What does an equivocal Lyme antibody test result indicate?

Understanding Equivocal Lyme Antibody Test Results

An equivocal Lyme antibody test result indicates that the test detected some antibodies to Borrelia burgdorferi but at levels insufficient to be considered definitively positive, requiring follow-up testing with Western blot to confirm or rule out Lyme disease. 1

Two-Tiered Testing Approach for Lyme Disease

The diagnosis of Lyme disease follows a standardized two-tiered approach:

1. First-tier screening test: Enzyme-linked immunosorbent assay (ELISA) or indirect fluorescent antibody test (IFA)

   • Results are reported as positive, negative, or equivocal/borderline

2. Second-tier confirmatory test: Western immunoblot (WB) test

   • Only performed when first-tier test is positive or equivocal
   • Helps distinguish true positives from false positives 1, 2

When You Get an Equivocal Result

An equivocal result on the first-tier test requires proceeding to Western blot testing to determine if the antibodies detected are truly specific to Borrelia burgdorferi. The Western blot looks for antibodies against specific Borrelia proteins and follows standardized interpretation criteria:

• IgM Western Blot: Positive if ≥2 of 3 specific bands are present
• IgG Western Blot: Positive if ≥5 of 10 specific bands are present 2

Clinical Significance of Equivocal Results

Equivocal results can occur for several reasons:

• Early infection: Antibody response may be developing but hasn't reached detectable levels
• Prior antibiotic treatment: Early treatment can blunt or prevent antibody response 1
• Cross-reactivity: Antibodies to other pathogens may cause partial reactivity 3
• Past infection: Antibodies may persist for months or years after successful treatment 1

Next Steps After an Equivocal Result

1. Complete the two-tiered testing: Proceed with Western blot testing 1

2. Consider timing of infection:

   • For suspected early Lyme disease (<30 days of symptoms): Both IgM and IgG Western blots should be performed
   • For suspected late Lyme disease (>30 days): Only IgG Western blot should be used as IgM may lead to false positives 2, 4

3. If Western blot is negative but clinical suspicion remains high:

   • Consider serological follow-up testing in 2-3 weeks if symptoms persist
   • Evaluate for alternative diagnoses 1

Important Caveats and Pitfalls

• High false-positive rates with IgM testing: IgM immunoblots have a high frequency of false-positive results (27.5% in one study), which can lead to unnecessary antibiotic treatment 4

• Cross-reactivity issues: Many B. burgdorferi proteins are recognized nonspecifically by antibodies directed against other pathogens (including Treponema pallidum, Epstein-Barr virus, Cytomegalovirus) 3

• Clinical correlation is essential: Serological results must always be interpreted in the context of clinical signs and symptoms 5

• Early treatment effect: Antibiotic treatment in early disease can delay or inhibit antibody response, potentially leading to false-negative results 6

• Geographic considerations: The predictive value of testing depends on the prevalence of Lyme disease in your region 6

When to Treat Without Waiting for Confirmatory Testing

In endemic areas, patients with classic erythema migrans (EM) rash (expanding annular lesion >5 cm) can be diagnosed and treated clinically without laboratory confirmation, as EM is present in 70-80% of Lyme disease cases 2.

Bottom Line

An equivocal Lyme antibody test is neither clearly positive nor negative and requires follow-up testing with Western blot for proper interpretation. Clinical context, including exposure history and symptoms, remains crucial for accurate diagnosis and appropriate management.