What is the appropriate workup for vasculitis?

Comprehensive Workup for Vasculitis

The appropriate workup for vasculitis requires ANCA testing, tissue biopsy, comprehensive laboratory evaluation, and imaging studies tailored to the suspected vessel size involvement, with management at centers of expertise. 1

Initial Assessment

Clinical Evaluation

• Structured clinical examination using validated assessment tools such as Birmingham Vasculitis Activity Score (BVAS) 2, 1
• Categorize patients according to disease severity to guide treatment decisions 2
• Assess for specific organ involvement:
  • Renal: hematuria, proteinuria, elevated creatinine
  • Pulmonary: hemoptysis, infiltrates
  • Skin: palpable purpura, ulcers, livedo reticularis
  • Constitutional: fever, weight loss, fatigue

Essential Laboratory Tests

1. Complete Blood Count with differential 1

   • Look for anemia, leukocytosis, eosinophilia (particularly important in Churg-Strauss syndrome)

2. Inflammatory Markers 1

   • Erythrocyte sedimentation rate (ESR)
   • C-reactive protein (CRP)

3. Renal Function Tests 1

   • Serum creatinine and estimated GFR
   • Urinalysis with microscopic examination (critical for detecting hematuria, red cell casts)
   • Quantification of proteinuria

4. Autoantibody Testing 2, 1

   • ANCA panel with immunofluorescence and ELISA for PR3/MPO (critical for ANCA-associated vasculitis)
   • Anti-nuclear antibodies (ANA)
   • Anti-glomerular basement membrane antibodies
   • Cryoglobulins

5. Complement Levels 1

   • C3 and C4 (low in immune complex vasculitis)

6. Viral Serology 1

   • Hepatitis B and C testing (essential, especially with liver involvement)
   • HIV testing

7. Immunoglobulin Levels 2, 1, 3

   • Particularly important before rituximab therapy
   • Monitor for hypoimmunoglobulinemia in patients on immunosuppressive therapy

Diagnostic Confirmation

Biopsy

• Gold standard for diagnosis 1
• Obtain tissue from the most clinically involved accessible site 1
• For temporal artery biopsy in suspected GCA, biopsy length should be at least 1 cm 1
• Do not delay treatment while awaiting biopsy results in rapidly progressive disease 1
• Perform direct immunofluorescence to distinguish IgA-associated vasculitis from IgG/IgM-associated vasculitis 4

Imaging Studies

• Selection based on suspected vessel size involvement 1
• For large vessel vasculitis (GCA, Takayasu):
  • CT/CTA, MRI/MRA, or FDG-PET/CT
• For medium vessel vasculitis:
  • CTA of affected regions (renal, mesenteric, coronary)
• For ANCA-associated vasculitis:
  • Chest imaging (X-ray or CT) to detect pulmonary involvement
  • Sinus CT for Granulomatosis with Polyangiitis (Wegener's)

Disease Categorization

ANCA-Associated Vasculitis Classification 2

1. Localized: Upper/lower respiratory tract disease without systemic involvement
2. Early systemic: Any, without organ-threatening disease
3. Generalized: Renal or organ-threatening disease, creatinine <500 μmol/L
4. Severe: Renal or vital organ failure, creatinine >500 μmol/L
5. Refractory: Progressive disease unresponsive to standard therapy

Monitoring Considerations

• Regular structured clinical assessment rather than ANCA testing alone should inform treatment decisions 2
• Periodic assessment of cardiovascular risk factors 2, 1
• Monitor for drug toxicity:
  • Complete blood count (for cytopenias)
  • Renal and liver function
  • Blood glucose in patients on glucocorticoids
  • Urinalysis for hematuria (particularly important in cyclophosphamide-treated patients) 2
• Test serum immunoglobulin levels before each course of rituximab and in patients with recurrent infections 2, 3

Important Caveats and Pitfalls

• Do not delay treatment while awaiting biopsy results in rapidly progressive disease 1
• A negative ANCA does not rule out vasculitis in the appropriate clinical context 2
• ANCA levels should not be used in isolation to guide treatment decisions 2
• Consider referral to specialized centers for complex cases or refractory disease 2, 1
• Monitor for hypoimmunoglobulinemia in patients receiving rituximab or cyclophosphamide 2, 3
• Be vigilant for infections, which are common complications in treated patients 3
• Consider secondary causes of vasculitis (infections, drugs, malignancy, connective tissue disorders) 4, 5

The comprehensive approach to vasculitis workup requires collaboration between rheumatology, nephrology, pulmonology, and other specialties depending on organ involvement. Early diagnosis and appropriate management are essential to improve outcomes and prevent permanent organ damage.