Granulomatosis with polyangiitis
Granulomatosis with polyangiitis (GPA) is an antineutrophil cytoplasmic antibody (ANCA)-associated necrotizing granulomatous vasculitis of the upper airway, lower airway, and kidney, most often with cytoplasmic ANCA (c-ANCA) targeting proteinase 3 (PR3). Diagnosis rests on the clinical triad, ANCA serology, and tissue biopsy showing pauci-immune vasculitis, and treatment begins with high-dose glucocorticoids plus rituximab or cyclophosphamide for organ-threatening disease, followed by rituximab or azathioprine maintenance.
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What this article covers
- Overview
Definition: granulomatosis with polyangiitis (GPA), formerly Wegener granulomatosis, is a necrotizing granulomatous vasculitis of small and medium vessels associated with antineutrophil cytoplasmic…
- Epidemiology
Most common ANCA-associated vasculitis: GPA is the most common of the three, with an annual incidence of 7 to 12 per million.
- Risk factors
Age and race: peak incidence between ages 65 and 70 years; more prevalent in white populations.
- Pathophysiology
ANCA specificity: the cytoplasmic immunofluorescence pattern (c-ANCA), produced by antibodies against PR3, predominates in GPA and is confirmed by an antigen-specific enzyme-linked immunosorbent assay.
- Clinical features
Upper airway disease: chronic sinusitis, nasal crusting, rhinorrhea, and epistaxis, with chondritis of the ears and nose progressing to septal perforation and saddle-nose deformity, plus otitis media…
- Differential diagnosis
Microscopic polyangiitis: shares pulmonary hemorrhage and pauci-immune crescentic glomerulonephritis, but spares the upper airway, has no granulomas on biopsy, and is predominantly…
- Diagnosis
What establishes the diagnosis: a compatible clinical picture (upper airway, lower airway, renal involvement) with c-ANCA/anti-PR3 positivity makes the diagnosis highly likely; the classification…
- Management
First, for organ-threatening or life-threatening disease, pulse then taper glucocorticoids: Methylprednisolone 500 to 1000 mg IV once daily for 3 days.
- Complications
End-stage kidney disease: the consequence of unchecked pauci-immune crescentic glomerulonephritis, in up to 25% of survivors within 4 years of diagnosis.
- Prognosis
Mortality has fallen with treatment: before effective immunosuppression, GPA mortality approached 90%; with glucocorticoids combined with rituximab or cyclophosphamide, mortality has declined to around 10%.
- Prevention
No primary prevention exists: GPA is idiopathic in most cases; when drug induced, stopping the offending agent is the only preventive measure.
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Related articles
- Microscopic polyangiitis
Microscopic polyangiitis (MPA) is a pauci-immune small-vessel vasculitis, almost always with perinuclear antineutrophil cytoplasmic antibody (p-ANCA) targeting myeloperoxidase (MPO), that causes rapidly progressive crescentic glomerulonephritis and pulmonary alveolar hemorrhage without the granulomas, eosinophilia, or upper-airway disease of its ANCA-associated siblings. Diagnosis combines urine microscopy, ANCA serology, and biopsy, and treatment is glucocorticoids plus rituximab or cyclophosphamide induction followed by rituximab or azathioprine maintenance.
- Eosinophilic granulomatosis with polyangiitis
Eosinophilic granulomatosis with polyangiitis (EGPA) is the rarest antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, defined by a three-phase course of late-onset asthma and rhinosinusitis, then peripheral and tissue eosinophilia, then small- and medium-vessel vasculitis with mononeuritis multiplex. ANCA is positive in only 40 to 60 percent of patients, cardiac involvement drives most mortality, and treatment is glucocorticoids alone for non-organ-threatening disease, glucocorticoids plus cyclophosphamide or rituximab for organ-threatening disease, and mepolizumab as steroid-sparing therapy.
- Vasculitis: an overview
Vasculitis is inflammation and necrosis of blood vessel walls, classified by the Chapel Hill scheme into large, medium, small (ANCA-associated versus immune-complex), and variable-vessel disease, each with a vessel-size-predicted clinical syndrome. Diagnosis requires excluding mimics such as infective endocarditis and cholesterol embolization before confirming with serology and biopsy, and treatment is glucocorticoid induction plus cyclophosphamide or rituximab for organ-threatening disease.
- Anti-glomerular basement membrane (anti-GBM) disease
Anti-glomerular basement membrane (anti-GBM) disease is a rare, rapidly progressive glomerulonephritis caused by circulating antibodies against the alpha-3 chain of type IV collagen, presenting with hematuria, acute kidney injury, and, in over half of patients, pulmonary hemorrhage (Goodpasture syndrome). Kidney biopsy showing crescentic glomerulonephritis with linear IgG staining plus a positive serum anti-GBM antibody confirms the diagnosis, and outcome depends critically on early treatment with plasma exchange, pulse glucocorticoids, and cyclophosphamide before dialysis dependence and diffuse crescents set in.
- Rapidly progressive glomerulonephritis
Rapidly progressive glomerulonephritis is a clinical syndrome defined by at least a 50% decline in glomerular filtration rate over days to weeks with extensive glomerular crescents on biopsy, most often from ANCA-associated, anti-glomerular basement membrane, or immune-complex glomerulonephritis. Untreated disease progresses to dialysis within days to weeks, so kidney biopsy and etiology-directed immunosuppression must begin urgently.