What serologic tests are recommended for diagnosing Lyme disease?

Recommended Serologic Tests for Diagnosing Lyme Disease

For diagnosing Lyme disease, a two-tiered serologic testing approach is recommended, consisting of an enzyme-linked immunoassay (EIA/ELISA) or immunofluorescence assay (IFA) as the first tier, followed by a Western immunoblot if the first test is positive or equivocal. 1

Two-Tiered Testing Algorithm

First Tier:

• ELISA or IFA test
• If positive or equivocal → proceed to second tier
• If negative → no further testing needed (unless high clinical suspicion persists)

Second Tier:

• Western immunoblot (WB) test
• For samples drawn within 4 weeks of symptom onset: Test both IgM and IgG
• For samples drawn >4 weeks after symptom onset: Test only IgG 1

Western Blot Interpretation Criteria:

• IgM Western Blot: ≥2 of 3 specific bands (21-24,39,41 kDa)
• IgG Western Blot: ≥5 of 10 specific bands (18,21-24,28,30,39,41,45,58,66,93 kDa) 1

Important Clinical Considerations

When to Test:

• Testing is appropriate for patients with:
  • Objective signs of Lyme disease (e.g., erythema migrans, arthritis, neurologic manifestations)
  • Appropriate exposure history in endemic areas 1
  • Acute disorders such as meningitis, painful radiculoneuritis, mononeuropathy multiplex, or acute cranial neuropathies 2

When NOT to Test:

• Routine testing is NOT recommended for patients with:
  • Typical amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease
  • Dementia or cognitive decline
  • New-onset seizures
  • Psychiatric illness 2, 1
  • Nonspecific symptoms without objective findings 1

Special Situations:

• For patients with classic erythema migrans in an endemic area:
  • Clinical diagnosis is sufficient
  • Treatment can begin immediately without laboratory confirmation 1
• For early localized disease:
  • Antibody response may be blunted or absent
  • Consider convalescent-phase serum collection 2-3 weeks after acute-phase sample if needed 2

Caveats and Pitfalls

1. Pretest Probability Matters: The value of Lyme testing depends heavily on pretest probability based on exposure history and clinical presentation. Testing in low-incidence regions or patients without travel to endemic areas has little diagnostic value. 1

2. Avoid Unvalidated Tests: Do not use unvalidated "alternative" laboratory tests that are not FDA-cleared, as they often report high false-positive rates (up to 58% in healthy controls). 1

3. Persistent Antibodies: Antibodies often persist for months or years after successfully treated or untreated infection. Thus, seroreactivity alone cannot be used as a marker of active disease. 2

4. Cross-Reactivity: Two-tiered testing helps reduce cross-reactivity with other spirochetal infections, but clinical data may still be needed to differentiate Lyme disease from other conditions. 1

5. PCR and Culture Limitations: While B. burgdorferi can be cultured from early erythema migrans lesions, this has limited diagnostic usefulness due to specialized media requirements. PCR has not been standardized for routine diagnosis of Lyme disease. 2

By following this evidence-based testing approach, clinicians can accurately diagnose Lyme disease while avoiding unnecessary testing and potential misdiagnosis.