Established and emerging concepts in Hirschsprung's-associated enterocolitis

Abstract

Hirschsprung's disease (HSCR) is a common cause of neonatal bowel obstruction and the approach to diagnosis and surgical treatment is well defined and accepted. Hirschsprung's-associated enterocolitis (HAEC) remains a frequent cause of pre-operative and post-operative morbidity and mortality, with unchanged treatment guidelines over multiple decades. Recent advances in our understanding of the genetics underlying HSCR have allowed the development of animal models, some of which recapitulate the HAEC phenotype. These animal models, along with recent translational studies, have implicated multiple facets of mucosal immunity and microbiome dysbiosis in the development of HAEC. Here, we will review the established epidemiology, modes of diagnosis and treatment of HAEC. Furthermore, we will explore emerging concepts in the pathogenesis of this disease; including animal models, alterations in mucosal immunity, dysbiosis of the intestinal microbiome, specific genetic susceptibility, and novel treatment modalities.

Keywords: Enterocolitis; Hirschsprung disease; Hirschsprung’s disease; Microbiome; Mucosal immunity; Pathogenesis.

Figure 1

Number of HAEC Publications in PubMed over time. A PubMed search for ((Hirschsprung[Title/Abstract] OR Hirschsprung’s[Title/Abstract]) AND Enterocolitis) was conducted on 31 December 2015 to determine the number of publications related to HAEC over time. The number of publications related to HAEC is increasing, with 25 in 2015.

Figure 2

Emerging Concepts in HAEC Pathogenesis. Recent studies in the EdnrB^−/− and EdnrB^NCC−/− mouse, along with human studies, have implicated facets of mucosal immunity (encompassing innate and adaptive immunity, as well as epithelial barrier defense mechanisms) and microbiome dysbiosis in the development of HAEC.