What is the test for Lyme disease?

Diagnostic Testing for Lyme Disease

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

Clinical Presentation and Testing Approach

• Erythema migrans (EM) rash: Patients with classic EM in an endemic area can be diagnosed clinically without laboratory confirmation

  • EM is defined as a gradually expanding annular lesion >5 cm in diameter
  • Approximately 70-80% of persons with Lyme disease have EM 2
  • Treatment can begin immediately without waiting for test results 1

• For patients without EM: Laboratory testing is necessary to confirm the diagnosis

  • Testing is most valuable for patients with:
    • Objective signs of Lyme disease (arthritis, neurologic manifestations)
    • Appropriate exposure history in endemic areas
    • Intermediate pretest probability

Two-Tiered Testing Algorithm

First Tier

• EIA or IFA that detects antibodies against Borrelia burgdorferi
• If positive or equivocal, proceed to second tier

Second Tier

• Western immunoblot (separate IgM and IgG tests)
• 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

Test Performance

• Sensitivity:
  • Early localized disease: 30-40% (window period while antibody response develops)
  • Early disseminated disease: 70-100%
  • Late disseminated disease: Nearly 100% 2
• Specificity: >95% across all stages 1

Timing Considerations

• IgM response appears first (within 1-2 weeks of infection)
• IgG response follows IgM (develops 2-4 weeks after infection)
• For early Lyme disease (<30 days of symptoms):
  • Both IgM and IgG Western blots should be performed
  • Consider acute and convalescent testing (2-3 weeks apart) if initial results are negative 2, 1
• For late Lyme disease (>30 days of symptoms):
  • Only IgG Western blot should be used (IgM may lead to false positives) 2

Novel Testing Approaches

Recent developments include:

1. Two-EIA approach: Replacing Western blot with a second EIA test

   • First EIA: Whole-cell sonicate EIA
   • Second EIA: C6 peptide EIA
   • Provides higher sensitivity for early Lyme disease (61% vs. 48%) with equivalent specificity (99.5%) compared to standard two-tiered testing 2, 3

2. Multiplex immunoassay: Measures VlsE1-IgG and pepC10-IgM antibodies simultaneously

   • 20.7% more sensitive for early-convalescent-phase disease than Western blotting
   • Equally specific (95.6%) 4

Common Pitfalls and Caveats

• False negatives in early disease due to window period before antibody development

  • Consider convalescent testing if clinical suspicion is high

• Persistent antibodies after successful treatment

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

• Low value of testing in low-probability scenarios

  • Testing patients with nonspecific symptoms in non-endemic areas has poor predictive value
  • Routine testing is not recommended for typical amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, dementia, new-onset seizures, or psychiatric illness 1

• Avoid unvalidated "alternative" tests

  • Use only FDA-cleared diagnostic tests
  • Alternative laboratory tests often report false-positive rates as high as 58% in healthy controls 1
  • Alternative immunoblot interpretive criteria demonstrate significantly more false-positive results (12.4-35.0%) compared to CDC criteria (1.0%) 5

The diagnostic approach should be guided by clinical presentation, exposure history, and timing of symptoms to maximize the accuracy of test results and ensure appropriate treatment.