What are the diagnostic criteria and treatment options for Lyme disease?

Diagnosis of Lyme Disease

The diagnosis of Lyme disease is primarily based on clinical findings, with serologic testing providing valuable supportive diagnostic information in patients with endemic exposure and objective clinical findings that indicate later-stage disseminated disease. 1

Diagnostic Approach

Clinical Diagnosis

• Early localized disease (Stage 1):
  • Erythema migrans (EM) is the only manifestation sufficiently distinctive to allow clinical diagnosis without laboratory confirmation 1
  • EM typically appears as an expanding red rash at the site of tick bite, often with central clearing
  • May be accompanied by flu-like symptoms (fever, headache, fatigue, myalgias)
  • Serologic testing is too insensitive in the acute phase (first 2 weeks) to be helpful diagnostically 1

Laboratory Testing

• Two-tiered serologic testing is recommended when clinical presentation is unclear or for later stages:

  1. Initial screening with enzyme-linked immunosorbent assay (ELISA) or indirect fluorescent antibody test
  2. If positive or equivocal, confirmation with Western blot (WB) test 1, 2

• Timing considerations for Western blot interpretation:

  • Samples drawn within 4 weeks of disease onset: Test for both IgM and IgG antibodies
  • Samples drawn more than 4 weeks after onset: Test for IgG only 3

Additional Diagnostic Methods

• Culture of B. burgdorferi:

  • Definitive but limited practical utility due to:
    • Need for special bacteriologic medium
    • Prolonged observation period (mean 3.5 weeks) 4
    • Low sensitivity except in early EM lesions (80% from biopsy specimens) 1

• PCR testing:

  • Can detect B. burgdorferi DNA in skin, blood, CSF, and synovial fluid
  • Not standardized for routine diagnosis 1
  • Skin biopsy PCR can identify additional cases missed by culture and serology 4

Diagnostic Pitfalls to Avoid

1. Relying solely on serologic testing for early disease diagnosis

   • False negatives are common in the first 2 weeks of infection 1, 5

2. Misinterpreting persistent antibodies as active infection

   • Antibodies often persist for months or years after successfully treated or untreated infection 1
   • Seroreactivity alone cannot be used as a marker of active disease

3. Using unvalidated test methods

   • Urine antigen tests or blood microscopy for Borrelia detection are not validated and should not be used 1

4. Routine testing in patients with nonspecific symptoms without objective findings

   • High risk of false-positive results in low-probability patients 3
   • Not recommended for patients with psychiatric illness, developmental disorders, or typical neurological diseases like ALS, MS, or Parkinson's 2

Treatment Approach

Early Localized Disease

• First-line treatments (14 days, range 10-21 days):
  • Doxycycline: 100 mg twice daily (adults); 4 mg/kg/day in 2 divided doses (children ≥8 years)
  • Amoxicillin: 500 mg three times daily (adults); 50 mg/kg/day in 3 divided doses (children)
  • Cefuroxime axetil: 500 mg twice daily (adults); 30 mg/kg/day in 2 divided doses (children) 2

Early Disseminated and Late Disease

• Neurologic Lyme disease (meningitis):

  • IV ceftriaxone: 2g once daily for 14 days (range 10-28 days) 2

• Facial nerve palsy:

  • Without CSF abnormalities: Oral regimen as for erythema migrans
  • With CSF abnormalities: Treatment as for meningitis 2

• Lyme arthritis:

  • Initial: Oral regimens as for early disease
  • Refractory cases: IV ceftriaxone 2g daily for 2-4 weeks 2

Post-Treatment Considerations

• Some patients may experience persistent symptoms after appropriate treatment (Post-Lyme Disease Syndrome)
• These symptoms are not due to persistent infection and do not respond to additional antibiotics 2
• Extended antibiotic courses beyond recommended durations are not supported by evidence 2

By following this evidence-based approach to diagnosis and treatment, clinicians can effectively manage Lyme disease while avoiding unnecessary testing and treatment.