What are the diagnostic criteria and treatment options for Lyme disease?

Lyme Disease Diagnosis and Treatment

Erythema migrans is the only manifestation of Lyme disease that is sufficiently distinctive to allow clinical diagnosis without laboratory confirmation, and patients with this presentation should be treated with oral antibiotics immediately without waiting for serologic testing results. 1

Diagnostic Criteria

Clinical Diagnosis

• Erythema migrans (EM): The hallmark presentation and most reliable diagnostic feature

  • Typically appears 3-30 days after tick bite
  • Usually >5 cm in diameter
  • May have homogeneous appearance or central clearing with target-like appearance
  • Often occurs at unusual sites for bacterial cellulitis (axilla, popliteal fossa, abdomen)
  • Not typically pruritic or scaly unless fading or treated with topical steroids 1
  • May have vesicles or pustules at center in ~5% of cases 1

• Differentiating from tick bite hypersensitivity reaction:

  • Hypersensitivity reactions are usually <5 cm and disappear within 24-48 hours
  • True EM increases in size over time
  • Marking borders with ink and observing for 1-2 days can help differentiate 1

Laboratory Testing

• For typical EM in endemic areas: No laboratory testing needed; diagnosis is clinical 1
• For atypical presentations or extracutaneous manifestations: Two-tiered serologic testing recommended
  1. Initial screening with ELISA or indirect fluorescent antibody test
  2. If positive/equivocal, confirmation with Western blot 2
• Timing considerations:
  • Serologic testing is insensitive in early disease (first 2 weeks) 1
  • If initial testing is negative but suspicion remains high, repeat testing 2-3 weeks later 1

Treatment Options

Early Localized Disease (Erythema Migrans)

• First-line treatments (strong recommendation, moderate-quality evidence) 1, 2:

  • Doxycycline: 100 mg twice daily for 10 days (adults)
  • Amoxicillin: 500 mg three times daily for 14 days (adults)
  • Cefuroxime axetil: 500 mg twice daily for 14 days (adults)

• Pediatric dosing:

  • Amoxicillin: 50 mg/kg/day in 3 divided doses (max 500 mg per dose)
  • Cefuroxime axetil: 30 mg/kg/day in 2 divided doses (max 500 mg per dose)
  • Doxycycline: 4.4 mg/kg/day in 2 divided doses (max 100 mg per dose) for children ≥8 years 2

• Second-line treatment:

  • Azithromycin: 5-10 days (7-day course preferred in the US) 1

Early Disseminated Disease

• Neurologic involvement:

  • Meningitis or radiculopathy: IV ceftriaxone 2g daily for 14 days (range 10-28 days)
  • Facial nerve palsy without CSF abnormalities: Oral regimen as for EM for 14 days
  • Facial nerve palsy with CSF abnormalities: Treatment as for meningitis 2

• Cardiac involvement:

  • Mild (1st-degree AV block): Oral regimen as for EM
  • Advanced heart block: Initial IV therapy, then complete course with oral antibiotics

Late Disease (Arthritis)

• Initial treatment: Same oral regimens as for EM but for 28 days
• For arthritis that fails to improve: IV ceftriaxone 2g daily for 2-4 weeks 2

Post-Exposure Prophylaxis

• Recommended only for high-risk tick bites meeting ALL criteria:

  1. Identified Ixodes spp. vector tick
  2. Tick attached for ≥36 hours
  3. Prophylaxis can be started within 72 hours of tick removal
  4. Local infection rate of ticks with B. burgdorferi ≥20% (parts of New England, mid-Atlantic states, Minnesota, Wisconsin) 1

• Prophylactic regimen: Single dose of doxycycline

  • Adults: 200 mg
  • Children ≥8 years: 4.4 mg/kg (maximum 200 mg) 1

Common Pitfalls to Avoid

1. Relying on serologic testing for early disease diagnosis

   • Antibody tests are often negative in the first 2 weeks 1
   • Treat EM based on clinical appearance without waiting for test results

2. Misinterpreting persistent symptoms

   • Post-Lyme Disease Syndrome does not respond to additional antibiotic therapy 2
   • Extended antibiotic courses beyond recommended durations are not supported by evidence

3. Inappropriate prophylaxis

   • Only provide prophylaxis for truly high-risk tick bites meeting all criteria
   • "Wait and watch" for low or equivocal risk bites 1

4. Confusing STARI with Lyme disease

   • Southern Tick-Associated Rash Illness (from lone star tick) can mimic EM
   • In areas endemic for both, treat as Lyme disease if distinction cannot be made 1

5. Using first-generation cephalosporins

   • These are ineffective against Borrelia burgdorferi 2

The clinical diagnosis and prompt treatment of Lyme disease are crucial for preventing progression to later stages with more severe complications. When erythema migrans is present in a patient with potential tick exposure in an endemic area, immediate treatment should be initiated without waiting for laboratory confirmation.