ANCA-associated vasculitis

The majority of patients with Wegener's granulomatosis (WG) or microscopic polyangiitis (MPA) have antineu-trophil cytoplasmic antibodies (ANCA) in their serum. This is particularly true of patients with "disseminated" disease, the great majority of whom are ANCA positive. WG and MPA are often termed "ANCA-associated vasculitides" (AAV), even though not all patients with these conditions have ANCA. The Churg-Strauss syndrome, another disorder classified as an AAV, is discussed in Chap. 23. Multiple antibodies may lead to positive immunofluores-cence testing for ANCA in either perinuclear (P-ANCA) or cytoplasmic (C-ANCA) patterns. However, only antibodies to myeloperoxidase (MPO) and proteinase-3 (PR3) are associated with the A AV. Antibodies directed against PR3 and MPO are termed PR3-ANCA and MPO-ANCA, respectively. WG may be associated with destructive upper respiratory tract disease, including saddle-nose deformity, erosive sinusitis, and subglottic stenosis. A host of ocular lesions may occur in the A AV, including episcleritis, scleritis, peripheral ulcerative keratitis, and orbital pseudotumor. Most of these lesions are more common in WG than in MPA. Lung disease in the AAV ranges from nodular lesions with a tendency to cavitate (in WG), to interstitial lung disease (MPA), and to alveolar hemorrhage (both WG and MPA). Segmental, necrotizing glomerulonephritis commonly accompanies the AAV. Because of the paucity of immunoreactants such as immunoglobulins and complement components in kidney biopsies relative to the biopsies from patients with immune complex-mediated glomerulonephritis, the glomerulonephritis of the A AV is termed "pauci-immune".