What is the workup for vasculitis?

Workup for Vasculitis

The workup for vasculitis requires tissue biopsy as the gold standard for diagnosis, combined with vessel size-specific imaging and targeted laboratory testing including ANCA, inflammatory markers, urinalysis, and organ-specific assessments based on clinical presentation. 1, 2

Initial Laboratory Evaluation

The essential first-line laboratory tests include:

• Complete blood count, comprehensive metabolic panel, ESR, and CRP to assess inflammation and organ function 1, 3
• Urinalysis with microscopic examination to detect hematuria, proteinuria, and red cell casts indicating renal involvement 4, 1
• ANCA testing using both indirect immunofluorescence and ELISA when small vessel vasculitis is suspected 1, 3, 2
• Renal function assessment using GFR estimating equations (MDRD or Cockcroft-Gault formula) 4
• Quantification of proteinuria to monitor glomerulonephritis activity 4

Autoimmune and Infectious Serologies

Additional serologic testing should target specific vasculitis types:

• Antinuclear antibodies (ANA) to evaluate for connective tissue disease-associated vasculitis 5, 6
• Hepatitis B and C serologies as HBV is associated with polyarteritis nodosa and HCV with cryoglobulinemic vasculitis 4, 5, 6
• Cryoglobulins and complement fractions (C3, C4) particularly when cryoglobulinemic vasculitis is suspected 5, 6
• IgA levels as IgA vasculitis (Henoch-Schönlein purpura) has distinct prognostic implications 7, 5

The 2017 revised international consensus recommends high-quality antigen-specific immunoassays as the preferred screening method for MPO- and PR3-ANCA, though up to 10% of patients with clinical features of ANCA-associated vasculitis may be ANCA-negative, requiring tissue biopsy for definitive diagnosis. 1

Tissue Biopsy Protocol

Biopsy of affected tissue remains the gold standard and should be obtained in most cases to confirm diagnosis. 4, 1, 2

The biopsy approach depends on clinical presentation:

• For cutaneous vasculitis: Obtain a biopsy extending to the subcutis from the most tender, reddish, or purpuric lesional skin; serial sections are often required 7
• Concomitant biopsy for direct immunofluorescence to distinguish IgA-associated vasculitis from IgG-/IgM-associated vasculitis 7, 5
• For ANCA-associated vasculitis with renal involvement: Kidney biopsy provides both diagnostic and prognostic information through assessment of glomerular, tubulointerstitial, and vascular histopathology 1
• The diagnostic yield of biopsies demonstrating either granuloma or vasculitis is over 70%, varying by organ sampled 1

Patients without confirmatory biopsy but with compatible clinical picture may be diagnosed if specific imaging or surrogate parameters are strongly suggestive of vasculitis AND patients with clinical diagnosis of MPA or Wegener's granulomatosis are anti-PR3/C-ANCA or anti-MPO/P-ANCA-positive. 4

Vessel Size-Specific Imaging

Imaging selection must be guided by suspected vessel size involvement:

Large Vessel Vasculitis

• For Giant Cell Arteritis: Temporal artery ultrasound shows 88% sensitivity and 97% specificity 1, 3
• MRI/MRA of head and neck identifies extracranial large artery involvement with high accuracy 3
• FDG-PET/CT demonstrates inflammatory cell accumulation in vessel walls; perform after 6 hours fasting with 120-180 minute delay post-injection for optimal accuracy 1, 3
• Temporal artery biopsy should be performed whenever GCA is suspected 3

Medium and Small Vessel Vasculitis

• Angiography, MRI/CT imaging, or neurophysiology when surrogate parameters suggest vasculitis, glomerulonephritis, or granuloma 4
• For Takayasu Arteritis: Thorough assessment of arterial tree using MRI/MRA or PET to document extent of involvement 3
• CT angiography with proper arterial phase imaging provides excellent spatial resolution 3

CNS Vasculitis

• MRI brain is the preferred initial imaging modality, with abnormal findings in >90% of cases 3
• Transcranial color-Doppler ultrasonography and MR imaging play important roles, though MR abnormalities are not diagnostic 4
• Cerebrospinal fluid analysis may reveal increased opening pressure, elevated protein, or lymphocytic pleocytosis 3
• Brain biopsy is the most specific diagnostic test for diffuse or multifocal CNS vasculitis, despite its invasive nature 3

Critical Clinical Scenarios

Acute kidney injury presenting with alveolar hemorrhage (pulmonary-renal syndrome) should immediately raise concern for vasculitis. 1

In this situation:

• Positive anti-GBM antibodies suggest anti-GBM disease 1
• Positive MPO or PR3-ANCA supports ANCA-associated vasculitis 1
• Pulmonary hemorrhage affects 10% of ANCA-associated vasculitis patients and increases mortality risk 1

Disease Classification and Staging

Once vasculitis is confirmed:

• Categorize based on vessel size: large vessel, medium vessel, small vessel, or variable vessel vasculitis 1, 3
• Clinical diagnosis should be based on ACR classification criteria or Chapel Hill Consensus Conference definitions 4
• For ANCA-associated vasculitis, categorize by disease severity: non-organ threatening, generalized, severe, or refractory disease 1, 2
• Use structured clinical assessment tools such as Birmingham Vasculitis Activity Score (BVAS) and Disease Extent Index at each visit 4, 2

Common Pitfalls to Avoid

• Do not rely solely on ANCA subtype for diagnosis, as up to 30% of MPA patients are PR3/C-ANCA-positive without typical Wegener's features, leading to potential misclassification 4
• Biomarkers such as CRP and ESR must be interpreted in the context of clinical findings, not in isolation 4
• Coexistence of pan-dermal small-vessel vasculitis and subcutaneous muscular-vessel vasculitis usually indicates connective tissue disease, ANCA-associated vasculitis, Behçet disease, or malignancy-associated vasculitis 7
• Exclude vasculitis-like syndromes (pseudovasculitis) such as thrombotic disorders including anti-phospholipid antibody syndrome 7

Patients with suspected vasculitis should be managed at centers with experience in vasculitis management to ensure optimal outcomes. 1, 2