What is the appropriate workup for a patient with suspected vasculitis?

Workup for Suspected Vasculitis

For patients with suspected vasculitis, immediately obtain ANCA testing using high-quality antigen-specific assays (both PR3-ANCA and MPO-ANCA), along with comprehensive laboratory evaluation including CBC, inflammatory markers (ESR, CRP), renal function tests, and urinalysis with microscopy, followed by tissue biopsy of affected organs whenever accessible to confirm the diagnosis. 1, 2

Essential Laboratory Testing

Primary Serologic Evaluation

• ANCA testing is the cornerstone of diagnosis for small-vessel vasculitis and should be performed using both indirect immunofluorescence and enzyme-linked immunosorbent assays (ELISA) as the primary method, with sensitivity of 80-90% for ANCA-associated vasculitis (AAV) 1, 2, 3
• Anti-nuclear antibodies (ANA) should be evaluated to assess for potential connective tissue diseases that may mimic or coexist with vasculitis 2
• Hepatitis B and C serologies are essential, particularly when liver involvement or associated risk factors are present 3

Baseline Laboratory Panel

• Complete blood count with differential to assess for anemia, leukopenia, or thrombocytopenia 2, 3
• Comprehensive metabolic panel including creatinine and liver function tests 2
• Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) as inflammatory markers 2, 3
• Complement levels (C3 and C4) should be obtained in all patients 3

Urinalysis and Renal Assessment

• Urinalysis with microscopic examination is mandatory to detect hematuria, proteinuria, and red cell casts that indicate glomerulonephritis 1, 2
• For suspected renal involvement, obtain 24-hour urine collection for protein quantification and creatinine clearance 2
• Glomerular hematuria or rapidly rising creatinine suggests organ-threatening disease requiring urgent intervention 1

Tissue Biopsy Strategy

• A positive biopsy is strongly supportive of vasculitis diagnosis and should be pursued whenever clinically affected tissue is accessible, as biopsy remains the gold standard for definitive diagnosis 1, 3, 4
• Kidney biopsy provides both definitive diagnosis and prognostic information in suspected renal vasculitis and should be performed when renal involvement is suspected 2
• Biopsy of skin lesions, nasal/sinus tissue, lung nodules, or nerve tissue should be obtained based on clinical manifestations 1, 4

Critical Caveat on Biopsy Timing

• In patients with positive ANCA serology and rapidly deteriorating organ function (particularly renal failure or pulmonary hemorrhage), treatment should NOT be delayed while waiting for biopsy results 5
• The risk of irreversible organ damage outweighs the benefit of histologic confirmation in life-threatening presentations 5

Imaging Studies by Clinical Presentation

For Large-Vessel Vasculitis Suspicion

• Temporal artery ultrasound shows 88% sensitivity and 97% specificity for giant cell arteritis, with the characteristic "halo sign" 6
• MRI/MRA of head, neck, and thoracic vessels can identify large-artery involvement 6
• FDG-PET/CT demonstrates inflammatory cell accumulation in vessel walls with high sensitivity, performed after 6 hours fasting with 120-180 minute delay post-injection 6

For Pulmonary Involvement

• Chest imaging (X-ray or CT) is recommended to evaluate for pulmonary involvement, including granulomas, infiltrates, cavitary lesions, or alveolar hemorrhage 2
• High-resolution CT provides superior detail for characterizing pulmonary nodules and interstitial changes 4

For CNS Vasculitis Suspicion

• MRI brain is the preferred initial imaging modality, with abnormal findings in >90% of CNS vasculitis cases 6
• Cerebrospinal fluid analysis may reveal elevated protein, lymphocytic pleocytosis, or increased opening pressure 6
• Cerebral angiography provides submillimeter resolution but should be reserved for cases where non-invasive imaging is inconclusive 6
• Brain biopsy is the most specific test for diffuse CNS vasculitis but is invasive and reserved for diagnostic uncertainty 6

Disease Severity Classification

• Patients must be categorized by disease severity to guide treatment intensity: organ-threatening manifestations include glomerulonephritis, pulmonary hemorrhage, meningeal involvement, CNS involvement, cardiac involvement, mesenteric involvement, and mononeuritis multiplex 1
• Non-organ-threatening manifestations include nasal/paranasal disease without bony erosion, skin involvement without ulceration, myositis, non-cavitating pulmonary nodules, and episcleritis 1

Important Diagnostic Pitfalls

• Approximately 10% of patients with clinical features of ANCA-associated vasculitis are ANCA-negative, requiring tissue biopsy for definitive diagnosis 2
• Angiography may be normal even when vasculitis is present, or findings may be nonspecific and not pathognomonic 3, 7
• Secondary causes of vasculitis (infection, drugs, malignancy, connective tissue disease) must be systematically excluded before diagnosing primary vasculitis 7, 8
• Serial measurements of acute phase reactants and ANCA levels are useful for monitoring disease activity, as ANCA persistence or rising levels may predict future relapse 5, 3

Multidisciplinary Consultation

• Patients with suspected vasculitis should be managed in close collaboration with centers experienced in vasculitis management, involving rheumatology, nephrology, pulmonology, neurology, and pathology expertise as needed 1, 2, 4