Vasculitis Panel: Diagnostic and Treatment Approach
Initial Laboratory Workup
For any patient with suspected vasculitis, the essential laboratory panel should include ANCA testing (both MPO and PR3 by high-quality antigen-specific immunoassays), complete blood count, inflammatory markers (ESR and CRP), comprehensive metabolic panel with renal function, urinalysis with microscopy, and autoimmune serologies. 1, 2, 3
Core Laboratory Tests
ANCA testing is the cornerstone serologic test and should be performed using high-quality antigen-specific immunoassays for MPO-ANCA and PR3-ANCA as the preferred screening method, rather than indirect immunofluorescence alone 1, 4, 5
Complete blood count with differential to assess for anemia, leukocytosis, thrombocytosis, or eosinophilia (particularly in eosinophilic granulomatosis with polyangiitis) 2, 6, 4
Inflammatory markers including ESR and CRP should be measured, though these are nonspecific and cannot distinguish vasculitis activity from infection 1, 4
Comprehensive metabolic panel with serum creatinine and estimated GFR using MDRD or Cockcroft-Gault formula to assess renal involvement 1, 2
Urinalysis with microscopic examination is critical to detect hematuria, proteinuria, and red blood cell casts that indicate glomerulonephritis 1, 2, 3
24-hour urine collection for protein and creatinine clearance when renal involvement is suspected 2
Additional Serologic Testing
Anti-nuclear antibodies (ANA) to evaluate for connective tissue diseases that can present with secondary vasculitis 2, 7
Anti-glomerular basement membrane (anti-GBM) antibodies, especially in pulmonary-renal syndrome presentations 1, 3, 5
Complement levels (C3, C4) and anti-C1q antibodies for immune complex-associated vasculitis 6, 4, 5
Hepatitis B and C serology, as hepatitis C is associated with cryoglobulinemic vasculitis and hepatitis B with polyarteritis nodosa 1, 6, 4
Cryoglobulins and immunoglobulin levels when cryoglobulinemic vasculitis is suspected 1, 4
Rheumatoid factor and anti-CCP antibodies if rheumatoid vasculitis is in the differential 5
Critical Diagnostic Considerations
About 10% of patients with clinical features of ANCA-associated vasculitis are persistently ANCA-negative, making tissue biopsy essential for definitive diagnosis in these cases. 1, 3
ANCA positivity (MPO or PR3) in the context of compatible clinical presentation strongly supports AAV diagnosis, with sensitivity of 75-95% in pauci-immune small vessel vasculitis 5
Up to 30% of microscopic polyangiitis patients may be PR3/C-ANCA positive without typical Wegener's granulomatosis features, so diagnosis should not rely solely on ANCA subtype 1
Tissue Biopsy Strategy
Biopsy of affected tissue remains the gold standard for vasculitis diagnosis and should be pursued whenever feasible, particularly for establishing new diagnoses or evaluating suspected relapses. 1, 3
Biopsy Site Selection by Organ Involvement
Kidney biopsy provides the highest diagnostic yield (up to 91.5% in GPA with renal involvement) and offers critical prognostic information through assessment of glomerular sclerosis and tubulointerstitial damage 1
Skin biopsy extending to subcutis from the most tender, purpuric lesion, with serial sections and direct immunofluorescence to distinguish IgA-associated (Henoch-Schönlein purpura) from IgG/IgM-associated vasculitis 7
Otorhinolaryngological biopsies in suspected GPA show inflammatory changes in up to 68.4% of cases 1
Lung biopsy: transbronchial biopsies have only 12% sensitivity for GPA, while open lung biopsies provide much higher diagnostic yield (>70%) despite being more invasive 1, 3
Temporal artery biopsy for suspected giant cell arteritis, with ultrasound showing 88% sensitivity and 97% specificity 3, 8
Important Biopsy Caveats
The risk of bleeding from percutaneous renal biopsy is higher in patients treated with plasma exchange, and increases with older age, elevated systolic blood pressure, and worse baseline renal function 1
In patients with positive MPO or PR3-ANCA and clinical presentation compatible with small-vessel vasculitis with rapidly progressive glomerulonephritis, do not delay immunosuppressive therapy while waiting for biopsy results 1
Imaging Studies
Vessel Size-Specific Imaging
Chest imaging (X-ray or CT) is essential to evaluate for pulmonary involvement, granulomas, infiltrates, or cavitary lesions in suspected AAV 2, 3
For large vessel vasculitis (giant cell arteritis, Takayasu arteritis): MRI/MRA or FDG-PET/CT to assess arterial tree involvement and vessel wall inflammation 3, 8
FDG-PET/CT should be performed after 6 hours of fasting with 120-180 minute delay post-injection for optimal diagnostic accuracy 8
CT angiography with proper arterial phase imaging provides excellent spatial resolution for Takayasu arteritis 8
CNS Vasculitis Imaging
MRI brain is the preferred initial imaging modality for suspected CNS vasculitis, with abnormal findings in >90% of cases 8, 9
Cerebral angiography has submillimeter resolution but is limited by its invasive nature 8, 9
Brain biopsy is the most specific diagnostic test for diffuse or multifocal CNS vasculitis 8, 9
Treatment Approach Based on Disease Severity
Patients with ANCA-associated vasculitis must be managed at centers with expertise in vasculitis management, with access to rapid diagnostic capabilities, all treatment modalities including rituximab and plasma exchange, intensive care, and acute hemodialysis. 1, 2
Remission Induction for Organ or Life-Threatening Disease
For generalized organ-threatening or life-threatening AAV, use cyclophosphamide OR rituximab combined with glucocorticoids 1, 3
Rituximab 375 mg/m² once weekly for 4 weeks is non-inferior to cyclophosphamide for achieving complete remission at 6 months (64% vs 53%) 10
Pulse intravenous methylprednisolone 1000 mg daily for 1-3 days, followed by oral prednisone 1 mg/kg/day (maximum 80 mg/day) with pre-specified tapering 10
Consider plasma exchange for rapidly progressive renal failure or pulmonary hemorrhage 1
Non-Organ Threatening Disease
- Methotrexate or mycophenolate mofetil with glucocorticoids for non-organ threatening disease 1
Remission Maintenance
After achieving remission, maintain with azathioprine, methotrexate, or rituximab combined with low-dose glucocorticoids 1, 3
Continue maintenance therapy for 2-5 years, then taper azathioprine or methotrexate, or stop rituximab 1
In the rituximab group from pivotal trials, 44% achieved complete remission at 6 and 12 months, and 38% maintained remission through 18 months 10
Disease Monitoring
Use structured assessment tools like the Birmingham Vasculitis Activity Score (BVAS) at each visit to evaluate disease activity 1, 3
Serial ANCA determination is recommended in AAV trials, though results must be interpreted in clinical context as levels don't always correlate with disease activity 1, 4, 5
Monitor serum immunoglobulin levels prior to each rituximab course and in patients with recurrent infections, as hypogammaglobulinemia can occur 1
Regular cardiovascular risk assessment is essential for all AAV patients 1
Investigate persistent unexplained hematuria in patients with prior cyclophosphamide exposure due to bladder cancer risk 1
Special Clinical Scenarios
Pulmonary-renal syndrome (acute kidney injury with alveolar hemorrhage) requires immediate serologic testing: positive anti-GBM antibodies suggest anti-GBM disease, while positive MPO or PR3-ANCA supports AAV diagnosis. 1, 3