Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Transplant. Sep 18, 2021; 11(9): 356-371
Published online Sep 18, 2021. doi: 10.5500/wjt.v11.i9.356
Voriconazole-associated periostitis: Pathophysiology, risk factors, clinical manifestations, diagnosis, and management
Anthony J Guarascio, Nitin Bhanot, Zaw Min
Anthony J Guarascio, Department of Pharmacy, Duquesne University School of Pharmacy, Pittsburgh, PA 15282, United States
Nitin Bhanot, Zaw Min, Division of Infectious Disease, Medicine Institute, Allegheny General Hospital, Allegheny Health Network, Pittsburgh, PA 15212, United States
Author contributions: Guarascio AJ and Min Z contributed equally to the initial version of paper; Bhanot N reviewed and revised the paper; all authors provided collaborative patient care, discussions, and full authorship of the manuscript.
Conflict-of-interest statement: All authors have no conflict-of-interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Zaw Min, MD, Assistant Professor, Division of Infectious Disease, Medicine Institute, Allegheny General Hospital, Allegheny Health Network, 420 East North Avenue, Suite 407, Pittsburgh, PA 15212, United States.
Received: April 7, 2021
Peer-review started: April 7, 2021
First decision: July 8, 2021
Revised: July 19, 2021
Accepted: August 27, 2021
Article in press: August 27, 2021
Published online: September 18, 2021

Voriconazole use has been associated with osteoarticular pain and periostitis, likely due to high fluoride content in the drug formulation. This phenomenon has been described primarily with high dosage or prolonged course of voriconazole therapy in immunocompromised and transplant patient populations. Patients typically present with diffuse bony pains associated with elevated serum alkaline phosphatase and plasma fluoride levels in conjunction with radiographic findings suggestive of periostitis. We provide a comprehensive review of the literature to highlight salient characteristics commonly associated with voriconazole-induced periostitis.

Keywords: Voriconazole, Periostitis, Fluoride, Fluorosis, Alkaline phosphatase

Core Tip: Voriconazole-induced periostitis is rare, and typically presents as bone pain following months of voriconazole treatment. Fluoride, present in voriconazole, deposits within the bony matrix causing bone pains and high serum alkaline phosphatase (ALP) with or without elevated plasma fluoride level. Evidence of periostitis is typically observed on skeletal imaging. Symptom relief occurs shortly after discontinuation of voriconazole, and normalization of serum ALP occurs in the following weeks to months. We herein discuss the pathophysiology and diagnosis of voriconazole-induced periostitis, its prevalence in different patient populations, and clinical outcomes.