Voriconazole-induced periostitis in stem cell transplant patient

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Voriconazole‑induced periostitis in stem cell transplant patient Alexandre E. Malek1,2 · Yara Saff3 · Victor E. Mulanovich1 Received: 24 February 2020 / Accepted: 11 May 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020

Keywords  Voriconazole · Periostitis · Stem cell transplant A 66-year-old woman with history of chronic kidney disease and T-cell lymphoma in remission after allogeneic hematopoietic stem cell transplantation (HCT) 5 years before, complicated by chronic skin graft-versus host disease off immunosuppression for 3 months before the current presentation. She was admitted with 4-week history of right ankle pain with no prior trauma or penetrating wound. She denied fever, fatigue or weight loss. The patient had invasive pulmonary aspergillosis, treated with voriconazole and kept on 200 mg twice daily as secondary prophylaxis for the last 4 years. Physical examination revealed distal right lower leg tenderness without inflammation. Laboratory studies showed white blood cell count, 5900/μL; creatinine, 1.59 mg/dL; mildly elevated alkaline phosphatase, 144 U/L (normal range 35–104 U/L). Ankle X-ray showed thick and irregular periostitis of distal tibia and fibula without any evidence of local tumor or infection (Fig. 1). Technetium bone scan showed increase cortical tracer uptake. The patient was diagnosed with voriconazole-induced periostitis. After discontinuing voriconazole, the bone pain started subsiding and patient remained free of symptoms on subsequent clinic follow-ups. Voriconazole is a trifluorinated triazole agent and its long-term use is associated with high fluoride level in serum and the skeletal system. Renal insufficiency predisposes to further fluoride accumulation that leads to osteoblast

stimulation resulting in exuberant growth of periosteal bone [1]. Other causes of periostitis include vitamin A and prostaglandin analogs-related periostitis, hypertrophic osteoarthropathy, thyroid achropachy, and hematologic malignancies such as leukemia [2]. The diagnosis is usually made by the presence of bone pain, elevation of serum alkaline phosphatase and characteristic features on radionuclide bone scan in the absence of other diagnoses [1, 3–6]. Our case highlights the importance of awareness of the long-term complications of voriconazole use, including bone pain, periostitis, and skin malignancies in patients receiving longterm voriconazole therapy [7], as early diagnosis is critical for reducing morbidity and long-term sequelae.

* Alexandre E. Malek [email protected] 1



Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA

2



Division of Infectious Diseases, Department of Internal Medicine, McGovern Medical School, University of Texas Health Science Center At Houston, Houston, TX, USA

3

Department of Internal Medicine, The Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University, Beirut, Lebano