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Voriconazole-Induced Periostitis & Enthesopathy in Solid Organ Transplant Patients: Case Reports
Monica Sircar1, Camille Kotton2, David Wojciechowski3
1Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
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.
Aim:
Here we present two cases of voriconazole-induced periostitis in solid organ transplant patients.
Case Presentation:
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.
Insights
Prolonged voriconazole treatment can cause periostitis, a painful bone condition, in solid organ transplant recipients. Early recognition of this voriconazole-induced musculoskeletal toxicity is crucial for improved patient outcomes.
Area of Science:
- Pharmacology
- Transplant Medicine
- Toxicology
Background:
- Voriconazole is a key antifungal agent for solid organ transplant (SOT) patients.
- Emerging evidence suggests a link between prolonged voriconazole use and periostitis.
Purpose of the Study:
- To report two cases of voriconazole-induced periostitis in SOT patients.
- To discuss potential mechanisms and clinical management strategies.
Main Methods:
- Case presentation of two SOT patients (liver and heart transplant) treated with voriconazole for fungal infections.
- Observation of voriconazole-induced toxicity, including severe bone pain.
Main Results:
- Both patients developed incapacitating bone pain during voriconazole therapy.
- One patient discontinued voriconazole due to toxicity; the other died from unrelated causes.
Conclusions:
- Voriconazole therapy can lead to periostitis in SOT patients.
- Potential causes include fluoride toxicity, inflammatory mediators, and altered drug metabolism.
- Monitoring blood voriconazole levels and assessing for musculoskeletal pain are recommended for patients on prolonged therapy (≥2 months, >500 mg/day).
- Workup may include alkaline phosphatase, voriconazole trough, fluoride levels, and bone scan.
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