DGBI Common in Children with Adequately Managed Celiac Disease, Study Finds

Findings from a recent study suggest disorders of gut-brain interaction (DGBI) are common in pediatric patients with celiac disease (CeD) despite adequate adherence to a gluten-free diet and declining tissue transglutaminase immunoglobulin A (TTG IgA) values.1

The retrospective chart review included nearly 200 pediatric CeD patients receiving care at Cincinnati Children's Hospital Medical Center (CCHMC) and found 43% of the cohort met Rome IV DGBI diagnostic criteria, primarily for functional constipation and functional abdominal pain, suggesting clinicians should consider DGBI in their patients who have persistent CeD symptoms despite adequate disease management.1

DGBI, formerly known as functional gastrointestinal disorders, are increasingly prevalent and significantly impact patients’ quality of life, but diagnosis is complicated by the fact that they share many similar symptoms with other organic gastrointestinal conditions, including CeD.2

“There are no studies evaluating the overlap between DGBI and CeD in US children. Better understanding this overlap is critical given that (1) the prevalence of DGBI is increasing, with studies suggesting approximately one-third of adults and 25% of children aged 4–18 years old meet DGBI diagnostic criteria and (2) the consequences of delayed or missed DGBI diagnosis are numerous, including increased healthcare costs and utilization,” Neha Santucci, MBBS, MD, director of the Disorders of Gut-Brain Interaction Program at the Neurogastroenterology and Motility Center and an associate professor in the department of pediatrics at the University of Cincinnati College of Medicine, and colleagues wrote.1

To address this gap in research, investigators conducted a retrospective chart review from 2016 to 2024 involving pediatric patients 4–21 years of age with biopsy-confirmed CeD diagnosis who had an initial visit with a pediatric gastroenterologist at CCHMC between 2016 and 2024, had ≥ 1 follow-up visit in the 9–24-month period after diagnosis, and demonstrated sustained decline in TTG IgA levels after implementing a strict gluten-free diet.1

Investigators classified patients into 2 groups. The control group (no-DGBI group) consisted of CeD patients who demonstrated TTG IgA decline, were asymptomatic at the 9–24-month follow-up visit, and remained asymptomatic at all subsequent visits. The DGBI group included CeD patients with TTG IgA decline who had persistent or new onset symptoms satisfying Rome IV criteria at any visit ≥ 9 months after diagnosis.1

Of the 663 patients with CeD diagnosis seen at CCHMC from 2016 to 2024, 191 met inclusion criteria and were included in the present analysis. The cohort was predominantly female (65%), Non-Hispanic (98%), and White (95%), with a median age at diagnosis of 11 (interquartile range, 6.09) years.1

Among the study cohort, 43% of patients met Rome IV diagnostic criteria for DGBI, most commonly functional constipation (33%) and functional abdominal pain (29%).1

Investigators assessed presenting symptoms, diagnostic severity, comorbid conditions, and family history to determine predictive factors of developing DGBI and found patients with abdominal pain (odds ratio [OR], 3.09; 95% CI, 1.57–6.31), constipation (OR, 2.19; 95% CI, 1.15–4.20), vomiting (OR, 2.36; 95% CI, 1.01–5.74), and nighttime pain awakening (OR, 9.76; 95% CI, 1.21–447.23) at the initial visit were more likely to develop a DGBI. Additionally, patients with complete villous blunting described in the pathology findings were at increased risk of DGBI (OR, 2.28; 95% CI, 1.22–4.29).1

Further analysis revealed having comorbid joint hypermobility syndrome (OR, 5.23; 95% CI, 1.56–22.74), headaches (OR, 3.47; 95% CI, 1.40–9.23), chronic musculoskeletal pain (OR, 3.20; 95% CI, 1.22–9.08), and chronic muscle pain (OR, 5.61; 95% CI, 1.08–55.60) were associated with an increased risk of developing DGBI, as was the presence of any comorbid psychiatric diagnosis (OR, 2.08; 95% CI, 1.09–4.01).1

Of note, sex, race, ethnicity, and presence of any family history of DGBI did not significantly increase the risk of DGBI diagnosis.1

“This study suggests DGBI are common in pediatric patients with CeD despite adequate adherence to a GFD and declining TTG IgA values. Further research is needed to understand how best to monitor patients with CeD after diagnosis, and whether ‘remission’ is something that can be determined based on serology, endoscopy, and/or symptoms,” investigators concluded.1 “Future multicenter prospective studies evaluating the prevalence and overlap of DGBI in children with CeD are also needed to better understand this interplay. In the meantime, this study underscores the importance of evaluating for and diagnosing DGBI when appropriate in children with adequately managed CeD to promote comprehensive care for patients.”

References

1. Krueger A, Patel U, Hardy J, et al. The prevalence and predictive factors of overlapping disorders of gut–brain interaction and celiac disease in children. Journal of Pediatric Gastroenterology and Nutrition. https://doi.org/10.1002/jpn3.70118.

2. Aziz I, Simrén M. The overlap between irritable bowel syndrome and organic gastrointestinal diseases. Lancet Gastroenterol Hepatol. doi:10.1016/S2468-1253(20)30212-0.