What are the best tests for diagnosing Lyme disease and vasculitis?

Best Diagnostic Tests for Lyme Disease and Vasculitis

For Lyme disease, the recommended diagnostic approach is a two-tiered serologic testing algorithm 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. 1, 2

Lyme Disease Diagnostic Testing

Standard Two-Tiered Testing (STT)

• First tier: EIA or IFA
• Second tier: Western immunoblot (WB)
  • For samples drawn within 4 weeks of symptom onset: Test both IgM and IgG
  • For samples drawn >4 weeks after symptom onset: Test IgG only

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) 2

Performance Characteristics:

• Sensitivity: Varies by disease stage
  • Early localized disease: 30-40% (poor sensitivity during window period)
  • Disseminated Lyme disease: 70-100%
• Specificity: >95% across all stages 1

Important Clinical Considerations:

1. Patients with classic erythema migrans (EM) in an endemic area can be diagnosed clinically without laboratory testing 2
2. Testing should be limited to patients with objective signs of Lyme disease and appropriate exposure history 2
3. Pretest probability based on exposure history and clinical presentation significantly affects test value 2

Emerging Alternative: Modified Two-Tiered Testing (MTT)

Recent research supports a modified two-tiered approach using two EIAs:

• First tier: Whole-cell sonicate EIA
• Second tier: C6 EIA

This approach shows improved sensitivity for early Lyme disease (61% vs 48% for STT) while maintaining high specificity (99.5%) 3, 4

Caution Regarding Alternative Testing

• Avoid unvalidated "alternative" laboratory tests that are not FDA-cleared 1, 2
• Alternative labs often report false-positive rates as high as 58% in healthy controls 1
• Only use FDA-cleared diagnostic tests to avoid misdiagnosis and inappropriate treatment 1, 2

Vasculitis Diagnostic Testing

For vasculitis, diagnostic testing must be tailored to the specific type of vasculitis suspected, as there is no single definitive test. The diagnostic approach typically includes:

1. Laboratory tests:

   • Complete blood count (CBC)
   • Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)
   • Antineutrophil cytoplasmic antibodies (ANCA)
   • Complement levels
   • Rheumatoid factor and anti-CCP antibodies
   • Hepatitis B and C serologies

2. Imaging studies:

   • Angiography (conventional, CT, or MR) for large and medium vessel vasculitis
   • Chest X-ray and high-resolution CT for pulmonary involvement

3. Tissue biopsy: The gold standard for definitive diagnosis of most vasculitis types

   • Target affected tissue (skin, kidney, lung, temporal artery, etc.)
   • Provides histopathological confirmation and helps classify the type of vasculitis

Type-Specific Testing:

• Large vessel vasculitis (Giant cell arteritis, Takayasu arteritis):

  • Temporal artery biopsy (for GCA)
  • Vascular imaging (CT angiography, MR angiography)

• Medium vessel vasculitis (Polyarteritis nodosa, Kawasaki disease):

  • Angiography
  • Tissue biopsy from affected organ

• Small vessel vasculitis (ANCA-associated, immune complex):

  • ANCA testing (PR3-ANCA and MPO-ANCA)
  • Kidney biopsy (if renal involvement)
  • Skin biopsy (if cutaneous manifestations)

Clinical Pitfalls to Avoid:

1. Relying solely on laboratory markers without clinical correlation
2. Delaying biopsy in suspected giant cell arteritis
3. Failing to consider vasculitis mimics (infections, malignancies, drug reactions)
4. Not obtaining adequate tissue samples for histopathological examination

By following these evidence-based diagnostic approaches, clinicians can accurately diagnose Lyme disease and vasculitis, leading to appropriate treatment and improved patient outcomes.