What is the recommended approach for testing and managing Lyme disease?

Lyme Disease Testing and Management

The recommended approach for Lyme disease testing is a two-tier serological testing strategy, with serum antibody testing as the preferred method over PCR or culture for diagnosis in most clinical scenarios. 1, 2

Diagnostic Approach

Clinical Diagnosis

• Erythema migrans (EM) rash should be diagnosed clinically rather than with laboratory testing 1
• EM characteristics:
  • Often presents as homogeneous or central redness rather than the classic "bull's-eye" appearance 3
  • Develops within days to 1 month after tick bite (median 7-10 days) 4
  • May be accompanied by flu-like symptoms including fatigue, headache, neck stiffness, arthralgia, myalgia, or low-grade fever 3

Laboratory Testing

• Two-tier serological testing is recommended:

  1. Initial screening with enzyme immunoassay (EIA) or immunofluorescence assay (IFA)
  2. If positive or equivocal, confirm with Western blot 1, 2

• For atypical skin lesions: Obtain acute-phase serum sample followed by convalescent-phase sample (2-3 weeks later) if initial result is negative 1

• For suspected neuroborreliosis:

  • Serum antibody testing is preferred over CSF PCR or culture 1
  • If CSF testing is performed, obtain simultaneous CSF and serum samples to determine CSF:serum antibody index 1

When to Test for Lyme Disease

Test for Lyme Disease in:

• Patients with EM rash in endemic areas (clinical diagnosis) 1
• Patients with atypical skin lesions suggestive of EM 1
• Patients with acute neurological disorders including:
  • Meningitis
  • Painful radiculoneuritis
  • Mononeuropathy multiplex
  • Acute cranial neuropathies (especially facial nerve palsy)
  • Spinal cord inflammation with epidemiologically plausible exposure 1

Do Not Test for Lyme Disease in:

• Patients with typical amyotrophic lateral sclerosis, relapsing-remitting multiple sclerosis, Parkinson's disease, dementia, or new-onset seizures 1
• Patients with psychiatric illness 1
• Children with developmental, behavioral, or psychiatric disorders 1
• Patients with nonspecific MRI white matter abnormalities without clinical or epidemiologic support for Lyme disease 1
• Patients with nonspecific symptoms (fatigue, arthralgia) without objective signs of infection 5

Treatment Recommendations

Early Localized Disease (Erythema Migrans)

• First-line oral antibiotics (10-14 days): 1, 2
  • 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)
• Second-line: Azithromycin (if unable to take doxycycline and beta-lactams) 1

Neurologic Manifestations

• For CNS involvement (meningitis, encephalitis): IV antibiotics preferred 1

  • IV ceftriaxone, cefotaxime, or penicillin G for 14-21 days 2

• For isolated facial nerve palsy without CSF abnormalities: Oral antibiotics as for EM 2

• For facial nerve palsy with CSF abnormalities: Treat as meningitis 2

Lyme Arthritis

• Initial treatment with oral antibiotics as for EM 2
• For persistent arthritis:
  • Second course of oral antibiotics for mild residual joint swelling
  • IV ceftriaxone 2g daily for 2-4 weeks for moderate to severe joint swelling with minimal response 2

Post-Treatment Considerations

• Most patients respond promptly to appropriate antibiotic treatment 3
• Prolonged antibiotic therapy beyond recommended durations provides no additional benefit and increases risk of adverse effects 2
• For persistent symptoms without evidence of active infection, consider alternative diagnoses such as fibromyalgia 2

Common Pitfalls to Avoid

1. Overdiagnosis: Avoid testing patients with nonspecific symptoms and low probability of disease 5
2. Overtreatment: Do not prescribe prolonged antibiotics for persistent symptoms without evidence of active infection 2, 6
3. Misdiagnosis: Consider alternative diagnoses in patients with persistent symptoms after appropriate treatment 2
4. Neglecting STARI: In regions where both STARI and Lyme disease are endemic, treat with antibiotics when unable to distinguish between the two 1

By following these evidence-based recommendations, clinicians can effectively diagnose and manage Lyme disease while avoiding unnecessary testing and treatment.