Sherrill, J.D. & Rothenberg, M.E. Genetic dissection of eosinophilic esophagitis provides insight into disease pathogenesis and treatment strategies. J. Allergy Clin. Immunol. 128, 23-32

Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio 45229, USA.
The Journal of allergy and clinical immunology (Impact Factor: 11.48). 05/2011; 128(1):23-32; quiz 33-4. DOI: 10.1016/j.jaci.2011.03.046
Source: PubMed


Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder of the esophagus that is compounded by both genetic predisposition and aberrant responses to environmental antigens, particularly those that are food derived. Data have indicated a unique transcriptional response in vivo that defines EoE and that appears to be partially attributable to the T(H)2 cytokine IL-13. Moreover, a number of genetic risk variants in proinflammatory and epithelial cell genes associate with EoE susceptibility, demonstrating novel heritable mechanisms that contribute to disease risk. Here we discuss recent advances in our understanding of the intrinsic (genetic) and extrinsic (environmental) components that illustrate the complex nature of EoE.

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    • "The identification of EoE as a disease occurred following investigations into treatment resistant patients with gastro-esophageal reflux disease (GERD) (3). The similarity in presentation of EoE and GERD necessitates the correlation of clinical and pathological findings and the establishment of diagnostic criteria differentiating the two diseases, to ensure accurate diagnosis and management (4). "
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    ABSTRACT: Eosinophilic esophagitis (EoE) is an emerging disease characterized by esophageal eosinophilia (>15eos/hpf), lack of responsiveness to acid-suppressive medication and is managed by allergen elimination and anti-allergy therapy. Although the pathophysiology of EoE is currently unsubstantiated, evidence implicates food and aeroallergen hypersensitivity in genetically predisposed individuals as contributory factors. Genome-wide expression analyses have isolated a remarkably conserved gene-expression profile irrespective of age and gender, suggesting a genetic contribution. EoE has characteristics of mainly TH2 type immune responses but also some TH1 cytokines, which appear to strongly contribute to tissue fibrosis, with esophageal epithelial cells providing a hospitable environment for this inflammatory process. Eosinophil-degranulation products appear to play a central role in tissue remodeling in EoE. This remodeling and dysregulation predisposes to fibrosis. Mast-cell-derived molecules such as histamine may have an effect on enteric nerves and may also act in concert with transforming growth factor-β to interfere with esophageal musculature. Additionally, the esophageal epithelium may facilitate the inflammatory process under pathogenic contexts such as in EoE. This article aims to discuss the contributory factors in the pathophysiology of EoE.
    Full-text · Article · May 2014 · Frontiers in Pediatrics
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    • "Current diagnostic criteria allow for the diagnosis of EoE in individuals with fewer than 15 eosinophils/hpf who have other abnormalities that are strongly associated with eosinophilic inflammation, such as eosinophilic microabscesses or extracellular eosinophil granules.1 The microscopic changes to the structure of the esophagus can manifest with gross structural changes that may suggest a diagnosis of EoE, including esophageal rings, furrows, whitish exudates or plaques and strictures.15,16 Esophageal rings can be fixed (also referred to as "esophageal trachealization") or transient (also described as "feline folds").1,2 "
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    ABSTRACT: Eosinophilic Esophagitis (EoE) is a chronic inflammatory disease of the esophagus triggered by an immune response that leads to symptoms of dysphagia, chest pain, and food impaction. EoE is a clinicopathologic syndrome that requires clinical symptoms and pathologic findings for a diagnosis. The inflammatory process and eosinophilic infiltration of the esophagus in EoE lead to fibrosis and structural changes within the esophagus that cause esophageal dysfunction. The biomechanics of the esophageal function in EoE have been explored using manometry, impedance planimetry, barium esophagograms, and endoscopic ultrasound. These studies have identified several biomechanical changes to the esophagus in EoE including pan-esophageal pressurization on manometry, changes in esophageal compliance with decreased distentisbility by impedance planimetry, decreased esophageal luminal diameter by esophagograms, and dysfunction in the esophageal longitudinal muscles by endoscopic ultrasound. Treatments for the disease involve dietary changes, immunosuppressive drugs, and dilation techniques. However, the data regarding the effect of these therapies on altering mechanical properties of the esophagus is limited. As the pathogenesis of esophageal dysfunction in EoE appears multifactorial, further study of the biomechanics of EoE is critical to better diagnose, monitor and treat the disease.
    Full-text · Article · Oct 2012 · Journal of neurogastroenterology and motility
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    ABSTRACT: La pathologie gastro-intestinale à éosinophiles peut toucher le tube digestif à tous ses niveaux, de l’oesophage au côlon. Parmi ses diverses formes allant de l’oesophagite à la gastrite, en passant par la gastro-entérite, vers la colite, l’oesophagite à éosinophiles se rencontre le plus fréquemment. Elle est souvent liée à un terrain d’atopie. Sa fréquence est peu importante, mais de plus en plus reconnue. L’interleukine 5 joue un rôle clé dans le recrutement des éosinophiles au niveau digestif. De ce fait, l’anticorps monoclonal anti-IL-5 a été récemment évalué dans le traitement de ces atteintes. Le but de notre travail est de décrire à travers quatre observations les caractéristiques cliniques, paracliniques, thérapeutiques et évolutives de cette atteinte.
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