Pathophysiology of Eosinophilic Esophagitis

Gastroenterology. 2018 Jan;154(2):333-345. doi: 10.1053/j.gastro.2017.06.065. Epub 2017 Jul 27.

Abstract

Eosinophilic esophagitis is an emerging disease that is distinguished from gastroesophageal reflux disease by the expression of a unique esophageal transcriptome and the interplay of early life environmental factors with distinct genetic susceptibility elements at 5q22 (TSLP) and 2p23 (CAPN14). Rare genetic syndromes have uncovered the contribution of barrier disruption, mediated in part by defective desmosomes and dysregulated transforming growth factor beta production and signaling, to eosinophilic esophagitis pathophysiology. Experimental modeling has defined a cooperative role of activated eosinophils, mast cells, and the cytokines IL-5 and IL-13, mediated by allergic sensitization to multiple foods. Understanding these processes is opening the way to better treatment based on disrupting allergic inflammatory and type 2 cytokine-mediated responses, including anti-cytokine therapeutics and dietary therapy.

Keywords: Allergy; Desmosome; Genetics; Inflammation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adult
  • Age Factors
  • Allergens / immunology
  • Biopsy
  • Child
  • Cytokines / genetics
  • Cytokines / immunology*
  • Cytokines / metabolism
  • Ehlers-Danlos Syndrome / epidemiology
  • Ehlers-Danlos Syndrome / immunology
  • Eosinophilic Esophagitis / epidemiology
  • Eosinophilic Esophagitis / etiology*
  • Eosinophilic Esophagitis / pathology
  • Eosinophilic Esophagitis / therapy*
  • Eosinophils / immunology*
  • Epigenesis, Genetic
  • Esophageal Stenosis / etiology
  • Esophageal Stenosis / immunology
  • Esophageal Stenosis / pathology
  • Esophagus / immunology
  • Esophagus / pathology*
  • Female
  • Fibrosis
  • Food Hypersensitivity / immunology*
  • Gastroesophageal Reflux / etiology
  • Gastroesophageal Reflux / pathology
  • Gastrointestinal Microbiome / immunology
  • Genetic Predisposition to Disease / genetics
  • Glucocorticoids / therapeutic use
  • Humans
  • Loeys-Dietz Syndrome / epidemiology
  • Loeys-Dietz Syndrome / immunology
  • Male
  • Mast Cells / immunology
  • Mast Cells / metabolism
  • Prevalence
  • Proton Pump Inhibitors / therapeutic use
  • Sex Factors
  • Transcriptome / genetics

Substances

  • Allergens
  • Cytokines
  • Glucocorticoids
  • Proton Pump Inhibitors

Supplementary concepts

  • Ehlers-Danlos syndrome type 3