庆大霉素软膏治疗无义突变引起的营养不良性大疱性表皮松解症的临床疗效观察

Clinical Efficacy of Gentamicin Ointment in the Treatment of Dystrophic Bullous Epidermolysis Caused by Nonsense Mutation

目的观察评价庆大霉素软膏外用治疗无义突变所致常染色体隐性营养不良性大疱性表皮松解症(RDEB)的有效性及安全性。方法 2018年3月-2019年2月,笔者采用随机、双盲、安慰剂对照的研究方法,安慰剂选用与庆大霉素软膏相同的赋形剂成分,招募基因检测确诊为无义突变导致的RDEB患者,通过安全性评估后,每例患者每日涂抹1次庆大霉素乳膏于患处(共30 d),分别进行疗效和安全性观察。治疗期间使用皮肤生活质量问卷(DLPI)和伯明翰大疱性表皮松解症严重程度评分(BEBS)对患者进行评估。结果共纳入4名患者,经基因检测均携带有杂合无义突变,年龄2~26岁。DLPI评分治疗前为(24.50±1.73)分,治疗后为(17.75±1.25)分。BEBS治疗前为(28.75±9.98)分,治疗后为(22.00±6.36)分。临床可见用药侧效果明显优于安慰剂侧,治疗期间与治疗后均无相关不良反应发生。免疫荧光显示患者Ⅶ型胶原纤维有部分表达。结论使用庆大霉素软膏治疗由无义突变引起的RDEB,可以提高患者皮损的愈合速度,减少起疱频率,显著改善患者生活质量,减轻日常护理的压力。

Objective To evaluate the efficacy and safety of gentamicin ointment in the treatment of recessive dystrophic epidermolysis bullosa(RDEB) caused by nonsense mutations.Methods From March 2018 to February 2019,a randomized,double-blind,placebo-controlled study was conducted in Xinhua Hospital.The placebo was selected from the same excipients as gentamicin ointment.Patients with RDEB was enrolled after their genetic test was diagnosed as nonsense mutations,and they were given a daily gentamicin cream on affected area(Day 1-Day 30).The efficacy and safety were observed separately.During the treatment,the skin quality of life questionnaire(DLPI) and the Birmingham epidermolysis bullosa severity score(BEBS) were used to evaluate the patients.Results A total of 4 patients were enrolled.All of them were heterozygous nonsense mutations,and the age was between 2~26 years.The DLPI score was(24.50±1.73) points before treatment and(17.75±1.25) points after treatment.The BEBS was(28.75±9.98) points before treatment and(22.00±6.36) point after treatment.The therapeutic effect of the research group was better than that of the placebo group.There was no significant side effects observed during the treatment period.The immunofluorescence showed that the type Ⅶ collagen was partially expressed in the basement membrane zone(BMZ) of patients.Conclusion The use of gentamicin ointment to treat RDEB caused by nonsense mutations can improve the healing process of skin lesions,and reduce the frequency of blistering.And it can improve the quality of life of patients significantly,while reducing the burden of nursing.