What is the appropriate work-up and treatment for a patient with suspected vasculitis?

Work-up for Vasculitis

Initial Laboratory Assessment

All patients with suspected vasculitis require a comprehensive initial laboratory panel including complete blood count with differential, comprehensive metabolic panel with creatinine, erythrocyte sedimentation rate, C-reactive protein, and urinalysis with microscopy. 1, 2

Essential First-Line Tests

• Complete blood count with differential assesses for anemia (common in active inflammation), leukocytosis, thrombocytosis, or cytopenias that may indicate bone marrow suppression or active disease 1
• Comprehensive metabolic panel including serum creatinine evaluates renal function, as acute kidney injury occurs frequently in vasculitis and guides treatment decisions 1
• Urinalysis at every visit is crucial to detect hematuria, proteinuria, and red blood cell casts suggesting glomerulonephritis—these findings indicate renal involvement requiring urgent intervention 1, 2
• ESR and CRP serve as inflammatory markers, though they are nonspecific and cannot distinguish vasculitis activity from infection or other inflammatory sources 1

Critical Autoimmune Serologies

• ANCA testing using both indirect immunofluorescence and ELISA is recommended when small vessel vasculitis is suspected, with high-quality antigen-specific immunoassays (MPO-ANCA and PR3-ANCA) as the preferred screening methodology 1, 3
• Anti-nuclear antibodies (ANA) should be evaluated to assess for connective tissue diseases that can present with secondary vasculitis 1, 2
• Important caveat: Approximately 10% of patients with clinical features of ANCA-associated vasculitis may be ANCA-negative, requiring tissue biopsy for definitive diagnosis 1, 2

Disease Categorization and Severity Assessment

Patients with ANCA-associated vasculitis should be categorized according to the European Vasculitis Study (EUVAS) disease severity levels to guide treatment decisions. 4

The EUVAS categories are:

• Localized: Upper/lower respiratory tract disease without systemic involvement or constitutional symptoms 4
• Early systemic: Any manifestation without organ-threatening or life-threatening disease 4
• Generalised: Renal or other organ-threatening disease with serum creatinine <500 μmol/L (5.6 mg/dL) 4
• Severe: Renal or vital organ failure with serum creatinine >500 μmol/L (5.6 mg/dL) 4
• Refractory: Progressive disease unresponsive to glucocorticoids and cyclophosphamide 4

Organ-Specific Evaluation

Renal Involvement

• 24-hour urine collection for protein and creatinine clearance when renal involvement is suspected 1, 2
• Kidney biopsy provides both diagnostic and prognostic information through assessment of glomerular, tubulointerstitial, and vascular histopathology, with diagnostic yield exceeding 70% 1

Pulmonary Involvement

• Chest X-ray or CT evaluates for pulmonary involvement, granulomas, infiltrates, or cavitary lesions 2

Imaging Studies by Vessel Size

Large Vessel Vasculitis (Giant Cell Arteritis, Takayasu Arteritis)

• Temporal artery ultrasound shows 88% sensitivity and 97% specificity for diagnosing giant cell arteritis 1, 5
• MRI/MRA of head, neck, and affected arterial territories identifies extracranial large artery involvement with high accuracy 1, 5
• FDG-PET/CT demonstrates inflammatory cell accumulation in vessel walls with high sensitivity and specificity, performed after 6 hours of fasting with 120-180 minute delay after injection 5

CNS Vasculitis

• MRI brain is the preferred initial imaging modality for suspected CNS vasculitis, with abnormal findings in >90% of cases 4, 5, 6
• MRI vessel wall imaging shows promise in differentiating CNS vasculitis from other cerebrovascular diseases, as inflammatory changes of the vessel wall differ between conditions 4
• Cerebrospinal fluid analysis may reveal increased opening pressure, elevated protein, or lymphocytic pleocytosis 5, 6
• Brain biopsy is the most specific diagnostic test for diffuse or multifocal CNS vasculitis, though limited by its invasive nature 5

Tissue Biopsy for Definitive Diagnosis

Tissue biopsy from clinically affected tissue provides definitive diagnosis and should be performed whenever accessible. 3, 7

• Skin biopsy extending to the subcutis should be taken from the most tender, reddish, or purpuric lesional skin, with serial sections often required for identifying the main vasculitic lesion 8
• Concomitant biopsy for direct immunofluorescence distinguishes IgA-associated vasculitis (Henoch-Schönlein purpura) from IgG-/IgM-associated vasculitis, which has prognostic significance 8

Monitoring During Follow-Up

Structured monitoring is essential to detect disease relapse, infection, and drug toxicity. 4

• Urinalysis at every clinic visit screens for infection, renal relapse, or bladder complications from cyclophosphamide 1
• Inflammatory markers (ESR, CRP) and renal function every 1-3 months to monitor disease status 1
• Complete blood count and liver function tests at similar intervals to screen for drug toxicity—an acute fall in white cell count or progressive leukopenia requires dose reduction or discontinuation of immunosuppressive drugs 4, 1
• Blood glucose monitoring periodically while on glucocorticoid therapy 4

Common Pitfalls to Avoid

• Do not rely solely on inflammatory markers: ESR and CRP are nonspecific and cannot distinguish between vasculitis activity and concomitant infection 1
• Do not miss ANCA-negative vasculitis: Approximately 10% of ANCA-associated vasculitis cases are ANCA-negative, requiring tissue biopsy 1, 2
• Do not delay biopsy: Angiography may be normal even when vasculitis is present, or findings may be nonspecific—tissue biopsy provides definitive diagnosis 3
• Recognize disease category changes: Patients may transition between EUVAS categories, requiring modification of treatment decisions (e.g., a patient with early systemic disease on methotrexate needs cyclophosphamide if organ-threatening manifestations develop) 4