A Clinician's Guide to Gluten Challenge.

Gluten challenge is an essential clinical tool that involves reintroducing or increasing the amount of gluten in the diet to facilitate diagnostic testing in celiac disease (CD). Nevertheless, there is no consensus regarding the applications of gluten timing, dosing, and duration in children. This review aims to summarize the current evidence, discuss practical considerations, and proposes a clinical algorithm to help guide testing in pediatric patients. Childhood development, social circumstances, and long-term health concerns must be considered when identifying a candidate for gluten challenge. Based on previous studies, the authors suggest baseline serology followed by a minimum of 3-6 grams of gluten per day for over 12 weeks to optimize diagnostic accuracy for evaluation of CD. A formal provider check-in at 4-6 weeks is essential so the provider and family can adjust dosing or duration as needed. Increasing the dose of gluten further may improve diagnostic yield if tolerated, although in select cases a lower dose and shorter course (6-12 weeks) may be sufficient. There is consensus that mild elevations in celiac serology (<10 times the upper limit of normal) or symptoms, while supportive are not diagnostic for CD. Current North American Society for Pediatric Gastroenterology, Hepatology and Nutrition guidelines recommend histologic findings of intraepithelial lymphocytosis, crypt hyperplasia, and villous atrophy as the accurate and most appropriate endpoint for gluten challenge.
Competing Interests: Dr Silvester has served on advisory boards for Alimentiv, Mozart Therapeutics, Takeda Pharmaceuticals, and Teva Pharmaceuticals. She has served as site-PI for clinical trials sponsored by Cour Pharmaceuticals and Takeda Pharmaceuticals and has research support from Milky Way Life Sciences. Dr Leonard has served on an advisory board for Mozart Therapeutics and 9Meters Biopharma and acted as a consultant for Anokion. She has served as site-PI for Takeda Pharmaceuticals. The remaining authors report no conflicts of interest.
(Copyright © 2023 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)