Granulomatosis with Polyangiitis (Wegener's)

Content of This Page

1- Definition and Terminology

2- Immunopathogenesis

3- ENT Manifestations

4- Pulmonary Manifestations

5– Renal Involvement

6- Neurological Involvement

7- Musculoskeletal and Skin Signs

8- Role of ANCA in GPA

9- Histopathological Findings

10- Treatment Overview

11- Prognosis and Monitoring

Definition and Terminology

  • GPA is a necrotising granulomatous vasculitis affecting small to medium vessels, part of the ANCA-associated vasculitides (AAV).

  • Previously known as Wegener’s granulomatosis, renamed to GPA to reflect its pathology and remove eponyms.

© image from Wikimedia Commons

Immunopathogenesis

  • Autoimmunity leads to production of PR3-ANCA (cytoplasmic-ANCA).

  • ANCA activates neutrophils, triggering:

    • Endothelial injury

    • Inflammatory necrosis

    • Granuloma formation

  • Combined vasculitis + granulomas explain multi-system organ damage.

ENT Manifestations

  • Occurs in >90% of cases.

  • Key signs:

    • Persistent rhinitis

    • Epistaxis

    • Nasal crusting or septal perforation

    • Saddle-nose deformity from cartilage collapse

    • Hearing loss due to otitis media or mastoiditis

–ENT disease is often the first manifestation.

Pulmonary Manifestations

  • Occur in ~50–70% of patients.

  • Typical features:

    • Cough, dyspnoea, haemoptysis

    • Nodular opacities, often bilateral and cavitating

    • Pulmonary haemorrhage in severe disease

  • Imaging: CXR or HRCT shows migrating infiltrates, nodules

Wegeners Granulomatosis © image from Wikimedia Commons

Renal Involvement

  • Seen in ~80% of patients over disease course.

  • Usually presents as rapidly progressive glomerulonephritis (RPGN):

    • Proteinuria, microscopic haematuria, red cell casts

    • May progress to renal failure within weeks

  • Biopsy shows: pauci-immune, crescentic glomerulonephritis

Ocular and Orbital Disease

  • Proptosis, optic nerve compression, or scleritis

  • Sclerokeratitis may occur — a severe, sight-threatening combination of scleritis and peripheral ulcerative keratitis

  • Early warning sign: loss of colour vision (suggests optic nerve involvement)

  • May mimic orbital mass or tumour on imaging

Sclerokeratitis © image from Wikimedia Commons

Neurological Involvement

  • Peripheral neuropathy: mononeuritis multiplex (e.g. foot drop)

  • CNS: rare but may include stroke, seizures, meningeal inflammation

Musculoskeletal and Skin Signs

  • Arthralgia or non-erosive arthritis

  • Purpura, nodules, ulcers from cutaneous vasculitis

  • Nailfold infarcts or digital gangrene

Role of ANCA in GPA

  • PR3-ANCA (c-ANCA): highly specific for GPA (~90% in active disease)

  • MPO-ANCA (p-ANCA): rare in GPA, more common in microscopic polyangiitis

  • ANCA titres may fall in remission but don’t always predict relapse

-Diagnosis is clinical + serological; biopsy helps confirm if unclear.

Histopathological Findings

Triad of:

  • Necrotising granulomatous inflammation

  • Vasculitis of small/medium vessels

  • Pauci-immune glomerulonephritis (on kidney biopsy)

Treatment Overview

a. Induction of Remission (organ-threatening disease)

  • IV methylprednisolone (3-day pulse), then oral taper

  • Cyclophosphamide or Rituximab (RAVE trial: equivalent efficacy)

b. Maintenance of Remission

  • Azathioprine, methotrexate, or mycophenolate

  • Continue low-dose steroids for several months

  • Monitor for relapse clinically and with CRP/creatinine

Prognosis and Monitoring

  • 5-year survival >80% with treatment.

  • Relapse occurs in ~50% of cases—especially in PR3-ANCA+ patients.

  • Major causes of morbidity:

    • Renal failure

    • Treatment-related infections

    • Chronic steroid complications

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