摘要目的:分析伏立康唑诱发骨膜炎的临床特点。方法:检索PubMed、中国知网等国内外数据库中伏立康唑诱发骨膜炎的病例报告类文献(截至2024年3月20日)。记录患者性别、年龄、既往病史,伏立康唑用药指征、用法用量,骨膜炎症状、检查结果、临床处理与转归等。根据常见不良事件评价标准(CTCAE)5.0版对不良反应严重程度进行分级。对收集的资料进行描述性统计分析。结果:纳入分析的患者共61例,男性26例,女性35例;年龄5个月~74岁,>60岁者33例;41例说明了感染真菌的类别,包括曲霉菌、组织胞浆菌、念珠菌、镰孢菌、阿萨希毛孢子菌,16例未具体说明真菌类别,4例未说明用药指征;48例(78.7%)为接受移植术后抗感染治疗。患者应用伏立康唑至出现骨膜炎的时间为12 d~2 920 d,中位发生时间为用药后270 d;53例报告了骨膜炎主要症状,均存在肌肉和骨骼疼痛,其中3级疼痛(重度)者13例,10例为接受移植术者;其他伴随症状包括疲劳、肌无力或肌萎缩、厌食、烦躁。42例报告了实验室检查结果,39例碱性磷酸酶(ALP)升高,7例骨特异性碱性磷酸酶(BALP)升高;59例报告了影像学检查结果,均存在多灶性骨膜炎、骨膜增厚、骨膜钙化或反应性新骨形成等特征性表现。出现伏立康唑诱发的骨膜炎后,50例患者停药后好转,1例减少剂量后好转,2例仅给予镇痛治疗后稍缓解,5例死亡(非骨膜炎导致)。结论:伏立康唑诱发骨膜炎多发于接受移植术后患者,潜伏期长,疼痛明显,可伴随ALP或BALP水平升高。停用伏立康唑,症状可缓解,严重疼痛者可给予镇痛治疗。
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abstractsObjective:To analyze the clinical characteristics of periostitis induced by voriconazole.Methods:The case reports of voriconazole-induced periostitis in PubMed, CNKI and other domestic and foreign databases were searched up to March 20, 2024. The patients′ gender, age, disease history, the indications, usage and dosage of voriconazole, as well as the symptoms, examination results, clinical treatments and outcomes of periostitis were recorded. The severity of adverse reactions was graded according to the Common Adverse Event Evaluation Criteria (CTCAE) version 5.0. Descriptive statistical analysis was performed on the collected data. Results:A total of 61 patients were included in the analysis, including 26 males and 35 females. Their age ranged from 5 months to 74 years, and 33 patients were more than 60 years. Fungal categories were described in 41 patients (including Aspergillus, Histoplasma, Candida, Fusarium, and Trichosporum asachii) and not described in 16 patients; indications of voriconazole were not reported in 4 patients. Forty-eight patients (78.7%) received the anti-infective therapy after transplantation. The time from application of voriconazole to occurrence of periostitis ranged from 12 days to 2 920 days, and the median time was 270 days after initial medication. The main symptoms of periostitis were reported in 53 patients and all of them had muscle and bone pain, including 13 cases of grade 3 pain (severe) and 10 cases of transplant recipients. Other concomitant symptoms included fatigue, muscle weakness or muscle atrophy, anorexia, and irritability. Laboratory test results were reported in 42 patients, 39 of which had increased alkaline phosphatase (ALP) and 7 had increased bone-specific alkaline phosphatase (BALP). Imaging findings were reported in 59 patients, all of which had specific manifestations such as multifocal periostitis, periosteal thickening, periosteum calcification or reactive new bone formation. After occurrence of periostitis, 50 patients were improved after voriconazole withdrawal and 1 patient was improved after reducing the dose; 2 patients only received analgesic treatment and the pain were slightly relieved; 5 patients died but not because of periostitis. Conclusions:Periostitis induced by voriconazole is more common in patients after transplantation, with long incubation period and obvious pain, which can be accompanied by increased ALP or BALP levels. The symptoms could be relieved after drug withdrawal and analgesic treatments could be given in patients with severe pain.
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