What is the recommended method for diagnosing Lyme disease?

Diagnostic Testing for Lyme Disease

Two-tiered serologic testing (EIA/ELISA followed by Western immunoblot) is the recommended method for diagnosing Lyme disease in patients with suspected disseminated infection, while patients with typical erythema migrans in endemic areas can be diagnosed clinically without laboratory testing. 1

Diagnostic Algorithm Based on Clinical Presentation

1. Patients with Erythema Migrans (EM)

• No laboratory testing required if classic EM is present in an endemic area 1
• EM is defined as a gradually expanding annular lesion >5 cm in diameter
• Occurs in approximately 70-80% of infected individuals
• Treatment can begin immediately based on clinical diagnosis

2. Patients without EM but with Suspected Lyme Disease

• Two-tiered serologic testing is required 1
  • First tier: Enzyme immunoassay (EIA) or immunofluorescent assay (IFA)
  • Second tier: If first tier is positive/equivocal, perform Western immunoblot
    • IgM Western blot: Positive if ≥2 of 3 bands present (21-24,39,41 kDa)
    • IgG Western blot: Positive if ≥5 of 10 bands present (18,21-24,28,30,39,41,45,58,66,93 kDa)

Pretest Probability Assessment

Pretest probability is crucial for proper test interpretation 1:

• High pretest probability:

  • Recent travel to or residence in endemic areas
  • Known tick exposure
  • Compatible clinical symptoms (arthritis, neurologic symptoms, carditis)

• Low pretest probability:

  • No travel to endemic areas
  • No known tick exposure
  • Nonspecific symptoms only

Special Clinical Scenarios

Neurologic Lyme Disease

• For suspected Lyme neuroborreliosis, serum antibody testing is recommended rather than PCR or culture of CSF or serum 1
• For patients with meningitis, painful radiculoneuritis, mononeuropathy multiplex, or acute cranial neuropathies in endemic areas, test for Lyme disease 1
• Do not routinely test for Lyme disease in patients with typical amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, dementia, or new-onset seizures 1

Facial Nerve Palsy

• In endemic areas, Lyme disease can cause up to 25% of facial nerve palsy cases 1
• Test for Lyme disease in patients with facial palsy who live in or have traveled to endemic areas 1

Lyme Arthritis

• Two-tiered serologic testing with IgG antibodies is necessary to confirm Lyme arthritis 2
• Consider geographic exposure, clinical presentation, and history of tick exposure when evaluating for Lyme arthritis 2

Alternative Testing Methods

PCR Testing

• Limited clinical utility due to low sensitivity and risk of contamination 1
• May be useful in specific situations:
  • Synovial fluid PCR: >75% sensitive for Lyme arthritis
  • CSF PCR: Only 38% sensitive for early neuroborreliosis and less for late neuroborreliosis
  • Blood PCR: Not recommended due to low sensitivity

Culture

• Not routinely recommended due to poor sensitivity and labor-intensive methods 1
• Consider only for research purposes or to confirm disease in previously unrecognized endemic areas

Common Pitfalls to Avoid

1. Overinterpreting Western blot bands: Presence of 1 IgM band or <4 IgG bands does not indicate a positive result 1

2. Testing in low-incidence regions: Positive predictive value of testing is only about 10% in non-endemic areas without travel history 1

3. Using unvalidated tests: Alternative tests (urine antigen tests, CD57 tests, home brew tests) lack clinical validation 1

4. Performing Western blot without first-tier EIA: This approach is not recommended for clinical diagnosis 1, 2

5. Misinterpreting persistent antibodies: IgG antibodies can persist for years after treated infection 2

6. Testing in non-specific syndromes: Routine testing is not recommended for patients with:

   • Developmental, behavioral, or psychiatric disorders 1
   • Nonspecific symptoms without epidemiologic support 1
   • Psychiatric illness 1

Testing for Reinfection

For patients with suspected reinfection:

• Detailed history and physical examination are essential
• Most reinfected patients will have EM
• For patients without EM, consider acute and convalescent serologic testing to detect increases in EIA titer or number of antibody bands 1

By following this evidence-based approach to Lyme disease testing, clinicians can ensure accurate diagnosis while avoiding unnecessary testing and potential misdiagnosis.