How to Order Lyme Titer
Order a two-tiered serologic testing approach: start with an enzyme immunoassay (EIA) or immunofluorescence assay (IFA), with reflex Western immunoblot (both IgM and IgG) performed only if the first test is positive or equivocal. 1
When to Order Testing
Test Only in Appropriate Clinical Scenarios
Order testing for patients with acute neurologic manifestations including meningitis, painful radiculoneuritis, mononeuropathy multiplex, acute cranial neuropathies (particularly cranial nerves VII and VIII), or spinal cord inflammation with epidemiologically plausible tick exposure 2
Order testing for patients with acute myocarditis/pericarditis of unknown cause in endemic areas, particularly if presenting with dyspnea, palpitations, chest pain, syncope, or conduction abnormalities 2
Do NOT order testing at the time of a tick bite, as antibodies are unlikely to be detectable and results would be misleading (representing either false-positives or evidence of prior infection, not current infection) 2
Do NOT routinely test patients with typical ALS, relapsing-remitting MS, Parkinson's disease, dementia, new-onset seizures, psychiatric illness, or developmental/behavioral disorders 2
The Specific Test Order
Two-Tiered Testing Protocol
First-tier test:
- Order: "Lyme disease antibody screen by EIA or IFA" 1, 3
- This serves as the screening test with high sensitivity for disseminated disease (88-100%) 1
Second-tier test (reflex only if first test is positive or equivocal):
- Order: "Lyme disease Western immunoblot, IgM and IgG" 1, 3
- Never order Western blot as a standalone test - this dramatically increases false-positive rates 3
Interpretation Criteria
For disease duration <6-8 weeks:
- IgM Western blot is valid and requires ≥2 of 3 specific bands (plus positive/equivocal EIA) 1
- IgG Western blot requires ≥5 of 10 specific bands 1
For disease duration >6-8 weeks:
- Only IgG Western blot is clinically interpretable 1
- IgM results should be disregarded in late disease to avoid false-positives 2
Critical Pitfalls to Avoid
Tests That Should NEVER Be Ordered
Do not order urine antigen tests - these lack validation and are not recommended by any guideline 1, 3
Do not order CD57 tests - these have no role in Lyme disease diagnosis 1, 3
Do not retest after treatment - antibodies persist for months to years after successful treatment and do not indicate active infection 1, 3
Geographic and Pretest Probability Considerations
In non-endemic areas without tick exposure, positive predictive value drops to only 10%, and only 0.7% of patients with arthritis or neuropathy actually have Lyme disease 1, 3
Geographic exposure history is the most crucial factor determining whether to test - even highly specific tests produce false-positives when pretest probability is low 3
Special Circumstances
Erythema Migrans in Endemic Areas
- Do NOT order serologic testing - diagnose clinically without laboratory confirmation 3
- Approximately 70-80% of Lyme disease patients present with erythema migrans 3
- Antibody testing has poor sensitivity (only 30-40%) during early infection due to the window period 3
Neuroborreliosis Suspected
- Order: "CSF analysis with cell count, differential, protein, and Lyme antibody index" 2
- Order concurrent serum sample for comparison 2
- Laboratory confirmation is achieved by demonstrating borrelia-specific intrathecal antibody production 2
Lyme Arthritis Suspected
- Consider: "Synovial fluid or synovial biopsy for Lyme PCR" 2
- Synovial fluid and serum display roughly equivalent antibody titers due to high protein permeability 2