What is the approach to diagnosing vasculitis?

Approach to Diagnosing Vasculitis

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

Initial Clinical Evaluation

• Structured clinical examination to detect multi-organ involvement:
  • Neurological manifestations (mononeuritis multiplex, peripheral neuropathy)
  • Constitutional symptoms (fever, weight loss, fatigue)
  • Skin lesions (purpura, nodules, ulcers)
  • Joint pain or arthritis
  • Respiratory symptoms (hemoptysis, cough, dyspnea)
  • Renal involvement (hematuria, proteinuria)

Laboratory Testing

Essential Initial Tests

• Complete blood count with differential
• Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)
  • Note: Elevated inflammatory markers are highly sensitive but not specific for vasculitis 2
• Serum creatinine and estimated GFR
• Urinalysis with microscopy (looking for red cell casts and dysmorphic erythrocytes) 1

Autoantibody Testing

• ANCA testing using both:
  • Antigen-specific immunoassays for PR3 and MPO (ELISA) - preferred first-line screening method 1, 3
  • Indirect immunofluorescence (if available)
• Anti-glomerular basement membrane (GBM) antibodies
• Anti-C1q antibodies (for immune complex-associated small-vessel vasculitis) 3

Additional Laboratory Tests

• Complement levels (C3, C4)
• Immunoglobulin levels
• Cryoglobulins
• Hepatitis B and C serology (especially with PAN suspicion) 1

Imaging Studies

Selection Based on Suspected Vessel Size

• Large vessel vasculitis (Takayasu arteritis, Giant Cell Arteritis):

  • MRI/MRA (detects vessel wall inflammation without radiation)
  • CT/CTA
  • FDG-PET/CT (detects inflammatory cells in vessel walls) 1

• Medium vessel vasculitis (Polyarteritis nodosa):

  • CTA of affected regions (renal, mesenteric, coronary) 1
  • Conventional angiography in selected cases

• Small vessel vasculitis:

  • Chest imaging (X-ray, CT) for pulmonary involvement
  • Renal imaging if indicated

Biopsy and Histopathology

• Obtain tissue from the most clinically involved accessible site 1
• Temporal artery biopsy should be performed whenever GCA is suspected, but should not delay treatment 2
  • Biopsy length should be at least 1 cm
  • Treatment prior to biopsy should not be delayed beyond 1-2 weeks of starting glucocorticoids
• Kidney biopsy should be considered in patients with suspected active kidney involvement 1
  • However, treatment should not be delayed in rapidly deteriorating patients with positive ANCA and compatible clinical picture

Diagnostic Algorithm

1. Clinical suspicion based on symptoms and signs
2. Initial laboratory workup (inflammatory markers, organ-specific tests)
3. Autoantibody testing (ANCA, anti-GBM, etc.)
4. Imaging based on suspected vessel size involvement
5. Biopsy of the most accessible affected organ/tissue
   • For GCA: Temporal artery biopsy (but start treatment if high clinical suspicion)
   • For ANCA-associated vasculitis: Kidney, lung, or skin biopsy as appropriate
   • For medium/large vessel vasculitis: Imaging may substitute when biopsy is not feasible

Special Considerations

• ANCA testing interpretation:

  • A positive ANCA test alone is not diagnostic and must be interpreted in clinical context 1
  • About 90% of patients with small-vessel vasculitis have ANCA directed primarily to MPO or PR3 1

• When biopsy is not possible:

  • Patients without confirmatory biopsy but with compatible clinical picture may be diagnosed if:
    1. Specific imaging techniques are strongly suggestive of vasculitis, OR
    2. Patients with clinical diagnosis are anti-PR3/C-ANCA or anti-MPO/P-ANCA positive 2

• Referral recommendation:

  • Patients with suspected vasculitis should be managed in collaboration with, or at centers of expertise 1

Common Pitfalls to Avoid

• Delaying treatment in cases with high clinical suspicion (especially GCA with risk of vision loss)
• Over-relying on ANCA without clinical correlation
• Missing vasculitis mimics (infections, malignancies, other inflammatory conditions)
• Inadequate biopsy samples (too small or from non-involved sites)
• Normal inflammatory markers do not rule out vasculitis (especially in partially treated cases)

By following this structured approach, clinicians can systematically evaluate patients with suspected vasculitis and reach an accurate diagnosis to guide appropriate treatment.