Long-term assessment of esophageal remodeling in patients with pediatric eosinophilic esophagitis treated with topical corticosteroids

Abstract

Background Eosinophilic esophagitis (EoE) is a chronic Th2 inflammatory disease characterized by tissue remodeling that leads to esophageal strictures and food impactions. Effects of therapy on long term remodeling in pediatric eosinophil-associated diseases has not been previously described. Objective To understand the long term control of esophageal remodeling in EoE Methods We assessed endoscopic and histologic remodeling and TGFβ1 expression in esophageal biopsies from children (n=32) with EoE treated with topical corticosteroids (TCS) over 10 years (mean=4.5). We utilized standardized EoE scoring tools to gauge endoscopic and symptom features. Results 738 biopsies from 246 endoscopic procedures were evaluated over 10 years. 486 biopsies had adequate lamina propria (LP) for evaluation of subepithelial remodeling. The severity of epithelial esophageal eosinophilia correlated with epithelial remodeling (basal zone hyperplasia, desquamation, and dilated intercellular spaces) (p<0.0001), LP eosinophilia (p<0.0001), and fibrosis (p<0.0001). Sixteen subjects were initial responders (<15 eosinophils per hpf) to TCS. Responders and non-responders spent 54% and 97% of their total disease duration with active EoE (p<0.001) and 23% and 53% (p<0.02) with maximal fibrosis scores, respectively. Responders had lower endoscopy scores during their disease duration (p=0.013). Having <15 eosinophils per hpf at any time correlated with lower fibrosis and endoscopic severity. TGFβ1 positive cells decreased in responders at the first biopsy but this was not sustained. Symptoms did not correlate with other disease features. Conclusions Children with EoE have substantial esophageal remodeling which associates with inflammation and that can improve in a sustainable manner with TCS. Although endoscopic features correspond to histologic features, symptoms did not correlate with inflammation or fibrosis.

Swallowed Fluticasone Propionate Is an Effective Long-Term Maintenance Therapy for Children With Eosinophilic Esophagitis

“…Rajan et al hypothesize that there may be distinct EoE phenotypes including “transient responders”, which may help explain our observation 41 .…”

“…The patients remained in the group for the intention to treat analysis. A recent publication by Rajan et al also did not find influence of PPI on eosinophilia or tissue remodeling 41 .…”

“…The authors described the main effect of swallowed topical steroids on fibrosis being exerted primarily via control of inflammation, as lower fibrosis scores correlated with decreased number of esophageal eosinophils, rather than with treatment duration and intensity of swallowed topical steroids 41 . This finding supports our observation that a decrease in peak esophageal eosinophil levels is significantly correlated with LP fibrosis reversal, with the underlying mechanism likely being inflammation control.…”

Compounded Oral Viscous Budesonide is Effective and Provides a Durable Response in Eosinophilic Esophagitis

“…For patients with an initial histologic response to compounded budesonide, over two-thirds continued to demonstrate a histologic response to the medication despite a 1 mg reduction from the initial dose. These results are similar though more favorable than findings from previous long-term studies of tCS in the management of EoE, [20,33] and they lend credence to some patients losing disease control with time. Our results also support previous work suggesting that steroid doses should be carefully reduced to avoid loss of histologic response.…”

Diminishing Effectiveness of Long-Term Maintenance Topical Steroid Therapy in PPI Non-Responsive Eosinophilic Esophagitis

“…18, 19 For each time period, we determined the mean ESS, maximum eosinophil count, mean steroid dose, and proportion of patients using a PPI. Kaplan–Meier analysis was used to calculate the durability of topical corticosteroids in maintaining histologic remission.…”