Overview
Disease Pattern and Organ Threat
Granulomatosis with polyangiitis (GPA) is an autoimmune, ANCA associated necrotizing vasculitis of small and medium vessels.
Granulomatosis with polyangiitis (GPA) is an autoimmune, ANCA-associated necrotizing vasculitis of small and medium vessels. Granulomatous inflammation and vascular injury most characteristically involve three connected regions: the upper airway, the lower respiratory tract, and the kidneys. Other organs, including the eyes, skin, peripheral nerves, heart, and gastrointestinal tract, may also be affected. GPA is most often associated with antibodies against proteinase 3 (PR3-ANCA), commonly reported with a cytoplasmic staining pattern called c-ANCA. In microscopic polyangiitis, MPO-ANCA with a perinuclear pattern is more common. The pattern is useful, but the antigen-specific antibody result and the patient’s organ findings matter more than the fluorescence label alone. ANCA can activate primed neutrophils. The neutrophils adhere to the endothelium, release oxidants and proteolytic enzymes, and injure vessel walls. In the glomeruli, this produces pauci-immune necrotizing and crescentic glomerulonephritis—“pauci-immune” means little or no immune-complex deposition is seen, not that the kidney injury is mild. The clinical picture reflects which vascular beds are inflamed: - Upper airway: persistent or recurrent sinus symptoms, nasal crusting, bloody nasal discharge, epistaxis, otitis, conductive or sensorineural hearing loss, cartilage destruction,...