Dr. Fiorito (00:04): Hi. I'm Theresa Fiorito, associate professor in the Department of Pediatrics at NYU Long Island School of Medicine and director for Family Travel Clinic at NYU Langone Hospital, Long Island in Mineola, New York. Welcome to this program titled Tick Talk: Recognizing and Diagnosing Lyme Disease. This is part one of a two-part series. In this activity, I will be discussing clinical symptoms and diagnosis of Lyme disease. In part two, I will discuss management of Lyme disease. Let's start with a question. You are seeing a five-year-old male in May with low grade fever, T-max 100.6 Fahrenheit, and fatigue. Mom is worried about Lyme disease because she pulled a tick off of her son yesterday evening. She has the tick with her. He has no other symptoms, he has no history of allergies, but he has never been on antibiotics before. What is the next best step? The correct answer is ask to see the tick. This is the tick that mom brought with her. It is an American dog tick. It does not carry Lyme disease. The vector for Lyme disease is the deer tick, also known as Ixodes scapularis. American dog ticks do not carry Lyme disease. There is not prophylaxis indicated for tick bites with any other type of tick than the tick that carries Lyme disease. With regard to chemoprophylaxis for tick bites, we first must think about the overall risk. In areas of high endemicity, for example New York, the overall risk of Lyme disease following a recognized tick bite is how high? 3%. But after a high-risk deer tick bite, which is defined as an engorged tick that has fed for over 72 hours, the risk of infection goes up. But even then, it's only 25%. The point being the risk of Lyme disease is extremely low after brief attachment. If you do not find an engorged tick, the risk is incredibly low. Brief attachment is defined as less than 36 hours, so you've found a flat deer tick. Testing of the tick for spirochete infection has a poor predictive value and is not recommended. Routine administration of antimicrobial prophylaxis after a deer tick bite is not recommended either. In areas of high-risk, however, a single prophylactic 200 mg dose or, for children under 45 kilos, 4.4 mgs per kg, a single dose of doxycycline can be used in children of any age to reduce the risk of acquiring Lyme disease after a deer tick bite. This recommendation for doxycycline has changed in recent years. The benefits of prophylaxis outweigh the risks when the tick is engorged because it means that it's been attached for 36 or more hours based on the exposure history. We'll go into that a little more and why that is. You must start prophylaxis within 72 hours of tick removal. If a patient comes to see you and says, "I was bit by a tick two weeks ago," prophylaxis is probably not going to be effective. If we look at the geographic distribution of Lyme disease, we see that the black-legged tick is found up and down the East Coast extending into the Midwest and the western black-legged tick dots the West Coast line. What's interesting, however, is comparing the distribution of the black-legged tick to the distribution of Lyme disease with a big focus in the northeastern United States despite the fact that the tick is found throughout the Eastern Seaboard. The reason for this is that in the South, the reservoir for the tick are lizards. Lizard blood is actually bacteriostatic to the Borrelia burgdorferi bacteria. In the Northeast, the reservoir or intermediate hosts are deer and white-footed mice. If we look at the transmission of Lyme disease, we can appreciate a peak that starts in about may and starts to go down in October. This correlates with the stage of the tick called nymphs. The nymphs are the biters. The nymphs are the ones that transmit disease. You can see that while adults are kind of found all year round, the nymphal peak in spring is what correlates with the start of Lyme disease. We appreciate a second peak in late summer into fall owing to the presence of larvae, which are responsible for cases of Lyme disease as well. A big question is how big are they? How big are these ticks and why it's so important to do tick checks? They're very tiny. The adult is about the size of a sesame seed. If you look at the picture on the right, it shows you both the adult female and male black-legged tick. You can appreciate that the female is black and red, and the nymph. The nymph is about the size of a poppy seed, and even smaller than that to the left is the larva. The black-legged tick is the smaller of the three species that carry tick-borne illnesses. It's not as easy to get Lyme disease as you might have previously thought. First of all, you need to get bitten with the right species, so only the deer tick, as discussed earlier, carries Lyme disease. That tick must be infected with the Lyme disease bacteria, which begs the question what percentage of ticks are infected? About 20% of nymphs, so one in five of the nymphal stage will be infected with the bacteria. About 50% of adult females will be infected with the Lyme bacteria, but the reason why it is not recommended to test the tick for the presence of the bacteria is because it's actually the nymphs that do most of the biting. They're young, they're hungry, they're looking