C (101.3°F). Her CXR is unchanged, and her WBC count is 900 with 25% neutrophils. After urine and blood cultures have been sent, what is the next step in management? 210 HIGH-YIELD FACTS IN INFECTIOUS DISEASE FIGURE 2.8-20. Rocky Mountain spotted fever. These erythematous macular lesions will evolve into a petechial rash that will spread centrally. (Reproduced with permission from Wolff K, Johnson RA. Fitzpatrick’s Color Atlas & Synopsis of Clinical Dermatology, 6th ed. New York: McGraw-Hill, 2009, Fig. 26-1.) OR BI TAL CE LLU LI TI S KEY FACT Orbital cellulitis can be distinguished from preseptal cellulitis by the following clinical features: restricted eye movements, ↓ visual acuity, diplopia, and proptosis. n n n KEY FACT n Neisseria conjunctivitis is an ocular emergency often requiring inpatient parenteral antibiotic therapy. Commonly due to infection of the paranasal sinuses; can lead to endophthalmitis and blindness. Usually caused by streptococci, staphylococci (including MRSA), and H influenzae (in children). In diabetic and immunocompromised patients, the zygomycetes Mucor and Rhizopus must be included in the differential. Hx/PE: Presents with acute-onset fever, proptosis, ↓ EOM, ocular pain, and ↓ visual acuity. Look for a history of ocular trauma/surgery or sinusitis. Palatal or nasal mucosal ulceration with coexisting maxillary and/or ethmoid sinusitis suggests mucormycosis or Rhizopus. Dx: Mostly clinical. Blood and tissue fluid culture; CT scan (to rule out orbital abscess and intracranial involvement). Tx: n Admit and give immediate IV antibiotics; request an ophthalmologic/ENT consult. n Abscess formation or a worsening condition may necessitate surgery. n Diabetic and immunocompromised patients should be treated with amphotericin B and surgical debridement (often associated with cavernous sinus thrombosis) if Mucor or Rhizopus is diagnosed. O TI TI S E XTE R NA n Admit the patient and begin IV antibiotics with an antipseudomonal β-lactam (eg, cefepime, piperacillintazobactam, meropenem, imipenem). Febrile, neutropenic patients who are on high-dose chemotherapy, have a hematologic malignancy, or have been neutropenic for > 14 days should be admitted for empiric IV antibiotics. n n An inflammation of the external auditory canal, also known as “swimmer’s ear.” Pseudomonas and Enterobacteriaceae are the most common etiologic agents. Both grow in the presence of excess moisture. Hx/PE: Presents with pain, pruritus, and possible purulent discharge. Examination reveals pain with movement of the tragus/pinna (unlike otitis media) and an edematous and erythematous ear canal. See the Pediatrics chapter for a discussion of otitis media. Dx: A clinical diagnosis. Obtain a culture for severe or refractory cases. Order a CT scan if the patient is toxic appearing. INFECTIOUS DISEASE TA B L E 2 . 8 - 10 . HIGH-YIELD FACTS IN 211 Common Causes of Infectious Conjunctivitis PATHOGEN CHARACTERISTICS DIAGNOSIS TREATMENT BACTERIAL Staphylococci, Foreign body sensation, purulent Gram stain and culture if Antibiotic drops/ointment. streptococci, discharge. severe. An emergency! Corneal involvement Gram stain shows gram-! IM ceftriaxone, PO ciprofloxacin or can lead to perforation and intracellular diplococci. ofloxacin. Inpatient treatment if Haemophilus, Pseudomonas, Moraxella N gonorrhoeae complicated. blindness. C trachomatis A–C Recurrent epithelial keratitis Giemsa stain, chlamydial Azithromycin, tetracycline, or in childhood; trichiasis, corneal cultures. erythromycin × 3–4 weeks. scarring, and entropion. The leading cause of preventable blindness worldwide. VIRAL Adenovirus (most Copious watery discharge, severe Contagious; self-limited. Topical common) ocular irritation, preauricular corticosteroids with supervision by an lymphadenopathy. Occurs in ophthalmologist. epidemics. n Tx: Clean the ear and give antibiotic and steroid eardrops. Add systemic antibiotics in patients with severe disease, immunodeficiency, or diabetes. Elderly diabetics and immunocompromised individuals are at risk for necrotizing otitis externa and may require IV antibiotics. KEY FACT Diabetics are at risk for malignant otitis externa. Miscellaneous Infections KEY FACT IN F E C T I V E EN D O C A R D I T IS Infection of the endocardium. Most commonly affects the heart valves, especially the mitral valve. Risk factors include rheumatic, congenital, or valvular heart disease; prosthetic heart valves; IV drug abuse; and immunosuppression. Etiologies are as follows (see also Table 2.8-11): n n n n n S aureus: The causative agent in > 80% of cases of acute bacterial endocarditis in patients with a history of IV drug abuse. Viridans streptococci: The most common pathogens for left-sided subacute bacterial endocarditis and following dental procedures in native valves. Coagulase-! Staphylococcus: The most common infecting organism in prosthetic valve endocarditis. Streptococcus bovis: S bovis endocarditis is associated with coexisting GI malignancy. Candida and Aspergillus species: Account for most cases of fungal endocarditis. Predisposing factors include long-term indwelling IV catheters, malignancy, AIDS, organ transplantation, and IV drug use. Otitis media should not cause pain with movement of the tragus/pinna. 212 HIGH-YIELD FACTS IN TA B L E 2 . 8 - 11 . INFECTIOUS DISEASE Causes of Endocarditis CULTURE-! (INCLUDES ACUTE S aureus (IV drug SUBACUTE MARANTIC Cancer (poor prognosis) Viridans streptococci Mets seed valves; emboli (native valve) abuse) HACEK) Haemophilus parainfluenzae S pneumoniae Enterococcus can cause cerebral Actinobacillus N gonorrhoeae S epidermidis (prosthetic infarcts Cardiobacterium valve) SLE Libman-Sacks endocarditis (autoantibody to valve) Eikenella S bovis (GI insult) Kingella Fungi Coxiella burnetii Brucella Bartonella MNEMONIC Presentation of endocarditis— HISTORY/PE n n JR = NO FAME Janeway lesions Roth’s spots Nail-bed (splinter) hemorrhage Osler’s nodes Fever Anemia Murmur Emboli n Constitutional symptoms are common (fever/FUO, weight loss, fatigue). Examination reveals a heart murmur. The mitral valve (mitral regurgitation) is more commonly affected than the aortic valve in non–IV drug users; more right-sided involvement is found in IV drug users (tricuspid valve > mitral valve > aortic valve). Osler’s nodes (small, tender nodules on the finger and toe pads), Janeway lesions (small peripheral hemorrhages; see Figure 2.8-21A), splinter hemorrhages (subungual petechiae; see Figure 2.8-21B), Roth’s spots (retinal hemorrhages), focal neurologic deficits from embolic stroke, and other embolic phenomena are also seen. A B Cutaneous manifestations of infective endocarditis. (A) Janeway lesions. Peripheral embolization to the sole leads to a cluster of erythematous macules known as Janeway lesions. (B) Splinter hemorrhages. The splinter hemorrhages shown along the distal aspect of the nail plate are due to emboli from subacute bacterial endocarditis. (Image A courtesy of FIGURE 2.8-21. the Armed Forces Institute of Pathology, Bethesda, MD, as published in Knoop KJ et al. Atlas of Emergency Medicine, 2nd ed. New York: McGraw-Hill, 2002: 384. Image B Courtesy of the Department of Dermatology, Wilford Hall USAF Medical Center and Brooke Army Medical Center, San Antonio, TX, as published in Knoop KJ et al. Atlas of Emergency Medicine, 2nd ed. New York: McGraw-Hill, 2002: 384.) INFECTIOUS DISEASE HIGH-YIELD FACTS IN 213 DIAGNOSIS n n Diagnosis is guided by risk factors, clinical symptoms, and the Duke criteria (see Table 2.8-12). The presence of 2 major, 1 major + 3 minor, or 5 minor criteria all merit the diagnosis of endocarditis. CBC with leukocytosis and left shift; ↑ ESR and CRP. TREATMENT n n Early empiric IV antibiotic treatment for acutely ill patients. Vancomycin is an appropriate choice for most patients. Tailor antibiotics once the causative agent is known. Acute valve replacement is sometimes necessary. The prognosis for prosthetic valve endocarditis is poor. Give antibiotic prophylaxis before dental work in patients with high-risk valvular disease (eg, those with previous endocarditis or a prosthetic valve). 1 A 41-year-old female returns to the ER a week after she was discharged for DKA treatment. Today she complains of low-grade fever, tenderness and swelling over her face, and a persistent nasal discharge with occasional blood. Physical examination demonstrates necrosis in the left nasal turbinates and left eye proptosis. Specimens from the sinuses show broad, nonseptate hyphae. What is the next most appropriate step in management? AN TH R A X Caused by the spore-forming gram-" bacterium Bacillus anthracis. Infection is an occupational hazard for veterinarians, farmers, and individuals who handle animal wool, hair, hides, or bone meal products. Also a biological weapon. B anthracis can cause cutaneous (most common), inhalation (most deadly), or GI anthrax. There is no person-to-person spread of anthrax. HISTORY/PE n n Cutaneous: Presents 1–7 days after skin exposure and penetration of spores. The lesion begins as a pruritic papule that enlarges to form an ulcer surrounded by a satellite bulbus/lesion with an edematous halo and a round, regular, raised edge. Regional lymphadenopathy is also characteristic. The lesion evolves into a black eschar within 7–10 days (see Figure 2.8-22). Inhalational: Presents with fever, dyspnea, hypoxia, hypotension, or symptoms of pneumonia (1–3 days after exposure), classically due to hemorrhagic mediastinitis. Patients typically do not have pulmonary infiltrates. TA B L E 2 . 8 - 12 . An 11-year-old African American male with a history of multiple hospitalizations for pain crises, all related to his sickle cell anemia, presents with fever and severe pain in his right hand. Examination shows an area of redness, tenderness, and swelling near the right second metatarsal. Labs show leukocytosis and an elevated ESR. MRI shows an area of ↑ intensity in the painful area. What pathogen is the most likely cause of his condition? Duke Criteria for the Diagnosis of Endocarditis CRITERIA Major 2 COMPONENTS At least 2 separate " blood cultures for a typical organism, persistent bacteremia with any organism, or a single " culture of Coxiella burnetii. Evidence of endocardial involvement (via transesophageal echocardiography or new murmur). Minor Predisposing risk factors. Fever ≥ 38.3°C (≥ 100.9°F). Vascular phenomena: Septic emboli, septic infarcts, mycotic aneurysm, Janeway lesions. Immunologic phenomena: Glomerulonephritis, Osler’s nodes. Roth’s spots. Microbiological evidence that does not meet major criteria. FIGURE 2.8-22. Cutaneous anthrax. Black eschar is seen on the fore- arm. (Courtesy of Dr. James H. Steele, Public Health Image Library, Centers for Disease Control and Prevention, Atlanta, GA, as published in Levinson W. Review of Medical Microbiology and Immunology, 11th ed. New York: McGraw-Hill, 2010, Fig. 5.) 214 HIGH-YIELD FACTS IN 1 Surgical debridement and amphotericin B. The patient has mucormycosis, a dangerous and aggressive infection found in diabetic and immunocompromised patients. Aggressive surgical debridement is warranted. INFECTIOUS DISEASE n GI: Occurs after the ingestion of poorly cooked, contaminated meat; can present with dysphagia, nausea/vomiting, bloody diarrhea, and abdominal pain. DIAGNOSIS Criteria for diagnosis include culture isolation or 2 nonculture supportive tests (PCR, immunohistochemical staining, or ELISA). CXR is the most sensitive test for inhalational disease (shows a widened mediastinum and pleural effusions). TREATMENT n n 2 S aureus. Salmonella is the second most common organism that causes osteomyelitis in patients with sickle cell disease and should always be considered in these patients. Ciprofloxacin or doxycycline plus 1–2 additional antibiotics for at least 14 days are first-line therapy for inhalational disease or cutaneous disease of the face, head, or neck. For other cutaneous disease, treat for 7–10 days. Postexposure prophylaxis (ciprofloxacin) to prevent inhalation anthrax should be continued for 60 days. OST E OM YE LITI S Bone or bone marrow infection 2° to direct spread from a soft tissue infection (80% of cases) is most common in adults, whereas infection due to hematogenous seeding (20% of cases) is more common in children (metaphyses of the long bones) and IV drug users (vertebral bodies). Common pathogens are outlined in Table 2.8-13. HISTORY/PE Presents with localized bone pain and tenderness along with warmth, swelling, erythema, and limited motion of the adjacent joint. Systemic symptoms (fevers, chills) and purulent drainage may be present. TA B L E 2 . 8 - 13 . Common Pathogens in Osteomyelitis IF THINK No risk factors S aureus. IV drug user S aureus or Pseudomonas. Sickle cell disease Salmonella. Hip replacement S epidermidis. Foot puncture wound Pseudomonas. Chronic S aureus, Pseudomonas, Enterobacteriaceae. Diabetic Polymicrobial, Pseudomonas, S aureus, streptococci, anaerobes. INFECTIOUS DISEASE DIAGNOSIS n n Labs: ↑ WBC count; ↑ ESR and CRP levels in most cases. Blood cultures may be ". Imaging: n X-rays are often ! initially but may show periosteal elevation within 10–14 days. Bone scans are sensitive for osteomyelitis but lack specificity. n MRI (the test of choice) will show ↑ signal in the bone marrow and associated soft tissue infection (see Figure 2.8-23). n Definitive diagnosis is made by bone aspiration with Gram stain and culture. Clinical diagnosis made by probing through the soft tissue to bone is usually sufficient, as aspiration carries a risk of infection. HIGH-YIELD FACTS IN 215 KEY FACT Osteomyelitis is associated with peripheral vascular disease, diabetes, penetrating soft tissue injuries, chronic decubitus ulcers, and IV drug abuse. TREATMENT n n Surgical debridement of necrotic, infected bone followed by IV antibiotics × 4–6 weeks. Empiric antibiotic selection is based on the suspected organism and Gram stain. Consider clindamycin plus ciprofloxacin, ampicillin/sulbactam, or oxacillin/nafcillin (for methicillin-sensitive S aureus); vancomycin (for MRSA); or ceftriaxone or ciprofloxacin (for gram-! bacteria). COMPLICATIONS Chronic osteomyelitis, sepsis, septic arthritis. Long-standing chronic osteomyelitis with a draining sinus tract may eventually lead to squamous cell carcinoma (Marjolin’s ulcer). FIGURE 2.8-23. Diskitis/osteomyelitis. Sagittal contrast-enhanced MRI shows destruction of a lower thoracic intervertebral disk with abnormal enhancement throughout the adjacent vertebral bodies (arrows) and a posterior rim-enhancing epidural abscess (arrowhead) in the spinal canal. (Reproduced with permission from Tintinalli JE et al. Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 6th ed. New York: McGraw-Hill, 2004, Fig. 305-5.) KEY FACT Diabetic osteomyelitis should be treated with antibiotics targeting gram-" organisms and anaerobes. 216 HIGH-YIELD FACTS IN INFECTIOUS DISEASE NOTES HIGH-YIELD FACTS IN MUSCULOSKELETAL Common Adult Orthopedic Injuries 218 Rheumatoid Arthritis 230 Common Peripheral Nerve Injuries 220 Scleroderma 232 Compartment Syndrome 220 Systemic Lupus Erythematosus 232 Carpal Tunnel Syndrome 221 Temporal Arteritis 233 Bursitis 222 Complex Regional Pain Syndrome 233 Tendinitis 222 Fibromyalgia 234 Low Back Pain 223 Polymyalgia Rheumatica 235 HERNIATED DISK 223 Pediatric Musculoskeletal Disorders 235 SPINAL STENOSIS 224 COMMON PEDIATRIC ORTHOPEDIC INJURIES 235 224 DUCHENNE MUSCULAR DYSTROPHY 235 Septic Arthritis 225 DEVELOPMENTAL DYSPLASIA OF THE HIP 236 Osteoarthritis 226 LEGG-CALVÉ-PERTHES DISEASE 237 SLIPPED CAPITAL FEMORAL EPIPHYSIS 238 Gout 226 SCOLIOSIS 239 Ankylosing Spondylitis 228 JUVENILE IDIOPATHIC ARTHRITIS 240 Polymyositis and Dermatomyositis 229 Osteosarcoma 217 218 HIGH-YIELD FACTS IN MUSCULOSKELETAL Common Adult Orthopedic Injuries Table 2.9-1 outlines the presentation and treatment of orthopedic injuries that commonly affect adults. TA B L E 2 . 9 - 1 . Common Adult Orthopedic Injuries INJURY Shoulder dislocation MECHANICS Anterior dislocation: Most common; the axillary nerve is at risk. Patients hold the arm in slight abduction TREATMENT Reduction followed by a sling and swath. Recurrent dislocations may need surgical treatment. and external rotation (see Figure 2.9-1). Posterior dislocation: Rare; associated with seizure and electrocutions. Patients hold the arm in adduction and internal rotation. Hip dislocation Anterior dislocation: Can injure the obturator nerve. Closed reduction followed by abduction pillow/bracing. Posterior dislocation: Most common (> 90%); occurs Evaluate with CT scan after reduction. via a posteriorly directed force on an internally rotated, flexed, adducted hip (“dashboard injury”). Associated with a risk of sciatic nerve injury and avascular necrosis (AVN) (see Figure 2.9-2). Colles’ fracture Involves the distal radius. Often results from a fall onto Closed reduction followed by application of a long-arm an outstretched hand, leading to a dorsally displaced, cast; open reduction if the fracture is intra-articular. dorsally angulated fracture. Commonly seen in the elderly (osteoporosis) and children. Scaphoid fracture The most commonly fractured carpal bone. May take 2 weeks for radiographs to show the fracture (see Figure 2.9-3). Assume a fracture if there is tenderness in the anatomical snuff box. Boxer’s fracture Fracture of the fifth metacarpal neck. Due to forward trauma of a closed fist (eg, punching a wall). Thumb spica cast. If displacement or scaphoid nonunion is present, treat with open reduction. With proximal-third scaphoid fractures, AVN may result from disruption of blood flow. Closed reduction and ulnar gutter splint; percutaneous pinning if the fracture is excessively angulated. If skin is broken, assume infection by human oral pathogens and treat with surgical irrigation, debridement, and IV antibiotics (covering Eikenella). Humerus fracture Direct trauma. May have radial nerve palsy leading to Hanging-arm cast vs. coaptation splint and sling. wrist drop and loss of thumb extension. Functional bracing. “Nightstick Ulnar shaft fracture resulting from self-defense with the Open reduction and internal fixation (ORIF) if significantly fracture” arm against a blunt object. displaced. Monteggia’s Diaphyseal fracture of the proximal ulna with subluxation ORIF of the shaft fracture and closed reduction of the fracture of the radial head. radial head. Galeazzi’s fracture Diaphyseal fracture of the radius with dislocation of the ORIF of the radius and casting of the fractured forearm in distal radioulnar joint. Results from a direct blow to the supination to reduce the distal radioulnar joint. radius. MUSCULOSKELETAL TA B L E 2 . 9 - 1 . HIGH-YIELD FACTS IN 219 Common Adult Orthopedic Injuries (continued) INJURY Hip fracture MECHANICS ↑ risk with osteoporosis. Presents with a shortened and externally rotated leg. Hip fractures can be radiographically occult, so a good TREATMENT ORIF. Displaced femoral neck fractures in elderly patients may require a hip hemiarthroplasty. Anticoagulate to ↓ the likelihood of DVTs. clinical history with ! radiographs warrants further evaluation with CT or MRI. Displaced femoral neck fractures: Associated with an ↑ risk of AVN and nonunion. Associated with DVTs. Femoral fracture Direct trauma. Beware of fat emboli, which present Intramedullary nailing of the femur. Irrigate and debride with fever, changes in mental status, dyspnea, hypoxia, open fractures. petechiae, and ↓ platelets. Tibial fracture Direct trauma. Watch for compartment syndrome. Casting vs. intramedullary nailing vs. ORIF. Open fractures An orthopedic emergency; patients must be taken to the OR urgently for irrigation and debridement; repair OR within 8–24 hours in light of the ↑ risk of infection. fracture. Treat with antibiotics and tetanus prophylaxis. Achilles tendon Presents with a sudden “pop” like a rifle shot. More likely Treat surgically followed by a long-leg cast for 6 weeks. with ↓ physical conditioning. rupture Examination shows limited plantar flexion and a " Thompson’s test (pressure on the gastrocnemius leading to absent foot plantar flexion). Knee injuries Present with knee instability and hematoma. MRI is the diagnostic test of choice. ACL: Treatment of MCL/LCL and meniscal tears can be n Result from a noncontact twisting mechanism, forced n " anterior drawer and Lachman tests. n Rule out a meniscal or MCL injury (MCL injury = " hyperextension, or impact to an extended knee. n conservative. Treatment of ACL injuries in active patients is generally surgical with graft from the patellar or hamstring tendons. valgus stress test; LCL injury = " varus stress test). Operative PCL reconstruction is reserved for highly The “classic” unhappy triad of knee injury involves competitive athletes with high-grade injuries. the ACL, the MCL, and the medial meniscus. However, Operative meniscal repair is for younger patients with lateral meniscal tears are more commonly seen in reparable tears or older patients with mechanical acute ACL injuries. symptoms who do not respond to conservative PCL: n Result from a posteriorly directed force on a flexed knee n " posterior drawer test. (eg, dashboard injury). Meniscal tears: n Result from an acute twisting injury or a degenerative n Clicking or locking may be present. n Examination shows joint line tenderness and a " tear in elderly patients. McMurray’s test. treatment. 220 HIGH-YIELD FACTS IN MUSCULOSKELETAL A B Anterior shoulder dislocation. AP (A) and scapular Y (B) radiographs of the right shoulder demonstrate anterior and inferior dislocation of the humeral head relative to the glenoid. (Reproduced with permission from USMLERx.com.) FIGURE 2.9-1. Common Peripheral Nerve Injuries Table 2.9-2 outlines the clinical findings of the most common peripheral nerve injuries. Compartment Syndrome Posterior hip dislocation. Posterior hip dislocation with FIGURE 2.9-2. concomitant fracture of the posterior wall and dome of the acetabulum. (Reproduced with permission from Doherty GM. Current Diagnosis & Treatment: Surgery, 13th ed. New York: McGraw-Hill, ↑ pressure within a confined space that compromises nerve, muscle, and soft tissue perfusion. Occurs primarily in the anterior compartment of the lower leg and forearm 2° to trauma (fracture or muscle injury) to the affected limb. HISTORY/PE n 2010, Fig. 40-13.) n KEY FACT Volkmann’s contracture of the wrist and fingers is caused by compartment syndrome, which can be associated with supracondylar humerus fractures. Presents with pain out of proportion to physical findings; pain with passive motion of the fingers and toes; and paresthesias, pallor, poikilothermia, pulselessness, and paralysis (the 6 P’s). Pulselessness occurs late, so pulses are usually detectable! DIAGNOSIS Measure compartment pressures (positive if ≥ 30 mm Hg); measure delta pressures (diastolic pressure – compartment pressure; also " if > 30 mm Hg). TREATMENT Immediate fasciotomy to ↓ pressures and ↑ tissue perfusion. MUSCULOSKELETAL HIGH-YIELD FACTS IN 221 Carpal Tunnel Syndrome (CTS) Entrapment of the median nerve at the wrist caused by ↓ size or space of the carpal tunnel, leading to paresthesias, pain, and occasionally paralysis. Can be precipitated by overuse of wrist flexors; associated with diabetes mellitus or thyroid dysfunction. Commonly occurs in pregnant and middle-aged women. HISTORY/PE n n n n n Presents with aching over the thenar area of the hand and proximal forearm. Paresthesias or numbness is seen in a median nerve distribution. Symptoms worsen at night or when the wrists are held in flexion. Examination shows thenar atrophy (if CTS is long-standing). Phalen’s maneuver and Tinel’s sign are ". FIGURE 2.9-3. Scaphoid fracture. PA radiograph of the right wrist shows a fracture (arrow) through the waist of the scaphoid. (Reproduced with permission from USMLERx.com.) DIAGNOSIS A clinical diagnosis, although EMG testing can be used to confirm. KEY FACT TREATMENT n n Splint the wrist in a neutral position at night and during the day if possible. Administer NSAIDs. Conservative treatment can include corticosteroid injection of the carpal canal. TA B L E 2 . 9 - 2 . Tinel’s sign: Tapping over a nerve elicits tingling in that nerve distribution— eg, tapping over the median nerve in the wrist elicits median nerve paresthesias. Common Peripheral Nerve Injuries CLINICAL NERVE Radial MOTOR DEFICIT SENSORY DEFICIT COMMON CAUSES Wrist extension. Dorsal forearm Humeral and hand (the fracture. FINDINGS Wrist drop. first 3 fingers). Median Carpal tunnel. Weak wrist Pronation, Palmar surface thumb (the first 3 flexion and opposition. fingers). flat thenar eminence. Ulnar Finger Palmar and Elbow abduction. dorsal surface dislocation. Claw hand. (the last 2 fingers). Axillary Abduction. Lateral Anterior shoulder. humeral — dislocation. Peroneal Dorsiflexion, Dorsal foot and eversion. lateral leg. Knee dislocation. Foot drop. A 37-year-old male is seen after a motorcycle accident. He complains of intense leg pain, tingling in his foot, and inability to move his toes. Examination reveals pain with passive motion of his toes and palpable dorsalis pedis pulses. An x-ray confirms a tibial fracture. What is the best treatment? 222 HIGH-YIELD FACTS IN MUSCULOSKELETAL n Surgical release of the carpal tunnel is a widely accepted treatment, particularly for fixed sensory loss, thenar weakness, or intolerable symptoms. COMPLICATIONS Permanent loss of sensation, hand strength, and fine motor skills. Bursitis Inflammation of the bursae by repetitive use, trauma, infection, or systemic inflammatory disease. A bursa is a flattened sac filled with a small amount of synovial fluid that serves as a protective buffer between bones and overlapping muscles. Common sites of bursitis include subacromial, olecranon, trochanteric, prepatellar, and infrapatellar bursae. HISTORY/PE Presents with localized tenderness, ↓ range of motion (ROM), edema, and erythema; patients may have a history of trauma or inflammatory disease. DIAGNOSIS Needle aspiration is indicated if septic bursitis is suspected; no labs or imaging is needed. TREATMENT n n n Conservative treatment includes rest, heat and ice, elevation, and NSAIDs. Intrabursal corticosteroid injection can be considered but is contraindicated if septic bursitis is suspected. Septic bursitis should be treated with 7–10 days of antibiotics. Tendinitis KEY FACT Oral fluoroquinolones are associated with an ↑ risk of tendon rupture and tendinitis. An inflammatory condition characterized by pain at tendinous insertions into bone associated with swelling or impaired function. It commonly occurs in the supraspinatus, biceps, wrist extensor, patellar, iliotibial band, posterior tibial, and Achilles tendons. Overuse is the most common cause. HISTORY/PE n n Presents with pain at a tendinous insertion that worsens with repetitive stress and resisted strength testing of the affected muscle group. Wrist flexor tendinitis (lateral epicondylitis, or tennis elbow) worsens with resisted extension of the wrist. DIAGNOSIS A clinical diagnosis. Consider a radiograph if there is a history of trauma. Immediate fasciotomy for compartment syndrome (within 6 hours to prevent muscle necrosis) followed by fracture stabilization. Remember that nonpalpable pulses are a late finding. TREATMENT n n n n Treat with rest and NSAIDs; apply ice for the first 24–48 hours. Consider splinting, bracing, or immobilization. Begin strengthening exercises once pain has subsided. If conservative treatment fails, consider surgical debridement. Never inject the Achilles tendon in view of the ↑ risk of rupture. Avoid repetitive injection. MUSCULOSKELETAL KEY FACT Low Back Pain (LBP) Table 2.9-3 outlines the motor, reflex, and sensory deficits with which low back pain is associated. H ER N I A T E D D I S K HISTORY/PE n n n n n Presents with sudden onset of severe, electricity-like LBP, usually preceded by several months of aching, “discogenic” pain. Common among middle-aged and older men. Exacerbated by ↑ intra-abdominal pressure or Valsalva (eg, coughing). Associated with sciatica, paresthesias, muscle weakness, atrophy, contractions, or spasms. A passive straight-leg raise ↑ pain (highly sensitive but not specific). A crossed straight-leg raise ↑ pain (highly specific but not sensitive). Large midline herniations can cause cauda equina syndrome. DIAGNOSIS n n n n Most LBP is mechanical, so bed rest is contraindicated. KEY FACT Causes include degenerative changes, trauma, or neck/back strain or sprain. Most common (95%) in the lumbar region, especially at L5–S1 (the most common site) and L4–L5 (the second most common site). n HIGH-YIELD FACTS IN 223 Red flags for LBP include age > 50, > 6 weeks of pain, a previous cancer history, severe pain, constitutional symptoms, neurologic deficits, and loss of anal sphincter tone. KEY FACT Bowel or bladder dysfunction (urinary overflow incontinence), impotence, and saddle-area anesthesia are consistent with cauda equina syndrome, which is a surgical emergency. Obtain an ESR and a plain radiograph if other causes of back pain are suspected (eg, infection, trauma, compression fracture). Order a stat MRI for cauda equina syndrome or for a severe or rapidly progressing neurologic deficit. Order an MRI if symptoms are refractory to conservative management. X-ray may show disk herniation (see Figure 2.9-4). TREATMENT n NSAIDs in scheduled doses, physical therapy, and local heat lead to resolution within 4 weeks in 80% of cases. Do not prescribe bed rest; continuation of regular activities is preferred. TA B L E 2 . 9 - 3 . Motor and Sensory Deficits in Back Pain FIGURE 2.9-4. ASSOCIATED DEFICIT NERVE ROOT L4 MOTOR Foot dorsiflexion (tibialis Disk herniation. Sagittal T2-weighted MRI of the lumbar spine shows posterior herniation of the L5–S1 disk. (Reproduced with permission from REFLEX SENSORY Patellar. Medial aspect of the lower leg. None. Dorsum of the foot and lateral Fauci AS et al. Harrison’s Principles of Internal Medicine, 17th ed. New York: McGraw-Hill, 2008, Fig. 16-4.) anterior). L5 Big toe dorsiflexion (extensor aspect of the lower leg. hallucis longus), foot eversion (peroneus muscles). S1 Plantar flexion (gastrocnemius/ soleus), hip extension (gluteus maximus). Achilles. Plantar and lateral aspects of the foot. A 55-year-old male with a history of prostate cancer presents with lower back pain and bilateral leg weakness. On examination, he is found to have point tenderness on the lumbar spine, hyperreflexia, and ↓ sensation in his legs. What is the best next step? 224 HIGH-YIELD FACTS IN MUSCULOSKELETAL n n Epidural injection or nerve block may be of benefit. Severe or rapidly evolving neurologic deficits and cauda equina syndrome are indications for surgical intervention. SP I NAL S TE NOS I S Narrowing of the lumbar or cervical spinal canal, leading to compression of the nerve roots and spinal cord. Most commonly due to degenerative joint disease; typically occurs in middle-aged or elderly patients. HISTORY/PE n n n Presents with neck pain, back pain that radiates to the arms or the buttocks and legs, and leg numbness/weakness. In lumbar stenosis, leg cramping is worse with standing and with walking. In lumbar stenosis, symptoms improve with flexion at the hips and bending forward, which relieves pressure on the nerves. DIAGNOSIS KEY FACT The most common benign bone tumor is osteochondroma. n n Radiographs show degenerative changes that include disk space narrowing, facet hypertrophy, and sometimes spondylolisthesis, leading to a narrowed spinal canal. MRI or CT shows spinal stenosis. TREATMENT KEY FACT Classic findings of Ewing’s sarcoma: a child 10–20 years of age with a multilayered “onion-skinning” finding on x-ray in the diaphyseal regions of the femur. KEY FACT Classic findings of a giant cell tumor of bone: a female 20–40 years of age presenting with knee pain and a mass, along with a “soap bubble” appearance on x-ray in the epiphyseal/metaphyseal region of long bones. n n n Mild to moderate: NSAIDs and abdominal muscle strengthening. Advanced: Epidural corticosteroid injections can provide relief. Refractory: Surgical laminectomy may achieve significant short-term success, but many patients will have a recurrence of symptoms. Osteosarcoma The second most common 1° malignant tumor of bone (after multiple myeloma). Tends to occur in the metaphyseal regions of the distal femur, proximal tibia, and proximal humerus; often metastasizes to the lungs. Risk factors include male gender and age 20–30. HISTORY/PE n n n n Presents as progressive and eventually intractable pain that worsens at night. Constitutional symptoms such as fever, weight loss, and night sweats may be present. Erythema and enlargement over the site of the tumor may be seen. See the Endocrinology chapter for a discussion of osteosarcoma vs. Paget’s disease. DIAGNOSIS Give steroids to relieve spinal cord compression resulting from likely bone metastasis. MRI is the best study, but preventing permanent neurologic disability is more important at this time. Remember to consider multiple myeloma, which presents almost identically. n n Radiographs can show Codman’s triangle (periosteal new-bone formation at the diaphyseal end of the lesion) or a “sunburst pattern” of the osteosarcoma (see Figure 2.9-5)—in contrast to the multilayered “onion skinning” that is classic for Ewing’s sarcoma and the “soap bubble” appearance of giant cell tumor of bone (see Figure 2.9-6). MRI and CT of the chest facilitate staging (soft tissue and bony invasion) and planning for surgery. MUSCULOSKELETAL A HIGH-YIELD FACTS IN 225 B Malignant bone tumors. (A) Osteosarcoma. Femoral radiograph shows the typical “sunburst” appearance of osteosarcoma (arrows). (B) Ewing’s sarcoma. The characteristic “onion skinning” of Ewing’s sarcoma (arrowhead) is evident in the proximal femur in this radiograph of the left hip. (Reproduced with permission from Kantarjian HM et al. MD Anderson Manual of Medi- FIGURE 2.9-5. cal Oncology, 1st ed. New York: McGraw-Hill, 2006, Fig. 33-7A and B.) TREATMENT n n Limb-sparing surgical procedures and pre- and postoperative chemotherapy (eg, methotrexate, doxorubicin, cisplatin, ifosfamide). Amputation may be necessary. Septic Arthritis An infection of the joint space that can occur after open injury or bacteremia. Prosthetic joints greatly ↑ the risk. Rheumatoid arthritis (RA) and osteoarthritis (OA) are also risk factors (see below). Bacteremia from endocarditis and IV drug use is also a major risk factor. HISTORY/PE Presents as a warm, red, immobile joint. Palpable effusions may also be present. Fevers and chills can be seen if the patient is bacteremic. DIAGNOSIS n n n The best test is joint aspiration. A WBC count > 80,000 mm3, a " Gram stain, or a " fluid culture all point to septic arthritis. The most common organisms are Staphylococcus, Streptococcus, and gram-! rods. TREATMENT Empirically treat with ceftriaxone and vancomycin until cultures come back; then modify therapy for specific organisms. Septic joints are treated with surgical debridement or serial aspirations. Giant cell tumor of the bone. Note the “soap bubble” ap- FIGURE 2.9-6. pearance at the proximal end of the tibia. The distal end of the femur (not shown) is another common location. (Reproduced with permission from Skinner HB. Current Diagnosis & Treatment in Orthopedics, 4th ed. New York: McGrawHill, 2006, Fig. 6-25.) 226 HIGH-YIELD FACTS IN MUSCULOSKELETAL Osteoarthritis (OA) A common, chronic, noninflammatory arthritis of the synovial joints. Characterized by deterioration of the articular cartilage and osteophyte bone formation at the joint surfaces. Risk factors include a " family history, obesity, and a history of joint trauma. Table 2.9-4 contrasts OA with RA. HISTORY/PE KEY FACT Heberden’s nodes: DIP enlargement. Bouchard’s nodes: PIP enlargement. Presents with crepitus, ↓ ROM, and initially pain that worsens with activity and weight bearing but improves with rest. Morning stiffness generally lasts for < 30 minutes. Stiffness is also experienced after periods of rest (“gelling”). DIAGNOSIS n n n Radiographs show joint space narrowing, osteophytes, subchondral sclerosis, and subchondral bone cysts (see Figure 2.9-7). Radiograph severity does not correlate with symptomatology. Synovial fluid shows straw-colored fluid, normal viscosity, and a WBC count < 2000 cells/µL. Laboratory tests, including inflammatory markers, are typically normal. TREATMENT n n Physical therapy, weight reduction, and NSAIDs. Intra-articular corticosteroid injections may provide temporary relief. Consider joint replacement (eg, total hip/knee arthroplasty) in advanced cases. Gout KEY FACT In a child with gout and inexplicable injuries, consider Lesch-Nyhan syndrome. Recurrent attacks of acute monoarticular arthritis resulting from intraarticular deposition of monosodium urate crystals due to disorders of urate metabolism. Risk factors include male gender, obesity, postmenopausal status in females, and binge drinking. TA B L E 2 . 9 - 4 . Osteoarthritis vs. Rheumatoid Arthritis VARIABLE History OSTEOARTHRITIS RHEUMATOID ARTHRITIS Affects the elderly; has slow Affects the young; presents with onset. Pain worsens with use. morning stiffness that improves with use. Joint involvement Affects the DIP, PIP, hips, and Affects the wrists, MCP, ankles, knees. knees, shoulders, hips, and elbows. Has a symmetrical distribution. Synovial fluid analysis and imaging WBC count < 2000 cells/µL; osteophytes. Joint space narrowing is seen on x-ray. Anti–cyclic citrullinated peptide (anti-CCP) antibodies. MUSCULOSKELETAL HIGH-YIELD FACTS IN 227 FIGURE 2.9-7. Osteoarthritis. Plain radiographs show joint space narrowing, osteophytes, and subchondral degenerative cysts involving the DIP and PIP joints, with sparing of the MCP. (Reproduced with permission from USMLERx.com.) HISTORY/PE n n n n n Presents with excruciating joint pain of sudden onset. Most commonly affects the first MTP joint (podagra) and the midfoot, knees, ankles, and wrists; the hips and shoulders are generally spared. Joints are erythematous, swollen, and exquisitely tender. Tophi (urate crystal deposits in soft tissue) may be seen with chronic disease (see Figure 2.9-8). Uric acid kidney stones are seen with chronic disease. Tophaceous gout. Note the slowly enlarging nodule of the right second toe in a 55-year-old alcoholic, hypertensive male on HCTZ. (Reproduced with permission from USMLERx. FIGURE 2.9-8. com.) KEY FACT Gout crystals appear yeLLow when paraLLel to the condenser. 228 HIGH-YIELD FACTS IN MUSCULOSKELETAL DIAGNOSIS KEY FACT n Causes of hyperuricemia: n ↑ cell turnover (hemolysis, blast crisis, tumor lysis, myelodysplasia, psoriasis) n Cyclosporine n Dehydration n Diabetes insipidus n Diet (eg, ↑ red meat, alcohol) n Diuretics n Lead poisoning n Lesch-Nyhan syndrome n Salicylates (low dose) n Starvation n n n TREATMENT n n KEY FACT Colchicine inhibits neutrophil chemotaxis and is most effective when used early during a gout flare. However, it can cause diarrhea and bone marrow suppression (neutropenia). Joint fluid aspirate shows needle-shaped, negatively birefringent crystals (vs. pseudogout; see Table 2.9-5). An elevated WBC count in the joint aspirate or peripheral blood may be seen during flares. Serum uric acid is usually ↑ (≥ 7.5 mg/dL), but patients may have normal levels. Punched-out erosions with overhanging cortical bone (“rat-bite” erosions) are seen in advanced gout. n Acute attacks: n High-dose NSAIDs (eg, indomethacin) are first line. Colchicine may also be used but is inferior to NSAIDs. n Steroids are used when NSAIDs are ineffective or contraindicated, as in renal disease. Maintenance therapy: n Allopurinol for overproducers, those with contraindications to probenecid treatment (tophi, renal stones, chronic kidney disease), and refractory cases; probenecid for undersecreters. n Allopurinol can ↓ the incidence of acute urate nephropathy. Weight loss and avoidance of triggers of hyperuricemia will prevent recurrent attacks in many patients. Avoid alcohol consumption. Ankylosing Spondylitis A chronic inflammatory disease of the spine and pelvis that leads to fusion of the affected joints. Strongly associated with HLA-B27. Risk factors include male gender and a " family history. HISTORY/PE n n n TA B L E 2 . 9 - 5 . Typical onset is in the late teens and early 20s. Presents with fatigue, intermittent hip pain, and LBP that worsens with inactivity and in the mornings. ↓ spine flexion (" Schober test), loss of lumbar lordosis, hip pain and stiffness, and ↓ chest expansion are seen as the disease progresses. Anterior uveitis and heart block may occur. Gout vs. Pseudogout DISORDER Gout HISTORY PHYSICAL FINDINGS Male, binge drinking, The first big toe is acute onset afterward. affected. Pseudogout (calcium Hemochromatosis or The wrists and knees are pyrophosphate hyperparathyroidism. affected. deposition disease [CPPD]) CRYSTAL SHAPE CRYSTAL BIREFRINGENCE Needle shaped. ! Rhomboid. " MUSCULOSKELETAL n Other forms of seronegative spondyloarthropathy must be ruled out, including the following: n Reactive arthritis (formerly known as Reiter’s syndrome): A disease of young men. The characteristic arthritis, uveitis, conjunctivitis, and urethritis usually follow an infection with Campylobacter, Shigella, Salmonella, Chlamydia, or Ureaplasma. n Psoriatic arthritis: An oligoarthritis that can include the DIP joints. Associated with psoriatic skin changes and sausage-shaped digits (dactylitis). X-rays show a classic “pencil in cup” deformity. n Enteropathic spondylitis: An ankylosing spondylitis–like disease characterized by sacroiliitis that is usually asymmetric and is associated with IBD. HIGH-YIELD FACTS IN 229 KEY FACT Reactive arthritis: “Can’t see (uveitis), can’t pee (urethritis), can’t climb a tree (arthritis).” DIAGNOSIS n n n n " HLA-B27 is found in 85–95% of cases. Radiographs may show fused sacroiliac joints, squaring of the lumbar vertebrae, development of vertical syndesmophytes, and bamboo spine (see Figure 2.9-9). ESR or CRP is ↑ in 75% of cases. ! RF; ! ANA. TREATMENT n n NSAIDs (eg, indomethacin) for pain; exercise to improve posture and breathing. Tumor necrosis factor (TNF) inhibitors or sulfasalazine can be used in refractory cases. Polymyositis and Dermatomyositis Polymyositis is a progressive, systemic connective tissue disease characterized by immune-mediated striated muscle inflammation. Dermatomyositis presents with symptoms of polymyositis plus cutaneous involvement, although the pathogenesis is different. Most often affect patients 50–70 years of age; the male-to-female ratio is 1:2. African Americans are affected more often than Caucasians. Ankylosing spondylitis. Frontal view of the thoracolumbar FIGURE 2.9-9. spine shows the classic “bamboo” appearance of the spine, which results from fusion of the vertebral bodies and posterior elements. (Reproduced with permission from Chen MY et al. Basic Radiology, 2nd ed. New York: McGrawHill, 2011, Fig. 7-45.) HISTORY/PE n n n Distinguished as follows: n Polymyositis: Presents with symmetric, progressive proximal muscle weakness, pain, and difficulty breathing or swallowing (advanced disease). n Dermatomyositis: Patients may have a heliotrope rash (a violaceous periorbital rash), “shawl sign” (a rash involving the shoulders, upper chest, and back), and/or Gottron’s papules (a papular rash with scales located on the dorsa of the hands, over bony prominences). Patients may also develop myocarditis and cardiac conduction deficits. Can be associated with an underlying malignancy, especially lung and breast carcinoma. DIAGNOSIS n n ↑ serum CK and anti-Jo-1 antibodies are seen (see Table 2.9-6). Muscle biopsy reveals inflammation and muscle fibers in varying stages of necrosis and regeneration. A 49-year-old male presents with a painful, swollen big toe after a night of heavy drinking. His home medications are lansoprazole, ASA, sildenafil, and psyllium. Which medication should he temporarily discontinue? 230 HIGH-YIELD FACTS IN MUSCULOSKELETAL Common Antibodies and Their Disease Associations TA B L E 2 . 