What is the recommended approach for investigating vasculitis?

Recommended Approach for Investigating Vasculitis

The diagnostic approach for vasculitis should include precise disease definition through clinical assessment, laboratory testing, appropriate imaging, and tissue biopsy, with ANCA testing being essential for small vessel vasculitis classification. 1, 2

Disease Definition and Classification

• Patients with suspected vasculitis should be classified according to published criteria using Chapel Hill Consensus Conference definitions and/or American College of Rheumatology classification criteria 3
• The definitive diagnosis should ideally be based on typical biopsy findings and/or highly specific immune phenomena (e.g., ANCA) 3
• Vasculitis should be categorized by vessel size (small, medium, or large) and predominant inflammatory cell type (neutrophilic, granulomatous, lymphocytic, or eosinophilic) 4
• Early diagnosis and aggressive treatment are essential to reduce morbidity and mortality 2

Laboratory Investigations

• Complete serological workup should include:

  • ANCA testing (including indirect immunofluorescence and ELISA) in appropriate clinical context 1, 5
  • Inflammatory markers (ESR, CRP) 6
  • Complete blood count 1
  • Renal function tests and urinalysis 5
  • Complement levels 1
  • Specific autoantibodies based on clinical suspicion 6
  • Hepatitis B and C serology to exclude secondary vasculitis 6
  • Cryoglobulin testing when appropriate 3

• For ANCA-associated vasculitis (AAV):

  • Anti-PR3 ANCA (c-ANCA) is associated with granulomatosis with polyangiitis (formerly Wegener's) 2
  • Anti-MPO ANCA (p-ANCA) is associated with microscopic polyangiitis 2
  • High-quality antigen-specific immunoassays are the preferred screening methodology 6

Imaging Studies

• For large vessel vasculitis (GCA or Takayasu arteritis):

  • Ultrasound is recommended as the first imaging modality in patients with suspected GCA 3
  • MRI may be used as an alternative to ultrasound 3
  • PET, CT, and/or ultrasound may be used for suspected Takayasu arteritis 3
  • Conventional angiography is not recommended as it has been superseded by other imaging modalities 3

• For small and medium vessel vasculitis:

  • Appropriate imaging studies should be performed based on clinical presentation and suspected organ involvement 5
  • MRI may be indicated for neurological manifestations 1

Histopathological Evaluation

• Tissue biopsy showing typical features of vasculitis is strongly recommended for definitive diagnosis 1, 5
• Biopsy should be taken from the earliest, most symptomatic lesion for optimal diagnostic yield 4
• Biopsy can differentiate active disease from damage as the cause of clinical decline 5
• For cutaneous vasculitis, biopsy is the gold standard and also necessary for detection of vascular immune complexes by direct immunofluorescence 7, 4

Differential Diagnosis

• It is essential to exclude:
  • Infections that can mimic vasculitis (e.g., bacterial endocarditis) 5
  • Drug-induced vasculitis 1, 2
  • Malignancy-associated vasculitis 7
  • Connective tissue diseases with vasculitic features 7

Special Considerations

• Patients with systemic vasculitis should be managed in collaboration with, or at centers of expertise 5
• A structured clinical assessment at each visit is essential to detect new organ involvement and differentiate between active vasculitis, infection, and other complications 5
• Fast-track clinic approaches combined with ultrasound examination have been shown to improve prognosis for GCA while being cost-effective 8

Common Pitfalls to Avoid

• Relying solely on ANCA results for diagnosis, as up to 30% of patients with microscopic polyangiitis can be PR-3/C-ANCA-positive without having typical features of granulomatosis with polyangiitis 3
• Delaying biopsy until after starting treatment, which may reduce diagnostic yield 4
• Misinterpreting elevated inflammatory markers as indicative of active vasculitis when they could represent infection or another source of inflammation 6
• Failing to consider drug-induced or infection-related vasculitis in the differential diagnosis 1, 5