Ultra-short celiac disease in children: histological and autoimmune features

Ultra-short celiac disease (USCD) represents a histopathological variant with selective involvement of the duodenal bulb. The mechanisms underlying the sparing of the second duodenal portion remain unclear. The histopathological progression of USCD under continued gluten exposure is not yet defined and represents a significant gap in current understanding. This retrospective study assessed histological changes in the duodenal bulb and second portion of the duodenum in pediatric patients who maintained gluten consumption until a definitive USCD diagnosis. Inclusion criteria required persistent dietary gluten intake, initial diagnosis confirmed by Marsh-Oberhuber classification, and elevated tissue transglutaminase (tTG) antibody levels. Fifteen out of 35 patients with USCD underwent repeat endoscopies. Villous atrophy was consistently confined to the first portion of the duodenum, with preservation of the second portion despite gluten exposure. Extensive celiac disease (ECD), characterized by involvement of the second portion of the duodenum, was associated with a significantly increased prevalence of short stature (p < 0.001) and iron deficiency anemia (p = 0.010), as well as substantially higher titers of tTG antibodies (p < 0.001). Both the USCD and ECD groups had similar rates of additional autoimmune diseases.  Conclusion: In children, USCD presents with a distinct and localized duodenal response to gluten. Although USCD presents with a milder clinical and serological profile, the comparable autoimmune burden underscores the necessity for accurate diagnosis and timely treatment. What is Known: • Patients with USCD typically demonstrate milder clinical symptoms and lower serological markers compared to those with more extensive small-intestinal involvement. • The histopathological response to ongoing gluten exposure in USCD has not been characterized to date. What is New: • USCD remains histologically confined to the duodenal bulb, with no progression to the second portion of the duodenum observed over time, even with continued gluten intake. • Isolated duodenal bulb involvement may be sufficient to initiate systemic autoimmunity in celiac disease, despite mild clinical and serological features.