产毒型艰难梭菌在炎症性肠病患儿中的感染率及阳性患儿的临床特点

Infection rate and clinical characteristics of toxigenic Clostridium difficile in children with inflammatory bowel disease

目的了解炎症性肠病(IBD)患儿产毒型艰难梭菌的感染率及阳性患儿的临床特点。方法回顾性研究。收集2015年7月至2016年10月首都医科大学附属北京儿童医院消化科收治的30例IBD患儿及同医院健康体检的30名对照儿童的粪便标本及临床资料,检测其艰难梭菌毒素基因,并分析毒素基因阳性患儿的临床特征。组间比较采用χ^2检验。结果IBD组30例(UC组、CD组各15例),艰难梭菌毒素基因阳性6例(UC 3例、CD 3例),产毒型艰难梭菌感染率为20%。基因型为艰难梭菌毒素A(tcdA)+艰难梭菌毒素B(tcdB)-5例,tcdA+tcdB+1例;健康对照组30名,产毒型艰难梭菌感染1例,感染率为3%,基因型为tcdA+tcdB-。两组儿童均未检测到二元毒素基因。IBD组粪便标本产毒型艰难梭菌感染率明显高于健康对照组,差异有统计学意义(χ^2=4.043,P=0.044)。UC组缓解期未检测出艰难梭菌毒素基因(0/1),轻度活动期中艰难梭菌毒素基因阳性1例(1/11),中度活动期阳性2例(2/3),不同疾病活动度之间产毒型艰难梭菌感染率差异有统计学意义(χ^2=4.000,P=0.046)。6例艰难梭菌毒素基因阳性患儿主要表现为腹泻、腹痛及便血,复发型者有突然加重的特点;所有阳性标本均检测到tcdA,1例合并tcdB+者黏液脓血便表现更重;5例完善结肠镜检查,未发现黄白色隆起或伪膜斑等艰难梭菌肠炎特异性表现;3例有抗菌药物暴露史;6例均对甲硝唑抗艰难梭菌治疗敏感;随访3个月,6例患儿均病情平稳,未复发。结论IBD患儿较健康儿童产毒型艰难梭菌感染率高。tcdA+tcdB+者临床表现更重。结肠镜检查无特异性表现。临床上应加强对IBD患儿产毒型艰难梭菌感染检测的认识。

Objective To explore the infection rate and clinical characteristics of toxigenic Clostridium difficile in children with inflammatory bowel disease(IBD).Methods From July 2015 to October 2016,the fecal samples and clinical data of 30 IBD children admitted to Department of Gastroenterology,Beijing Children′s Hospital,Capital Medical University,as well as the specimens and data of 30 healthy children were collected in the meantime.The toxin gene of Clostridium difficile was detected and clinical characteristics of children with positive toxin gene were analyzed retrospectively.χ^2 test was used to compare the variables between groups.Results Among the 30 IBD patients,15 were in ulcerative colitis(UC)group and 15 in Crohn′s disease(CD)group.In the IBD group,6(3 in UC and 3 in CD group)had positive result of toxigenic Clostridium difficile(20%),among whom 5 were toxin Clostridium difficile A(tcdA)+toxin Clostridium difficile B(tcdB)-,and 1 was tcdA+tcdB+.In the healthy group,only one had positive result of toxigenic Clostridium difficile(3%),which was tcdA+tcdB-.Binary toxin gene was negative in both groups.The infection rate of toxigenic Clostridium difficile in IBD group was significantly higher than that in healthy control group(χ^2=4.043,P=0.044).In UC group,no Clostridium difficile toxin gene was detected during the remission period(0/1),one case was positive for toxin gene(1/11)during mild active period,and 2 cases were(2/3)during moderately active period.There were significant differences in the infection rate of toxigenic Clostridium difficile between patients in different active period(χ^2=4.000,P=0.046).The main manifestations of the 6 cases were diarrhea,abdominal pain and bloody stool,and the relapsed case was characterized by sudden aggravation.TcdA was detected in all toxin gene positive samples,and 1 case combined with tcdB had more serious bloody mucopurulent stool.Five cases had colonoscopy,but there was no obvious characteristics of toxigenic Clostridium difficile colitis such as yellow white plaques or pseudomembranous spot.Three cases had antibiotic exposure history.All 6 cases were sensitive to metronidazole treatment,and stable without relapse during the 3-month follow-up.Conclusions The infection rate of toxigenic Clostridium difficile in children with IBD is higher than that in healthy children.The patients with both tcdA and tcdB could have more serious clinical symptoms,although there may not be specific pathological changes of toxigenic Clostridium difficile colitis.The recognition of toxigenic Clostridium difficile infection in IBD children should be strengthened in clinical work.