Rocky Mountain spotted fever (RMSF) diagnosis relies on clinical (fever, rash, myalgia) and epidemiologic (tick exposure) criteria. However, a clinical diagnosis of RMSF is difficult to establish, and laboratory findings are nonspecific. Even so, basic laboratory tests should be obtained, including the following: complete blood count (CBC), electrolytes, renal function tests, liver function tests, and coagulation panel. 
After exposure to vector ticks, patients who develop fever, petechial rash, and vomiting require antibiotic therapy. Antibiotic therapy should be initiated before laboratory confirmation is available.
Laboratory findings can include the following:
White blood cell (WBC) count - Leukopenia is present initially, then mild leukocytosis; patients usually have a normal WBC count
Platelets - Thrombocytopenia (< 150,000 cells/µL) occurs in 32-52% of patients; abnormalities indicative of DIC are present in severely ill patients
Hemoglobin and hematocrit - Anemia is present in 5-24% of patients
Aminotransferase levels - Mildly elevated in 36-62% of patients
Hyponatremia - Present in 19-56% of cases
Bilirubin levels – Increased in 8-9% of patients.
Mild cerebrospinal fluid pleocytosis with monocyte predominance
Azotemia - Develops in 12-14% of cases
Prothrombin time and activated partial thromboplastin time - May be elevated
Anemia, an increased blood urea nitrogen (BUN) level, or abnormal liver function test results are found in 30% of patients. Late findings associated with advanced disease include signs of multiorgan failure, such as elevated BUN, creatinine, and creatinine kinase levels.
Diagnosis is confirmed based on indirect immunofluorescent antibody (IFA) test results, latex agglutination, or enzyme immunoassay. Serology specific for R rickettsii infection develops within 6-8 weeks. Serologic test results are negative prior to convalescence.
Isolation of R rickettsii from the blood is possible, but few laboratories perform this isolation because of biohazard concerns. This is an insensitive test because most Rickettsia is found in the vascular endothelial cells, not in the bloodstream.
Obtain a chest radiograph in patients who appear significantly ill or have abnormal lung findings on physical examination. Chest radiographs that show an early pulmonary infiltrate should prompt consideration of a different diagnosis.
Computed tomography (CT) scanning or magnetic resonance imaging (MRI) are indicated for altered mental status or neurologic deficits and may reveal infarction, edema, and meningeal enhancement.
Lumbar puncture usually is performed as part of the workup for suspected meningitis. Pleocytosis is found in 34-38% of cases. Usually 10-100 cells/µL with either lymphocytic or polymorphonuclear cell predominance are found. Increased protein is found in 30-35% of cases; the glucose level usually is normal.
The Weil-Felix test is used to detect cross-reacting antibodies against Proteus vulgaris antigens OX-2 and OX-19. This test lacks sensitivity and specificity, and better tests are now available. If the Proteus titer is greater than or equal to 1:320 or if a 4-fold or greater rise to either Proteus OX-19 or OX-2 antigens is observed, an RMSF case that is clinically compatible is considered probable.
Electrocardiography may be used to indicate whether myocardial or conduction abnormalities are present.
Direct immunofluorescent microscopy, if available, may be used for rapid histologic diagnosis of Rocky Mountain spotted fever (RMSF). Immunofluorescent or immunoperoxidase staining of R rickettsii in a biopsy skin or organ specimen is sensitive (73%) and specific (100%).  However, because direct immunofluorescence has a 30% false-negative rate, patients should be treated even if the test is negative and the suspicion is high.
Antibodies to specific rickettsial antigens are detected by indirect immunofluorescence (most specific), latex agglutination, and enzyme immunoassay. The diagnostic titer is 1:64 for indirect immunofluorescence and latex agglutination.
Amplification of R rickettsii deoxyribonucleic acid (DNA) with polymerase chain reaction (PCR) assay has not been proven to be a sensitive diagnostic method except for later in the disease course, particularly in fatal cases. It has been successful when applied to biopsy skin samples during rickettsioses and also when applied to ticks. According to Walker and Raoult in 2000, the primers used amplify genes of the 17-kD protein citrate synthetase and rickettsial OmpA and allow the identification of any rickettsial organism.
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