When do you treat a positive Lyme (Lyme disease) immunoassay?

Treatment of Positive Lyme Immunoassay

A positive Lyme immunoassay should only be treated when it is confirmed by a Western blot as part of the two-tiered testing approach AND the patient has clinical manifestations consistent with Lyme disease. 1

Diagnostic Algorithm for Lyme Disease

Two-Tiered Testing Approach

1. First-tier screening test: ELISA or indirect fluorescent antibody test
2. Second-tier confirmatory test: Western blot (IgM and IgG)
   • For IgM Western blot: ≥2 of 3 specific bands (21-24,39, and 41 kDa) must be present
   • For IgG Western blot: ≥5 of 10 specific bands must be present

Clinical Correlation

The decision to treat depends on both laboratory findings and clinical presentation:

• Treat immediately without waiting for serology results if:

  • Patient presents with erythema migrans (EM) rash in an endemic area 1
  • EM is pathognomonic and sufficient for diagnosis without laboratory confirmation 2

• Treat with positive two-tiered testing (positive ELISA + positive Western blot) if:

  • Patient has symptoms consistent with early disseminated or late Lyme disease 1
  • Clinical manifestations include neurologic, cardiac, or musculoskeletal involvement 2

• Do NOT treat if:

  • Only the first-tier test is positive with negative Western blot 1
  • Patient has nonspecific symptoms without objective findings of Lyme disease 1
  • Patient is in a non-endemic area with low pretest probability 2

Important Considerations

Pretest Probability

The decision to test and treat should consider the patient's pretest probability based on:

• Geographic exposure in endemic areas
• Season of potential exposure
• Known tick bite or outdoor activities in tick habitats
• Presence of characteristic symptoms

In low-incidence regions, positive predictive value of serologic testing may be as low as 10% without recent travel to endemic areas 2.

Timing of Testing

• Antibodies may be absent in up to 50% of patients with early Lyme disease at initial presentation 3
• Most patients will become seropositive within the first month of illness, even with treatment 3
• Consider follow-up testing only if symptoms consistent with Lyme disease develop after initial negative testing 1

Common Pitfalls to Avoid

1. Overinterpreting positive screening tests: A positive ELISA alone without Western blot confirmation has poor specificity and should not guide treatment decisions 1

2. Treating based on serology alone: Serologic testing should support clinically suspected cases, not replace clinical judgment 1

3. Confusing antibody persistence with active infection: Antibodies can persist for months to years after successful treatment and do not indicate ongoing infection 1, 2

4. Prolonged antibiotic courses: Extended antibiotic treatment for non-specific symptoms is not supported by evidence and may lead to unnecessary side effects 1

5. Ignoring geographic context: In non-endemic areas, even clinical signs considered consistent with Lyme disease have poor predictive value 2

Treatment Recommendations

When treatment is indicated based on clinical presentation and confirmed serology:

• Early localized or early disseminated disease:

  • Doxycycline 100 mg orally twice daily for 10-21 days 1
  • Alternatives: amoxicillin or cefuroxime

• Late disseminated disease:

  • Lyme arthritis: Oral antibiotics for 28 days
  • Neurologic Lyme disease: IV ceftriaxone for 14-28 days
  • Lyme carditis: IV antibiotics initially, then transition to oral therapy 1

Most patients with early Lyme disease respond promptly to appropriate antibiotic therapy, with clinical improvement typically evident within 48 hours 1, 4.