9 - 6 . ANTIBODY DISEASE ASSOCIATION ANA SLE Anti-CCP RA Anticentromere CREST syndrome Anti-dsDNA SLE Antihistone Drug-induced SLE Anti-Jo-1 Polymyositis/dermatomyositis Antimitochondrial Primary biliary cirrhosis Antinuclear Scleroderma Anti-Scl-70 Scleroderma Anti-Sm SLE Anti–smooth muscle Autoimmune hepatitis Antitopoisomerase I Scleroderma Anti-TSHR Graves’ disease c-ANCA Vasculitis, especially Wegener’s p-ANCA Vasculitis, microscopic polyangiitis Rheumatoid factor RA U1RNP antibody Mixed connective tissue disease TREATMENT n n High-dose corticosteroids with taper after 4–6 weeks to ↓ the maintenance dose. Azathioprine and/or methotrexate can be used as steroid-sparing agents. Rheumatoid Arthritis (RA) ASA (aspirin). This patient is having an acute gout attack, and ASA can cause ↓ excretion of uric acid by the kidney. A systemic autoimmune disorder characterized by chronic, destructive, inflammatory arthritis with symmetric joint involvement that results in synovial hypertrophy and pannus formation, ultimately leading to erosion of adjacent cartilage, bone, and tendons. Risk factors include female gender, age 35–50, and HLA-DR4. MUSCULOSKELETAL HISTORY/PE n n n n Presents with insidious onset of morning stiffness for > 1 hour along with painful, warm swelling of multiple symmetric joints (wrists, MCP joints, ankles, knees, shoulders, hips, and elbows) for > 6 weeks. Fever, fatigue, malaise, anorexia, and weight loss may also be seen. In late cases, ulnar deviation of the fingers is seen with MCP joint hypertrophy (see Figure 2.9-10A). Also presents with ligament and tendon deformations (eg, swan-neck and boutonnière deformities), vasculitis, atlantoaxial subluxation (intubation risk), and keratoconjunctivitis sicca. DIAGNOSIS n n Labs: n ↑ RF (IgM antibodies against Fc IgG) is seen in > 75% of cases. n The presence of anti-CCP antibodies is more specific than RF. n ↑ ESR may also be seen. n Anemia of chronic disease is common. n Synovial fluid aspirate shows turbid fluid, ↓ viscosity, and an ↑ WBC count (3000–50,000 cells/µL). Radiographs: n Early: Soft tissue swelling and juxta-articular demineralization. n Late: Symmetrical joint space narrowing and erosions (see Figure 2.910B). TREATMENT n n NSAIDs (can be ↓ or discontinued following successful treatment with disease-modifying antirheumatic drugs [DMARDs]). DMARDs should be started early and include methotrexate (the best initial DMARD to start with), hydroxychloroquine, and sulfasalazine. Second-line agents include TNF inhibitors, rituximab (anti-CD20), and leflunomide. A HIGH-YIELD FACTS IN 231 KEY FACT Keratoconjunctivitis sicca 2° to Sjögren’s syndrome is a common ocular manifestation of RA. KEY FACT Felty’s syndrome is characterized by RA, splenomegaly, and neutropenia. KEY FACT The DIP joint is spared in RA but is involved in OA. KEY FACT Hydroxychloroquine causes retinal toxicity. B Rheumatoid arthritis. (A) Note the typical ulnar deviation of the MCP joints and swelling of the MCP and PIP joints. Multiple subcutaneous rheumatoid nodules are also seen. (B) Hand radiograph shows symmetric erosions and joint space narrowing involving the MCP (arrow), carpal (arrowhead), and radioulnar (curved arrow) joints. Ulnar deviation at the MCP joint is also noted. (Image A FIGURE 2.9-10. reproduced with permission from Wolff K et al. Fitzpatrick’s Dermatology in General Medicine, 7th ed. New York: McGraw-Hill, 2008, Fig. 161-1A. Image B reproduced with permission from USMLERx.com.) 232 HIGH-YIELD FACTS IN MUSCULOSKELETAL MNEMONIC CREST syndrome: Calcinosis Raynaud’s phenomenon Esophageal dysmotility Sclerodactyly Telangiectasias Scleroderma Also called systemic sclerosis; characterized by inflammation that leads to progressive tissue fibrosis through excessive deposition of type I and type III collagen. Commonly manifests as CREST syndrome (limited form), but can also occur in a diffuse form involving the skin as well as the GI, GU, renal, pulmonary, and cardiovascular systems. Risk factors include female gender and age 35–50. HISTORY/PE n n n Examination may reveal symmetric thickening of the skin of face and/or distal extremities. CREST syndrome involves Calcinosis, Raynaud’s phenomenon, Esophageal dysmotility, Sclerodactyly, and Telangiectasias. The diffuse form can lead to pulmonary fibrosis, cor pulmonale, acute renal failure, and malignant hypertension. DIAGNOSIS n n n n RF and ANA may be ". Anticentromere antibodies are specific for CREST syndrome (see Table 2.9-6). Anti-Scl-70 (antitopoisomerase 1) antibodies are associated with diffuse disease and a poor prognosis (see Table 2.9-6). Eosinophilia may be seen. TREATMENT n n n Corticosteroids for acute flares; penicillamine can be used for skin changes. Calcium channel blockers for Raynaud’s phenomenon. ACEIs for renal disease and for prevention of a scleroderma renal crisis. COMPLICATIONS Mortality is due to pulmonary hypertension and complications of pulmonary hypertension. MNEMONIC Systemic Lupus Erythematosus (SLE) Criteria for SLE— DOPAMINE RASH Discoid rash Oral ulcers Photosensitivity Arthritis Malar rash Immunologic criteria Neurologic symptoms (lupus cerebritis, seizures) Elevated ESR Renal disease ANA " Serositis (pleural or pericardial effusion) Hematologic abnormalities A multisystem autoimmune disorder related to antibody-mediated cellular attack and deposition of antigen-antibody complexes. African American women are at highest risk. Usually affects women of childbearing age. HISTORY/PE n n Presents with nonspecific symptoms such as fever, anorexia, weight loss, and symmetric joint pain. The mnemonic DOPAMINE RASH summarizes the criteria for diagnosing SLE (see also Figure 2.9-11). Patients with 4 of the criteria are likely to have SLE (96% sensitive and specific). DIAGNOSIS n A " ANA is highly sensitive but not specific. Anti-dsDNA and anti-Sm antibodies are highly specific but not as sensitive (see Table 2.9-6). MUSCULOSKELETAL HIGH-YIELD FACTS IN 233 Drug-induced SLE: " antihistone antibodies are seen in 100% of cases but are nonspecific. n Neonatal SLE: Associated with " anti-Ro antibodies transmitted from mother to neonate. The following may also be seen: n Antiphospholipid antibodies. n Anemia, leukopenia, and/or thrombocytopenia. n Proteinuria and/or casts. n n TREATMENT n n n NSAIDs for mild joint symptoms. Corticosteroids for acute exacerbations. Corticosteroids, hydroxychloroquine, cyclophosphamide, and azathioprine can be used for progressive or refractory cases. A few have specific uses: n Hydroxychloroquine: Can be used for isolated skin and joint involvement. n Cyclophosphamide: Used for severe cases of lupus nephritis. Be sure to get a renal biopsy for patients with nephritic symptoms! Temporal Arteritis Also called giant cell arteritis; due to subacute granulomatous inflammation of the large vessels, including the aorta, external carotid (especially the temporal branch), and vertebral arteries. The most feared manifestation is blindness 2° to occlusion of the central retinal artery (a branch of the internal carotid artery). Risk factors include polymyalgia rheumatica (affects almost half of patients), age > 50, and female gender. HISTORY/PE n n Presents with new headache (unilateral or bilateral); scalp pain and temporal tenderness; and jaw claudication. Fever, permanent monocular blindness, weight loss, and myalgias/ arthralgias (especially of the shoulders and hips) are also seen. DIAGNOSIS n n n ESR > 50 (usually > 100) mm/hr. Ophthalmologic evaluation. Temporal artery biopsy: Look for thrombosis; necrosis of the media; and lymphocytes, plasma cells, and giant cells. TREATMENT n n Begin high-dose prednisone immediately to prevent ocular involvement (or involvement of the remaining eye after onset of monocular blindness). Obtain a biopsy, but do not delay treatment. Conduct a follow-up eye exam. Complex Regional Pain Syndrome A pain syndrome accompanied by loss of function and autonomic dysfunction, usually occurring after trauma. The disease has 3 phases: acute/ traumatic → dystrophic phase → atrophic phase. FIGURE 2.9-11. SLE. The malar rash of SLE is a red-to-purple, continuous plaque extending across the bridge of the nose and to both cheeks. (Reproduced with permission from Bondi EE. Dermatology: Diagnosis and Therapy, 1st ed. Stamford, CT: Appleton & Lange, 1991: 395.) KEY FACT Libman-Sacks endocarditis: Noninfectious vegetations often seen on the mitral valve in association with SLE and antiphospholipid syndrome. KEY FACT SLE can cause a " VDRL or RPR test! KEY FACT SLE and RA both affect the MCP and PIP joints; the difference is that SLE is nondeforming. 234 HIGH-YIELD FACTS IN MUSCULOSKELETAL HISTORY/PE n n n n n Diffuse pain occurs out of proportion to the initial injury, often in a nonanatomic distribution. Pain can occur at any time relative to the initial injury. Loss of function of the affected limb is seen. Sympathetic dysfunction occurs and may be documented by skin, soft tissue, or blood flow changes. Skin temperature, hair growth, and nail growth may ↑ or ↓. Edema may be present. DIAGNOSIS A clinical diagnosis, but objective evidence of changes in skin temperature, hair growth, or nail growth may be present. TREATMENT n n n n Medications include NSAIDs, corticosteroids, low-dose TCAs, gabapentin, pregabalin, and calcitonin (no oral medications are consistently effective). Physical therapy modalities may be helpful. Chemical sympathetic blockade may relieve symptoms. Referral to a chronic pain specialist is appropriate for complicated cases. Fibromyalgia n n n A chronic pain disorder characterized by soft tissue and axial skeletal pain in the absence of joint pain. Inflammation is notably absent (see Table 2.9-7). Hx/PE: Most common in women 30–50 years of age; associated with depression, anxiety, sleep disorders, IBS, and cognitive disorders (“fibro fog”). Dx: Multiple (≥ 11 of 18) tender points over all 4 body quadrants and the axial skeleton must be present for diagnosis. The presence of < 11 of 18 tender points or non-fibromyalgia-associated tender points is known as myofascial pain syndrome. T A B L E 2 . 9 - 7. Fibromyalgia vs. Polymyalgia Rheumatica CHARACTERISTIC Age and sex FIBROMYALGIA Middle-aged women (30–50 years POLYMYALGIA RHEUMATICA Women > 50 years of age. of age). Location Various. Shoulder and pelvic girdle. ESR Normal. Markedly ↑ (> 100 mm/hr). Muscle Normal. Normal. Classic Anxiety, stress, point tenderness, Temporal arteritis; response to findings ! workup. steroids. Treatment Antidepressants, NSAIDs, rest. Low-dose prednisone. biopsy MUSCULOSKELETAL n Tx: Antidepressants (an SSRI/TCA combination and 2 SNRIs have proven efficacy), gabapentin, pregabalin, muscle relaxants, and physical therapy (stretching, heat application, hydrotherapy). Avoid narcotics. Polymyalgia Rheumatica n n n n Risk factors include female gender and age > 50 (see Table 2.9-7). Hx/PE: n Presents with pain and stiffness of the shoulder and pelvic girdle musculature with difficulty getting out of a chair or lifting the arms above the head. n Other symptoms include fever, malaise, and weight loss. Weakness is generally not appreciated on exam. Dx: Labs reveal a markedly ↑ ESR, often associated with anemia. Tx: Low-dose prednisone (10–20 mg/day). Pediatric Musculoskeletal Disorders C OM M O N PE D I A T R I C O R TH O P E D IC INJU R I E S Table 2.9-8 outlines the presentation and treatment of common pediatric orthopedic injuries. DU C HE N N E M U SC U LA R DY S T R O PH Y ( DM D ) An X-linked recessive disorder resulting from a deficiency of dystrophin, a cytoskeletal protein. Onset is usually at 3–5 years of age. HISTORY/PE n n n n n Affects axial and proximal muscles more than distal muscles. May present with progressive clumsiness, fatigability, difficulty standing or walking, difficulty walking on toes (gastrocnemius shortening), Gowers’ maneuver (using the hands to push off the thighs when rising from the floor), and waddling gait. Pseudohypertrophy of the gastrocnemius muscles is also seen. Mental retardation is common. Table 2.9-9 outlines the differential diagnosis of DMD and Becker muscular dystrophy. DIAGNOSIS ! dystrophin immunostain; ↑ CK. n n n EMG shows polyphasic potentials and ↑ recruitment. Muscle biopsy shows necrotic muscle fibers from degeneration and variation in fiber size with fibrosis from regeneration. TREATMENT Physical therapy is necessary to maintain ambulation and to prevent contractures. Liberal use of tendon release surgery may prolong ambulation. HIGH-YIELD FACTS IN 235 236 HIGH-YIELD FACTS IN TA B L E 2 . 9 - 8 . MUSCULOSKELETAL Orthopedic Injuries in Children INJURY Clavicular fracture MECHANICS The most commonly fractured long bone in children. TREATMENT Figure-of-eight sling vs. arm sling. May be birth related (especially in large infants); can be associated with brachial nerve palsies. Usually involves the middle third of the clavicle, with the proximal fracture end displaced superiorly owing to the pull of the sternocleidomastoid. Greenstick fracture Incomplete fracture involving the cortex of only 1 Reduction with casting. Order films at 10–14 days. side (tension side) of the bone. Nursemaid’s elbow Radial head subluxation that typically occurs as a Manual reduction by gentle supination of the elbow result of being pulled or lifted by the hand. Presents at 90 degrees of flexion. No immobilization. with pain and refusal to bend the elbow. Torus fracture Buckling of the compression side of the cortex of a Cast immobilization for 3–5 weeks. long bone 2° to trauma. Usually occurs in the distal radius or ulna. Supracondylar humerus The most common pediatric elbow fracture. Tends fracture to occur at 5–8 years of age. Proximity to the Cast immobilization; closed reduction with percutaneous pinning if significantly displaced. brachial artery ↑ the risk of Volkmann’s contracture (results from compartment syndrome of the forearm). Beware of brachial artery entrapment (remember to do a radial artery pulse test). See Figure 2.9-12. Osgood-Schlatter disease Overuse apophysitis of the tibial tubercle. Causes ↓ activity for 2–3 months or until asymptomatic. A localized pain, especially with quadriceps contraction, neoprene brace may provide symptomatic relief. in active young boys. Salter-Harris fracture Fractures of the growth plate in children. Classified Closed vs. open reduction to obtain appropriate by fracture pattern: alignment, followed by immobilization. n I: Physis (growth plate). n II: Metaphysis and physis. n III: Epiphysis and physis. n IV: Epiphysis, metaphysis, and physis. n V: Crush injury of the physis. COMPLICATIONS Mortality is due to pulmonary congestion caused by high-output cardiac failure (stemming from cardiac fibrosis). DE VE LOP M E NTAL D YS P LAS I A OF T HE HI P Also called congenital hip dislocation; can result in subluxed or dislocated femoral heads, leading to early degenerative joint disease of the hips. Dislocations result from poor development of the hip due to lax musculature and from excessive uterine packing in the flexed and adducted position (eg, MUSCULOSKELETAL TA B L E 2 . 9 - 9 . HIGH-YIELD FACTS IN 237 DMD vs. Becker Muscular Dystrophy VARIABLE DMD BECKER MUSCULAR DYSTROPHY Onset 3–5 years. 5–15 years and beyond. Life expectancy Teens. 30s–40s. Mental retardation Common. Uncommon. Western blot Dystrophin is markedly ↓ or Dystrophin levels are normal, but absent. protein is abnormal. FIGURE 2.9-12. Supracondylar humerus fracture. Radiograph of the left breech presentation), leading to excessive stretching of the posterior hip capsule and contractures. HISTORY/PE n n n n n Most commonly found in first-born females born in the breech position. Barlow’s maneuver: Posterior pressure is placed on the inner aspect of the abducted thigh, and the hip is then adducted, leading to an audible “clunk” as the femoral head dislocates posteriorly. Ortolani’s maneuver: The thighs are gently abducted from the midline with anterior pressure on the greater trochanter. A soft click signifies reduction of the femoral head into the acetabulum. Allis’ (Galeazzi’s) sign: The knees are at unequal heights when the hips and knees are flexed (the dislocated side is lower). Asymmetric skin folds and limited abduction of the affected hip are also seen. DIAGNOSIS n n n Early detection is critical to allow for proper hip development. Ultrasound may be helpful, especially after 10 weeks of age. Radiographs are unreliable until patients are > 4 months of age because of the lack of ossification of the neonatal femoral head. TREATMENT n n n n Begin treatment early. < 6 months: Splint with a Pavlik harness (maintains the hip flexed and abducted). To prevent AVN, do not flex the hips > 60 degrees. 6–15 months: Spica cast. 15–24 months: Open reduction followed by spica cast. COMPLICATIONS n n Joint contractures and AVN of the femoral head. Without treatment, a significant defect is likely in patients < 2 years of age. LEG G -CA L V É - PE R TH E S D IS E A S E Idiopathic AVN of the femoral head (see Figure 2.9-13). Most commonly found in boys 4–10 years of age. Usually a self-limited disease, with symptoms lasting < 18 months. elbow shows a medial supracondylar humerus fracture (arrow) with displacement of the distal fracture fragment (arrowhead) following trauma in a 9-year-old boy. (Reproduced with permission from USMLERx. com.) 238 HIGH-YIELD FACTS IN MUSCULOSKELETAL A A A A A FIGURE 2.9-13. B B B Legg-Calvé-Perthes disease. AVN of the femoral head. (Reproduced with permission from Skinner HB. Cur- rent Diagnosis & Treatment in Orthopedics, 2nd ed. Stamford, CT: Appleton & Lange, 2000: 543.) MNEMONIC HISTORY/PE n Differential diagnosis of pediatric limp— n STARTSS HOTT n Septic joint Tumor Avascular necrosis (Legg-Calvé-Perthes) Rheumatoid arthritis/JIA Tuberculosis Sickle cell disease SCFE Henoch-Schönlein purpura Osteomyelitis Trauma Toxic synovitis n Generally asymptomatic at first, but patients can develop a painless limp. If pain is present, it can be in the groin or anterior thigh, or it may be referred to the knee. Limited abduction and internal rotation; atrophy of the affected leg. Usually unilateral (85–90%). TREATMENT n n n Observation is sufficient if there is limited femoral head involvement or if full ROM is present. If extensive or if there is ↓ ROM, consider bracing, hip abduction with a Petrie cast, or an osteotomy. The prognosis is good if the patient is < 6 years of age and has full ROM, ↓ femoral head involvement, and a stable joint. SLI P P E D C AP I TAL F E M OR AL E P I PH YS I S (SC F E) Separation of the proximal femoral epiphysis through the growth plate, leading to inferior and posterior displacement of the femoral head relative to the femoral neck. The name is misleading because the epiphysis remains within the acetabulum while the metaphysis moves anteriorly and superiorly. Risk factors include obesity, age 11–13, male gender, and African American ethnicity. Associated with hypothyroidism and other endocrinopathies. HISTORY/PE n n n Typically presents with acute or insidious groin or knee pain and a painful limp. Acute cases present with restricted ROM and, commonly, inability to bear weight. Inability to bear weight differentiates unstable from stable SCFE. MUSCULOSKELETAL n n Bilateral in 40–50% of cases. Characterized by limited internal rotation and abduction of the hip. Flexion of the hip results in an obligatory external rotation 2° to physical displacement that is observed as further loss of internal rotation with hip flexion. DIAGNOSIS n n Radiographs of both hips in AP and frog-leg lateral views reveal posterior and inferior displacement of the femoral head (see Figure 2.9-14). In patients under the 10th percentile of height, rule out hypothyroidism with TSH. TREATMENT n n n The disease is progressive, so treatment should begin promptly. No weight bearing should be allowed until the defect is surgically stabilized. Percutaneous single-screw fixation is the most common treatment for stable SCFE. COMPLICATIONS Chondrolysis, AVN of the femoral head, and premature hip osteoarthritis leading to hip arthroplasty. SC O L IO S I S A lateral curvature of the spine > 10 degrees. It is sometimes associated with kyphosis or lordosis. Most commonly idiopathic, developing in early adolescence. Other etiologies are congenital or associated with neuromuscular, ver- FIGURE 2.9-14. Slipped capital femoral epiphysis. Frog-leg AP radiograph demonstrates medial and inferior displacement of the right femoral epiphysis (red arrow) relative to the femoral neck. In comparison, the left side (blue arrow) is normal. (Reproduced with permission from USMLERx.com.) HIGH-YIELD FACTS IN 239 240 HIGH-YIELD FACTS IN MUSCULOSKELETAL tebral, or spinal cord disease. The male-to-female ratio is 1:7 for curves that progress and require treatment. HISTORY/PE n n Idiopathic disease is usually identified during school physical screening. Vertebral and rib rotation deformities are accentuated by the Adams forward bending test. DIAGNOSIS Radiographs of the spine (posterior, anterior, and full-length views). TREATMENT n n n Close observation for < 20 degrees of curvature. Spinal bracing for 20–49 degrees of curvature in patients with remaining growth. Curvature may progress even with bracing. Surgical correction for > 50 degrees of curvature. COMPLICATIONS Severe scoliosis can create restrictive lung disease. J UVE NI LE I DI OP ATHI C AR TH R I TI S (JI A ) A nonmigratory, nonsuppurative mono- and polyarthritis with bony destruction that occurs in patients ≤ 16 years of age and lasts > 6 weeks. Formerly known as juvenile rheumatoid arthritis. Approximately 95% of cases resolve by puberty. More common in girls than in boys. HISTORY/PE n n Can be accompanied by fever, nodules, erythematous rashes, pericarditis, and fatigue. Subtypes are as follows: n Pauciarticular: An asymmetric arthritis that involves < 4 joints. Associated with an ↑ risk of iridocyclitis that leads to blindness if left untreated. n Polyarticular: Resembles RA with symmetric involvement of multiple (5 or more) small joints. Systemic features are less prominent; carries a ↓ risk of iridocyclitis. n Acute febrile (systemic, Still’s disease): The least common subtype; manifests as arthritis with daily high, spiking fevers and a maculopapular, evanescent, salmon-colored rash. Hepatosplenomegaly and serositis may also be seen. No iridocyclitis is present; remission may occur within 1 year. Occurs equally in girls and boys. DIAGNOSIS n n n There is no diagnostic test for JIA. Labs: n A " RF is found in 15% of cases. n ANA may be ", especially in the pauciarticular subtype. n ↑ ESR, WBC count, and platelets. Imaging: Soft tissue swelling and osteoporosis may be seen. TREATMENT NSAIDs or corticosteroids; methotrexate is second-line therapy. HIGH-YIELD FACTS IN NEUROLOGY Clinical Neuroanatomy 242 Vascular Disorders 243 ALZHEIMER’S DISEASE 265 STROKE 243 VASCULAR DEMENTIA 266 SUBARACHNOID HEMORRHAGE 247 FRONTOTEMPORAL DEMENTIA (PICK’S DISEASE) 266 INTRACEREBRAL HEMORRHAGE 249 NORMAL PRESSURE HYDROCEPHALUS 267 SUBDURAL HEMATOMA 250 CREUTZFELDT-JAKOB DISEASE 268 EPIDURAL HEMATOMA 251 Movement Disorders 268 251 HUNTINGTON’S DISEASE 268 PARKINSON’S DISEASE 269 Headaches MIGRAINE HEADACHE 253 Dementia 265 CLUSTER HEADACHE 253 Neoplasms 270 TENSION-TYPE HEADACHE 254 Neurocutaneous Disorders 272 CAVERNOUS SINUS THROMBOSIS 254 NEUROFIBROMATOSIS 272 255 TUBEROUS SCLEROSIS 273 Seizure Disorders PARTIAL SEIZURES 255 TONIC-CLONIC (GRAND MAL) SEIZURES 256 BROCA’S APHASIA 274 ABSENCE (PETIT MAL) SEIZURES 257 WERNICKE’S APHASIA 274 STATUS EPILEPTICUS 257 INFANTILE SPASMS (WEST SYNDROME) 258 LENNOX-GASTAUT SYNDROME Vertigo and Dizziness Aphasia 274 Coma 274 258 Nutritional Deficiencies 276 258 Ophthalmology 277 VISUAL FIELD DEFECTS 277 ACUTE PERIPHERAL VESTIBULOPATHY (LABYRINTHITIS AND VESTIBULAR NEURITIS) 259 GLAUCOMA 277 MÉNIÈRE’S DISEASE 259 CATARACTS 278 VESTIBULAR MIGRAINE 260 AGE-RELATED MACULAR DEGENERATION 278 SYNCOPE 260 RETINAL VASCULAR OCCLUSION 279 BENIGN PAROXYSMAL POSITIONAL VERTIGO Disorders of the Neuromuscular Junction MYASTHENIA GRAVIS 258 261 261 LAMBERT-EATON MYASTHENIC SYNDROME 262 MULTIPLE SCLEROSIS 262 GUILLAIN-BARRÉ SYNDROME 263 AMYOTROPHIC LATERAL SCLEROSIS 264 241 242 HIGH-YIELD FACTS IN NEUROLOGY Clinical Neuroanatomy Tables 2.10-1 through 2.10-4 and Figure 2.10-1 outline critical aspects of clinical neuroanatomy, including cranial nerve functions; the clinical presentation of common facial nerve lesions; spinal cord anatomy and functions; and pertinent clinical reflexes. TA B L E 2 . 10 - 1 . Cranial Nerve Functions NERVE CN FUNCTION TYPE MNEMONIC Olfactory I Smell Sensory Some Optic II Sight Sensory Say Oculomotor III Eye movement, pupillary constriction, lens accommodation, eyelid Motor Marry opening Trochlear IV Eye movement Motor Money Trigeminal V Mastication, facial sensation (including orbits, sinuses, tongue, teeth, Both But and buccal mucosa), intracranial sensation (including meninges and blood vessels) Abducens VI Eye movement Motor My Facial VII Facial movement, taste from the anterior two-thirds of the tongue, Both Brother lacrimation, salivation (submandibular and sublingual glands), eyelid closing Vestibulocochlear VIII Hearing, balance Sensory Says Glossopharyngeal IX Taste from the posterior third of the tongue, oropharyngeal sensation, Both Big Both Brains swallowing (stylopharyngeus), salivation (parotid gland), monitoring carotid body and sinus chemo- and baroreceptors, gag reflex Vagus X Taste from the epiglottic region, swallowing, palatal elevation, talking, thoracoabdominal viscera, monitoring aortic arch chemo- and baroreceptors Accessory XI Head turning, shoulder shrugging Motor Matter Hypoglossal XII Tongue movement Motor Most (Adapted with permission from Le T et al. First Aid for the USMLE Step 1 2011. New York: McGraw-Hill, 2011: 416.) NEUROLOGY Facial Nerve Lesions TA B L E 2 . 10 - 2 . TYPE UMN lesion HIGH-YIELD FACTS IN 243 DESCRIPTION COMMENTS Lesion of the motor cortex or the connection between the cortex ALexander Bell with STD: AIDS, and the facial nucleus. Contralateral paralysis of the lower face only. LMN lesion Ipsilateral paralysis of the upper and lower face. Bell’s palsy Complete destruction of the facial nucleus itself or its branchial efferent fibers (facial nerve proper). Peripheral ipsilateral facial paralysis with inability to close the eye on the involved side. Can occur idiopathically; gradual recovery is seen in most cases. Lyme, Sarcoid, Tumors, Diabetes. Face area of motor cortex Corticobulbar tract (UMN Facial lesion = nucleus central facial) Upper division Lower division LMN lesion Seen as a complication in AIDS, Lyme disease, Sarcoidosis, Tumors, and Diabetes. CN VII (LMN lesion = Bell´s palsy) (Adapted with permission from Le T et al. First Aid for the USMLE Step 1 2011. New York: McGraw-Hill, 2011: 419.) Vascular Disorders ST R O K E KEY FACT Acute onset of focal neurologic deficits resulting from disruption of cerebral circulation. Many classifications exist, but the most common comparison involves ischemic (80%) and hemorrhagic (20%). Table 2.10-5 contrasts modifiable and nonmodifiable risk factors associated with stroke. Etiologies are as follows: TA B L E 2 . 10 - 3 . TRACT Spinal Tract Functions FUNCTION DECUSSATION Lateral Movement of Pyramidal, at the corticospinal contralateral limbs. cervicomedullary ORIGIN 1° motor cortex. junction. Dorsal column Fine touch, Arcuate fibers at the Pacini’s and medial lemniscus vibration, conscious medulla. Meissner’s tactile disks, muscle proprioception. spindles, and Golgi tendon organs. Spinothalamic Pain, temperature. Ventral white Free nerve endings, commissure at the pain fibers. spinal cord level. Stroke is the third most common cause of death and the leading cause of major disability in the United States. 244 HIGH-YIELD FACTS IN NEUROLOGY TA B L E 2 . 10 - 4 . Clinical Reflexes DISTRIBUTION LOCATION COMMENTS Reflexes count up in order. Biceps = C5 nerve root. C5, 6 C7, 8 L3, 4 S1, 2 Triceps = C7 nerve root. S1, 2 Patella = L4 nerve root. L3, 4 Achilles = S1 nerve root. C5, 6 Babinski––dorsiflexion of the big toe C7, 8 and fanning of other toes; sign of UMN lesion, but normal reflex in the first year of life. (Adapted with permission from Le T et al. First Aid for the USMLE Step 1 2011. New York: McGraw-Hill, 2011: 414.) n n n Atherosclerosis of the extracranial vessels (internal/common carotid, basilar, and vertebral arteries). Lacunar infarcts in regions supplied by perforating vessels (result from chronic hypertension, hypercholesterolemia, or diabetes). Cardiac or aortic emboli: n Thromboemboli: Atrial fibrillation (AF), ventricular hypokinesis, prosthetic valves, marantic endocarditis. n Atheroemboli: Aortic arch atherosclerosis. Poliomyelitis and WerdnigHoffmann disease: lower motor neuron lesions only, due to destruction of anterior horns; flaccid paralysis Complete occlusion of anterior spinal artery; spares dorsal columns and tract of Lissauer FIGURE 2.10-1. Multiple sclerosis: mostly white matter of cervical region; random and asymmetric lesions, due to demyelination; scanning speech, intention tremor, nystagmus Tabes dorsalis (3° syphilis): degeneration of dorsal roots and dorsal columns; impaired proprioception, locomotor ataxia ALS: combined upper and lower motor neuron deficits with no sensory deficit; both upper and lower motor neuron signs Syringomyelia: crossing fibers of spinothalamic tract damaged; bilateral loss of pain and temperature sensation Vitamin B12 neuropathy and Friedreich´s ataxia: demyelination of dorsal columns, lateral corticospinal tracts, and spinocerebellar tracts; ataxic gait, hyperreflexia, impaired position and vibration sense Spinal cord lesions. (Reproduced with permission from Le T et al. First Aid for the USMLE Step 1 2009. New York: McGraw-Hill, 2009: 389.) NEUROLOGY TA B L E 2 . 10 - 5 . HIGH-YIELD FACTS IN 245 Modifiable and Nonmodifiable Risk Factors for Stroke MODIFIABLE RISK FACTORS NONMODIFIABLE RISK FACTORS “Live the way a COACH SHoulDD”: FAME: CAD Family history of MI or stroke Obesity Age > 60 Atrial fibrillation Male gender Carotid stenosis Ethnicity (African American, Hispanic, Asian) Hypercholesterolemia Smoking Hypertension Diabetes Drug use (cocaine, IV drugs) Infectious emboli: Bacterial endocarditis. Paradoxical emboli: Via patent foramen ovale. Hypercoagulable states: Include those associated with antiphospholipid antibodies, activated protein C resistance, malignancy, and OCPs in the context of smoking. Craniocervical dissection: Trauma, fibromuscular dysplasia (young females), inflammatory/infectious diseases. Other causes: Venous sinus thrombosis, sickle cell anemia, vasculitis (eg, giant cell arteritis). n n n n n HISTORY/PE Symptoms are dependent on the vascular territory affected: n n n n n n Middle cerebral artery (MCA): Aphasia (dominant hemisphere), neglect (nondominant hemisphere), contralateral paresis and sensory loss in the face and arm, gaze preference toward the side of the lesion, homonymous hemianopsia. Anterior cerebral artery (ACA): Contralateral paresis and sensory loss in the leg; cognitive or personality changes. Posterior cerebral artery (PCA): Homonymous hemianopsia, memory deficits, dyslexia/alexia. Basilar artery: Coma, “locked-in” syndrome, cranial nerve palsies (eg, diplopia), apnea, visual symptoms, drop attacks, dysphagia, dysarthria, vertigo, “crossed” weakness and sensory loss affecting the ipsilateral face and contralateral body. Basal ganglia lacunar: Pure motor or sensory stroke, dysarthria–clumsy hand syndrome, ataxic hemiparesis. TIA: A transient neurologic deficit that lasts < 24 hours (most last < 1 hour) and is determined to be of ischemic etiology. Many TIAs have MRI-! presentations, and some (~ 30–50%) are associated with small, asymptomatic strokes on diffusion-weighted MRI. DIAGNOSIS n n Immediate labs include CBC with platelets, cardiac enzymes and troponin, electrolytes, BUN, creatinine, serum glucose, PTT, PT, INR, lipid profile, and O2 saturation. Emergent head CT without contrast (see Figure 2.10-2A) to differentiate ischemic from hemorrhagic stroke and to identify potential candidates for thrombolytic therapy. Strokes < 6 hours old are usually not visible on CT scan. MNEMONIC The 4 “deadly D’s” of posterior circulation strokes— Diplopia Dizziness Dysphagia Dysarthria 246 HIGH-YIELD FACTS IN A NEUROLOGY B C FIGURE 2.10-2. Acute ischemic stroke. Acute left hemiparesis in a 62-year-old woman. (A) Noncontrast head CT with loss of gray and white matter differentiation and asymmetrically decreased size of the right lateral ventricle in a right MCA distribution (indicating mass effect). (B) Diffusion-weighted MRI with reduced diffusion in the same distribution, consistent with an acute infarct; diffusion-weighted sequences are the most sensitive modality for diagnosing an acute ischemic infarct. (C) MRA shows the cause: an abrupt occlusion of the proximal right MCA (arrow). Compare with the normal left MCA (arrowhead). (Reproduced with permission from USMLERx.com.) MNEMONIC n MCA stroke can cause CHANGes: n Contralateral paresis and sensory loss in n the face and arm Homonymous hemianopsia Aphasia (dominant) Neglect (nondominant) Gaze preference toward the side of the lesion n MRI (see Figure 2.10-2B) to identify early ischemic changes (eg, diffusion-weighted MRI is sensitive for acute stroke with changes as early as 20 minutes after an ischemic event). ECG and an echocardiogram if embolic stroke is suspected. Vascular studies of intracranial and extracranial disease include carotid ultrasound, transcranial Doppler, MRA, CT angiography, and conventional angiography (see Figure 2.10-2C). Screen for hypercoagulable states in patients with a history of thrombosis, in the setting of a first stroke, or in patients < 50 years of age. TREATMENT Acute treatment measures are as follows: n n Hemorrhagic stroke: See the discussion of parenchymal hemorrhage. Ischemic stroke: n tPA is indicated if administered within 3 hours of symptom onset, but contraindications must first be ruled out. Be aware of potential bleeding or angioedema. n Intra-arterial thrombolysis can be used for select patients within 6 hours of a major stroke from MCA occlusion if such patients are not suitable candidates for IV tPA. n ASA is associated with ↓ morbidity and mortality in acute ischemic stroke presenting ≤ 48 hours from onset. n ICU admission should be considered, especially for large strokes, comatose patients, or those who are unable to protect their airways for possible intubation. n Monitor for signs and symptoms of brain swelling, ↑ ICP, and herniation. Serial CTs are helpful in the evaluation of deteriorating patients. As a temporizing measure, treat with mannitol and hyperventilation. n Allow permissive hypertension and hypoxemia to maintain perfusion of ischemic cerebral tissue. However, in the setting of severe hyperten- NEUROLOGY n n sion (systolic BP > 220 or diastolic BP > 120 mm Hg) or hemorrhagic stroke, treat with IV labetalol or nicardipine infusion. For the administration of tPA, the patient’s systolic BP must be < 185 and diastolic BP < 110 mm Hg. Treat fever and hyperglycemia, as both are associated with worse prognoses in the setting of acute stroke. Prevent and treat poststroke complications such as aspiration pneumonia, UTI, and DVT. Preventive and long-term treatment measures are as follows: n n n n ASA, clopidogrel: If stroke is 2° to small vessel disease or thrombosis, or if anticoagulation is contraindicated. Carotid endarterectomy: If stenosis is > 70% in symptomatic patients or > 60% in asymptomatic patients (contraindicated in 100% occlusion; see Figure 2.10-3). Anticoagulation: In new AF or hypercoagulable states, the target INR is 2–3. In cases involving a prosthetic valve, the target INR is 3–4 or add an antiplatelet agent. Management of hypertension, hypercholesterolemia, and diabetes (hypertension is the single greatest risk factor for stroke). HIGH-YIELD FACTS IN 247 MNEMONIC Contraindications to tPA therapy— SAMPLE STAGES Stroke or head trauma within the last 3 months Anticoagulation with INR > 1.7 or prolonged PTT MI (recent) Prior intracranial hemorrhage Low platelet count (< 100,000/mm3) Elevated BP: Systolic > 185 or diastolic > 110 mm Hg Surgery in the past 14 days TIA (mild symptoms or rapid improvement of symptoms) Age < 18 GI or urinary bleeding in the past 21 days Elevated (> 400 mg/dL) or ↓ (< 50 mg/dL) blood glucose Seizures present at the onset of stroke SU B A R A C H N O I D H E M O R R H A G E ( SAH ) Etiologies of SAH include trauma, berry aneurysms, AVM, and trauma to the circle of Willis. HISTORY/PE n n Aneurysmal SAH presents with an abrupt-onset, intensely painful “thunderclap” headache, often followed by neck stiffness. Other signs of meningeal irritation, including photophobia, nausea/vomiting, and meningeal stretch signs, may also be seen. A B FIGURE 2.10-3. Vascular studies pre- and postendarterectomy. (A) Carotid arteriogram showing stenosis of the proximal internal carotid artery. (B) Postoperative arteriogram with restoration of the normal luminal size following endarterectomy. (Reproduced with permission from Way LW. Current Surgical Diagnosis & Treatment, 10th ed. Stamford, CT: Appleton & Lange, 1994: 763.) KEY FACT CN III palsy with pupillary involvement is associated with berry aneurysms. 248 HIGH-YIELD FACTS IN KEY FACT SAH = “the worst headache of my life” with sudden onset. Migraine = a gradually worsening headache (peak intensity > 30 minutes). NEUROLOGY n n In the absence of neurosurgical intervention, rapid development of obstructive hydrocephalus or seizures often leads to ↓ arousal or frank coma and death. More than one-third of patients will give a history of a “sentinel bleed” days to weeks earlier marked by an abrupt-onset headache, often with nausea/vomiting, or transient diplopia that completely resolved in a matter of minutes to hours. DIAGNOSIS n n n Immediate head CT without contrast (see Figure 2.10-4, left panel) to look for blood in the subarachnoid space. Sensitivity is > 95% in patients with severe SAH but is much lower in those with normal mental status. Immediate LP if CT is ! to look for RBCs, xanthochromia (yellowish CSF due to breakdown of RBCs), ↑ protein (from the RBCs), and ↑ ICP. Note that LP results can be falsely ! both in the first 6–12 hours (because xanthochromia has not yet developed) and after the first 24–28 hours (because xanthochromia has resolved). Four-vessel angiography (or equivalent noninvasive angiography such as CT angiography with 3D reconstructions) should be performed once SAH Subarachnoid hemorrhage. Noncontrast CT (left) showing SAH filling the basilar cisterns and sylvian fissures (straight arrows). The curved arrow shows the dilated temporal horns of the lateral ventricles/hydrocephalus. Coned-down images (right) from a catheter angiogram (A), a CT angiogram (B), and an MRA (C) show a saccular aneurysm arising from the anterior communicating artery (arrow). (Left image reproduced with permission from Tintinalli JE et al. Tintin- FIGURE 2.10-4. alli’s Emergency Medicine: A Comprehensive Study Guide, 6th ed. New York: McGraw-Hill, 2004, Fig. 237-4. Right image reproduced with permission from Doherty GM. Current Diagnosis & Treatment: Surgery, 13th ed. New York: McGraw-Hill, 2010, Fig. 36-6.) NEUROLOGY n has been confirmed (see Figure 2.10-4A–C). Noninvasive angiography is warranted in high-risk cases and in those with high clinical suspicion even if CT and LP are unrevealing. Call neurosurgery. TREATMENT n n n n n Prevent rebleeding (most likely to occur in the first 48 hours) by maintaining systolic BP < 150 mm Hg until the aneurysm is clipped or coiled. Prevent vasospasm and associated neurologic deterioration (most likely to occur 5–7 days after SAH) by administering calcium channel blockers (CCBs), IV fluids, and pressors to maintain BP. ↓ ICP by raising the head of the bed and instituting hyperventilation in an acute setting (< 30 minutes after onset). Treat hydrocephalus through a lumbar drain or serial LPs. Surgical clipping is the definitive treatment for aneurysms. Endovascular coiling is also a safe option for many aneurysms. IN T R A C E R E B R A L HE M O R R H A G E n n n n Risk factors include hypertension, tumor, amyloid angiopathy (in the elderly), anticoagulation, and vascular malformations (AVMs, cavernous hemangiomas). Hx/PE: Presents with focal motor and sensory deficits that often worsen as the hematoma expands. A sudden-onset severe headache, nausea/ vomiting, seizures, lethargy, or obtundation may also be seen. Dx: Immediate noncontrast head CT (see Figure 2.10-5). Look for mass effect or edema that may predict herniation. Tx: Similar to that of SAH. Elevate the head of the bed and institute antiseizure prophylaxis. Surgical evacuation may be necessary if mass effect is present. Several types of herniation may occur, including central, uncal, subfalcine, and tonsillar (see Figure 2.10-6 and Table 2.10-6). C H P T Intracerebral hemorrhage. Noncontrast head CT shows an intraparenchymal hemorrhage (H) and surrounding edema (arrows) centered in the left putamen, a common location for hypertensive hemorrhage. C, P, and T denote the normal contralateral caudate, putamen, and thalamus. (Reproduced with permission from Fauci AS et al. Harrison’s Principles of Internal FIGURE 2.10-5. Medicine, 17th ed. New York: McGraw-Hill, 2008, Fig. 364-17.) HIGH-YIELD FACTS IN 249 MNEMONIC Conditions associated with berry aneurysms that can MAKE an SAH more likely: Marfan’s syndrome Aortic coarctation Kidney disease (autosomal dominant, polycystic) Ehlers-Danlos syndrome Sickle cell anemia Atherosclerosis History (familial) 250 HIGH-YIELD FACTS IN NEUROLOGY Falx cerebri Supratentorial mass 1 Lateral ventricles 2 3 4 Brainstem Uncus Tentorium cerebelli Cerebellar tonsil Sites of herniation syndromes. (1) Cingulate herniation under the falx cerebri. (2) Downward transtentorial (central) herniation. (3) Uncal herniation. (4) Cerebellar tonsillar herniation into the foramen magnum. Coma and death result when these herniations compress the brainstem. (Adapted with permission from Simon RP et al. Clinical Neurology, 4th ed. Stamford, CT: FIGURE 2.10-6. Appleton & Lange, 1999: 314.) S U BDU R AL HE M ATOM A n n Typically occurs following head trauma (usually falls or assaults), leading to rupture of bridging veins and accumulation of blood between the dura and arachnoid membranes. Common in the elderly and alcoholics. Hx/PE: Presents with headache, changes in mental status, contralateral hemiparesis, and focal neurologic findings. Changes may be subacute or chronic. May present as pseudodementia in the elderly. TA B L E 2 . 10 - 6 . Clinical Presentation of Herniation Syndromes TYPE OF HERNIATION Cingulate herniation PRESENTATION Occurs 2° to mass lesions of the frontal lobes. No specific signs or symptoms; frequently seen on head CT. Downward transtentorial Occurs when large supratentorial mass lesions push the (central) herniation midbrain inferiorly. Presents with a rapid change in mental status; bilaterally small and reactive pupils; Cheyne-Stokes respirations; and flexor or extensor posturing. Uncal herniation Occurs 2° to mass lesions of the middle fossa. CN III becomes entrapped, leading to a fixed and dilated ipsilateral pupil followed by an eye that is deviated “down and out.” Ipsilesional hemiparesis (“false localizing”) results from compression of the cerebral peduncle (opposite the mass lesion) against the tentorial edge. Cerebellar tonsillar herniation Occurs 2° to posterior fossa mass lesions. Tonsillar into the foramen magnum herniation → medullary compression → respiratory arrest. Usually rapidly fatal. NEUROLOGY Dx: CT demonstrates a crescent-shaped, concave hyperdensity acutely (isodense subacutely; hypodense chronically) that does not cross the midline (see Figure 2.10-7A). Tx: Surgical evacuation if symptomatic. Subdural hematomas may regress spontaneously. n n EPIDURAL HEMATOMA n n n n Usually a result of a lateral skull fracture leading to a tear of the middle meningeal artery. Hx/PE: Obvious, severe trauma induces an immediate loss of consciousness followed by a lucid interval (minutes to hours). Uncal herniation leads to coma with a “blown pupil” (fixed and dilated ipsilateral pupil) and ultimately contralateral hemiparesis. Dx: CT shows a lens-shaped, convex hyperdensity limited by the sutures (see Figure 2.10-7B). Tx: Emergent neurosurgical evacuation. May quickly evolve to brain herniation and death 2° to the arterial source of bleeding. Headaches Causes of headache include the following: n Acute (onset seconds to minutes): n Primary: New migraine/cluster headache. n Vascular/ischemic: Aneurysmal SAH, cerebral venous thrombosis, cavernous sinus thrombosis, craniocervical dissection, acute severe hypertension (eg, pheochromocytoma), ischemic stroke/intraparenchymal hemorrhage (headache is usually not the presenting manifestation), pituitary apoplexy. n ↑ ICP: Colloid cyst, obstructive hydrocephalus. n Acute ocular disease: Angle-closure glaucoma. A B FIGURE 2.10-7. Subdural vs. epidural hematoma. (A) Subdural hematoma. Note the crescent shape and the mass effect with midline shift. (B) Epidural hematoma with a classic biconvex lens shape. (Reproduced with permission from Aminoff MJ. Clinical Neurology, 3rd ed. Stamford, CT: Appleton & Lange, 1996: 296.) HIGH-YIELD FACTS IN 251 KEY FACT Mental status changes associated with an expanding epidural hematoma occur within minutes to hours and classically include a lucid interval. With a subdural hematoma, such changes can occur within days to weeks. KEY FACT A “blown pupil” suggests impending brainstem compression. 252 HIGH-YIELD FACTS IN NEUROLOGY n KEY FACT Recent-onset headaches warrant immediate workup! 