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.

中文翻译：

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伏立康唑诱发干细胞移植患者骨膜炎

一名 66 岁女性，有慢性肾病和 T 细胞淋巴瘤病史，5 年前同种异体造血干细胞移植 (HCT) 后缓解，并发慢性皮肤移植物抗宿主病，3 个月前停止免疫抑制治疗介绍。她因右脚踝疼痛 4 周病史入院，既往无外伤或穿透伤。她否认发烧、疲劳或体重减轻。患者患有侵袭性肺曲霉病，接受伏立康唑治疗，并在过去 4 年中每天两次服用 200 mg 作为二级预防。体格检查显示右小腿远端压痛，无炎症。实验室研究显示白细胞计数，5900/μL；肌酐，1.59 毫克/分升；碱性磷酸酶轻度升高，144 U/L（正常范围 35-104 U/L）。踝关节 X 线显示胫腓骨远端厚且不规则的骨膜炎，没有任何局部肿瘤或感染的证据（图 1）。锝骨扫描显示皮质示踪剂摄取增加。该患者被诊断为伏立康唑诱发的骨膜炎。停用伏立康唑后，骨痛开始消退，患者在随后的临床随访中仍无症状。伏立康唑是一种三氟化三唑类药物，长期使用会导致血清和骨骼系统中的高氟化物水平。肾功能不全易导致氟化物进一步积聚，导致成骨细胞刺激，从而导致骨膜骨的旺盛生长 [1]。骨膜炎的其他原因包括维生素 A 和前列腺素类似物相关骨膜炎、肥厚性骨关节病、甲状腺无睾症、和血液系统恶性肿瘤，如白血病[2]。在没有其他诊断的情况下，通常通过存在骨痛、血清碱性磷酸酶升高和放射性核素骨扫描的特征性特征来做出诊断 [1, 3-6]。我们的案例强调了对长期使用伏立康唑治疗的患者了解使用伏立康唑的长期并发症的重要性，包括骨痛、骨膜炎和皮肤恶性肿瘤 [7]，因为早期诊断对于减少发病率和长期后遗症至关重要。