Granulomatosis With Polyangiitis (Wegener Granulomatosis): Then and Now

Godman and Churg proposed the name Wegener's granulomatosis and defined the essential features as granulomatous inflammation and necrotizing vasculitis involving, typically, the upper respiratory tract, lung, and kidney. They suggested that GPA, allergic angiitis, and granulomatosis (later known as Churg-Strauss syndrome, now "eosinophilic granulomatosis with polyangiitis" [EGPA]), and what were referred to as "microscopic forms of periarteritis nodosa," now "microscopic polyangiitis," were related entities producing small-vessel vasculitis. We currently recognize these diseases as the spectrum of pauci-immune ANCA (anti-neutrophil cytoplasmic antibody)-associated small-vessel vasculitis, in contrast to small-vessel vasculitis characterized by immune complex deposits. ANCAs are antibodies directed against the neutrophil proteins proteinase 3 (PR3, usually associated with GPA) and myeloperoxidase (MPO, usually associated with microscopic polyangiitis and EGPA). A modern definition of GPA discloses that it can affect any organ in the body, characteristically with upper respiratory tract involvement. In the lung it is associated with necrotizing nodules and/or capillaritis with hemorrhage. It has been proposed that these forms of vasculitis should in the future be primarily classified by using ANCA specificity-that is, PR3 or MPO-as a disease definition, based on observations that the type of ANCA is what determines the location/pattern of organ involvement.