1. Focal neurologic deficits: Rule out more serious etiologies with CT or MRI. 2. Abrupt onset: Rule out SAH with a CT and LP. n Subacute (onset hours to days): n Primary: New migraine/tension-type headache. n Infectious: Viral syndrome, meningitis, cranial infections (acute sinusitis, dental infections, orbital infections, cavernous sinus infections, otitis media/mastoiditis), encephalitis. n Vascular/ischemic: Temporal arteritis, subacute severe hypertension (eg, hypertensive encephalopathy, eclampsia), intracranial hypotension (eg, spontaneous, post-LP), subdural hematoma, carbon monoxide, lead poisoning in children (rare). n Subacutely ↑ ICP: Large tumor, progressive hydrocephalus, altitude sickness, pseudotumor cerebri. n Subacute ocular disease: Keratitis, iritis, scleritis, orbital infection. Chronic/episodic: n Primary: Migraine, cluster headache, tension-type headache. n Infectious: Chronic sinusitis. n Other: Medication overuse (eg, caffeine withdrawal, “rebound” headaches from NSAID or analgesic overuse), trigeminal or other neuralgias (eg, glossopharyngeal, postherpetic), TMJ disorders, cervical arthritis. HISTORY/PE n n KEY FACT “Oh, my headache is fine!” Remember— not all dangerous headaches hurt (eg, temporal arteritis)! Conduct full general and neurologic exams, including a funduscopic exam. Evaluate the following: n Chronicity: Recent or recently changed headaches warrant immediate workup if they are not clearly migraines or other 1° headache disorders. n Intensity: Severe headaches are more likely to be dangerous. n Location: Posterior headaches are less likely to be benign, especially in children. n Duration: Headaches lasting > 72 hours are atypical for migraines. n Diurnal variation: Cluster headaches and those from ↑ ICP usually occur or worsen at night. n Triggers: Examples include chocolate and red wine in migraines. n Provocative factors: Lying down may worsen high-ICP headaches; standing up may exacerbate low-ICP headaches. n Palliative factors: Examples include sleep alleviating migraine headaches. n Associated symptoms/signs: n Significant findings include fever or rash (consider meningitis or other infectious causes), jaw claudication (specific for temporal arteritis), or constitutional symptoms such as weight loss (associated with neoplastic, inflammatory, or infectious conditions). n Photophobia, nausea, and vomiting are associated with migraine, aneurysmal SAH, and meningitis; neck stiffness is more likely to accompany the last 2 conditions. n Neurologic sequelae: Look for diplopia, mental status changes or associated symptoms (numbness, weakness, dizziness, ataxia, visual disturbances), papilledema, or pupillary abnormalities (partial CN III palsy or Horner’s syndrome). n Patient risk factors: High-risk patients are > 50 years of age, immunocompromised, or with preexisting malignancy. DIAGNOSIS n n n If SAH is suspected, obtain a head CT without contrast. If CT is !, LP is mandatory. Obtain a CBC to rule out systemic infections. If temporal arteritis is suspected, obtain an ESR. NEUROLOGY n HIGH-YIELD FACTS IN 253 A CT/MRI is needed for suspected SAH, ↑ ICP, or focal neurologic findings. Use CT without contrast to evaluate acute hemorrhage. MI G R A I N E HE A D A CH E n n n n n n Affects females more often than males; may be familial. Associated with vascular and brain neurotransmitter (serotonin) changes. Pain is ultimately linked to trigeminal nucleus activation in the brainstem. Onset is usually by the early 20s. Auras may occur with or without the pain of migraine headache. Triggers include certain foods (eg, red wine), fasting, stress, menses, OCPs, bright light, and disruptions in normal sleep patterns. Hx/PE: n Presents with a throbbing headache (> 2 hours but usually < 24 hours, and almost always < 72 hours in duration) that is associated with nausea, vomiting, photophobia, and noise sensitivity. Headache is usually relieved by sleep and darkness. n Classic migraines: Often unilateral and preceded by a visual aura in the form of either scintillating scotomas (bright or flashing lights) or visual field cuts. n Common migraines: May be bilateral and periorbital without preceding auras. Dx: Based on the history and an otherwise ! workup. Tx: n Avoid known triggers. n Abortive therapy includes triptans (first-line therapy after OTC NSAIDs have failed), metoclopramide, and various analgesics. Consider symptomatic treatment for nausea. n Prophylaxis for frequent or severe migraines includes anticonvulsants (eg, gabapentin, topiramate), TCAs (eg, amitriptyline), β-blockers (propranolol), and CCBs. KEY FACT If a 20-year-old female develops headaches after drinking red wine, think migraine. CL U S T E R H E A D A C H E n n n n Males are affected more often than females; average age of onset is 25. Hx/PE: n Presents as a brief, excruciating, unilateral periorbital headache that lasts 30 minutes to 3 hours, during which the patient tends to be extremely restless. n Attacks tend to occur in clusters, affecting the same part of the head at the same time of day (commonly during sleep) and in a certain season of the year. n Associated symptoms include ipsilateral lacrimation of the eye, conjunctival injection, Horner’s syndrome, and nasal stuffiness. Dx: Classic presentations with a history of repeated attacks over an extended period of time require no evaluation. First episodes require a workup to exclude disorders associated with Horner’s syndrome (eg, carotid artery dissection, cavernous sinus infection). Tx: n Acute therapy: High-flow O2, dihydroergotamine, octreotide, sumatriptan or zolmitriptan. n Prophylactic therapy: Transitional (prednisone, ergotamine), maintenance (verapamil, methysergide, lithium, valproic acid, topiramate). KEY FACT If a 25-year-old male wakes up repeatedly during the night with unilateral periorbital pain associated with ipsilateral lacrimation, think cluster headache. 254 HIGH-YIELD FACTS IN NEUROLOGY TE NSI ON- TYP E H E ADAC HE KEY FACT If a 30-year-old female complains of headaches at the end of the day that worsen with stress and improve with relaxation or massage, think tensiontype headache. n n n n KEY FACT Tension-type headaches are the most common type of headache diagnosed in adults. Considered by some to be a milder form of migraine headache. Hx/PE: Presents with tight, bandlike pain that is not associated with sensory phobia, nausea/vomiting, or auras and is brought on by fatigue or stress. Nonspecific symptoms (eg, anxiety, poor concentration, difficulty sleeping) may also be seen. Usually occurs at the end of the day. Dx: A diagnosis of exclusion. Be particularly aware of giant cell arteritis in patients > 50 years of age with new headaches; always obtain an ESR even if headaches are mild and unassociated with constitutional or vascular symptoms. Tx: Relaxation, massage, hot baths, and avoidance of exacerbating factors. NSAIDs and acetaminophen are first-line abortive therapy, but triptans may also be considered. CAVE R NOU S S I NU S THR OM BO SIS The usual etiology involves a suppurative process of the orbit, nasal sinuses, or central face that leads to septic thrombosis of the cavernous sinus. Nonseptic thrombosis is rare; S aureus is the most common causative agent. The syndrome can also be seen with nonbacterial agents, particularly fungi (Mucor or Aspergillus species). Current antimicrobials have greatly ↓ both incidence and mortality. HISTORY/PE n n n n Headache is the most common presenting symptom. Patients may present with orbital pain, edema, diplopia (2° to oculomotor, abducens, or trochlear nerve involvement), or visual disturbances and may describe a recent history of sinusitis or facial infection. On examination, they typically appear ill and have a fever. Additional signs may include red eye, proptosis, ptosis, or ophthalmoplegia of the affected eye (partial or complete). Changes in mental status such as confusion, drowsiness, or coma suggest spread to the CNS or sepsis. Late findings include meningismus or systemic signs of sepsis. DIAGNOSIS n n n n n Lab studies show an ↑ WBC count. Blood cultures reveal the causative agent in up to 50% of cases. CSF exam may reveal ↑ protein consistent with a parameningeal reaction unless there is frank meningitis. MRI (with gadolinium and MR venography) is the principal means of confirming the anatomic diagnosis; CT angiography and CT venography are also often used for diagnosis. Biopsy of paranasal sinuses or other affected tissue is often necessary in fungal cases for organism identification by histology and culture. TREATMENT n Treat aggressively and empirically with a penicillinase-resistant penicillin (nafcillin or oxacillin) plus a third- or fourth-generation cephalosporin (eg, ceftriaxone or cefepime) to provide broad-spectrum coverage pending blood culture results. Potential anaerobic infection from sinus or dental sources should be covered with metronidazole. Vancomycin can be added to address potential MRSA involvement. Antifungal therapy is required for fungal cases. NEUROLOGY n n HIGH-YIELD FACTS IN 255 IV antibiotics are recommended for at least 3–4 weeks. Surgical drainage may be necessary if there is no response to antibiotics within 24 hours. Seizure Disorders Paroxysmal events associated with aberrant electrical activity in the brain detectable by EEG, leading to changes in neurologic perception or behavior. An aura is experienced by 50–60% of patients with epilepsy. See Table 2.10-7 for common etiologies by age. To further narrow down the etiology of a seizure, assess the following: n n n n n Determine whether the patient has a history of epilepsy (ie, a history of unprovoked and recurrent seizures). Other seizures may be self-limited and may resolve once an underlying medical condition has been identified and treated. Elevated serum prolactin levels are consistent with an epileptic seizure in the immediate postictal period. Non-neurologic etiologies include hypoglycemia, hyponatremia, hypocalcemia, hyperosmolar states, hepatic encephalopathy, uremia, porphyria, drug overdose (cocaine, antidepressants, neuroleptics, methylxanthines, lidocaine), drug withdrawal (alcohol and other sedatives), eclampsia, hyperthermia, hypertensive encephalopathy, head trauma, and cerebral hypoperfusion. Seizures with a focal onset (or focal postictal deficit) suggest focal CNS pathology. They may be the presenting sign of a tumor, stroke, AVM, infection, hemorrhage, or developmental abnormality. First-time seizures that resolve after a single episode are usually not treated with antiseizure medications when the underlying cause is unknown. PA R T I A L S E IZ U R ES Arise from a discrete region, or an “epileptogenic focus,” in 1 cerebral hemisphere and do not by themselves cause loss of consciousness unless they secondarily generalize. T A B L E 2 . 1 0 - 7. Causes of Seizure by Age Group CHILDREN INFANTS ADULTS (2–10) ADOLESCENTS (18–35) ADULTS (35+) Perinatal Idiopathic Idiopathic Trauma Trauma injury Infection Trauma Alcoholism Stroke Infection Trauma Drug Brain tumor Metabolic Metabolic Febrile Congenital withdrawal AVM disorders Alcoholism Brain tumor A 23-year-old female presents to the ER with a first-time seizure during the eighth month of her first pregnancy. Is this seizure more likely to be related to her pregnancy or to a preexisting condition? 256 HIGH-YIELD FACTS IN KEY FACT NEUROLOGY HISTORY/PE n If a patient presents wth progressive jerking of successive body regions and hallucinations but without loss of consciousness, think simple partial seizures. KEY FACT n If a patient presents with an episode of lip smacking associated with an impaired level of consciousness and followed by confusion, think complex partial seizures. Simple partial seizures: n May include motor features (eg, jacksonian march, or the progressive jerking of successive body regions) as well as sensory, autonomic, or psychic features (eg, fear, déjà vu, hallucinations). n Do not involve alteration of consciousness. n A postictal focal neurologic deficit (eg, hemiplegia/hemiparesis, or Todd’s paralysis) is possible and usually resolves within 24 hours. Often confused with acute stroke (ruled out by MRI). Complex partial seizures: n Typically involve the temporal lobe (70–80%) with bilateral spread of the aberrant electrical discharge. n Involve an impaired level of consciousness. n Characterized by auditory or visual hallucinations, déjà vu, and automatisms (eg, lip smacking, chewing, or even walking). n Postictal confusion/disorientation and amnesia are characteristic. DIAGNOSIS n KEY FACT Both simple partial and complex partial seizures may evolve into 2° generalized tonic-clonic (grand mal) seizures. n n Obtain an EEG to rule out pseudoseizures and to find an epileptogenic focus if present. Rule out systemic causes with a CBC, electrolytes, calcium, fasting glucose, LFTs, a renal panel, RPR, ESR, and a toxicology screen. A focal seizure implies a focal brain lesion. Evaluate by MRI or CT with contrast. TREATMENT n n n n For acute seizures lasting longer than 2 minutes, use IV benzodiazepines and phenytoin. In cases of systemic 2° seizures, treat the underlying cause. Recurrent partial seizures: Phenytoin, oxcarbazepine, carbamazepine (Tegretol), phenobarbital, and valproic acid can be administered as monotherapy. In children, phenobarbital is the first-line anticonvulsant. Intractable temporal lobe seizures: Consider anterior temporal lobectomy. TONI C -C LONI C (G R AND M AL) S E I ZU R ES KEY FACT If a patient presents with clonic movements associated with loss of consciousness and incontinence, think tonic-clonic (grand mal) seizures. Primarily idiopathic. Partial seizures can evolve into secondarily generalized tonic-clonic seizures. HISTORY/PE n n This first-time seizure is most likely 2° to the patient’s pregnancy as opposed to a preexisting seizure disorder. Her presentation is most consistent with eclampsia, which typically follows preeclampsia, a serious complication of high blood pressure during pregnancy. Presents with sudden onset of loss of consciousness with tonic extension of the back and extremities, continuing with 1–2 minutes of repetitive, symmetric clonic movements. Marked by incontinence and tongue biting. Patients may appear cyanotic during the ictal period. Consciousness is slowly regained in the postictal period, but patients are confused and may prefer to sleep; muscle aches and headaches may be present. DIAGNOSIS Diagnosed by the history and EEG (typically shows 10-Hz activity during the tonic phase and slow waves during the clonic phase). NEUROLOGY HIGH-YIELD FACTS IN 257 TREATMENT n n n n Protect the airway. Treat the underlying cause if known. 1° generalized tonic-clonic seizures: Phenytoin, fosphenytoin, or valproate constitutes first-line therapy. Lamotrigine or topiramate may be used as adjunctive therapy. Secondarily generalized tonic-clonic seizures: Treatment is the same as that for partial seizures. ABS E N CE (PE T IT M A L) S E I Z U R ES n n n n Begin in childhood; subside before adulthood. Often familial. Hx/PE: Present with brief (5- to 10-second), often unnoticeable episodes of impaired consciousness occurring up to hundreds of times per day. Patients are amnestic during and immediately after seizures and may appear to be daydreaming or staring. Eye fluttering or lip smacking is common. Dx: EEG shows classic 3-per-second spike-and-wave discharges (remember classic EEG findings, but do not worry about learning how to read them!). Hyperventilation can trigger these seizures. Tx: Ethosuximide is the first-line agent. Valproic acid is second line. ST A T U S E PI L E PT IC U S A medical emergency consisting of prolonged (> 10-minute) or repetitive seizures that occur without a return to baseline consciousness. May be either convulsive (the more medically urgent form) or nonconvulsive. n n Common causes include anticonvulsant withdrawal/noncompliance, anoxic brain injury, EtOH/sedative withdrawal or other drug intoxication, metabolic disturbances (eg, hyponatremia), head trauma, and infection. Death usually results from the underlying medical condition and may occur in 10% of cases of status epilepticus. DIAGNOSIS n n n n Determine the underlying cause with pulse oximetry, CBC, electrolytes, calcium, glucose, ABGs, LFTs, BUN/creatinine, ESR, antiepileptic drug levels, and a toxicology screen. Obtain an EEG and brain imaging, but defer testing until the patient is stabilized. Obtain a stat head CT to evaluate for intracranial hemorrhage. Obtain an LP in the setting of fever or meningeal signs, but only after a CT scan has been obtained to assess the safety of the LP. TREATMENT n n n n n Maintain ABCs; consider rapid intubation for airway protection. Administer thiamine, followed by glucose and naloxone to presumptively treat potential etiologies. Give an IV benzodiazepine (lorazepam or diazepam) plus a loading dose of fosphenytoin. If seizures continue, intubate and load with phenobarbital. Consider an IV sedative (midazolam or pentobarbital) and initiate continuous EEG monitoring. Initiate a meticulous search for the underlying cause. KEY FACT If you see petit mal seizures, think about the classic EEG finding of 3-per-second spike-and-wave discharges. KEY FACT If a child is brought from school to her pediatrician after experiencing multiple intermittent 5-second episodes of staring into space, think absence (petit mal) seizures. 258 HIGH-YIELD FACTS IN NEUROLOGY I NF ANTI LE S P AS MS ( W ES T S YNDR OM E ) n n n KEY FACT If a male infant is brought to the hospital with muscular jerks and an uncle who had the same problem, think infantile spasms (West syndrome). n n A form of generalized epilepsy that typically begins within 6 months of birth. May be idiopathic or 2° to a variety of conditions, including PKU, perinatal infections, hypoxic-ischemic injury, and tuberous sclerosis. Affects males more often than females; associated with a " family history. Hx/PE: Presents with tonic, bilateral, symmetric jerks of the head, trunk, and extremities that tend to occur in clusters of 5–10; arrest of psychomotor development occurs at the age of seizure onset. The majority of patients have mental retardation. Dx: Look for an abnormal interictal EEG characterized by hypsarrhythmia. Tx: Hormonal therapy with ACTH, prednisone, and clonazepam or valproic acid. Medications may treat the spasms but have little impact on patients’ long-term prognosis. LE NNOX -G AS TAU T S YNDR OM E n n n n A form of childhood onset seizures that is often refractory to treatment. Hx/PE: Presents with daily multiple seizures, often nocturnal tonic seizures. Classically appears between ages 2 and 6; more common in males than in females. Strongly associated with mental retardation, behavior disorders, and delayed psychomotor development. Dx: Look for an abnormal interictal EEG characterized by slow spike-andwave complexes. Tx: Usually treatment resistant. Vertigo and Dizziness B E NI G N PAR OX YSM AL P OS I TI ONAL VE R TI G O ( BP P V) n n n MNEMONIC With BPPV, it’s all in the name: Benign = otolith (not a tumor). Paroxysmal = sudden, temporary episodes lasting < 1 minute. Positional = triggered by turning in bed or reaching overhead. Vertigo = vertigo or dizziness is the main symptom. n A common cause of recurrent peripheral vertigo resulting from a dislodged otolith that leads to disturbances in the semicircular canals (95% posterior, 5% horizontal). Hx/PE: Patients present with transient, episodic vertigo (lasting < 1 minute) and mixed upbeat-torsional nystagmus triggered by changes in head position (eg, while turning in bed, getting in and out of bed, or reaching overhead). Patients may complain of nonvertiginous dizziness or lightheadedness. Nausea and vomiting are uncommon owing to the shortlived nature of the stimulus. Dx: n Dix-Hallpike maneuver: Have the patient turn his or her head 45 degrees right or left and go from a sitting to a supine position while quickly turning the head to the side. If vertigo and the typical nystagmus (upbeat and toward the affected shoulder) are reproduced, BPPV is the likely diagnosis. n Nystagmus that persists for > 1 minute, gait disturbance, or nausea/ vomiting that is out of proportion to nystagmus should raise concern for a central lesion. Tx: n Eighty percent of cases can be resolved with a modified Epley maneuver (a 270-degree head rotation from the Dix-Hallpike testing position). NEUROLOGY n HIGH-YIELD FACTS IN 259 The condition usually subsides spontaneously in weeks to months, but 30% recur within a year. Antivertigo medications (eg, meclizine) are generally contraindicated, as they inhibit central compensation, which may lead to chronic unsteadiness. AC U T E PE R IP H E R A L V E ST I B U L O PATHY ( LABYR I NTHI TI S A N D V ES T IB U LA R N E U R IT IS ) n n n Hx/PE: n Presents with acute onset of severe vertigo, head-motion intolerance, and gait unsteadiness accompanied by nausea, vomiting, and nystagmus. n Auditory or aural symptoms (labyrinthitis) may include unilateral tinnitus, ear fullness, or hearing loss. Without auditory or aural symptoms, the condition is known as vestibular neuritis. n Labyrinthitis (with auditory symptoms) is mimicked by lateral pontine/ cerebellar stroke (AICA territory). Vestibular neuritis (without auditory symptoms) is mimicked by lateral medullary/cerebellar stroke (PICA territory). Dx: n A diagnosis of exclusion once the more serious causes of vertigo (eg, cerebellar stroke) have been ruled out. n Acute peripheral vestibulopathy demonstrates the following: n An abnormal vestibulo-ocular reflex as determined by a bedside head impulse test (ie, rapid head rotation from lateral to center while staring at the examiner’s nose). n A predominantly horizontal nystagmus that always beats in 1 direction, opposite the lesion. n No vertical eye misalignment by alternate cover testing. n If patients are “high risk”—ie, if they have atypical eye findings or neurologic symptoms or signs, cannot stand independently, have head or neck pain, are > 50 years of age, or have 1 or more stroke risk factors— MRI with diffusion-weighted imaging is indicated. Tx: Acute treatment consists of corticosteroids given < 72 hours after symptom onset and vestibular sedatives (eg, meclizine). The condition usually subsides spontaneously within weeks to months. KEY FACT If you see someone with vertigo and vomiting for 1 week after having been diagnosed with a viral infection, think acute vestibular neuritis. MÉN IÈ R E ’S DI S E A SE n n n n A cause of recurrent vertigo with auditory symptoms that affects at least 1 in 500 in the United States. More common among females. Hx/PE: Presents with recurrent episodes of severe vertigo, hearing loss, tinnitus, or ear fullness, often lasting hours to days. Nausea and vomiting are typical. Patients progressively lose low-frequency hearing over years and may become deaf on the affected side. Dx: The diagnosis is made clinically and is based on a thorough history and physical. Two episodes lasting ≥ 20 minutes with remission of symptoms between episodes, hearing loss documented at least once with audiometry, and tinnitus or aural fullness are needed to make the diagnosis once other causes (eg, TIA, otosyphilis) have been ruled out. Tx: n Classically, a low-sodium diet and diuretic therapy were first-line treatments. As theories of pathogenesis have shifted, many clinicians have begun to treat patients with “migraine diets,” lifestyle changes, prophy- KEY FACT Ménière’s disease consists of recurrent episodes, but unlike BPPV, these usually last hours to days. 260 HIGH-YIELD FACTS IN NEUROLOGY n lactic antimigraine medications, and occasionally benzodiazepines or antiemetics. For severe unilateral cases, ablative therapies (eg, intratympanic gentamicin to ablate the labyrinth, vestibular nerve section) have been used with some success. V ES TI BU LAR M I G R AI NE KEY FACT n n Unlike Ménière’s disease, vestibular migraine usually has no associated auditory or aural symptoms. n KEY FACT Rule out vertebral artery dissection in those with persistent head or neck pain and intermittent isolated dizziness or vertigo. n A cause of recurrent vertigo (usually without auditory symptoms) that affects roughly 10% of migraine sufferers. More common among females. Hx/PE: Presents with recurrent episodes of mild dizziness to severe vertigo lasting minutes to days. Nausea, vomiting, and photophobia are common; headaches are variably present and may be mild or severe. Patients have no substantial deficits in between spells, but balance may deteriorate over decades. Dx: n The diagnosis is usually made clinically on the basis of a thorough history and physical to exclude other causes. n Patients who would otherwise qualify for a diagnosis of Ménière’s save the absence of auditory symptoms and documented hearing loss are likely to have vestibular migraine. A history of photo- or phonophobia during the episode, particularly if dizziness is associated with headache, is highly suggestive. n The diagnosis is one of exclusion, and care should be taken to ensure that patients do not have intermittent dizziness due to TIA. In patients < 50 years of age, a history of recent trauma or of severe, abrupt-onset, or persistent pain (> 72 hours) should raise concern for vertebral artery dissection with TIAs. n A brain MRI with vascular imaging (eg, MRA) is sometimes indicated to assess potential intracranial pathology, particularly cerebrovascular disease. Tx: Can usually be prevented through migraine medication, diet, or lifestyle changes. Benzodiazepines or antiemetics may be tried. Surgical therapies are not indicated. S YNC OP E n n n One of the most common causes of loss of consciousness 2° to an abrupt drop in cerebral perfusion. Etiologies include cardiac arrhythmias and cardiac outflow obstruction, vasovagal syncope, orthostatic hypotension, micturition-related syncope, basilar TIAs, and idiopathic causes. Presyncope is described as a feeling of imminent loss of consciousness without actual fainting. Commonly confused with seizures. Hx/PE: n Patients may report a trigger (eg, standing for a long period of time, fear/sight of blood, Valsalva maneuver). n Typically follows a prodrome of lightheadedness or dizziness, muffled sounds, constricting vision, diffuse weakness, diaphoresis, or pallor. Leads to loss of consciousness and muscle tone for < 30 seconds and recovery within seconds. Dx: n Structural CNS causes (eg, basilar TIA, intermittent obstructive hydrocephalus) are rare among patients who return to normal mental status and have a normal neurologic examination after a brief loss of consciousness. NEUROLOGY Seizures are more likely if limb jerking is unilateral or lasts > 30 seconds; if there is prolonged confusion after the episode; or if the patient bites the lateral aspect of his or her tongue. n Unless there is a clear vasovagal faint in a young patient without cardiac disease or risk factors, place all patients on telemetry or Holter monitoring to evaluate for arrhythmia, and rule out myocardial ischemia with an ECG and cardiac enzymes. Obtain an EEG to rule out seizures. Consider an echocardiogram, a tilt-table test, or neuroimaging, especially vascular. Tx: Treat the underlying cause; avoid triggers. n n Disorders of the Neuromuscular Junction MYA ST H E N I A G R A V I S An autoimmune disorder caused by antibodies that bind to postsynaptic acetylcholine (ACh) receptors located at the neuromuscular junction. Most often affects young adult females, and can be associated with thyrotoxicosis, thymoma, and other autoimmune disorders. HISTORY/PE n n n Presents with fluctuating fatigable ptosis or double vision, bulbar symptoms (eg, dysarthria, dysphagia), and proximal muscle weakness. Symptoms typically worsen as the day progresses but fluctuate dramatically. Patients may report difficulty climbing stairs, rising from a chair, brushing their hair, and swallowing. Myasthenic crisis is rare but includes the potentially lethal complications of respiratory compromise and aspiration. DIAGNOSIS n n n n n n Edrophonium (Tensilon test): Anticholinesterase leads to rapid amelioration of symptoms. Rarely used today owing to the risk of bradycardia and discontinuation of production lines. Ice test: Place a pack of ice on 1 eye for 5 minutes; ptosis resolves transiently. An abnormal single-fiber EMG and/or a decremental response to repetitive nerve stimulation can yield additional confirmation. AChR antibodies are " in 80% of patients; anti–muscle-specific kinase (anti-MuSK) antibodies are " in 5%. Chest CT is used to evaluate for thymoma. Eighty-five percent of patients with myasthenia gravis and a thymoma have " antibodies against striated muscle. Follow serial FVCs to determine the need to intubate. TREATMENT n n n n n Anticholinesterases (pyridostigmine) are used for symptomatic treatment. Prednisone and other immunosuppressants (eg, azathioprine, cyclosporine, MMF) are the mainstays of treatment. In severe cases, plasmapheresis or IVIG may provide temporary relief (days to weeks). Resection of thymoma can be curative. Avoid giving certain antibiotics (eg, aminoglycosides) and drugs (eg, β-blockers) to patients with myasthenia gravis. HIGH-YIELD FACTS IN 261 262 HIGH-YIELD FACTS IN NEUROLOGY LAM BE R T-E ATON MYA S THE NI C S YNDR OM E A paraneoplastic autoimmune disorder caused by antibodies directed toward presynaptic calcium channels in the neuromuscular junction. Small cell lung carcinoma is a significant risk factor (60% of cases). Hx/PE: Presents with weakness of proximal muscles along with depressed or absent DTRs. Extraocular, respiratory, and bulbar muscles are typically spared. Dx: Repetitive nerve stimulation reveals a characteristic incremental response. Also diagnosed by autoantibodies to presynaptic calcium channels and a chest CT indicative of a lung neoplasm. Tx: n Treat small cell lung carcinoma; tumor resection may reverse symptoms. n 3,4-diaminopyridine or guanidine can be given; acetylcholinesterase inhibitors (eg, pyridostigmine) can be added to either regimen. n Corticosteroids and azathioprine can be combined or used alone for immunosuppression in cases where a neoplasm cannot be identified and an autoimmune cause is suspected. n n n KEY FACT Repetitive nerve stimulation reveals a characteristic incremental response in Lambert-Eaton myasthenic syndrome but shows a decremental response in myasthenia gravis. n MU LTI P LE S C LE R OSIS ( MS ) Although the pathogenesis of MS is unclear, there is evidence of an autoimmune etiology in genetically susceptible individuals who are exposed to environmental triggers such as viral infections. Such potential etiologies are thought to be T-cell mediated. The female-to-male ratio is 3:2, and onset is typically between 20 and 40 years of age. MS becomes more common with increasing distance from the equator during childhood. Subtypes are relapsing-remitting, 1° progressive, 2° progressive, and progressive relapsing (see Table 2.10-8). HISTORY/PE n TA B L E 2 . 10 - 8 . Presents with multiple neurologic complaints that are separated in time and space and are not explained by a single lesion. As the disease progresses, permanent deficits may accumulate. Subtypes of Multiple Sclerosis RELAPSING-REMITTING 1° PROGRESSIVE 2° PROGRESSIVE PROGRESSIVE RELAPSING Relapses Yes. No acute episodes. Yes. Yes. Progression None. From onset. Not at onset; begins to From onset. progress later. Course of symptoms Percentage of cases Full recovery, or deficits Minor remissions and Relapses, minor Full recovery, or may remain after each plateaus may take place remissions, and plateaus progressive deficits episode. during progression. may take place during may remain after each progression. episode. Develops after relapsing- 15% 66% 19% at onset Prognosis remitting type. Best. Worse. Worse. Worse. NEUROLOGY n n n n Limb weakness, optic neuritis, paresthesias, diplopia, vertigo, nystagmus, gait unsteadiness, urinary retention, sexual and bowel dysfunction, depression, and cognitive impairment are also seen. Symptoms classically worsen transiently with hot showers. Attacks are unpredictable but on average occur every 1.5 years, lasting for 2–8 weeks. Neurologic symptoms can come and go or be progressive. Those with a relapsing and remitting history have the best prognosis. Lhermitte’s sign, demonstrated by vibratory/electrical sensations traveling up or down the neck and back with flexion, generally suggests the presence of cervical myelitis. DIAGNOSIS n n n HIGH-YIELD FACTS IN 263 KEY FACT The classic triad (Charcot’s triad) in MS is scanning speech, intranuclear ophthalmoplegia, and nystagmus. KEY FACT Pregnancy may be associated with a ↓ in MS symptoms. MRI shows multiple, asymmetric, often periventricular white matter lesions (Dawson’s fingers), especially in the corpus callosum. Active lesions enhance with gadolinium. CSF reveals mononuclear pleocytosis (> 5 cells/µL), an ↑ IgG index, or at least 2 oligoclonal bands not found in the serum (nonspecific). Abnormal somatosensory or visual evoked potentials may also be present. TREATMENT n n n n n n Corticosteroids should be given during acute exacerbations. Immunomodulators alter relapse rates in relapsing-remitting MS and include interferon-β1a (Avonex/Rebif), interferon-β1b (Betaseron), and copolymer-1 (Copaxone). Natalizumab is an effective second-line therapy but carries a 1:500 risk for JC virus–mediated progressive multifocal leukoencephalopathy (PML). Mitoxantrone can be given for worsening relapsing-remitting or progressive MS. Alternative treatments include cyclophosphamide, IVIG, and plasmapheresis. Symptomatic therapy is crucial and includes baclofen for spasticity; cholinergics for urinary retention; anticholinergics for urinary incontinence; carbamazepine or amitriptyline for painful paresthesias; and antidepressants for clinical depression. KEY FACT For optic neuritis, give IV, not oral, corticosteroids. GU ILLA IN - BA R R É S Y N D R O M E (GBS ) An acute, rapidly progressive, acquired demyelinating autoimmune disorder of the peripheral nerves that results in weakness. Also known as acute inflammatory demyelinating polyneuropathy. Associated with recent Campylobacter jejuni infection, viral infection, or influenza vaccination. Approximately 85% of patients make a complete or near-complete recovery (may take up to 1 year). The mortality rate is < 5%. HISTORY/PE n n Classically presents with progressive (over days), symmetric, ascending paralysis (distal to proximal) involving the trunk, diaphragm, and cranial nerves. Atypical presentations are common, including variants that begin with cranial involvement or progress unpredictably to involve the respiratory muscles. Autonomic dysregulation, areflexia, and dysesthesias may be present. DIAGNOSIS n Evidence of diffuse demyelination is seen on nerve conduction studies, which show ↓ nerve conduction velocity. MNEMONIC The 5 A’s of GBS: Acute inflammatory demyelinating polyradiculopathy Ascending paralysis Autonomic neuropathy Arrhythmias Albuminocytologic dissociation 264 HIGH-YIELD FACTS IN NEUROLOGY n Supported by a CSF protein level > 55 mg/dL with little or no pleocytosis (albuminocytologic dissociation). TREATMENT n n n Admit to the ICU for cases of impending respiratory failure. Plasmapheresis and IVIG are first-line treatments. Corticosteroids are not indicated. Aggressive physical rehabilitation is imperative. AM YOTR OP HI C L ATE R AL S C LE R OS IS ( AL S ) KEY FACT A 55-year-old male presents with slowly progressive weakness in his left upper extremity and later his right, associated with fasciculations and atrophy, but without bladder disturbance and with a normal cervical MRI. Think ALS. A chronic, progressive degenerative disease of unknown etiology characterized by loss of upper and lower motor neurons. Also known as Lou Gehrig’s disease. ALS has an unrelenting course and almost always progresses to respiratory failure and death, usually within 5 years of diagnosis. Males are more commonly affected than females, and onset is generally between ages 40 and 80. HISTORY/PE n n n Presents with asymmetric, slowly progressive weakness (over months to years) affecting the arms, legs, diaphragm, and lower cranial nerves. Some patients initially present with fasciculations. Weight loss is common. Associated with UMN and/or LMN signs (see Table 2.10-9). Eye movements and sphincter tone are generally spared. Tongue atrophy and fasciculations may be apparent. Emotional lability is a common feature. DIAGNOSIS n KEY FACT Some 25% of people have “bulbar onset” ALS, which presents with difficulty swallowing, loss of tongue motility, and difficulty speaking (slurred or nasal quality). n n n The clinical presentation is usually diagnostic. Involvement of the tongue (CN XII) or oropharyngeal muscles (CN IX, X), known as “bulbar” involvement, suggests pathology above the foramen magnum and generally excludes the most common differential, cervical spondylosis with compressive myelopathy, as a cause. EMG/nerve conduction studies reveal widespread denervation and fibrillation potentials. Such studies are principally performed to exclude other demyelinating motor neuropathies. CT/MRI of the cervical spine is done to exclude structural lesions, particularly in those without bulbar involvement. TREATMENT Supportive measures and patient education. TA B L E 2 . 10 - 9 . UMN vs. LMN Signs CLINICAL FEATURES UMN LMN Pattern of Pyramidal (arm extensors, leg weakness flexors) Variable Tone Spastic (↑); initially flaccid (↓) Flaccid (↓) DTRs ↑ (initially ↓ or normal) ↓ Miscellaneous signs Babinski’s, other CNS signs Atrophy, fasciculations NEUROLOGY HIGH-YIELD FACTS IN 265 Dementia A chronic, progressive, global decline in multiple cognitive areas. Alzheimer’s disease accounts for 60–80% of cases. The differential diagnosis is described in the mnemonic DEMENTIAS. Take care not to confuse delirium and dementia (see the Psychiatry chapter). Table 2.10-10 and the sections below contrast the time course, diagnostic criteria, and treatment of common types of dementia. A 59-year-old female presents to her primary care physician with concerns about worsening memory, difficulty participating in her daily activities, restlessness, and difficulty sleeping for the past 3 months. What is the most likely diagnosis? AL Z H E IM E R ’S D I SE AS E (A D) Risk factors include age, female gender, a family history, Down syndrome, and low educational status. Pathology involves neurofibrillary tangles, neuritic plaques with amyloid deposition, amyloid angiopathy, and neuronal loss. HISTORY/PE n n Amnesia for newly acquired information is usually the first presenting sign, followed by language deficits, acalculia, depression, agitation, psychosis, and apraxia (inability to perform skilled movements). Mild cognitive impairment may precede AD by 10 years. Survival is 5–10 years from the onset of symptoms, with death usually occurring 2° to aspiration pneumonia or other infections. Except for the mental state, the physical examination is generally normal. DIAGNOSIS n A diagnosis of exclusion suggested by clinical features and by an insidiously progressive cognitive course without substantial motor impairment. TA B L E 2 . 10 - 10 . MNEMONIC Differential diagnosis— DEMENTIAS NeuroDegenerative diseases Endocrine Metabolic Exogenous Neoplasm Trauma Infection Affective disorders Stroke/Structural Types of Dementia TYPE Alzheimer’s disease TIME COURSE Gradual. (AD) PATHOLOGY IMAGING/STUDIES Diffuse atrophy with enlarged PET imaging shows nonspecific bilateral temporoparietal ventricles, senile plaques, and hypometabolism. neurofibrillary tangles. Vascular dementia Abrupt. — Brain imaging reveals evidence of old infarctions or extensive deep white-matter changes 2° to chronic ischemia. Pick’s disease Gradual. Pick bodies (round MRI/CT show frontotemporal atrophy. intraneuronal inclusions). Normal pressure Gradual/abrupt. — CT/MRI reveal ventricular enlargement. Abrupt. Prion proteins on biopsy. MRI with diffusion-weighted imaging may show ↑ T2 and hydrocephalus (NPH) Creutzfeldt-Jakob disease (CJD) FLAIR intensity in the putamen and the head of the caudate and is also used to exclude structural brain lesions. EEG shows pyramidal signs and periodic sharp waves. 266 HIGH-YIELD FACTS IN NEUROLOGY n n Pseudodementia. The key difference between pseudodementia and AD is that in pseudodementia, the patient is actively concerned about memory loss. n n Definitively diagnosed on autopsy. MRI or CT may show atrophy and can rule out other causes, particularly vascular dementia, NPH, and chronic subdural hematoma. CSF is normal. Neuropsychological testing can help distinguish dementia from depression. Hypothyroidism, vitamin B12 deficiency, and neurosyphilis should be ruled out in atypical cases. TREATMENT n n Prevention of associated symptoms: n Provide supportive therapy for the patient and family. n Treat depression, agitation, sleep disorders, hallucinations, and delusions. Prevention of disease progression: Cholinesterase inhibitors (donepezil, rivastigmine, galantamine, tacrine) are first-line therapy for mild to moderate disease. Tacrine is associated with hepatotoxicity and is less often used. Memantine, an NMDA receptor antagonist, may slow decline in moderate to severe disease. V ASC U LAR DE M E NTI A Dementia associated with a history of stroke and cerebrovascular disease is the second most common type of dementia. Risk factors include age, hypertension, diabetes, embolic sources, and a history of stroke. KEY FACT If a patient shows abrupt changes in symptoms over time rather than a steady decline, think vascular dementia. DIAGNOSIS Criteria for the diagnosis of vascular dementia include the presence of dementia and 2 or more of the following: n n Focal neurologic signs on examination. Symptom onset that was abrupt, stepwise, or related to stroke. TREATMENT Protocols for the prevention and treatment of vascular dementia are the same as those for stroke. F R ONTOTE M P OR AL D E M E NTI A (P I C K ’S D ISE A S E ) A rare, progressive form of dementia characterized by atrophy of the frontal and temporal lobes. HISTORY/PE n n Patients present with significant changes in behavior and personality early in the disease. Other symptoms include speech disturbance, inattentiveness, compulsive behaviors, and occasionally extrapyramidal signs. Unlike Parkinson’s disease, frontotemporal dementia rarely begins after age 75. DIAGNOSIS The diagnosis is suggested by clinical features and by evidence of circumscribed frontotemporal atrophy revealed by MRI or CT. TREATMENT Treatment is symptomatic. NEUROLOGY HIGH-YIELD FACTS IN 267 N OR M A L P R E S SU R E H Y D R O CE P H ALU S ( NP H) A potentially treatable form of dementia that is thought to arise from impaired CSF outflow from the brain. HISTORY/PE Symptoms include the classic triad of dementia, gait apraxia, and urinary incontinence. Headaches and other signs of ↑ ICP (eg, papilledema) typically do not appear, although continuous ICP monitoring may reveal spikes of elevated pressure. DIAGNOSIS n n The diagnosis is suggested by clinical features. The gait is classically described as “magnetic” or with “feet glued to the floor,” as the forefoot is not completely dorsally extended. CT or MRI shows ventricular enlargement out of proportion to sulcal atrophy (see Figure 2.10-8). TREATMENT LP or continuous lumbar CSF drainage for several days may cause clinically significant improvement of the patient’s symptoms. If so, surgical CSF shunting is the treatment of choice. Normal pressure hydrocephalus. T2-weighted MRI from a 60-year-old female with slowly developing urinary incontinence, gait instability, and early dementia shows marked dilation of the lateral ventricles (red arrows). This is out of proportion to the sulci (yellow arrow), which appear normal. (Reproduced with permission from USMLERx.com.) FIGURE 2.10-8. KEY FACT NPH = “Wet (incontinence), Wobbly (apraxia), and Wacky (dementia).” 268 HIGH-YIELD FACTS IN NEUROLOGY CR E U TZF E LDT-JAK OB DIS E ASE ( CJD ) Although it is the most common prion disease, CJD remains an extremely rare form of dementia. CJD is a member of the transmissible spongiform encephalopathies, all of which are characterized by spongy degeneration, neuronal loss, and astrocytic proliferation. In CJD, an abnormal protease-resistant prion protein accumulates in the brain. HISTORY/PE KEY FACT If a patient presents with rapid cognitive decline over the course of weeks to months, think CJD. n n CJD causes a subacute dementia with ataxia or startle-induced myoclonic jerks with rapid clinical decline that is noted weeks to months after symptom onset. New-variant CJD (mad cow disease) is a more slowly progressive prion disease seen in younger people with a history of eating contaminated beef or contaminated human brains (kuru). DIAGNOSIS n n n n Suggested by clinical features. The differential diagnosis often includes limbic encephalitis, Hashimoto’s (steroid-responsive) encephalopathy, and toxic encephalopathy (eg, lithium or bismuth). Elevated levels of CSF 14-3-3 and tau protein are seen. Definitive diagnosis can be made only by brain biopsy or autopsy. Specimens must be handled with special precautions to prevent transmission. TREATMENT Currently, there is no effective treatment. Most patients die within 1 year of symptom onset. Movement Disorders HU NTI NG TON’S DI S E AS E (HD ) A rare, hyperkinetic, autosomal dominant disease involving multiple abnormal CAG triplet repeats (< 29 is normal) within the HD gene on chromosome 4. The number of repeats typically expands in subsequent generations, leading to earlier expression and more severe disease (anticipation). Life expectancy is 20 years from the time of diagnosis. KEY FACT HISTORY/PE n If a 43-year-old male patient presents with sudden onset of chorea, irritability, and antisocial behavior and his father experienced these symptoms at a slightly older age, think Huntington’s disease. n Presents at 30–50 years of age with gradual onset of chorea (sudden onset of purposeless, involuntary dancelike movements), altered behavior, and dementia (begins as irritability, clumsiness, fidgetiness, moodiness, and antisocial behavior). Weight loss and depression may also be seen. DIAGNOSIS n n A clinical diagnosis confirmed by genetic testing. CT/MRI show cerebral atrophy (especially of the caudate and putamen; see Figure 2.10-9). Molecular genetic testing is conducted to determine the number of CAG repeats. NEUROLOGY A HIGH-YIELD FACTS IN 269 B FIGURE 2.10-9. Atrophy of the cerebral and caudate nuclei in Huntington’s disease. (A) Noncontrast CT in a 54-year-old patient with Huntington’s disease shows atrophy of the caudate nuclei (arrows) and diffuse cerebral atrophy with ex vacuo dilation of the lateral ventricles. (B) A normal 54-year-old subject (arrows on caudate nuclei). (Reproduced with permission from Ropper AH, Samuels MA. Adams & Victor’s Principles of Neurology, 9th ed. New York: McGraw-Hill, 2009, Fig. 39-4.) TREATMENT n n n There is no cure, and disease progression cannot be halted. Treat symptomatically. Reserpine or tetrabenazine can be given to minimize unwanted movements. Psychosis should preferably be treated with atypical antipsychotics to ↓ the risk of extrapyramidal side effects or tardive dyskinesia. SSRIs are first-line therapy for depression. Genetic counseling should be offered to offspring. PA R K IN S O N ’ S DI SE A SE An idiopathic hypokinetic disorder that usually begins after age 50–60 and is attributable to dopamine depletion in the substantia nigra. It is characterized pathologically by Lewy bodies, which are intraneuronal eosinophilic inclusions. HISTORY/PE n n n The “Parkinson’s tetrad” consists of the following: n Resting tremor (eg, “pill rolling”). n Rigidity: “Cogwheeling” due to the combined effects of rigidity and tremor. n Bradykinesia: Slowed movements as well as difficulty initiating movements. Festinating gait (a wide leg stance with short accelerating steps) without arm swing is also seen. n Postural instability: Stooped posture, impaired righting reflexes, freezing, falls. Other manifestations: Masked facies, memory loss, and micrographia. Parkinsonism is the broader clinical phenotype of bradykinesia and rigidity (with or without substantial tremor) and is often caused by disorders other than idiopathic Parkinson’s disease, most commonly multiple subcortical infarcts (“vascular parkinsonism”). KEY FACT A significant difference between the gait abnormalities of Parkinson’s and that of NPH is preservation of arm swing in NPH. A 65-year-old male presents to his internist with 10 years of bilateral hand tremors. His mother and older brother have similar tremors. He denies difficulty concentrating, trouble with rising from seated positions, or recent falls. What is the most likely diagnosis? 