What is the recommended testing approach for diagnosing Lyme disease?

Recommended Testing Approach for Lyme Disease

The recommended diagnostic approach for Lyme disease is a two-tiered serologic testing algorithm consisting of an enzyme-linked immunoassay (EIA/ELISA) followed by a Western immunoblot if the first test is positive or equivocal. 1

Testing Strategy Based on Clinical Presentation

Patients with Erythema Migrans (EM)

• For patients with classic erythema migrans in an endemic area:
  • Clinical diagnosis is sufficient
  • Treatment can begin immediately without laboratory confirmation
  • No testing required 1

Patients without EM but with Suspected Early Lyme Disease

• Two-tiered serologic testing is recommended:
  • First tier: EIA/ELISA
  • Second tier: Western immunoblot (if first test is positive/equivocal)
• For samples drawn within 4 weeks of symptom onset:
  • Test both IgM and IgG antibodies
• For samples drawn >4 weeks after symptom onset:
  • Test only IgG antibodies 1

Interpretation of Western Blot Results

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

Importance of Pretest Probability

The value of Lyme disease testing depends heavily on pretest probability, which is determined by:

1. Exposure history - Critical factor in determining likelihood of infection
2. Geographic location - Endemic areas vs. non-endemic areas
3. Clinical presentation - Objective signs consistent with Lyme disease 2

Testing Recommendations Based on Pretest Probability:

• High pretest probability: Results unlikely to change management (treat empirically)
• Intermediate pretest probability: True positive more likely than false positive
• Low pretest probability: False positive more likely than true positive 2

Special Testing Situations

Lyme Arthritis

• PCR testing of synovial fluid has >75% sensitivity
• Can provide increased diagnostic certainty in seropositive patients 1

Suspected Reinfection

• Detailed history and physical examination are essential
• Most patients will have EM
• For patients without EM:
  • Serologic testing is still recommended but interpret with caution
  • Consider acute and convalescent-phase serologic testing to detect increases in EIA titer or antibody bands 2

Neurologic Lyme Disease

• CSF analysis may be helpful
• Compare spinal fluid to blood serologies to demonstrate specific antibody production in CSF 3

Common Pitfalls to Avoid

1. Testing patients with low pretest probability

   • Positive results have little diagnostic value in non-endemic areas or patients without travel to endemic regions 2
   • Even clinical signs considered consistent with Lyme disease have poor predictive value in low-incidence regions 1

2. Misinterpreting persistent antibodies

   • Antibodies often persist for months or years after successfully treated infection
   • Seroreactivity alone cannot be used as a marker of active disease 1

3. Using unvalidated "alternative" laboratory tests

   • Avoid tests that are not FDA-cleared
   • Alternative tests often report false-positive rates as high as 58% in healthy controls 1

4. Relying on IgM Western blot beyond 4 weeks

   • After 4 weeks, only IgG Western blot should be used for diagnosis 1

5. Failure to recognize EM rash

   • Diagnosis of EM is often missed (23% in one study)
   • EM is sufficient for diagnosis and immediate treatment without laboratory confirmation 4

By following this evidence-based approach to Lyme disease testing, clinicians can improve diagnostic accuracy and ensure appropriate treatment, ultimately reducing morbidity associated with both untreated Lyme disease and unnecessary antibiotic exposure.