A systematic review of celiac disease recommendations for children with Down syndrome

This systematic review critically compares current international guidelines and recommendations from major medical organizations on the management of celiac disease (CD) in individuals with Down syndrome (DS), in light of the increased disease prevalence and the diagnostic challenges posed by overlapping clinical and immunological features. A comprehensive search of PubMed, Embase, Scopus, and international association websites (through June 1, 2025) identified guidelines, position papers, and expert statements endorsed by national or international bodies. Two reviewers independently screened and selected studies, and guideline quality was assessed using the AGREE II tool. Of 929 records identified, seven clinical practice guidelines, and two clinical practice reports were included. Recommendations varied widely, ranging from universal screening (e.g., British Society of Paediatric Gastroenterology, Hepatology and Nutrition [BSPGHAN], Down Syndrome Medical Interest Group [DSMIG], European Society for the Study of Coeliac Disease [ESsCD], European Society for Pediatric Gastroenterology, Hepatology, and Nutrition [ESPGHAN] and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition [NASPGHAN]) to symptom-based testing (e.g., American Academy of Pediatrics [AAP], American Gastroenterological Association [AGA], American College of Gastroenterology [ACG], and National Institute for Health and Care Excellence [NICE]). While there is consensus on serologic screening using tissue transglutaminase IgA (tTG-IgA) and total IgA, interpretation is complicated by the high prevalence of selective IgA deficiency in DS, often necessitating IgG-based testing. HLA genotyping is not generally recommended for routine screening but may help exclude CD in non-susceptible individuals and support biopsy-sparing diagnostic pathways. In conclusion, marked heterogeneity exists among current guidelines. Harmonized, evidence-based recommendations are needed. HLA-DQ2/DQ8 genotyping should be used primarily for its high negative predictive value to exclude CD in non-susceptible individuals with DS. This tiered approach offers a clinically actionable strategy to reduce diagnostic delays, minimize unnecessary procedures, and improve care equity for children with DS.