270 HIGH-YIELD FACTS IN NEUROLOGY n KEY FACT There are 4 PaRTS to Parkinson’s: Postural instability, Rigidity (cogwheeling), Tremor (“pill rolling”), and Slowed movements (bradykinesia). n Nonidiopathic causes of parkinsonism include viral encephalitis (postencephalitic parkinsonism), trauma (dementia pugilistica), and toxins such as manganese, MPTP (“designer drugs”), and, iatrogenically, neuroleptics (tardive dyskinesia). These disorders are often diagnosed when levodopa/carbidopa fail to produce a clinical response. Other L-dopa-unresponsive mimics of Parkinson’s disease include progressive supranuclear palsy and multiple-system atrophy. TREATMENT n KEY FACT n n n Parkinson’s disease—dopamine deficiency. Alzheimer’s disease—ACh and norepinephrine deficiencies. Myasthenia gravis—absent ACh activity. n n n n n Levodopa/carbidopa combination therapy is the mainstay of treatment. Levodopa is a dopamine precursor that can cross the blood-brain barrier. Carbidopa blocks the peripheral conversion of levodopa to prevent the side effects of levodopa (nausea and vomiting). Dopamine agonists (ropinirole, pramipexole, bromocriptine) can be used for treatment in early disease. Apomorphine is another dopamine agonist that can be used for rescue therapy if a sudden additional dose is needed. Selegiline (an MAO-B inhibitor) may be neuroprotective and may ↓ the need for levodopa. Catechol-O-methyltransferase (COMT) inhibitors (entacapone or tolcapone) are not given alone but ↑ the availability of levodopa to the brain and may ↓ motor fluctuations. Amantadine has mild antiparkinsonian activity and may improve akinesia, rigidity, and tremor. It can be used for temporary, short-term monotherapy early in the course of the disease. If medical therapy is insufficient, surgical pallidotomy or chronic deep brain stimulators may produce clinical benefit. Neoplasms KEY FACT Intracranial neoplasms may be 1° (30%) or metastatic (70%). n Most CNS tumors are metastatic. The most common 1° CNS tumors in adults are glioblastoma multiforme and meningioma. The most common 1° CNS tumors in children are medulloblastomas and astrocytomas. n n Of all 1° brain tumors, 40% are benign, and these rarely spread beyond the CNS. Metastatic tumors are most often from 1° lung, breast, kidney, and GI tract neoplasms and melanoma. They occur at the gray-white junction; may be multiple discrete nodules; and are characterized by rapid growth, invasiveness, necrosis, and neovascularization. More common in males than in females, except for meningiomas. HISTORY/PE n n Essential tremor. Remember that bilateral tremors are less common in Parkinson’s disease, and patients with Parkinson’s are more likely to present with multiple symptoms. n Symptoms depend on tumor type and location (see Tables 2.10-11 and 2.10-12), local growth and resulting mass effect, cerebral edema, or ↑ ICP 2° to ventricular obstruction. Although headaches are often thought of as the main presenting symptom, only 31% of patients present with headache at diagnosis, and only 8% have headache as the sole presenting feature. Seizures or slowly progressive focal motor deficits are the most common presenting features. When ↑ ICP is the presenting feature, symptoms include headache, nausea/vomiting, and diplopia (false localizing CN VI palsies). However, in the era of neuroimaging, it is relatively rare for patients to present with ↑ ICP. Hemispheric tumors often produce visual field abnormalities and neuropsychiatric symptoms, including personality changes, lethargy, syncope, cognitive decline, aphasia, apraxia, and depression. Parasellar lesions usually present with visual loss and/or diplopia. Posterior fossa lesions tend NEUROLOGY TA B L E 2 . 10 - 11 . HIGH-YIELD FACTS IN 271 Common 1° Neoplasms in Adults TUMOR PATHOLOGY Astrocytoma PRESENTATION TREATMENT Resection if possible; radiation. Arises in brain parenchyma. Low- Presents with seizures, focal grade astrocytomas are relatively deficits, or headache; has a uncommon. protracted course. Has a better prognosis than glioblastoma multiforme. Glioblastoma multiforme High mitotic activity and either The most common 1° brain Surgical removal/ (grade IV astrocytoma) endothelial proliferation or tumor. Presents with headache, resection. Radiation and necrosis in tumor, leading to ring- seizures, or focal deficits. chemotherapy have variable enhancing lesions on MRI. Progresses rapidly and has a poor results. prognosis (< 1 year from the time of prognosis). Meningioma Originates from the dura mater Presentation depends on Surgical resection; radiation for or arachnoid. location; often related to cranial unresectable tumors. neuropathy or is an incidental finding. Has a good prognosis; incidence ↑ with age. Imaging may reveal dural tail. Derived from Schwann cells. Acoustic neuroma Presents with ipsilateral tinnitus, Observation; surgical removal. hearing loss, vertigo, and late (schwannoma) signs of CN V–VII or brainstem compression. n to present with gait ataxia or cranial nerve deficits and/or ↑ ICP from obstructive hydrocephalus. Metastases that tend to present with intracranial hemorrhage include renal cell carcinoma, thyroid papillary cancer, choriocarcinoma, and melanoma. TA B L E 2 . 10 - 12 . KEY FACT Lung and Skin Go to the BRain: Lung, Skin, GI, Breast, Renal. Common 1° Neoplasms in Children TUMOR Medulloblastoma Ependymoma PATHOLOGY PRESENTATION TREATMENT A primitive neuroectodermal tumor. Highly malignant; may seed the Surgical resection coupled with Arises from the fourth ventricle and subarachnoid space. May cause radiation and chemotherapy. causes ↑ ICP. obstructive hydrocephalus. May arise from the ependyma of a Low grade. May cause obstructive ventricle (commonly the fourth) or hydrocephalus. Surgical resection; radiation. the spinal cord. Craniopharyngioma The most common suprasellar tumor in children. Calcification is common. Benign. May cause hypopituitarism. Surgical resection. 272 HIGH-YIELD FACTS IN KEY FACT NEUROLOGY DIAGNOSIS n Two-thirds of 1° brain tumors in adults are supratentorial. One-third of those in children are supratentorial. n KEY FACT Symptoms of ↑ ICP: n Nausea n Vomiting n Diplopia n Headache that is worse in the morning, with bending over, or with recumbency Contrast CT and MRI with and without gadolinium to localize and determine the extent of the lesion. Gadolinium-enhanced MRI is generally better for visualizing soft tissue tumors and vascularity, but CT is preferred for evaluating skull base lesions and for emergencies (eg, obstructive hydrocephalus) when an MRI cannot be rapidly acquired. Histologic diagnosis via CT-guided biopsy or surgical tumor debulking/ removal. TREATMENT n n n n Resection (if possible), radiation, and chemotherapy. Therapy is highly dependent on tumor type, histology, progression, and site (see Tables 2.10-11 and 2.10-12). Corticosteroids can be used to ↓ vasogenic edema and ICP. Management is often palliative. Seizure prophylaxis can be used in patients who have had a seizure. Neurocutaneous Disorders NE U R OF I BR OM ATOS I S ( NF ) The most common neurocutaneous disorder. There are 2 major types: neurofibromatosis 1 (NF1, or von Recklinghausen’s syndrome) and neurofibromatosis 2 (NF2). Both obey autosomal dominant inheritance. The NF genes are located on chromosome 17 and 22, respectively, for NF1 and NF2. HISTORY/PE n n FIGURE 2.10-10. Neurofibromas associated with neurofibromatosis. (Reproduced with permission from USMLERx.com.) Diagnostic criteria for NF1 include 2 or more of the following: n Six café au lait spots (each ≥ 5 mm in children or ≥ 15 mm in adults). n Two neurofibromas of any type (see Figure 2.10-10). n Freckling in the axillary or inguinal area. n Optic glioma. n Two Lisch nodules (pigmented iris hamartomas). n Bone abnormality (eg, kyphoscoliosis). n A first-degree relative with NF1. Diagnostic criteria for NF2 are as follows: n Bilateral acoustic neuromas or a first-degree relative with NF2 and either unilateral acoustic neuromas or 2 of any of the following: neurofibromas, meningiomas, gliomas, or schwannoma. n Other features include seizures, skin nodules, and café au lait spots. DIAGNOSIS n n KEY FACT TREATMENT n NF1 and NF2 are clinically evident by ages 15 and 20, respectively. MRI of the brain, brainstem, and spine with gadolinium. Conduct a complete dermatologic exam, ophthalmologic exam, and family history. Auditory testing is recommended. n There is no cure; treatment is symptomatic (eg, surgery for kyphoscoliosis or debulking of tumors). Acoustic neuromas and optic gliomas can be treated with surgery or radiosurgery. Meningiomas may be resected. NEUROLOGY HIGH-YIELD FACTS IN 273 T U B E R O US S CLE R O SI S Affects many organ systems, including the CNS, skin, heart, retina, and kidneys. Obeys autosomal dominant inheritance. HISTORY/PE n n n n n n Presents with convulsive seizures (infantile spasms in infants), “ash-leaf” hypopigmented lesions on the trunk and extremities, and mental retardation (↑ likelihood with early age of onset). Other skin manifestations include sebaceous adenomas (small red nodules on the nose and cheeks in the shape of a butterfly) and a shagreen patch (a rough papule in the lumbosacral region with an orange-peel consistency). Two retinal lesions are recognized: (1) mulberry tumors, which arise from the nerve head; and (2) phakomas, which are round, flat, gray lesions located peripherally in the retina. Symptoms are 2° to small benign tumors that grow on the face, eyes, brain, kidney, and other organs. Mental retardation and CHF from cardiac rhabdomyoma may also be seen. Renal involvement may include hamartomas, angiomyolipomas, or, rarely, renal cell carcinoma. DIAGNOSIS n n n Diagnosis is usually clinical. Skin lesions are enhanced by a Wood’s UV lamp. Imaging: n Head CT: Reveals calcified tubers within the cerebrum in the periventricular area. Lesions may on rare occasion transform into malignant astrocytomas. n ECG: Evaluate for rhabdomyoma of the heart, especially in the apex of the left ventricle (affects > 50% of patients). n Renal ultrasound: May reveal angiomyolipomas, cysts, or, rarely, renal cell carcinoma. n Renal CT: May show angiomyolipomas (these lesions are also thought to be responsible for the cystic or fibrous pulmonary changes sometimes seen in tuberous sclerosis patients). n CXR: May reveal pulmonary lesions or cardiomegaly 2° to rhabdomyoma. TREATMENT n n n Treatment should be based on symptoms (eg, cosmetic surgery for adenoma sebaceum). Simple partial or complex partial seizures can be controlled with oxcarbazepine or carbamazepine; lamotrigine can be given for generalized seizures. Treat infantile spasms with ACTH or vigabatrin. Surgical intervention may be indicated in the setting of ↑ ICP or for seizures associated with an epileptogenic focus or severe developmental delay. KEY FACT If you see infantile spasms in the setting of a hypopigmented lesion on the child’s trunk, consider tuberous sclerosis. 274 HIGH-YIELD FACTS IN NEUROLOGY Aphasia A general term for speech and language disorders. Usually results from insults (eg, strokes, tumors, abscesses) to the “dominant hemisphere” (the left hemisphere in > 95% of right-handed people and 60–80% of left-handed people). B R OC A’S A P HAS I A n KEY FACT n So many names, it’s a wonder we are talking about aphasias! n Broca’s aphasia = motor aphasia, expressive aphasia, or nonfluent aphasia. n Wernicke’s aphasia = sensory aphasia, fluent aphasia, or receptive aphasia. n A disorder of language production, including writing, with intact comprehension. Due to an insult to Broca’s area in the posterior inferior frontal gyrus (see Figure 2.10-11). Often 2° to a left superior MCA stroke. Also known as motor aphasia. Hx/PE: n Presents with impaired speech production, frustration with awareness of deficits, arm and facial hemiparesis, hemisensory loss, and apraxia of the oral muscles. Speech is described as “telegraphic” and agrammatical with frequent pauses. n In true Broca’s aphasia, repetition is impaired. If repetition is intact, the deficit is called transcortical motor aphasia (TMA), which is due to a lesion around Broca’s area. Tx: Speech therapy (varying outcomes with intermediate prognosis). W E R NI C K E ’S AP HA S I A KEY FACT n n Broca’s aphasia—posterior inferior frontal gyrus. Wernicke’s aphasia—left posterior superior temporal gyrus. n n n KEY FACT BROca’s is BROken and Wernicke’s is Wordy. n A disorder of language comprehension with intact yet nonsensical production. Due to an insult to Wernicke’s area in the left posterior superior temporal (perisylvian) gyrus. Often 2° to left inferior/posterior MCA embolic stroke (see Figure 2.10-11). Hx/PE: n Presents with preserved fluency of language with impaired repetition and comprehension, leading to “word salad.” Patients are unable to follow commands; make frequent use of neologisms (made-up words) and paraphasic errors (word substitutions); and show lack of awareness of deficits. n In true Wernicke’s aphasia, repetition is impaired. If repetition is intact, the deficit is called transcortical sensory aphasia (TSA), which is due to a lesion around Wernicke’s area. Tx: Treat the underlying etiology and institute speech therapy. Coma Motor speech area (Broca) Arcuate fasciculus Language comprehension area (Wernicke) A state of unconsciousness marked by a profound suppression of responses to external and internal stimuli (ie, a state of unarousable unresponsiveness). Lesser states of impaired arousal are known as “obtundation” or “stupor.” Coma is due to either catastrophic structural CNS injury or diffuse metabolic dysfunction. Coma indicates bilateral dysfunction of both cerebral hemispheres or the brainstem (pons or higher); when structural, coma usually results from bilateral pathology. Causes include the following: FIGURE 2.10-11. Broca’s and Wernicke’s areas. (Reproduced with permission n from Waxman SG. Clinical Neuroanatomy, 26th ed. n New York: McGraw-Hill, 2010, Fig. 21-1.) Diffuse hypoxic/ischemic encephalopathy (eg, postcardiac arrest). Diffuse axonal injury from high-acceleration trauma (eg, motor vehicle accidents). NEUROLOGY n n n n n n n HIGH-YIELD FACTS IN 275 Brain herniation (eg, cerebral mass lesion, SAH with obstructive hydrocephalus). Widespread infection (eg, viral encephalitis or advanced bacterial meningitis). Massive brainstem hemorrhage or infarction (eg, pontine myelinolysis). Electrolyte disturbances (eg, hypoglycemia). Exogenous toxins (eg, opiates, benzodiazepines, EtOH, other drugs). Generalized seizure activity or postictal states. Endocrine (eg, severe hypothyroidism) or metabolic dysfunction (eg, thiamine deficiency). HISTORY/PE n n Obtain a complete medical history from witnesses, including current medications (eg, sedatives). Conduct thorough medical and neurologic exams, including assessments of mental status, spontaneous motor activity, muscular tone, breathing pattern, funduscopy, pupillary response, eye movements (including the doll’seye maneuver if the neck has been cleared from fracture), corneal reflex, cold-water caloric testing, gag reflex, and motor or autonomic responses to noxious stimuli applied to the limbs, trunk, and face (eg, retromandibular pressure, nasal tickle). DIAGNOSIS n n n n n Typically made by a combination of the history/physical and laboratory tests or neuroimaging. Check glucose, electrolytes, calcium, a renal panel, LFTs, ABGs, a toxicology screen, and blood and CSF cultures. Other metabolic tests (eg, TSH) may be performed based on the clinical index of suspicion. Obtain a head CT without contrast before other imaging to evaluate for hemorrhage or structural changes. Imaging should precede LP in light of the risk of herniation. Obtain an MRI to exclude structural changes and ischemia (eg, brainstem). EEG may be both diagnostic and prognostic. Rule out catatonia, hysterical or conversion unresponsiveness, “locked-in” syndrome, or persistent vegetative state (PVS), all of which can be confused with true coma (see Table 2.10-13). n “Locked-in” syndrome: Patients are awake and alert but can move only their eyes and eyelids. Associated with central pontine myelinolysis, brainstem stroke, and advanced ALS. TA B L E 2 . 10 - 13 . Differential Diagnosis of Coma VARIABLE Alertness “LOCKED-IN” SYNDROME PVS COMA BRAIN DEATH Wakeful and alert with Wakefulness without Unconscious; no sleep- Unconscious; no sleep- retained cognitive awareness. Eyes open. wake cycles. Eyes closed. wake cycles. Central pontine Diffuse cortical injury or See above. Same as coma. myelinolysis, brainstem hypoxic ischemic injury. abilities. Most common causes stroke, advanced ALS. Voluntary motor ability Eyes and eyelids. None. None. None. Respiratory drive Yes. Yes. Yes. None. 276 HIGH-YIELD FACTS IN NEUROLOGY n PVS: Characterized by normal wake-sleep cycles but lack of awareness of self or the environment. The most common causes are trauma with diffuse cortical injury or hypoxic ischemic injury. TREATMENT KEY FACT Initial treatment should consist of the following measures: n Artificial life support can be discontinued only after 2 physicians have declared the patient legally brain dead. n n n Stabilize the patient: Attend to ABCs. Reverse the reversible: Administer DONT—Dextrose, Oxygen, Naloxone, and Thiamine. Identify and treat the underlying cause and associated complications. Prevent further damage. Nutritional Deficiencies Table 2.10-14 describes neurologic syndromes commonly associated with nutritional deficiencies. TA B L E 2 . 10 - 14 . VITAMIN Neurologic Syndromes Associated with Nutritional Deficiencies SYNDROME Thiamine Wernicke’s (vitamin B1) encephalopathy SIGNS/SYMPTOMS The classic triad consists of CLASSIC PATIENTS Alcoholics, hyperemesis, TREATMENT Reversible almost encephalopathy (disorientation, starvation, renal immediately inattentiveness, confusion, coma), dialysis, AIDS. Can with thiamine ophthalmoplegia (nystagmus, be brought on or administration. lateral rectus palsy, conjugate gaze exacerbated by Always give palsy, vertical gaze palsy), and high-dose glucose thiamine before ataxia (polyneuropathy; cerebellar administration. glucose. and vestibular dysfunction leading to problems standing or walking). Korsakoff’s dementia Above plus anterograde and Same as above. retrograde amnesia, horizontal Usually occurs in the nystagmus, and confabulations. “resolution” phase of Irreversible. Wernicke’s syndrome that was treated too late or inadequately. Cyano- Combined system Gradual, progressive onset. Patients with pernicious B12 injections or large cobalamin disease (CSD) or Symmetric paresthesias, stocking- anemia; strict vegetarians; oral doses. (vitamin B12)a subacute combined glove sensory neuropathy, leg status post gastric or ileal degeneration of the stiffness, spasticity, paraplegia, resection; ileal disease posterior and lateral bowel and bladder dysfunction, sore (eg, Crohn’s); alcoholics or columns of the spinal tongue. Dementia. others with malnutrition. Irritability; personality changes Alcoholics; patients with Reversible if corrected without the neurologic symptoms pernicious anemia. early. cord; peripheral neuropathy. Folatea Folate deficiency of CSD. a Associated with ↑ homocysteine and an ↑ risk of vascular events. NEUROLOGY HIGH-YIELD FACTS IN 277 Ophthalmology V IS U A L F I E L D DE F E CT S Figure 2.10-12 illustrates common visual field defects and the anatomic areas with which they are associated. GL A U CO M A In the eye, aqueous humor is produced by the ciliary body on the iris, travels through the pupil into the anterior chamber, and is then drained via the trabecular meshwork in the angle of the anterior chamber. n n Any process that disrupts this natural flow can ↑ intraocular pressure (IOP), damaging the optic nerve and causing visual field deficits. Glaucoma is the result of such damage to the nerve. Open-angle glaucoma is much more common in the United States than closed-angle glaucoma. Closed-Angle Glaucoma ■ n n Occurs when the iris dilates and pushes against the lens of the eye, disrupting flow of aqueous humor into the anterior chamber. Pressure in the posterior chamber then pushes the peripheral iris forward and blocks the angle. Risk factors include family history, older age, Asian ethnicity, hyperopia, prolonged pupillary dilation (prolonged time in a dark area, stress, medications), anterior uveitis, and lens dislocation. Hx/PE: n Presents with extreme eye pain, blurred vision, headache, nausea, and vomiting. n A hard, red eye is seen (from acute closure of a narrow anterior chamber angle); the pupil is dilated and nonreactive to light. Defect in visual field of Lt. eye 1 Rt. eye Lt. 2 3 Optic chiasm Rt. Optic nerve 2 Lateral geniculate body 5 4 1 3 Optic tract 4 Meyer's loop Dorsal optic radiation 5 6 Calcarine fissure Visual cortex 6 Visual field defects. (1) Right anopsia. (2) Bitemporal hemianopsia. (3) Left homonymous hemianopsia. (4) Left upper quadrantic anopsia (right temporal lesion). (5) Left lower quadrantic anopsia (right parietal lesion). (6) Left hemianopsia with macular sparing. FIGURE 2.10-12. A 45-year-old Caucasian male presents to the ER with sudden-onset headache and a right-sided dilated pupil. His right pupil is nonreactive to light and hard to the touch. What is the most likely diagnosis, and what medications should be avoided in this patient? 278 HIGH-YIELD FACTS IN NEUROLOGY If it resolves spontaneously prior to presentation (eg, with pupillary constriction in sunlight), ophthalmologic examination may reveal narrow angles in 1 or both eyes. Dx: Diagnosis is based on clinical history and examination. Those that resolve may mimic a migraine headache with blurred vision. Tx: A medical emergency that can cause blindness. Treatment to ↓ IOP is as follows: n Eyedrops (timolol, pilocarpine, apraclonidine). n Systemic medications (oral or IV acetazolamide, IV mannitol). n Laser peripheral iridotomy, which creates a hole in the peripheral iris, is curative and may be performed prophylactically. n Do not give any medications that cause pupillary dilation. n KEY FACT n n A headache is a headache is a headache? Closed-angle glaucoma headaches are triggered by darkness (due to pupillary dilation). Migraine headaches are triggered by bright lights. Open-Angle Glaucoma n n n FIGURE 2.10-13. Open-angle glaucoma with an increased cup-to-disk ratio. (Reproduced with permission from USMLERx. com.) n KEY FACT n Open-angle glaucoma generally occurs bilaterally, but angle-closure glaucoma occurs unilaterally. Flow of aqueous humor through the trabecular meshwork is limited, increasing IOP. A diseased trabecular meshwork obstructs proper drainage of the eye, leading to a gradual ↑ in pressure and progressive vision loss. Risk factors include age > 40 years, African American ethnicity, diabetes, and myopia. Hx/PE: n Should be suspected in patients > 35 years of age who need frequent lens changes and have mild headaches, visual disturbances, and impaired adaptation to darkness. n Usually asymptomatic until late in the clinical course. n Characterized by gradual loss of peripheral vision. n Cupping of the optic nerve head is seen on funduscopic exam (see Figure 2.10-13). Dx: Tonometry, ophthalmoscopic visualization of the optic nerve, and visual field testing are most important. A diseased trabecular meshwork obstructs proper drainage of the eye, gradually increasing pressure and leading to progressive vision loss. Tx: n Treat with topical β-blockers (timolol, betaxolol) to ↓ aqueous humor production or with pilocarpine to ↑ aqueous outflow. n Carbonic anhydrase inhibitors may also be used. n If medication fails, laser trabeculoplasty or a trabeculectomy can improve aqueous drainage. CATAR AC T S n n n Lens opacification resulting in obstructed passage of light. Associated with diabetes, hypertension, advanced age, and exposure to radiation. Hx/PE: Presents with loss of visual acuity and difficulty with night vision. Tx: No medical therapy is available. Surgical lens removal and replacement. AG E -RE LATE D M AC U LAR DE G E NE R ATI ON ( AM D) Closed-angle glaucoma. Avoid pupildilating medications such as atropine, which will ↑ IOP and prevent drainage of aqueous humor. More common among Caucasians, females, smokers, and those with a family history. HISTORY/PE n n Presents with painless loss of central vision. Early signs include distortion of straight lines. Atrophic (“dry”) macular degeneration: Responsible for 80% of cases. Causes gradual vision loss. NEUROLOGY n Exudative or neovascular (“wet”) macular degeneration: Much less common, but associated with more rapid and severe vision damage. DIAGNOSIS Funduscopy by an ophthalmologist reveals drusen and/or pigmentary changes in patients with atrophic AMD. Hemorrhage and subretinal fluid are suggestive of exudative AMD (see Figure 2.10-14). HIGH-YIELD FACTS IN 279 KEY FACT In the United States, macular degeneration is the leading cause of permanent bilateral visual loss in the elderly. TREATMENT n n Atrophic AMD: n No treatment is currently available, although a combination of vitamins (vitamin C, vitamin E, beta-carotene, and zinc) has been found to slow disease progression. n An ↑ mortality rate from high doses of vitamin E and an elevated lung cancer incidence among individuals on beta-carotene supplementation may require modification of this regimen for smokers. Exudative AMD: n VEGF inhibitors have been shown to improve vision (ranibizumab, bevacizumab) or slow visual loss (pegaptanib) in patients with exudative AMD. n Photodynamic therapy with verteporfin, which involves use of a laser to selectively target retinal vessels, may be useful in conjunction with VEGF inhibitors. RET IN A L V A S C U L A R O CC L U SIO N n n n Occurs in elderly patients and is often idiopathic. Hx/PE: n Central retinal artery occlusion: Presents with sudden, painless, unilateral blindness. The pupil reacts to a near stimulus but is sluggishly reactive to direct light. Patients present with a cherry-red spot on the fovea, retinal swelling (whitish appearance to the nerve fiber layer), and retinal arteries that may appear bloodless. n Central retinal vein occlusion: Characterized by rapid, painless vision loss of variable severity. Associated with hypertension. A choked, swollen optic disk with hemorrhages, venous stasis retinal hemorrhages, cotton-wool spots, and edema of the macula may be seen on funduscopic exam. Tx: n Central retinal artery occlusion: Treatments should be applied immediately before irreversible retinal infarction and permanent blindness ensue. n Intra-arterial thrombolysis of the ophthalmic artery within 8 hours of onset of symptoms may produce benefit in some patients, although evidence remains controversial. n Other treatments applied but of unclear benefit include decreasing IOP through drainage of the anterior chamber, ocular massage and high-flow oxygen, or IV acetazolamide. n Central retinal vein occlusion: Laser photocoagulation has variable results. FIGURE 2.10-14. Macular degeneration with evidence of drusen and fibrosis in the macula. (Reproduced with permission from USMLERx.com.) 280 HIGH-YIELD FACTS IN NEUROLOGY NOTES HIGH-YIELD FACTS IN OBSTETRICS Physiology of Normal Pregnancy 282 Obstetric Complications of Pregnancy 302 THE BASICS OF PREGNANCY 282 ECTOPIC PREGNANCY 302 DIAGNOSIS OF PREGNANCY 282 INTRAUTERINE GROWTH RESTRICTION 302 NORMAL PHYSIOLOGY OF PREGNANCY 282 FETAL MACROSOMIA 305 Prenatal Care 283 POLYHYDRAMNIOS 305 Prenatal Diagnostic Testing 285 QUAD SCREENING 286 PREGNANCY-ASSOCIATED PLASMA PROTEIN A 286 CHORIONIC VILLUS SAMPLING 286 AMNIOCENTESIS 287 Teratology 288 Maternal-Fetal Infections 288 Spontaneous Abortion 288 Elective Termination of Pregnancy 292 Normal Labor and Delivery 292 OBSTETRIC EXAMINATION 292 FETAL HEART RATE MONITORING 293 ANTEPARTUM FETAL SURVEILLANCE 295 OBSTETRIC ANALGESIA AND ANESTHESIA 297 Medical Complications of Pregnancy OLIGOHYDRAMNIOS 305 RH ISOIMMUNIZATION 306 GESTATIONAL TROPHOBLASTIC DISEASE 306 MULTIPLE GESTATIONS 308 Abnormal Labor and Delivery 308 SHOULDER DYSTOCIA 308 FAILURE TO PROGRESS 309 RUPTURE OF MEMBRANES 309 PRETERM LABOR 311 FETAL MALPRESENTATION 312 INDICATIONS FOR CESAREAN SECTION 313 EPISIOTOMY 313 Puerperium 313 POSTPARTUM HEMORRHAGE 313 POSTPARTUM INFECTIONS 313 SHEEHAN’S SYNDROME (POSTPARTUM PITUITARY NECROSIS) 315 297 LACTATION AND BREASTFEEDING 315 HYPEREMESIS GRAVIDARUM 297 MASTITIS 315 DIABETES IN PREGNANCY 298 GESTATIONAL AND CHRONIC HYPERTENSION 299 PREECLAMPSIA AND ECLAMPSIA 300 ANTEPARTUM HEMORRHAGE 302 281 282 HIGH-YIELD FACTS IN OBSTETRICS Physiology of Normal Pregnancy THE BAS I C S OF P R E G NANC Y The following terms and concepts are central to an understanding of the physiologic processes of pregnancy. n n n n KEY FACT A G3P1 woman is one who has had 3 pregnancies but only 1 birth beyond 20 weeks’ GA and/or an infant who weighs at least 500 g. Gravidity: The number of times a woman has been pregnant. Parity: n The number of pregnancies that led to a birth beyond 20 weeks’ gestational age or an infant weighing > 500 g. n In prenatal assessment, P#### expresses the number of term deliveries, the number of preterm deliveries, the number of abortuses, and the number of living children. Developmental age (DA): The number of weeks and days since fertilization; usually unknown. Gestational age (GA): The number of weeks and days measured from the first day of the last menstrual period (LMP). GA can also be determined by: n Fundal height: Umbilicus – 20 weeks + 2–3 cm/week thereafter. n Fetal heart tones (Doppler): Typically 10–12 weeks. n Quickening, or appreciation of fetal movement: Occurs at 17–18 weeks at the earliest. n Ultrasound: n Measures fetal crown-rump length (CRL) at 6–12 weeks. n Measures biparietal diameter (BPD), femur length (FL), and abdominal circumference (AC) from 13 weeks. n Ultrasound measurement of GA is most reliable during the first trimester. DI AG NOS I S OF P R E G NANC Y KEY FACT Get a quantitative β-hCG: n To diagnose and follow ectopic pregnancy. n To monitor trophoblastic disease. n To screen for fetal aneuploidy. β-hCG n n n n The standard for diagnosing pregnancy. Produced by the placenta; peaks at 100,000 mIU/mL by 10 weeks’ GA. ↓ throughout the second trimester; levels off in the third trimester. hCG levels double approximately every 48 hours during early pregnancy. This is often used to diagnose ectopic pregnancy when doubling is abnormal. Ultrasound n n Used to confirm an intrauterine pregnancy. The gestational sac is visible by: n Five weeks’ GA. n A β-hCG in the range of 1000–1500 IU/mL. NOR M AL P HYS I OLOG Y OF P R E G NANC Y The normal physiologic changes that occur during pregnancy are graphically illustrated according to system in Figures 2.11-1 and 2.11-2. OBSTETRICS Renal Renal flow Increases 25–50%. Glomular filtration rate Increases early, then plateaus. Increases from about 60–70 g to about 900–1200 g. Body weight Average 11-kg (25-lb) increase. +40 +30 +20 low Uterine weight Glomerular filtration rate +50 al f FIGURE 2.11-1. PATTERN n Re Weight PARAMETER % change SYSTEM +10 0 0 Prenatal Care The goal of prenatal care is to prevent, diagnose, and treat conditions that can lead to adverse outcomes in pregnancy. Expected weight gain, nutrition, and exercise recommendations are outlined in Table 2.11-1. See Table 2.11-2 for some important factors that can cross the placenta. Recommendations for Standard Prenatal Care CATEGORY Weight gain RECOMMENDATIONS Guidelines for weight gain in pregnancy: n Excessive gain: > 1.5 kg/mo. n Inadequate gain: < 1.0 kg/mo. Guidelines according to prepregnancy body mass index (BMI): Nutrition n Underweight (BMI < 19.8): 12–18 kg. n Acceptable (BMI 19.8–26.0): 11–16 kg. n Overweight (BMI 26.1–29.0): 7–11 kg. n Severely overweight (BMI > 29.0): 7 kg. Guidelines for nutritional supplementation: n An additional 100–300 kcal/day; 500 kcal/day during breastfeeding. n Folic acid supplements (↓ neural tube defects for all reproductive-age women): 0.4 mg/day, or 4 mg/day for women with a history of neural tube defects in prior pregnancies. n Iron: Starting at the first visit, 30 mg/day of elemental iron (or 150 mg of n Calcium: 1300 mg/day for women < 19 years of age; 1000 mg/day for iron sulfate). those > 19 years of age. Additional guidelines for complete vegetarians: Exercise 12 24 Weeks 36 Renal and uterine/body weight changes in normal pregnancy. (Reproduced with permission from Gardner DG, Shoback D. Greenspan’s Basic & Clinical Endocrinology, 8th ed. New York: McGraw-Hill, 2007, Fig. 17-2A.) TA B L E 2 . 11- 1 . HIGH-YIELD FACTS IN 283 n Vitamin D: 10 µg or 400 IU/day. n Vitamin B12: 2 µg/day. Thirty minutes of moderate exercise daily. OBSTETRICS SYSTEM PARAMETER Cardiovascular Heart rate Gradually increases 20%. Blood pressure Gradually decreases 10% by 34 weeks, then increases to prepregnancy values. Stroke volume Cardiac output Increases to maximum at 19 weeks, then plateaus. Rises rapidly by 20%, then gradually increases an additional 10% by 28 weeks. +30 rd Ca +20 ia c t outpu Rate +10 0 Blood p ressure −10 Peripheral venous distention Progressive increase to term. Peripheral vascular resistance Progressive decrease to term. Respiratory rate Unchanged. +20 Tidal volume Increases by 30–40%. +10 Expiratory reserve Gradual decrease. Vital capacity Unchanged. Respiratory minute volume Increases by 40%. +40 , me me volu u l vo te al inu Tid ry m o rat +30 % change Pulmonary PATTERN % change 284 HIGH-YIELD FACTS IN pi res 0 Respiratory rate, vital capacity −10 Ex pir −20 ato ry −30 res erv e −40 +60 +50 Hematocrit Decreases slightly. Fibrinogen Increases. Electrolytes Unchanged. e m vo lu oo d +30 +20 en og Bl Increases by 50% in second trimester. % change +40 Volume Blood in ibr F +10 Electrolytes 0 Hema −10 tocrit −20 +60 tim pt yi n g +40 em +30 c Increases. as tri Gastric emptying time +20 G Decreases. % change Sphincter tone e +50 Gastrointestinal +10 0 0 FIGURE 2.11-2. 12 24 Weeks 36 Cardiopulmonary, hematologic, and GI changes in normal pregnancy. (Reproduced with permission from Gardner DG, Shoback D. Greenspan’s Basic & Clinical Endocrinology, 8th ed. New York: McGraw-Hill, 2007, Fig. 17-2B.) OBSTETRICS TA B L E 2 . 11- 2 . Factors That Can Cross the Placenta IMMUNOGLOBULINS IgG ORGANISMS DRUGS Toxoplasmosis See the teratology discussion Rubella below. HIV Parvovirus CMV Enteroviruses Treponema pallidum Listeria monocytogenes Parvovirus B19 Prenatal Diagnostic Testing Table 2.11-3 outlines a typical prenatal diagnostic testing schedule by week. The sections that follow describe each recommended screening modality. TA B L E 2 . 11- 3 . Prenatal Diagnostic Testing Schedule WEEKS Prenatal visits PRENATAL DIAGNOSTIC TESTING Weeks 0–28: Every 4 weeks. Weeks 29–35: Every 2 weeks. Weeks 36–birth: Every week. Initial visit Heme: CBC, Rh factor, type and screen. Infectious disease: UA and culture, rubella antibody titer, HBsAg, RPR/VDRL, cervical gonorrhea and chlamydia, PPD, HIV, Pap smear (to check for dysplasia). Consider HCV and varicella based on history. If indicated: HbA1c, sickle cell screening. Discuss genetic screening: Tay-Sachs disease, cystic fibrosis. 9–14 weeks Offer PAPP-A + nuchal transparency + free β-hCG +/− chorionic villus sampling (CVS). 15–22 weeks Offer maternal serum α-fetoprotein (MSAFP) or quad screen (AFP, estriol, β-hCG, and inhibin A) +/− amniocentesis. 18–20 weeks Ultrasound for full anatomic screen. 24–28 weeks One-hour glucose challenge test for gestational diabetes screen. 28–30 weeks RhoGAM for Rh-! women (after antibody screen). 35–40 weeks Group B strep culture (GBS); repeat CBC. 34–40 weeks Cervical chlamydia and gonorrhea cultures, HIV, RPR in high-risk patients. HIGH-YIELD FACTS IN 285 286 HIGH-YIELD FACTS IN OBSTETRICS QU AD SC R E E NI NG n n n KEY FACT n Still UNDERage at 18: trisomy 18 = ↓ AFP, ↓ estriol, ↓ β-hCG, ↓ inhibin A. KEY FACT 2 up, 2 down: trisomy 21 = ↓ AFP, ↓ estriol, ↑ β-hCG, ↑ inhibin A. Quad screening consists of the following 4 elements (see also Table 2.114): 1. MSAFP 2. Inhibin A 3. Estriol 4. β-hCG MSAFP is produced by the fetus and enters the maternal circulation. Results are reported as multiples of the median (MoMs). n Measurement results depend on accurate gestational dating. n MSAFP is rarely tested alone, as quad screening has ↑ sensitivity for detecting chromosomal abnormalities. Elevated MSAFP (> 2.5 MoMs) is associated with: n Open neural tube defects (anencephaly, spina bifida) n Abdominal wall defects (gastroschisis, omphalocele) n Multiple gestation n Incorrect gestational dating n Fetal death n Placental abnormalities (eg, placental abruption) Reduced MSAFP (< 0.5 MoM) is associated with: n Trisomy 21 and 18 n Fetal demise n Inaccurate gestational dating P R E G NANC Y-AS S OC I ATE D P LAS M A P R OT E I N A ( P AP P -A) n n n Recommended at weeks 9–14. PAPP-A + nuchal transparency + free β-hCG can detect ~ 91% of cases of Down syndrome and ~ 95% of cases of trisomy 18. Advantages: n A screen of low-risk pregnant women (< 35 years of age). n Available earlier than CVS and less invasive than CVS (see below). CHOR I ONI C VI LLU S SAM P LI NG ( CVS) Table 2.11-5 outlines the relative advantages and disadvantages of CVS and amniocentesis (see also Figure 2.11-3). TA B L E 2 . 11- 4 . Quad Screening MSAFP ESTRIOL INHIBIN A β-hCG Trisomy 18 ↓ ↓ ↓ ↓ Trisomy 21 ↓ ↓ ↑ ↑ OBSTETRICS TA B L E 2 . 11- 5 . CVS vs. Amniocentesis VARIABLE CVS AMNIOCENTESIS GA 10–12 weeks. 15–20 weeks. Procedure Transcervical or transabdominal Transabdominal aspiration aspiration of placental tissue. of amniotic fluid using an ultrasound-guided needle. Advantages Genetically diagnostic. Genetically diagnostic. Available at an earlier GA. Disadvantages Risk of fetal loss is 1%. Premature rupture of membranes Cannot detect open neural tube (PROM), chorioamnionitis, fetalmaternal hemorrhage. defects. Limb defects are associated with CVS at < 9 weeks. AM N I O CE N TE S IS Indicated for the following: n n n n In women who will be > 35 years of age at the time of delivery. In conjunction with an abnormal quad screen. In Rh-sensitized pregnancy to obtain fetal blood type or to detect fetal hemolysis. To evaluate fetal lung maturity via a lecithin-to-sphingomyelin ratio ≥ 2.5 or to detect the presence of phosphatidylglycerol (performed during the third trimester). Ultrasound transducer Placenta FIGURE 2.11-3. Chorionic villus sampling. (Reproduced with permission from Cunningham FG et al. Wil- liams Obstetrics, 23rd ed. New York: McGraw-Hill, 2010, Fig. 13-7.) HIGH-YIELD FACTS IN 287 288 HIGH-YIELD FACTS IN OBSTETRICS Teratology Major defects are apparent in about 3% of births and in roughly 4.5% of children by 5 years of age. Table 2.11-6 outlines common teratogenic agents. MNEMONIC Maternal-Fetal Infections TORCHeS pathogens: Toxoplasmosis Othera Rubella CMV Herpes simplex virus HIV Syphilis n Parvovirus, varicella, Listeria, TB, malaria, fungi. a n May occur at any time during pregnancy, labor, and delivery. Common sequelae include the following: n Premature delivery n CNS abnormalities n Anemia n Jaundice n Hepatosplenomegaly n Growth retardation The most common pathogens involved can be remembered through use of the mnemonic TORCHeS (see also Table 2.11-7). KEY FACT Pregnant women should not change the cat’s litterbox. Spontaneous Abortion (SAB) The loss of POC prior to the 20th week of pregnancy. More than 80% of cases occur in the first trimester. Risk factors are as follows: n n n n Chromosomal abnormalities: A factor in approximately 50% of SABs in the first trimester, 20–30% in second-trimester losses, and 5–10% in thirdtrimester losses. Maternal factors: n Inherited thrombophilias: Factor V Leiden, prothrombin, antithrombin, proteins C and S, methylene tetrahydrofolate reductase (hyperhomocysteinemia). n Immunologic issues: Antiphospholipid antibodies; alloimmune factors. n Anatomic issues: Uterine abnormalities, incompetent cervix, cervical conization or loop electrosurgical excision procedure (LEEP), cervical injury, DES exposure, anatomic abnormalities of the cervix. n Endocrinologic issues: Diabetes mellitus (DM), hypothyroidism, progesterone deficiency. n Other: Maternal trauma, ↑ maternal age, infection, dietary deficiencies. Environmental factors: Tobacco, alcohol, caffeine (> 500 mg of caffeine per day), toxins, drugs, radiation. Fetal factors: Anatomic malformation. HISTORY/PE See Table 2.11-8 for types of SAB. DIAGNOSIS n n ↓ levels of hCG. Ultrasound can identify: n The gestational sac 5–6 weeks from the LMP. n The fetal pole at 6 weeks. n Fetal cardiac activity at 6–7 weeks. OBSTETRICS TA B L E 2 . 11- 6 . HIGH-YIELD FACTS IN 289 Common Teratogenic Agents and Their Associated Defects DRUGS AND CHEMICALS ACEIs DEFECTS Fetal renal tubular dysplasia and neonatal renal failure, oligohydramnios, intrauterine growth restriction (IUGR), lack of cranial ossification. Alcohol Fetal alcohol syndrome (growth restriction before and after birth, mental retardation, midfacial hypoplasia, renal and cardiac defects). Consumption of > 6 drinks per day is associated with a 40% risk of fetal alcohol syndrome. Androgens Virilization of females; advanced genital development in males. Carbamazepine Neural tube defects, fingernail hypoplasia, microcephaly, developmental delay, IUGR. Cocaine Bowel atresias; congenital malformations of the heart, limbs, face, and GU tract; microcephaly; IUGR; cerebral infarctions. Diethylstilbestrol (DES) Clear cell adenocarcinoma of the vagina or cervix, vaginal adenosis, abnormalities of the cervix and uterus or testes, possible infertility. Lead ↑ spontaneous abortion (SAB) rate; stillbirths. Lithium Congenital heart disease (Ebstein’s anomaly). Methotrexate ↑ SAB rate. Organic mercury Cerebral atrophy, microcephaly, mental retardation, spasticity, seizures, blindness. Phenytoin IUGR, mental retardation, microcephaly, dysmorphic craniofacial features, cardiac defects, fingernail hypoplasia. Radiation Microcephaly, mental retardation. Medical diagnostic radiation delivering < 0.05 Gy to the fetus has no teratogenic risk. Streptomycin and kanamycin Hearing loss; CN VIII damage. Tetracycline Permanent yellow-brown discoloration of deciduous teeth; hypoplasia of tooth enamel. Thalidomide Bilateral limb deficiencies, anotia and microtia, cardiac and GI anomalies. Trimethadione and Cleft lip or cleft palate, cardiac defects, microcephaly, mental retardation. paramethadione Valproic acid Neural tube defects (spina bifida); minor craniofacial defects. Vitamin A and derivatives ↑ SAB rate, microtia, thymic agenesis, cardiovascular defects, craniofacial dysmorphism, microphthalmia, cleft lip or cleft palate, mental retardation. Warfarin (wages war on the fetus) Nasal hypoplasia and stippled bone epiphyses, developmental delay, IUGR, ophthalmologic abnormalities. 290 HIGH-YIELD FACTS IN T A B L E 2 . 1 1 - 7. DISEASE Toxoplasmosis Rubella CMV HSV OBSTETRICS Diagnosis and Treatment of Common Congenital Infections TRANSMISSION SYMPTOMS DIAGNOSIS Serologic testing. TREATMENT PREVENTION Pyrimethamine Avoid exposure + sulfadiazine. to cat feces Transplacental; Hydrocephalus 1° infection via Intracranial calcifications consumption Chorioretinitis during pregnancy; of raw meat or Ring-enhancing lesions on MRI spiramycin contact with cat prophylaxis for the feces. third trimester. Serologic testing. Symptomatic. Immunize before Transplacental Purpuric “blueberry muffin” rash in the first Cataracts pregnancy; vaccinate trimester. Mental retardation the mother after Hearing loss delivery if serologic Patent ductus arteriosus (PDA) titers remain !. Primarily Petechial rash Urine culture; PCR Postpartum transplacental. Periventricular calcifications of amniotic fluid. ganciclovir. Intrapartum Skin, eye, and mouth infections Serologic testing. Acyclovir. transmission if Life-threatening CNS/systemic Perform a C-section if lesions are present at delivery. infection the mother has N/A active lesions; transplacental transmission is rare. HIV Often asymptomatic ELISA, Western Highly active AZT or nevirapine in delivery, or Failure to thrive blot. antiretroviral pregnant women via breast milk. Bacterial infections therapy with HIV; perform ↑ incidence of upper and lower (HAART). elective C-section In utero, at if viral load is respiratory diseases > 1000. Treat infants with prophylactic AZT; avoid breastfeeding. Syphilis Intrapartum; Maculopapular skin rash Dark-field transplacental Lymphadenopathy microscopy, transmission is Hepatomegaly VDRL/RPR, possible. “Snuffles”: mucopurulent rhinitis FTA-ABS. Osteitis Late congenital syphilis: n Saber shins n Saddle nose n CNS involvement n Hutchinson’s triad: peg-shaped central incisors, deafness, interstitial keratitis Penicillin. Penicillin in pregnant women who test ". OBSTETRICS TA B L E 2 . 11- 8 . Types of SAB TYPE Complete Incomplete SYMPTOMS/SIGNS DIAGNOSIS TREATMENT POC are expelled. Closed os. Pain ceases, but spotting may persist. Ultrasound shows an empty uterus. Some POC are expelled; bleeding/ Open os. Manual uterine aspiration (MUA) or Ultrasound shows retained fetal D&C. mild cramping. Visible tissue on exam. Threatened HIGH-YIELD FACTS IN 291 None. tissue. No POC are expelled; uterine Closed os + intact membranes + fetal Pelvic rest for 24–48 hours and bleeding +/− abdominal pain. cardiac motion on ultrasound. follow-up ultrasound to assess the viability of conceptus. Inevitable Missed No POC are expelled; uterine Open os +/− rupture of membranes MUA, D&C, misoprostol, or expectant bleeding and cramps. (ROM). management. No POC are expelled. No fetal cardiac Closed os. MUA, D&C, or misoprostol. motion; no uterine bleeding. Brownish vaginal discharge. Septic Intrauterine No fetal cardiac activity; retained fetal tissue on ultrasound. Endometritis leading to septicemia. Hypotension, hypothermia, ↑ WBC Maternal mortality is 10–15%. count. Absence of fetal cardiac activity. Uterus small for GA; no fetal heart Induce labor; evacuate the uterus tones or movement on ultrasound. (D&E) to prevent DIC at GA > 16 fetal demise MUA, D&C, and IV antibiotics. weeks. Recurrenta If early in pregnancy, often due to chromosomal abnormalities. If later in pregnancy, often due Karyotyping of both parents. Surgical cerclage procedures to suture Hypercoagulability workup of mother. the cervix closed until labor or ROM Evaluate for uterine abnormalities. occurs with subsequent removal to hypercoagulable states (eg, SLE, factor V Leiden, protein S prior to delivery. Restriction of activities. deficiency). Incompetent cervix should be suspected with a history of painless dilation of the cervix and delivery of a normal fetus between 18 and 32 weeks. a Defined as 2 or more consecutive SABs or a total of 3 SABs in 1 year. A 17-year-old G1P0 female with a history of genital HSV presents at 37 weeks in labor. What is the appropriate management of the patient at delivery? 