What is the appropriate initial evaluation for a patient suspected of having granulomatosis with polyangiitis (Wegener disease)?

Initial Evaluation of Suspected Granulomatosis with Polyangiitis (Wegener Disease)

Immediately order PR3-ANCA testing and perform a systematic assessment of the upper respiratory tract, lungs, and kidneys, as PR3-ANCA is positive in 80-90% of cases and is highly specific for GPA. 1, 2

Essential Laboratory Investigations

Perform these baseline tests in all suspected cases:

• Complete blood count with differential to assess for anemia, leukocytosis, and thrombocytosis 1, 3
• PR3-ANCA (c-ANCA) testing using high-quality antigen-specific assays—this is the critical first diagnostic step with 84-85% sensitivity 1, 3, 2
• Renal function tests including creatinine and BUN to detect kidney involvement 1, 3
• Urinalysis with microscopy looking specifically for hematuria, proteinuria, and red blood cell casts 1, 3, 2
• 24-hour proteinuria or urine protein-to-creatinine ratio if urinalysis shows abnormalities 4
• Inflammatory markers including ESR and CRP to assess disease activity 1, 3

Required Imaging Studies

• Chest CT scan is mandatory and more sensitive than conventional radiographs for detecting pulmonary nodules, infiltrates, or cavitation 3, 2
• Sinus CT scan when upper respiratory symptoms are present (nasal crusting, epistaxis, chronic sinusitis occur in 70-100% of cases) 1, 2

Clinical Assessment Focus

Look for these characteristic manifestations during examination:

Upper Respiratory Tract (Present in >90% of Cases)

• Nasal examination for crusting, stuffiness, epistaxis, and septal perforation 1, 3
• ENT consultation with nasal endoscopy to evaluate for chronic rhinosinusitis, nasal polyps, and friable erythematous mucosa 4, 1
• Audiometry if hearing loss or otitis media is suspected 4

Pulmonary Manifestations

• Assess for cough, hemoptysis (present in >95% with lower respiratory tract disease), and dyspnea 1
• Pulmonary function tests to evaluate for restrictive or obstructive patterns and assess for subglottic stenosis 4, 1

Renal Involvement

• Look for signs of glomerulonephritis: proteinuria, hematuria, and declining renal function 1, 3
• Kidney biopsy should be performed if there is significant proteinuria (>1 g/day), glomerular hematuria, or unexplained renal dysfunction to confirm pauci-immune necrotizing crescentic glomerulonephritis 4, 1, 3

Systemic Manifestations

• Examine skin for palpable purpura or other vasculitic lesions 1, 3
• Assess for peripheral neuropathy through neurological examination 1, 3
• Electromyography and nerve conduction studies if neuropathy is suspected 4, 1
• Ophthalmologic evaluation for scleritis or other ocular manifestations 1, 3

Tissue Biopsy for Confirmation

• Biopsy of affected organs is strongly recommended when feasible to demonstrate necrotizing vasculitis with granulomatous inflammation 1, 3
• Nasal biopsies frequently lack diagnostic features; therefore, obtain tissue from lung or kidney when these organs are involved 1
• The definitive diagnosis requires the combination of characteristic clinical features, positive PR3-ANCA, and histologic confirmation 1, 3

Disease Activity Assessment

• Birmingham Vasculitis Activity Score (BVAS) should be calculated to quantify disease activity across multiple organ systems 1, 3, 2
• Five-Factor Score (FFS) helps predict mortality risk 1, 3

Critical Diagnostic Pitfalls to Avoid

• Do not rely solely on ACR classification criteria for diagnosis—these were developed for research classification, not clinical diagnosis, and should not be used as diagnostic criteria 3, 5
• Do not dismiss the diagnosis if ANCA is negative—approximately 10-20% of GPA cases are ANCA-negative, particularly in limited disease 1, 6
• Do not mistake subglottic stenosis symptoms for asthma—investigate abnormal inspiratory and expiratory flow-volume loops 1
• Recognize that nasal biopsies often fail to show diagnostic features—pursue lung or kidney biopsy when these organs are involved 1

Key Differential Diagnoses to Exclude

• Eosinophilic granulomatosis with polyangiitis (EGPA) is distinguished by blood eosinophilia >10%, elevated IgE, asthma, and MPO-ANCA (not PR3-ANCA) positivity in only 35-40% of cases 1, 3
• Microscopic polyangiitis lacks granulomatous inflammation and upper respiratory tract involvement 3
• IgA vasculitis and cryoglobulinemic vasculitis show immune-complex deposition on biopsy, whereas GPA demonstrates a pauci-immune pattern 1