Potential for Improving Therapy and Defining New Research Targets in Eosinophilic Oesophagitis Based on Understanding of Immunopathogenesis

Murch, Simon H.*; Allen, Katrina; Chong, Sonny; Dias, Jorge Amil§; Papadopoulou, Alexandra||; on Behalf of the Eosinophilic Oesophagitis Working Group of ESPGHAN

Journal of Pediatric Gastroenterology & Nutrition: October 2013 - Volume 57 - Issue 4 - p 529–534
doi: 10.1097/MPG.0b013e3182a212ab
Consensus Statement

Objectives: This review considers the potential for therapeutic advances in the management of eosinophilic oesophagitis (EoE) based on recently increased understanding of the pathophysiology of the disorder.

Methods: This is a review of publications characterising mucosal changes and leucocyte recruitment patterns in human and experimental EoE.

Results: EoE, although diagnosed by epithelial infiltration of eosinophils, is actually a transmural inflammation in which eosinophil recruitment occurs via the deeper layers. Penetration of eosinophils into the epithelium is variable, explaining the need for multiple biopsies to diagnose what may be a clearly visible disorder. Fibrosis and neuromuscular dysfunction both occur within the subepithelial tissues. Recent murine studies have identified that T-cell recruitment underpins antigen-specific oesophageal eosinophil recruitment. Involvement of innate immunity is also suggested by the role of invariant natural killer T cells in experimental EoE.

Conclusions: Looking beyond present therapeutic options with a view to future studies, we identify T cells as candidates for “upstream therapy” if antigen specificity or homing markers are determined. Evidence of aeroallergen sensitisation suggests the possibility of lymphocyte priming within nasal-associated lymphoid tissue or Waldeyer ring, with the potential for topical therapy. We consider acquired neuromuscular dysfunction as a therapeutic target in acute symptomatic deterioration or bolus obstruction. We assess possible similarities with therapeutic stratagems for chronic asthma, recognising at the same time the anatomic specificity of the oesophagus and the difficulty in delivering effective topical medication to subepithelial tissues in this location compared with the airway.

*Division of Metabolic and Vascular Health, Warwick Medical School, Coventry, UK

Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, Australia

Department of Paediatrics, St Mary's Hospital for Children, Carshalton, UK

§Department of Paediatrics, Hospital St João, Porto, Portugal

||Department of Paediatrics, Athens Children's Hospital, Athens, Greece.

Address correspondence and reprint requests to Professor Simon H. Murch, Division of Metabolic and Vascular Health, Warwick Medical School, Clinical Sciences Building, Clifford Bridge Road, Coventry CV2 2DX, UK (e-mail: s.murch@warwick.ac.uk).

Received 18 June, 2013

Accepted 19 June, 2013

Additional members of the ESPGHAN Eosinophilic Esophagitis Working Group (in alphabetical order): H. Antunes (Portugal), M.K.H. Auth (UK), C. Dupont (France), R. Garcia-Puig (Spain), C. Gutiérrez Junquera (Spain), M. Fotoulaki (Greece), M. Furman (UK), C.M.F. Kneepkens (Netherlands), A. Kostovski (FYROM), R. Orel (Slovenia), C. Spray (UK), A. Staiano (Italy), M. Thomson (UK), V. Urbonas (Lithuania), Y. Vandenplas (Belgium), and N. Zevit (Israel).

The authors report no conflicts of interest.

© 2013 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,