GRANULOMATOSIS | Wegener's Disease

Abstract

Wegener's granulomatosis (WG) is a potentially life-threatening chronic inflammatory disease of as yet unknown etiology, characterized by necrotizing granulomatous lesions and an autoimmune vasculitis mediated by antineutrophil cytoplasmatic autoantibody (ANCA). The histopathologic hallmark is the triad of granulomatous inflammation, necrosis and vasculitis. WG usually takes a biphasic course starting in the upper and/or lower respiratory tract (so-called localized WG) with subsequent generalization with prominent clinical features of systemic vasculitis. Approximately 95% of patients with active generalized WG are ANCA positive, which is usually directed against ‘Wegener's autoantigen’ proteinase 3 (PR3). In vitro and animal models suggest that the interaction of ANCA with cytokine-primed neutrophils results in premature activation, respiratory burst, and degranulation of neutrophil granulocytes with subsequent endothelial cell damage and necrotizing vasculitis. Altered T-cell responses with predominant Th1-type cytokine release might facilitate autoantigen recognition in WG. WG is a multifocal inflammatory disease that affects most often the upper and lower tract and the kidneys, but involvement of any other organ such as eye, skin, heart, gastrointestinal tract, central and peripheral nervous system may occur and give rise to serious or life-threatening complications. In few cases involvement of the upper and/or lower respiratory tract may be the only manifestation for years (localized WG). Cyclophosphamide plus steroids (NIH-scheme) is the standard therapy for the induction of remission in severe organ- or life threatening disease followed by azathioprine or other drugs for the maintenance of remission. In localized and early systemic WG trimetoprim-sulfamethoxazole and/or less aggressive immunosuppressions (e.g., MTX) can induce remission.