Master Lyme disease — from recognizing erythema migrans and avoiding unnecessary testing to managing disseminated Lyme and post-exposure prophylaxis. Learn practical, evidence-based strategies you can use in the clinic. We’re joined by Dr. Sophie Woolston MD, infectious diseases expert and clinician-educator. (MaineHealth)
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Dr. Woolston reports no relevant financial disclosures. The Curbsiders report no relevant financial disclosures.
Lyme disease is a tick-borne infectious disease caused by the spirochete Borrelia burgdorferi (Smith 2025). It was first identified in Lyme, Connecticut, in 1977 (Schoen 2020). Historically, the Northeastern United States has been considered the primary hotspot. However, the geographic range of Lyme disease has expanded in recent years, spreading into the Mid-Atlantic region, westward toward the Mississippi River, and south of the Great Lakes (Schoen 2020).
Although tick-borne illnesses are most common in mid-to-late spring and summer due to above-freezing temperatures and increased outdoor activity, infection can occur at any time of year when temperatures are above freezing.
When evaluating patients, clinicians should assess for common symptoms including fever, joint pain, and rash (Smith 2025). It is also important to ask about recent outdoor exposure, including hiking, gardening, or contact with pets that may have brought ticks indoors. Caregivers and employees at facilities and hospitals can also carry ticks inside.
Early Localized Lyme disease occurs days to weeks after a tick bite. The hallmark finding is an erythema migrans (EM) rash, classically described as a targetoid lesion with a central area of necrosis at the bite site, surrounded by clearing and an outer ring of erythema (Smith 2025). However, the absence of this rash does not exclude Lyme disease and the rash can be quite heterogenous. Patients may also experience fever, myalgias, and arthralgias. Diagnosis at this stage is primarily clinical.
Early Disseminated Lyme disease develops weeks to months after infection and occurs in approximately 15–25% of patients. Dr. Woolston commonly sees this in patients presenting with Lyme carditis, which may manifest as AV nodal block, cardiomyopathy, or myopericarditis. Neurologic involvement can include cranial neuropathies, peripheral neuropathies, meningitis (rare), or encephalitis (rare) (Schoen 2020). Patients may also have migratory arthralgias and, less commonly, multiple EM lesions, hepatitis, or renal involvement.
Late Lyme disease most commonly presents as Lyme arthritis, characterized by monoarticular or oligoarticular joint swelling, redness, and achiness (Schoen 2020). Diagnosis may be supported by synovial fluid PCR testing.
Post-treatment Lyme syndrome may occur in up to 15% of treated patients (Aucott 2022). It is important to validate patients’ symptoms while also evaluating for other potential causes, such as autoimmune conditions that may be causing the patient’s fatigue. Of note, a recent study showed patients with PTLS also have more frequent incidence of anemia, hyperlipidemia, and osteoarthritis (Chung 2023). There are no established diagnostic criteria or proven treatments for this syndrome, and prolonged antibiotic therapy has not been shown to improve outcomes (Marques 2022).

Testing for Lyme disease can be challenging due to both false-negative and false-positive results, as well as variation in test performance depending on the stage of illness.
In Early Localized Lyme disease, particularly when an erythema migrans (EM) rash is present, serologic testing is not recommended. Antibody tests may be falsely negative early in infection. Per Dr. Woolston, if you see a classic erythema migrans rash in a patient with potential tick exposure, you may begin treatment immediately without any testing.
Additionally, Lyme antibody testing can remain positive for years after initial infection, even after appropriate treatment (Kalish 2001). This means that a positive antibody test may not necessarily indicate active infection.
Lyme testing typically involves a two-tier testing approach with the enzyme immunoassay which is then confirmed with the Western Blot (Smith 2025). Per Dr. Woolston, a positive test result is an IgM that is positive 2 of 3 bands and an IgG that is positive > 5 of 10 bands. Comparing previous testing may also be helpful as the presence of new bands (and/or more bands) may signify a new infection.
Coinfection can be common with Lyme– the most common coinfections are anaplasmosis and babesiosis (Duik-Wasser 2015). If there is concern for additional tick diseases, Dr. Woolston recommends a tick panel (which includes anaplasmosis and babesiosis) in addition to Lyme. Testing for anaplasmosis and babesiosis is generally PCR and babesiosis requires parasite smear as well. Dr. Woolston shares that if a patient is very sick and has symptoms concerning for a tick-borne disease, she is most concerned about babesiosis (Duik-Wasser 2015).

