Laboratory Testing for Lyme Disease
The recommended laboratory test for Lyme disease is two-tiered serologic testing: an initial enzyme immunoassay (EIA/ELISA) or immunofluorescence assay (IFA), followed by reflex Western immunoblot (both IgM and IgG) only if the first test is positive or equivocal. 1, 2
When to Order Testing
Do not order laboratory testing if the patient has erythema migrans (EM) in a Lyme-endemic area—this is a clinical diagnosis. 1 Approximately 70-80% of Lyme disease patients present with EM, defined as a gradually expanding annular lesion >5 cm in diameter. 1
Order testing for patients without EM who have:
- Acute neurologic manifestations (meningitis, cranial neuropathies, radiculoneuritis) with plausible tick exposure 2
- Cardiac manifestations (myocarditis, pericarditis, conduction abnormalities) in endemic areas 2
- Large-joint arthritis suggestive of late disseminated disease 1
Understanding Test Performance
The sensitivity of two-tiered testing varies dramatically by disease stage:
- Early localized disease: 30-40% sensitive (due to the antibody window period) 1
- Disseminated disease: 70-100% sensitive 1
- Specificity: >95% across all stages 1
For cardiovascular manifestations specifically, the two-tiered approach has 88-100% sensitivity for disseminated disease manifestations including carditis. 2
Interpreting Western Immunoblot Results
Disease duration determines which immunoglobulin class is interpretable:
- Disease duration <6-8 weeks: IgM Western blot is valid and requires ≥2 of 3 specific bands 2
- Disease duration >6-8 weeks: Only IgG Western blot is clinically interpretable, requiring ≥5 of 10 specific bands 2
This timing distinction is critical because IgM false positives are common in later disease stages. 2
Geographic Considerations and Pretest Probability
Testing has minimal diagnostic value in non-endemic areas without travel history to endemic regions (Northeast and Upper Midwest United States). 1 A retrospective study in North Carolina (low-incidence state) showed only 10% positive predictive value for patients without recent travel to endemic areas, and only 0.7% of patients with arthritis or neuropathy actually had Lyme disease. 1
Even in patients with cardiovascular disease presenting with cardiac symptoms, geographic exposure history remains the most crucial factor governing pretest probability. 1
Critical Pitfalls to Avoid
Never order urine antigen tests or CD57 tests for Lyme disease—these lack validation and are not recommended by any guideline. 2
Never retest after treatment completion. Antibodies persist for months to years after successful treatment and do not indicate active infection. 2
Do not test at the time of tick bite. Antibodies are unlikely to be detectable and results would be misleading. 2
Do not order single-tier testing (Western blot alone without initial EIA). The two-tiered approach is essential to maximize specificity. 1
Initial testing may be negative in early cardiac Lyme disease. 3 If clinical suspicion remains high based on exposure history, EM rash, and cardiac manifestations, repeat testing in 4-6 weeks is recommended, as the antibody response may still be developing. 3
Additional Testing for Cardiac Lyme Disease
For patients with suspected Lyme carditis (particularly those with conduction abnormalities like AV block):
- Obtain 12-lead ECG to document conduction abnormalities 4, 5
- Check troponin levels (may be elevated in myopericardial involvement) 3
- Echocardiography to assess for myocardial or pericardial involvement 5
Endomyocardial biopsy can support the diagnosis in severe cases but is rarely necessary, as most Lyme carditis responds to antibiotic therapy without invasive procedures. 6, 5