DEFINITION OF GRANULOMATOSIS WITH POLYANGIITIS (WEGENER’S)
Granulomatosis with polyangiitis (Wegener’s) is a distinct clinicopathologic entity characterized by granulomatous vasculitis of the upper and lower respiratory tracts together with glomerulonephritis. In addition, variable degrees of disseminated vasculitis involving both small arteries and veins may occur.
INCIDENCE AND PREVELANCE OF GRANULOMATOSIS WITH POLYANGIITIS (WEGENER’S)
Granulomatosis with polyangiitis (Wegener’s) is an uncommon disease with an estimated prevalence of 3 per 100,000. It is extremely rare in blacks compared with whites; the male-to-female ratio is 1:1. The disease can be seen at any age; ~15% of patients are <19 years of age, but only rarely does the disease occur before adolescence; the mean age of onset is ~40 years.
PATHOLOGY AND PATHOGENESIS OF GRANULOMATOSIS WITH POLYANGIITIS (WEGENER’S)
The histopathologic hallmarks of granulomatosis with polyangiitis (Wegener’s) are necrotizing vasculitis of small arteries and veins together with granuloma formation, which may be either intravascular or extravascular (Fig. 356-2). Lung involvement typically appears as multiple, bilateral, nodular cavitary infiltrates (Fig. 356-3), which on biopsy almost invariably reveal the typical necrotizing granulomatous vasculitis. Upper airway lesions, particularly those in the sinuses and nasopharynx, typically reveal inflammation, necrosis, and granuloma formation, with or without vasculitis.
Lung histology in granulomatosis with polyangiitis (Wegener’s). This area of geographic necrosis has a serpiginous border of histiocytes and giant cells surrounding a central necrotic zone. Vasculitis is also present with neutrophils and lymphocytes infiltrating the wall of a small arteriole (upper right). (Courtesy of William D. Travis, MD; with permission.)
Computed tomography scan of a patient with granulomatosis with polyangiitis (Wegener’s). The patient developed multiple, bilateral, and cavitary infiltrates.
In its earliest form, renal involvement is characterized by a focal and segmental glomerulitis that may evolve into a rapidly progressive crescentic glomerulonephritis. Granuloma formation is only rarely seen on renal biopsy. In contrast to other forms of glomerulonephritis, evidence of immune complex deposition is not found in the renal lesion of granulomatosis with polyangiitis (Wegener’s). In addition to the classic triad of disease of the upper and lower respiratory tracts and kidney, virtually any organ can be involved with vasculitis, granuloma, or both.
The immunopathogenesis of this disease is unclear, although the involvement of upper airways and lungs with granulomatous vasculitis suggests an aberrant cell-mediated immune response to an exogenous or even endogenous antigen that enters through or resides in the upper airway. Chronic nasal carriage of Staphylococcus aureus has been reported to be associated with a higher relapse rate of granulomatosis with polyangiitis (Wegener’s); however, there is no evidence for a role of this organism in the pathogenesis of the disease.
Peripheral blood mononuclear cells ...