Granulomatosis with polyangiitis (GPA)

Board exam relevance: in 6 of 105 exam reports · rank 59

Synonyms: Wegener granulomatosis, ANCA vasculitis, c-ANCA, PR3-ANCA, saddle nose
Specialty: Internal medicine · Rheumatology & immunology
Images: X-ray 1 · Histology 1 · Gross specimen 1 · Blood smear & cytology 1
Last updated: 10/2026 · Dr. Pascal Bafteh

Contents

Images (4)
Definition
Classification
Occurrence & epidemiology
Aetiopathogenesis
Clinical features
Histology
Diagnosis
Keep learning in the app
Further reading (open access)
Cross-references

Images (4)

Granulomatosis with polyangiitis (GPA) – Chest X-ray: bilateral, partly nodular opacities in both lungs in pulmonary GPA — Chest X-ray: bilateral, partly nodular opacities in both lungs in pulmonary GPAImage: Tom Buur (Wikimedia Commons) · CC BY-SA 4.0 · Source

Granulomatosis with polyangiitis (GPA) – Lung histology (H&E): necrotising granulomatous inflammation with vessel wall involvement and a mixed infiltrate — Lung histology (H&E): necrotising granulomatous inflammation with vessel wall involvement and a mixed infiltrateImage: Nephron (Wikimedia Commons) · CC BY-SA 3.0 · Source

Granulomatosis with polyangiitis (GPA) – gross specimen: Lung specimen: well-demarcated whitish nodule with central necrosis — Lung specimen: well-demarcated whitish nodule with central necrosisImage: Yale Rosen from USA (Wikimedia Commons) · CC BY-SA 2.0 · Source

Granulomatosis with polyangiitis (GPA) – Indirect immunofluorescence on neutrophils: granular cytoplasmic pattern (c-ANCA) caused by PR3 antibodies — Indirect immunofluorescence on neutrophils: granular cytoplasmic pattern (c-ANCA) caused by PR3 antibodiesImage: Simon Caulton (Wikimedia Commons) · CC BY-SA 3.0 · Source

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Definition

Granulomatosis with polyangiitis (GPA, formerly Wegener granulomatosis) is an ANCA-associated vasculitis with necrotizing granulomatous inflammation, vasculitis of small and medium-sized vessels, and focal necrotizing, often crescentic glomerulonephritis. Involvement of the upper and lower respiratory tract and kidneys is typical; in principle, any organ may be affected.

Classification

In the 2012 Chapel Hill nomenclature, GPA, together with microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis, belongs to the ANCA-associated small-vessel vasculitides. The 2022 ACR/EULAR classification criteria assign positive or negative points to clinical, laboratory, biopsy, and imaging features and thereby distinguish GPA, MPA, and EGPA. Typical GPA features in these criteria are nasal involvement, cartilaginous involvement, PR3 or c-ANCA, granulomas or giant cells on biopsy, pulmonary nodules or cavities, and sinusitis on imaging.

Occurrence & epidemiology

Incidence varies by population; a large UK cohort found 11.8 per million person-years. GPA is most common in people of European ancestry but occurs in all ethnic groups and at any age. The mean age at onset is 40 years.

Aetiopathogenesis

It is an autoimmune disease with antibodies against proteinase 3 (PR3) in the cytoplasm of neutrophils. Inflammation affects tissues as well as vessels; the vasculitic component may be small or large. Early micronecrosis with neutrophils (microabscesses) progresses to larger, geographic necrosis.

Clinical features

Onset is insidious or acute; respiratory symptoms often predominate initially, and the kidney is affected later.

Upper respiratory tract: sinus pain, serosanguineous or purulent nasal discharge, epistaxis, crusts, ulcers, septal perforation, saddle nose, subglottic stenosis with hoarseness and stridor.
Ears: otitis, sensorineural hearing loss, vertigo.
Eyes: conjunctivitis, scleritis, uveitis, retinal vasculitis, retro-orbital pseudotumor with proptosis and vision loss.
Lower respiratory tract: nodules with or without cavitation, infiltrates, alveolar hemorrhage with hemoptysis.
Kidney: glomerulonephritis up to the rapidly progressive form with hypertension and edema.
Skin and nerves: palpable purpura, nodules, livedo, ulcers; mononeuritis multiplex, cranial nerve deficits.
Myalgias, arthralgias, nonerosive arthritis; deep venous thrombosis during active disease.

Histology

Granulomas of histiocytic epithelioid cells, often with multinucleated giant cells, together with plasma cells, lymphocytes, neutrophils, and eosinophils. Central "geographic" necrosis is rimmed by lymphocytes, plasma cells, macrophages, and giant cells as well as palisading histiocytes. In the kidney, the most common finding is a pauci-immune, focal necrotizing glomerulonephritis with crescents.

Diagnosis

Laboratory tests: ESR and CRP elevated, albumin and total protein decreased, sometimes anemia and thrombocytosis; creatinine, urinalysis with dysmorphic red cells and red cell casts, 24-hour urine protein.
ANCA: immunofluorescence followed by ELISA; in active disease usually c-ANCA with antibodies against PR3. ANCA also occur in other conditions (e.g., endocarditis, cocaine use, lupus, tuberculosis); the positive predictive value is about 50 %.
Imaging: sinonasal CT (mucosal thickening, septal perforation, bone destruction); chest CT, because radiographs may miss nodules and cavities.
Biopsy of affected tissue confirms the diagnosis; lung tissue most likely shows the full picture, nasal biopsies rarely. A pauci-immune necrotizing glomerulonephritis on renal biopsy supports the diagnosis. Infections (mycobacteria, fungi) are excluded by stains and cultures.

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