292 HIGH-YIELD FACTS IN OBSTETRICS n n Abnormal pregnancy is seen as a small, irregular intrauterine sac without a fetal pole on transvaginal ultrasound. Administer RhoGAM if the mother is Rh !. Elective Termination of Pregnancy It has been estimated that 50% of all pregnancies in the United States are unintended. Some 25% of all pregnancies end in elective abortion. Options for elective abortion depend on GA and patient preferences (see Table 2.11-9). Normal Labor and Delivery OBS TE TR I C E X AM I NATI ON n n n Leopold’s maneuvers are used to determine fetal lie (longitudinal or transverse) and, if possible, fetal presentation (breech or cephalic). Cervical examination: n Evaluate dilation, effacement, station, cervical position, and cervical consistency. n Confirm or determine fetal presentation. n Determine fetal position through palpation of the fetal sutures and fontanelles. n Conduct a sterile speculum exam if ROM is suspected. n Determine station, or engagement of the fetal head relative to a line through the ischial spines of the maternal pelvis. ! station = fetal head superior to this line; " station = fetal head inferior to this line. Table 2.11-10 depicts the normal stages of labor. TA B L E 2 . 11- 9 . Elective Termination of Pregnancy TRIMESTER PROCEDURE First Medical management: (90% therapeutic n abortions [TABs]) Oral mifepristone (low dose) + oral/vaginal TIMING Up to: 49 days’ GA misoprostol n IM/oral methotrexate + oral/vaginal 49 days’ GA misoprostol n Vaginal or sublingual or buccal misoprostol 59 days’ GA (high dose), repeated up to 3 times Surgical management: Second (10% TABs) n Manual aspiration n D&C with vacuum aspiration Obstetric management: Induction of labor (typically with prostaglandins, amniotomy, and oxytocin) If the patient has any active lesions at the time of delivery, perform a C-section. Surgical management: D&E 13 weeks’ GA 13–24 weeks’ GA (depending on state laws) Same as above OBSTETRICS TA B L E 2 . 11- 10 . HIGH-YIELD FACTS IN 293 Stages of Labor DURATION STAGE STARTS/ENDS PRIMIPAROUS MULTIPAROUS COMMENTS First Latent Onset of labor to 3–4 cm 6–11 hrs 4–8 hrs Active 4 cm to complete cervical 4–6 hrs (1.2 cm/hr) 2–3 hrs (1.5 cm/hr) Complete cervical dilation 0.5–3.0 hrs 5–30 min to delivery of infant Third Delivery of infant to delivery Prolongation seen with cephalopelvic disproportion. dilation (10 cm) Second Prolongation seen with excessive sedation/hypotonic uterine contractions. dilation Baby goes through all cardinal movements of delivery. 0–0.5 hr 0–0.5 hr of placenta Uterus contracts and placenta separates to establish hemostasis. F E TA L H E A R T R ATE ( F H R ) M O N I TOR I NG n n Monitoring can be performed with an electrode attached to the fetal scalp (a method that yields more precise results), or external monitoring can be conducted using Doppler ultrasound (a less invasive option). Continuous electronic FHR monitoring has not been shown to be more effective than appropriate intermittent monitoring in low-risk patients. Recommendations for FHR Monitoring n n Patients without complications: Review FHR tracings. n First stage of labor: Every 30 minutes. n Second stage of labor: Every 15 minutes. Patients with complications: Review FHR tracings. n First stage of labor: Every 15 minutes. n Second stage of labor: Every 5 minutes. Components of FHR Evaluation n n n n Rate (normal = 110–160 bpm): n FHR < 110 bpm: Bradycardia. Can be caused by congenital heart malformations or by severe hypoxia (2° to uterine hyperstimulation, cord prolapse, or rapid fetal descent). n FHR > 160 bpm: Tachycardia. Causes include hypoxia, maternal fever, and fetal anemia. Variability: See Figures 2.11-4 and 2.11-5. n Undetectable variability: Indicates severe fetal distress. n Minimal variability: < 6 bpm. Indicates fetal hypoxia or the effects of opioids, magnesium, or sleep cycle. n Normal variability: 6–25 bpm. n Marked variability: > 25 bpm. May indicate fetal hypoxia; may occur before a ↓ in variability. n Sinusoidal variability: Points to serious fetal anemia; a pseudosinusoidal pattern may also occur during maternal meperidine use. Accelerations: Onset of an ↑ in FHR to a peak in < 30 seconds. Reassuring because they indicate fetal ability to appropriately respond to the environment. Decelerations: See Table 2.11-11. A 23-year-old G1P0 female at 15 weeks’ GA presents with abdominal pain and mild bleeding from the cervix. On pelvic examination, some products of conception (POC) are found to be present in the vaginal vault. What test is necessary to determine the next step in management? 294 HIGH-YIELD FACTS IN OBSTETRICS 240 210 180 B 150 A 120 90 60 30 100 80 60 40 20 0 FIGURE 2.11-4. Varying (variable) fetal heart rate decelerations. 240 210 180 150 120 90 60 30 100 80 Ultrasound should be performed to determine if all the POC have been expelled (ie, if the uterus is empty). If so, it is a complete abortion and the POC should be sent to pathology to confirm fetal tissue with no other treatment. If POC are retained, it is an incomplete abortion, and manual uterine aspiration or D&C is indicated. Medical management with misoprostol may also be appropriate. 60 40 20 0 Late fetal heart rate decelerations. Late decelerations due to uteroplacental insufficiency resulting from placental abruption. Immediate cesarean delivery was performed. Umbilical artery pH was 7.05 and PO2 was 11 mm Hg. (Adapted with permission from Cun- FIGURE 2.11-5. ningham FG et al. Williams Obstetrics, 23rd ed. New York: McGraw-Hill, 2010, Fig. 18-17.) OBSTETRICS TA B L E 2 . 11- 11 . Types of Fetal Deceleration TYPE Early HIGH-YIELD FACTS IN 295 DESCRIPTION ETIOLOGY A visually apparent, gradual (onset Head compression from the to nadir in > 30 sec) ↓ in FHR with uterine contraction (normal). SCHEMATIC a return to baseline that mirrors the uterine contraction. Late A visually apparent, gradual (onset Uteroplacental insufficiency and to nadir in > 30 sec) ↓ in FHR with fetal hypoxemia. return to baseline whose onset, nadir, and recovery occur after the beginning, peak, and end of uterine contraction, respectively. Variable An abrupt (onset to nadir in < 30 Umbilical cord compression. sec), visually apparent ↓ in FHR below baseline lasting ≥ 15 sec but < 2 min. (Illustrations reproduced with permission from Cunningham FC et al. Williams Obstetrics, 23rd ed. New York: McGraw-Hill, 2010, Figs. 18-14, 18-16, and 18-18.) AN TE P A RT U M F ET A L S U R V E ILLANC E In general, antepartum fetal surveillance is used in pregnancies in which the risk of antepartum fetal demise is ↑. Testing is initiated in most at-risk patients at 32–34 weeks (or 26–28 weeks if there are multiple worrisome risk factors present). The following assessments are made: n Fetal movement assessment: n Assessed by the mother as the number of fetal movements over 1 hour. n The average time to obtain 10 movements is 20 minutes. n Maternal reports of ↓ fetal movements should be evaluated by means of the tests described below. 296 HIGH-YIELD FACTS IN OBSTETRICS n n n Nonstress test (NST): n Performed with the mother resting in the lateral tilt position (to prevent supine hypotension). n FHR is monitored externally by Doppler along with a tocodynamometer to detect uterine contractions. Acoustic stimulation may be used. n “Reactive” NST (normal response): Two accelerations ≥ 15 bpm above baseline (if > 32 weeks GA; ≥ 10 bpm if < 32 weeks GA) lasting for at least 15 seconds over a 20-minute period (see Figure 2.11-6). n “Nonreactive” NST: Fewer than 2 accelerations over a 20-minute period. n Perform further tests (eg, a biophysical profile, or BPP). n Lack of FHR accelerations may occur with any of the following: GA < 32 weeks, fetal sleeping, fetal CNS anomalies, and maternal sedative or narcotic administration. Contraction stress test (CST): n Performed in the lateral recumbent position. n FHR is monitored during spontaneous or induced (via nipple stimulation or oxytocin) contractions. n Reactivity is determined from fetal heart monitoring, as with the NST. n The procedure is contraindicated in women with preterm membrane rupture or known placenta previa; those with a history of uterine surgery; and those who are at high risk for preterm labor. n “Positive” CST: n Defined by late decelerations following 50% or more of contractions in a 10-minute window. n Raises concerns about fetal compromise. n Delivery is usually warranted. n “Negative” CST: n Defined as no late or significant variable decelerations within 10 minutes and at least 3 contractions. n Highly predictive of fetal well-being in conjunction with a normal NST. n “Equivocal” CST: Defined by intermittent late decelerations or significant variable decelerations. BPP: Uses real-time ultrasound to assign a score of 2 (normal) or 0 (abnormal) to 5 parameters: fetal tone, breathing, movement, amniotic fluid volume, and NST. Scoring is as follows: 180 180 150 150 120 120 90 Fetal movement FIGURE 2.11-6. Acceleration Doppler 90 60 60 30 30 100 100 75 75 50 50 25 25 0 0 Reactive nonstress test. (Adapted with permission from Cunningham FG et al. Williams Obstetrics, 23rd ed. New York: McGraw-Hill, 2010, Fig. 15-7.) OBSTETRICS 8–10: Reassuring for fetal well-being. 6: Considered equivocal. Term pregnancies are usually delivered with this profile. n 0–4: Extremely worrisome for fetal asphyxia; strong consideration should be given to immediate delivery if no other explanation is found. Amniotic fluid index (AFI): sum of the measurements of the deepest cord-free amniotic fluid measured in each of the abdominal quadrants. Modified biophysical profile (mBPP): n NST + AFI. n A normal test consists of a reactive NST and an AFI > 5 cm. Umbilical artery Doppler velocimetry: n Used only when IUGR is suspected. n With IUGR, there is a reduction and even a reversal of umbilical artery diastolic flow. Oligohydramnios (AFI < 5 cm) always warrants further workup. n n n n n n O B S T ET R I C A N A LG E S I A A ND ANE S THE S I A n n n n HIGH-YIELD FACTS IN 297 KEY FACT A ! CST is good; a " one is bad. MNEMONIC When performing a BPP, remember to— Test the Baby, MAN! Fetal Tone Fetal Breathing Fetal Movement Amniotic fluid volume Nonstress test Uterine contractions and cervical dilation result in visceral pain (T10–L1). Descent of the fetal head and pressure on the vagina and perineum result in somatic pain (pudendal nerve, S2–S4). In the absence of a medical contraindication, maternal request is a sufficient medical indication for pain relief during labor. Absolute contraindications to regional anesthesia (epidural, spinal, or combination) include the following: n Refractory maternal hypotension n Maternal coagulopathy n Maternal use of a once-daily dose of low-molecular-weight heparin within 12 hours n Untreated maternal bacteremia n Skin infection over the site of needle placement n ↑ ICP caused by a mass lesion Medical Complications of Pregnancy HYP E R E M E S IS G R A VI D A R U M Defined as persistent vomiting not related to other causes, acute starvation (usually large ketonuria), and weight loss (usually at least a 5% ↓ from prepregnancy weight). n n More common in first pregnancies, multiple gestations, and molar pregnancies. ↑ β-hCG and ↑ estradiol have been implicated in its pathophysiology. KEY FACT If “morning sickness” persists after the first trimester, think hyperemesis gravidarum. HISTORY/PE Distinguish from “morning sickness,” acid reflux, gastroenteritis, hyperthyroidism, and neurologic conditions. DIAGNOSIS n n Check β-hCG level and ultrasound to rule out molar pregnancy. Evaluate for ketonemia, ketonuria, hyponatremia, and hypokalemic, hypochloremic metabolic alkalosis. Measure liver enzymes, serum bilirubin, and serum amylase/lipase. KEY FACT The first step in the diagnosis of hyperemesis gravidarum is to rule out molar pregnancy with ultrasound +/− β-hCG. 298 HIGH-YIELD FACTS IN OBSTETRICS TREATMENT n n n n n Administer vitamin B6. Doxylamine (an antihistamine) PO. Promethazine or dimenhydrinate PO/PR. If severe: Metoclopramide, ondansetron, prochlorperazine, or promethazine IM/PO. If dehydrated: IV fluids, IV nutritional supplementation, and dimenhydrinate IV. DI ABET E S I N P R E G NANC Y Diabetes in pregnancy is divided into 2 categories: n n Gestational: Onset occurs during pregnancy. Pregestational: Onset is prior to pregnancy. Gestational Diabetes Mellitus Carbohydrate intolerance of variable severity that is first diagnosed during pregnancy. Occurs in 3–5% of all pregnancies, usually in late pregnancy. HISTORY/PE n n Typically asymptomatic. May present with edema, polyhydramnios, or a large-for-GA infant (> 90th percentile). DIAGNOSIS n n Conduct a 1-hour 50-g glucose challenge test: n Venous plasma glucose is measured 1 hour later. n Performed at 24–28 weeks. n Values ≥ 140 mg/dL are considered abnormal. Confirm with an oral 3-hour (100-g) glucose tolerance test showing any 2 of the following: n Fasting: > 95 mg/dL. n One hour: > 180 mg/dL. n Two hours: > 155 mg/dL. n Three hours: > 140 mg/dL. TREATMENT n KEY FACT Keys to the management of gestational diabetes: (1) the ADA diet; (2) insulin if needed; (3) ultrasound for fetal growth; and (4) NST beginning at 30–32 weeks if GDMA2 (requiring insulin or an oral hypoglycemic). n Mother: n Start with the ADA diet, regular exercise, and strict glucose monitoring (4 times a day). n Tight maternal glucose control (fasting glucose < 90 mg/dL; 1- to 2-hour postprandial glucose < 140 mg/dL) improves outcomes. n Add insulin if dietary control is insufficient. n Give intrapartum insulin and dextrose to maintain tight control during delivery. Fetus: n Obtain periodic ultrasound and NSTs to assess fetal growth and wellbeing. n It may be necessary to induce labor at 39–40 weeks if insulin or an oral hypoglycemic agent is necessary for glucose control. OBSTETRICS HIGH-YIELD FACTS IN 299 COMPLICATIONS More than 50% of patients go on to develop glucose intolerance and/or type 2 DM later in life. Pregestational Diabetes and Pregnancy Observed in 1% of all pregnancies. Insulin requirements may ↑ as much as threefold. Poorly controlled DM is associated with an ↑ risk of congenital malformations, fetal loss, and maternal/fetal morbidity during labor and delivery. KEY FACT Greater than 8, investigate! If HbA1c is > 8%, look for congenital abnormalities. TREATMENT n n n Mother: n Renal, ophthalmologic, neural tube, and cardiac evaluation to assess for end-organ damage. n Strict glucose control (diet, exercise, insulin therapy, and frequent selfmonitoring) to minimize fetal defects. n Fasting morning: ≤ 90 mg/dL. n Two-hour postprandial: < 120 mg/dL. Fetus: n 18–20 weeks: n Ultrasound to determine fetal age and growth. n Evaluate for cardiac anomalies and polyhydramnios. n Quad screen to screen for developmental anomalies. n 32–34 weeks: n Close fetal surveillance (eg, NST, CST, BPP). n Admit if maternal DM has been poorly controlled or fetal parameters are a concern. n Serial ultrasounds for fetal growth. Delivery and postpartum: n Maintain normoglycemia (80–100 mg/dL) during labor with an IV insulin drip and hourly glucose measurements. n Consider early delivery in the setting of poor maternal glucose control, preeclampsia, macrosomia, or evidence of fetal lung maturity. n Cesarean delivery should be considered in the setting of an estimated fetal weight (EFW) > 4500 g. n Encourage breastfeeding with an appropriate ↑ in caloric intake. n Continue glucose monitoring postpartum. Insulin needs rapidly ↓ after delivery. COMPLICATIONS See Table 2.11-12. GE S T AT IO N A L A N D C H R O N IC H YP E RT E NS I ON Defined as follows: n n Gestational hypertension: n Idiopathic hypertension without significant proteinuria (< 300 mg/L). n Develops at > 20 weeks’ GA. n As many as 25% of patients may go on to develop preeclampsia. Chronic hypertension: n Present before conception and at < 20 weeks’ GA. n May persist for > 12 weeks postpartum. n Up to one-third of patients may develop superimposed preeclampsia. KEY FACT If UA before 20 weeks reveals glycosuria, think pregestational diabetes. KEY FACT Hyperglycemia in the first trimester suggests preexisting diabetes and should be managed as pregestational diabetes. 300 HIGH-YIELD FACTS IN OBSTETRICS TA B L E 2 . 11- 12 . Complications of Pregestational Diabetes Mellitus MATERNAL COMPLICATIONS DKA (type 1) or hyperglycemic hyperosmolar nonketotic coma (type 2) FETAL COMPLICATIONS Macrosomia or IUGR Cardiac and renal defects Preeclampsia/eclampsia Neural tube defects (eg, sacral agenesis) Cephalopelvic disproportion (from Hypocalcemia macrosomia) and need for C-section Polycythemia Preterm labor Hyperbilirubinemia Infection Hypoglycemia from hyperinsulinemia Polyhydramnios Respiratory distress syndrome (RDS) Postpartum hemorrhage Birth injury (eg, shoulder dystocia) Maternal mortality Perinatal mortality TREATMENT n n n Monitor BP closely. Treat with appropriate antihypertensives (eg, methyldopa, labetalol, nifedipine). Do not give ACEIs or diuretics. n ACEIs are known to lead to uterine ischemia. n Diuretics can aggravate low plasma volume to the point of uterine ischemia. COMPLICATIONS Similar to those of preeclampsia (see below). P R E E C LAMP S I A AN D E C LAM P S I A Distinguished as follows: MNEMONIC n The classic triad of preeclampsia— It’s not just HyPE Hypertension Proteinuria Edema n n MNEMONIC HELLP syndrome: Hemolysis Elevated LFTs Low Platelets Preeclampsia: n New-onset hypertension (systolic BP ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg) and n Proteinuria (> 300 mg of protein in a 24-hour period) occurring at > 20 weeks’ GA. Eclampsia: New-onset grand mal seizures in women with preeclampsia. HELLP syndrome: A variant of preeclampsia with a poor prognosis. n Consists of hemolytic anemia, elevated liver enzymes, and low platelets (see mnemonic). n The etiology is unknown, but clinical manifestations are explained by vasospasm leading to hemorrhage and organ necrosis. n Risk factors include nulliparity, African American ethnicity, extremes of age (< 20 or > 35), multiple gestation, molar pregnancy, renal disease (due to SLE or type 1 DM), a family history of preeclampsia, and chronic hypertension. HISTORY/PE See Table 2.11-13 for the signs and symptoms of preeclampsia and eclampsia. OBSTETRICS TA B L E 2 . 11- 13 . Presentation of Preeclampsia and Eclampsia DISEASE SEVERITY Mild preeclampsia HIGH-YIELD FACTS IN 301 SIGNS AND SYMPTOMS Usually asymptomatic. BP ≥ 140/90 on 2 occasions > 6 hours apart. Proteinuria (> 300 mg/24 hrs or 1–2 " urine dipsticks). Edema. Severe BP > 160/110 on 2 occasions > 6 hours apart. preeclampsia Renal: Proteinuria (> 5 g/24 hrs or 3–4 " urine dipsticks) or oliguria (< 500 mL/24 hrs). Cerebral changes: Headache, somnolence. Visual changes: Blurred vision, scotomata. Other: Hyperactive reflexes/clonus; RUQ pain; hemolysis, elevated liver enzymes, thrombocytopenia (HELLP syndrome). Eclampsia The most common signs preceding an eclamptic attack are headache, visual changes, and RUQ/epigastric pain. Seizures are severe if not controlled with anticonvulsant therapy. TREATMENT The only cure for preeclampsia/eclampsia is delivery of the fetus. n n n Preeclampsia: n Close to term or worsening preeclampsia: Induce delivery with IV oxytocin, prostaglandin, or amniotomy. n Far from term: Treat with modified bed rest and expectant management. n Prevent seizures with a continuous magnesium sulfate drip. n Watch for signs of magnesium toxicity (loss of DTRs, respiratory paralysis, coma). n Continue seizure prophylaxis for 24 hours postpartum. n Treat magnesium toxicity with IV calcium gluconate. Severe preeclampsia: n Control BP with labetalol and/or hydralazine (goal < 160/110 mm Hg with a diastolic BP of 90–100 mm Hg to maintain fetal blood flow). n Continuous magnesium sulfate drip. n Deliver by induction or C-section when the mother is stable. Eclampsia: n ABCs with supplemental O2. n Seizure control/prophylaxis with magnesium. n If seizures recur, give IV diazepam. n Monitor magnesium blood levels and magnesium toxicity. n Monitor fetal status. n Control BP (labetalol and/or hydralazine). n Limit fluids; Foley catheter for strict I/Os. n Initiate delivery if the patient is stable and convulsions are controlled. n Postpartum management is the same as that for preeclampsia. n Seizures may occur antepartum (25%), intrapartum (50%), or postpartum (25%); most occur within 48 hours after delivery. KEY FACT Signs of severe preeclampsia are persistent headache or other cerebral or visual disturbances, persistent epigastric pain, and hyperreactive reflexes. A 36-year-old G1P0 female with a history of SLE at 36 weeks’ GA presents with headache and RUQ pain. She is admitted and found to have a BP of 165/100 and 170/105 mm Hg when tested twice 6 hours apart, as well as 3+ protein on urine dipstick. Once her BP has been controlled with labetalol, what are the next steps in management? 302 HIGH-YIELD FACTS IN OBSTETRICS COMPLICATIONS n n ANT E PAR TU M HE M OR R HAG E KEY FACT With third-trimester bleeding, think anatomically: n Vagina: Bloody show, trauma n Cervix: Cervical cancer, cervical/ vaginal lesion n Placenta: Placental abruption, placenta previa n Fetus: Fetal bleeding Preeclampsia: Prematurity, fetal distress, stillbirth, placental abruption, seizure, DIC, cerebral hemorrhage, serous retinal detachment, fetal/maternal death. Eclampsia: Cerebral hemorrhage, aspiration pneumonia, hypoxic encephalopathy, thromboembolic events, fetal/maternal death. n n n n Any bleeding that occurs after 20 weeks’ gestation. Complicates 3–5% of pregnancies. The most common causes are placental abruption and placenta previa (see Table 2.11-14 and Figure 2.11-7). Other causes include other forms of abnormal placentation (eg, placenta accreta), ruptured uterus, genital tract lesions, and trauma. Obstetric Complications of Pregnancy EC T OPI C P R E G NANC Y MNEMONIC The classic triad of ectopic pregnancy PAVEs the way for diagnosis: Pain (abdominal) Amenorrhea Vaginal bleeding Ectopic pregnancy Most often tubal, but can be abdominal, ovarian, or cervical. HISTORY/PE n n n Presents with abdominal pain and vaginal spotting/bleeding, although some patients are asymptomatic. Associated with etiologies that cause scarring to the fallopian tubes, including a history of PID, pelvic surgery, DES use, or endometriosis. The differential includes surgical abdomen, abortion, ovarian torsion, PID, and ruptured ovarian cyst. DIAGNOSIS KEY FACT Unstable patients or those with signs of peritoneal irritation (eg, rebound tenderness) require emergent surgical intervention. Approach a woman of reproductive age presenting with abdominal pain as a ruptured ectopic pregnancy until proven otherwise. n n TREATMENT n n The patient has severe preeclampsia. Start a magnesium sulfate drip for seizure prophylaxis and deliver by induction or C-section when the mother is stable. Look for a " pregnancy test and a transvaginal ultrasound showing an empty uterus (see Figure 2.11-8). Confirm with a serial hCG without appropriate hCG doubling. Medical treatment (methotrexate) is sufficient for small, unruptured tubal pregnancies. Surgical options include salpingectomy or salpingostomy with evacuation (laparoscopy vs. laparotomy). COMPLICATIONS Tubal rupture and hemoperitoneum (an obstetric emergency). I NT R AUT E R I NE G R OWT H RE S T R I CT I ON ( I U G R) Defined as an EFW less than the 10th percentile for GA. OBSTETRICS TA B L E 2 . 11- 14 . Placental Abruption vs. Placenta Previa VARIABLE Pathophysiology HIGH-YIELD FACTS IN 303 PLACENTAL ABRUPTION PLACENTA PREVIA Premature (before delivery) separation of normally Abnormal placental implantation: implanted placenta. n Total: The placenta covers the cervical os. n Marginal: The placenta extends to the margin of the os. n Low lying: The placenta is in close proximity to the os. Incidence 1 in 100. 1 in 200. Risk factors Hypertension, abdominal/pelvic trauma, tobacco or Prior C-sections, grand multiparity, advanced maternal cocaine use, previous abruption, rapid decompression of age, multiple gestation, prior placenta previa. an overdistended uterus, excessive stimulation. Symptoms Painful, dark vaginal bleeding that does not spontaneously cease. Abdominal pain; uterine hypertonicity. Painless, bright red bleeding that often ceases in 1–2 hours with or without uterine contractions. Usually no fetal distress. Fetal distress. Diagnosis Primarily clinical. Transabdominal/transvaginal ultrasound sensitivity is Transabdominal/transvaginal ultrasound sensitivity is > 95%; look for an abnormally positioned placenta. only 50%; look for a retroplacental clot. Most useful for ruling out previa. Management Stabilize patients with mild abruption and a premature fetus; manage expectantly (hospitalize; start IV and fetal monitoring; type and cross blood; bed rest). Moderate to severe abruption: Immediate delivery is indicated (vaginal delivery with amniotomy if mother Do not perform a vaginal exam! Stabilize patients with a premature fetus; manage expectantly. Give tocolytics. Serial ultrasound to assess fetal growth; resolution of partial previa. and fetus are stable and delivery is expected soon; Betamethasone to help with fetal lung maturity. C-section for maternal or fetal distress). Deliver by C-section. Indications for delivery include labor, life-threatening bleeding, fetal distress, documented fetal lung maturity, and 36 weeks’ GA. Complications Hemorrhagic shock. ↑ risk of placenta accreta. DIC occurs in 10% of patients. Vasa previa (fetal vessels crossing the internal os). Recurrence risk is 5–16% and ↑ to 25% after 2 previous Preterm delivery, PROM, IUGR, congenital anomalies. abruptions. Recurrence risk is 4–8%. Fetal hypoxia. HISTORY/PE Risk factors include the following: n n n n Maternal systemic disease leading to uteroplacental insufficiency (intrauterine infection, hypertension, anemia) Maternal substance abuse Placenta previa Multiple gestations 0 cm 0 cm x 0 cm Pelvic in 1 1 Pelvic in Pla nta ce x 0 cm Pla nta ce nta ce nta ce 1 Pelvic in let rv Ce i Pla D rv Ce i let rv Ce i Pla rv Ce i let C x B 1 A OBSTETRICS x 304 HIGH-YIELD FACTS IN Placental implantation. (A) Normal placenta. (B) Low implantation. (C) Partial placenta previa. (D) Complete placenta previa. (Adapted with permission from DeCherney AH. Current Obstetric & Gynecologic Diagnosis & Treatment, 8th ed. Stamford, CT: Appleton & Lange, 1994: 404.) FIGURE 2.11-7. DIAGNOSIS n n Confirm serial fundal height measurements with ultrasound. Ultrasound the fetus for EFW. TREATMENT n n Explore the underlying etiology and correct if possible. If the patient is near due date, administer steroids (eg, betamethasone) to accelerate fetal lung maturity; requires 48 hours prior to delivery. CM A B Normal intrauterine pregnancy and ectopic pregnancy. Transvaginal ultrasound showing (A) a normal intrauterine pregnancy with a gestational sac containing a yolk sac within the uterine cavity, and (B) a complex mass (CM)/ectopic pregnancy adjacent to an empty uterus. (Reproduced with permission from Tintinalli JE et al. Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 6th ed. New York: McGraw-Hill, 2004, Figs. 113- FIGURE 2.11-8. 15 and 113-22.) OBSTETRICS n n Perform fetal monitoring with NST, CST, BPP, and umbilical artery Doppler velocimetry. A nonreassuring status near term may prompt delivery. COMPLICATIONS ↑ perinatal morbidity and mortality. F E TA L M A CR O S O M I A n n n n Defined as a birth weight > 95th percentile. A common sequela of gestational diabetes. Dx: Weigh the newborn at birth (prenatal diagnosis is imprecise). Tx: Planned cesarean delivery may be considered for an EFW > 5000 g in women without diabetes and for an EFW > 4500 g in women with diabetes. Cx: ↑ risk of shoulder dystocia (leading to brachial plexus injury and ErbDuchenne palsy) as birth weight ↑. P OL Y H Y D R A M N I O S n n n n n An AFI > 20 on ultrasound. May be present in normal pregnancies, but fetal chromosomal developmental abnormalities must be considered. Etiologies include the following: n Maternal DM n Multiple gestation n Isoimmunization n Pulmonary abnormalities (eg, cystic lung malformations) n Fetal anomalies (eg, duodenal atresia, tracheoesophageal fistula, anencephaly) n Twin-twin transfusion syndrome Hx/PE: Usually asymptomatic. Dx: Fundal height greater than expected. Evaluation includes ultrasound for fetal anomalies, glucose testing for DM, and Rh screen. Tx: Etiology specific. Cx: Preterm labor, fetal malpresentation, cord prolapse. O L IG O H Y DR A M N I O S n n n n n An AFI < 5 on ultrasound. Usually asymptomatic, but IUGR or fetal distress may be present. Etiologies include the following: n Fetal urinary tract abnormalities (eg, renal agenesis, GU obstruction) n Chronic uteroplacental insufficiency n ROM Dx: The sum of the deepest amniotic fluid pocket in all 4 abdominal quadrants on ultrasound. Tx: Rule out inaccurate gestational dates. Treat the underlying cause if possible. Cx: n Associated with a 40-fold ↑ in perinatal mortality. n Other complications include musculoskeletal abnormalities (eg, clubfoot, facial distortion), pulmonary hypoplasia, umbilical cord compression, and IUGR. HIGH-YIELD FACTS IN 305 306 HIGH-YIELD FACTS IN OBSTETRICS R h I S OIM M U NIZATI ON In this condition, fetal RBCs leak into the maternal circulation, and maternal anti-Rh IgG antibodies form that can cross the placenta, leading to hemolysis of fetal Rh RBCs (erythroblastosis fetalis; see Figure 2.11-9). There is an ↑ risk among an Rh-! women who have had a previous SAB or TAB as well as among those who have undergone a previous delivery with no RhoGAM given. DIAGNOSIS Sensitized Rh-! mothers with titers > 1:16 should be closely monitored with serial ultrasound and amniocentesis for evidence of fetal hemolysis. TREATMENT In severe cases, initiate preterm delivery when fetal lungs are mature. Prior to delivery, intrauterine blood transfusions may be given to correct a low fetal hematocrit. PREVENTION n n n If the mother is Rh ! at 28 weeks and the father is Rh " or unknown, give RhoGAM (Rh immune globulin). If the baby is Rh ", give the mother RhoGAM postpartum. Give RhoGAM to Rh-! mothers who undergo abortion or who have had an ectopic pregnancy, amniocentesis, vaginal bleeding, or placenta previa/ placental abruption. Type and screen is critical; follow β-hCG closely and prevent pregnancy for 1 year. COMPLICATIONS n n Hydrops fetalis when fetal hemoglobin is < 7 g/dL. Fetal hypoxia and acidosis, kernicterus, prematurity, death. G E S TAT I ONAL TR OP HOBLAS T I C D I S E AS E ( G TD) A range of proliferative trophoblastic abnormalities that can be benign or malignant. n n Benign GTD: Includes complete and incomplete molar pregnancies (see Table 2.11-15). Malignant GTD: Molar pregnancy may progress to malignant GTD, including: n Invasive moles: 10–15%. n Choriocarcinoma: 2–5%. – – – – – – A + + S + – + – + B – S + – + S – + – – + – –+ + – + + + C S – – – S – – – S + S D – S + – + S + – – – S S – E Rh isoimmunization. (A) Rh-negative mother prior to pregnancy. (B) Rh-positive fetus in Rh-negative mother. (C) Placental separation. (D) After delivery, the mother develops antibodies (S) to Rh antigen. (E) Rh-positive fetus in the next pregnancy. Maternal antibodies, from Rh isoimmunization at the time of the previous delivery, cross the placenta and cause hemolysis of red blood cells in the fetus. (Reproduced with permission from DeCherney FIGURE 2.11-9. AH, Nathan L. Current Diagnosis & Treatment Obstetrics & Gynecology, 10th ed. New York: McGraw-Hill, 2007, Fig. 15-1.) OBSTETRICS TA B L E 2 . 11- 15 . Complete vs. Incomplete Moles VARIABLE Mechanism COMPLETE INCOMPLETE Sperm fertilization of an empty Normal ovum fertilized by 2 sperm ovum n Karyotype 46,XX 69,XXY Fetal tissue No fetal tissue Contains fetal tissue Complications of malignant GTD include pulmonary or CNS metastases and trophoblastic pulmonary emboli. HISTORY/PE n n Presents with first-trimester uterine bleeding, hyperemesis gravidarum, preeclampsia/eclampsia at < 24 weeks, and uterine size greater than dates. Risk factors include extremes of age (< 20 or > 40 years) and a diet deficient in folate or beta-carotene. DIAGNOSIS n n n n n n No fetal heartbeat is detected. Pelvic examination may reveal enlarged ovaries (bilateral theca-lutein cysts) or expulsion of grapelike molar clusters into the vagina. Labs show markedly ↑ serum β-hCG (usually > 100,000 mIU/mL). Pelvic ultrasound reveals a “snowstorm” appearance with no gestational sac or fetus present (see Figure 2.11-10). CXR may show lung metastases D&C reveals “cluster-of-grapes” tissue. Molar pregnancy. Transvaginal ultrasound shows a large, complex intrauterine mass with cystic regions that have the characteristic appearance of grapes. (Reproduced FIGURE 2.11-10. with permission from Tintinalli JE et al. Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 6th ed. New York: McGraw-Hill, 2004, Fig. 113-27.) 113-27 HIGH-YIELD FACTS IN 307 308 HIGH-YIELD FACTS IN OBSTETRICS TREATMENT n n n n Evacuate the uterus and follow with weekly β-hCG. Treat malignant disease with chemotherapy (methotrexate or dactinomycin) Treat residual uterine disease with hysterectomy Chemotherapy and irradiation are highly effective for metastases. MU LTI P LE GE S T ATI ONS n n n n n n Affect 3% of all live births. Since 1980, the incidence of monozygotic (identical) twins has remained steady, while the incidence of dizygotic (fraternal) and higher-order births has ↑. Hx/PE: Characterized by rapid uterine growth, excessive maternal weight gain, and palpation of 3 or more large fetal parts on Leopold’s maneuvers. Dx: Ultrasound; hCG, human placental lactogen, and MSAFP are elevated for GA. Tx: n Multifetal reduction and selective fetal termination is an option for higher-order multiple pregnancies. n Antepartum fetal surveillance for IUGR. n Management by a high-risk specialist is recommended. Cx: n Maternal: Patients are 6 times more likely to be hospitalized with complications of pregnancy. n Fetal: Complications include twin-to-twin transfusion syndrome, IUGR, preterm labor, and a higher incidence of congenital malformations. Abnormal Labor and Delivery SHOU L DE R DYS TOC I A Affects 0.6–1.4% of all deliveries in the United States. Risk factors include obesity, diabetes, a history of a macrosomic infant, and a history of prior shoulder dystocia. DIAGNOSIS Diagnosed by a prolonged second stage of labor, recoil of the perineum (“turtle sign”), and lack of spontaneous restitution. TREATMENT In the event of dystocia, be the mother’s HELPER: n n n n n n Help reposition. Episiotomy. Leg elevated (McRoberts’ maneuver; see Figure 2.11-11). Pressure (suprapubic). Enter the vagina and attempt rotation (Wood’s screw). Reach for the fetal arm. OBSTETRICS FIGURE 2.11-11. Leg elevation (McRoberts’ maneuver). The leg positioning illustrated here can be used to assist in a delivery where the infant is at risk for shoulder dystocia. (Reproduced with permission from Cunningham FG et al. Williams Obstetrics, 23rd ed. New York: McGraw-Hill, 2010, Fig. 20-15.) FAI LUR E T O P R O G R E S S Associated with chorioamnionitis, occiput posterior position, nulliparity, and elevated birth weight. DIAGNOSIS Q Q First-stage protraction or arrest: Labor that fails to produce adequate rates of progressive cervical change. Prolonged second-stage arrest: Arrest of fetal descent. See Table 2.11-16 for definitions based on parity and anesthesia. TREATMENT See Table 2.11-16. COMPLICATIONS Q Q Q Chorioamnionitis leads to fetal infection, pneumonia, and bacteremia. Permanent injury occurs in 10%. The risk of postpartum hemorrhage is 11%; that of fourth-degree laceration is 3.8%. R UP T UR E OF ME MB R A N E S ( R O M) Distinguished as follows: Q Q Spontaneous ROM: Occurs after or at the onset of labor. Premature ROM: Occurs > 1 hour before onset of labor. May be precipitated by vaginal or cervical infections, abnormal membrane physiology, or cervical incompetence. HIGH-YIELD FACTS IN 309 310 HIGH-YIELD FACTS IN OBSTETRICS TA B L E 2 . 11- 16 . STAGE Failure to Progress DEFINITION TREATMENTa FIRST STAGE: FAILURE TO HAVE PROGRESSIVE CERVICAL CHANGE Latent n Prima: > 20 hrs Therapeutic rest via parenteral n Multi: > 14 hrs analgesia; oxytocin; amniotomy; cervical ripening. Active n Prima: > 2 hrs Amniotomy; oxytocin; C-section if the n Multi: > 2 hrs after reaching 3–4 cm previous interventions are ineffective. SECOND STAGE: ARREST OF FETAL DESCENT n Prima: > 2 hrs; > 3 hrs with epidural n Multi: > 1 hr; > 2 hrs with epidural Close observation with a ↓ in epidural rate and continued oxytocin. Assisted vaginal delivery (forceps or vacuum). C-section. a Augmentation with oxytocin should be considered when contraction frequency is < 3 in a 10-minute period or intensity of contraction is < 25 mm Hg above baseline. n n Preterm premature ROM (PPROM): ROM occurring at < 37 weeks’ gestation. Prolonged ROM: ROM occurring > 18 hours prior to delivery. Risk factors include low socioeconomic status (SES), young maternal age, smoking, and STDs. HISTORY/PE Patients often report a “gush” of clear or blood-tinged amniotic fluid. Uterine contractions may be present. DIAGNOSIS n n n n KEY FACT To minimize the risk of infection, do not perform digital vaginal exams on women with PROM. n n n A sterile speculum exam reveals pooling of amniotic fluid in the vaginal vault. Nitrazine paper test is " (paper turns blue, indicating alkaline pH of amniotic fluid). Fern test is " (a ferning pattern is seen under a microscope after amniotic fluid dries on a glass slide). Ultrasound to assess amniotic fluid volume. If the diagnosis is uncertain, ultrasound-guided transabdominal instillation of indigo carmine dye can be used to check for leakage (unequivocal test). Minimize infection risk; do not perform digital vaginal exams on women who are not in labor or for whom labor is not planned immediately. Check fetal heart tracing, maternal temperature, WBC count, and uterine tenderness for evidence of chorioamnionitis. TREATMENT n Depends on GA and fetal lung maturity. n Term: First check GBS status and fetal presentation; then labor may be induced or the patient can be observed for 24–72 hours. OBSTETRICS HIGH-YIELD FACTS IN 311 > 34–36 weeks’ GA: Labor induction may be considered. < 32 weeks’ GA: Expectant management with bed rest and pelvic rest. Antibiotics: To prevent infection and to prolong the latency period in the absence of infection. Antenatal corticosteroids: n Give betamethasone or dexamethasone × 48 hours. n Promotes fetal lung maturity in the absence of intra-amniotic infection prior to 32 weeks’ GA. If signs of infection or fetal distress develop, give antibiotics (ampicillin and gentamicin) and induce labor. n n n n n COMPLICATIONS Preterm labor and delivery, chorioamnionitis, placental abruption, cord prolapse. P RE T E R M L A B O R Onset of labor between 20 and 37 weeks’ gestation. The 1° cause of neonatal morbidity and mortality. n n Risk factors include multiple gestation, infection, PROM, uterine anomalies, previous preterm labor or delivery, polyhydramnios, placental abruption, poor maternal nutrition, and low SES. Most patients have no identifiable risk factors. HISTORY/PE Presents with menstrual-like cramps, onset of low back pain, pelvic pressure, and new vaginal discharge or bleeding. DIAGNOSIS n n n n n Requires the following: n Regular uterine contractions (3 or more contractions of 30 seconds each over a 30-minute period) and n Concurrent cervical change at < 37 weeks’ gestation. Assess for contraindications to tocolysis such as infection, nonreassuring fetal testing, or placental abruption. Sterile speculum exam to rule out PROM. Ultrasound to rule out fetal or uterine anomalies, verify GA, and assess fetal presentation and amniotic fluid volume. Obtain cultures for chlamydia, gonorrhea, and GBS; obtain a UA and urine culture. TREATMENT n n n n Hydration and bed rest. Tocolytic therapy (β-mimetics, MgSO4, CCBs, PGIs) unless contraindicated. Steroids to accelerate fetal lung maturation. Penicillin or ampicillin for GBS prophylaxis if preterm delivery is likely. COMPLICATIONS RDS, intraventricular hemorrhage, PDA, necrotizing enterocolitis, retinopathy of prematurity, bronchopulmonary dysplasia, death. KEY FACT Preterm labor = regular uterine contractions + concurrent cervical change at < 37 weeks’ gestation. 312 HIGH-YIELD FACTS IN OBSTETRICS FE TAL M ALP R E S E NT AT I ON Any presentation other than vertex (ie, head closest to birth canal, chin to chest, occiput anterior). Risk factors include prematurity, prior breech delivery, uterine anomalies, poly- or oligohydramnios, multiple gestations, PPROM, hydrocephalus, anencephaly, and placenta previa. HISTORY/PE Breech presentations are the most common form and involve presentation of the fetal lower extremities or buttocks into the maternal pelvis (see Figure 2.11-12). Subtypes include the following: KEY FACT Breech presentation is the most common fetal malpresentation. n n n Frank breech (50–75%): The thighs are flexed and the knees are extended. Footling breech (20%): One or both legs are extended below the buttocks. Complete breech (5–10%): The thighs and knees are flexed. TREATMENT n n n n Follow: Up to 75% spontaneously change to vertex by week 38. External version: If the fetus has not reverted spontaneously, a version may be attempted by applying directed pressure to the maternal abdomen to turn the infant to vertex. The success rate is roughly 50%. Risks of version are placental abruption and cord compression, so be prepared for an emergency C-section if needed. Trial of breech vaginal delivery: Attempt only if delivery is imminent. Complications include cord prolapse and/or head entrapment. Elective C-section: Recommended given the lower risk of fetal morbidity. Single footling breech Frank breech Complete breech FIGURE 2.11-12. Types of breech presentations. (Reproduced with permission from DeCherney AH. Current Obstetric & Gynecologic Diagnosis & Treatment, 8th ed. Stamford, CT: Appleton & Lange, 1994: 411.) OBSTETRICS HIGH-YIELD FACTS IN 313 IN DI CA T IO N S F O R CE S A R E A N S E CT I ON See Table 2.11-17 for indications. For both elective and indicated cesarean delivery, sodium citrate should be used in the mother to ↓ gastric acidity and prevent acid aspiration syndrome. EP IS I O T O M Y n n n n Surgical extension of the vaginal opening into the perineum. Can be median (midline) or mediolateral. Complications include the following: n Extension to the anal sphincter (third degree) or rectum (fourth degree): More common with midline episiotomy. n Other: Bleeding, infection, dyspareunia, rectovaginal fistula formation or maternal death (rare). Routine use of episiotomy is not recommended. Puerperium P OST P A RTU M HE M O R R H A G E n n n n n A loss of > 500 mL of blood for vaginal delivery or > 1000 mL for C-section. May occur before, during, or after delivery of the placenta. Table 2.11-18 summarizes common causes. Complications include the following: n Acute blood loss (potentially fatal). n Anemia due to chronic blood loss (predisposes to puerperal infection). n Sheehan’s syndrome. Severe postpartum hemorrhage may be controlled with uterine artery embolization. P OST P A RTU M I N F E C T I O N S n A temperature ≥ 38°C for at least 2 of the first 10 postpartum days (not including the first 24 hours). T A B L E 2 . 1 1 - 1 7. KEY FACT Postpartum endometritis: n Fever > 38°C within 36 hours n Uterine tenderness n Malodorous lochia Indications for Cesarean Section MATERNAL FACTORS Prior classical C-section (vertical incision predisposes to uterine rupture with FETAL AND MATERNAL FACTORS Cephalopelvic disproportion (the most common cause of 1° C-section) FETAL FACTORS Fetal malposition (eg, posterior chin, transverse lie, shoulder presentation) Placenta previa/placental abruption Fetal distress Active genital herpes infection Failed operative vaginal delivery Cord compression/prolapse Cervical carcinoma Postterm pregnancy (relative indication) Erythroblastosis fetalis (Rh incompatibility) vaginal delivery) Maternal trauma/demise HIV infection Prior transverse C-section (relative indication) 314 HIGH-YIELD FACTS IN TA B L E 2 . 