Complications of enterostomy and related risk factor analysis of very early onset inflammatory bowel disease with interleukin-10 signalling deficiency: a single-centre retrospective analysis

Very early onset inflammatory bowel disease (VEOIBD) in children under the age of 6 years diagnosed with IBD is often associated with a monogenetic disorder [1]. More than 60 genes associated with VEOIBD have been identified through next-generation sequencing and genetic linkage analysis [2, 3].

Interleukin-10 (IL10)/interleukin-10 receptor (IL10R) mutations have been identified in a subset of infants with severe VEOIBD. Our group studied a large cohort of patients with VEOIBD caused by IL-10R defects [4, 5]. This type of VEOIBD often presents as perianal diseases and intestinal ulcers, perforation, and obstruction; VEOIBD responds poorly to medical therapies and requires early surgical interventions [4, 6]. Elective surgery and emergency surgery are often performed in children with severe gastroenterological symptoms [7].

However, descriptions of enterostomy in VEOIBD patients, especially those with IL10R gene mutations, are scarce. This retrospective study aims to describe the characteristics of VEOIBD patients with IL10R mutation after enterostomy, enterostomy complications and related risk factors.

VEOIBD, especially with IL10/IL10R signalling pathway deficiency, is characterized by severe enterocolitis, perianal disease and proctitis involving the colon and terminal ileum [12]. The lesions associated with IL10 are distributed from the jejunum to the anorectum, and the terminal ileum and colon are the most frequently involved sites. Stricture, perforation, abscess, fistula, and severe perianal disease are common complications in IL10R-mutation IBD patients. Surgery is indicated after medical treatment is unsuccessful or after disease complications develop [13, 14]. However, published data on the complications, possible risk factors and other postoperative outcomes in IL10R-mutation IBD patients are scarce.

For paediatric IBD patients, the benefits of enterostomy include alleviation of disease severity, extended lifespan and reduced risk of death [14‐16]. Although surgery is never curative for paediatric IBD patients, it has the ability to transform the disease process. For monogenic VEOIBD, timely enterostomy may offer opportunities for further HSCT [17]. In our study, 22 IL10R-mutation patients underwent enterostomy, and 12 patients underwent an emergency operation because of intestinal obstruction or perforation. Surgical procedures such as ileostomy and colostomy can induce remission of the disease.

Fahy et al. reported that in paediatric patients with severe refractory Crohn’s colitis, total colectomy offers an opportunity to improve nutrition and growth and reduce steroid use with a reasonable likelihood of restoring intestinal continuity [18]. Maxwell et al. reported that in paediatric patients with refractory colonic IBD, a diverting ileostomy can be a successful intervention to induce clinical stability [19]. In our study, the surgical approach allowed patients to decrease the use of metronidazole, thalidomide and other drugs. The patients experienced disease remission and developmental growth after enterostomy, with an increase in albumin levels, weight for age Z-scores and BMI Z-scores. Furthermore, 7 patients gained the opportunity to undergo HSCT, and 6 patients presented successful immune reconstitution and symptom remission after enterostomy.

For severe VEOIBD with IL10 gene mutations, appropriate surgical treatments should be used. Emergency operation indications, such as intestinal perforation, complete obstruction, or generalized peritonitis, may occur. For medically resistant patients or those with severe perianal disease, elective surgeries should be considered [15]. Leeds et al. reported that delayed operations for acute ulcerative colitis were associated with increased postoperative complications, increased lengths of stay, and increased hospital costs. Therefore, immediate surgical intervention for medically refractory ulcerative colitis is suggested [20]. Pigneur et al. reported that of 10 VEOIBD patients with IL10 signalling pathway defects, 8 patients underwent surgery, 5 patients were clinically stable after HSCT, 2 patients died of B-cell lymphoma before HSCT and 1 patient stabilized without treatment [21]. Our group obtained the same results: 5 patients died after emergency surgery because of severe infection and/or malnutrition. After elective enterostomy, only 1 patient died because of sepsis during HSCT. The timing of enterostomy and the age at enterostomy should be considered. The benefits of selective enterostomy were superior to those of emergency enterostomy. Prophylactic enterostomy at an earlier stage may be indicated in some cases. The most common indications for elective surgery include severe perianal diseases, such as strictures and fistulas; severe intestinal infection with persistent diarrhoea and septicaemia; and aggressive disease after medical treatment. The risk of life-threatening infections will increase in cases of delayed or unnecessary operations. Therefore, the timing of surgery is particularly important for these patients. According to our group’s experience and the published literature, if aggravated infection or abdominal distension and intestinal dynamic obstruction occur, an enterostomy should be performed immediately [7, 22].

The management of severe VEOIBD with IL10 gene mutations remains a challenge despite significant advances in medical and surgical therapies [15, 23, 24]. The burden of surgery and postoperative complications in children with IBD should be considered [25, 26]. In our study, although the drug expenditure decreased after enterostomy because of remission, the total expenditure did not decrease significantly because of the additional expenses associated with stoma care. Furthermore, more than 50% of patients experienced complications after colostomy, and the complication rate remained considerably high. Wound infection, wound dehiscence, reoperation, short bowel syndrome, etc. occurred in our patients. Stoma care and routine assessments were important. Stoma construction apart from the primary incision may also reduce complications. Furthermore, stoma closure was another issue for the patients who underwent enterostomy.

Assa et al. reported that for paediatric Crohn’s disease (CD), complicated presentations at diagnosis were associated with an increased risk of surgery (HR = 2.7, P < 0.001), and for ulcerative colitis, severe disease at diagnosis was associated with an increased risk of colectomy (HR = 3.5, P = 0.002) [27]. Ladd et al. reported that a multivariable analysis indicated that malnutrition corresponded with increased odds of complications in mild and severely malnourished patients (mild OR = 2.1 [P = 0.04], severe OR 3.26 [P = 0.03]) [9]. In our study, the multivariate logistic regression analysis showed that although there was no significant difference, the CRP level and wPCDAI showed tendencies to be independent risk factors.

Our study had limitations. One limitation was the small sample of enterostomy patients because VEOIBD with an IL10R gene mutation is still a rare disease. Therefore, there was no significant difference in the independent risk factors. Second, increased mortality may have influenced the long-term complication rate for enterostomy. Finally, it was difficult to objectively define the patients’ disease severity because VEOIBD occurred at a very young age.

Our study demonstrated the benefits of enterostomy in IL10R-mutation VEOIBD patients. The timing, associated complications and related risk factors of enterostomy should be considered.