Diagnostic Criteria for Granulomatosis with Polyangiitis (GPA)
The diagnosis of Granulomatosis with Polyangiitis requires a combination of clinical features, laboratory testing (particularly PR3-ANCA), and histopathological findings, with biopsy of affected tissue being the gold standard for confirmation whenever possible. 1
Core Diagnostic Elements
- PR3-ANCA Testing: PR3-ANCA is detected in 84-85% of patients with GPA and strongly supports the diagnosis when combined with compatible clinical features 1
- Tissue Biopsy: Recommended to confirm diagnosis whenever possible, with biopsy sites chosen based on clinical involvement (kidney, lung, skin, or nasal mucosa) 1, 2
- Histopathological Features: Necrotizing vasculitis of small vessels, extensive "geographic" necrosis, and granulomatous inflammation are cardinal histologic features 3, 2
Clinical Manifestations
- Upper Respiratory Tract: Sinusitis, nasal crusting, epistaxis, saddle nose deformity, and otitis media 1, 4
- Lower Respiratory Tract: Pulmonary nodules, infiltrates, cavitary lesions, and alveolar hemorrhage 3, 4
- Renal Involvement: Necrotizing glomerulonephritis presenting as hematuria, proteinuria, and varying degrees of renal insufficiency 4, 2
- Other Manifestations: Skin lesions, peripheral neuropathy, ocular inflammation, and arthralgia 5, 2
Laboratory Testing
- ANCA Testing: Both PR3-ANCA and MPO-ANCA should be tested using high-quality antigen-specific assays 1
- Other Laboratory Tests: Complete blood count with differential, renal function tests, and urinalysis 1
Imaging Studies
- Chest CT: More sensitive than conventional radiographs for detecting pulmonary manifestations 1
- Sinus CT: Should be performed when upper respiratory tract involvement is suspected 1
- MRI: Useful for detecting central nervous system lesions, pachymeningitis, retro-orbital lesions, or subglottic inflammation 1
Disease Activity Assessment
- Birmingham Vasculitis Activity Score (BVAS): Primary validated tool for assessing disease activity 7
- Five-Factor Score (FFS): Predicts mortality risk in established vasculitis 7
Differential Diagnosis
- Eosinophilic Granulomatosis with Polyangiitis (EGPA): Distinguished by asthma, eosinophilia, and predominantly MPO-ANCA positivity (when ANCA-positive) 8
- Microscopic Polyangiitis: Typically lacks granulomatous inflammation and upper airway involvement 8
- Other conditions: IgA vasculitis, cryoglobulinaemia (which typically show immune deposits, absent in GPA) 8
Diagnostic Pitfalls and Challenges
- ANCA-Negative GPA: Approximately 10-20% of GPA cases are ANCA-negative, making diagnosis more challenging 6
- Limited Disease Forms: Localized forms affecting only one organ system may have lower ANCA positivity rates (around 50%) 4
- Concomitant Infections: Can mask or mimic disease activity and complicate diagnosis 5
- Non-specific Presentations: Constitutional symptoms like fever, weight loss, and arthralgia may delay diagnosis 6, 2
Monitoring Recommendations
- Serial ANCA Testing: Recommended but should not be used in isolation for treatment decisions 7
- Structured Evaluation: Regular assessment for new organ involvement at each clinical visit 7
- Immunoglobulin Monitoring: Important in patients treated with rituximab 7
By systematically evaluating clinical features, laboratory findings, imaging studies, and histopathology, clinicians can establish a diagnosis of GPA and initiate appropriate treatment to reduce morbidity and mortality associated with this condition.