11- 18 . Common Causes of Postpartum Hemorrhage VARIABLE Risk factors OBSTETRICS UTERINE ATONY GENITAL TRACT TRAUMA Uterine overdistention (multiple gestation, macrosomia, Precipitous labor. Placenta accreta/increta/percreta. Operative vaginal delivery (forceps, Placenta previa. vacuum extraction). polyhydramnios). Exhausted myometrium (rapid or prolonged labor, oxytocin RETAINED PLACENTAL TISSUE Uterine leiomyomas. Large infant. Preterm delivery. Inadequate episiotomy repair. Previous C-section/curettage. Manual and visual inspection of the Manual and visual inspection of the lower genital tract for any laceration placenta and uterine cavity for > 2 cm long. missing cotyledons. stimulation). Uterine infection. Conditions interfering with contractions (anesthesia, myomas, MgSO4). Diagnosis Palpation of a soft, enlarged, “boggy” uterus. The most common cause of Ultrasound may also be used to postpartum hemorrhage (90%). inspect the uterus. Treatmenta Bimanual uterine massage (usually Surgical repair of the physical defect. Manual removal of remaining placental tissue. successful). Curettage with suctioning (carries risk Oxytocin infusion. Methergine (methylergonovine) if not of uterine perforation). hypertensive. Prostaglandin (PGF2a). a For all uterine causes, when bleeding persists after conventional therapy, uterine/internal iliac artery ligation, uterine artery embolization, or hysterectomy can be lifesaving. n n MNEMONIC n The 7 W’s of postpartum fever (10 days postdelivery): Womb (endomyometritis) Wind (atelectasis, pneumonia) Water (UTI) Walk (DVT, pulmonary embolism) Wound (incision, episiotomy) Weaning (breast engorgement, abscess, mastitis) Wonder drugs (drug fever) Risk factors for postpartum endometritis include emergent C-section, PROM, prolonged labor, multiple intrapartum vaginal exams, intrauterine manipulations, delivery, low SES, young age, prolonged ruptured membranes, bacterial colonization, and corticosteroid use. Tx: Broad-spectrum empiric IV antibiotics (eg, clindamycin and gentamicin) until patients have been afebrile for 48 hours (24 hours for chorioamnionitis). Add ampicillin for complicated cases. Cx: Septic pelvic thrombophlebitis. n Pelvic infection leads to infection of the vein wall and intimal damage, leading in turn to thrombogenesis. The clot is then invaded by microorganisms. n Suppuration follows, with liquefaction, fragmentation, and, finally, septic embolization. n Presents with abdominal and back pain and a “picket-fence” fever curve (“hectic” fevers) with wide swings from normal to as high as 41°C (105.8°F). n Diagnose with blood cultures and CT looking for a pelvic abscess. n Treat with broad-spectrum antibiotics and anticoagulation with heparin × 7–10 days. OBSTETRICS HIGH-YIELD FACTS IN 315 S H E E H A N ’ S SY N D R O M E ( PO S T PAR TU M P ITU I TAR Y NE C R OS I S ) n n n n Pituitary ischemia and necrosis that lead to anterior pituitary insufficiency 2° to massive obstetric hemorrhage and shock. Hx/PE: n The 1° cause of anterior pituitary insufficiency in adult females. n The most common presenting syndrome is failure to lactate (due to ↓ prolactin levels). n Other symptoms include weakness, lethargy, cold insensitivity, genital atrophy, and menstrual disorders. Dx: Provocative hormonal testing and MRI of the pituitary and hypothalamus to rule out tumor or other pathology. Tx: Replacement of all deficient hormones. Some patients may recover TSH and even gonadotropin function after cortisol replacement alone. LA C TA T IO N A N D B R E A ST F E ED ING n n n n n n n n During pregnancy, ↑ estrogen and progesterone result in breast hypertrophy and inhibition of prolactin release. After delivery of the placenta, hormone levels ↓ markedly and prolactin is released, stimulating milk production. Periodic infant suckling leads to further release of prolactin and oxytocin, which stimulate myoepithelial cell contraction and milk ejection (“letdown reflex”). Colostrum (“early breast milk”) contains protein, fat, secretory IgA, and minerals. Within 1 week postpartum, mature milk with protein, fat, lactose, and water is produced. High IgA levels in colostrum provide passive immunity for the infant and protect against enteric bacteria. Other benefits include the following: n ↓ incidence of infant allergies. n ↓ incidence of early URIs and GI infections. n Facilitation of mother-child bonding. n Maternal weight loss. Contraindications to breastfeeding include HIV infection, active HBV and HCV infection, and use of certain medications (eg, tetracycline, chloramphenicol). MA ST I TI S Cellulitis of the periglandular tissue caused by nipple trauma from breastfeeding coupled with the introduction of bacteria, usually S aureus, from the infant’s pharynx into the nipple ducts. HISTORY/PE n n n Symptoms often begin 2–4 weeks postpartum. Symptoms are usually unilateral and include the following: n Breast tenderness n A palpable mass n Erythema, edema, warmth, and possible purulent nipple drainage Significant fever, chills, and malaise may also be seen. KEY FACT Breastfeeding is contraindicated in maternal HIV infection, active hepatitis, and use of certain medications. 316 HIGH-YIELD FACTS IN OBSTETRICS DIAGNOSIS n n Differentiate from simple breast swelling. Infection is suggested by focal symptoms, an ↑ WBC count, and fever. TREATMENT KEY FACT n n The treatment of mastitis includes antibiotics and continued breastfeeding. n Continued breastfeeding to prevent the accumulation of infected material (or use of a breast pump in patients who are no longer breastfeeding). PO antibiotics (dicloxacillin, cephalexin, amoxicillin/clavulanate, azithromycin, clindamycin). Targeted breast ultrasound to assess for abscess. If present, treat with incision and drainage. HIGH-YIELD FACTS IN GYNECOLOGY Menarche and Normal Female Development 318 Normal Menstrual Cycle 318 Gynecologic Neoplasms 335 UTERINE LEIOMYOMA (FIBROIDS) 335 ENDOMETRIAL CANCER 336 Menopause 319 CERVICAL CANCER 337 Contraception 320 VULVAR CANCER 340 Abnormalities of the Menstrual Cycle 320 VAGINAL CANCER 341 1° AMENORRHEA/DELAYED PUBERTY 320 OVARIAN CANCER 341 2° AMENORRHEA 323 1° DYSMENORRHEA 324 2° DYSMENORRHEA 325 ABNORMAL UTERINE BLEEDING 326 Reproductive Endocrinology 328 CONGENITAL ADRENAL HYPERPLASIA 328 POLYCYSTIC OVARIAN SYNDROME 329 INFERTILITY 330 Gynecologic Infections 330 CYST AND ABSCESS OF BARTHOLIN’S DUCT 330 VAGINITIS 331 CERVICITIS 332 PELVIC INFLAMMATORY DISEASE 332 TOXIC SHOCK SYNDROME 334 Pelvic Organ Prolapse 343 Urinary Incontinence 344 Pediatric Gynecology 345 PEDIATRIC VAGINAL DISCHARGE 345 PRECOCIOUS PUBERTY 346 Breast Disorders 347 FIBROCYSTIC CHANGE 347 FIBROADENOMA 348 BREAST CANCER 349 Sexual Assault 351 317 318 HIGH-YIELD FACTS IN GYNECOLOGY Menarche and Normal Female Development n n n Thelarche: Breast development; usually occurs between the ages of 8 and 11. Menarche: The first menstrual cycle; onset generally occurs between the ages of 10 and 16. Figure 2.12-1 graphically illustrates the stages of normal female development. Normal Menstrual Cycle The progression of a normal menstrual cycle is as follows (see also Figure 2.12-2): n n n Follicular phase (days 1–13): n May vary, but typically lasts ∼ 13 days. n ↑ FSH → growth of follicles → ↑ estrogen production. n Results in the development of straight glands and thin secretions of the uterine lining (proliferative phase). Ovulation (day 14): n LH and FSH spike, leading to rupture of the ovarian follicle and release of a mature ovum. n Ruptured follicular cells involute and create the corpus luteum. Luteal phase (days 15–28): n The length of time (14 days) that the corpus luteum can survive without further LH stimulation. GIRLS HEIGHT SPURT GROWTH RATE Height 2 in/y Weight 6 lb/y MENARCHE PEAK Height 3 in/y Weight 17.5 lb/y AGE RANGE 11.5–16.5 y AGE RANGE 10-16.5 y Average height 62.5 in (158.5 cm) Average weight 106 lb (48 kg) BREAST Breast buds begin. AGE RANGE 8–13 years SEXUAL MATURITY 2 RATING Breast and areola grow. 3 Nipple and areola from separate mound, protruding from breast. Areola rejoins breast contour and development is complete. AGE RANGE 12.5–18.5 years 4 5 PUBIC HAIR Initial hair is straight and fine. AGE RANGE 8–14 years AGE FIGURE 2.12-1. 11 years Pubic hair Hair looks like becomes an adult’s but limited coarse, darkens, in area. and spreads. 12 years 13 years Inverted triangular pattern is established. AGE RANGE 12.5–16.5 years 14 years 15 years Normal female development. (Reproduced with permission from Hay WW Jr et al. Cur- rent Diagnosis & Treatment: Pediatrics, 19th ed. New York: McGraw-Hill, 2008, Fig. 3-4.) GYNECOLOGY FSH LH Follicular phase Primary Antral Dominant Ovarian follicles HIGH-YIELD FACTS IN 319 Luteal phase Ovulation Corpus luteum Corpus albicans Inhibin B Inhibin A E2 Prog Endo Proliferative FIGURE 2.12-2. Secretory Normal menstrual cycle. (Reproduced with permission from Fauci AS et al. Harrison’s Principles of Internal Medicine, 17th ed. New York: McGraw-Hill, 2008, Fig. 341-8.) n n The corpus luteum produces estrogen and progesterone, allowing the endometrial lining to develop thick endometrial glands with thick secretions (secretory phase). In the absence of implantation, the corpus luteum cannot be sustained, and the endometrial lining sloughs off. Menopause Cessation of menses for a minimum of 12 months as a result of cessation of follicular development. HISTORY/PE n n n The average age of onset is 51 years. Symptoms include hot flashes, vaginal atrophy, insomnia, anxiety/ irritability, poor concentration, mood changes, dyspareunia, and loss of libido. “Premature menopause” is cessation of menses before age 40. DIAGNOSIS n n A clinical diagnosis. The following studies are not routine but may be helpful: n Labs: ↑ FSH; then ↑ LH. n Lipid profile: ↑ total cholesterol, ↓ HDL. TREATMENT n n Vasomotor symptoms: n Hormone replacement therapy (HRT; combination estrogen and progestin): n May ↑ the incidence of breast cancer. n ↑ cardiovascular morbidity and mortality. n Contraindications include vaginal bleeding, breast cancer (known or suspected), untreated endometrial cancer, a history of thromboembolism, chronic liver disease, and hypertriglyceridemia. n Non-HRT: SSRI/SNRIs, clonidine, and/or gabapentin to ↓ the frequency of hot flashes. Vaginal atrophy: Topical estrogen preparations. KEY FACT Currently, HRT is not recommended as first-line treatment for menopausal symptoms. 320 HIGH-YIELD FACTS IN KEY FACT GYNECOLOGY n Once a woman is postmenopausal, she should be routinely screened for osteoporosis. KEY FACT Contraception Eighty-five percent of women who are sexually active with no contraception will become pregnant within 1 year. n Multiple sexual partners and nulliparity are not absolute contraindications to IUD use. Osteoporosis: DEXA scan is used to measure bone mineral density (BMD). Treat with daily calcium and vitamin D supplementation and exercise +/− bisphosphonates. n n KEY FACT Combined hormonal methods of contraception protect against endometrial and ovarian cancer. Table 2.12-1 describes the effectiveness of contraceptive methods along with their relative advantages and disadvantages. See Table 2.12-2 for contraindications to common methods of contraception. Emergency contraception (EC) methods prevent pregnancy after unprotected sex or contraceptive failure. Table 2.12-3 describes the various methods of EC. Abnormalities of the Menstrual Cycle 1° AM E NOR R HE A/ DE LA YED P U BE R TY Defined as the absence of menses by age 16 with 2° sexual development present, or the absence of 2° sexual characteristics by age 14. HISTORY/PE n n Absence of 2° sexual characteristics (no estrogen production): Etiologies are as follows: n Constitutional growth delay: The most common cause. n 1° ovarian insufficiency: Most commonly Turner’s syndrome. Look for a history of radiation and chemotherapy. n Central hypogonadism: May be caused by a variety of factors, including the following: n Undernourishment, stress, hyperprolactinemia, or exercise. n CNS tumor or cranial irradiation. n Kallmann’s syndrome (isolated gonadotropin deficiency) associated with anosmia. Presence of 2° sexual characteristics (estrogen production but other anatomic or genetic problems): Etiologies include the following: n Müllerian agenesis: Absence of two-thirds of the vagina; uterine abnormalities. n Imperforate hymen: Presents with hematocolpos (blood in the vagina) that cannot escape, along with a bulging hymen. n Complete androgen insensitivity: Patients present with breast development (aromatization of testosterone to estrogen) but are amenorrheic and lack pubic hair. DIAGNOSIS KEY FACT The first step in the workup of 1° or 2° amenorrhea is a pregnancy test! n n Get a pregnancy test. Obtain a bone age radiograph (PA left hand) to determine if bone age is consistent with pubertal onset (> 12 years in girls). n If the patient is of short stature (bone age < 12 years) with normal growth velocity, constitutional growth delay (the most common cause of 1° amenorrhea) is the probable cause. GYNECOLOGY TA B L E 2 . 12 - 1 . HIGH-YIELD FACTS IN 321 Contraceptive Methods METHOD MECHANISM ADVANTAGES DISADVANTAGES MOST EFFECTIVE: > 99% Implanon (progestin-only Inhibits ovulation; ↑ cervical Effective for up to 3 years. Weight gain, depression, irregular implant) mucus viscosity. Immediate fertility once removed. periods. Safe with breastfeeding. IUD with progestin Foreign body results in Effective for up to 5 years. Spotting (up to 6 months), acne. (Mirena) inflammation; progesterone Immediate fertility once removed. Risk of uterine puncture (1/1000). leads to cervical thickening and Safe with breastfeeding. endometrial decidualization. Lighter periods; less cramping. Foreign body results in Effective for up to 10 years. inflammation; copper has a Immediate fertility once removed. spermicidal effect. Safe with breastfeeding. Risk of uterine puncture (1/1000). Surgical sterilization Permanently effective; safe with Tubal ligation: Irreversible; (vasectomy, tubal breastfeeding. Copper T IUD (ParaGard) ↑ cramping and bleeding (5–10%). ↑ ectopic pregnancy. Vasectomy: Most failures are due ligation) to not waiting for 2 ! semen samples. VERY EFFECTIVE: 90–99% Depo-Provera IM injection every 3 months. (medroxyprogesterone) Lighter or no periods. Each shot works for 3 months. Safe with breastfeeding. Irregular bleeding and weight gain. Decreases in BMD (reversible). Delayed fertility after discontinuation (up to 10 months). Ortho Evra (“the patch”) Combined weekly estrogen and Periods may be more regular. Thromboembolism risk (especially progestin dermal patch. Weekly administration. in smokers and those > 35 years of age). NuvaRing (“the ring”) Combined low-dose progestin and Can make periods more regular. May ↑ vaginal discharge. estrogen vaginal ring. Three weeks—continuous; Spotting (first 1–2 months). 1 week—no ring. Safe to use continuously. (continues) 322 HIGH-YIELD FACTS IN TA B L E 2 . 12 - 1 . GYNECOLOGY Contraceptive Methods (continued) METHOD MECHANISM ADVANTAGES OCPs (combination Inhibit FSH/LH, suppressing estrogen and progestin) ovulation; thicken cervical mucus; decidualize endometrium. ↓ risk of ovarian and endometrial cancers. a Predictable, lighter, less painful menses. Can improve acne. DISADVANTAGES Requires daily compliance. Breakthrough bleeding (10–30%). Thromboembolism risk (especially in smokers and those > 35 years of age). Immediate fertility upon cessation. Progestin-only “minipills” Thicken cervical mucus. Safe with breastfeeding. Requires strict compliance with daily timing. MODERATELY EFFECTIVE: 75–90% Male condoms A latex sheath covers the penis. The only method that effectively Possible allergy to latex or protects against pregnancy and spermicides. STDs, including HIV. Diaphragm with Some protection against STDs. Must be fitted by the provider. Female condom Some protection against STDs. Can be difficult to use. Fertility awareness No side effects. Requires the partner’s spermicide methods participation. No STD/HIV protection. LESS EFFECTIVE: 68–74% Withdrawal No side effects. No STD/HIV protection. Not recommended as a 1° method. Spermicide May be used as a 2° method. Not recommended as a 1° method. a Other combined hormonal methods (eg, patch, ring) may also protect against endometrial and ovarian cancer; however, data are still lacking given their relatively recent introduction. If bone age is > 12 years but there are no signs of puberty, obtain LH/ FSH levels and consider where the problem is on the HPA axis (see Table 2.12-4). Ultrasound to evaluate the ovaries. Normal breast development and no uterus: Obtain a karyotype to evaluate for androgen insensitivity syndrome (XY). Normal breast development and uterus: Measure prolactin and obtain an MRI to assess the pituitary gland. n n n n GYNECOLOGY TA B L E 2 . 12 - 2 . HIGH-YIELD FACTS IN 323 Contraindications to Common Methods of Contraception ESTROGEN-CONTAINING HORMONAL METHODSa IUDS (MIRENA AND COPPER) Pregnancy Known or suspected pregnancy A history of stroke or DVT Unexplained vaginal bleeding Breast cancer Current purulent cervicitis Undiagnosed abnormal vaginal bleeding Active (within 3 months) or recurrent PID Estrogen-dependent cancer Confirmed symptomatic actinomycosis on culture (but not asymptomatic A benign or malignant liver neoplasm Current tobacco use and age > 35 colonization) A bicornuate or septate uterus Cervical or uterine cancer A Pap smear with a squamous intraepithelial lesion or 2 atypical Pap smears A history of heart valve replacement or artificial joints Copper T alone: n Copper intolerance (allergy to copper, Wilson’s disease) n Severe dysmenorrhea and/or menorrhagia Mirena alone: a n Levonorgestrel allergy n Breast cancer n Acute liver disease or liver tumor Includes OCPs, NuvaRing, and Ortho Evra. TREATMENT n n n Constitutional growth delay: No treatment is necessary. Hypogonadism: Begin HRT with estrogen alone at the lowest dose. Twelve to 18 months later, begin cyclic estrogen/progesterone therapy (if the uterus is present). Anatomic: Generally requires surgical intervention. 2 ° A M E N O R R H EA Defined as the absence of menses for 6 consecutive months in women who have passed menarche. 1 A 56-year-old female presents with complaints of insomnia, vaginal dryness, and lack of menses for 13 months. What is the most likely diagnosis? DIAGNOSIS n n Get a pregnancy test. If !, measure TSH and prolactin. n ↑ TSH: Indicates hypothyroidism. n ↑ prolactin (inhibits the release of LH and FSH): Points to a pituitary pathology. Order an MRI of the pituitary to look for a prolactinsecreting pituitary adenoma. 2 A 16-year-old female presents with ↓ appetite, insomnia, and amenorrhea for 3 months. What is the most likely diagnosis, and how will you confirm it? 324 HIGH-YIELD FACTS IN GYNECOLOGY TA B L E 2 . 12 - 3 . Emergency Contraceptive Methods METHOD ADVANTAGES DISADVANTAGES “Morning-after pill”a Combined estrogen/ Available over the counter. progestin (75% effective) Does not disrupt embryo postimplantation. Can be used as bridge Nausea, vomiting, fatigue, headache, dizziness, breast tenderness. No protection against STDs. contraception. Safe for all women. Progestin only (80% Same as above. effective) Fewer nausea/vomiting side Same as above. effects than combined EC. Copper T IUD (99% Can be used as EC and High initial cost of insertion. effective) continued for up to 10 years Must be inserted by the b of contraception. provider. No protection against STDs. a Used within 120 hours of unprotected sex. b Used within 7 days of unprotected sex. n n 1 The most likely diagnosis is menopause. As a clinical diagnosis, menopause does not require the ordering of any tests. However, if you are trying to rule it out as a cause of 2° amenorrhea, you may consider ordering an FSH level. Elevation is suggestive of menopause. n TREATMENT n n n 2 The most likely diagnosis is pregnancy. Confirm with a β-hCG. Initiate a progestin challenge (10 days of progestin): See Figure 2.12-3 for an algorithm of the diagnostic workup. " progestin challenge (withdrawal bleed): Indicates anovulation that n is likely due to noncyclic gonadotropin secretion, pointing to PCOS or idiopathic anovulation. ! progestin challenge (no bleed): Indicates uterine abnormality or esn trogen deficiency. Signs of hyperglycemia (polydipsia, polyuria) or hypotension: Conduct a 1-mg overnight dexamethasone suppression test to distinguish congenital adrenal hyperplasia (CAH), Cushing’s syndrome, and Addison’s disease. If clinical virilization is present: Measure testosterone, DHEAS, and 17-hydroxyprogesterone. n Mild pattern: PCOS, CAH, or Cushing’s syndrome. n Moderate to severe pattern: Look for an ovarian or adrenal tumor. Hypothalamic: Reverse the underlying cause and induce ovulation with gonadotropins. Tumors: Excision; medical therapy for prolactinomas (eg, bromocriptine, cabergoline). Premature ovarian failure (age < 40 years): If the uterus is present, treat with estrogen plus progestin replacement therapy. 1° DYS M E NOR R HEA Menstrual pain associated with ovulatory cycles in the absence of pathologic findings. Caused by uterine vasoconstriction, anoxia, and sustained contractions mediated by an excess of prostaglandin (PGF2α). GYNECOLOGY TA B L E 2 . 12 - 4 . Etiologies of 1° Amenorrhea ESTROGEN/ Constitutional GnRH LH/FSH PROGESTERONE ETIOLOGY ↓ ↓ ↓ (prepuberty Puberty has levels) not started. growth delay Hypogonadotropic ↓ ↓ ↓ Hypothalamic or pituitary hypogonadism problem. Hyper- ↑ ↑ ↓ Ovaries gonadotropic have failed hypogonadism to produce estrogen. Anovulatory ↑ ↑ ↑ PCOS or a problem with problem estrogen receptors. Anatomic problem Normal Normal Normal Menstrual blood cannot get out. HISTORY/PE n n n Presents with low, midline, spasmodic pelvic pain that often radiates to the back or inner thighs. Cramps occur in the first 1–3 days of menstruation and may be associated with nausea, diarrhea, headache, and flushing. There are no pathologic findings on pelvic exam. DIAGNOSIS A diagnosis of exclusion. Rule out 2° dysmenorrhea (see below). TREATMENT NSAIDs; topical heat therapy; combined OCPs, Mirena IUD. 2 ° D Y S M E N O R R H EA Menstrual pain for which an organic cause exists. Common causes include endometriosis and adenomyosis, fibroids, adhesions, polyps, and PID. HISTORY/PE n n Patients may have a palpable uterine mass, cervical motion tenderness, adnexal tenderness, a vaginal or cervical discharge, or visible vaginal pathology (mucosal tears, masses, prolapse). However, normal abdominal and pelvic exams do not rule out pathology. See Table 2.12-5 for distinguishing features of endometriosis vs. adenomyosis. HIGH-YIELD FACTS IN 325 326 HIGH-YIELD FACTS IN GYNECOLOGY Progestin challenge No withdrawal bleed Withdrawal bleed LH ↑ ↑ = PCOS ↑↑ = premature menopause FSH ↓ ↓ ↑ Idiopathic anovulation Hypergonadotropic hypogonadism/ovarian failure Cyclic estrogen/progesterone test Withdrawal bleed Hypogonadotropic hypogonadism FIGURE 2.12-3. No withdrawal bleed Endometrial or anatomic problem Workup of 2° amenorrhea. DIAGNOSIS n n n Obtain a β-hCG to exclude ectopic pregnancy. Order the following: n CBC with differential to rule out infection or neoplasm. n UA to rule out UTI. n Gonococcal/chlamydial swabs to rule out STDs/PID. Look for pelvic pathology causing pain (see Table 2.12-5). TREATMENT Treatment is etiology specific. ABNOR MAL U TE R I NE B LE E DI NG KEY FACT Postmenopausal vaginal bleeding is cancer until proven otherwise. Normal menstrual bleeding ranges from 2 to 7 days. Dysfunctional uterine bleeding (DUB) is a diagnosis of exclusion that is defined as follows: n n Abnormal uterine bleeding without evidence of an underlying cause. May be ovulatory or anovulatory. HISTORY/PE n Assess the extent of bleeding: n Oligomenorrhea: An ↑ length of time between menses (35–90 days between cycles). n Polymenorrhea: Frequent menstruation (< 21-day cycle); anovular. n Menorrhagia: ↑ amount of flow (> 80 mL of blood loss per cycle) or prolonged bleeding (flow lasting > 8 days); may lead to anemia. GYNECOLOGY TA B L E 2 . 12 - 5 . Endometriosis vs. Adenomyosis VARIABLE Definition HIGH-YIELD FACTS IN 327 ENDOMETRIOSIS Functional endometrial glands and stroma outside the ADENOMYOSIS Endometrial tissue in the myometrium of the uterus. uterus. History/PE Cyclical pelvic and/or rectal pain and dyspareunia. Classic triad of noncyclical pain, menorrhagia, and an enlarged uterus. Diagnosis Requires direct visualization by laparoscopy or laparotomy. Classic lesions have a blue-black (“raspberry”) or dark brown (“powder-burned”) appearance. Treatment Ultrasound is useful but cannot always distinguish between leiomyoma and adenomyosis. MRI can aid in diagnosis but is costly. The ovaries may have endometriomas (“chocolate cysts”). Ultimately a pathologic diagnosis. Pharmacologic: Inhibit ovulation. Combination OCPs (first Pharmacologic: Largely symptomatic relief. NSAIDs (first line), GnRH analogs (leuprolide), danazol, NSAIDs, or progestins. Conservative surgical treatment: Excision, cauterization, or ablation of the lesions and lysis of adhesions. Twenty percent of patients can become pregnant subsequent to treatment. Definitive surgical treatment: Total abdominal line) plus OCPs or progestins. Conservative surgical treatment: Endometrial ablation or resection using hysteroscopy. Complete eradication of deep adenomyosis is difficult and results in high treatment failure. Definitive surgical treatment: Hysterectomy is the only definitive treatment. hysterectomy/bilateral salpingo-oophorectomy (TAH/BSO) +/− lysis of adhesions. Complications Infertility (the most common cause among menstruating Can rarely progress to endometrial carcinoma. women > 30 years of age). Metrorrhagia: Bleeding between periods. Menometrorrhagia: Excessive and irregular bleeding. On pelvic examination, look for an enlarged uterus, a cervical mass, or polyps to assess for myomas, pregnancy, or cervical cancer. n n n DIAGNOSIS n n n n n n n β-hCG: To rule out ectopic pregnancy. CBC: To evaluate for anemia. Pap smear: To rule out cervical cancer. TFTs: To rule out hyper-/hypothyroidism and hyperprolactinemia. Platelet count, PT/PTT: To rule out von Willebrand’s disease and factor XI deficiency, primarily in adolescent patients. Ultrasound: To look for uterine masses, polycystic ovaries, and thickness of the endometrium. Endometrial biopsy should be performed: n If the endometrium is ≥ 4 mm in a postmenopausal woman, or n If the patient is > 35 years of age with risk factors for endometrial hyperplasia (eg, obesity, diabetes). TREATMENT n Heavy bleeding: n High-dose estrogen IV stabilizes the endometrial lining and typically stops bleeding within 1 hour. KEY FACT Pregnancy is the most common cause of abnormal uterine bleeding and amenorrhea. Always check a pregnancy test! KEY FACT First-line treatment of abnormal uterine bleeding consists of NSAIDs to ↓ blood loss! 328 HIGH-YIELD FACTS IN GYNECOLOGY If bleeding is not controlled within 12–24 hours, a D&C is often indicated. Ovulatory bleeding: n NSAIDs to ↓ blood loss. n If the patient is hemodynamically stable, give OCPs or a Mirena IUD. Anovulatory bleeding: n The goal is to convert proliferative endometrium to secretory endometrium (to ↓ the risk of endometrial hyperplasia/cancer). n Progestins × 10 days to stimulate withdrawal bleeding. n Desmopressin to cause a rapid ↑ in von Willebrand’s factor and factor VIII (young patients who may also have a bleeding disorder). n OCPs. n Mirena IUD. If medical management fails: n D&C. n Hysteroscopy: To identify endometrial polyps or to perform directed uterine biopsies. n Hysterectomy or endometrial ablation: Appropriate for the following: n Women who fail or do not want hormonal treatment. n Women who have symptomatic anemia and/or who experience a disruption in their quality of life from persistent, unscheduled bleeding. n n KEY FACT OCPs and the Mirena IUD are highly effective treatment options for menorrhagia. n KEY FACT Complications of abnormal uterine bleeding are anemia and endometrial hyperplasia +/− carcinoma. n Reproductive Endocrinology C ONG E NI TAL A D R E NA L H YP E RP LAS IA ( C AH) A deficiency of at least 1 enzyme required for the biochemical synthesis of cortisol from cholesterol (see Figure 2.12-4). Includes the following: Cholesterol 17α-Hydroxylase CH3 CH3 C C O ACTH Cholesterol desmolase CH3 3β-Hydroxysteroid dehydrogenase C HO O C O CH2OH C O 11-Deoxycorticosterone CH2OH O 11β-Hydroxylase C O C DHEA sulfate Dehydroepiandrosterone HO O Androstenedione O O OH Testosterone O CH2OH O C HO Corticosterone FIGURE 2.12-4. Sulfokinase 11-Deoxycortisol HO O O O OH 17-Hydroxyprogesterone CH2OH Progesterone 21β-Hydroxylase O OH 17-Hydroxypregnenolone CH3 Pregnenolone HO 17,20-Lyase O OH Estradiol Cortisol O Glucocorticoid biosynthesis pathway. (Reproduced with permission from Barrett KE et al. Ganong’s Review of Medical Physiology, 23rd ed. New York: McGraw-Hill, 2010, Fig. 22-7.) GYNECOLOGY n n 21-hydroxylase deficiency: The most severe, classic form; presents as a newborn female infant with ambiguous genitalia and life-threatening salt wasting. 11β-hydroxylase deficiency: Α less common cause of adrenal hyperplasia. HIGH-YIELD FACTS IN 329 KEY FACT n n HISTORY/PE Presents with excessive hirsutism, acne, amenorrhea and/or abnormal uterine bleeding, infertility, and, rarely, a palpable pelvic mass. n Hirsutism = male hair pattern. Virilization = frontal balding, muscularity, clitoromegaly, and deepening of the voice. Defeminization = ↓ breast size; loss of feminine adipose tissue. DIAGNOSIS n n n n ↑ androgens (testosterone > 2 ng; DHEAS > 7 µg/mL): Rule out adrenal or ovarian neoplasm. ↑ serum testosterone: Suspect an ovarian tumor. ↑ DHEAS: Suspect an adrenal source (adrenal tumor, Cushing’s syndrome, CAH). ↑ 17-OH progesterone levels (either basally or in response to ACTH stimulation). TREATMENT n n Glucocorticoids (eg, prednisone). Medical therapy for adrenal and ovarian disorders prevents new terminal hair growth but does not resolve hirsutism. Laser ablation, electrolysis, or conventional hair removal techniques must be used to remove unwanted hair. P O L Y C Y S T IC O VA R IAN S Y N DR O ME ( P COS ) PCOS has a prevalence of 6–10% among U.S. women of reproductive age. Diagnosis requires 2 of the following 3 criteria: 1. Polycystic ovaries 2. Oligo-/anovulation 3. Clinical or biochemical evidence of hyperandrogenism HISTORY/PE n n n KEY FACT The most severe form of PCOS is HAIR-AN syndrome: HyperAndrogenism, Insulin Resistance, and Acanthosis Nigricans. Look for a high BP and obesity (BMI > 30). Stigmata of hyperandrogenism or insulin resistance include menstrual cycle disturbances, hirsutism, obesity, acne, androgenic alopecia, and acanthosis nigricans. Women with PCOS are also at ↑ risk for the following: n Type 2 diabetes mellitus (DM) n Insulin resistance n Infertility n Metabolic syndrome—insulin resistance, obesity, atherogenic dyslipidemia, and hypertension DIAGNOSIS n n Biochemical hyperandrogenemia: ↑ testosterone (total +/− free); DHEAS, DHEA. Exclude other causes of hyperandrogenism: n TSH, prolactin. n 17-OH progesterone to rule out nonclassical CAH. n Consider screening in the setting of clinical signs of Cushing’s syndrome (eg, moon facies, buffalo hump, abdominal striae) or acromegaly (eg, ↑ head size). A 23-year-old female presents with fever and abdominal pain of 2 days’ duration. She has a " chandelier sign. Antibiotics are started. What is the next step in management? 330 HIGH-YIELD FACTS IN GYNECOLOGY n n F I G U R E 2 . 1 2 - 5 . Polycystic ovary with prominent multiple cysts. (Reproduced with permission from DeCherney AH, Nathan R. Current Diagnosis & Treatment: Obstetrics & Gynecol- TREATMENT n ogy, 10th ed. New York: McGraw-Hill, 2007, Fig. 40-3.) n n KEY FACT Combined hormonal contraception or progestin ↓ the risk of endometrial hyperplasia/carcinoma among women with PCOS. Evaluate for metabolic abnormalities: n Two-hour oral glucose tolerance test. n Fasting lipid and lipoprotein levels (total cholesterol, HDL, LDL, triglycerides). Optional tests: n Ultrasound: Look for > 8 small, subcapsular follicles forming a “pearl necklace” sign (see Figure 2.12-5). Seen in roughly two-thirds of women with PCOS. n Gonadotropins: ↑ LH/FSH ratio (> 2:1). n 24-hour urine for free cortisol: Adult-onset CAH or Cushing’s syndrome. Women who are not attempting to conceive: Treat with a combination of OCPs, progestin, and metformin (or other insulin-sensitizing agents). Women who are attempting to conceive: Clomiphene +/− metformin is first-line treatment for ovulatory stimulation. Symptom-specific treatment: n Hirsutism: Combination OCPs are first line; antiandrogens (spironolactone, finasteride) and metformin may also be used. n Cardiovascular risk factors and lipid levels: Diet, weight loss, and exercise plus potentially lipid-controlling medication (eg, statins). COMPLICATIONS ↑ risk of early-onset type 2 DM; ↑ risk of miscarriages; ↑ long-term risk of breast and endometrial cancer due to unopposed estrogen secretion. I N F E R TI LI TY n n The inability to conceive after 12 months of normal, regular, unprotected sexual activity. 1° infertility is characterized by no prior pregnancies; 2° infertility occurs in the setting of at least 1 prior pregnancy. Etiologies are shown in Figure 2.12-6 and Table 2.12-6. Gynecologic Infections CYS T AND ABS C E S S OF BAR THOLI N’S DU CT Obstruction of the gland leads to pain, swelling, and abscess formation. HISTORY/PE n n n Presents with periodic painful swelling on either side of the introitus along with dyspareunia. A fluctuant swelling 1–4 cm in diameter is seen in the inferior portion of either labium minus. Tenderness is evidence of active infection. TREATMENT A pelvic ultrasound to rule out tuboovarian abscess. n n n Asymptomatic cysts: No therapy +/– warm soaks. Abscess: Aspiration or incision and drainage with Word catheter insertion to prevent reaccumulation; culture for Chlamydia and other pathogens. Antibiotics are unnecessary unless cellulitis is present. GYNECOLOGY HIGH-YIELD FACTS IN 331 Infertility 14% of reproductive-age women 5 million couples in the U.S. Female causes 58% Male causes 25% Primary hypogonadism ( FSH) 30–40% Amenorrhea/ ovulatory dysfunction 46% Hypothalamic/ pituitary causes 51% FIGURE 2.12-6. Tubal defect 38% Secondary hypogonadism ( FSH, LH) 2% Endometriosis 9% Polycystic ovary syndrome 30% Unexplained 17% Disordered sperm transport 10–20% Unknown 40–50% Other 7% Premature ovarian failure 12% Uterine or outflow tract disorders 7% Causes of infertility. (Reproduced with permission from Fauci AS et al. Harrison’s Principles of Internal Medicine, 17th ed. New York: McGraw-Hill, 2008, Fig. 341-9.) V AG I N IT IS A spectrum of conditions that cause vulvovaginal symptoms such as itching, burning, irritation, and abnormal discharge. The most common causes are bacterial vaginosis, vulvovaginal candidiasis, and trichomoniasis (see Table 2.12-7). HISTORY/PE n n n n Presents with a change in discharge, malodor, pruritus, irritation, burning, swelling, dyspareunia, and dysuria. Normal secretions are as follows: n Midcycle estrogen surge: Clear, elastic, mucoid secretions. n Luteal phase/pregnancy: Thick and white secretions; adhere to the vaginal wall. Conduct a thorough examination of the vulva, vaginal walls, and cervix. If there are many WBCs and no organism on saline smear, suspect Chlamydia. DIAGNOSIS/TREATMENT n n n Cervical fluid for vaginal pH, amine (whiff) test, wet mount (with saline), and 10% potassium hydroxide (KOH) microscopy. In patients with a purulent discharge, numerous leukocytes on wet prep, cervical friability, and any symptoms of PID, order DNA tests or cultures for Neisseria gonorrhoeae or Chlamydia trachomatis to rule out cervicitis. Treatment is etiology specific (see Table 2.12-7). KEY FACT Criteria for the clinical diagnosis of bacterial vaginosis (3 of 4 are required): n Abnormal whitish-gray discharge n Vaginal pH > 4.5 n " amine (whiff) test n Clue cells comprise > 20% of epithelial cells on wet mount 332 HIGH-YIELD FACTS IN TA B L E 2 . 12 - 6 . GYNECOLOGY Infertility Workup ETIOLOGY HISTORY/PE Male causes DIAGNOSIS TREATMENT Testicular injury or infection TSH Treatment of hormonal deficiency Medications (corticosteroids, Prolactin Intrauterine insemination (IUI) Karyotype (to rule out Klinefelter’s Donor insemination cimetidine, spironolactone) In vitro fertilization (IVF) Thyroid or liver disease syndrome) Signs of hypogonadism Semen analysis Intracytoplasmic sperm injection Age (incidence ↑ with age) Basal body temperature Treatment depends on the etiology Symptoms of hyper-/hypothyroidism Ovulation predictor Galactorrhea Midluteal progesterone Menstrual cycle abnormalities Early follicular FSH +/− estradiol level Varicocele Ovulatory factors (ovarian reserve) (eg, levothyroxine, dopamine) Induction of ovulation with clomiphene, gonadotropins, and pulsatile GnRH TSH, prolactin, androgens IUI Ovarian sonography (antral follicle IVF count) Endometrial biopsy (luteal-phase defect) Tubal/pelvic History of PID, appendicitis, Hysterosalpingogram factors endometriosis, pelvic adhesions, Endometrial biopsy endometriomas or fibroids IVF tubal surgery Cervical factors Laparoscopic resection or ablation of Abnormal Pap smears, postcoital Pap smear IUI with washed sperm bleeding, cryotherapy, conization, or Physical examination IVF DES exposure in utero Antisperm antibodies C E R VICI TI S KEY FACT IUDs do not ↑ PID risk. n n n Inflammation of the uterine cervix. Etiologies are as follows: n Infectious (most common): Chlamydia, gonococcus, Trichomonas, HSV, HPV. n Noninfectious: Trauma, radiation exposure, malignancy. Hx/PE: Yellow-green mucopurulent discharge; " cervical motion tenderness; absence of other signs of PID. Dx/Tx: See the discussion of STDs in the Infectious Disease chapter. P E LVIC I NF LAM M ATOR Y DI S EA S E ( PI D) KEY FACT The chandelier sign is defined as severe cervical motion tenderness that makes the patient “jump for the chandelier” on examination. A polymicrobial infection of the upper genital tract. Associated with N gonorrhoeae (one-third of cases), C trachomatis (one-third of cases), and endogenous aerobes/anaerobes. Risk factors include non-Caucasian ethnicity, douching, smoking, multiple sex partners, and prior STDs and/or PID. HISTORY/PE n n Presents with lower abdominal pain, fever and chills, menstrual disturbances, and a purulent cervical discharge. Cervical motion tenderness (chandelier sign) and adnexal tenderness are also seen. GYNECOLOGY T A B L E 2 . 1 2 - 7. VARIABLE HIGH-YIELD FACTS IN 333 Causes of Vaginitis BACTERIAL VAGINOSIS TRICHOMONAS YEAST Incidence 15–50% (most common). 5–50%. 15–30%. Etiology Reflects a shift in vaginal flora. Protozoal flagellates (an STD). Usually Candida albicans. Risk factors Pregnancy, > 1 sexual partner, female Unprotected sex with multiple DM, broad-spectrum antibiotic use, sexual partner, frequent douching. partners. pregnancy, corticosteroids, HIV, OCP use, ↑ frequency of intercourse. History Odor, ↑ discharge. ↑ discharge, odor, pruritus, dysuria. Pruritus, dysuria, burning, ↑ discharge. Exam Discharge Wet mount a Mild vulvar irritation. “Strawberry petechiae” in the upper Erythematous, excoriated vulva/ vagina/cervix. vagina. Homogenous, grayish-white, fishy/ Profuse, malodorous, yellow-green, Thick, white, curdy texture without stale odor. frothy. odor. “Clue cells” (epithelial cells coated Motile trichomonads (flagellated — with bacteria; see Figure 2.12-7); organisms that are slightly larger than shift in vaginal flora (↑ cocci, WBCs). ↓ lactobacilli). KOH prep " “whiff” test (fishy smell). — Treatment PO or vaginal metronidazole or Single-dose PO metronidazole or vaginal clindamycin. Hyphae (see Figure 2.12-7). Topical azole or PO fluconazole. tinidazole. Treat partners; test for other STDs. Complications Chorioamnionitis/endometritis, Same as for bacterial vaginosis. infection, preterm delivery, miscarriage, PID. a If there are many WBCs and no organism on saline smear, suspect Chlamydia. DIAGNOSIS n n n n Diagnosed by the presence of acute lower abdominal or pelvic pain plus 1 of the following: n Uterine tenderness n Adnexal tenderness n Cervical motion tenderness A WBC count > 10,000 cells/µL has poor positive and negative predictive value for PID. Order a β-hCG to rule out pregnancy. Ultrasound may show thickening or dilation of the fallopian tubes, fluid in the cul-de-sac, a multicystic ovary, or tubo-ovarian abscess. TREATMENT n Antibiotic treatment should not be delayed while awaiting culture results. All sexual partners should be examined and treated appropriately. MNEMONIC Acute causes of pelvic pain— A ROPE Appendicitis Ruptured ovarian cyst Ovarian torsion/abscess PID Ectopic pregnancy 334 HIGH-YIELD FACTS IN GYNECOLOGY A B Causes of vaginitis. (A) Candidal vaginitis. Candida albicans organisms are evident on KOH wet mount. (B) Gardnerella vaginalis. Note the granular epithelial cells (“clue cells”) and indistinct cell margins. (Image A reproduced with permission from Wolff K et al. Fitz- FIGURE 2.12-7. patrick’s Color Atlas & Synopsis of Clinical Dermatology, 5th ed. New York: McGraw-Hill, 2005: 717. Image B reproduced with permission from USMLERx.com.) n n n KEY FACT Mild and subclinical PID is a major cause of tubal factor infertility, ectopic pregnancy, and chronic pelvic pain due to pelvic scarring. Outpatient regimens: n Regimen A: Ofloxacin or levofloxacin × 14 days +/− metronidazole × 14 days. n Regimen B: Ceftriaxone IM × 1 dose or cefoxitin plus probenecid plus doxycycline × 14 days +/− metronidazole × 14 days. Inpatient antibiotic regimens: n Cefoxitin or cefotetan plus doxycycline × 14 days. n Clindamycin plus gentamicin × 14 days. Surgery: n Drainage of a tubo-ovarian/pelvic abscess is appropriate if the mass persists after antibiotic treatment; the abscess is > 4–6 cm; or the mass is in the cul-de-sac in the midline and drainable through the vagina. n If the abscess is dissecting the rectovaginal septum and is fixed to the vaginal membrane, colpotomy drainage is appropriate. n If the patient’s condition deteriorates, perform exploratory laparotomy. n Surgery may range from TAH/BSO with lysis of adhesions in severe cases to conservative surgery for women who desire to maintain fertility. COMPLICATIONS n n n Repeated episodes of infection, chronic pelvic pain, dyspareunia, and ectopic pregnancy. Infertility (10% after the first episode, 25% after the second episode, and 50% after a third episode). Fitz-Hugh–Curtis syndrome (presents with associated perihepatitis, RUQ pain, abnormal liver function, and shoulder pain). TOX IC SHO C K S YNDR OM E ( TS S) Caused by preformed S aureus toxin (TSST-1); often occurs within 5 days of the onset of a menstrual period in women who have used tampons. The incidence in menstruating women is now 6–7:100,000 annually. Nonmenstrual cases are nearly as common as menstrual cases. HISTORY/PE n Presents with abrupt onset of fever, vomiting, and watery diarrhea, with a fever of 38.9°C (102°F) or higher. GYNECOLOGY n n n A diffuse macular erythematous rash is also seen. Nonpurulent conjunctivitis is common. Desquamation, especially of the palms and soles, generally occurs during recovery within 1–2 weeks of illness. DIAGNOSIS Blood cultures are ! because symptoms result from preformed toxin and are not due to the invasive properties of the organism. HIGH-YIELD FACTS IN 335 KEY FACT TSS is a rare but potentially fatal reaction to S aureus toxin. Diagnosis is clinical because the reaction is to the toxin, not to the bacterium itself. The first steps in treatment are rapid rehydration and antibiotic treatment. TREATMENT n n n n Rapid rehydration. Antistaphylococcal drugs (nafcillin, oxacillin); vancomycin for women with penicillin allergy. Corticosteroids can reduce the severity of illness and ↓ fever. Manage renal or cardiac failure. COMPLICATIONS n n The mortality rate associated with TSS is 3–6%. Three major causes of death are ARDS, intractable hypotension, and hemorrhage 2° to DIC. Gynecologic Neoplasms Gynecologic cancers include uterine, endometrial, ovarian, cervical, and vulvar neoplasms. Ovarian cancer carries the highest mortality. UT E R IN E L E IO M Y O M A ( F I B R O I D S) The most common benign neoplasm of the female genital tract. They present as discrete, round, firm, and often multiple tumors composed of smooth muscle and connective tissue. n n n Tumors are estrogen and progesterone sensitive, often increasing in size during pregnancy and decreasing after menopause. Malignant transformation to leiomyosarcoma is rare (0.1–0.5%). Prevalence is 25% among Caucasian women and 50% among African American women. KEY FACT Uterine myomas are benign but can cause infertility or menorrhagia. HISTORY/PE n n The majority of cases are asymptomatic. Symptomatic patients may present with the following: n Bleeding: Longer, heavier periods; anemia. n Pressure: Pelvic pressure and bloating; constipation and rectal pressure; urinary frequency or retention. n Pain: 2° dysmenorrhea, dyspareunia. n Pelvic symptoms: A firm, nontender, irregular enlarged (“lumpybumpy”), or cobblestone uterus may be felt on physical examination. DIAGNOSIS n n n CBC: To look for anemia. Ultrasound: To look for uterine myomas; can also exclude ovarian masses. MRI: Can delineate intramural and submucous myomas. KEY FACT If a uterine mass continues to grow after menopause, suspect malignancy. 336 HIGH-YIELD FACTS IN GYNECOLOGY TREATMENT n n Pharmacologic: n NSAIDs. n Combined hormonal contraception. n Medroxyprogesterone acetate or danazol to slow or stop bleeding. n GnRH analogs (leuprolide or nafarelin) to ↓ the size of myomas, suppress further growth, and ↓ surrounding vascularity. Also used prior to surgery. Surgery: Emergent surgery is indicated for torsion of a pedunculated myoma. n Women of childbearing years: Abdominal or hysteroscopic myomectomy. n Women who have completed childbearing: Total or subtotal abdominal or vaginal hysterectomy. n Uterine artery embolization (~ 25% will need further invasive treatment). COMPLICATIONS Infertility may be due to a myoma that distorts the uterine cavity and plays a role similar to that of an IUD. END OM E TR IAL C ANCE R KEY FACT Eighty percent of women with endometrial carcinoma have vaginal bleeding, but only 5–10% of women with abnormal vaginal bleeding have endometrial cancer. Type I endometrioid adenocarcinomas derive from atypical endometrial hyperplasia and are the most common female reproductive cancer in the United States. Type II cancers derive from serous or clear cell histology (see Table 2.12-8). Although Type II cancers tend to be more aggressive, diagnosis and management are similar for both types. HISTORY/PE n n n Vaginal bleeding (early finding). Pain (late finding). Metabolic syndrome. TA B L E 2 . 12 - 8 . VARIABLE Types of Endometrial Cancer TYPE I: ENDOMETRIOID TYPE II: SEROUS Epidemiology 75% of endometrial cancers. 25% of endometrial cancers. Etiology Unopposed estrogen stimulation Unrelated to estrogen; the p53 (eg, tamoxifen use, exogenous mutation is present in 90% of estrogen-only therapy). cases. Hyperplasia and atypical None. Precursor lesion hyperplasia. Mean age at 55 years. 67 years. Favorable. Poor. diagnosis Prognosis GYNECOLOGY HIGH-YIELD FACTS IN 337 DIAGNOSIS Endometrial/endocervical biopsy. Pelvic ultrasound shows a thickened endometrium leading to hypertrophy and neoplastic change (see Figure 2.12-8). n n KEY FACT Hormonal contraceptives are protective against endometrial cancer. TREATMENT High-dose progestins for women of childbearing age. TAH/BSO +/− radiation for postmenopausal women. TAH/BSO with adjuvant chemotherapy for advanced-stage cancer. n n n C E R V I C A L CA NC E R KEY FACT Screening of asymptomatic women for endometrial cancer is not recommended. The upper third of the cervix (endocervix) is composed of columnar cells (similar to the lower uterine segment). The lower two-thirds (ectocervix) is made up of squamous cells (similar to the vagina). The exposure of columnar cells to an acidic vaginal pH results in metaplasia to squamous cells. The normal squamocolumnar junction (transformation zone) is located in the ectocervix and can be exposed to carcinogens, resulting in cervical intraepithelial neoplasia (CIN), an abnormal proliferation or overgrowth of the basal cell layer. n n n HPV DNA is found in 99.7% of all cervical carcinomas. HPV 16 is the most prevalent type in squamous cell carcinoma; HPV 18 is most prevalent in adenocarcinoma. Additional risk factors for cervical cancer include immunosuppression, infection with HIV or a history of STDs, tobacco use, high parity, and OCPs. The Gardasil vaccine may protect against HPV types 6, 11, 16, and 18 and may also prevent the development of cervical cancer. HISTORY/PE n n Metrorrhagia, postcoital spotting, and cervical ulceration are the most common signs. A bloody or purulent, malodorous, nonpruritic discharge may appear after invasion. F A B F I G U R E 2 . 