What is the initial workup for suspected vasculitis?

Initial Workup for Suspected Vasculitis

Begin with essential laboratory tests (CBC, CMP, ESR, CRP, urinalysis), ANCA testing for small vessel disease, and obtain tissue biopsy from affected organs whenever accessible, as biopsy remains the gold standard for definitive diagnosis. 1, 2

Laboratory Evaluation

Essential Initial Tests

• Complete blood count with differential to assess for anemia, thrombocytopenia, or leukocytosis 1, 2
• Comprehensive metabolic panel including creatinine to evaluate renal function 1, 2
• Inflammatory markers: ESR and CRP are critical for diagnosis and monitoring, though they lack specificity 3, 1
• Urinalysis is mandatory to detect hematuria, proteinuria, and red cell casts suggesting glomerulonephritis 1, 2

Autoimmune Serologies

• ANCA testing using both indirect immunofluorescence AND ELISA when small vessel vasculitis (granulomatosis with polyangiitis, microscopic polyangiitis) is suspected 3, 1, 2
• The 2017 international consensus recommends high-quality antigen-specific immunoassays (MPO-ANCA and PR3-ANCA) as the preferred screening method 1
• Important caveat: Approximately 10% of patients with clinical ANCA-associated vasculitis are ANCA-negative, requiring tissue biopsy for diagnosis 1, 2
• Anti-nuclear antibodies to evaluate for connective tissue diseases 2
• Hepatitis B and C serologies, particularly when liver involvement or cryoglobulinemia is present 4

Organ-Specific Testing

• 24-hour urine collection for protein and creatinine clearance when renal involvement is suspected 2
• Serum cryoglobulins if HCV-related vasculitis is considered 3

Imaging Studies

Selection Based on Vessel Size

Large Vessel Vasculitis (Giant Cell Arteritis, Takayasu Arteritis)

• Temporal artery ultrasound shows 88% sensitivity and 97% specificity for Giant Cell Arteritis 1, 5
• MRI/MRA of affected arterial territories provides thorough assessment of the arterial tree 3, 1, 5
• FDG-PET/CT demonstrates inflammatory cell accumulation in vessel walls with high sensitivity and specificity; perform after 6 hours fasting with 120-180 minute delay post-injection 1, 5
• CT angiography provides excellent spatial resolution and can detect vessel wall alterations before luminal changes 3, 5

CNS Vasculitis

• MRI brain is the preferred initial modality, showing abnormalities in >90% of cases 3, 5
• MRI is more sensitive than CT except for large ischemic infarctions and hemorrhage 3
• Transcranial color-Doppler ultrasonography may assist in detecting CNS vasculitic alterations 3
• Cerebral angiography provides submillimeter resolution but is invasive 5

Pulmonary Involvement

• Chest X-ray or CT to evaluate for infiltrates, cavitary lesions, or pulmonary hemorrhage 2

Tissue Biopsy - The Gold Standard

General Principles

• Biopsy of affected tissue is strongly recommended to establish new diagnosis and evaluate suspected relapse 3, 1, 6
• Biopsy provides both diagnostic confirmation and prognostic information 3, 1
• The diagnostic yield for demonstrating granuloma or vasculitis exceeds 70%, varying by organ sampled 1

Organ-Specific Biopsy Approaches

Renal Biopsy

• Provides definitive diagnosis and prognostic information through assessment of glomerular, tubulointerstitial, and vascular histopathology 1, 2
• Diagnostic yield for pauci-immune glomerulonephritis in GPA reaches 91.5% 3

Temporal Artery Biopsy

• Should be performed whenever Giant Cell Arteritis is suspected, but should not delay treatment initiation 3
• Contralateral biopsy is not routinely indicated 3

Cutaneous Biopsy

• Extend biopsy to subcutis from the most tender, reddish, or purpuric lesional skin 6
• Serial sections often required to identify the main vasculitic lesion 6
• Obtain concomitant specimen for direct immunofluorescence to distinguish IgA-associated vasculitis (Henoch-Schönlein purpura) from IgG/IgM-associated vasculitis 6, 7

Otorhinolaryngological Biopsy

• In GPA, biopsies may show inflammatory changes in up to 68.4% of cases 3

Lung Biopsy

• Transbronchial biopsies show only 12% positivity for GPA but 66.7% for EGPA 3
• Invasive procedures provide higher diagnostic yield 3

Brain Biopsy

• Most specific test for diffuse or multifocal CNS vasculitis, though limited by invasive nature 5

Peripheral Nerve Biopsy

• Sural nerve biopsy with intraepidermal nerve fiber density assessment when peripheral neuropathy is suspected 3

Critical Clinical Scenarios

Pulmonary-Renal Syndrome

• Acute kidney injury with alveolar hemorrhage should immediately raise concern for vasculitis 1
• Positive anti-GBM antibodies suggest anti-GBM disease; positive MPO or PR3-ANCA supports ANCA-associated vasculitis 1
• Pulmonary hemorrhage affects 10% of ANCA-associated vasculitis patients and increases mortality risk 1

Management Setting

All patients with suspected vasculitis should be managed in close collaboration with, or at, centers of expertise to ensure optimal outcomes and access to specialized diagnostic capabilities 3, 1, 2