Skeletal fluorosis after prolonged voriconazole therapy.

Abstract

A 6-year-old girl underwent allogeneic hematopoietic stem cell transplantation for a relapsing acute myelogenous leukemia. She developed severe chronic graft-versus-host disease which required immunosuppressive therapies, including a prolonged course of high-dose steroids. She also presented a thrombotic microangiopathy complicated by renal failure requiring dialysis. Eleven months after transplantation, she was diagnosed with pulmonary and cerebral aspergillosis, prompting initiation of intravenous voriconazole. Unusually high doses were needed (11 mg/kg/dose every 8 hours) in order to achieve therapeutic plasmatic trough concentrations above 1 to 2 mg/L. After 2 months, she was transitioned to oral voriconazole at equivalent dosing. Six months after being on oral voriconazole, she complained of fatigue and diffuse musculoskeletal pain, initially attributed to her steroid treatment. Radiographs (Figure 1) of her femurs showed diffuse osteopenia and pronounced bilateral periosteal reactions with exostosis (arrows). ... The diagnosis of osseous fluorosis induced by prolonged voriconazole therapy was suspected and confirmed by a very high fluoride plasma concentration of 27.0 µmol/L (0.25 to 1.0 µmol/L). Her alkaline phosphatase level was also increased at 627 U/L (134 to 518 U/L), with a known normal baseline level preceding therapy. Voriconazole was discontinued and oral posaconazole was substituted in its place. Five months after voriconazole discontinuation, her musculoskeletal symptoms resolved and her fluoride plasma concentration decreased to 1.30 µg/mL.