- Clinical science
Granulomatosis with polyangiitis (GPA, previously known as Wegener's granulomatosis) is a systemic vasculitis that affects both small and medium-sized vessels. Patients typically initially suffer from a limited form that may consist of constitutional symptoms and localized manifestations such as chronic sinusitis, rhinitis, otitis media, ocular conditions, and/or skin lesions. In later stages, more serious manifestations may arise, including pulmonary complications and glomerulonephritis, although the skin, eyes, and heart may also be involved. Diagnosis is based on laboratory testing (positive for PR3-ANCA/c-ANCA), imaging, and biopsy of affected organs, which demonstrate necrotizing granulomatous inflammation. GPA is treated with immunosuppressive drugs, typically consisting of glucocorticoids combined with methotrexate, cyclophosphamide, or rituximab. Relapses are common.
- Sex: ♂ = ♀
- Peak incidence: 65–74 years
- Affects white patients disproportionately; African-American patients are rarely affected.
Epidemiological data refers to the US, unless otherwise specified.
- GPA is a type of
- The following processes play a key role in the pathophysiology of GPA:
Binding of PR3-ANCA to PR3 activates neutrophils → release of neutrophilic inflammatory mediators, formation of neutrophil extracellular traps, complement activation → damage to endothelial cells of small blood vessels
- Constitutional symptoms: fever; , night sweats, weight loss, arthralgias
- ENT involvement(∼ 90% of cases): often the first clinical manifestation
- Lower respiratory tract (∼ 95% of cases): potentially life-threatening
- Renal involvement (∼ 80% of cases): potentially life-threatening
- Skin lesions (∼ 45% of cases)
- Ocular involvement (∼ 45% of cases)
- Cardiac involvement (∼ 33% of cases): potentially life-threatening
- Chest x-ray/CT: multiple bilateral cavitating nodular lesions
A biopsy is necessary to confirm the diagnosis!
|Granulomatosis with polyangiitis (GPA)||Microscopic polyangiitis|
The differential diagnoses listed here are not exhaustive.
- If mild disease; → glucocorticoids + methotrexate (MTX)
- If moderate to severe disease; → glucocorticoids + either cyclophosphamide or rituximab
- Glucocorticoids should be tapered gradually as soon as the patient begins responding to the immunosuppressant agent.
- In the case of concurrent plasmapheresis :
- Remission maintenance : immunosuppressive drugs (e.g., azathioprine, rituximab or methotrexate).
- Without adequate treatment, the mortality rate is approx. 90% within 2 years.
- 5-year survival with adequate treatment is approx. 80%.