Granulomatosis with Polyangiitis

Granulomatosis with Polyangiitis is a systemic necrotizing vasculitis affecting small and medium blood vessels, characterized by the triad of granulomatous inflammation, necrotizing vasculitis, and glomerulonephritis. The disease results from ANCA-associated immune mechanisms, with most patients positive for c-ANCA (anti-PR3 antibodies). The pathophysiology involves abnormal T cell and B cell function leading to generation of anti-PR3 autoantibodies and activated neutrophils that trigger vessel inflammation. The disease typically affects upper respiratory tract (sinusitis, nasal involvement with crusting and bleeding), lungs (hemoptysis, pulmonary nodules), and kidneys (necrotizing glomerulonephritis with crescent formation). Systemic features include fever, weight loss, and constitutional symptoms. Untreated disease rapidly progresses to end-stage renal disease and lung failure with high mortality. Diagnosis requires integration of clinical features, ANCA serology, and tissue histology showing granulomatous inflammation and necrotizing vasculitis.