Clinical Implications and Pathogenesis of Esophageal Remodeling in Eosinophilic Esophagitis

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Key points

  • Remodeling changes in eosinophilic esophagitis include epithelial basal zone hyperplasia, lamina propria fibrosis, expansion of the muscularis propria, and increased vascularity.

  • Esophageal inflammation in eosinophilic esophagitis drives the remodeling process with mediators that include IL-5, IL-13, TGFβ1, mast cells, fibroblasts, and eosinophils.

  • Recent studies have provided increasing evidence that the primary symptoms of esophageal dysfunction in children and adults as well as clinical

Definition of esophageal remodeling

The concept of eosinophil-associated tissue remodeling stems from diseases such as the hypereosinophilic syndrome and asthma. Remodeling can be defined as tissue changes in target organs that result in end organ dysfunction. Remodeling is associated with histologic alterations, such as fibrosis and angiogenesis, which are caused by changes in cellular function, phenotype, and products. Remodeling itself may not be a pathogenic process, as it could be considered to represent a protective

Pathogenesis of esophageal remodeling in EoE

Inflammatory mediators and cells clearly play a role in driving esophageal remodeling (Table 1, Fig. 2). Animal models demonstrate that mice lacking eosinophils or the eosinophilopoetic cytokine interleukin (IL)-5, have significantly less collagen deposition and fibronectin expression than their wild-type littermates.4, 5 In addition, mice that have decreased esophageal eosinophils also have decreased basal zone hyperplasia.5 Importantly, a lack of eosinophils, even in the presence of IL-5

Relationship of esophageal remodeling with clinical manifestations and complications

The clinical presentations of EoE reflect esophageal dysfunction. These functional changes in the esophagus likely reflect esophageal remodeling. In adults, EoE is dominated by symptoms of dysphagia and food impaction, whereas in children symptoms more commonly mimic gastroesophageal reflux disease (GERD) with dysphagia and food impactions becoming more prominent in adolescence. In adult subjects, there are 2 determinants for esophageal food impaction risk: (1) a reduction in luminal diameter

Barium Radiography

A variety of methods have been used in clinical practice and investigative studies to demonstrate the remodeling consequences of EoE (Table 2). One of the oldest methods to evaluate the structure of the gastrointestinal tract is barium radiography. Early case series demonstrated the association of marked restriction of the esophageal luminal caliber with EoE, characterized as a narrow caliber or small-caliber esophagus.32 Fig. 4 illustrates the diffuse nature of this finding. The multiple,

Effectiveness of available therapies for remodeling in EoE

EoE therapies are rapidly evolving as the mechanisms underlying the disease become better understood. Most drugs are in the early stages of development and none are currently approved by regulatory authorities for use in patients outside of clinical trials. Elimination diet therapy has demonstrated effectiveness similar to medical therapies in terms of resolution of mucosal eosinophilic inflammation. The primary end points used to judge the efficacy of therapies are symptoms and esophageal

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