A novel clustering of down syndrome and coeliac disease complicated by enteritis and small intestinal strictures: a case series
- Author(s)
- Kanagasundaram, C; Efklides, J; Koh, E; Ryan, S; Elliott, T; Prideaux, L; Kong, XF; Yeoh, SW; Cruickshank, J; Tye-Din, JA;
- Journal Title
- Therapeutic Advances in Gastroenterology
- Abstract
- Down syndrome (DS) increases risk for autoimmune conditions, including coeliac disease (CeD). Here, we report five adults with DS and biopsy-proven CeD who developed enteritis and symptomatic small bowel stricturing, a clustering not previously described in this population. All five patients had confirmed DS and CeD, and despite apparent adherence to a gluten-free diet, all developed small bowel strictures requiring endoscopic intervention, most commonly at the duodenal D1/D2 junction. Stricture histology demonstrated active CeD with varying degrees of inflammation and fibrosis. Three patients had elevated faecal calprotectin without consistent colonic pathology, suggesting enteritis as an important inflammatory driver. Two patients responded well to open capsule budesonide with symptom resolution and histological improvement. One patient showed no sustained benefit from multiple immunosuppressive agents, including corticosteroids, azathioprine, and infliximab, requiring repeated endoscopic dilatations. Differential diagnoses, including Crohn's disease, tuberculosis, nonsteroidal anti-inflammatory drug (NSAID) enteropathy, refractory CeD, and cryptogenic multifocal ulcerating stenosing enteritis were excluded based on clinical history, imaging, and histological findings. No granulomas or aberrant T-cell populations were identified. We propose this clustering may reflect a shared pathogenic mechanism linked to the interferonopathy of DS. Trisomy 21 causes overexpression of interferon receptors, creating heightened interferon signalling. Combined with CeD-triggered interferon production from gluten exposure, this may drive amplified immune activation, chronic enteritis, and fibrotic stricture formation. This hypothesis warrants further investigation through transcriptomic and immunohistochemical studies. Clinicians should consider this clustering in DS patients with CeD who present with persistent gastrointestinal symptoms. Given the underlying biology, JAK inhibitors may represent a promising therapeutic option for this phenotype and merit future study.; Reporting a new association between Down syndrome, coeliac disease, and inflammation with narrowing of the bowel People with Down syndrome have a higher risk of autoimmune diseases like coeliac disease. In this report, we describe five adults with Down syndrome and coeliac disease who developed inflammation and narrowing (strictures) of the small intestine. The response to immune-suppressing treatment was variable, and all needed procedures to treat the strictures. We postulate that the combination of Down syndrome, coeliac disease, and small bowel strictures could be due to a shared underlying cause, such as higher levels of specific kinds of immune receptors in people with Down syndrome. Doctors should think about this possibility when Down syndrome patients have ongoing gut symptoms.; eng
- Keywords
- Down syndrome; coeliac disease; intestinal strictures; trisomy 21
- Research Division(s)
- Immunology
- PubMed ID
- 42130809
- Publisher's Version
- https://doi.org/10.1177/17562848261446854
- Open Access at Publisher's Site
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Creation Date: 2026-05-25 11:04:07
Last Modified: 2026-05-25 11:04:18