低剂量依托泊苷治疗难治性成人斯蒂尔病的临床分析

Low dose efficacy of etoposide on conventional treatment-refractory adult-onset Still disease

目的探讨低剂量依托泊苷对难治性AOSD的疗效。方法对2014年12月至2017年9月在上海交通大学附属仁济医院南院风湿免疫科住院的24例应用依托泊苷治疗的难治性AOSD进行回顾性分析。采用t检验、Mann-Whitney U检验、χ2检验进行数据分析。结果24例患者平均年龄（38±13）岁。中位病程2.5个月（1个月至14年）。11例继发噬血细胞性淋巴组织细胞增多症（HLH）/巨噬细胞活化综合征（MAS）。依托泊苷治疗的中位剂量575 mg（150-1400 mg），中位疗程4周（2周至10个月）。依托泊苷改善患者的临床表现及实验室指标，并表现出激素助减效应。依托泊苷最常见的不良反应为感染，其次为血细胞减少、胃肠道反应及脱发。24例患者中，2例死亡，22例患者存活。存活患者平均随访14个月（1-32个月），其中4例单用激素治疗，18例应用激素加免疫抑制剂治疗，患者病情均平稳无复发。结论低剂量依托泊苷用于治疗难治性AOSD，可快速诱导临床症状及实验室指标的改善；患者总体耐受性尚可，感染为最常见不良反应。其更为确切的疗效及安全性，有待于更为严格的前瞻性随机对照临床研究验证。

ObjectiveTo assess the efficacy of low-dose etoposide in patients with adult-onset Still disease （AOSD） refractory to conventional treatment.MethodsThis was a retrospective study of etoposid treat-ment in 24 patients with conventional treatment-refractory AOSD. Mann-Whitney U-test, Student＇s t test and chi-squared test were used for analysis.ResultsThe age of the patients was （38±13） years. The median dur-ation of AOSD before etoposide initiation was 2.5 months [interquartile range （IQR）] 1 month to 14 years）. The median dosageof etoposide was 575 mg （IQR 150-1 400 mg）. The median treatment course was 4 weeks （IQR 2 weeks to 10 months）. Etoposide treatment resulted in rapid and maintained improvement in both clinical and laboratory parameters. The median dosage of methylprednisolone was also reduced. The most common side effectwas infection, and other side effects were mild leukopenia or neutropenia, gastrointestinal effects and hair loss. Two patients died and 22 patients survived. With an average follow-up of 14 months （IQR 1-32 months）, 4 of which were treated with corticosteroid alone, and 18 patients were treated with corticosteroid plus immunosuppressive agents. The patient＇s condition was stable without disease flare.ConclusionEtopo-side treatment is associated with rapid and maintained clinical and laboratory improvement in patients with refractory AOSD. Infection is the most common side effect. It is necessary to carry out large samples and long-term follow-up clinical studies to evaluate its exact effect and safety.