2012-Seminars EGID review (original) (raw)

2012- Seminars-Eosinophilic gastrointestinal disease

2013

Your article is protected by copyright and all rights are held exclusively by Springer-Verlag. This e-offprint is for personal use only and shall not be self-archived in electronic repositories. If you wish to self-archive your work, please use the accepted author's version for posting to your own website or your institution's repository. You may further deposit the accepted author's version on a funder's repository at a funder's request, provided it is not made publicly available until 12 months after publication.

Eosinophilic esophagitis: New insights in pathogenesis and therapy

World Journal of Gastrointestinal Pharmacology and Therapeutics, 2016

Eosinophilic esophagitis (EoE) is a clinico-pathological entity with esophageal symptoms and dense esophageal eosinophilic infiltration throughout the esophagus that may persist despite treatment with proton pump inhibitors. This eosinophilic infiltration is usually absent in the stomach, small intestine and colon, although there are a number of reports of patients with a multiorgan involvement. EoE is associated with abnormalities involving TH2-dependent immunity, with multiple environmental factors strongly contributing to disease expression. The layer of the esophagus affected by the eosinophilic infiltration causes the specific symptoms. Esophageal involvement results mostly in dysphagia for solids that can be severe enough to cause recurrent esophageal obstruction with typical endoscopic features suggesting esophageal remodeling and pathological changes of eosinophilic infiltration of the mucosa, sub-epithelial fibrosis and muscle hypertrophy. This disease is frequently associated with other allergic conditions such as allergic asthma, allergic dermatitis and eosinophilia. The treatment of patients with EoE depends on the severity of the symptoms and of the inflammatory process as well as to their response to a gradual step-up treatment. The first line of treatment consists of steroid containing local inhalers. If unresponsive they are then treated with oral steroids. Intravenous interleukin blockers seem to have a consistent positive therapeutic effect.

The Pathophysiology of Eosinophilic Esophagitis

Frontiers in Pediatrics, 2014

Eosinophilic Oesophagitis (EoE) is an emerging disease characterised 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. Eosinophildegranulation 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 TGF-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.

EOSINOPHILIC ESOPHAGITIS: A LITERATURE REVIEW (Atena Editora)

EOSINOPHILIC ESOPHAGITIS: A LITERATURE REVIEW (Atena Editora), 2024

A esophagitis eosinofílica (EoE) is a chronic esophageal condition with an immunological and allergic etiology, characterized by symptoms related to esophageal dysfunction and histological findings of inflammation predominantly involving eosinophils. The aim of this study was to analyze recent research on aspects related to EoE. Methodology involved a search of scientific articles indexed in PubMed and EBSCO databases between 2018 and 2023, yielding 161 articles. Inclusion criteria included articles published within the last 5 years, with full-text availability. Paid articles and those published more than 5 years ago were excluded, resulting in the selection of 25 articles. Results and Discussion: EoE is a globally distributed disease with increasing incidence. Its primary immunological mechanism involves Th2 cells. External factors stimulate Th2 cells to produce interleukins (IL) such as IL-4, IL-5, and IL-13, with the contribution of an IgE-mediated pathway and other mediators like eotaxin-3. Symptoms vary with age and can resemble those of GERD. In children up to preschool age, symptoms include food refusal or intolerance and poor weight gain, while school-aged children commonly experience vomiting, epigastric pain, heartburn, and regurgitation. Treatment of EoE aims to mitigate esophageal inflammation to alleviate symptoms, prevent complications such as esophageal remodeling and fibrosis, and improve patient quality of life. Therapeutic approaches include medications like Proton Pump Inhibitors (PPIs), swallowed topical corticosteroids (fluticasone and budesonide), dietary interventions, mechanical dilation, and biologic medications. Dupilumab 300 mg weekly is the first selective systemic immunomodulatory biologic therapy approved for EoE in patients aged 12 and older, showing clinically significant benefits with a favorable safety profile compared to non-selective systemic immunosuppressants. Conclusion: Diagnosis of EoE is based on clinical and pathological evidence, including symptoms of esophageal dysfunction, mucosal changes, eosinophilic infiltration, and inflammation observed during endoscopy and biopsy. Treatment focuses on reducing esophageal inflammation to alleviate symptoms, prevent complications, and improve patient quality of life.

