Granulomatosis with polyangiitis (GPA; previously referred to as Wegener granulomatosis) is a systemic vasculitis that affects both small and medium-sized vessels. Patients typically initially present with a limited form that consists of constitutional symptoms and localized manifestations, such as chronic sinusitis, rhinitis, otitis media, ocular involvement, and/or skin lesions. More serious manifestations may develop in later stages, including pulmonary complications and glomerulonephritis; the heart may also be involved. Testing modalities include laboratory studies, imaging, and biopsy. Diagnosis is confirmed by biopsy findings of necrotizing granulomatous inflammation. Pharmacotherapy consists of immunosuppressive drugs, typically glucocorticoids combined with methotrexate, cyclophosphamide, or rituximab. Relapses are common.
- 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: often the first clinical manifestation
- Chronic rhinitis/sinusitis: nasopharyngeal ulcerations → nasal septum perforation → saddle nose deformity (depression of the nasal dorsum)
- Chronic otitis and/or mastoiditis
- In some cases, thick, purulent discharge, sometimes containing blood
- Oral ulcers
- Strawberry gingivitis: a characteristic feature of granulomatosis with polyangiitis characterized by painful, erythematous, gingival inflammation with petechiae that results in the appearance of the surface of a strawberry 
- Lower respiratory tract: potentially life-threatening
- Renal involvement: potentially life-threatening
- Skin lesions
- Ocular involvement
- Cardiac involvement: potentially life-threatening
General principles 
- Suspect GPA in patients with either:
- Consult rheumatology.
- Obtain laboratory and imaging studies to:
- Determine the extent and severity of organ involvement
- Rule out differential diagnoses (e.g., infection, neoplasm)
- Characteristic histopathological findings confirm the diagnosis.
- Routine studies
- Serology: ANCA (positive in ∼ 90% of patients) 
Imaging studies 
- Obtain a chest X-ray or CT chest for all patients to assess for lung involvement.
- Supportive findings
- Multiple bilateral cavitating nodular lesions
- Pulmonary hemorrhage
Consider additional studies to assess for organ involvement as needed, e.g.:
- Kidney ultrasound
- CT paranasal sinuses
- Cardiac studies (e.g., ECG, TTE): Consider in patients with cardiac symptoms.
- Consider in all patients to confirm the diagnosis.
- In patients with renal disease, a kidney biopsy may be required to assess for relapse and/or irreversible damage.
- Samples: may be obtained from any affected tissue
- Findings 
|Granulomatosis with polyangiitis (GPA)||Microscopic polyangiitis|
The differential diagnoses listed here are not exhaustive.
General principles 
- Consult rheumatology and other specialties (e.g., nephrology, pulmonology, otorhinolaryngology) as required.
- The goal of pharmacotherapy is to achieve remission within 3 months. 
- Plasmapheresis may be considered in certain patients, e.g., patients with concomitant anti-GBM disease. 
- Manage hemoptysis and ARDS urgently, if present.
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Induction of remission
Indication: patients with active disease
- Nonsevere disease
- Severe disease (i.e., organ- or life-threatening)
Indication: patients who initially presented with severe disease
- Slowly taper glucocorticoids to the minimum effective dose. 
- Glucocorticoid-sparing agents: e.g., rituximab (preferred), methotrexate, or azathioprine
- Duration of treatment: typically ≥ 18 months
Management of associated symptoms 
- Assess ASCVD risk and manage as indicated.
- Patients with sinonasal disease
- Patients with end-stage renal disease: Consider referral for kidney transplantation.
Supportive care 
- Monitor for .
- Consider .