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Lyme arthritis typically causes intermittent attacks of oligoarticular arthritis in a few large joints, especially the knee. A small percentage of patients may develop chronic arthritis, again affecting primarily the knee. The diagnosis is usually based on the presence of this characteristic clinical picture, exposure in an endemic area, and a positive IgG antibody response to B. burgdorferi determined by ELISA and Western blotting. In addition, spirochetal DNA can often be detected in joint fluid by PCR. Joint involvement in this infection can usually be treated successfully with a 1- or 2-month course of oral doxycycline or amoxicillin, but patients with certain genetic and immune markers may have persistent arthritis despite treatment with oral or intravenous antibiotics. If patients have persistent arthritis despite a second course of antibiotics and if the results of PCR testing are negative, the author treats such patients with anti-inflammatory agents or arthroscopic synovectomy.