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Coccidioidomycosis is an invasive fungal infection caused by the inhalation of aerosolized spores of Coccidioides spp., which reside in the arid soil of the southwestern United States and northern Mexico. The primary infection occurs in the lungs; however, less than 40% of patients are symptomatic. Dissemination of coccidioidomycosis is rare (1-5%), but can lead to extra pulmonic disease involving any organ. Skeletal coccidioidomycosis occurs in 10% to 50% of disseminated infections. Skeletal coccidioidomycosis is a chronic and progressive infection that eventually results in bone destruction and loss of function and often involves adjacent structures such as joints, muscles, tendons and other soft tissues. This infection is frequently multifocal with axial skeletal involvement. Although radiographs and other imaging methods identify relevant abnormalities, histopathologic examination with culture of the involved bone is the only means to confirm the diagnosis. Serologic testing is adjunctive, and complement fixation titers can be evaluated serially to assess response to treatment. Skeletal coccidioidomycosis is difficult to treat, and a combination of medical therapy and surgical debridement often is needed. Early diagnosis and treatment are critical to avoid long-term problems.