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Granulomatosis With Polyangiitis (GPA)

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Granulomatosis With Polyangiitis (GPA)

Granulomatosis with polyangiitis (GPA), previously called Wegener granulomatosis, is an autoimmune disease in which the body’s immune system attacks small and medium-sized blood vessels.

Also called

Wegener’s granulomatosis — older term

ICD-10

M31.30

Specialty

Pulmonology

Onset

Chronic

Reviewed

July 2026

On This Page

Overview

What is it? An ANCA-associated vasculitis that damages blood vessels. Commonly affects: Nose and sinuses, lungs, kidneys.

This causes inflammation (vasculitis) and granuloma formation

Etiology & Risk Factors

-Etiology :

  • Unknown (idiopathic) in most cases.
  • Often occurs after respiratory tract infections, although the exact cause is not known.
  • It is an autoimmune disease in which PR3-ANCA antibodies activate neutrophils, leading to inflammation and damage of small and medium-sized blood vessels.

-Risk Factors :

  • Age: Most common between 40–60 years.
  • Sex: Men and women are affected equally.
  • Possible trigger: Respiratory tract infections may precede the disease.

Pathophysiology

Unknown trigger (idiopathic, sometimes after respiratory infection) → PR3-ANCAautoantibodies form → PR3-ANCA binds to proteinase-3 (PR3) on neutrophils →Neutrophil activation → Release of inflammatory mediators + neutrophil extracellular traps (NETs) + complement activation → Damage to small and medium-sized blood vessel endothelium → Necrotizing granulomatous vasculitis → Inflammation and tissue injury → ENT disease (sinusitis/rhinitis), lung disease, and rapidly progressive glomerulonephritis (kidney involvement)

Clinical Presentation

General: Fever, weight loss, fatigue

  • ENT (most common): Chronic sinusitis, blocked/bloody nose, ear infections, saddle nose deformity
  • Lungs: Cough, shortness of breath, hemoptysis
  • Kidneys: Hematuria, rapidly progressive glomerulonephritis (RPGN)
  • Skin: Purpura, ulcers
  • Eyes: Conjunctivitis, corneal ulcers

History Taking

  • Do you have chronic sinus pain or a blocked nose?
  • Have you had nosebleeds or bloody nasal discharge? Do you have a persistent cough?
  • Have you coughed up blood (hemoptysis)?
  • Do you feel short of breath?
  • Have you noticed blood in your urine or dark urine?
  • Have you had fever, weight loss, or fatigue?
  • Have you had ear infections or hearing problems?
  • Do you have eye redness, pain, or vision changes?
  • Have you developed a skin rash or ulcers?

Physical Examination

-Look for:

  • General: Fever, weight loss

  • Nose/ENT: Nasal ulcers, saddle nose deformity, bloody/purulent nasal discharge

  • Lungs: Crackles, signs of hemoptysis

  • Skin: Purpura, ulcers

  • Eyes: Conjunctivitis, red eyes, corneal ulcers

  • Mouth: Oral ulcers, strawberry gingivitis

    Key Physical Signs

  • Saddle nose deformity

  • Purpura

     

  • Strawberry gingivitis

  • Conjunctivitis

Investigations of Granulomatosis With Polyangiitis (GPA)

  • Blood tests
  • PR3-cANCA (most important)
  • CBC
  • ESR, CRP
  • Urea, creatinine (renal function)
  • Urine tests
  • Urinalysis: hematuria, proteinuria Urine microscopy: RBC casts
  • Imaging
  • Chest X-ray/CT chest (lung involvement)
  • CT paranasal sinuses (sinus disease)
  • Confirmatory test
  • Biopsy (kidney or lung preferred): necrotizing granulomatous vasculitis

Diagnosis of Granulomatosis With Polyangiitis (GPA)

  • Diagnosis is based on clinical features + investigations, and is confirmed by biopsy.

-Most important diagnostic findings:

  • ENT + lung + kidney involvement (typical clinical picture)
  • PR3-cANCA positive
  • Urinalysis: Hematuria, proteinuria, RBC casts
  • Chest X-ray/CT: Pulmonary nodules or pulmonary hemorrhage Biopsy (gold standard): Necrotizing granulomatous vasculitis
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Related Topics

Management of Granulomatosis With Polyangiitis (GPA)

  • Refer to rheumatology (and other specialists as needed). Glucocorticoids (first-line treatment).

-Add an immunosuppressant :

  • Methotrexate (non-severe disease)
  • Rituximab (preferred for severe disease)
  • Cyclophosphamide (alternative for severe disease)
  • -Maintenance therapy : Gradually taper steroids and continue rituximab, methotrexate, or azathioprine.
  • Supportive care: Monitor for treatment side effects and consider Pneumocystis pneumonia prophylaxis.
  • Plasmapheresis: May be considered in selected patients (e.g., with concomitant anti-GBM disease).

Complications

  • Rapidly progressive glomerulonephritis (RPGN) → kidney failure
  • Pulmonary hemorrhage (diffuse alveolar hemorrhage) → life-threatening hemoptysis
  • Pulmonary fibrosis
  • Pulmonary hypertension
  • Cardiac involvement (pericarditis, myocarditis, myocardial infarction)
  • Relapse is common
  • The most serious complications are kidney failure and pulmonary hemorrhage, with diffuse alveolar hemorrhage being a common cause of death.

Prognosis of Granulomatosis With Polyangiitis (GPA)

  • Without treatment: < 20% 1-year survival.
  • With appropriate treatment: Approximately 80% 5-year survival. Diffuse alveolar hemorrhage is a common cause of death.
  • Relapses are common, so long-term follow-up is needed.

Key Points / Clinical Pearls of Granulomatosis With Polyangiitis (GPA)

  • Autoimmune ANCA-associated vasculitis affecting small and medium-sized blood vessels.
  • Mainly affects the nose/sinuses, lungs, and kidneys.
  • PR3-cANCA is the most important antibody.
  • Classic triad: ENT disease + Lung disease + Glomerulonephritis (RPGN).
  • Common symptoms: chronic sinusitis, cough, hemoptysis, hematuria.
  • Biopsy is the gold standard and shows necrotizing granulomatous vasculitis.
  • Main treatment: Glucocorticoids + immunosuppressant (methotrexate, rituximab, or cyclophosphamide).
  • Major complications: Kidney failure and pulmonary hemorrhage.
  • Relapses are common, so long-term follow-up is required.
  • Early diagnosis and treatment greatly improve survival.
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  • National Center for Biotechnology Information (NIH). ANCA-Associated Vasculitis, StatPearls.
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