What is the approach to diagnosing and treating vasculitis?

Diagnosis of Vasculitis

The diagnosis of vasculitis requires tissue biopsy showing typical features (necrotizing vasculitis, granulomatous inflammation, or glomerulonephritis) as the gold standard, but patients with compatible clinical presentations can be diagnosed without biopsy if they have positive ANCA testing (for small-vessel disease) or characteristic imaging findings combined with exclusion of mimics like infection and malignancy. 1, 2

Initial Classification by Vessel Size

• Categorize suspected vasculitis by vessel size involvement to guide diagnostic workup: large vessel (Takayasu arteritis, giant cell arteritis), medium vessel (polyarteritis nodosa), small vessel (ANCA-associated vasculitis, microscopic polyangiitis), or variable vessel vasculitis 2, 3
• Use American College of Rheumatology classification criteria or Chapel Hill Consensus Conference definitions as the framework for clinical diagnosis 1

Essential Laboratory Evaluation

Initial laboratory testing should include: 2, 4

• Complete blood count with differential
• Comprehensive metabolic panel including renal function
• Inflammatory markers: ESR and CRP (must be interpreted in clinical context, not in isolation) 1, 4
• Urinalysis with microscopic examination looking specifically for hematuria, proteinuria, red cell casts, and dysmorphic erythrocytes 1, 2, 4
• Quantification of proteinuria if present 1, 4

For suspected small-vessel vasculitis: 2, 4

• ANCA testing using BOTH indirect immunofluorescence AND antigen-specific ELISA for PR3 and MPO - the 2017 revised international consensus recommends high-quality antigen-specific immunoassays as the preferred screening method 2
• Note that up to 10% of patients with clinical ANCA-associated vasculitis may be ANCA-negative, requiring tissue biopsy for definitive diagnosis 2
• PR3/C-ANCA is highly sensitive for granulomatosis with polyangiitis (Wegener's), though up to 30% of microscopic polyangiitis patients may also be PR3-positive 1

For specific vasculitis subtypes: 1

• Hepatitis C virus quantitative testing and circulating cryoglobulins for suspected cryoglobulinemic vasculitis
• Hepatitis B serology for suspected HBV-associated polyarteritis nodosa

Tissue Biopsy Strategy

Biopsy of affected tissue remains the diagnostic gold standard with over 70% diagnostic yield when appropriate organs are sampled. 1, 2

For ANCA-associated vasculitis: 2, 4

• Kidney biopsy provides both diagnostic AND prognostic information through assessment of glomerular, tubulointerstitial, and vascular histopathology 2
• Look for necrotizing vasculitis, granulomatous inflammation, or pauci-immune glomerulonephritis 1

Biopsy can be omitted if: 1

1. Specific imaging (angiography, MRI/CT, neurophysiology) strongly suggests vasculitis, glomerulonephritis, or granuloma, OR
2. Patients with clinical diagnosis of microscopic polyangiitis or granulomatosis with polyangiitis are anti-PR3/C-ANCA or anti-MPO/P-ANCA positive

Surrogate clinical parameters supporting diagnosis without biopsy include: 1

• Fixed pulmonary infiltrates, nodules, or cavitations
• Subglottic stenosis
• Retro-orbital granuloma
• Red cell casts or dysmorphic erythrocytes in urine
• Diffuse alveolar hemorrhage (affects 10% of ANCA-associated vasculitis patients with increased mortality risk) 2
• Rapid-onset mononeuritis multiplex
• Episcleritis

Imaging Studies by Vessel Size

For large vessel vasculitis (giant cell arteritis, Takayasu arteritis): 2, 3

• Temporal artery ultrasound shows 88% sensitivity and 97% specificity for giant cell arteritis 2, 3
• MRI/MRA of head and neck or thorough arterial tree assessment with high accuracy 3
• FDG-PET/CT demonstrates inflammatory cell accumulation in vessel walls - perform after 6 hours fasting with 120-180 minute delay after injection for optimal accuracy 3
• CT angiography with proper arterial phase imaging provides excellent spatial resolution for Takayasu arteritis 3

For suspected CNS vasculitis: 3

• MRI brain is the preferred initial modality (abnormal in >90% of cases)
• Cerebrospinal fluid analysis may reveal elevated protein or lymphocytic pleocytosis
• Cerebral arteriography has submillimeter resolution but is invasive
• Brain biopsy is most specific but limited by invasive nature

Disease Activity Assessment

Use structured clinical assessment tools at each visit: 1, 4

• Birmingham Vasculitis Activity Score (BVAS) - Grade A recommendation 1
• Disease Extent Index (DEI) 1, 4
• Vasculitis Damage Index (VDI) for assessing permanent damage 1, 4
• Short Form 36 (SF-36) for quality of life assessment 1

Categorize disease severity for treatment planning: 2, 4

• Non-organ threatening
• Generalized disease
• Severe disease
• Refractory disease

Define activity states clearly: 1, 4

• Remission
• Response
• Refractory disease
• Relapse

Critical Clinical Scenarios

Pulmonary-renal syndrome (acute kidney injury with alveolar hemorrhage): 2

• Immediately test for anti-GBM antibodies (suggests anti-GBM disease if positive)
• Test MPO and PR3-ANCA (supports ANCA-associated vasculitis if positive)
• This presentation carries increased mortality risk and requires urgent diagnosis

Monitoring During Follow-up

Serial monitoring should include: 1, 4

• Regular urinalysis with microscopic examination
• Periodic inflammatory markers (CRP/ESR) and renal function assessment
• Serial ANCA measurements in ANCA-associated vasculitis 1
• Renal function assessed by GFR using MDRD or Cockcroft-Gault formula 1
• Full blood count and liver function tests 4
• Blood glucose while on glucocorticoid therapy 4
• Structured clinical assessment should guide treatment decisions rather than ANCA levels alone 4

Common Pitfalls to Avoid

• Do not diagnose based solely on ANCA subtype - up to 30% of microscopic polyangiitis patients are PR3/C-ANCA positive without typical granulomatosis with polyangiitis features 1
• Do not use classification criteria (ACR, Chapel Hill) as diagnostic criteria - they are designed for research classification, not primary diagnosis 1
• Always exclude infections and malignancies before confirming vasculitis diagnosis, as these can mimic vasculitis clinically 1
• Biopsy results may be falsely negative - clinical judgment with supportive testing can establish diagnosis 1

Referral Considerations

• Patients with suspected vasculitis should be managed at centers with expertise in vasculitis management to ensure optimal outcomes 2, 4
• Patients with refractory disease require referral to expert centers for potential clinical trial enrollment 4