新生儿炎症性肠病的临床特征及基因诊断研究

Research of the clinical features and gene diagnosis in neonates with inflammatory bowel disease

目的分析2例新生儿期起病的炎症性肠病临床特点及基因诊断结果,以提高对该病的认识和临床诊疗水平。方法2018年至2019年,解放军总医院第七医学中心八一儿童医院共收治2例新生儿期起病的炎症性肠病患儿。对2例诊断为新生儿炎症性肠病的患儿行结肠镜检查,并行病理活检,采用直接测序法对患儿进行白细胞介素-10受体A(interleukin-10 receptor A,IL-10RA)基因突变检测。同时在万方医学网、中国知网、PubMed等数据库中组合检索相关文献并分析。结果①例1患儿女孩,生后以发热、腹泻起病,多发口腔溃疡,C反应蛋白反复升高,抗感染治疗无效,行肠镜检查提示结肠多发糜烂溃疡,全外显子基因测序分析结果提示,基因IL-10RA存在一处纯合突变。抗炎治疗效果不理想,放弃治疗后死亡。例2患儿男孩,患儿生后反复腹泻,伴有发热,入院第16天行结肠镜检查提示结肠多发溃疡,病理检查提示大肠黏膜组织中度慢性炎伴轻-中度急性炎及局部糜烂。诊断炎症性肠病,予抗炎治疗后,患儿病情好转出院。②文献复习:经查阅文献,中文文献数据库检索出新生儿炎性肠病文献10篇,PubMed检索出4篇。国内文献多以病例报道为主。新生儿炎症性肠病以发热、腹泻为特征,常见口腔溃疡和肛周病变。血清自身抗体检测阳性率低,药物治疗效果欠佳。基因检测可存在IL-10RA基因突变。结论对于不明原因腹泻,体重增长不满意,尤其是伴有发热、口腔溃疡者,需高度警惕新生儿期起病的炎症性肠病,应积极行消化内镜及基因检测,以尽早确诊并予规范治疗。

Objective To analyze the clinical characteristics and gene diagnosis of 2 cases of neonatal onset inflammatory bowel disease(IBD),then to improve the level of clinical diagnosis and treatment.Methods From 2018 to 2019,two newborns with IBD were diagnosed in Bayi Children's Hospital,Seventh Medical Center of PLA General Hospital.Clinical data were collected,and the clinical characteristics were summarized.Enteroscopy was performed on two newborns,and pathological biopsies were performed.Interleukin-10 receptor A(IL-10RA)gene mutations were detected by direct sequencing.Relevant literatures searched from Wanfang data,China national knowledge infrastructure(CNKI),PubMed and other databases were reviewed and analyzed.Results①Case 1 was a girl with fever,diarrhea and multiple oral ulcers after birth.C reactive protein increased repeatedly.Anti-infective treatment was ineffective.Enteroscopy was performed.Examination revealed multiple ulcerative ulcers in the colon.Analysis of the whole exon gene sequence revealed that there was a homozygous mutation in the IL-10RA gene.The anti-inflammatory treatment effect was not satisfactory,and she died after giving up the treatment.Case 2 was a boy with diarrhea and fever.Enteroscopy was performed on the 16th day of admission,and revealed multiple colonic ulcers.Pathological examination revealed moderate chronic inflammation of the colonic mucosal tissue with mild-moderate acute inflammation and local erosion.After being diagnosed as neonatal IBD,and received anti-inflammatory treatment,he improved and was discharged.②Literatures review:after being reviewed,10 literatures on neonatal IBD were retrieved from the Chinese literature database,and 4 literatures were retrieved from PubMed.Domestic literature was mainly based on case reports.Neonatal IBD was characterized by fever,diarrhea.Oral ulcers and perianal lesions were common.The positive rate of serum autoantibodies was low,and the effect of drug therapy was poor.Genetic testing showed the presence of mutations in the IL-10RA gene.Conclusions For those with unexplained diarrhea and unsatisfactory weight gain,especially those with fever and oral ulcers,they need to be highly vigilant against IBD that develops during the neonatal period.Active digestive endoscopy and genetic testing should be performed to confirm the diagnosis as soon as possible,and early standard treatment is needed.