Doxycycline is first-line therapy for Lyme disease because it is inexpensive and generally well tolerated. Early Lyme is typically treated for 10 days (Raffetin 2025). The main side effect is photosensitivity, which can cause severe sunburn-like reactions, so patients should be counseled on sun protection. For pregnant patients or those who cannot take doxycycline, amoxicillin or cefuroxime are alternatives. Cefuroxime is less well studied for Lyme arthritis.
For Early Disseminated Lyme disease, if the patient is very ill and/or hospitalized, Dr. Woolston recommends starting with IV ceftriaxone and then transitioning to PO doxycycline once they are improving (and continuing for a 21-28 day course).
For Late Lyme disease, treatment usually consists of a four-week course of oral doxycycline, as antibiotic penetration into joint tissue may require longer therapy (Raffetin2025).
If a patient presents within 72 hours of a tick bite, post-exposure prophylaxis with a single 200 mg dose of doxycycline is recommended (Skar 2024). Because patients may not clearly remember when the bite occurred, Dr. Woolston shares that she keeps a lower threshold to prescribe prophylaxis in order to reduce the risk of disseminated disease.
Dr. Woolston shared that, excitingly, a Lyme vaccine is currently in phase three trials and should be available in several years. A previous Lyme vaccine was withdrawn from the market due to public concerns about possible links to autoimmune conditions; however, these associations were not scientifically validated (Sanicas 2026).

To prevent tick bites, Dr. Woolston recommends:
To remove a tick, use tweezers to grasp the tick as close to its mouth as possible. Use gentle but consistent pressure to pull steadily until the tick is removed. The tick’s grip can be strong on human skin, so it may take many rounds of gentle traction to pull it off (Smith 2025). After removal of the tick, consider disposing via flushing down a toilet or crushing the tick with a hard object.

In Dr. Woolston’s practice, she validates patients who come to her with concerns of chronic symptoms after Lyme Disease as the symptoms they are feeling are real and can be debilitating. Dr. Woolston emphasizes that there has been no evidence for long-term antibiotics in alleviating symptoms for patients who experience Post Treatment Lyme Disease Syndrome and multiple studies showing no benefit (Klempner 2001, Berende 2016). Antibiotics can also cause harmful side effects such as C.diff and line-associated infections. For patients interested in exploring alternative treatments, Dr. Woolston recommends discussing the financial cost and side effects from treatments that are not well-studied (e.g., hyperbaric therapy, ozone therapy). Emphasis should be placed on ways to manage inflammation with exercise, diet, and healthy habits.
Listeners will review basic principles of Lyme disease including presentation, diagnosis, and management.
After listening to this episode listeners will…
Garbitelli, B, Surani, Z, Woolston S, Williams PN, Watto MF. “#516 Lyme Disease Primer”. The Curbsiders Internal Medicine Podcast. thecurbsiders.com/category/curbsiders-podcast March 2, 2026.
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Written and Produced by: Beth Gasperlin MD
Show Notes, Infographics, and Cover Art by: Zoya Surani
Hosts: Matthew Watto MD, FACP; Paul Williams MD, FACP, Beth Gasperlin MD
Reviewer: Leah Witt MD
Showrunners: Matthew Watto MD, FACP; Paul Williams MD, FACP
Technical Production: PodPaste
Guest: Sophie Woolston MD
The Curbsiders are partnering with VCU Health Continuing Education to offer continuing education credits for physicians and other healthcare professionals. Visit curbsiders.vcuhealth.org and search for this episode to claim credit.
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