What are the steps to diagnose vasculitis?

Diagnostic Approach to Vasculitis

The definitive diagnosis of vasculitis requires a combination of clinical assessment, laboratory testing, imaging studies, and in most cases, histopathological confirmation through biopsy, which remains the gold standard for diagnosis. 1

Step-by-Step Diagnostic Algorithm

1. Clinical Assessment

• Perform a structured clinical examination to detect multi-organ involvement 1
• Look for specific manifestations:
  • Skin: palpable purpura, nodular erythema, livedo racemosa, ulcers, digital gangrene 2
  • Respiratory: infiltrates, nodules, cavitations, alveolar hemorrhage 3
  • Renal: hematuria, proteinuria, elevated creatinine 4
  • Neurological: mononeuritis multiplex, peripheral neuropathy 1
  • Constitutional: fever, weight loss, fatigue 5

2. Laboratory Testing

First-line Tests

• Complete blood count with differential
• Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) 6
• Comprehensive metabolic panel including renal function
• Urinalysis with microscopy (look for red cell casts, dysmorphic erythrocytes) 1
• ANCA testing using both:
  • Indirect immunofluorescence (to detect cytoplasmic or perinuclear patterns)
  • Antigen-specific immunoassays for PR3 and MPO (ELISA) 1, 4

Second-line Tests (Based on Clinical Suspicion)

• Complement levels (C3, C4)
• Immunoglobulin levels
• Cryoglobulins
• Hepatitis B and C serology (especially with PAN suspicion) 1, 7
• Anti-GBM antibodies (to rule out anti-GBM disease or dual-positive disease) 4
• Rheumatoid factor, ANA, anti-dsDNA (if connective tissue disease suspected) 6

3. Imaging Studies

• Selection based on suspected vessel size involvement:

  • Large vessel vasculitis: CT/CTA, MRI/MRA, or FDG-PET/CT 1
  • Medium vessel vasculitis: CTA of affected regions (renal, mesenteric, coronary) 1
  • Small vessel vasculitis: Chest imaging (X-ray, CT) for pulmonary involvement 3

• For specific vessel types:

  • CTA: Excellent spatial resolution, can be acquired as biphasic or triphasic study 1
  • MRI/MRA: Useful for assessing vessel wall inflammation without radiation 1
  • FDG-PET/CT: Detects inflammatory cells in vessel walls, particularly useful for large vessel vasculitis 1

4. Biopsy - Gold Standard

• Obtain tissue from the most clinically involved accessible site 1, 5
• Diagnostic yield of biopsies demonstrating either granuloma or vasculitis exceeds 70% 1
• Extend biopsy to subcutis from the most tender, reddish, or purpuric lesional skin 2
• For cutaneous vasculitis: Perform concurrent direct immunofluorescence to distinguish IgA-associated (Henoch-Schönlein purpura) from IgG/IgM-associated vasculitis 2
• For renal involvement: Kidney biopsy should be considered but treatment should not be delayed in rapidly deteriorating patients with positive ANCA and compatible clinical picture 4

Special Considerations

ANCA Testing Interpretation

• A positive ANCA test alone is not diagnostic and must be interpreted in clinical context 4
• PR3-ANCA is highly associated with Granulomatosis with Polyangiitis (formerly Wegener's)
• MPO-ANCA is more common in Microscopic Polyangiitis 1, 4

When to Suspect Different Types of Vasculitis

• Large vessel: Takayasu arteritis (age ≤40), Giant Cell Arteritis (age >50) 3
• Medium vessel: Polyarteritis nodosa (associated with HBV), Kawasaki disease 1
• Small vessel: ANCA-associated (GPA, MPA, EGPA) or immune complex (HSP, cryoglobulinemic) 6

Diagnostic Pitfalls to Avoid

• Delaying treatment in rapidly deteriorating patients while waiting for biopsy results 4
• Relying solely on ANCA testing without clinical correlation 4
• Failing to consider mimics of vasculitis (thrombotic disorders, infections, malignancies) 2, 3
• Using inadequate biopsy samples (too small or from non-active lesions) 2

Management Considerations

• Patients with suspected vasculitis should be managed in collaboration with, or at centers of expertise 1
• Early diagnosis and treatment are essential for improving survival and reducing organ damage 4

Remember that vasculitis diagnosis requires a comprehensive approach, and no single test is sufficient. The combination of clinical presentation, laboratory findings, imaging studies, and histopathology provides the most accurate diagnosis.