Laboratory Testing Indications and Treatment for Lyme Disease
Laboratory testing for Lyme disease should only be performed when there is a moderate pretest probability (20-80%) of disease, with testing specifically indicated for patients in endemic areas or with travel history to endemic areas who present with symptoms consistent with disseminated Lyme disease but without erythema migrans. 1, 2
Diagnostic Testing Indications
When Testing is NOT Indicated
- Patients with classic erythema migrans (EM) rash in endemic areas should be treated empirically without laboratory testing 2
- Routine laboratory testing for Bell's palsy is not recommended unless the patient is from or has traveled to a Lyme-endemic area 1
- Testing in low-risk populations (pretest probability <20%) leads to more false positives than true positives 3
When Testing IS Indicated
Endemic area exposure with:
- Symptoms of disseminated Lyme disease without EM
- Neurological symptoms (meningitis, facial palsy in endemic areas)
- Cardiac involvement (heart block, myocarditis)
- Arthritis, particularly recurrent large-joint arthritis
Specific testing indications for Bell's palsy:
- Patient lives in or has traveled to a Lyme-endemic area
- In endemic areas, Lyme disease can cause up to 25% of facial paralysis cases 1
Recommended Testing Approach
Two-Tiered Testing Algorithm
- First tier: Enzyme-linked immunoassay (EIA/ELISA) or immunofluorescence assay (IFA)
- Second tier: If first tier is positive or equivocal, confirm with Western immunoblot
Interpretation Criteria
- Positive IgM Western blot: ≥2 of 3 specific bands (21-24,39, and 41 kDa)
- Positive IgG Western blot: ≥5 of 10 specific bands 2
Testing Limitations
- Low sensitivity (30-40%) during early infection (window period)
- High specificity (>95%) during all stages of disease
- Antibodies persist for months/years after successful treatment 1, 2
Treatment Recommendations
Early Localized Disease (EM rash)
- First-line: Doxycycline 100 mg orally twice daily for 14-21 days 2
- Alternatives:
- Amoxicillin 500 mg orally three times daily for 14-21 days
- Cefuroxime axetil 500 mg orally twice daily for 14-21 days 2
Early Disseminated Disease
- Facial palsy without other neurologic involvement: Oral regimens as above 2, 4
- Meningitis, radiculopathy, or other neurologic manifestations: IV ceftriaxone 2 g daily for 14-28 days 2
- Cardiac involvement:
- Hospitalization and IV antibiotics for symptomatic patients or those with advanced heart block
- Transition to oral therapy after clinical improvement 2
Late Disease (Arthritis)
- Oral regimens as above for 28 days
- Consider IV ceftriaxone for persistent symptoms 2
Special Populations
- Pregnant/lactating patients: Avoid doxycycline; use amoxicillin or cefuroxime 2
- Children <8 years: Avoid doxycycline; use amoxicillin 50 mg/kg/day in 3 divided doses (max 500 mg per dose) 2
Common Pitfalls to Avoid
Testing without appropriate pretest probability:
Misinterpreting persistent antibodies:
- Antibodies can persist for months/years after successful treatment
- Positive serology alone does not indicate active infection 2
Overlooking coinfections:
- Consider testing for Babesia microti or Anaplasma phagocytophilum with:
- Severe initial symptoms
- High-grade fever persisting >48 hours despite therapy
- Unexplained cytopenias 2
- Consider testing for Babesia microti or Anaplasma phagocytophilum with:
Prolonged antibiotic courses:
- Extended treatment for non-specific symptoms is not supported by evidence
- May lead to unnecessary side effects 2
Relying on PCR or culture alone:
- PCR has limited sensitivity for blood and CSF
- Culture is labor-intensive with poor sensitivity 1
By following these evidence-based guidelines for laboratory testing and treatment, clinicians can optimize outcomes while avoiding unnecessary testing and treatment for patients with suspected Lyme disease.