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24例中毒性表皮坏死松解症临床回顾性研究
A Clinical Retrospective Study of 24 Cases of Toxic Epidermal Necrolysis
【作者】 王玮；
【导师】 周梅娟；
【作者基本信息】 大连医科大学 ， 皮肤病与性病学（专业学位）， 2020， 硕士
【摘要】 目的:本研究通过对24例中毒性表皮坏死松解症(toxic epidermal necrolysis,TEN)住院患者的诱发因素、临床特点、检查结果、并发症、严重程度、治疗方法等进行整理、分析,以进一步认识本病,并为其治疗提供参考。方法:收集我院近10年诊断为TEN的住院患者,共计24例。整理临床资料,计算SCORTE评分和预期死亡数,分为单用糖皮质激素组及糖皮质激素联合静脉注射人免疫球蛋白(IVIG)组,比较各组间的体温下降时间、皮疹控制时间及激素维持量前使用时间,评估各治疗方法间的疗效差异。结果:1.本研究共收集患者24例,男女比为1:1,除外其中2例儿童,平均发病年龄为53.04±21.26岁。2.24例患者中既往有药物过敏史的为6例(25%),主要为青霉素类。3.24例患者中既往有基础疾病者19例(79.17%),主要为高血压、肾功能不全、脑出血及糖尿病。4.24例患者中发疹前有明确用药史的有20例(83.33%),常见的药物为抗生素类15例(62.5%),解热镇痛药8例(33.33%)。抗生素主要为头孢及青霉素类药物。5.临床表现主要以皮疹及发热为首发症状,分别为12例(50%)及8例(33.33%)。24例患者均有黏膜损害,其中口腔黏膜损害16例(66.67%),双眼结膜炎15例(62.5%),外阴损害11例(45.83%)。6.实验室检查主要有血常规异常、肝肾功能损害、电解质紊乱、低蛋白血症、空腹血糖偏高。皮肤糜烂面分泌物微生物培养结果主要为金黄色葡萄球菌及表皮葡萄球菌。7.并发症:出现肺部感染3例(12.5%);类固醇继发高血压3例(12.5%);类固醇性糖尿病1例(4.17%);神经兴奋1例(4.17%);阴道粘连1例(4.17%);泌尿系感染1例(4.17%);腹膜炎1例(4.17%)。8.死亡率:根据SCORTEN评分系统,总预期死亡4.9例,实际死亡2例(P>0.05)9.治疗:22例患者系统使用糖皮质激素治疗,其中16例行糖皮质激素冲击治疗(I组),6例常规量激素治疗(II组)。I、II组的体温下降时间分别为4.31±2.67天、4.67±1.86天,(P=0.178);皮疹控制时间分别为6.31±4.13天、6±5.25天,(P=0.319);激素维持量前使用时间分别为7.31±2.36天、6.5±2.59天,(P=0.874),糖皮质激素冲击治疗与常规治疗量相比,不能明显缩短体温下降时间、皮疹控制时间及激素维持量前使用时间(P均>0.05)。另外单用糖皮质激素治疗的患者7例(GC组),糖皮质激素联合IVIG治疗15例(GC+IVIG组)。GC组及GC+IVIG组的体温下降时间分别为3.71±1.98天、4.73±2.63天,(P=0.273);皮疹控制时间分别为5.42±4.83天、6.21±4.50天,(P=0.838);激素维持量前使用时间分别为7.14±3.48天、7.07±1.83天,(P=0.052),糖皮质激素联合IVIG治疗与单用激素相比也不能明显缩短体温下降时间、皮疹控制时间及激素维持量前使用时间(P均>0.05)。根据入院至初始应用IVIG的时间分A组(1-3天,N=8例)及B组(4-6天,N=7例)。A、B两组的体温下降时间分别为3.0±0.93天、6.71±2.56天,(P=0.027);皮疹控制时间分别为6.13±5.46天、6.33±3.33天,(P=0.292);激素维持量前使用时间分别为6.75±2.12天、7.43±1.51天,(P=0.368),入院3天内应用IVIG可有效缩短体温下降时间(P=0.027),但未能明显缩短皮疹控制时间及激素维持量前使用时间(P>0.05)。结论:1.TEN的常见致敏药物主要为抗生素及解热镇痛药,其中抗生素主要为头孢类及青霉素类。2.TEN的临床表现常以皮疹为首发症状,还有发热、黏膜损害等,黏膜受累常见依次为口腔、眼部及外阴。3.TEN暂无具有特异性诊断价值的实验室指标,但可伴有多系统损伤,且在治疗过程中可发生多种并发症,常见为继发感染、类固醇性高血压、糖尿病等。4.SCORTEN评分可有助于预测预期死亡率。5.TEN应用大剂量糖皮质激素冲击治疗与激素常规治疗剂量相比,不能明显缩短体温下降时间、皮疹控制时间及激素维持量前使用时间;糖皮质激素联合IVIG与单用糖皮质激素治疗相比也不能明显缩短病程;入院3天内应用IVIG可有效缩短体温下降时间,不能明显缩短皮疹控制时间及激素维持量前使用时间。
【Abstract】 Objective: To analyze the predisposing factors,clinical characteristics,test results,complications,severity,and treatment methods of the 24 cases of toxic epidermal necrolysis(TEN),so as to improve the understanding of the disease,and to provide references for the treatment.Methods: A retrospective study was performed on 24 patients who were diagnosed with TEN and hospitalized in XX hospital through the past 10 years.The clinical data of the patients were collected and analyzed.SCORTEN score and expected death number were calculated based on the data.The patients were divided into the group treated with glucocorticoid monotherapy,and the group treated with glucocorticoid combined with intravenous immunoglobulin(IVIG).The efficacy of therapeutic modalities was assessed by the following parameters: the fever relief time,the period of lesion improvement and the course of glucocorticoid before reduction to the maintenance does.Results: 1.A total of 24 patients were identified in this study,of which the male to female ratio was 1:1;Excluding 2 children,the average age of onset was 53.04 ± 21.26 years old.2.6 patients(25%)had a history of drug allergy in this study,the agents were mainly penicillin.3.There were 9 patients(79.17%)with previous underlying diseases,mainly including hypertension,renal insufficiency,cerebral hemorrhage,and diabetes.4.20 patients(83.33%)had a positive history of medication before the onset,the main causative agents were antibiotics(62.5%)and antipyretic analgesics(33.33%).Among them,cephalosporins and penicillins were the most common antibiotics.5.Clinical manifestations: The initial symptoms mainly presented erythra and fever,which were 12 cases(50%)and 8 cases(33.33%),respectively.All