Clinical Implications and Pathogenesis of Esophageal Remodeling in Eosinophilic Esophagitis

Abstract

In eosinophilic esophagitis (EoE), remodeling changes are manifest histologically in both the epithelium as well as in the subepithelium where lamina propria (LP) fibrosis, expansion of the muscularis propria and increased vascularity occur. The major clinical symptoms and complications of EoE are largely consequences of esophageal remodeling. Important mediators of the process include IL-5, IL-13, TGFβ1, mast cells, fibroblasts and eosinophils. Methods to detect remodeling effects include upper endoscopy, histopathology, barium esophagram, endoscopic ultrasonography, esophageal manometry, and functional luminal imaging. These modalities provide evidence of organ dysfunction that include focal and diffuse esophageal strictures, expansion of the mucosa and subepithelium, esophageal motor abnormalities and reduced esophageal distensibility. Complications of food impaction and perforations of the esophageal wall have been associated with reduction in esophageal caliber and increased esophageal mural stiffness. The therapeutic benefits of topical corticosteroids and elimination diet therapy in resolving mucosal eosinophilic inflammation of the esophagus are evident. Available therapies, however, have demonstrated variable ability to reverse existing remodeling changes of the esophagus. Systemic therapies that include novel, targeted biologic agents have the potential of addressing subepithelial remodeling. Esophageal dilation remains a useful, adjunctive therapeutic maneuver in symptomatic adults with esophageal stricture. As novel treatments emerge, it is essential that therapeutic endpoints account for the fundamental contributions of esophageal remodeling to overall disease activity.

Esophageal dilation in eosinophilic esophagitis

“…Recently, we confirmed these findings in 29 EoE patients finding that average intrabolus pressure (a measure of distal pressurization) was significantly higher in patients with fibrostenotic versus inflammatory EoE (18.6 mmHg vs 12.6 mmHg, p < 0.05) (36). These esophageal pressurization events in EoE likely reflect reduced esophageal distensibility secondary to remodeling with strictures and are less likely due to inflammation alone (10).…”

“…The pathogenesis of EoE and remodeling is complex and will only be briefly summarized in this chapter. Recommended readings are by S. Aceves and colleagues (9,10) with Figure 1 summarizing the key interleukins and cytokines with their clinical consequences.…”

“…In adults the two determinants for esophageal food impaction seem to be 1) narrowed esophageal lumen and 2) decreased esophageal distensibility (i.e. decreased compliance or increased rigidity) (10). Esophageal strictures are present in 30% to 80% of adult EoE patients (1), whereas decreased distensibility is reported in more than 70% of adult EoE patients (10).…”

“…decreased compliance or increased rigidity) (10). Esophageal strictures are present in 30% to 80% of adult EoE patients (1), whereas decreased distensibility is reported in more than 70% of adult EoE patients (10). In contrast, strictures are uncommonly found in children (< 5%), even though food impactions occur in up to 30% of subjects (10).…”

“…A recent case report described an adult with features of EoE with manometric features consistent with achalasia. The patient's dysphagia and manometry M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT 10 improved with systemic corticosteroid treatment (33). Reports of traditional esophageal manometry in 100 EoE adults found that approximately 53% of patients had esophageal motility disorders, usually nonspecific peristaltic abnormalities or low LES pressures (6).…”