1 2 - 8 . Endometrial cancer. (A) Sagittal endovaginal ultrasound image demonstrates a mass (arrow) in the lower uterine segment endometrial canal, with fluid (F) distending the canal in the fundus. (B) Gross specimen from a different patient shows a large mass filling the endometrial canal and invading the myometrium. (Image A reproduced with permission from USMLERx.com. Image B reproduced with permission from Schorge JO et al. Williams Gynecology. New York: McGraw-Hill, 2008, Fig. 33-16.) 338 HIGH-YIELD FACTS IN GYNECOLOGY SCREENING n n n The American Congress of Obstetricians and Gynecologists (ACOG) currently recommends that screening for cervical cancer begin at age 21. ACOG previously recommended that cervical screening begin 3 years after the onset of sexual activity or by age 21, whichever occurred first. More recently, however, it was determined that despite the high incidence of HPV infection among sexually active adolescents, invasive cervical cancer was relatively rare among women < 21 years of age. Screening for cervical cancer should consist of the following (see also Table 2.12-9): n Pap smear with conventional cervical cytology: Once every 2 years, or n Pap smear with liquid-based cervical cytology: Once every 2 years. Additional changes to screening guidelines are as follows: n n KEY FACT n Fifty percent of women with cervical cancer had not had a Pap smear in the 3 years preceding their diagnosis, and another 10% had not been screened in 5 years. n n Women ≥ 30 years of age who have had 3 consecutive normal tests may be tested once every 3 years. Women ≥ 30 years of age can be screened with HPV DNA testing for high-risk strands. Screening can be discontinued for women ≥ 70 years of age who have had 3 or more normal Pap smears. Women with DES exposure and/or immunocompromised status (including HIV positivity) should continue to be screened as long as they do not have a life-limiting condition. Women who have had the HPV vaccine should continue to be screened. DIAGNOSIS The diagnosis and follow-up of specific subtypes of cervical lesions should be as follows (these guidelines do not apply to adolescents and pregnant women): 1. ASC-US: All nonpregnant women with cervical cytology showing ASC-US should have the following: n HPV DNA testing: n If !: Repeat Pap smear at 12 months. n If ": Colposcopy. OR TA B L E 2 . 12 - 9 . NUMERICAL Classification Systems for Pap Smears DYSPLASIA CIN BETHESDA SYSTEM 1 Benign Benign Normal 2 Benign with Benign with Normal, atypical inflammation inflammation squamous cells (ASC) 3 Mild dysplasia CIN I LSIL 3 Moderate dysplasia CIN II HSIL 3 Severe dysplasia CIN III HSIL 4 Carcinoma in situ CIN III HSIL 5 Invasive cancer Invasive cancer Invasive cancer GYNECOLOGY Repeat cytology at 6 and 12 months: n If both Pap smears are ! at 6 and 12 months, return to routine screening. n If either Pap smear is " for ASC-US or higher, proceed to colposcopy. OR n Colposcopy. ASC-H: All nonpregnant women with cervical cytology showing ASC-H should have colposcopy. LSIL: All nonpregnant, premenopausal women with cervical cytology showing LSIL should have colposcopy and then proceed as follows: n If unsatisfactory or no visible lesion: Endocervical sampling. n If CIN 2, 3: See the management of CIN below. n If no CIN 2, 3: Repeat Pap smear at 6 and 12 months OR conduct HPV testing at 12 months. n Postmenopausal women should have reflex HPV DNA testing, colposcopy, or a repeat Pap smear at 6 and 12 months. n Pregnant women should defer colposcopy until 6 weeks postpartum. AGC: n All women with cervical cytology showing AGC should have colposcopy with endocervical sampling. n Women > 35 years of age or those with abnormal bleeding raising concern for endometrial neoplasia should have colposcopy with endocervical and endometrial sampling. HSIL: All nonpregnant women with cervical cytology showing HSIL should have colposcopy with endocervical sampling and then proceed as follows: n If CIN 2, 3: Excision or ablation of lesion. n If no CIN 2, 3: Excision or observation with Pap smear and colposcopy every 6 months for a year OR immediate loop electrosurgical excision (LEEP). n Persistent HSIL should be treated with excision. n Pregnant women should have colposcopy without endocervical curettage. n 2. 3. 4. 5. TREATMENT For noninvasive disease, treatment based on biopsy results for noninvasive lesions (stage 0 disease) is as follows: n n n n CIN I: n The mainstay of treatment is close observation. n For women > 21 years of age, Pap smear screening at 6 and 12 months and/or HPV DNA testing at 12 months is indicated. n For women ≤ 21 years of age, HPV testing is not recommended. n After 2 ! Pap smears or a ! DNA test, patients can be managed with routine annual follow-up. Persistent CIN I: n Ablation: Cryotherapy or laser ablation, or n Excision: LEEP; laser and cold-knife conization. CIN II and III: n Ablation: Cryotherapy or laser ablation, or n Excision: LEEP; laser and cold-knife conization. n Hysterectomy is a treatment option for recurrent CIN II or III. Postablative or excisional therapy follow-up is as follows: n CIN I, II, or III with ! margins: Pap smear at 12 months and/or HPV testing. n CIN II or III with " margins: Pap smear at 6 months; consider a repeat endocervical curettage. HIGH-YIELD FACTS IN 339 KEY FACT Subtypes of cervical lesions: n ASC-US: Atypical squamous cells of undetermined significance n ASC-H: Atypical squamous cells— cannot exclude HSIL n LSIL: Low-grade intraepithelial lesion n AGC: Atypical glandular cells of undetermined significance n HSIL: High-grade squamous intraepithelial lesion 340 HIGH-YIELD FACTS IN GYNECOLOGY n If margins are unknown, obtain a Pap smear at 6 months and HPV DNA testing at 12 months. Treatment based on biopsy results for invasive disease is as follows (for staging, see Figure 2.12-9): n n n Microinvasive carcinoma (stage IA1): Treat with cone biopsy and close follow-up or simple hysterectomy. Stages IA2, IB1, IIA: May be treated either with radical hysterectomy with concomitant radiation and chemotherapy or with radiation plus chemotherapy alone. Stages IB2, IIB, III, IV: Treat with radiation therapy plus concurrent cisplatin-based chemotherapy. PROGNOSIS n n n The overall 5-year relative survival rate for carcinoma of the cervix is 68% in Caucasian women and 55% in African American women. Survival rates are inversely proportionate to the stage of cancer: n Stage 0: 99–100%. n Stage IA: > 95%. n Stage IB-IIA: 80–90%. n Stage IIB: 65%. n Stage III: 40%. n Stage IV: < 20%. Almost two-thirds of patients with untreated carcinoma of the cervix die of uremia when ureteral obstruction is bilateral. V U LVAR CAN CE R Risk factors include HPV (types 16, 18, and 31), lichen sclerosus, infrequent medical exams, diabetes, obesity, hypertension, cardiovascular disease, and immunosuppression. Vulvar intraepithelial neoplasia (VIN) is precancerous and is more commonly found in premenopausal women. Stage 0 I II III IV Extent of tumor Carcinoma in-situ Confined to cervix 100% 85% Disease to pelvic wall or lower 1/3 of vagina 35% Invades bladder rectum or metastasis 5-year survival Disease beyond cervix but not to pelvic wall or lower 1/3 of vagina 65% 28% 21% 4% Stage at presentation 47% Uterine cavity Fundus Uterine wall 7% Pelvic side wall Fallopian tube Corpus Internal os Cervix External os IIB IIA IIIA IIIB Vagina Staging of cervical cancer. Anatomic display of the stages of cervix cancer, defined by location, extent of tumor, frequency of presentation, and 5-year survival. (Repro- FIGURE 2.12-9. duced with permission from Fauci AS et al. Harrison’s Principles of Internal Medicine, 17th ed. New York: McGraw-Hill, 2008, Fig. 93-1.) GYNECOLOGY HISTORY/PE n n Presents with pruritus, pain, or ulceration of the mass. Additional symptoms include the following: n Early: Lesions may appear white, pigmented, raised, thickened, nodular, or ulcerative. n Late: Presents with a large, cauliflower-like or hard ulcerated area in the vulva. DIAGNOSIS Vulvar punch biopsy for any suspicious lesions or persistent vulvar pruritus, especially in postmenopausal women. TREATMENT n n High-grade VIN: Topical chemotherapy, laser ablation, wide local excision, skinning vulvectomy, and simple vulvectomy. Invasive: n Radical vulvectomy and regional lymphadenectomy, or n Wide local excision of the 1° tumor with inguinal lymph node dissection +/− preoperative radiation, chemotherapy, or both. V AG I N AL C A N C E R Accounts for 1–2% of all gynecologic malignancies. Risk factors include immunosuppression, chronic irritation (eg, long-term pessary use or prolapse of female organs), low socioeconomic status, radiation for cervical cancer, hysterectomy for dysplasia, multiple sexual partners, and DES exposure. Etiologies are as follows: n n Postmenopausal women: Usually squamous cell carcinoma. Younger women: Usually other histologic types (eg, adenocarcinoma, clear cell adenocarcinoma from DES). HISTORY/PE n n Presents with abnormal vaginal bleeding, an abnormal discharge, or postcoital bleeding. Found in the upper third of the vagina in 75% of patients. DIAGNOSIS Cytology, colposcopy, and biopsy. TREATMENT n n n Local excision of involved areas when they are few and small. Extensive involvement of the vaginal mucosa may require partial or complete vaginectomy. Invasive disease requires radiation therapy or radical surgery. O VA R IA N CA N C E R Most ovarian tumors are benign, but malignant tumors are the leading cause of death from reproductive tract cancer. Risk factors include the following: n n Age, low parity, ↓ fertility, or delayed childbearing. A " family history. Patients with 1 affected first-degree relative have a 5% lifetime risk. With 2 or more affected first-degree relatives, the risk is 7%. HIGH-YIELD FACTS IN 341 342 HIGH-YIELD FACTS IN KEY FACT Frequency of female genital tract cancers: endometrial > ovarian > cervical. Number of deaths: ovarian > endometrial > cervical. GYNECOLOGY n n n The BRCA1 mutation carries a 45% lifetime risk of ovarian cancer. The BRCA2 mutation is associated with a 25% lifetime risk. Lynch II syndrome, or hereditary nonpolyposis colorectal cancer (HNPCC), is associated with an ↑ risk of colon, ovarian, endometrial, and breast cancer. OCPs taken for 5 years or more ↓ risk by 29%. HISTORY/PE n n n n n Both benign and malignant ovarian neoplasms are generally asymptomatic. Mild, nonspecific GI symptoms or pelvic pressure/pain may be seen. Early disease is typically not detected on routine pelvic exam. Some 75% of woman present with advanced malignant disease, as evidenced by abdominal pain and bloating, a palpable abdominal mass, and ascites. Table 2.12-10 differentiates the benign and malignant characteristics of pelvic masses. DIAGNOSIS n KEY FACT Any palpable ovarian or adnexal mass in a premenarchal or postmenopausal patient is suggestive of an ovarian neoplasm. n Tumor markers (see Table 2.12-11): ↑ CA-125 is associated with epithelial cell cancer (90% of ovarian cancers) but is used only as a marker for progression and recurrence. n Premenopausal women: ↑ CA-125 may point to benign disease such as endometriosis. n Postmenopausal women: ↑ CA-125 (> 35 units) indicates an ↑ likelihood that the ovarian tumor is malignant. Transvaginal ultrasound: Used to screen high-risk women and as the first step in the workup of symptomatic women (eg, pelvic fullness, pelvic pain). TA B L E 2 . 12 - 10 . Benign vs. Malignant Pelvic Masses FINDING BENIGN MALIGNANT EXAMINATION: PELVIC MASS Mobility Mobile Fixed Consistency Cystic Solid or firm Location Unilateral Bilateral Cul-de-sac Smooth Nodular TRANSVAGINAL ULTRASOUND: ADNEXAL MASS Size < 8 cm > 8 cm Consistency Cystic Solid or cystic and solid Septations Unilocular Multilocular Location Unilateral Bilateral Other Calcifications Ascites GYNECOLOGY Ovarian Tumor Markers TA B L E 2 . 12 - 11 TUMOR MARKER Epithelial CA-125 Endodermal sinus AFP Embryonal carcinoma AFP, hCG Choriocarcinoma hCG Dysgerminoma LDH Granulosa cell Inhibin TREATMENT Treatment of ovarian masses is as follows: n n n Premenarchal women: Masses > 2 cm in diameter require close clinical follow-up and often surgical removal. Premenopausal women: n Observation is appropriate for asymptomatic, mobile, unilateral, simple cystic masses < 8–10 cm in diameter. Most resolve spontaneously. n Surgically evaluate masses > 8–10 cm in diameter and those that are complex and/or unchanged on repeat pelvic examination and ultrasound. Postmenopausal women: n Closely follow with ultrasound asymptomatic, unilateral simple cysts < 5 cm in diameter with a normal CA-125. n Surgically evaluate palpable masses. Treatment of ovarian cancer is as follows: n n n Surgery: n Surgical staging: TAH/BSO with omentectomy and pelvic and paraaortic lymphadenectomy. n Benign neoplasms warrant tumor removal or unilateral oophorectomy. Postoperative chemotherapy: Routine except for women with early-stage or low-grade ovarian cancer. Radiation therapy: Effective for dysgerminomas. PREVENTION n n Women with the BRCA1 gene mutation should be screened annually with ultrasound and CA-125 testing. Prophylactic oophorectomy is recommended by age 35 or whenever childbearing is completed. OCP use ↓ the risk of ovarian cancer. Pelvic Organ Prolapse Risk factors for pelvic organ prolapse include vaginal birth, genetic predisposition, advancing age, prior pelvic surgery, connective tissue disorders, and ↑ intra-abdominal pressure associated with obesity or straining with chronic constipation. HIGH-YIELD FACTS IN 343 344 HIGH-YIELD FACTS IN GYNECOLOGY HISTORY/PE n n Presents with the sensation of a bulge or protrusion in the vagina (see Figure 2.12-10). Urinary or fecal incontinence, a sense of incomplete bladder emptying, and/or dyspareunia are also seen. DIAGNOSIS The degree of prolapse can be evaluated by having the woman perform the Valsalva maneuver while in the lithotomy position. TREATMENT n n n Supportive measures include a high-fiber diet and weight reduction in obese patients and limitation of straining and lifting. Pessaries may reduce prolapse and are helpful in women who do not wish to undergo surgery or who are chronically ill. The most common surgical procedure is vaginal or abdominal hysterectomy with vaginal vault suspension. Urinary Incontinence Defined as the involuntary loss of urine due to either bladder or sphincter dysfunction. HISTORY/PE n n n Table 2.12-12 outlines the types of incontinence along with their distinguishing features and treatment (see also the mnemonic DIAPPERS). Exclude fistula in cases of total incontinence. Look for neurologic abnormalities in cases of urge incontinence (spasticity, flaccidity, rectal sphincter tone) or distended bladder in overflow incontinence. Slight prolapse Normal Marked prolapse (procidentia) FIGURE 2.12-10. Uterine prolapse. Different degrees of uterine prolapse are illustrated. (Reproduced with permission from DeCherney AH, Nathan L. Current Diagnosis & Treatment Obstetrics & Gynecology, 10th ed. New York: McGraw-Hill, 2007, Fig. 44-3.) GYNECOLOGY TA B L E 2 . 12 - 12 . Types of Incontinence TYPE Total HIGH-YIELD FACTS IN 345 HISTORY OF URINE LOSS Uncontrolled loss at all times and in all positions. MECHANISM Loss of sphincteric efficiency TREATMENT Surgery. (previous surgery, nerve damage, cancer infiltration). Abnormal connection between the urinary tract and the skin (fistula). After ↑ intra-abdominal pressure Stress (coughing, sneezing, lifting). Urethral sphincteric insufficiency due to laxity of pelvic floor musculature. Kegel exercises and pessary. Vaginal vault suspension surgery. Common in multiparous women or after pelvic surgery. Urgea Strong, unexpected urge to void that Detrusor hyperreflexia or sphincter Anticholinergic medications or TCAs; is unrelated to position or activity. dysfunction due to inflammatory behavioral training (biofeedback). conditions or neurogenic disorders of the bladder. Overflow b Chronic urinary retention. Chronically distended bladder with ↑ intravesical pressure that just exceeds Placement of urethral catheter in acute settings. the outlet resistance, allowing a small Treat underlying diseases. amount of urine to dribble out. Timed voiding. a Etiologies include inhibited contractions, local irritation (cystitis, stone, tumor), and CNS causes. b Etiologies include physical agents (tumor, stricture), neurologic factors (lesions), and medications. DIAGNOSIS/TREATMENT n n n n n n Obtain a UA and urine culture to exclude UTI. Voiding diary. Consider urodynamic testing. Serum creatinine to exclude renal dysfunction. Obtain a cystogram to demonstrate fistula sites and descensus of the bladder neck. Table 2.12-12 outlines treatment options according to subtype. Pediatric Gynecology MNEMONIC Causes of urinary incontinence without specific urogenital pathology— DIAPPERS Delirium/confusional state Infection Atrophic urethritis/vaginitis Pharmaceutical Psychiatric causes (especially depression) Excessive urinary output (hyperglycemia, hypercalcemia, CHF) P E DI A T R I C V AG I N A L D I S CH A R G E Restricted mobility Stool impaction Etiologies of vaginal discharge in pediatric patients include the following: n Infectious vulvovaginitis: May present with a malodorous, yellow-green, purulent discharge. Causes include the following: n Group A streptococcus: The most common infectious cause. n Candida: May be associated with diabetes (rare in the pediatric population). n STDs: May result from sexual abuse. KEY FACT Pediatric vaginal discharge may be normal, but STDs resulting from sexual abuse must be ruled out and, if found, reported to Child Protective Services. 346 HIGH-YIELD FACTS IN GYNECOLOGY n n n Noninfectious vulvovaginitis: Causes include contact dermatitis and eczema. Foreign objects. Sarcoma botryoides (rhabdomyosarcoma): A malignancy with lesions that have the appearance of “bunches of grapes” within the vagina. P R ECOC I OU S P U BE R TY Onset of 2° sexual characteristics in a child < 8 years of age. Subtypes are as follows (see also Table 2.12-13): n n KEY FACT If onset of 2° sexual characteristics is seen by age 8, work up for precocious puberty by determining bone age and conducting a GnRH stimulation test to distinguish central from peripheral precocious puberty. Central precocious puberty: Early activation of hypothalamic GnRH production. Peripheral precocious puberty: Results from GnRH-independent mechanisms. HISTORY/PE n n Signs of estrogen excess (breast development and possibly vaginal bleeding): Suggest ovarian cysts or tumors. Signs of androgen excess (pubic and/or axillary hair, enlarged clitoris, and/or acne): Suggest adrenal tumors or CAH. DIAGNOSIS Figure 2.12-11 illustrates an algorithm for the workup of precocious puberty. TREATMENT n n Central precocious puberty: Leuprolide is first-line therapy; physical changes regress or cease to progress. Peripheral precocious puberty: Treat the cause. n Ovarian cysts: No intervention is necessary, as cysts will usually regress spontaneously. n CAH: Treat with glucocorticoids. Surgery is not required for the treatment of ambiguous genitalia. n Adrenal or ovarian tumors: Require surgical resection. n McCune-Albright syndrome: Antiestrogens (tamoxifen) or estrogen synthesis blockers (ketoconazole or testolactone) may be effective. TA B L E 2 . 12 - 13 . Causes of Precocious Pubertal Development CENTRAL (GnRH DEPENDENT) PERIPHERAL (GnRH INDEPENDENT) Constitutional (idiopathic) CAH Hypothalamic lesions (hamartomas, Adrenal tumors tumors, congenital malformations) Dysgerminomas McCune-Albright syndrome (polyostotic fibrous dysplasia) Hydrocephalus Gonadal tumors CNS infections Exogenous estrogen, oral (OCPs) or topical CNS trauma/irradiation Ovarian cysts (females) Pineal tumors (rare) Neurofibromatosis with CNS involvement Tuberous sclerosis HIGH-YIELD FACTS IN 347 GYNECOLOGY Determine bone age with hand and wrist radiographs Bone age within 1 year of chronological age Bone age > 2 years of chronological age Puberty has not started, or Puberty has just begun Puberty started > 12 months ago, or Puberty recently started and progressing rapidly GnRH agonist (leuprolide) stimulation test + Central precocious puberty + − LH response Peripheral precocious puberty − + CNS tumor FIGURE 2.12-11. Constitutional precocious puberty Ultrasound of ovaries, gonads, and/or adrenals Ovarian cyst Adrenal tumor Gonadal tumor − Exogenous estrogen CAH Workup of precocious puberty. Breast Disorders F I B R O C Y S T IC C HA N G E The most common of all benign breast conditions. It involves exaggerated stromal tissue response to hormones and growth factors. n n n Findings include cysts (gross and microscopic), papillomatosis, adenosis, fibrosis, and ductal epithelial hyperplasia. Primarily affects women 30–50 years of age; rarely found in postmenopausal woman. Associated with trauma and caffeine use. HISTORY/PE n n n Cyclic bilateral mastalgia and swelling, with symptoms most prominent just before menstruation. Rapid fluctuation in the size of the masses is common. Other symptoms include an irregular, bumpy consistency to the breast tissue. DIAGNOSIS n n n See Figure 2.12-12 for an algorithm of a breast mass workup. Mammography is of limited use. Ultrasound can help differentiate a cystic from a solid mass. KEY FACT The differential diagnosis of a breast mass includes fibrocystic disease, fibroadenoma, mastitis/abscess, fat necrosis, and breast cancer. 348 HIGH-YIELD FACTS IN GYNECOLOGY Suspicious mass: -Age > 35 -Family history -Firm, rigid -Axillary adenopathy -Skin changes Nonsuspicious mass: -Age < 35 -No family history -Movable, fluctuant -Size change w/cycle FNA Mammography Core or excisional biopsy Solid Cyst DCIS/cancer: Treat as indicated Cytology Benign or inconclusive Malignant Treatment Repeat FNA or open surgical biopsy FIGURE 2.12-12. Clear fluid, mass disappears Residual mass or thickening Bloody fluid Follow-up monthly × 3 Excisional biopsy Excisional biopsy Negative: Reassure, routine follow-up Workup of a breast mass. n n KEY FACT Intraductal papilloma and mammary duct ectasia are common causes of bloody nipple discharge. n Fine-needle aspiration (FNA) of a discrete mass that is suggestive of a cyst is indicated to alleviate pain as well as to confirm the cystic nature of the mass. Excisional biopsy is indicated if no fluid is obtained or if the fluid is bloody on aspiration. There is an ↑ risk of breast cancer if ductal epithelial hyperplasia or cellular atypia is present. TREATMENT n n n Dietary modifications (eg, caffeine restriction). Danazol can address severe pain but is rarely used in view of its side effects (acne, hirsutism, edema). Consider OCPs, which ↓ hormonal fluctuations. FI BR OADE NOM A A benign, slow-growing breast tumor with epithelial and stromal components. The most common breast lesion in women < 30 years of age. Cystosarcoma phyllodes is a large fibroadenoma. HISTORY/PE n n Presents as a round or ovoid, rubbery, discrete, relatively mobile, nontender mass 1–3 cm in diameter. Masses are usually solitary, although up to 20% of patients develop multiple fibroadenomas. GYNECOLOGY n n HIGH-YIELD FACTS IN 349 Tumors do not change during the menstrual cycle. Does not occur after menopause unless the patient is on HRT. DIAGNOSIS n n n Breast ultrasound to differentiate cystic from solid masses. Needle biopsy or FNA. Excision with pathologic exam if the diagnosis remains uncertain. TREATMENT Excision is curative, but recurrence is common. B RE A S T C ANC E R The most common cancer (affects 1 in 8 women) and the second most common cause of cancer death in women (after lung cancer). Sixty percent occur in the upper outer quadrant. Risk factors include the following (most women have no risk factors): n n n n n n n Female gender; older age. A personal history of breast cancer. Breast cancer in a first-degree relative. BRCA1 and BRCA2 mutations (associated with early onset). A high-fat and low-fiber diet. A history of fibrocystic change with cellular atypia. ↑ exposure to estrogen (nulliparity, early menarche, late menopause, first full-term pregnancy after age 35). KEY FACT ↑ exposure to estrogen (early menarche, late menopause, nulliparity) ↑ the risk of breast cancer. HISTORY/PE Ninety percent of breast cancers are found by the patient. Clinical manifestations include the following: n n n n Early findings: May present as a single, nontender, firm-to-hard mass with ill-defined margins or as mammographic abnormalities with no palpable mass. Later findings: Skin or nipple retraction, axillary lymphadenopathy, breast enlargement, redness, edema, pain, fixation of the mass to the skin or chest wall. Late findings: n Ulceration; supraclavicular lymphadenopathy; edema of the arm; metastases to the bone, lung, and liver. n Prolonged unilateral scaling erosion of the nipple with or without discharge (Paget’s disease of the nipple). Metastatic disease: n Back or bone pain, jaundice, weight loss. n A firm or hard axillary node > 1 cm. n Axillary nodes that are matted or fixed to the skin (stage III); ipsilateral supraclavicular or infraclavicular nodes (stage IV). DIAGNOSIS n Screening: n Postmenopausal women: Mammography. Look for ↑ density with microcalcifications and irregular borders. Mammography can detect lesions roughly 2 years before they become clinically palpable (see Figure 2.12-13A). n Premenopausal women: Ultrasound for women < 30 years of age; can distinguish a solid mass from a benign cyst (see Figure 2.12-13B). A 27-year-old woman palpates a 1 cm × 1cm new breast mass on selfexamination. What is the first step in the workup of the mass? 350 HIGH-YIELD FACTS IN A GYNECOLOGY B C Breast cancer. Mediolateral oblique (A) and craniocaudal (B) views from a mammogram demonstrate a spiculated mass with a satellite mass (circle) in the central and outer upper right breast. A targeted breast ultrasound (C) in a different patient demonstrates a hypoechoic mass (arrow) that is taller than it is wide and demonstrates dense posterior acoustic shadowing. (Reproduced with permission from FIGURE 2.12-13. USMLERx.com.) KEY FACT n In a postmenopausal woman with a new breast lesion, maintain a high degree of clinical suspicion for breast cancer. KEY FACT n n The first step in the workup of a suspicious mass in postmenopausal women and in those > 30 years of age is a mammogram. For premenopausal women < 30 years of age, get an ultrasound. n Biopsy of suspicious lesions: n FNA: A good initial biopsy, especially for lesions close to the skin; however, it is a small sample with a high false-! rate. FNA may also be used to follow response to treatment. n Core needle biopsy: A larger sample that allows testing for receptor status. n Open biopsy: Provides tissue for a more accurate diagnosis and allows immediate resection of tumor; however, requires taking the patient to the OR. Tumor markers for recurrent breast cancer: Include CEA and CA 15-3 or CA 27-29. Receptor status of tumor: Determine estrogen receptor (ER), progesterone receptor (PR), and HER2/neu status. Metastatic disease: n Labs: ↑ ESR, ↑ alkaline phosphatase (liver and bone metastases), ↑ calcium. n Imaging: CXR; CT of the chest, abdomen, and pelvis; brain MRI. PET and bone scans can also be useful. TREATMENT n n Ultrasound. The patient is < 30 years of age, so ultrasound is the preferred means of distinguishing a solid mass from a cyst. Pharmacologic: n All hormone receptor–" patients should receive tamoxifen. n ER-! patients should receive chemotherapy. n Trastuzumab, a monoclonal antibody that binds to HER2/neu receptors on the cancer cell, is highly effective in HER2/neu-expressive cancers. Surgical options include the following: n Partial mastectomy (lumpectomy) plus axillary dissection followed by radiation therapy. n Modified radical mastectomy (total mastectomy plus axillary dissection). GYNECOLOGY n n Contraindications to breast-conserving therapy (lumpectomy) include large tumor size, subareolar location, multifocal tumors, fixation to the chest wall, prior radiation to the chest wall, or involvement of the nipple or overlying skin. Stage IV disease should be treated with radiotherapy and hormonal therapy; mastectomy may be required for local symptom control. PROGNOSIS n n n n TNM staging (I–IV) is the most reliable indicator of prognosis. ER- and PR-" status is associated with a favorable course. Cancer localized to the breast has a 75–90% cure rate. With spread to the axilla, the 5-year survival rate is 40–50%. Aneuploidy is associated with a poor prognosis. COMPLICATIONS Pleural effusion occurs in 50% of patients with metastatic breast cancer; edema of the arm is common. Sexual Assault The most frequently unreported crime in the United States. Physicians are often required to evaluate sexual assault victims and collect evidence. Most rape victims are women; however, men may also be victims of rape. HISTORY/PE n n Take a full history, including contraceptive use, last time of coitus, condom use prior to the assault, drug or alcohol use, a history of STDs, a description of the assailant, location and time of the assault, circumstances of the assault (eg, penile penetration, use of condoms, extragenital acts, use or display of weapons), and the patient’s actions since the assault (eg, douching, bathing, brushing teeth, urination/defecation, changing clothes). Conduct a complete physical examination, making note of any signs of trauma, along with a detailed pelvic examination, including a survey of the external genitals, vagina, cervix, and anus. DIAGNOSIS n n n Gonorrhea and chlamydia smear/culture (including rectal if appropriate); serologic testing for HIV, syphilis, HSV, HBV, and CMV. Serum pregnancy test. Blood alcohol level; urine toxicology screen. TREATMENT n n n n n n STD treatment/prophylaxis (ceftriaxone plus azithromycin). HIV risk assessment and possible postexposure prophylaxis. EC for pregnancy prevention. Refer for psychological counseling. Arrange for follow-up with the same physician or with another provider if more appropriate. Follow-up should include repeat screening for STDs, repeat screening for pregnancy, and a discussion of coping methods with appropriate referrals for psychiatric care if needed. HIGH-YIELD FACTS IN 351 KEY FACT Breast cancer stages: n Stage I: Tumor size < 2 cm. n Stage II: Tumor size 2–5 cm. n Stage III: Axillary node involvement. n Stage IV: Distant metastasis. 352 HIGH-YIELD FACTS IN GYNECOLOGY NOTES HIGH-YIELD FACTS IN PEDIATRICS Child Abuse 354 BRONCHIOLITIS 375 Congenital Heart Disease 355 CROUP (LARYNGOTRACHEOBRONCHITIS) 376 VENTRICULAR SEPTAL DEFECT 355 EPIGLOTTITIS 377 ATRIAL SEPTAL DEFECT 357 PATENT DUCTUS ARTERIOSUS 357 COARCTATION OF THE AORTA 358 TRANSPOSITION OF THE GREAT VESSELS 359 TETRALOGY OF FALLOT 359 APGAR SCORING 382 360 CONGENITAL MALFORMATIONS 382 Development DEVELOPMENTAL MILESTONES 360 GROWTH 360 SEXUAL DEVELOPMENT 362 Genetic Disease CYSTIC FIBROSIS Gastroenterology 362 362 366 INTUSSUSCEPTION 366 PYLORIC STENOSIS 367 MECKEL’S DIVERTICULUM 368 HIRSCHSPRUNG’S DISEASE 368 MENINGITIS 378 PERTUSSIS (WHOOPING COUGH) 379 VIRAL EXANTHEMS 380 Neonatology 382 NEONATAL JAUNDICE 382 RESPIRATORY DISTRESS SYNDROME 383 Neurology 386 CEREBRAL PALSY 386 FEBRILE SEIZURES 386 Oncology 387 LEUKEMIA 387 NEUROBLASTOMA 388 WILMS’ TUMOR 389 CHILDHOOD BONE TUMORS 389 Preventive Care 389 MALROTATION WITH VOLVULUS 369 NECROTIZING ENTEROCOLITIS 369 ANTICIPATORY GUIDANCE 389 370 HEARING AND VISION SCREENING 390 CHILDHOOD VACCINATIONS 390 LEAD POISONING 391 Immunology IMMUNODEFICIENCY DISORDERS 370 KAWASAKI DISEASE 374 JUVENILE IDIOPATHIC ARTHRITIS 374 Infectious Disease ACUTE OTITIS MEDIA 375 375 353 354 HIGH-YIELD FACTS IN PEDIATRICS Child Abuse Also known as nonaccidental trauma; includes neglect as well as physical, sexual, and psychological maltreatment of children. Suspect abuse if the history is discordant with physical findings or if there is a delay in obtaining appropriate medical care. Certain injuries in children, such as retinal hemorrhages and specific fracture types, are pathognomonic for abuse. KEY FACT HISTORY/PE n Suspect sexual abuse if there is genital trauma, bleeding, or discharge. In females, consider vaginal foreign body as an alternative diagnosis, especially in the setting of a foul-smelling vaginal discharge, bleeding, and pain. n n n n KEY FACT Neisseria gonorrhoeae isolated on a vaginal culture is definitive evidence of sexual abuse. Chlamydia trachomatis is not because it can be acquired from the mother during delivery and can persist for up to 3 years. KEY FACT DIAGNOSIS n n n n Mongolian spots, which are common in the first few years of life, look like bruises and may be mistaken for abuse. Suspect abuse if the story is not consistent with the injury pattern or with the child’s developmental age. For example, take note if the parents claim that their 2-month-old child “rolled off the couch” (2-month-olds can’t roll yet). Risk factors: Look for parents with a history of alcoholism or drug use, children with mental retardation or a handicap, and repeated hospitalizations. Infants: Abuse or neglect in infants may present as apnea, seizures, feeding intolerance, excessive irritability, somnolence, or failure to thrive (FTT). Older children: Neglect in older children may present as poor hygiene or behavioral abnormalities. Examination findings: n Bruises: n The most common physical sign of abuse. n Geometric patterns include stocking-glove burns, cigarette burns, and belt marks. n Found in atypical places such as the face or thighs. n Burns: n A well-demarcated line on the buttocks suggests forced immersion in hot water. n Look for cigarette burns or iron-shaped burns. n Fractures: n Spiral fractures of the humerus and femur: Suggest abuse in children < 3 years of age. n Epiphyseal-metaphyseal “bucket fractures”: Suggest shaking or jerking of the child’s limbs; highly diagnostic of physical abuse in an infant. n Posterior rib fractures: Usually caused by squeezing of the chest. n Rule out conditions that mimic abuse—eg, bleeding disorders or Mongolian spots (resemble bruises; see Figure 2.13-1), osteogenesis imperfecta (may mimic fractures), bullous impetigo (may look like cigarette burns), and “coining” (an alternative treatment in certain cultures). An x-ray skeletal survey and bone scan can show fractures in various stages of healing. X-rays may not show fractures until 1–2 weeks after injury (although they may show evidence of prior trauma in children < 3 years of age); by contrast, bone scans may show fractures within 48 hours. If sexual abuse is suspected, test for gonorrhea, syphilis, chlamydia, HIV, and sperm (within 72 hours of assault). Rule out shaken baby syndrome (SBS) by performing an ophthalmologic exam for retinal hemorrhages and a noncontrast CT for subdural hematomas. Infants with SBS often do not exhibit external signs of abuse. Consider an MRI to visualize white matter changes associated with violent shaking and the extent of intra- and extracranial bleeds. PEDIATRICS HIGH-YIELD FACTS IN 355 FIGURE 2.13-1. Mongolian spots. These spots, which are common and are not pathologic in the first few years of life, often resemble bruises. (Reproduced with permission from Wolff K et al. Fitzpatrick’s Dermatology in General Medicine, 7th ed. New York: McGraw-Hill, 2008, Fig. 73-16.) TREATMENT n n n Document injuries, including location, size, shape, color, and the nature of all lesions, bruises, or burns. Notify Child Protective Services for possible removal of the child from the home. Hospitalize if necessary to stabilize injuries or to protect the child. MNEMONIC Cyanotic heart defects— Congenital Heart Disease Intrauterine risk factors for congenital heart disease include maternal drug use (alcohol, lithium, thalidomide, phenytoin), maternal infections (rubella), and maternal illness (diabetes mellitus [DM], PKU). Disease is classified by the presence or absence of cyanosis: n n Acyanotic conditions (“pink babies”): Have left-to-right shunts in which oxygenated blood from the lungs is shunted back into the pulmonary circulation. Cyanotic conditions (“blue babies”): Have right-to-left shunts in which deoxygenated blood is shunted into the systemic circulation. The 5 T’s that have right-to-left shunts Truncus arteriosus = ONE arterial vessel overriding ventricles Transposition of the great vessels = TWO arteries switched Tricuspid atresia (THREE) Tetralogy of Fallot (FOUR) Total anomalous pulmonary venous return = FIVE words Out of the 5 T’s, only Transposition presents with severe cyanosis within the first few hours of life. Table 2.13-1 lists common congenital and other pediatric heart conditions along with their disease associations. MNEMONIC V E N T R I CU LA R S E PT A L D E F E CT ( V S D) A condition in which an opening in the ventricular septum allows blood to flow between ventricles. VSD is the most common cause of congenital heart disease. It is more common among patients with Apert’s syndrome (cranial deformities, fusion of the fingers and toes), Down syndrome, fetal alcohol syndrome, TORCH syndrome (toxoplasmosis, other agents, rubella, CMV, HSV), cri du chat syndrome, and trisomies 13 and 18. Noncyanotic heart defects— The 3 D’s VSD ASD PDA 356 HIGH-YIELD FACTS IN PEDIATRICS TA B L E 2 . 13 - 1 . Pediatric Heart Conditions and Their Disease Associations CONDITION DISORDER ASD and endocardial cushion defects Down syndrome. PDA Congenital rubella. Coarctation of the aorta Turner’s syndrome (many also have bicuspid aortic valve). Coronary artery aneurysms Kawasaki disease. Congenital heart block Neonatal lupus. Supravalvular aortic stenosis Williams syndrome. Conotruncal abnormalities Tetralogy of Fallot (overriding aorta), truncus arteriosus, DiGeorge syndrome (tetralogy), velocardiofacial syndrome. Ebstein’s anomaly Maternal lithium use during pregnancy. Heart failure Neonatal thyrotoxicosis. Asymmetric septal hypertrophy and Maternal diabetes. transposition of the great vessels KEY FACT HISTORY/PE n VSD is the most common cause of congenital heart disease. n Small defects: Usually asymptomatic at birth, but examination reveals a harsh holosystolic murmur heard best at the lower left sternal border. Large defects: n Can present as frequent respiratory infections, dyspnea, FTT, and CHF. n If present, the holosystolic murmur is softer and more blowing but can be accompanied by a systolic thrill, crackles, hepatomegaly, a narrow S2 with an ↑ P2, and a mid-diastolic apical rumble reflecting ↑ flow across the mitral valve. DIAGNOSIS n n n Echocardiogram is diagnostic. ECG can demonstrate LVH and may show both LVH and RVH with larger VSDs. CXR may show cardiomegaly and ↑ pulmonary vascular markings. TREATMENT n n n Most small VSDs close spontaneously; asymptomatic patients should be monitored via echocardiography. Antibiotic prophylaxis may be considered during procedures but is indicated only if the VSD was previously repaired with prosthetic material. Surgical repair is indicated in symptomatic patients who fail medical management, children < 1 year of age with signs of pulmonary hypertension, and older children with large VSDs that have not ↓ in size over time. Treat existing CHF with diuretics (initial treatment), inotropes, and ACEIs. PEDIATRICS HIGH-YIELD FACTS IN 357 AT R IA L S E P T A L D E F E C T (A S D ) A condition in which an opening in the atrial septum allows blood to flow between the atria, leading to left-to-right shunting. Associated with Holt-Oram syndrome (absent radii, ASD, first-degree heart block), fetal alcohol syndrome, and Down syndrome. KEY FACT ASD has a fixed, widely split S2. HISTORY/PE n n n Ostium primum defects present in early childhood with findings of a murmur or fatigue with exertion (also seen in Down syndrome). Ostium secundum defects (more common) tend to present in late childhood or early adulthood. Symptom onset and severity depend on the size of the defect. Symptoms of easy fatigability, frequent respiratory infections, and FTT may be observed, but patients are frequently asymptomatic. Examination reveals a right ventricular heave; a wide and fixed, split S2; and a systolic ejection murmur at the left upper sternal border (from ↑ flow across the pulmonary valve). There may also be a mid-diastolic rumble at the left lower sternal border. KEY FACT ASDs and VSDs rarely present at birth. Remember that ASDs, VSDs, and PDAs are acyanotic conditions unless Eisenmenger’s syndrome has developed (right-to-left shunt, cyanotic). DIAGNOSIS n n n Echocardiogram with color flow Doppler reveals blood flow between the atria (diagnostic), paradoxical ventricular wall motion, and a dilated right ventricle. ECG may show RVH and right atrial enlargement. PR prolongation is common. CXR reveals cardiomegaly and ↑ pulmonary vascular markings. TREATMENT n n Close to 90% of defects close spontaneously, and most do not require treatment. Surgical or catheter closure is indicated in infants with CHF and in patients with more than a 2:1 ratio of pulmonary to systemic blood flow. Early correction prevents complications such as arrhythmias, right ventricular dysfunction, and Eisenmenger’s syndrome. KEY FACT In Eisenmenger’s syndrome, left-to-right shunt leads to pulmonary hypertension and shunt reversal. PA T E N T D U C T US A R T E R I O SU S (PD A) Failure of the ductus arteriosus to close in the first few days of life, leading to an acyanotic left-to-right shunt from the aorta to the pulmonary artery. Risk factors include maternal first-trimester rubella infection, prematurity, and female gender. HISTORY/PE n n Typically asymptomatic; patients with large defects may present with FTT, recurrent lower respiratory tract infections, lower extremity clubbing, and CHF. Examination reveals a continuous “machinery murmur” at the second left intercostal space at the sternal border, a loud S2, wide pulse pressure, and bounding peripheral pulses. DIAGNOSIS n A color flow Doppler demonstrating blood flow from the aorta into the pulmonary artery is diagnostic. KEY FACT In infants presenting in a shocklike state within the first few weeks of life, look for: 1. Sepsis 2. Inborn errors of metabolism 3. Ductal-dependent congenital heart disease, usually left-sided lesions (as the ductus is closing) 4. Congenital adrenal hyperplasia 358 HIGH-YIELD FACTS IN PEDIATRICS n n KEY FACT Come IN and CLOSE the door: give INdomethacin to CLOSE a PDA. With larger PDAs, echocardiography shows left atrial and left ventricular enlargement. ECG may show LVH, and CXR may reveal cardiomegaly if lesions are large. TREATMENT n n Give indomethacin unless the PDA is needed for survival (eg, transposition of the great vessels, tetralogy of Fallot, hypoplastic left heart) or if indomethacin is contraindicated (eg, intraventricular hemorrhage). If indomethacin fails or if the child is > 6–8 months of age, surgical closure is required. COAR C TATI ON OF THE AOR TA KEY FACT Coarctation of the aorta is associated with Turner’s syndrome. Constriction of a portion of the aorta, leading to ↑ flow proximal to and ↓ flow distal to the coarctation. Occurs just below the left subclavian artery in 98% of patients. The condition is associated with Turner’s syndrome, berry aneurysms, and male gender. More than two-thirds of patients have a bicuspid aortic valve. HISTORY/PE n n n n n KEY FACT n Coarctation is a cause of 2° hypertension in children. Often presents in childhood with asymptomatic hypertension (upper extremity hypertension). A murmur may be heard over the back between the scapulae. Lower extremity claudication, syncope, epistaxis, and headache may be present. The classic physical examination finding is a systolic BP that is higher in the upper extremities; the difference in BP between the left and right arm can indicate the point of coarctation. Additional findings include weak femoral pulses, radiofemoral delay, a short systolic murmur in the left axilla, and a forceful apical impulse. In infancy, critical coarctation requires a patent PDA for survival. Such infants may present in the first few weeks of life in a shocklike state when the PDA closes. Differential cyanosis may be seen with lower O2 saturation in the left arm and lower extremities (postductal areas) as compared to the right arm (preductal area). DIAGNOSIS n n n Echocardiography and color flow Doppler are diagnostic. CXR in young children may demonstrate cardiomegaly and pulmonary congestion. In older children, the following compensatory changes may be seen: LVH on ECG; the “3” sign on CXR due to pre- and postdilatation of the coarctation segment with aortic wall indentation; and “rib notching” due to collateral circulation through the intercostal arteries. TREATMENT n n n If severe coarctation presents in infancy, the ductus arteriosus should be kept open with prostaglandin E1 (PGE1). Surgical correction or balloon angioplasty is controversial. Monitor for restenosis, aneurysm development, and aortic dissection. PEDIATRICS HIGH-YIELD FACTS IN 359 T R A N S PO SIT IO N O F T H E G R E A T VES S E LS The most common cyanotic congenital heart lesion in the newborn. In this condition, the aorta is connected to the right ventricle and the pulmonary artery to the left ventricle, creating parallel pulmonary and systemic circulations. Without a septal defect (ASD or VSD) and a PDA, it is incompatible with life. A PDA alone is usually not sufficient to allow adequate mixing of blood. Risk factors include diabetic mothers and, rarely, DiGeorge syndrome. KEY FACT Transposition is the most common congenital heart condition, presenting with cyanosis within the first 24 hours of birth. MNEMONIC HISTORY/PE n n Critical illness and cyanosis typically present within first few hours after birth. Reverse differential cyanosis may be seen if left ventricular outflow tract obstruction (eg, coarctation, aortic stenosis) is also present. Examination reveals tachypnea, progressive hypoxemia, and extreme cyanosis. Some patients have signs of CHF, and a single loud S2 is often present. There may not be a murmur if no VSD is present. If a VSD is present, a systolic murmur may be heard at the left sternal border. DIAGNOSIS n n Echocardiography. CXR may show a narrow heart base, absence of the main pulmonary artery segment, an “egg-shaped silhouette,” and ↑ pulmonary vascular markings. TREATMENT n n n Start IV PGE1 to maintain or open the PDA. If surgery is not feasible within the first few days of life or if the PDA cannot be maintained with prostaglandin, perform balloon atrial septostomy to create or enlarge an ASD. Surgical correction (arterial or atrial switch) is definitive. DiGeorge syndrome— CATCH 22 Cardiac abnormalities (transposition) Abnormal facies Thymic aplasia Cleft palate Hypocalcemia 22q11 deletion KEY FACT Transposition of the great vessels is the most common cyanotic heart disease of newborns. Tetralogy of Fallot is the most common cyanotic heart disease of childhood. T ET R A LO G Y O F F A L L O T Consists of pulmonary stenosis, overriding aorta, RVH, and VSD. The most common cyanotic congenital heart disease in children. Early cyanosis results from right-to-left shunting across the VSD. As right-sided pressures ↓ in the weeks after birth, the shunt direction reverses and cyanosis may ↓. If the degree of pulmonary stenosis is severe, the right-sided pressures may remain high and cyanosis may worsen over time. Risk factors include maternal PKU and DiGeorge syndrome. HISTORY/PE n n n n n Presents in infancy or early childhood with dyspnea and fatigability. Cyanosis is frequently absent at birth but develops over the first 2 years of life; the degree of cyanosis often reflects the extent of pulmonary stenosis. Infants are often asymptomatic until 4–6 months of age, when CHF may develop and manifest as diaphoresis with feeding or tachypnea. Children often squat for relief during hypoxemic episodes called “tet spells,” which ↑ systemic vascular resistance. Hypoxemia may lead to FTT or mental status changes. Examination reveals a systolic ejection murmur at the left upper sternal border (right ventricular outflow obstruction), a right ventricular heave, and a single S2. A 2-year-old girl is playing on the floor in a squatting position while in the waiting room. The skin around her mouth has a grayish-blue hue, and when she stands up, she suddenly begins to pant and appears cyanotic. When she goes back to a squatting position, she begins to breathe comfortably again. Which 4 anomalies define this patient’s condition? 