of the 24 patients had mucosal involvement,the proportion of oral mucosa,ocular mucosa and vulvar mucosa were 66.67%,62.5%,45.83%,respectively.6.Laboratory examination mainly showed abnormal blood routine,liver and kidney dysfunction,electrolyte disturbances,hypoproteinemia,and elevated fasting blood glucose.The bacteria culture of skin secretions mainly showed Staphylococcus aureus and Staphylococcus epidermidis.7.Complications: In the study,pneumonia occurred in 3 patients(12.5%);steroid hypertension occurred 3 patients(12.5%);steroid diabetes occurred 1 patients(4.17%);nerve excitement occurred 1 patient(4.17%);vaginal adhesions occurred 1 patient(4.17%);urinary tract infection occurred 1 patient(4.17%);peritonitis occurred 1 patient(4.17%).8.Mortality: According to the SCORTEN,we calculated the total expected death was 4.9 cases,while the actual death was 2 cases(P> 0.05).9.Treatment: 22 patients were treated with glucocorticoids,of which 16 cases were treated with pulsed high-dose(Group I)while 6 cases received conventional dose(Group II).The days of the fever relief were 4.31±2.67 and 4.67±1.86(P=0.178),the days of the improvement of lesions were 6.31±4.13 and 6±5.25(P=0.319),the days before maintenance dose of glucocorticoid were 7.31±2.36 and 6.5±2.59(P=0.874).Comparing to the conventional dose,the therapy of pulsed high-dose glucocorticoid could not significantly reduce the time of the fever relief,the period of lesion improvement,or the course of glucocorticoid before reduction to the maintenance dose(P>0.05);7 patients were treated with glucocorticoid monotherapy(Group GC),while 15 patients were treated with glucocorticoid combined with IVIG(Group GC+IVIG).The days of the fever relief were 3.71±1.98 and 4.73±2.63(P=0.273),the days of the improvement of lesions were 5.42±4.83 and 6.21±4.50(P=0.838),the days before maintenance dose of glucocorticoid were 7.14±3.48 and 7.07±1.83(P=0.052).Comparing to glucocorticoid monotherapy,glucocorticoid combined with IVIG could not significantly reduce the time of the fever relief,the period of lesion improvement,or the course of glucocorticoid before reduction to the maintenance dose(p>0.05);Administration with IVIG within the first 3 days of hospitalization could effectively reduce the fever relief time(P=0.027),but failed to significantly shorten the period of lesion improvement and the course of glucocorticoid before reduction to the maintenance dose(P> 0.05).Conclusion: 1.The main causative agents of TEN are antibiotics and antipyretic analgesics,antibiotics mainly include cephalosporins and penicillins.2.Erythra is the most common initial symptom,in addition fever and mucosal lesions,etc.The most common mucosal lesions are oral,eye and vulva in turn.3.There is no laboratory index of specific diagnostic value in the case of TEN.Besides,TEN may be accompanied by multiple organ damage.A variety of complications can occur during the treatment,such as secondary infections,steroid hypertension and diabetes,etc.4.SCORTEN score can help predict the expected mortality.5.Comparing to the conventional dose glucocorticoid therapy,the therapy of pulsed high-dose glucocorticoid could not significantly reduce the fever relief time,the period of lesion improvement or the course of glucocorticoid before reduction to the maintenance dose;Comparing to glucocorticoid monotherapy,the glucocorticoid combined with IVIG therapy could not significantly reduce the fever relief time,the period of lesion improvement or the course of glucocorticoid before reduction to the maintenance dose;Treatment with IVIG within the first 3 days of hospitalization could effectively reduce the fever relief time,but failed to significantly shorten the period of lesion improvement and the course of glucocorticoid before reduction to the maintenance dose.