Low TTG-IgA associated with isolated bulb pathology in pediatric celiac disease: Implications in a no-biopsy approach era

Objectives Duodenal involvement in celiac disease (CD) can be patchy, with a subset of patients demonstrating histopathological involvement limited to the bulb. This study evaluates whether bulb-restricted CD represents a distinct subgroup associated with lower titers of immunoglobulin A anti-tissue transglutaminase antibody (TTG-IgA) compared to distal duodenal CD in pediatric patients. Additionally, we assess the impact of a no-biopsy approach for pediatric CD with TTG-IgA >= 10 times the upper limit of normal (TTG-IgA >= 10x ULN) on the relative frequency of bulb-restricted CD among biopsied patients. Methods Incident pediatric CD cases were identified retrospectively between 2017 and 2022. A no-biopsy approach for TTG-IgA >= 10x ULN was locally implemented in 2020. Serum TTG-IgA was categorized as negative, equivocal, positive TTG-IgA <10x ULN, and positive TTG-IgA >= 10x ULN. Biopsies were classified by Marsh score and site of involvement. Results Of the 405 cases included (mean age = 9.6 years, female-to-male ratio = 2.1:1), bulb-restricted CD was present in 7.4%. TTG-IgA was negative or equivocal in 60.0% of bulb-restricted CD, compared to 5.3% of distal duodenal CD (odds ratio [OR] = 26.6; 95% confidence interval [CI] = [11.1-63.3], p < 0.001). Notably, no bulb-restricted CD cases attained TTG-IgA >= 10x ULN, compared to 48.5% of distal duodenal CD. Following local implementation of the no-biopsy approach for TTG-IgA >= 10x ULN, the relative percentage of bulb-restricted CD significantly increased from 4.6% to 12.4% (OR = 2.9, 95% CI = [1.4-6.4], p = 0.004). Conclusion Pediatric CD with isolated bulb pathology presents with lower serum TTG-IgA titers than cases with distal duodenal involvement. Implementation of the no-biopsy approach increased the relative proportion of bulb-limited CD, as these cases were not associated with TTG-IgA >= 10x ULN.