Novel Insights into the Pathogenesis of Hirschsprung's-associated Enterocolitis

Abstract

Objective:To systematically summary the updated results about the pathogenesis of Hirschsprung's-associated enterocolitis (HAEC). Besides, we discussed the research key and direction based on these results.Data Sources:Our data cited in this review were obtained mainly from PubMed from 1975 to 2015, with keywords “Hirschsprung enterocolitis”, “Hirschsprung's enterocolitis”, “Hirschsprung's-associated enterocolitis”, “Hirschsprung-associated enterocolitis”, “HAEC”, and “EC”.Study Selection:Articles regarding the pathogenesis of HAEC were selected, and the articles mainly regarding the diagnosis, surgical approach, treatment, and follow-up were excluded.Results:Several factors, mainly including mucus barrier, intestinal microbiota, and immune function, as well as some other factors such as genetic variations and surgical reasons, have been found to be related to the pathogenesis of HAEC. Changed quantity and barrier property of mucus, different composition of microbiota, and an abnormal immune state work together or separately trigger HAEC.Conclusions:The maintenance of intestinal homeostasis is due to a well cooperation of microbiota, mucus barrier, and immune system. If any part presents abnormal, intestinal homeostasis will be broken. Meanwhile, for patients with Hirschsprung's disease or HAEC, dysfunction of these parts has been found. Thus, the happening of HAEC may be mainly attributed to the disorders of intestinal microbiota, mucus barrier, and immune system.

Is intestinal stasis sufficient by itself in promoting enterocolitis in a non-genetic rat model of Hirschsprung’s disease?

“…However, this mechanism does not explain neither the occurrence of HE in patients with HD without distended bowel (such as those after decompressive colostomy, or those with surgically corrected HD) nor the presence of HE lesions in the aganglionic bowel segment. 11,15 This paradox has led researchers to investigate the effects of many other factors of the development of HE, acting independently or in concert, such as microbiome alteration and impaired mucosal barrier function. These can be caused by variations in the components and amount of mucus, immunological deficiency, either local or systemic, with deficient white cell function, mucosal immunity defects, increased prostaglandin E1 activity, impaired motility associated with protein sensitization, and sucrase-isomaltase deficiency.…”

“…These can be caused by variations in the components and amount of mucus, immunological deficiency, either local or systemic, with deficient white cell function, mucosal immunity defects, increased prostaglandin E1 activity, impaired motility associated with protein sensitization, and sucrase-isomaltase deficiency. 11,12,[16][17][18][19][20] These conditions could be the expression of the complex genetics of HD. 21 Increased HE risk in patients with Down syndrome, 22,23 cartilage-hair hypoplasia, 24 family history of HD, and female sex point to a possible genetic contribution to the etiology of HE.…”

“…9 This led to the investigation of additional possible HE causative factors, such as deficiency of the immune system and compromise of local intestinal mucus production. [10][11][12] These factors could be inherited through complex HD genetics. 4 The goal of this study was to investigate whether aganglionosis-induced intestinal stasis can by itself cause HE.…”

Hirschsprung\'s Disease-Related Giant Sigmoid Volvulus Complicated by Refractory Hypertension in an Elderly Man

“…HD is a congenital disorder caused by sparse ganglion cells or intestinal neuronal dysplasia or nerve fibers dysplasia in both submucosal and myenteric plexuses and the transitional segment of colon during development [ 6 , 7 ]. Those disorders lead to the functional obstruction manifesting as severe chronic constipation and colorectal distension, which can result in SV [ 20 , 21 ]. HD mostly causes SV in infants and children and is rare in elderly patients.…”

Laparoscopic-assisted endorectal pull-through for Hirschsprung’s disease. A retrospective study

“…Postoperative bowel dysfunction presents as enterocolitis in 6-30% of patients and as constipation and soiling in 11-35% of patients. 1 , 2 One possible reason for this dysfunction is that the proximal bowel remains “abnormal”, or it could be due to inaccurate preoperative screening or inappropriate surgical technique. 3 In this study, we summarized our experience with the laparoscopic-assisted endorectal pull-through procedure (LAEPT).…”