免疫缺陷伴发的炎症性肠病的临床特征及急诊外科治疗

Clinical features and surgical treatments for acute inflammatory bowel disease accompanied by genetic immunodeficiency

目的分析免疫缺陷伴发的炎症性肠病的临床特征及急性发作期手术干预的时机和手术方案的选择,总结病因及病因学治疗的相关方法,为该类疾病的内外科综合治疗提供临床经验。方法回顾性研究2015年1月至2017年6月在复旦大学附属儿科医院进行手术治疗的免疫缺陷伴发的严重炎症性肠病患儿的临床资料,统计免疫缺陷性肠病的病因、遗传学背景、临床表现、手术指征、手术方案、肠管累及范围、后续综合治疗情况及预后情况。9例患儿纳入本研究,男4例,女5例,发病年龄4 d至2岁(中位年龄17 d)。全部患儿均有明确免疫缺陷性疾病,其中4例为IL10RA基因突变导致的IL-10受体缺乏;X连锁的无丙种球蛋白血症2例和免疫球蛋白缺乏症1例,分别为BTK基因和SH2D1A基因突变所致。1例ITGB2基因突变导致的白细胞黏附缺陷综合征。1例CYBB基因突变引起的慢性肉芽肿病。主要症状是长期或反复腹泻、发热(8例),常见并发症包括复发性或复杂性肛瘘(6例)、顽固性口腔溃疡(4例)、体表或腹腔脓肿(2例)等。主要手术指征包括肠梗阻(6例)、肠道感染无法控制(2例)、气腹(1例)。根据术中探查病变受累肠段分布在距屈氏韧带20 cm小肠到直肠,手术方式包括bishop造瘘(3例)、分离式双腔造瘘(2例)、病变肠管旷置单腔造瘘近远端健康肠管一期吻合(2例)、袢式造瘘(1例)、近端单腔造瘘远端封闭(1例)。结果术后3例出现伤口感染裂开;1例出现内瘘,经保守治疗愈合;仅1例因粘连性肠梗阻再次手术。6例炎症控制后进行了脐血干细胞移植,5例恢复良好,1例因嵌合失败死于感染;2例定期补充丙球,恢复良好;1例术后放弃治疗后死亡。7例存活患儿中5例进行了二期或三期的pena手术、肛瘘切除术、造瘘关闭术,目前结束治疗定期门诊随访中。另外2例肠道炎症控制满意,等待造瘘关闭手术中。结论基因突变导致的免疫缺陷伴发的炎症性肠病发病早、病情重、药物治疗效果差。若基因检测明确存在致病突变,应早期积极进行外科干预,旷置病变肠段以利炎症控制。术后伤口感染裂开是最常见并发症。结合干细胞移植、补充免疫球蛋白等综合治疗措施可使该类患儿获得满意的治疗效果。

Objective To analyze the timing of surgical intervention and the choice of surgical options during acute episodes of inflammatory bowel disease (IBD) with immunodeficiency due to genetic abnormality, to summarize the etiologies and the therapies of genetic immunodeficiency and to provide clinical rationales for comprehensive treatments of these diseases. Methods A retrospective review was conducted for the clinical data of children with severe IBD undergoing emergency operations from January 2015 to June 2017. The etiologies, genetic backgrounds, clinical manifestations, surgical indications, surgical approaches, intestinal involvements, postoperative comprehensive treatments and outcomes were analyzed. There were 4 boys and 5 girls with a median age of onset of 17 (4-730) days. All of them had immunodeficiency disease caused by definite genetic abnormalities, including IL-10 receptor deficiency (n=4), X-linked agammaglobulinemia caused by IL10RA (n=1) and BTK gene mutation (n=1) respectively. There was one case of immunoglobulin deficiency syndrome, leukocyte adhesion deficiency syndrome, chronic granuloma and mutations of SH2D1A, ITGB2 and CYBB respectively. Chronic or recurrent diarrhea and fever were most common symptoms (8/9), recurrent or complicated anal fistula (6/9), intractable oral ulcer (3/9) and surface or abdominal abscess (2/9) were common concomitant symptoms. Major surgical indications included intestinal obstruction (n=6), refractory intestinal infection (n=2) and pneumoperitoneum (n=1). According to the findings of intraoperative exploration, the lesions were distributed in different locations from upper jejunum to rectum. Primary enterostomy was performed. Results There were wound infection (n=3) and dehiscence (n=1). One case was re-operated for adhesive intestinal obstruction. After infection control, 6 children underwent subsequent cord blood stem cell transplantation. Five cases recovered well while another one died from infection due to chimera failure. Two cases received supplement immunoglobulin regularly. Among 7 patients with immune function recovery, 5 patients underwent Pena procedure, anal fistulectomy and stoma closure in Ⅱ/Ⅲ stage with regular outpatient follow-ups while another 2 patients waited for stoma closure after an adequate control of intestinal inflammation. Conclusions Immunodeficiency caused by genetic abnormality is associated with an early onset of inflammatory bowel disease, severe illness and a poor therapeutic efficacy. Early surgical intervention should be performed for diverting affected intestine for infection control. Wound infection and dehiscence are two common operative complications. Satisfactory therapeutic efficacy may be achieved through comprehensive treatments.