for a meal. If you find the bacteria an adult female, it doesn't necessarily denote infection. Another key point about Lyme disease is how long the tick has been on you. Just because the tick is positive for the bacteria does not mean that the tick has transmitted Lyme disease to you. Chances of transmission increase with time attached if the tick is infected. If you look at these figures, you can see that transmission only starts to occur around 48 hours and only 12% of transmission occurs at 48 hours. You can appreciate that this dramatically increases at 72 hours, with almost 100% transmission at 96 hours. This is why a tick bite is considered high-risk if it's been attached for 72 hours or more. "36 hours," you say. "But why?" Well, the bacteria is not in the saliva of the tick. The bacteria is actually in the gut of the tick, so first the tick has to get on you, then it has to find a nice place to attach, then it has to take a blood meal. Once it takes a blood meal, it starts to engorge. It then regurgitates that blood meal back into you at the bite site, and that is when the bacteria goes into your body and transmission of Lyme disease occurs. Looking at a timeline, the average length of time between the tick bite and the onset of symptoms is anywhere from three days to a month later, with a median of 11 days. 50% of people will clear early localized disease without treatment, 50% of people will go on to have early disseminated disease, which consists of things like Bell's palsy or carditis. We'll talk more about that in a little bit. The time from the tick bite to the appearance of, say, a Bell's palsy is three to 10 weeks, and those who do not have early disseminated disease or who do not clear it will go on to have what's known as late disseminated disease. That can present anywhere from two to 12 months later. Very commonly in our office, we see patients in January or February with late disseminated disease because they were bit by a tick the summer prior. Focusing a little bit more on early localized disease. Early localized disease are what's classically known as a bullseye rash. The bullseye is initially... It's actually very rare. It starts as a red, round, irregular rash. It's not warm, which distinguishes it from cellulitis, and in the center it may actually have a necrotic area or a purplish discoloration at the site of the tick bite. In children of note, this rash is more common in the head and the neck area so important to check the scalp. The big question is how do you know that this rash is lyme? It expands, it grows bigger every day. Early localized Lyme disease is never an emergency so you can take a day and make sure that you can appreciate the expansion. As the rash expands, the middle part will clear and you will appreciate more of that bullseye. What if you missed it? The rash lasts for an average of one week to four weeks, so if it's there and it's Lyme disease there's no reason to think it's there one day and gone the next. Sometimes this rash is accompanied by fever or what we call summer flu-like symptoms, some fatigue, some arthralgias, some malaise. Focusing in on early and late disseminated disease. Early disseminated disease can be multiple erythema migrans, so multiple of those bullseye lesions. It can be a Bell's palsy, it can be any cranial nerve palsy, but cranial nerve VII or Bell's palsy is most common. It can be a meningitis, which is a very non-specific meningitis that occurs in the summer, or carditis, which involves various degrees of AV block. Any of these symptoms can also be accompanied by, again, the summer flu-like symptoms. The major manifestation of late disseminated disease is arthritis. Not arthralgia, arthritis. Not pain, but swelling. The typical presentation is monoarticular, so a big boggy football of a knee, and the joint swelling is significantly out of proportion to the pain. The patient may complain of pain and stiffness, but usually the knee is much more swollen than it is painful. (14:04): Here's another question. You see a seven-year-old patient with this rash. What testing do you order? Please go ahead and answer. Okay. The correct answer is if you see the rash, treat it. Do not do blood work because what percentage of patients with early localized Lyme disease will have positive serology? Not many, 20 to 30%. The diagnosis of Lyme disease is clinical, okay? So you recognize the clinical illness in people with plausible geographic exposure, anyone in the Northeast. Early Lyme disease, as I said, is clinical and it has that characteristic skin lesion, the big hallmark of which is expansion. Serological testing is not recommended at this stage. (15:09): Now, what if you saw a 16-year-old male and he has fatigue and arthralgias? Mom reports he's a straight A student but suddenly he's having difficulty concentrating with memory lapse. What Lyme testing should you order? Please go ahead and answer. Okay, so this is very important to touch upon, the diagnosis of Lyme disease in patients with fatigue and arthralgias. If you take away nothing else from this talk, take away this. Non-specific symptoms are almost never the only evidence of Lyme disease. I don't like to use extremes, almost and never, but this is one time I will make