Vasculitis Work-Up
For suspected vasculitis, immediately obtain ANCA testing (PR3 and MPO antibodies), complete blood count with differential, comprehensive metabolic panel, urinalysis with microscopy, inflammatory markers (ESR/CRP), and chest imaging, while simultaneously pursuing tissue diagnosis through biopsy of the most accessible affected organ or vascular imaging depending on vessel size involved 1, 2.
Initial Clinical Assessment
Suspect vasculitis when patients present with:
- Unexplained ischemic events or multi-organ involvement
- Palpable purpura, glomerulonephritis, or multiple mononeuropathy
- Constitutional symptoms with inflammatory arthritis or polymyalgia rheumatica
- Unexplained renal dysfunction with active urinary sediment 3, 4
The diagnostic approach must be tailored to vessel size, as this determines both organ involvement patterns and appropriate imaging modalities 4.
Laboratory Work-Up by Vessel Size
Small Vessel Vasculitis (ANCA-Associated Vasculitis)
Core serological testing:
- ANCA by immunofluorescence and antigen-specific ELISA (PR3-ANCA and MPO-ANCA) - positive in 75-95% of pauci-immune small vessel vasculitis 2
- Complete blood count with differential (assess for eosinophilia in EGPA)
- Comprehensive metabolic panel (renal function)
- Urinalysis with microscopy - critical for detecting glomerulonephritis 1
- ESR and CRP
- Hepatitis B, C, and HIV serology (to exclude secondary vasculitis) 2
Additional testing when indicated:
- Anti-GBM antibodies if rapidly progressive glomerulonephritis
- Complement levels (C3, C4) and cryoglobulins if immune complex vasculitis suspected
- Anti-C1q antibodies
- Chest imaging (CT preferred) for pulmonary involvement 1
Large Vessel Vasculitis (GCA/Takayasu Arteritis)
Imaging is the primary diagnostic modality 5, 6:
- Temporal and axillary artery ultrasound bilaterally - first-line for suspected GCA, looking for non-compressible "halo sign" (intima-media thickening) 5, 6
- For Takayasu arteritis: ultrasound of common carotid and subclavian arteries, or MR-angiography/CT-angiography/PET-CT 5
- ESR and CRP (typically markedly elevated)
- Complete blood count (anemia of chronic disease, thrombocytosis)
Critical timing consideration: Ultrasound should be performed within fast-track clinics before glucocorticoid initiation when possible, though treatment should not be delayed if imaging unavailable - the halo sign can persist for days after glucocorticoid initiation 6.
Tissue Diagnosis
Structured clinical assessment should guide treatment decisions, not ANCA or B cell testing alone 1. However, tissue confirmation remains the gold standard when safely obtainable:
- Biopsy the most accessible affected organ: kidney (if glomerulonephritis), skin (if purpura), nerve/muscle (if neuropathy), lung (if nodules/infiltrates)
- Temporal artery biopsy for GCA if ultrasound inconclusive (though ultrasound now integrated into classification criteria) 5
- Brain/leptomeningeal biopsy for suspected CNS vasculitis only when other diagnoses excluded - note that negative biopsy doesn't exclude vasculitis due to segmental nature 7
Critical Exclusions
Before diagnosing primary vasculitis, exclude secondary causes:
- Infections (hepatitis B/C, HIV, endocarditis)
- Malignancy
- Drug-induced vasculitis
- Connective tissue diseases (SLE, rheumatoid arthritis) 3, 2
Multidisciplinary Coordination
AAV requires management by centers with vasculitis expertise given rarity, heterogeneity, and life-threatening potential 1. Coordinate with:
- Rheumatology (treatment coordination)
- Nephrology (if renal involvement)
- Pulmonology (if lung involvement)
- Radiology/vascular interventionalists (for imaging interpretation) 4
Common Pitfalls
- Do not wait for ANCA results to initiate treatment in organ-threatening or life-threatening disease - ANCA can be negative in 5-25% of cases 2
- Do not rely on ANCA titers alone for treatment decisions - use structured clinical assessment 1
- Ultrasound findings require experienced interpretation to avoid false positives from atherosclerosis or other non-inflammatory conditions 6
- Normal biopsy doesn't exclude vasculitis due to patchy vessel involvement 7
Baseline Assessment Before Treatment
Once diagnosis established, obtain before immunosuppression: