Lyme disease: Clinical sciences

Last updated: January 30, 2025

Lyme disease: Clinical sciences

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Decision-Making Tree

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Lyme disease is an infectious disease caused by the spirochete Borrelia Burgdorferi. It’s most commonly transmitted via the Ixodes Scapularis deer tick in Lyme-endemic areas like the Northeastern and Midwestern United States. After a tick bite, spirochetes replicate at the site of infection, causing symptoms ranging from an isolated rash to neurological, cardiac, and musculoskeletal involvement. Depending on the timing of infection and clinical presentation, Lyme disease is classified into early localized, early disseminated, and late Lyme disease.

If your patient presents with chief concerns suggesting Lyme disease, your first step is to perform a focused history and physical. Let’s start with early localized Lyme disease! Your patient will report a known tick bite or exposure to a Lyme-endemic area in the last 4 weeks. Other symptoms may include fever, a non-painful rash, and non-specific symptoms, such as headache, myalgias, and fatigue. On physical exam, you’ll see a single skin lesion called erythema migrans, which looks like a red, warm, and swollen rash with central clearing that may resemble a bullseye! With these findings, diagnose early Lyme disease, and treat empirically with oral doxycycline for 10 days.

Here’s a high-yield fact! Erythema migrans is found in 80% Lyme disease cases, most commonly appearing in the groin, axilla, and thighs. If a patient’s rash does not have typical characteristics of erythema migrans, you can delay treatment until laboratory testing confirms the presence of Borrelia antibodies. Early in the course of infection, initial testing can be negative, so if clinical suspicion remains high, consider retesting in 2 to 3 weeks, which is the time required for the immune system to produce antibodies.

And now a clinical pearl! Prophylactic treatment with a single 200-milligram dose of doxycycline orally is recommended after a tick bite within 72 hours of tick removal. However, you should give prophylactic treatment only if the tick is an Ixodes species, the tick bite occurred in a highly endemic area, the tick was attached for at least 36 hours, and it’s been less than 72 hours from tick removal. If all of these criteria aren’t met, just observe, and treat if the patient develops erythema migrans.

Now, if patients don’t get treated during the early localized stage, they can progress to early disseminated Lyme disease. These individuals usually report a history of a known tick bite or exposure to a Lyme-endemic area in the last 12 weeks. Additionally, early disseminated Lyme can affect a variety of organs and body systems, so your patient may report a range of symptoms. These may include diffuse cutaneous involvement; cardiac manifestations like chest pain or bradycardia; or neurologic symptoms, such as cranial nerve palsies or paresthesias.

In this case, suspect early disseminated Lyme disease, and order an enzyme immunoassay, also called EIA, which detects Borrelia antibodies. You’ll also need to order a Western blot for confirmation. As an alternative, instead of Western Blot testing, you can use a second EIA test for confirmation. Confirmatory testing is recommended due to the high false-positive rate associated with EIA testing.

If the results come back negative, you should consider alternative diagnoses. However, if the EIA and Western blot or consecutive EIA tests are positive, diagnose early disseminated Lyme disease and assess your patient for organ involvement.

First up is multiple erythema migrans! In this case, history reveals a known tick bite or exposure to a Lyme-endemic area in the last 12 weeks. This patient also reports more than one rash site, and the physical exam shows more than one site of a red, swollen rash with central clearing. With these findings, diagnose early disseminated Lyme disease manifested as multiple erythema migrans! Note that the skin rash is not due to multiple tick bites, instead, it occurs as spirochetes work their way from the blood to infect the skin at different locations. With this characteristic presentation, no testing is necessary, and you can treat empirically with oral doxycycline for 10 days.

Next we have Lyme carditis. Your patient could report cardiac manifestations, such as chest pain, palpitations, dyspnea, or syncope; but keep in mind that they could also be asymptomatic! The physical exam may reveal tachypnea, bradycardia, or a pericardial friction rub indicating pericarditis. In this case, you should think of Lyme carditis and order a 12-lead ECG. The combination of symptoms and ECG findings will guide your treatment.

Asymptomatic patients with an ECG showing first-degree AV block and a PR interval of less than 300 milliseconds can be treated with doxycycline for 21 days. On the other hand, symptomatic patients, or those with an ECG revealing second- or third-degree AV block, prolonged PR interval of 300 milliseconds or more, or arrhythmias like a junctional bradycardia bundle branch block, need to be treated with IV ceftriaxone for 21 days and monitored with cardiac telemetry.

Okay, moving on to early disseminated Lyme disease with neurologic involvement! In this case, your patient may report cranial nerve palsies. The classical one is cranial nerve VII, known as the facial nerve, leading to Bell palsy; these patients will report weakness of one or both sides of their face, drooling, and difficulty closing their eyelids. Other neurological symptoms your patient may experience include pain and paresthesia due to radiculoneuritis; or fever, headache, and photophobia indicating meningitis.

Sources

  1. "Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 Guidelines for the Prevention, Diagnosis and Treatment of Lyme Disease" Clin Infect Dis (2021)
  2. "Harrison's Principles of Internal Medicine, 21e" McGraw Hill (2022)
  3. "Updated CDC Recommendation for Serologic Diagnosis of Lyme Disease" MMWR Morb Mortal Wkly Rep (2019)
  4. "Lyme disease: diagnosis and treatment" Curr Opin Rheumatol (2020)