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.
Allergic components of eosinophilic esophagitis Spergel, Jonathan; Aceves, Seema S.
Journal of allergy and clinical immunology,
July 2018, 2018-07-00, 20180701, Volume:
142, Issue:
1
Journal Article
Peer reviewed
Open access
Eosinophilic esophagitis (EoE) is a disorder of increasing prevalence worldwide, causing clinical symptoms of vomiting, failure to thrive, and dysphagia and complications of esophageal remodeling ...with strictures and food impactions. Molecular profiling demonstrates EoE to be an eosinophil-predominant disorder with a TH2 cytokine profile reminiscent of other allergic diseases, such as asthma, allergic rhinitis, and atopic dermatitis. Environmental antigens in the form of foods and aeroallergens induce eosinophil, basophil, mast cell, and T-cell infiltration. Pathogenesis depends on local epithelial immune activation with production of thymic stromal lymphopoietin and eotaxin-3. Complications mirror asthmatic airway pathogenesis, with increases in subepithelial collagen deposition, angiogenesis, and smooth muscle hypertrophy. The removal of instigating antigens, especially foods, causes disease resolution in more than 50% of adults and children. The prevalence of concurrent atopic disorders in patients with EoE and the need to control antigen-specific TH2 inflammation underscore the importance of testing for allergens and treating the entire atopic subject to control the potential interplay between organ-specific allergic responses.
Diagnosis and treatment of eosinophilic esophagitis Gonsalves, Nirmala P.; Aceves, Seema S.
Journal of allergy and clinical immunology,
January 2020, 2020-01-00, 20200101, Volume:
145, Issue:
1
Journal Article
Peer reviewed
Open access
Eosinophilic esophagitis (EoE) is an eosinophil-rich, TH2 antigen–mediated disease of increasing pediatric and adult worldwide prevalence. Diagnosis requires greater than or equal to 15 eosinophils ...per high-power field on light microscopy. Symptoms reflect esophageal dysfunction, and typical endoscopic features include linear furrows, white plaques, and concentric rings. Progressive disease leads to pathologic tissue remodeling, with ensuing esophageal rigidity and loss of luminal diameter caused by strictures. Therapies include proton pump inhibitors, elimination diets, and topical corticosteroids. Effective treatment can reverse tissue fibrosis in some patients, as well as decrease the rate of food impactions. Esophageal dilation might be required to increase luminal patency. The chronic nature of EoE necessitates long-term therapy to avoid disease recurrence and complications. This review serves the function of providing the current state-of-the-art diagnostic criteria and disease management for adult and pediatric EoE.
Background Esophageal eosinophilia can be proton pump inhibitor (PPI) resistant or responsive, representing 2 entities known as eosinophilic esophagitis (EoE) and PPI-responsive esophageal ...eosinophilia (PPI-REE), respectively. Although they present with similar clinical features, EoE is accepted to be an antigen-driven, TH 2-associated allergic disorder, whereas the cause of PPI-REE remains a mystery. Objective In this study, our aim was to investigate the pathogenesis of PPI-REE by using a recently described EoE diagnostic panel (EDP) composed of a set of 94 esophageal transcripts and to determine whether PPI therapy reverses any esophageal transcriptional abnormalities. Methods We evaluated the EDP signature in biopsy samples obtained from adult and pediatric patients with PPI-REE from 4 institutions and compared the pre- and post-PPI therapy expression profiles of these subjects with those of patients with active EoE. Results The EDP differentiated patients with EoE from control subjects with 100% accuracy among the 4 clinical sites. Bioinformatics analysis revealed largely overlapping transcriptomes between patients with PPI-REE and those with EoE, including the genes for eosinophil chemotaxis ( eotaxin 3, CCL26) , barrier molecules ( desmoglein 1, DSG1) , tissue remodeling ( periostin, POSTN) , and mast cells ( carboxypeptidase A, CPA3) . PPI monotherapy alone almost completely reversed the allergic inflammatory transcriptome of patients with PPI-REE. Furthermore, we identified a set of candidate genes to differentiate patients with EoE from those with PPI-REE before treatment. Conclusion These findings provide definitive evidence that PPI-REE is a disease entity with significant molecular overlap with EoE, suggesting that many patients with PPI-REE represent a continuum of the same pathogenic allergic mechanisms that underlie EoE and thus might constitute a subphenotype of patients with EoE. The ability of PPI therapy to nearly entirely reverse gene expression associated with PPI-REE, particularly that associated with classic features of allergic inflammation, provides new insight into potential disease etiology and management strategies for patients with significant esophageal eosinophilia.