Eosinophilic esophagitis in children: doubts and future perspectives

Journal of Translational Medicine, 2019

Background: Eosinophilic esophagitis (EoE) is a chronic immune-mediated inflammatory disorder and represents the leading cause of food impaction. The pathogenesis of EoE is the result of an interplay between genetic, environmental and host immune system factors. New therapeutic approaches for EoE have been proposed. In this manuscript we review the current evidence regarding EoE management in pediatric age, with a particular focus on new findings related to the efficacy and safety of monoclonal antibodies. Main body: Conventional therapies have failed in treating some patients with EoE, which then requires aggressive procedures such as esophageal dilatation. The most effective available medical therapy for EoE is swallowed topic corticosteroids (fluticasone propionate and budesonide), which have two main drawbacks: they are related to wellknown adverse effects (especially in the paediatric population), and there are not enough long-term data to confirm that they are able to reverse the remodelling process of the esophageal mucosa, which is the major cause of EoE symptoms (including dysphagia, abdominal pain, nausea, obstruction, perforation and vomiting). The monoclonal antibodies appear to be an interesting therapeutic approach. However, the studies conducted until now have shown substantial histological improvement not coupled with significant clinical improvements and no significant relationship between a decreasing number of eosinophils and clinical symptoms, highlighting the importance in the pathogenesis of EoE of cells such as T-helper cells, mast cells, B cells, epithelial cells and natural killer cells. Conclusions: Monoclonal antibodies targeting a signal involved in the pathogenesis of EoE may not break the complex self-propagating inflammatory activation responsible for perpetuation of the inflammatory response and the development of symptoms and complications. We speculate that combined biological therapies targeting more than one molecule or cell may provide better results, with conventional therapies potentially enhancing the effects of antibodies. However, further studies should aim to find the best therapeutic approach to target the cells involved in the remodelling process and to reverse the histological changes in this complex clinical condition.

Eosinophilic Esophagitis: Review and Update

Frontiers in medicine, 2018

Eosinophilic esophagitis (EoE) was first described in the 1990s, showing an increasing incidence and prevalence since then, being the leading cause of food impaction and the major cause of dysphagia. Probably, in a few years, EoE may no longer be considered a rare disease. This article discusses new aspects of the pathogenesis, symptoms, diagnosis, and treatment of EoE according to the last published guidelines. The epidemiological studies indicate a multifactorial origin for EoE, where environmental and genetic factors take part. EoE affects both children and adults and it is frequently associated with atopic disease and IgE-mediated food allergies. In patients undergoing oral immunotherapy for desensitization from IgE-mediated food allergy the risk of developing EoE is 2.72%. Barrier dysfunction and T-helper 2 inflammation is considered to be pathogenetically important factors. There are different patterns of clinical presentation varying with age and can be masked by adaptation h...

Eosinophilic esophagitis: From pathophysiology to treatment

World journal of gastrointestinal pathophysiology, 2015

Eosinophilic esophagitis (EoE) is a chronic immune disease, characterized by a dense eosinophilic infiltrate in the esophagus, leading to bolus impaction and reflux-like symptoms. Traditionally considered a pediatric disease, the number of adult patients with EoE is continuously increasing, with a relatively higher incidence in western countries. Dysphagia and food impaction represent the main symptoms complained by patients, but gastroesophageal reflux-like symptoms may also be present. Esophageal biopsies are mandatory for the diagnosis of EoE, though clinical manifestations and proton pump inhibitors responsiveness must be taken into consideration. The higher prevalence of EoE in patients suffering from atopic diseases suggests a common background with allergy, however both the etiology and pathophysiology are not completely understood. Elimination diets are considered the first-line therapy in children, but this approach appears less effective in adults patients, who often requi...