biopsy will show leukocytoclastic vasculitis with necrotic changes and granulomatous inflammation (clumps of typically arranged white blood cells) on microscopy. These granulomas are the main reason for the name granulomatosis with polyangiitis, although it is not an essential feature. Nevertheless, necrotizing granulomas are a hallmark of this disease. However, many biopsies can be nonspecific and 50% provide too little information for the diagnosis of GPA. Classification Granulomatosis with polyangiitis is part of a larger group of vasculitic syndromes called systemic vasculitides or necrotizing vasculopathies, all of which feature an autoimmune attack by an abnormal type of circulating antibody termed ANCAs (antineutrophil cytoplasmic antibodies) against small and medium-size blood vessels. Apart from GPA, this category includes eosinophilic granulomatosis with polyangiitis (EGPA) and microscopic polyangiitis. Although GPA affects small- and medium-size vessels, it is formally classified as one of the small vessel vasculitides in the Chapel Hill system. Criteria In 1990, the American College of Rheumatology accepted classification criteria for GPA. These criteria were not intended for diagnosis, but for inclusion in randomized controlled trials. Two or more positive criteria have a sensitivity of 88.2% and a specificity of 92.0% of describing GPA. Nasal or oral inflammation: painful or painless oral ulcers or purulent or bloody nasal discharge Lungs: abnormal chest X-ray with: nodules, infiltrates or cavities Kidneys: urinary sediment with: microscopic hematuria or red cell casts Biopsy: granulomatous inflammation within the arterial wall or in the perivascular area According to the Chapel Hill Consensus Conference (CHCC) on the nomenclature of systemic vasculitis (1992), establishing the diagnosis of GPA demands: a granulomatous inflammation involving the respiratory tract, and a vasculitis of small to medium-size vessels. Several investigators have compared the ACR and Chapel Hill criteria. Treatment GPA treatment depends on its severity and whether it has caused organ damage. Severe disease The standard treatment for severe GPA is to induce remission with immunosuppressants such as rituximab or cyclophosphamide in combination with high-dose corticosteroids. Plasmapheresis is sometimes recommended for very severe manifestations of GPA, such as diffuse alveolar hemorrhage and rapidly progressive glomerulonephritis (as seen in pulmonary-renal syndrome). The use of plasmapheresis in those with GPA and acute kidney failure (renal vasculitis) might reduce progression to end-stage kidney disease at three months. Oral and intravenous cyclophosphamide are both effective for induction of GPA remission. Oral cyclophosphamide at a dose of 2 mg/kg/day was the standard treatment for many years; this regimen resulted in