Hirschsprung Disease Tied To Increased Risk Of Inflammatory Bowel Disease

Children with Hirschsprung disease may be at increased risk for developing inflammatory bowel disease, a Canadian study suggests.

Researchers examined data on 716 children diagnosed with Hirschsprung since 1991 in Ontario, as well as almost 3.4 million children without this diagnosis.

A total of 18 children (2.5%) with Hirschsprung disease developed inflammatory bowel disease (IBD), an incidence rate of 168.8 per 100,000 person-years. By comparison, a total of 7,109 children (0.2%) without Hirschsprung disease developed IBD, an incidence rate of 14.2 per 100,000 person-years.

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"Most Hirschsprung disease is diagnosed at birth or soon after and most post-Hirschsprung inflammatory bowel disease is diagnosed years later," said lead study author Dr. Charles Bernstein, director of the IBD Clinical and Research Center at the University of Manitoba in Winnipeg, Canada.

While the study wasn't designed to determine causality, it's possible that the abnormalities in the gut microbiome triggered by Hirschsprung disease may lead inflammatory bowel disease to develop, Dr. Bernstein said by email.

Children with Hirschsprung disease had a significantly higher risk of developing IBD overall (hazard ratio 11.8), as well as a significantly higher risk of Crohn's disease (HR 15.9) and ulcerative colitis (HR 6.5).

Both conditions are associated with defects in microbiome composition, epithelial barrier integrity, and mucosal immunity, but a single common predisposing factor has not yet been identified, said Dr. Allan Goldstein, a professor of surgery at Harvard Medical School and chief of pediatric surgery at Massachusetts General Hospital in Boston.

"We know that there is close communication between enteric neurons and immune cells in the normal intestine," Dr. Goldstein, who wasn't involved in the study, said by email.

Despite removing the aganglionic bowel at the time of pull-through surgery for Hirschsprung disease, there is evidence that the neurons in the remaining bowel are not entirely normal, Dr. Goldstein said. This poorly characterized enteric neuronal abnormality may lead to aberrant communication with immune cells and thereby create a pro-inflammatory environment in the intestine that is more susceptible to the development of IBD, Dr. Goldstein added.

One limitation of the study is that researchers used administrative data and lacked complete information on the phenotype and course of IBD, the study team notes in the Journal of Pediatrics. Researchers also didn't follow patients into adulthood to see how Hirschsprung disease related to IBD later in life.

Even so, the results underscore the importance of monitoring children with Hirschsprung disease for any signs or symptoms of IBD, Dr. Goldstein said.

One challenge of caring for children with Hirschsprung disease is diagnosing and treating Hirschsprung-associated enterocolitis (HAEC), which is a significant complication of the disease, Dr. Goldstein said.

"The symptoms of HAEC can overlap with those of IBD (chronic diarrhea, bloody stool), while the treatments are very different," Goldstein said. "Some patients with Hirschsprung disease struggle with ongoing symptoms and failed attempts to treat HAEC when in fact the problem may be IBD."

—Lisa Rapaport

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