In eosinophilic esophagitis (EoE), remodeling changes are manifest histologically in the epithelium and subepithelium where lamina propria fibrosis, expansion of the muscularis propria, and increased ...vascularity occur. The clinical symptoms and complications of EoE are largely consequences of esophageal remodeling. Available therapies have demonstrated variable ability to reverse existing remodeling changes of the esophagus. Systemic therapies have the potential of addressing subepithelial remodeling. Esophageal dilation remains a useful, adjunctive therapeutic maneuver in symptomatic adults with esophageal stricture. As novel treatments emerge, it is essential that therapeutic end points account for the fundamental contributions of esophageal remodeling to overall disease activity.
Chronic eosinophilic inflammation has been associated with tissue remodeling in a number of disease states including the hypereosinophilic syndrome (HES), asthma, and, more recently, eosinophilic ...esophagitis (EoE). Remodeling occurs in the epithelial and subepithelial esophageal tissue, and includes basal zone hyperplasia, epithelial mesenchymal transition, fibrosis, angiogenesis, and smooth muscle hypertrophy/hyperplasia. Previously, research on the clinical impacts of tissue remodeling has been limited by a paucity of human tissue. However, in EoE, recurrent biopsies are required for diagnosis and management. As such, investigators are able to study the associations between tissue changes and clinical disease features. A number of profibrotic and proangiogenic factors are elevated in EoE, including TGF-β1, CCL-18, FGF-9, VEGF, and VCAM-1. Both eosinophils and mast cells produce a number of these factors. TGF-β1 appears to be a master regulator of end-organ dysfunction in EoE and can cause esophageal epithelial mesenchymal transition, fibrosis, and smooth muscle contraction. The requirement for eosinophils, the eosinophilopoietic interleukin, IL-5, and the canonical TGF-β1 signaling pathway for EoE-associated fibrosis, has been invoked using gene-deficient mice. The clinical consequences of eosinophil-associated tissue fibrosis can be devastating, such as endomyocardial fibrosis and heart failure in HES. In EoE, tissue remodeling appears to be the mechanism for multiple cardinal disease complications including esophageal rigidity, strictures, narrowing, and food impactions, as well as the clinical hallmark of dysphagia. Therapies that may be able to reduce or reverse EoE-associated remodeling include topical corticosteroids, anti-IL-5, and food antigen avoidance.
Eosinophilic esophagitis (EoE) is a clinicopathologic disease of increasing prevalence in children and adults. The triggering antigen in EoE is often a food that initiates a cascade of Th2-associated ...interleukins such as interleukin-5 and interleukin-13 and chemokines such as eotaxin-3 as well as esophageal eosinophilia and mastocytosis. Amino acid-based formulas have high efficacy rates in EoE and constitute the first evidence for food-triggered esophageal eosinophilia. Animal models have demonstrated the sufficiency of food antigens in triggering both the inflammatory and remodeling complications of EoE. Food elimination diets that are followed by single food introduction with repeat biopsy have proven the efficacy of empiric and allergy testing based elimination diets in children and adults. Although the ideal allergy test for identifying food antigens in EoE remains to be elucidated, the utility of food skin prick combined with atopy patch testing has been shown in large pediatric cohorts. By comparison, smaller, non-U.S. adult cohorts have not had similar results. Currently, a positive test on food allergy evaluation suggests a food trigger for EoE but does not substitute for biopsy-based tissue evaluation after food removal and reintroduction. The higher rates of food anaphylaxis in children with EoE, potential loss of tolerance to immunoglobulin E-positive foods that can occur with food avoidance, and the high rates of other atopic diatheses in EoE subjects all support the evaluation of EoE subject by an allergist, consideration for allergy testing, and an integrated approach by allergists, gastroenterologists, and pathologists in EoE management.
Eosinophilic esophagitis (EoE) is a chronic inflammatory condition of the esophagus. Many new studies have been reported recently that describe EoE management. An expert panel was convened by the ...American Gastroenterological Association Institute and the Joint Task Force on Allergy-Immunology Practice Parameters to provide a technical review to be used as the basis for an updated clinical guideline. This technical review was developed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. Eighteen focused EoE management questions were considered, with 15 answered using the GRADE framework and 3 with a narrative summary. There is moderate certainty in the evidence that topical glucocorticosteroids effectively reduce esophageal eosinophil counts to <15 per high-power field over a short-term treatment period of 4–12 weeks, but very low certainty about the effects of using topical glucocorticosteroids as maintenance therapy. Multiple dietary strategies may be effective in reducing esophageal eosinophil counts to <15 per high-power field over a short-term treatment period, with moderate certainty for elemental diets, low certainty for empiric 2-, 4-, and 6-food elimination diets, and very low certainty that allergy-based testing dietary eliminations have a higher failure rate compared to empiric diet elimination. There is very low certainty for the effect of proton pump inhibitors in patients with esophageal eosinophilia. Although esophageal dilation appears to be relatively safe, there is no evidence that it reduces esophageal eosinophil counts. There is very low certainty in the effects of multiple other medical treatments for EoE: anti–interleukin-5 therapy, anti–interleukin-13 therapy, anti-IgE therapy, montelukast, cromolyn, and anti-TNF therapy.
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