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Granulomatosis with polyangiitis is a systemic vasculitis of unknown etiology, characterized by necrotizing granulomas. It is an autoimmune disease affecting small- and medium-sized vessels of upper and lower respiratory tract, kidneys, and other organs. We described a case of a patient with otitis media with effusion as the first manifestations of granulomatosis with polyangiitis. A 54-year-old female presented as an urgent case with history of a severe otalgia, hearing loss, vertigo, and fever. The patient was treated with diagnosis of otitis media with effusion and acute rhinosinusitis, but without significant success. She developed an acute kidney dysfunction as a sign of glomerulonephritis with rapidly progressive renal failure. Diagnosis of granulomatosis with polyangiitis was confirmed after the histopathological analysis of kidney tissue, not by analysis of middle ear and paranasal sinus mucosa specimens. The patient was treated according to generally accepted protocol, and over time, there was an almost complete recovery.