Granulomatosis with polyangiitis

Granulomatosis with polyangiitis (GPA), formerly known as Wegener's granulomatosis, is a rare systemic autoimmune disease characterized by necrotizing granulomatous inflammation and vasculitis (inflammation of blood vessels), primarily affecting small- to medium-sized blood vessels. The disease most commonly involves the upper respiratory tract (sinuses, nose, ears), the lungs, and the kidneys, though it can affect virtually any organ system. GPA belongs to the group of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides, with most patients testing positive for cytoplasmic ANCA (c-ANCA) directed against proteinase 3 (PR3). Key symptoms vary depending on the organs involved but frequently include chronic sinusitis, nasal crusting and epistaxis (nosebleeds), saddle nose deformity due to nasal cartilage destruction, cough, hemoptysis (coughing up blood), pulmonary nodules or infiltrates, and kidney disease (glomerulonephritis) that can progress to renal failure if untreated. Other manifestations may include joint pain, skin lesions (purpura, ulcers), eye inflammation (scleritis, orbital pseudotumor), peripheral neuropathy, and constitutional symptoms such as fever, fatigue, and weight loss. The disease can present in a limited form affecting primarily the upper and lower respiratory tract, or in a severe generalized form with life-threatening renal and pulmonary involvement. Without treatment, generalized GPA carries a very poor prognosis. Modern treatment has dramatically improved outcomes and typically involves two phases: induction of remission using immunosuppressive agents such as cyclophosphamide or rituximab combined with glucocorticoids, followed by maintenance therapy with agents such as rituximab, azathioprine, or methotrexate to prevent relapse. Plasma exchange may be considered in severe cases with rapidly progressive glomerulonephritis or pulmonary hemorrhage. Despite effective therapies, relapses are common, occurring in a significant proportion of patients, and long-term monitoring is essential. Avacopan (a complement C5a receptor inhibitor) has been approved as an adjunctive treatment, offering a glucocorticoid-sparing approach.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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