What are the initial steps for testing and diagnosing vasculitis?

Initial Testing and Diagnosis of Vasculitis

The initial steps for testing and diagnosing vasculitis should include ANCA testing (including indirect immunofluorescence and ELISA), tissue biopsy of affected organs, structured clinical assessment, and basic laboratory tests including urinalysis. 1, 2

Diagnostic Algorithm for Suspected Vasculitis

Step 1: Laboratory Testing

• ANCA testing - Perform both indirect immunofluorescence and ELISA

  • Test for both MPO-ANCA and PR3-ANCA using high-quality antigen-specific assays 2
  • PR3-ANCA is highly specific for granulomatosis with polyangiitis (GPA)
  • MPO-ANCA is essential for diagnosing microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA) 2
  • Important caveat: A negative ANCA does not exclude vasculitis, particularly in limited forms of disease 2

• Basic laboratory tests 1, 3:

  • Complete blood count with differential (to assess for anemia, leukocytosis, eosinophilia)
  • Comprehensive metabolic panel (renal and liver function)
  • Inflammatory markers (ESR, CRP)
  • Urinalysis with microscopic examination (crucial for detecting renal involvement)
  • Complement levels (C3, C4)
  • Hepatitis B and C serology (particularly important with liver involvement) 3
  • Cryoglobulins (for suspected cryoglobulinemic vasculitis) 2

Step 2: Tissue Biopsy

• Biopsy of affected tissue is the gold standard for diagnosis 1
  • Target clinically affected tissue for highest diagnostic yield
  • Diagnostic yield of biopsies demonstrating either granuloma or vasculitis is over 70% 1
  • Yield varies according to organ sampled, operator skill, and sampling method
  • For cutaneous vasculitis, biopsy should extend to the subcutis from the most tender, reddish, or purpuric lesional skin 4
  • Consider direct immunofluorescence to distinguish IgA-associated vasculitis from IgG/IgM-associated vasculitis 4

Step 3: Imaging Studies

• Select imaging based on suspected vessel size 2:
  • Large vessels: CT/CTA, MRI/MRA, or FDG-PET/CT
  • Medium vessels: CTA of affected regions (renal, mesenteric, coronary)
  • Small vessels: MRI/MRA or FDG-PET/CT
• Angiography may confirm diagnosis with specific organ involvement
  • Note that angiography may be normal even when vasculitis is present 3

Step 4: Disease Classification and Severity Assessment

• Categorize patients with ANCA-associated vasculitis according to different levels of severity to assist treatment decisions 1
• Consider vessel size affected for classification 5:
  • Large vessels: Takayasu arteritis, giant cell arteritis
  • Medium vessels: Polyarteritis nodosa
  • Small vessels: ANCA-associated vasculitis (GPA, MPA, EGPA), IgA vasculitis (Henoch-Schönlein purpura)

Important Clinical Considerations

1. Referral to expertise: Patients with suspected primary small and medium vessel vasculitis should be managed in collaboration with, or at centers of expertise 1

2. Structured clinical assessment: A comprehensive evaluation of all organ systems is essential as multiorgan involvement is common 1

   • Look specifically for:
     • Skin manifestations (palpable purpura, nodules, ulcers)
     • Respiratory symptoms (hemoptysis, shortness of breath)
     • Renal involvement (hematuria, proteinuria)
     • Neurologic symptoms (mononeuritis multiplex, sensory neuropathy)
     • Constitutional symptoms (fever, weight loss, fatigue)

3. Do not delay treatment while waiting for biopsy results in ANCA-positive patients with compatible clinical presentation, especially in rapidly deteriorating patients 2

4. Serial monitoring of ANCA levels, inflammatory markers, and organ function is useful for assessing disease activity and predicting relapse 2, 3

Pitfalls to Avoid

• Relying solely on ANCA status for diagnosis or treatment decisions 2
• Failing to obtain tissue biopsy when clinically feasible 1, 3
• Not considering vasculitis mimics (thrombotic disorders, infections, malignancies) 4, 6
• Delaying treatment in cases of rapidly progressive disease 2
• Inadequate evaluation for secondary causes of vasculitis (infections, connective tissue diseases, malignancies) 4, 6

By following this structured approach to testing and diagnosis, clinicians can efficiently identify and classify vasculitis, leading to appropriate and timely treatment decisions that will improve patient outcomes.