Vasculitides associated with serum positivity for
antineutrophil cytoplasmic antibodies (ANCAs) are a well-established subgroup affecting small- to medium-sized vessels that are commonly recognized as
ANCA-associated vasculitis, which includes necrotizing granulomatous
vasculitis (NGV) [formerly
Wegener granulomatosis],
microscopic polyangiitis (MPA), and
Churg-Strauss syndrome. NGV usually starts as a granulomatous disease of the respiratory tract and progresses to systemic disease with
proteinase 3 (PR3)-ANCA-associated
vasculitis, suggesting an aberrant cell-mediated immune response to exogenous or endogenous
antigens in the respiratory tract and resulting in
granuloma formation. In NGV, granulomata may represent lymphoid structures ultimately responsible for PR3-ANCA production. In both NGV and MPA, necrotizing
glomerulonephritis and necrotizing pulmonary capillaritis may well result from an injury orchestrated by
ANCA. Untreated NGV and MPA normally are rapidly progressive and fatal. Pulmonary capillaritis with alveolar
hemorrhage is a severe complication in patients with MPA and NGV. Because
plasma exchange removes circulating ANCAs and other
proteins from the blood, its use has been advocated in critical situations of severe renal and pulmonary involvement. However, no studies of
plasma exchange in
ANCA-associated vasculitis focused on pulmonary involvement have been reported. Dissecting the mechanisms of
inflammation may identify molecular targets for future
therapies in
ANCA-associated vasculitis. Thus,
biological agents are emerging as potential
therapies in refractory cases. Notably,
rituximab and
infliximab have been trialed with apparent initial clinical success.