Clinical Presentation of Granulomatosis with Polyangiitis (GPA)
Granulomatosis with polyangiitis (GPA) is characterized by inflammation of small to medium-sized blood vessels with typical features including nasal crusting, stuffiness, epistaxis, scleritis, upper respiratory tract involvement, and often kidney disease when accompanied by active urinary sediment. 1
Key Clinical Manifestations
Upper Respiratory Tract and ENT Involvement
- Nasal crusting, stuffiness, and epistaxis (nosebleeds) are common presenting symptoms 1
- Chronic rhinosinusitis with possible nasal polyps 1
- Otitis media and hearing loss may occur 1
- Nasal septal perforation can develop in advanced cases 1
- Scleritis and other ocular manifestations 1
Pulmonary Manifestations
- Pulmonary infiltrates and nodules are common 1
- Alveolar hemorrhage can occur in severe cases 1, 2
- Dyspnea and pleuritic chest pain may be presenting symptoms 2
- Decreased breath sounds and dullness to percussion at affected lung areas 2
Renal Involvement
- Glomerulonephritis is a hallmark feature, though not always present at initial presentation 1, 2
- May manifest as proteinuria, hematuria, and varying degrees of kidney failure 1
- Rapidly progressive glomerulonephritis with extensive crescent formation in severe cases 3
Other Systemic Manifestations
- Fever, fatigue, and weight loss are common constitutional symptoms 2
- Peripheral neuropathy may occur 1
- Skin lesions including palpable purpura 1
- Arthralgia and myalgia 1
Laboratory Findings
ANCA Testing
- Anti-neutrophil cytoplasmic antibodies (ANCA) testing should be performed in all suspected cases 1
- PR3-ANCA (c-ANCA) is highly specific to GPA and present in 80-90% of cases 1, 4
- ANCA positivity is not essential for diagnosis but has high diagnostic value 4, 5
Other Laboratory Tests
- Leukocytosis is common 2
- Elevated inflammatory markers (ESR, CRP) 4
- Urinalysis may show hematuria and proteinuria in cases with renal involvement 1
Diagnostic Evaluation
Imaging Studies
- Chest CT may show consolidation, nodules, or cavitary lesions 2
- Sinus CT can reveal mucosal thickening, bony destruction, or masses in the nasal cavity and sinuses 2
Histopathology
- Biopsy of affected organs is paramount for definitive diagnosis 2
- Characteristic findings include:
Disease Classification and Assessment
- The Birmingham Vasculitis Activity Score (BVAS) is the primary validated tool for assessing disease activity 6
- The Five-Factor Score (FFS) predicts mortality risk 6
- BVAS/WG evaluates manifestations across multiple systems including systemic, cutaneous, mucous/ocular, ENT, pulmonary, cardiovascular, gastrointestinal, and renal 6
Treatment Approach
Induction Therapy
- Initial therapy includes glucocorticoids combined with either rituximab or cyclophosphamide 1, 7
- For severe disease with organ-threatening manifestations, combination therapy is essential 7, 3
- Plasma exchange may be considered in cases with pulmonary hemorrhage or severe renal involvement 1, 3
Maintenance Therapy
- Options include azathioprine, methotrexate, rituximab, or co-trimoxazole 1
- Rituximab maintenance has shown efficacy in reducing relapses 5
Prognosis and Monitoring
- Without treatment, GPA has high mortality rates 5
- With appropriate treatment, remission can be achieved in more than 80% of cases 5
- Relapses occur in more than 50% of cases despite treatment 5
- Regular monitoring of ANCA levels is recommended, though decisions should not be based solely on ANCA titers 6
- Monitoring for treatment-related complications is essential 7
Common Pitfalls in Diagnosis
- GPA can mimic infectious diseases, particularly lung abscess or chronic sinusitis, leading to delayed diagnosis 2
- Initial screening with ANCA serology is recommended in patients with suggestive clinical findings 2
- Multisystem involvement may not be apparent at initial presentation, requiring high clinical suspicion 2
- Negative ANCA does not rule out the diagnosis, especially in limited forms of the disease 4