Voriconazole-Induced Diffuse Periostitis

Voriconazole treatment has been associated with diffuse periostitis, especially in immunocompromised patients who have had transplants or are on immunosuppressants. Here, we present a case of diffuse periostitis induced by prophylactic low-dose voriconazole for pulmonary aspergillosis.

A 66-year-old woman presented with 1 year of progressive, diffuse bone pain most prominent over the left shoulder and bilateral hips. She had a history of sarcoidosis requiring a single orthotopic lung transplant. Left phalangeal soft tissue swelling and painful nodules without clubbing were noted on examination. Prophylactic voriconazole 200 mg twice a day for pulmonary aspergillosis was prescribed for over 7 years. Elevated levels of alkaline phosphatase (469 units/L [reference range, 38-126]), bone-specific alkaline phosphatase (125 μg/L [0-20]), and parathyroid hormone (137 pg/mL [8-54]) and normal c-telopeptide level (842 pg/mL [34-1037]) were noted. Radiographs showed "multifocal periostitis" in both hip joints and bilateral proximal femurs, findings suggestive of voriconazole-induced periostitis deformans. Voriconazole was discontinued, and the patient improved symptomatically, despite persistent bone deformities on imaging.

Diffuse bone pain can be due to various pathologies, including metabolic or inflammatory diseases and bone tumors. Voriconazole-induced periostitis is caused by skeletal fluorosis, which can result in diffuse bone pain. It is a clinical diagnosis that is supported with radiologic findings, including focal, nodular, dense, and irregular periosteal reactions. Biochemical evaluation may reveal elevated alkaline phosphatase levels, but it is usually related to normal voriconazole trough levels. Periostitis is a benign condition, and discontinuation of the drug usually leads to clinical improvement.

Voriconazole-induced periostitis should be considered as a diagnosis in elderly, immunosuppressed patients with diffuse bone pain on antifungal treatment. Early recognition of voriconazole-induced periostitis may result in both improved patient clinical outcomes and avoidance of unnecessary diagnostic testing.