title: Voriconazole-Induced Periostitis & Enthesopathy in Solid Organ Transplant Patients: Case Reports.
abstract: BACKGROUND
  Voriconazole is frequently used to treat fungal infections in solid organ transplant patients. Recently, there have been reports suggesting that prolonged voriconazole therapy may lead to periostitis.
  
  
  OBJECTIVE
  Here we present two cases of voriconazole-induced periostitis in solid organ transplant patients.
  
  
  METHODS
  Voriconazole was given to two transplant patients-one with a liver transplant and the second with a heart transplant, to treat their fungal infections. Both developed voriconazole-induced toxicity. While undergoing voriconazole therapy, they had incapacitating bone pain. The liver transplant patient had to be taken off voriconazole, and the heart transplant patient succumbed to non-voriconazole related causes.
  
  
  CONCLUSIONS
  Voriconazole therapy in two solid organ transplant patients resulted in periostitis. We provide potential etiologies underlying voriconazole-induced periostitis, including fluoride toxicity, abnormalities in the pulmonary vascular bed leading to the production of downstream inflammatory mediators, and abnormal pharmacokinetics of hepatic drug metabolism. In addition to monitoring blood voriconazole trough levels, we suggest careful assessment for musculoskeletal pain in patients undergoing voriconazole treatment for two months or more, particularly if their daily dosages of voriconazole exceed 500 mg per day. Appropriate workup should include measurement of alkaline phosphatase, voriconazole trough and fluoride levels as well as a bone scan. Overall, early recognition of voriconazole-induced musculoskeletal toxicity is important for better morbidity outcomes.
authors.affiliation: Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Monica
authors.initials: M
authors.lastname: Sircar
authors.affiliation: Division of Infectious Disease, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Camille
authors.initials: C
authors.lastname: Kotton
authors.affiliation: Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA; MGH Transplant Center, Departments of Medicine and Surgery, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: David
authors.initials: D
authors.lastname: Wojciechowski
authors.affiliation: Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA; MGH Transplant Center, Departments of Medicine and Surgery, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Kassem
authors.initials: K
authors.lastname: Safa
authors.affiliation: Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA; MGH Transplant Center, Departments of Medicine and Surgery, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Hannah
authors.initials: H
authors.lastname: Gilligan
authors.affiliation: Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA; MGH Transplant Center, Departments of Medicine and Surgery, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Eliot
authors.initials: E
authors.lastname: Heher
authors.affiliation: Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA; MGH Transplant Center, Departments of Medicine and Surgery, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Winfred
authors.initials: W
authors.lastname: Williams
authors.affiliation: Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Ravi
authors.initials: R
authors.lastname: Thadhani
authors.affiliation: Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA; MGH Transplant Center, Departments of Medicine and Surgery, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Nina
authors.initials: N
authors.lastname: Tolkoff-Rubin
keywords: Drug Metabolism; Enthesopathy; Organ Transplant; Periostitis; Voriconazole