Granulomatosis with Polyangiitis
GPA is a primary vasculitis characterized by:
- Upper and lower respiratory tract involvement with granulomatous vasculitis of mostly small vessels, extravascular granulomatous inflammation, and necrosis
- Glomerulonephritis that is pauci-immune, focal and segmental, necrotizing, and often crescentic
- Strong association with c-ANCA and anti-proteinase 3 (PR3) antibodies
Generalized GPA implies involvement of all three major anatomic sites (upper respiratory tract, lungs, kidneys). Limited GPA is defined as the absence of renal involvement. Notably, limited GPA tends to present as a granulomatous disorder without vasculitic features. Only 10% of cases evolve to generalized GPA.
The true prevalence and incidence of GPA are unknown, but it is a rare disorder. It is much less common than other rheumatologic disorders. The mean age at diagnosis is 41 years. Although the age range is 5 to 78 years, only 16% of patients are <18 years of age. Males and females are equally affected.
The presence of GPA is indicated by:
- Nasal or oral inflammation (ulcers, purulent or bloody secretions).
- Abnormal chest x-ray: fixed infiltrates, nodules, caverns
- Abnormal urine sediment: haematuria or ery-cylinder
- Granulomas in biopsy in arterial wall or perivascular
GPA can be diagnosed without biopsy evidence if the following findings are present:
- Lung: fixed infiltrates (>1month), nodules or caverns; bronchial stenosis
- Oral or nasal ulcers; crusts or bloody secretions; sinusitis, otitis media, mastoiditis >3 months; retroorbital masses, saddle nose, subgottic stenosis.
- Glomerulonephritis: haematuria with ery-cylinder, >10 dysmorphic erys; 2+ haematuria or proteinuria in uristix.
- ANCA positivity
Persistent pulmonary infiltrates over 1 month are suggestive of GPA
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SYNDROME |
EXAMPLE |
DISTINGUISHING FEATURES |
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Primary vasculitis syndromes |
EGPA |
Atopic history |
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Marked eosinophilia |
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Microscopic polyangiitis |
Destructive upper airway disease unusual |
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Cavitary pulmonary nodules unusual |
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Absence of granuloma |
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Angiocentric immunoproliferative lesions |
Lymphomatoid granulomatosis |
Glomerulonephritis unusual |
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Pulmonary renal syndromes |
Goodpasture disease |
Anti-basement membrane antibodies |
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Immunofluorescence: linear deposition |
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Immune complex disease (e.g., SLE) |
ANA, anti-dsDNA and Sm antibodies |
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Immunofluorescence: granular deposition |
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Granulomatous infections |
Mycobacterium |
Proper stains and cultures |
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Fungi |
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Actinomycosis |
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Syphilis |
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Intranasal drug abuse |
Cocaine |
Antineutrophil elastase antibodies |
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Predominantly nasal septal pathology (CIMDL) |
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Pseudovasculitis syndromes |
Atrial myxoma |
Echocardiography |
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Subacute bacterial endocarditis |
Blood cultures |
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Cholesterol emboli syndrome |
Echocardiography (transesophageal) |
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Angiography |
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Skin biopsy |
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Neoplastic |
Lethal midline granuloma |
Nose/palate destruction |
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NK T cell lymphoma |
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CIMDL, Cocaine-induced midline destructive lesion, which is usually associated with p-ANCA directed against human neutrophil elastase. |
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