血浆置换疗法治疗重症大疱性类天疱疮的疗效观察

Clinical effect of plasma exchange therapy on severe bullous pemphigoid

目的探讨血浆置换疗法治疗重症大疱性类天疱疮的临床疗效和作用机制.方法选择2015年2月1日至2019年6月1日武汉市第一医院重症医学科(ICU)治疗的64例重症大疱性类天疱疮患者,按随机数字表法分为常规治疗组(给予常规糖皮质激素和免疫抑制剂治疗)与联合血浆置换组(在常规治疗的基础上给予血浆置换治疗),每组32例.于治疗前及治疗10d后,分别采用酶联免疫吸附试验(ELISA)检测两组患者的血清自身抗体〔抗BP180抗体及其抗体亚型(IgG1、IgG4)〕水平,采用鲎试剂法检测血浆内毒素水平,采用ELISA法检测血浆炎性因子〔肿瘤坏死因子(TNF-α)、白细胞介素-6(IL-6)、白细胞介素-8(IL-8)〕水平.观察两组患者治疗前后的血清自身抗体、内毒素和血浆炎性因子水平,比较两组治疗2周后的多器官功能障碍综合征(MODS)发生率、病死率、机械通气时间、ICU住院时间以及临床疗效.结果治疗后两组的抗BP180抗体、IgG1、IgG4、血浆内毒素、TNF-α、IL-6、IL-8水平均较治疗前降低,且联合血浆置换组治疗后上述指标水平均明显低于常规治疗组〔抗BP180抗体(U/mL):46.2±13.5比75.4±19.4,IgG1(U/mL):0.29±0.14比0.41±0.22,IgG4(U/mL):0.16±0.08比0.23±0.12,内毒素(EU/mL):1.1±0.2比2.5±0.4,TNF-α(μg/L):69.4±8.5比104.3±19.6,IL-6(μg/L):89.1±13.8比164.8±24.7,IL-8(μg/L):186.4±32.7比286.1±47.6,均P<0.05〕.联合血浆置换组的MODS发生率〔9.4%(3/32)比31.2%(10/32)〕、病死率〔0(0/32)比9.4%(3/32)〕、机械通气时间〔(3.3±0.4)d比(5.7±1.4)d〕、ICU住院时间〔(10.4±1.7)d比(14.5±2.6)d〕均明显低于常规治疗组,总有效率明显高于常规治疗组〔96.9%(31/32)比78.1%(25/32)〕,差异均有统计学意义(均P<0.05).结论血浆置换联合常规糖皮质激素治疗重症大疱性类天疱疮效果明显优于单纯的糖皮质激素治疗,其机制可能与降低抗BP180抗体及IgG1、IgG4水平、血浆内毒素水平以及炎性因子水平有关.

Objective To investigate the clinical effect and mechanism of plasma exchange therapy on severe bullous pemphigoid.Methods Sixty-four patients with severe bullous pemphigoid in Intensive Care Unit(ICU)of Wuhan No.1 Hospital from February 1,2015 to June 1,2019 were selected and divided into routine treatment group(treated with routine glucocorticoid and immunosuppressant)and combined plasma exchange group(treated with plasma exchange on the basis of routine treatment)according to random number table method,32 cases in each group.Before and 10 days after treatment,the levels of serum autoantibodies[anti-BP180 antibody and its antibody subtypes(IgG1,IgG4)]were declined by enzyme linked immunosorbent assay(ELISA),the level of endotoxin in plasma was declined by limulus amebocyte lysate,and the levels of inflammatory cytokines[tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and interleukin-8(IL-8)]in plasma were declined by ELISA.The levels of serum autoantibodies,endotoxin and plasma inflammatory factors were observed before and after treatment in the two groups,and the incidence of multiple organ dysfunction syndrome(MODS),fatality rate,mechanical ventilation time,duration of ICU stay and clinical effect after two weeks of treatment in the two groups were compared.Results After treatment,the levels of anti-BP180 antibody,IgG1,IgG4,plasma endotoxin,TNF-α,IL-6 and IL-8 in two groups were lower than those before treatment,and the levels of above indexes in combined plasma exchange group were significantly lower than those in conventional treatment group[anti-BP180 antibody(U/mL):46.2±13.5 vs.75.4±19.4,IgG1(U/mL):0.29±0.14 vs.0.41±0.22,IgG4(U/mL):0.16±0.08 vs.0.23±0.12,endotoxin(EU/mL):1.1±0.2 vs.2.5±0.4,TNF-α(μg/L):69.4±8.5 vs.104.3±19.6,IL-6(μg/L):89.1±13.8 vs.164.8±24.7,IL-8(μg/L):186.4±32.7 vs.286.1±47.6,all P<0.05].The incidence of MODS[9.4%(3/32)vs.31.2%(10/32)],mortality[0(0/32)vs.9.4%(3/32)],duration of mechanical ventilation[(3.3±0.4)d vs(5.7±1.4)d],and duration of ICU stay[(10.4±1.7)d vs.(14.5±2.6)d]in combined plasma exchange group were significantly lower than those in conventional treatment group,and the total effective rate was significantly higher than that in the conventional treatment group[96.9%(31/32)vs.78.1%(25/32)].The differences were statistically significant(all P<0.05).Conclusions The effect of plasma exchange therapy combined with routine glucocorticoid on severe bullous pemphigoid is better than that of glucocorticoid alone.The mechanism may be related to the reduction of anti-BP180 antibody,IgG1,IgG4,plasma endotoxin and inflammatory factor levels.