Pathophysiology of Eosinophilic Esophagitis

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

Authors

Kelly M O'Shea¹, Seema S Aceves², Evan S Dellon³, Sandeep K Gupta⁴, Jonathan M Spergel⁵, Glenn T Furuta⁶, Marc E Rothenberg⁷

Affiliations

¹ Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
² Division of Allergy Immunology, Center for Immunity, Infection and Inflammation, University of California San Diego and Rady Children's Hospital San Diego, California.
³ Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
⁴ Division of Pediatric Gastroenterology, Hepatology and Nutrition, University of Illinois College of Medicine at Peoria and Children's Hospital of Illinois, Peoria, Illinois.
⁵ Division of Allergy and Immunology, The Children's Hospital of Philadelphia and Department of Pediatrics, Perelman School of Medicine at University of Pennsylvania, Philadelphia, Pennsylvania.
⁶ Digestive Health Institute, Gastrointestinal Eosinophilic Diseases Program, Section of Pediatric Gastroenterology, Hepatology and Nutrition, Children's Hospital Colorado and Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado.
⁷ Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio. Electronic address: marc.rothenberg@cchmc.org.

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

Pathophysiology of Eosinophilic Esophagitis

Authors

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Abstract

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