Wegener granulomatosis (Granulomatosis with Polyangiitis): Evolving concepts in treatment

Wegener granulomatosis (WG), the most common of the pulmonary granulomatous vasculitides, typically involves the upper respiratory tract, lower respiratory tract (bronchi and lung), and kidney, with varying degrees of disseminated vasculitis. The term Granulomatosis with Polyangiitis (Wegener) was recently proposed to replace the older term, WG. The term granulomatosis with polyangiitis can be abbreviated to GPA, with the idea that the eponym Wegener would be omitted over time. Cardinal histologic features include a necrotizing vasculitis involving small vessels, extensive geographic necrosis, and granulomatous inflammation. Clinical manifestations of WG are protean; virtually any organ can be involved. The spectrum and severity of the disease are heterogeneous, ranging from indolent disease involving only one site to fulminant, multiorgan vasculitis. The pathogenesis of WG has not been elucidated, but both cellular and humoral components are involved. Circulating antibodies against cytoplasmic components of neutrophils [anti-neutrophil cytoplasmic antibodies (c-ANCAs)] likely play a role in the pathogenesis, and often correlate with activity of the disease. Treatment strategies are evolving. Cyclophosphamide (CYC) plus corticosteroids (CSs) is the mainstay of therapy for generalized, multisystemic WG. Historically, the combination of CYC plus CS was used for a minimum of 12 months, but concern about late toxicities associated with CYC has led to novel treatment approaches. Currently, short-course (3 to 6 months) induction treatment with CYC plus CS, followed by maintenance therapy with less toxic agents (e.g., methotrexate, azathioprine) is recommended. Further, methotrexate combined with CS may be adequate for limited, non-life-threatening WG. Recent studies suggest that rituximab may be useful for induction therapy or CYC-refractory WG. The role of other immunomodulatory agents (including trimethoprim-sulfamethoxazole) is also explored.