Long term control of remodeling in pediatric eosinophilic esophagitis

Published Online: August 8, 2015

Eosinophilic esophagitis (EoE) is a disease of increasing worldwide prevalence that causes dysphagia, pain, and poor growth in children. EoE complications include esophageal rigidity, narrowing, food impactions, and strictures. These complications are caused by tissue remodeling that includes epithelial basal cell hyperplasia, subepithelial fibrosis, and smooth muscle hypertrophy. EoE therapy is geared toward controlling inflammation and remodeling improves concurrent with inflammatory control following short term therapy in children. However, the extent to which remodeling can be controlled by long-term therapy in children is not clear. These questions are important if remodeling is the mechanism leading to disease complications since childhood or shorter disease durations may provide a window of opportunity for long-term disease control.

Recently published in The Journal of Allergy and Clinical Immunology (JACI), Rajan et al report the pattern of esophageal remodeling in 32 children treated with topical corticosteroids (TCS) for mean of 4.5 years (maximum of 10 years). Among the group studied, 50% were initial responders (defined as <15 epithelial eosinophils per high power field). Histologic features of basal zone hyperplasia, dilated intercellular spaces, and fibrosis were scored using a published histology scoring tool. The inflammatory and remodeling response to TCS in the epithelium and subepithelium were compared between the responders and non-responders. Endoscopic features and clinical symptoms were assessed in the children over time.

Over their disease duration and at each endoscopic procedure during the study period, responders had lower epithelial and lamina propria (subepithelial) eosinophils, epithelial remodeling and fibrosis than non-responders. TGFb1 positive cells were lower in the responders at the first biopsy post-therapy but this was not sustained. Overall, responders had lower endoscopy scores at the majority of endoscopic instances but symptoms did not correspond with any parameters. Although responders were significantly more controlled in terms of epithelial eosinophilia and remodeling for the duration on TCS, after about 2.5 years there were increases in epithelial and subepithelial eosinophilia as well as fibrosis despite continued therapy. The numbers of TGFb1 positive cells correlated with the degree of fibrosis among the responders. Low mucosal eosinophilia correlated with low lamina propria eosinophilia, as well as low epithelial remodeling and endoscopy scores. Generally, fibrosis was increased when disease duration was longer. Persistent stricture or progression to stricture occurred only in the non-responder group, suggesting that persistent remodeling and lack of response to therapy could increase the risk of complications.

EoE is a persistent disease in children that shows long term improvement on chronic therapy. The persistence of remodeling in non-responders underscores the need for additional therapies in EoE. Longer studies in larger cohorts of children on TCS and on other EoE-directed therapies will be interesting to shed further light on how to control esophageal remodeling and disease complications in EoE.   

The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.

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