When should I get tested for Lyme disease?

When to Get Tested for Lyme Disease

Testing for Lyme disease should be performed when there are clinical symptoms and epidemiologic exposure to ticks, not as a routine screening test, with the two-tier testing approach recommended for accurate diagnosis. 1

Appropriate Timing for Lyme Disease Testing

Early Localized Disease (0-30 days)

• Clinical diagnosis is preferred over testing in patients with erythema migrans (EM) rash in endemic areas
• EM is sufficiently distinctive to allow clinical diagnosis without laboratory confirmation 1
• Testing during this phase often yields false negatives due to the delayed antibody response (typically negative in first 3 weeks) 2

Early Disseminated Disease (days to weeks after infection)

• Testing recommended when patients present with:
  • Multiple/secondary erythema migrans lesions
  • Neurologic manifestations (meningitis, cranial neuropathy, radiculoneuritis) 1
  • Cardiac symptoms (palpitations, lightheadedness, chest pain, syncope) 3
  • Joint and muscle pain with objective signs of swelling

Late Disseminated Disease (weeks to months after infection)

• Testing strongly recommended for:
  • Intermittent joint swelling/pain (especially large weight-bearing joints)
  • Chronic neurological symptoms
  • Persistent symptoms with history of tick exposure in endemic areas

Recommended Testing Approach

Two-Tier Testing Protocol

1. First tier: Enzyme-linked immunosorbent assay (ELISA) or indirect fluorescent antibody test
2. Second tier: Western immunoblot (WB) test to confirm positive or equivocal first-tier results 1

Timing-Specific Testing Recommendations

• Within first 4 weeks of symptoms: Perform both IgM and IgG Western blot if first-tier test is positive 1
• After 4 weeks of symptoms: Only IgG Western blot should be used, as IgM becomes unreliable (high false-positive rate) 1

When NOT to Test for Lyme Disease

• Asymptomatic individuals without known tick exposure
• Non-specific symptoms without objective signs in low-risk areas 4
• Patients with typical:
  • Amyotrophic lateral sclerosis
  • Relapsing-remitting multiple sclerosis
  • Parkinson's disease
  • Dementia or cognitive decline
  • New-onset seizures 1
• Children with developmental, behavioral, or psychiatric disorders 1
• Patients with psychiatric illness as the primary presentation 1
• Chronic cardiomyopathy of unknown cause 1

Special Testing Considerations

Specimen Selection

• Serum is the preferred specimen for antibody testing
• PCR of synovial fluid/tissue may be helpful in seropositive patients with suspected Lyme arthritis 1
• Skin biopsy is not generally recommended for routine diagnosis 1

Interpretation Pitfalls

• Antibodies often persist for months or years after successful treatment, so seroreactivity alone cannot be used as a marker of active disease 1
• Early antibiotic treatment can blunt or prevent antibody response 1
• False-positive results are common in low-probability scenarios 4

Testing in Suspected Post-Treatment Lyme Disease Syndrome

• Additional testing is not recommended for patients with persistent non-specific symptoms (fatigue, pain, cognitive issues) after standard treatment without objective evidence of reinfection or treatment failure 1, 5
• Persistent symptoms may be due to non-infectious processes that are no longer antibiotic-sensitive 6

By following these evidence-based guidelines for Lyme disease testing, clinicians can avoid unnecessary testing while ensuring appropriate diagnosis and treatment for those with true Lyme disease, ultimately improving patient outcomes related to morbidity, mortality, and quality of life.