What is the initial step in diagnosing and treating Lyme disease?

Diagnostic Approach for Lyme Disease

The initial step in diagnosing Lyme disease is two-tiered serologic testing consisting of an enzyme-linked immunoassay (EIA/ELISA) or immunofluorescence assay (IFA) followed by a Western immunoblot if the first test is positive or equivocal, except in cases of classic erythema migrans in endemic areas where clinical diagnosis is sufficient to begin immediate treatment. 1

Clinical Diagnosis of Early Lyme Disease

• Patients with classic erythema migrans (EM) in an endemic area can be diagnosed clinically without laboratory testing, and treatment should begin immediately 1
• EM characteristics:
  • Expanding annular skin lesion (mean diameter 16 cm, range 6-73 cm)
  • Often appears at the site of a tick bite (noted in only 25% of cases)
  • May be accompanied by systemic symptoms including fatigue (54%), arthralgia (44%), myalgia (44%), headache (42%), fever/chills (39%), and stiff neck (35%) 2

Laboratory Testing Approach

Two-Tiered Testing Algorithm

1. First tier: EIA or IFA
2. Second tier: Western immunoblot if first tier is positive or equivocal
   • For samples drawn within 4 weeks of symptom onset: Test both IgM and IgG
   • For samples drawn >4 weeks after symptom onset: Test only IgG 1

Interpretation Criteria for Western Blot

• IgM Western Blot: ≥2 of 3 specific bands (21-24,39,41 kDa)
• IgG Western Blot: ≥5 of 10 specific bands (18,21-24,28,30,39,41,45,58,66,93 kDa) 1

Treatment Considerations

• Treatment should be initiated immediately upon clinical diagnosis of erythema migrans without waiting for laboratory confirmation 1
• For patients with Lyme arthritis, oral antibiotic therapy for 28 days is recommended 3
• For patients with Lyme disease-associated parenchymal involvement of the brain or spinal cord, intravenous antibiotics are recommended over oral antibiotics 3

Important Caveats and Pitfalls

Avoid Unvalidated Testing

• Use only FDA-cleared two-tiered testing methods
• Avoid unvalidated "alternative" laboratory tests that are not FDA-cleared, as they often report false-positive rates as high as 58% in healthy controls 1

Consider Pretest Probability

• Testing has limited value in low-incidence regions or patients without travel to endemic areas
• Limit testing to patients with objective signs of Lyme disease and appropriate exposure history 1

Avoid Unnecessary Testing

• Routine testing for Lyme disease is not recommended for patients with:
  • Typical amyotrophic lateral sclerosis
  • Multiple sclerosis
  • Parkinson's disease
  • Dementia
  • New-onset seizures
  • Psychiatric illness 3, 1

Post-Treatment Considerations

• For patients with persistent or recurring nonspecific symptoms following recommended treatment for Lyme disease, additional antibiotic therapy is not recommended 3
• There is no convincing biological evidence for the existence of symptomatic chronic B. burgdorferi infection after appropriate treatment 3

Special Clinical Scenarios

• Lyme carditis: ECG should only be performed in patients with signs or symptoms consistent with Lyme carditis (dyspnea, edema, palpitations, lightheadedness, chest pain, syncope) 3
• Neurologic manifestations: Testing is recommended for patients with facial palsy who live in or have traveled to endemic areas 1
• Lyme arthritis: All patients should be seropositive by two-tier testing that includes an ELISA and IgG immunoblot; PCR testing of synovial fluid can add increased diagnostic certainty in seropositive patients 1

By following this diagnostic approach, clinicians can accurately diagnose Lyme disease and initiate appropriate treatment to prevent progression to more severe manifestations of the disease.