Overview

Eosinophilic Esophagitis
Recently, a new, clinical/pathologic form of esophagitis has been described, known as eosinophilic esophagitis (EoE). This condition was first recognized as a separate entity from gastroesophageal reflux-induced esophagitis in 1995, and its incidence is increasing in North America.

Since the discovery of EoE many studies have focused on the characteristics of the infiltrating intraepithelial eosinophils. EoE is limited to the esophagus and characterized by an intense infiltration of eosinophils in the esophageal mucosa. The specific cytokines and cells (mast cells and CD4+ cells) associated with EoE suggest a Th2 phenotype for this disease. Experimental models of EoE in animals sensitized to environmental and food antigens suggest an important role for interleukin-5 (IL-5) for eosinophil activation and eotaxin-3 for esoinophil recruitment into tissue. Increased numbers of mast cells, T lymphocytes and anti-IgE staining cells in the esophageal mucosa have also been observed in EoE. Dendritic cells are present in small numbers in esophagus, but these are mostly submucosal and are not increased in EoE.

EoE is diagnosed by observing large numbers of intraepithelial eosinophils in biopsies (>15 per high power field) and excluding other disorders. Little is understood about EoE in humans, most importantly the inciting event, pathogenesis and what perpetuates the inflammation. Eosinophils degranulate, releasing stored mediators that damage the epithelium. Approximately 75-80% of patients presenting with EoE have a history of atopy. Patients may improve on an elemental diet, devoid of antigen, and partially resolve with treatment involving elimination of specific foods. It is possible that esophageal eosinophilia is a reactive change resulting from loss of tolerance to ingested antigen. Degradation of antigen in the stomach by proteases may explain why this disease is limited to the esophagus.

Recent Research Contributions


Mast cells

We discovered that atopic and non-atopic eosinophilic oesophagitis are distinguished by immunoglobulin E-bearing intraepithelial mast cells, implying unique pathophysiologic mechanisms in these subgroups of patients.  From Mulder et al. Histopathology, Sept 2012.









HLA-DR in EoE

We have shown that esophageal epithelial cells are able to present antigen via MHC class II in vitro and have also found evidence for this process occuring in an ex vivo co-culture model of esophageal epithelial cells and T helper cells.
From Mulder et al. American Journal of Pathology 178(2):744-753, Feb 2011.






FGF9 in the Esophagus Figure

We have also discovered a growth factor (fibroblast growth factor 9, FGF9) is produced from esophageal epithelial cells when they are exposed to the eosinophil product major basic protein. The production of FGF9 has a paracrine/autocrine effect on the epithelial cells that produce it, inducing their proliferation. This discovery is the first mechanistic link between eosinophils and the basal cell hyperplasia seen in eosinophilic esophagitis. From Mulder et al. Gut 58(2):166-73, Feb 2009.



We were the first to describe the presence of the extracellular calcium sensing receptor on the esophageal mucosa and detail its contribution to pathophysiology of the esophageal mucosa.
From Justinich et al. American Journal of Physiology - GI and Liver Physiology 294:120-129, Jan 2008.


Grants and Funding
Our research has been funded by the Physician's Services Incorporated and the Canadian Institutes of Health Research.