The pathogenesis of Hirschsprung’s disease-associated enterocolitis

Hirschsprung’s disease-associated enterocolitis (HAEC) remains the most life-threatening complication in Hirschsprung disease (HD) patients. The pathogenesis of HAEC has not been determined and many hypotheses regarding the etiology of HAEC have been proposed. These include a possible causal relationship between the abnormal enteric nervous system development in HD and the development of enterocolitis. Based on the complex genetic causes of HD that have been discovered and the resultant heterogeneous group of patients that exists, the causes of HAEC are likely multiple. New insights regarding the relationship of the role of the enteric nervous system and its interaction between intestinal barrier function, innate host immunity, and commensal microflora have been discovered, which may shed light on this perplexing problem. This review presents current known risk factors of HAEC and the proposed theories and supporting evidence for the potential etiologies of HAEC.