Differential changes in mast cells with food reintroduction in children with eosinophilic esophagitis

Intraepithelial mast cells (MCs) are increased in eosinophilic esophagitis (EoE) and reduced with elimination of dietary antigens. Single food reintroduction can identify triggers of eosinophilia; however, the extent to which specific foods trigger intraepithelial mastocytosis remains unknown. We hypothesized that specific foods drive different degrees of MC inflammation. We previously reported a prospective pediatric EoE cohort treated with a 4-food elimination diet (4FED) with removal of soy, egg, wheat, and milk. We retrieved unstained slides in which baseline, 4FED, and post-4FED diet reintroduction time points were available. Slides were stained with tryptase, and intraepithelial MCs were counted. Comparisons were made by stratifying patients by eosinophilia, basal cell hyperplasia (BCH), endoscopic abnormalities, and symptoms. Pearson correlation was assessed for MCs with eosinophilic, endoscopic, and BCH severity; symptoms; and a novel mucosal activity score combining endoscopic and histologic structural severity. Slides were available from 37 patients with at least 1 food reintroduced. MCs were significantly reduced with 4FED. Wheat led to increased intraepithelial MCs in the upper esophagus and with food-induced eosinophilia, while milk led to significantly increased MCs in the upper and lower esophagus and was significantly associated with patients with food-triggered eosinophilia, endoscopic abnormalities, BCH, and symptoms. MCs best correlated with the mucosal activity score during milk reintroduction. In children with EoE, MCs are reduced with 4FED. During milk reintroduction, significant increases in MCs were observed with all metrics of inflammation along with moderate correlation with structural mucosal activity that was not seen with other foods. This suggests that milk exerts unique effects either directly or indirectly on MCs in the esophagus in EoE patients.