糖尿病患者服用二肽基肽酶Ⅳ抑制剂后发生大疱性类天疱疮32例临床特征分析

Analysis of clinical characteristics of bullous pemphigoid developing after the treatment with dipeptidyl peptidase-Ⅳinhibitors in 32 patients with diabetes mellitus

目的探讨糖尿病患者服用二肽基肽酶Ⅳ抑制剂(DPP4i)后发生的大疱性类天疱疮(BP)的临床特征。方法收集沈阳市第七人民医院2014年1月至2020年12月病房收治的合并糖尿病的BP患者116例,分为BP发病前应用DPP4i治疗糖尿病的DPP4i-BP组和未应用DPP4i治疗的普通BP组,分析和比较两组的一般临床资料、皮损面积、实验室指标、治疗方案、预后,记录DPP4i-BP组患者服用DPP4i与BP诊断的时间间隔。计量资料多组间比较采用单因素方差分析,两组间比较采用独立样本t检验,组内前后比较采用配对t检验;计数资料组间比较采用卡方检验。结果DPP4i-BP组32例,年龄(77.17±15.32)岁,男女比例为15∶17;普通BP组84例,年龄(76.65±19.32)岁,男女比例为43∶41。DPP4i-BP组开始服用DPP4i药物到诊断BP的时间间隔为(14.61±3.93)个月,其中维格列汀的间隔时间最短,为(5.42±2.84)个月,与西格列汀、利格列汀、沙格列汀比较差异有统计学意义(F=8.93,P<0.001)。与普通BP组相比,DPP4i-BP组病情重度患者多,为16例(50%),两组间差异有统计学意义(Z=2.63,P=0.008)。两组抗BP180抗体阳性患者的比例差异无统计学意义(χ2=0.03,P=0.870)。治疗前后DPP4i-BP组抗BP180抗体水平均高于普通BP组(P=0.015、<0.001),且降低幅度小于后者(t=5.11,P<0.001)。两组控制病情所需的糖皮质激素平均有效剂量差异无统计学意义(t=1.00,P=0.322)。DPP4i-BP组控制病情所需平均时间较长(t=6.72,P<0.001),并且更需要联合免疫抑制剂或其他药物(t=10.05,P=0.002)。开始系统治疗后6个月内,普通BP组病情出现反复的病例比例(17例,27.86%)明显高于DPP4i-BP组(2例,7.69%,χ2=4.35,P=0.037)。并且,6个月时,普通BP组糖皮质激素平均剂量显著高于DPP4i-BP组(t=7.04,P<0.001)。结论DPP4i类降糖药中,BP发病前服用维格列汀患者最多,服药与BP发病时间间隔最短。DPP4i-BP患者治疗初期可能不易控制,但预后较好。

Objective To investigate clinical characteristics of bullous pemphigoid(BP)developing after the treatment with dipeptidyl peptidase-Ⅳinhibitors(DPP4i)in patients with diabetes mellitus.Methods A total of 116 inpatients with BP complicated by diabetes mellitus were collected from the Seventh People′s Hospital of Shenyang between January 2014 and December 2020,and divided into 2 groups:DPP4i-BP group treated with DPP4i before the onset of BP,and general BP group receiving no treatment with DPP4i.General clinical data,skin lesion area,laboratory indicators,treatment regimens,and prognosis were analyzed and compared between the above 2 groups,the time interval from the administration of DPP4i to the diagnosis of BP was recorded in the DPP4i-BP group.One-way analysis of variance was used to compare measurement data among multiple groups,two-independent-sample t test was used for comparisons between two groups,and paired t-test for intra-group comparisons before and after treatment;chi-square test was used to compare enumeration data between groups.Results There were 32 patients aged 77.17±15.32 years in the DPP4i-BP group,with a male-to-female ratio being 15∶17;there were 84 patients aged 76.65±19.32 years in the general BP group,with a male-to-female ratio being 43∶41.The time interval from the administration of DPP4i to the diagnosis of BP was 14.61±3.93 months in the DPP4i-BP group.The time interval for vildagliptin was the shortest(5.42±2.84 months),and there was a significant difference in the time interval among vildagliptin,sitagliptin,linagliptin and saxagliptin(F=8.93,P<0.001).The proportion of patients with severe BP was significantly higher in the DPP4i-BP group(16 cases,50%)than in the general BP group(25 cases,29.76%;Z=2.63,P=0.008).There was no significant difference in the positivity rate of anti-BP180 antibody between the two groups(χ2=0.03,P=0.870).However,the level of anti-BP180 antibody was significantly higher in the DPP4i-BP group than in the general BP group before and after treatment(P=0.015,<0.001,respectively),and the decrease in the level of anti-BP180 antibody was significantly less in the DPP4i-BP group than in the general BP group after treatment(t=5.11,P<0.001).There was no significant difference in the average effective dose of glucocorticoids required to control the disease between the two groups(t=1.00,P=0.322).However,the DPP4i-BP group showed a significant increase in the average time required to control the disease and in the proportion of patients requiring combined treatment with immunosuppressants or other drugs compared with the general BP group(t=6.72,10.05,P<0.001,=0.002,respectively).Within 6 months after the start of systemic treatment,the recurrence rate was significantly higher in the general BP group(17 cases,27.86%)than in the DPP4i-BP group(2 cases,7.69%;χ2=4.35,P=0.037);at 6 months,the average dose of glucocorticoids was also significantly higher in the general BP group than in the DPP4i-BP group(t=7.04,P<0.001).Conclusions Among the DPP4i hypoglycemic drugs,vildagliptin was the most common drug administrated by patients before the onset of BP,with the shortest interval from the administration to the onset of BP.DPP4i-BP may be difficult to control at the early stage,but the prognosis is good.