360 HIGH-YIELD FACTS IN PEDIATRICS DIAGNOSIS n n n Echocardiography and catheterization. CXR shows a “boot-shaped” heart with ↓ pulmonary vascular markings. Remember that a VSD may result in ↑ pulmonary vascular markings. ECG shows right-axis deviation and RVH. TREATMENT KEY FACT Both transposition of the great vessels and tetralogy of Fallot are initially treated with PGE1 but are definitively treated with surgical correction. n n n Development KEY FACT Signs of autism include no babbling and/or gesturing by 12 months, no single words by 16 months, no 2-word phrases by 24 months, failure to make eye contact, and other signs of deficits in language or social skills. Lesions with severe pulmonary stenosis or atresia require immediate PGE1 to keep the PDA open along with urgent surgical consultation. Treat hypercyanotic “tet spells” with O2, propranolol, phenylephrine, the knee-chest position, fluids, and morphine. Temporary palliation can be achieved through the creation of an artificial shunt (eg, balloon atrial septostomy) before definitive surgical correction (Blalock-Taussig shunt). DEV E LOP M E NTAL M I LE STONE S Table 2.13-2 highlights major developmental milestones, with commonly tested milestones highlighted in bold. Table 2.13-3 summarizes critical milestones in language development. G R OW TH KEY FACT Newborns can lose up to 10% of their birth weight but will regain the weight by 2 weeks of life. At each well-child check, height, weight, and head circumference are plotted on growth charts specific for gender and age: n n KEY FACT Infants with FTT will first fall off of the weight curve, then the height curve, and finally the head circumference curve. n n The anomalies included in the mnemonic PROVe—Pulmonary stenosis, RVH, Overriding aorta, and VSD—define tetralogy of Fallot. n Head circumference: Measured routinely in the first 2 years. ↑ head circumference may indicate hydrocephalus or tumor; ↓ head circumference can point to microcephaly (eg, TORCH infections). Height and weight: Measured routinely until adulthood. The pattern of growth is more important than the raw numbers. Infants may lose 5–10% of birth weight (BW) over the first few days but should return to their BW by 14 days. Infants can be expected to double their BW by 4–5 months, triple by 1 year, and quadruple by 2 years. FTT: Persistent weight less than the fifth percentile for age or “falling off the growth curve” (ie, crossing 2 major percentile lines on a growth chart). Classified as follows: n Organic: Due to an underlying medical condition such as cystic fibrosis, congenital heart disease, celiac sprue, pyloric stenosis, chronic infection (eg, HIV), and GERD. n Nonorganic: Primarily due to psychosocial factors such as maternal depression, neglect, or abuse. A careful dietary history and close observation of maternal-infant interactions (especially preparation of formula and feeding) are critical to diagnosis. Children should be hospitalized if there is evidence of neglect or severe malnourishment. Calorie counts and supplemental nutrition (if breastfeeding is inadequate) are mainstays of treatment. PEDIATRICS TA B L E 2 . 13 - 2 . Developmental Milestones AGE a GROSS MOTOR Lifts head/chest when 2 months FINE MOTOR Tracks past midline. HIGH-YIELD FACTS IN 361 LANGUAGE Alerts to sound; coos. Recognizes parent; exhibits social smile. prone. 4–5 months SOCIAL/COGNITIVE Rolls front to back, back to Grasps rattle. front (4 months). Laughs and squeals; Enjoys looking around; orients to voice; begins to laughs. make consonant sounds. Sits unassisted. 6 months Transfers objects; Babbles. anxiety. demonstrates raking grasp. 9–10 months Crawls; pulls to stand. Demonstrates stranger Uses 3-finger (immature) Says “mama/dada” Waves bye-bye; plays pincer grasp. (nonspecific); says first pat-a-cake. word at 11 months. 12 months 2 years Walks alone; throws Uses 2-finger (mature) Uses 1–3 words; follows Imitates actions; exhibits object. pincer grasp. 1-step commands. separation anxiety. Walks up/down steps; Builds tower of 6 cubes. Uses 2-word phrases. Follows 2-step commands; jumps. 3 years removes clothes. Rides tricycle; climbs stairs Copies a circle; uses with alternating feet (3–4 utensils. Uses 3-word sentences. Brushes teeth with help; washes/dries hands. years). 4 years 5 years Copies a cross (square at Knows colors and some Exhibits cooperative play; 4.5 years). numbers. plays board games. Skips; walks backward for Copies a triangle; ties Uses 5-word sentences. Exhibits domestic role long distances. shoelaces; knows left and Hops. playing; plays dress-up. right; prints letters. a For premature infants < 2 years of age, chronological age must be adjusted for gestational age. For example, an infant born at 7 months’ gestation (2 months early) would be expected to perform at the 4-month level at the chronological age of 6 months. TA B L E 2 . 13 - 3 . Major Milestones in Language Development AGE MILESTONE 12 months 1 word, 1-step command 15 months 5 words 18 months 8 words 2 years 2-word phrases, 2-step commands 3 years 3-word phrases 362 HIGH-YIELD FACTS IN PEDIATRICS S E X U AL DE VE LOP M E NT n n Tanner staging: Performed to assess sexual development in boys and girls (see Figure 2.13-2). Stage 1 is preadolescent; stage 5 is adult. Increasing stages are assigned for testicular and penile growth in boys and breast growth in girls; pubic hair development is used for both stages. n Girls: The average age of puberty is 10.5 years. The average age of menarche in U.S. girls is 12.5 years. n Boys: The average age of puberty is 11.5 years. Variants of normal sexual development are as follows (see also Figure 2.13-2): n Precocious puberty: Any sign of 2° sexual maturation in girls < 8 years or boys < 9 years of age. Often idiopathic; may be central or peripheral (see the Gynecology chapter). n Delayed puberty: No testicular enlargement in boys by age 14, or no breast development or pubic hair in girls by age 13. n Constitutional growth delay: A normal variant, and the most common cause of delayed puberty. The growth curve lags behind others of the same age but is consistent. There is often a ! family history, and children catch up and ultimately achieve target height potential. n Pathological puberty delay: Rarely, due to systemic disease (eg, IBD), malnutrition (eg, anorexia nervosa), gonadal dysgenesis (eg, Klinefelter’s syndrome, Turner’s syndrome), or endocrine abnormalities (eg, hypopituitarism, hypothyroidism, Kallmann’s syndrome, androgen insensitivity syndrome, Prader-Willi syndrome). Genetic Disease Tables 2.13-4 and 2.13-5 outline common genetic diseases and their associated abnormalities. CYS TI C F I BR OSIS ( C F) An autosomal recessive disorder caused by mutations in the CFTR gene (chloride channel) on chromosome 7 and characterized by widespread exo- Normal sexual development: GIRLS: thelarche (breast buds) pubarche (pubic hair) growth spurt menarche (menses) BOYS: gonadarche (testicles enlarge) pubarche (pubic hair) adrenarche (axillary and facial hair, voice changes) growth spurt Variants of normal sexual development: GIRLS: Precocious puberty 8 years 13 years Delayed puberty BOYS: Precocious puberty 9 years 14 years Delayed puberty FIGURE 2.13-2. Patterns of sexual development in girls vs. boys. PEDIATRICS TA B L E 2 . 13 - 4 . HIGH-YIELD FACTS IN 363 Genetic Diseases DISEASE Down syndrome GENETIC ABNORMALITY Meiotic nondisjunction (95%), robertsonian translocation (4%), or mosaicism (1%) COMMON CHARACTERISTICS The most common chromosomal disorder and cause of mental retardation. Associated with advanced maternal age. Presents with mental retardation, a flat facial profile, upslanted eyes with epicanthal folds, a simian crease, general hypotonia, atlantoaxial instability, and extra neck folds (nuchal folds are sometimes seen on prenatal ultrasound). Associated with duodenal atresia, Hirschsprung’s disease, and congenital heart disease. The most common malformation is AV canal (60%); ASDs, VSDs, and PDAs (20%) and complex congenital heart disease make up the remainder. Also associated with an ↑ risk of acute lymphocytic leukemia (ALL), hypothyroidism, and early-onset Alzheimer’s. Edwards’ Trisomy 18 Presents with severe mental retardation, rocker-bottom feet, low-set ears, micrognathia, clenched hands (overlapping fourth and fifth digits), and a syndrome prominent occiput. Associated with congenital heart disease. May have horseshoe kidneys. Death usually occurs within 1 year of birth. Patau’s syndrome Trisomy 13 Presents with severe mental retardation, microphthalmia, microcephaly, cleft lip/palate, holoprosencephaly, “punched-out” scalp lesions, polydactyly, and omphalocele. Associated with congenital heart disease. Death usually occurs within 1 year of birth. Klinefelter’s 47, XXY syndrome (male) Characterized by the presence of an inactivated X chromosome (Barr body). Associated with advanced maternal age. One of the most common causes of hypogonadism in males. Presents with testicular atrophy, a eunuchoid body shape, tall stature, long extremities, gynecomastia, and female hair distribution. Treat with testosterone (prevents gynecomastia; improves 2° sexual characteristics). Turner’s syndrome 45, XO (female) Missing 1 X chromosome; no Barr body. Not associated with advanced maternal age. The most common cause of 1° amenorrhea; due to ovarian dysgenesis (↓ estrogen). Features include short stature, shield chest, widely spaced nipples, a webbed neck, coarctation of the aorta (↓ femoral pulses), and/or bicuspid aortic valve. May present with lymphedema of the hands and feet in the neonatal period. May have horseshoe kidney. Double Y males 47, XYY Observed with ↑ frequency among inmates of penal institutions. Phenotypically normal; patients are very tall with severe acne and antisocial behavior (seen in 1–2% of XYY males). (continues) 364 HIGH-YIELD FACTS IN TA B L E 2 . 13 - 4 . PEDIATRICS Genetic Diseases (continued) DISEASE GENETIC ABNORMALITY COMMON CHARACTERISTICS Phenylketonuria Autosomal recessive; Tyrosine becomes essential and phenylalanine builds up excess phenyl ketones. (PKU) ↓ phenylalanine Screened for at birth. hydroxylase or ↓ Normal at birth; presents within the first few months of life. tetrahydrobiopterin Presents with mental retardation, fair hair and skin, eczema, blond hair, blue eyes, and a musty urine odor. cofactor Associated with an ↑ risk of heart disease. Modify diet by decreasing phenylalanine (artificial sweeteners) and increasing tyrosine. A mother with PKU who wants to become pregnant must restrict her diet as above before conception. Fragile X syndrome An X-linked dominant The second most common cause of genetic mental retardation. defect affecting the Presents with large jaw, testes, and ears and with autistic behaviors. methylation and A triplet repeat disorder that may show genetic anticipation. expression of the FMR1 gene crine gland dysfunction. CF is the most common severe genetic disease in the United States and is most frequently found in Caucasians. HISTORY/PE n n n n KEY FACT Almost all cases of meconium ileus are due to CF. n n Fifty percent of patients present with FTT or chronic sinopulmonary disease. Characterized by recurrent pulmonary infections (especially with Pseudomonas and S aureus) with subsequent cyanosis, digital clubbing, chronic cough (the most common pulmonary symptom), dyspnea, bronchiectasis, hemoptysis, chronic sinusitis, rhonchi, rales, hyperresonance to percussion, and nasal polyposis. Fifteen percent of infants present with meconium ileus (bilious vomiting in the newborn). Patients usually have greasy stools and flatulence; other prominent GI symptoms include pancreatitis, rectal prolapse, hypoproteinemia, biliary cirrhosis, jaundice, and esophageal varices. GI symptoms are more prominent in infancy; pulmonary manifestations predominate thereafter. Additional symptoms include type 2 DM, “salty-tasting” skin, male infertility (agenesis of the vas deferens), and unexplained hyponatremia. Patients are at risk for fat-soluble vitamin deficiency (vitamins A, D, E, and K) 2° to malabsorption and may present with manifestations of these deficiencies. DIAGNOSIS KEY FACT The sweat chloride test has traditionally been considered the gold standard for the diagnosis of CF, but confirmatory genetic analysis is now routinely done. n n n n Diagnosed by a sweat chloride test > 60 mEq/L in those < 20 years of age and > 80 mEq/L in adults. Confirmed by genetic testing. ABG shows hypochloremic alkalosis in severe cases. Most states now perform mandatory newborn screening, but occasional false !s occur, so children must be brought in for a sweat test to distinguish disease from a carrier state. PEDIATRICS TA B L E 2 . 13 - 5 . HIGH-YIELD FACTS IN 365 Lysosomal Storage Diseases DISEASE Fabry’s disease ETIOLOGY Caused by a deficiency of α-galactosidase A that leads to accumulation of MODE OF INHERITANCE/NOTES X-linked recessive. ceramide trihexoside in the heart, brain, and kidneys. The first sign is severe neuropathic limb pain; also presents with joint swelling. Skin involvement takes the form of angiokeratomas and telangiectasias. Findings include renal failure and an ↑ risk of stroke and MI (thromboembolic events). Krabbe’s disease Absence of galactosylceramide and galactoside (due to Autosomal recessive. galactosylceramidase deficiency), leading to the accumulation of galactocerebroside in the brain. Characterized by progressive CNS degeneration, optic atrophy, spasticity, and death within the first 3 years of life. Gaucher’s disease Caused by a deficiency of glucocerebrosidase that leads to the Autosomal recessive. accumulation of glucocerebroside in the brain, liver, spleen, and bone marrow. Gaucher’s cells have a characteristic “crinkled paper” appearance with enlarged cytoplasm. May present with anemia and thrombocytopenia. The infantile form results in early, rapid neurologic decline. The adult form (more common) is compatible with a normal life span and does not affect the brain. Niemann-Pick disease A deficiency of sphingomyelinase that leads to the buildup of sphingomyelin cholesterol in reticuloendothelial and parenchymal cells and tissues. Autosomal recessive. No man PICKs (Niemann-PICK) his nose with his sphinger. Patients with type A die by age 3. May present with a cherry-red spot and hepatosplenomegaly. Tay-Sachs disease An absence of hexosaminidase that leads to GM2 ganglioside Tay-SaX lacks heXosaminidase. accumulation. Infants may appear normal until 3–6 months of age, when weakness begins and development slows and regresses. An exaggerated startle response may be seen. Death occurs by age 3. Presents with a cherry-red spot but no hepatosplenomegaly. The carrier rate is 1 in 30 Jews of European descent (1 in 300 for others). Metachromatic leukodystrophy A deficiency of arylsulfatase A that leads to the accumulation of sulfatide Autosomal recessive. in the brain, kidney, liver, and peripheral nerves. Demyelination leads to progressive ataxia and dementia. Hurler’s syndrome A deficiency of α-L-iduronidase. Autosomal recessive. Leads to corneal clouding, mental retardation, and gargoylism. Hunter’s syndrome A deficiency of iduronate sulfatase. X-linked recessive. A mild form of Hurler’s syndrome with no corneal clouding and mild Hunters need to see (no corneal mental retardation. clouding) to aim for the X. 366 HIGH-YIELD FACTS IN PEDIATRICS TREATMENT Pulmonary manifestations are managed with chest physical therapy, bronchodilators, corticosteroids, antibiotics (should cover Pseudomonas), and DNase. Administer pancreatic enzymes and fat-soluble vitamins A, D, E, and K for malabsorption. Nutritional counseling and support with a high-calorie and high-protein diet are essential for health maintenance. Patients who have severe disease but can tolerate surgery may be candidates for lung or pancreas transplants. Life expectancy was once ~ 20 years, but with newer treatments it is increasing to past age 30. n n n n Gastroenterology I NTUS S US C E P TI ON A condition in which a portion of the bowel invaginates or “telescopes” into an adjacent segment, usually proximal to the ileocecal valve (see Figure 2.13-3A). The most common cause of bowel obstruction in the first 2 years of life (males > females); usually seen between 3 months and 3 years of age. The cause is often unknown. Risk factors include conditions with potential lead points, including Meckel’s diverticulum, intestinal lymphoma (> 6 years of age), HenochSchönlein purpura, parasites, polyps, adenovirus or rotavirus infection, celiac disease, and CF. HISTORY/PE n n Presents with abrupt-onset, colicky abdominal pain in apparently healthy children, often accompanied by flexed knees and vomiting. The child may appear well in between episodes if intussusception is released. The classic triad is abdominal pain, vomiting, and bloody mucus in stool (“currant jelly stool,” a late finding that is hemoccult !). A B Intussusception. (A) Ileocolic intussusception, the most common location in children. (B) Transabdominal ultrasound shows the classic “target sign” of intussusception in cross-section. (Image A reproduced with permission from Doherty GM. Current Diagnosis & Treatment: Surgery, FIGURE 2.13-3. 13th ed. New York: McGraw-Hill, 2010, Fig. 43-12. Image B reproduced with permission from Ma OJ et al. Emergency Ultrasound, 2nd ed. New York: McGraw-Hill, 2008, Fig. 9-15A.) PEDIATRICS HIGH-YIELD FACTS IN 367 On examination, look for abdominal tenderness, a ! stool guaiac, a palpable “sausage-shaped” RUQ abdominal mass, and absence of bowel in the RLQ (“empty” on palpation). n DIAGNOSIS/TREATMENT Abdominal plain films are often normal early in the disease, but later they may show small bowel obstruction, perforation, or a soft tissue mass. Ultrasound is the test of choice and may show a “target sign” (see Figure 2.13-3B). Correct any volume or electrolyte abnormalities, check CBC for leukocytosis, and consider an NG tube for decompression. In the setting of high clinical suspicion, an air-contrast barium enema should be performed without delay, as it is diagnostic in > 95% of cases and curative in > 80%. If the child is unstable or has peritoneal signs or if enema reduction is unsuccessful, perform surgical reduction and resection of gangrenous bowel. n n n KEY FACT In most cases of intussusception, an air-contrast barium enema is both diagnostic and therapeutic. PY L O R IC S T E N O SI S Hypertrophy of the pyloric sphincter, leading to gastric outlet obstruction. More common in firstborn males; associated with tracheoesophageal fistula, a maternal history of pyloric stenosis, and erythromycin ingestion. HISTORY/PE n n n Nonbilious emesis typically begins around 3 weeks of age and progresses to projectile emesis after most or all feedings. Babies initially feed well but eventually suffer from malnutrition and dehydration. Examination may reveal a palpable olive-shaped, mobile, nontender epigastric mass and visible gastric peristaltic waves. DIAGNOSIS n Abdominal ultrasound is the imaging modality of choice and reveals a hypertrophic pylorus (see Figure 2.13-4). L GB A B FIGURE 2.13-4. Hypertrophic pyloric stenosis. (A) Schematic representation of a hypertrophied pylorus. The arrow denotes protrusion of the pylorus into the duodenum. (B) Longitudinal ultrasound of the pylorus showing a thickened pyloric musculature (X’s) over a long pyloric channel length (plus signs). L = liver; GB = gallbladder. (Image A adapted with permission from Doherty GM. Current Diagnosis & Treatment: Surgery, 13th ed. New York: McGraw-Hill, 2010, Fig. 43-9. Image B reproduced with permission from USMLERx.com.) A newborn presents with lymphedema of the hands and feet, ↓ femoral pulses, a webbed neck, widely spaced nipples, short fourth metacarpals, and nail dysplasia. What form of hormone replacement therapy will the child need in the future? 368 HIGH-YIELD FACTS IN KEY FACT The classic metabolic derangement in pyloric stenosis is hypochloremic, hypokalemic metabolic alkalosis (due to persistent emesis of HCl). PEDIATRICS n Barium studies show a narrow pyloric channel (“string sign”) or a pyloric beak. TREATMENT n n Correct existing dehydration and acid-base/electrolyte abnormalities. Surgical correction with pyloromyotomy. ME C K E L’S DI VE R TI C U LU M MNEMONIC Meckel’s rule of 2’s: Most common in children under 2 2 times more common in males Contains 2 types of tissue (pancreatic and gastric) 2 inches long Found within 2 feet of the ileocecal valve Occurs in 2% of the population Caused by failure of the omphalomesenteric (or vitelline) duct to obliterate. The resulting heterotopic gastric tissue causes ulcers and bleeding. The most common congenital abnormality of the small intestine, affecting up to 2% of children (more common in males). Most frequently occurs in children < 2 years of age. HISTORY/PE n n n Typically asymptomatic, and often discovered incidentally. Classically presents with sudden, intermittent, painless rectal bleeding. May result in complications such as intestinal obstruction, diverticulitis (which may mimic acute appendicitis), volvulus, and intussusception. DIAGNOSIS n n A Meckel scintigraphy scan (technetium-99m pertechnetate; detects ectopic gastric tissue) is diagnostic. Plain films have limited value but can be useful in diagnosing obstruction or perforation. TREATMENT In the presence of active bleeding, treatment is surgical excision of the diverticulum together with the adjacent ileal segment (ulcers frequently develop in adjacent ileum). HI RSC H SP R U NG ’S DI S E AS E Congenital lack of ganglion cells in the distal colon, leading to uncoordinated peristalsis and ↓ motility. Associated with male gender, Down syndrome, Waardenburg’s syndrome, and multiple endocrine neoplasia (MEN) type 2. HISTORY/PE n n Estrogen replacement therapy for ovarian dysgenesis. Without exogenous estrogen, this child will be at ↑ risk of delayed puberty and osteoporosis later in life. Neonates present with failure to pass meconium within 48 hours of birth, accompanied by bilious vomiting and FTT; children with less severe lesions may present later in life with chronic constipation. Physical examination may reveal abdominal distention and explosive discharge of stool following a rectal examination; lack of stool in the rectum; or abnormal sphincter tone. DIAGNOSIS n n Barium enema is the imaging study of choice and reveals a narrowed distal colon with proximal dilation. Plain films reveal distended bowel loops with a paucity of air in the rectum. Anorectal manometry detects failure of the internal sphincter to relax after distention of the rectal lumen. It is typically used in atypical presentations or older children. PEDIATRICS n Rectal biopsy confirms the diagnosis and reveals absence of the myenteric (Auerbach’s) plexus and submucosal (Meissner’s) plexus along with hypertrophied nerve trunks enhanced with acetylcholinesterase stain. TREATMENT Traditionally a 2-stage surgical repair is used involving the creation of a diverting colostomy at the time of diagnosis, followed several weeks later by a definitive “pull-through” procedure connecting the remaining colon to the rectum. MA LR O T A T I O N WIT H V O L VU L U S Congenital malrotation of the midgut results in abnormal positioning of the small intestine (cecum in the right hypochondrium) and formation of fibrous bands (Ladd’s bands). Bands predispose to obstruction and constriction of blood flow. HISTORY/PE n n Often presents in the first month of life with bilious emesis, crampy abdominal pain, distention, and passage of blood or mucus in the stool. Postsurgical adhesions can lead to obstruction and volvulus at any point in life. DIAGNOSIS n n AXR may reveal the characteristic “bird-beak” appearance and air-fluid levels but may also appear normal. If the patient is stable, an upper GI is the study of choice and shows an abnormal location of the ligament of Treitz. Ultrasound may be used, but its sensitivity is contingent on the experience of the ultrasonographer. TREATMENT n n NG tube insertion to decompress the intestine; IV fluid hydration. Emergent surgical repair when volvulus is gastric; surgery or endoscopy when volvulus is intestinal. N E C R O T IZ IN G EN T E R O C O L IT IS ( N E C) A condition in which a portion of the bowel undergoes necrosis. The most common GI emergency in neonates; most frequently seen in premature infants, but can occur in full-term infants as well. HISTORY/PE n n Symptoms usually present within the first few days or weeks of life and are nonspecific, including feeding intolerance, delayed gastric emptying, abdominal distention, and bloody stools. Symptoms may rapidly progress to intestinal perforation, peritonitis, abdominal erythema, and shock. Maintain a high index of suspicion. DIAGNOSIS n Lab findings are nonspecific and may show hyponatremia, metabolic acidosis, leukopenia or leukocytosis with left shift, thrombocytopenia, and coagulopathy (DIC with prolonged PT/aPTT and a ! D-dimer). HIGH-YIELD FACTS IN 369 KEY FACT The definitive diagnosis of Hirschsprung’s disease requires a rectal biopsy. 370 HIGH-YIELD FACTS IN KEY FACT Pneumatosis intestinalis on plain films is pathognomonic for NEC in neonates. PEDIATRICS n n Plain abdominal radiographs may show dilated bowel loops, pneumatosis intestinalis (intramural air bubbles representing gas produced by bacteria within the bowel wall; see Figure 2.13-5), portal venous gas, or abdominal free air. Serial abdominal plain films should be taken every 6 hours. Ultrasound may also be helpful in discerning free air, areas of loculation or walled-off abscesses, and bowel necrosis. TREATMENT n n n Initiate supportive measures, including NPO, an orogastric tube for gastric decompression, correction of dehydration and electrolyte abnormalities, TPN, and IV antibiotics. Indications for surgery are perforation (free air under the diaphragm) or worsening radiographic signs on serial abdominal plain films. An ileostomy with mucous fistula is typically performed, with a reanastomosis later. Complications include formation of intestinal strictures and short-bowel syndrome. Immunology I M M U NODE F I C I E NC Y DI SOR DE RS KEY FACT Flashback to immunology: n B cells: Make immunoglobulins and are responsible for immunity against extracellular bacteria. n T cells: Responsible for immunity against intracellular bacteria, viruses, and fungi. Congenital immunodeficiencies are rare and often present with chronic or recurrent infections (eg, chronic thrush), unusual or opportunistic organisms, incomplete treatment response, or FTT. Categorization is based on the single immune system component that is abnormal (see also Table 2.13-6). n B-cell deficiencies: Most common (50%). Typically present after 6 months of age with recurrent sinopulmonary, GI, and urinary tract infections with encapsulated organisms (H influenzae, Streptococcus pneumoniae, Neisseria meningitidis). Treat with IVIG (except for IgA deficiencies). FIGURE 2.13-5. Pneumatosis intestinalis. Short arrows highlight pneumatosis intestinalis on an AXR of a patient with necrotizing enterocolitis. (Reproduced with permission from Brunicardi FC et al. Schwartz’s Principles of Surgery, 9th ed. New York: McGraw-Hill, 2010, Fig. 39-19.) PEDIATRICS TA B L E 2 . 13 - 6 . Pediatric Immunodeficiencies DISORDER DESCRIPTION HIGH-YIELD FACTS IN INFECTION RISK/TYPE 371 DIAGNOSIS/TREATMENT B-CELL DISORDERS Bruton’s congenital agammaglobulinemia An X-linked recessive B-cell Life threatening; characterized deficiency found only in boys. Symptoms begin after 6 months of age, when maternal IgG Quantitative immunoglobulin levels. by encapsulated Pseudomonas, If low, confirm with B- and T-cell S pneumoniae, and Haemophilus subsets (B cells are absent; T cells infections after 6 months of age. are often high). Absent tonsils (transferred transplacentally) is and other lymphoid tissue may no longer active. provide a clue. Treat with prophylactic antibiotics and IVIG. Common variable immunodeficiency (CVID) ↑ pyogenic upper and lower Usually a combined B- and T-cell respiratory infections. defect. ↑ risk of lymphoma and All Ig levels are low (in the 20s autoimmune disease. and 30s). Quantitative immunoglobulin levels; confirm with B- and T-cell subsets. Treat with IVIG. Normal B-cell numbers; ↓ plasma cells. Symptoms usually present later in life (15–35 years of age). IgA deficiency Mild; the most common immunodeficiency. ↓ IgA levels only. Usually asymptomatic; patients may develop recurrent respiratory or GI infections (Giardia). Anaphylactic transfusion reaction Quantitative IgA levels; treat infections. Do not give IVIG, as it can lead to the production of anti-IgA antibodies. due to anti-IgA antibodies is a common presentation. T-CELL DISORDERS Thymic aplasia See the mnemonic CATCH 22. (DiGeorge syndrome) Presents with tetany (2° to Variable risk of infection. ↑↑↑ Absolute lymphocyte count; infections with viruses, fungi, mitogen stimulation response; hypocalcemia) in the first days and Pneumocystis jiroveci delayed hypersensitivity skin of life. (PCP) pneumonia. testing. X-ray may show absent thymic shadow. Treat with bone marrow transplantation and IVIG for antibody deficiency; give PCP prophylaxis. Thymus transplantation is an alternative. (continues) 372 HIGH-YIELD FACTS IN TA B L E 2 . 13 - 6 . PEDIATRICS Pediatric Immunodeficiencies (continued) DISORDER DESCRIPTION INFECTION RISK/TYPE DIAGNOSIS/TREATMENT COMBINED DISORDERS Ataxia-telangiectasia Progressive cerebellar ataxia and oculocutaneous telangiectasias. Caused by a DNA repair defect. ↑ incidence of malignancies, No specific treatment; may require including non-Hodgkin’s IVIG depending on the severity of lymphoma, leukemia, and gastric the Ig deficiency. carcinoma. Severe combined Severe lack of B and T cells due to Severe, frequent bacterial Treat with bone marrow or stem immunodeficiency a defect in stem cell maturation infections; chronic candidiasis; cell transplantation and IVIG for (SCID) and ↓ adenosine deaminase. opportunistic organisms. antibody deficiency. Requires PCP prophylaxis. Referred to as “bubble boy disease” because children are confined to an isolated, sterile environment. Wiskott-Aldrich syndrome ↑↑ risk of atopic disorders, An X-linked recessive disorder seen only in males. lymphoma/leukemia, and infection Symptoms usually present at birth. from S pneumoniae, S aureus, and Patients have ↑ IgE/IgA, ↓ IgM, and H influenzae type b (encapsulated organisms; think back to how IgM thrombocytopenia. functions). The classic presentation involves bleeding, eczema, and recurrent Treatment is supportive (IVIG and antibiotics). Patients rarely survive to adulthood. Patients with severe infections may be treated with bone marrow transplantation. otitis media. Remember the mnemonic WIPE: Wiskott-Aldrich Infections Purpura (thrombocytopenic) Eczema PHAGOCYTIC DISORDERS Chronic An X-linked (2⁄3) or autosomal- Chronic skin, lymph node, granulomatous recessive (1⁄3) disease with pulmonary, GI, and urinary tract disease (CGD) deficient superoxide production infections; osteomyelitis and by PMNs and macrophages. hepatitis. Anemia, lymphadenopathy, and Infecting organisms are catalase hypergammaglobulinemia may ! (S aureus, E coli, Candida, be present. Klebsiella, Pseudomonas, Aspergillus). May have granulomas of the skin and GI/GU tracts. Absolute neutrophil count with neutrophil assays. The nitroblue tetrazolium test is diagnostic for CGD. Treat with daily TMP-SMX; make judicious use of antibiotics during infections. IFN-γ can ↓ the incidence of serious infection. Bone marrow transplantation and gene therapy are new therapies. Leukocyte adhesion A defect in the chemotaxis of Recurrent skin, mucosal, and deficiency leukocytes. pulmonary infections. May present as omphalitis in the newborn No pus with minimal inflammation in wounds (due to a chemotaxis defect). period with delayed separation of High WBCs in blood. the umbilical cords. Bone marrow transplantation is curative. PEDIATRICS TA B L E 2 . 13 - 6 . HIGH-YIELD FACTS IN 373 Pediatric Immunodeficiencies (continued) DISORDER Chédiak-Higashi syndrome DESCRIPTION INFECTION RISK/TYPE An autosomal recessive disorder ↑↑ incidence of overwhelming that leads to a defect in pyogenic infections with neutrophil chemotaxis/ Streptococcus pyogenes, S aureus, microtubule polymerization. and Pseudomonas species. DIAGNOSIS/TREATMENT Look for giant granules in neutrophils. Bone marrow transplantation is the treatment of choice. The syndrome includes partial oculocutaneous albinism, peripheral neuropathy, and neutropenia. Job’s syndrome A defect in neutrophil chemotaxis. Recurrent S aureus infections and Treat with penicillinase-resistant Remember the mnemonic FATED: abscesses. antibiotics and IVIG. Coarse Facies Abscesses (S aureus) Retained primary Teeth Hype-IgE (eosinophilia) Dermatologic (severe eczema) COMPLEMENT DISORDERS C1 esterase An autosomal dominant disorder Can lead to life-threatening airway Total hemolytic complement deficiency (hereditary with recurrent episodes of edema. (CH50) to assess the quantity and angioedema) angioedema lasting 2–72 hours function of complement. Purified and provoked by stress or trauma. C1 esterase and FFP can be used prior to surgery. Terminal complement Inability to form membrane attack deficiency (C5–C9) complex (MAC). Recurrent Neisseria infections, meningococcal or gonococcal. Meningococcal vaccine and appropriate antibiotics. Rarely, lupus or glomerulonephritis. Bruton’s congenital agammaglobulinemia can be confused with transient hypogammaglobulinemia of infancy (THI), as both are characterized by ↑ susceptibility to infections at ~ 6 months of age, when transplacental maternal IgG is no longer active. B cells are ↓ in Bruton’s, whereas those in THI are normal. n Bruton’s and CVID also have similar symptoms, but the latter is found in males ~ 6 months of age, whereas CVID is seen in older males and females (15–35 years of age), and its symptoms are less severe. T-cell deficiencies: Tend to present earlier (1–3 months) with opportunistic and low-grade fungal, viral, and intracellular bacterial infections (eg, mycobacteria). 2° B-cell dysfunction may also be seen. Phagocyte deficiencies: Characterized by mucous membrane infections, abscesses, and poor wound healing. Infections with catalase-! organisms (eg, S aureus), fungi, and gram-" enteric organisms are common. Complement deficiencies: Present in children with congenital asplenia or splenic dysfunction (sickle cell disease). Characterized by recurrent bacterial infections with encapsulated organisms. n n n n A 3-month-old infant with a heart murmur has recurrent hospitalizations for fungal and viral infections. A CXR shows no thymic shadow, and the infant’s serum calcium level is low. What other defects are common in patients with this disorder? 374 HIGH-YIELD FACTS IN PEDIATRICS KAW A S AK I DI SE AS E KEY FACT Untreated Kawasaki disease can lead to coronary aneurysms and even MI! A multisystemic acute vasculitis that primarily affects young children (80% are < 5 years of age), particularly those of Asian ancestry. Divided into acute, subacute, and chronic phases. DIAGNOSIS n MNEMONIC Kawasaki disease symptoms— CRASH and BURN Conjunctivitis Rash Adenopathy (unilateral) Strawberry tongue Hands and feet (red, swollen, flaky skin) BURN (fever > 40°C [> 104°F] for ≥ 5 days) n KEY FACT Kawasaki disease and scarlet fever may both present with “strawberry tongue,” rash, desquamation of the hands and feet, and erythema of the mucous membranes. However, children with scarlet fever have normal lips and no conjunctivitis. n Acute phase: Lasts 1–2 weeks and presents with the following symptoms (fever plus 4 or more of the criteria below are required for diagnosis): n Fever (usually > 40°C [> 104°F]) for at least 5 days. n Bilateral, nonexudative, painless conjunctivitis sparing the limbic area. n A polymorphous rash (primarily truncal). n Cervical lymphadenopathy (often painful and unilateral, with at least 1 node > 1.5 cm). n Diffuse mucous membrane erythema (eg, “strawberry tongue”); dry, red, chapped lips. n Erythema of the palms and soles; indurative edema of the hands and feet; late desquamation of the fingertips (in the subacute phase). n Other manifestations include sterile pyuria, gallbladder hydrops, hepatitis, and arthritis. Subacute phase: Begins after the abatement of fever and typically lasts for an additional 2–3 weeks. Manifestations are thrombocytosis and elevated ESR. Untreated children may begin to develop coronary artery aneurysms (40%); all patients should be assessed by echocardiography at diagnosis. Chronic phase: Begins when all clinical symptoms have disappeared; lasts until ESR returns to baseline. Untreated children are at risk of aneurysmal expansion and MI. TREATMENT n n n High-dose ASA (for inflammation and fever) and IVIG (to prevent aneurysms). Low-dose ASA is then continued, usually for 6 weeks. Children who develop coronary aneurysms may require chronic anticoagulation with ASA or other antiplatelet medications. Corticosteroids may be used in IVIG-refractory cases, but routine use is not recommended. JUV E NI LE I D I OP ATHI C AR THR I TI S ( J I A) An autoimmune disorder manifesting as arthritis with “morning stiffness” and gradual loss of motion that is present for at least 6 weeks in a patient < 16 years of age. Formerly known as juvenile rheumatoid arthritis (JRA). DIAGNOSIS n This infant has DiGeorge syndrome. Remember the mnemonic CATCH 22: Cardiac abnormalities, Abnormal facies, Thymic aplasia, Cleft palate, Hypocalcemia, chromosome 22. n n Pauciarticular (oligoarthritis): Most common; involves 4 or fewer joints (usually weight-bearing); usually ANA ! and RF ". Involves young females; uveitis is common and requires slit-lamp examination for evaluation. No systemic symptoms. Polyarthritis: Involves 5 or more joints; symmetric. RF positivity is rare and indicates severe disease; younger children may be ANA ! with milder disease. Systemic symptoms are rare. Systemic-onset (Still’s disease): May present with recurrent high fever (usually > 39°C [> 102.2°F]), hepatosplenomegaly, and a salmon-colored macular rash; usually RF and ANA ". PEDIATRICS HIGH-YIELD FACTS IN 375 TREATMENT n n NSAIDs and strengthening exercises. Corticosteroids (for carditis) and immunosuppressive medications (methotrexate, anti-TNF agents such as etanercept) are second-line agents. Infectious Disease AC U T E OT IT I S ME DI A A suppurative infection of the middle ear cavity that is common in children. Up to 75% of children have at least 3 episodes by age 2. Common pathogens include S pneumoniae, nontypable H influenzae, Moraxella catarrhalis, and viruses such as influenza A, RSV, and parainfluenza virus. HISTORY/PE Symptoms include ear pain, fever, crying, irritability, difficulty feeding or sleeping, vomiting, and diarrhea. Young children may tug on their ears. DIAGNOSIS Signs on otoscopic exam reveal an erythematous tympanic membrane (TM), bulging or retraction of the TM, loss of TM light reflex, and ↓ TM mobility (test with an insufflator bulb). TREATMENT n n High-dose amoxicillin (80–90 mg/kg/day) × 10 days for empiric therapy. Resistant cases may require amoxicillin/clavulanic acid. Complications include TM perforation, mastoiditis, meningitis, cholesteatomas, and chronic otitis media. Recurrent otitis media can cause hearing loss with resultant speech and language delay. Chronic otitis media may require tympanostomy tubes. BRO N CH IO LI T I S An acute inflammatory illness of the small airways in the upper and lower respiratory tracts that primarily affects infants and children < 2 years of age, often in the fall or winter. RSV is the most common cause; others include parainfluenza, influenza, and metapneumovirus. Progression to respiratory failure is a potentially fatal complication. For severe RSV, risk factors include age < 6 months, male gender, prematurity, heart or lung disease, and immunodeficiency. HISTORY/PE n n n n Presents with low-grade fever, rhinorrhea, cough, and apnea (in young infants). Examination reveals tachypnea, wheezing, intercostal retractions, crackles, prolonged expiration, and hyperresonance to percussion. An ↑ respiratory rate is the earliest and most sensitive vital sign change. Although presentation can be highly variable, symptoms generally peak on day 3 or 4. KEY FACT RSV is the most common cause of bronchiolitis. Parainfluenza is the most common cause of croup. 376 HIGH-YIELD FACTS IN PEDIATRICS DIAGNOSIS n n n Predominantly a clinical diagnosis; routine cases do not need blood work or a CXR. A CXR may be obtained to rule out pneumonia and may show hyperinflation of the lungs with flattened diaphragms, interstitial infiltrates, and atelectasis. Nasopharyngeal aspirate to test for RSV is highly sensitive and specific but has little effect on management (infants should be treated for bronchiolitis whether RSV is ! or not). TREATMENT n n n n n Treatment is primarily supportive; treat mild disease with outpatient management using fluids and nebulizers if needed. Hospitalize if signs of severe illness are present. Treat inpatients with contact isolation, hydration, and O2. A trial of aerosolized albuterol may be attempted; albuterol therapy should be continued only if it is effective. Corticosteroids are not indicated. Ribavirin is an antiviral drug that has a controversial role in bronchiolitis treatment. It is sometimes used in high-risk infants with underlying heart, lung, or immune disease. RSV prophylaxis with injectable poly- or monoclonal antibodies (RespiGam or Synagis) is recommended in winter for high-risk patients ≤ 2 years of age (eg, those with a history of prematurity, chronic lung disease, or congenital heart disease). CR OU P ( LAR YNG OTR AC HE OBR ONC HI TIS ) An acute viral inflammatory disease of the larynx, primarily within the subglottic space. Pathogens include parainfluenza virus type 1 (most common), 2, and 3 as well as RSV, influenza, and adenovirus. Bacterial superinfection may progress to tracheitis. HISTORY/PE Prodromal URI symptoms are typically followed by low-grade fever, mild dyspnea, inspiratory stridor that worsens with agitation, a hoarse voice, and the characteristic barking cough (usually at night). DIAGNOSIS n n n Diagnosed by clinical impression; often based on the degree of stridor and respiratory distress. AP neck film may show the classic “steeple sign” from subglottic narrowing (see Figure 2.13-6), but this finding is neither sensitive nor specific. Table 2.13-7 differentiates croup from epiglottitis and tracheitis. TREATMENT n n n Mild cases: Outpatient management with cool mist therapy and fluids. Moderate cases: May require supplemental O2, oral or IM corticosteroids, and nebulized racemic epinephrine. Severe cases (eg, respiratory distress at rest, inspiratory stridor): Hospitalize and give nebulized racemic epinephrine. PEDIATRICS HIGH-YIELD FACTS IN FIGURE 2.13-6. Croup. AP radiograph of the neck in this 1-year-old with inspiratory stridor and cough shows the classic “steeple sign” (arrow) consistent with the subglottic narrowing of laryngotracheobronchitis. (Reproduced with permission from Stone CK, Humphries RL. Current Diagnosis & Treatment: Emergency Medicine, 6th ed. New York: McGraw-Hill, 2008, Fig. 30-10A.) E P IG LO T T I T I S A serious and rapidly progressive infection of supraglottic structures (eg, the epiglottis and aryepiglottic folds). Prior to immunization, H influenzae type b was the 1° pathogen. Common causes now include Streptococcus species, nontypable H influenzae, and viral agents. HISTORY/PE n n n Presents with acute-onset high fever (39–40°C [102–104°F]), dysphagia, drooling, a muffled voice, inspiratory retractions, cy