the exception. Lyme testing is not recommended for these patients because almost all positive serologic test results are false positives. The tests aren't very good. We'll go into that in a little bit. On this slide, I've just shown some examples of the literature that support this. This is not my personal belief. Although non-specific symptoms such as fatigue, arthralgias, and headache can accompany Lyme disease, they're almost never the only evidence of Lyme disease. Here's some literature to support that. (17:48): Looking further and a little bit closer at the testing. It's a two-tiered approach, which is very important to know. The first part is an enzyme immunoassay or immunofluorescence and the second tier or the second test is a western blot. Very important to do both of these and to do them in a tiered approach, so doing the EIA as a screening test and if positive reflexing to a western blot. You must never do a western blot in the absence of an EIA. If the EIA is positive and they've had signs or symptoms for more than 30 days, it's only the IgG antibodies on the western blot that we want to focus on because this would tell us it would be a disseminated picture. If the patient has had signs or symptoms for less than or equal to 30 days, we would look at both the IgM and the IgG on the western blot. (18:45): Here's another question for you. You are seeing an eight-year-old male for follow-up. He has just completed a 28-day course of doxycycline for Lyme arthritis. He was initially diagnosed based on a swollen knee and the following labs. His EIA or his screening test was very positive at greater than 12. His Lyme IgM western blot was zero out of three and his Lyme IgG on western blot was 10 out of 10. Mom would like to know when is best to repeat serology. What do you tell her? Please choose one of the following. Okay. I alluded to this before, but to go into it a little more deeply there are a lot of problems with serologic testing for Lyme disease. You can be positive for years, so your IgM antibodies can stay elevated even if you've been cured. As such, someone who has tested once for Lyme should never be tested again using blood work. The EIA or the screening test is associated with a lot of false positives. There are cross-reactive antibodies in patients with other spirochete infections, so patients with syphilis, for example. There's cross-reaction with certain viral infections, so patients with Epstein-Barr virus or infectious mono can be positive on Lyme testing. There's cross-reaction with autoimmune diseases, things like lupus. There's even antibodies that cross-react with spirochetes of our normal oral flora. Those are the problems with the screening test. It casts a wide net as it is a screening test, but there are also problems with the more specific test, the western blot. The western blot doesn't detect antibodies against the bacteria. It detects antibodies against proteins that are found in the bacteria, so many uninfected patients will have antibodies against these proteins of this bacteria because they are found in other places. There's one protein called the p41. That is positive in 55% of healthy people. Other caveats. As we talked about earlier, in patients with early localized disease or a single erythema migrans the antibody test results are only positive 20 to 30% of the time. Furthermore, there is a suggested blunting of the antibody response associated with antibiotic use so you may never be positive, and a positive serologic test does not necessarily denote active infection. It can reflect previous asymptomatic infection, we don't know how many people get infected with Lyme disease and have symptoms versus don't have symptoms, or can reflect a previously cured clinical infection. As such, someone tested once for Lyme should never be tested again using blood work. To comment on the question that was most recently asked, test results generally cannot be used to assess activity or relapse of past infection. As such, someone tested once for Lyme, you guessed it, should never be tested again using blood work. A quick note on the C6 peptide. The C6 peptide detects antibody to a peptide of the variable surface antigen or the [inaudible 00:22:20] of Borrelia burgdorferi bacteria. This appears to have an improved sensitivity for adults with early Lyme disease. When it's used alone, its specificity is slightly lower than that of standard two-tier testing, the EIA reflexing to the western blot, but it is helpful when you're differentiating Lyme disease from other tickborne illnesses, for example southern tick-associated rash illness or STARI, and it also can confirm infection in patients who maybe have been infected in Europe, different strains. Just some key takeaways from this Tick Talk. Lyme disease is a series of specific clinical illnesses, a bullseye rash, a Bell's palsy, a big boggy swollen knee. It is only in the presence of these symptoms and clinical suspicion should you order blood work, and only in disseminated disease. Please join me for part two of this talk where we delve further into treatment and management of Lyme disease. Thank you for participating in this activity. Please continue on to answer the questions that follow and complete the evaluation.