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Dietary elimination therapy has been for a long time an option for patients with eosinophilic esophagitis (EoE) and remains the only therapy targeting the cause of the disease. Different dietary approaches have been described along the last 3 decades, and cumulative evidence has defined the effectiveness and usefulness of each approach. Elemental diets are highly effective to induce EoE remission, but unpractical in most patients. Allergy testing-directed food restrictions resulted inefficient to induce remission in a significant proportion of patients (especially adults) and show a low concordance with the dietary causes of EoE. Empiric elimination diets are currently considered the most effective drug-free treatment for patients of all ages with EoE, after widely providing reproducible results. Highly restrictive empiric six-food elimination diets have paved the way to most efficient and less restrictive step-up approaches, which now include four-food and two-food elimination diets. The potential role of milk-elimination, especially in children, should be also considered. Multiple factors including demographics, nutritional status, patient and family lifestyles, social and financial support, and acceptance of repeated endoscopies influence the results of dietary therapy. Dietary therapy in EoE should be patient centered, and the patients and/or their families together with the medical provider should participate in the decision to set up this treatment. This article updates recent knowledge on dietary therapy for EoE and provides guideline to choose the most suitable alternative for patients with EoE, as well as practical tips to achieve the best results in clinical practice.

Introduction: Eosinophilic esophagitis (EoE) is a non-Immunoglobulin E-mediated food allergy that currently represents the main cause of dysphagia and food impaction in children and young adults. Diet remains the only therapy targeting the cause of the disease. Relevant advances in recent years allow novel approaches to dietary therapy in EoE., Areas Covered: An up-to-date review on dietary therapy for EoE is provided, as a potential first-line anti-inflammatory therapy able to induce and maintain remission in a significant proportion of patients. Unpractical elemental diets and suboptimal food allergy testing-directed food restrictions paved the way for empiric elimination diets, which currently are to be considered as the most effective drug-free treatment for EoE. After largely restrictive empiric six-food elimination diets, most efficient step-up approaches now include four-food and two-food elimination diets. The potential of milk-elimination is also discussed., Expert Commentary: An empiric elimination diet step-up strategy should be currently considered as the initial approach for dietary treatment in EoE patients of all ages. Compared to a top-down strategy, step-up diets reduce the need for endoscopic procedures, shorten diagnostic process times, and avoid unnecessary restrictions. Furthermore, early identification of responders with few food triggers may select best candidates for maintenance dietary therapy.

Purpose of Review: The aim of this review is to highlight recent advances in dietary therapy for eosinophilic esophagitis (EoE)., Recent Findings: An empiric elimination diet step-up strategy is now well established as the initial approach for dietary treatment. The most common food triggers are by far cow's milk, followed by wheat and egg. Legumes seem to be important solely in Spain and other Mediterranean countries, where they are regularly consumed. Retrospective efficacy data on cow's milk elimination diet in children vary from 25 to 65%. The recently described esophageal prick test did not detect local reaction to the most common food triggers described for EoE., Summary: Within the step-up approach, the specific food group or groups to be first eliminated and whether if it will depend on the geographical setting and food consumption habits remain unknown. Prospective studies on cow's milk elimination diet in children and adults are definitely warranted. Better food allergy testing, identifying specific antigens involved in each food group, should be developed for an individualized therapy. As for disease prevention, we undoubtedly need to understand why foods we have been consuming since the Neolithic age have caused EoE just over the past few decades.

Eosinophilic esophagitis is a chronic, immune-mediated esophageal disease triggered predominantly, but not exclusively, by food antigens. Presently, available food allergy tests are suboptimal to predict food triggers for eosinophilic esophagitis, especially in adults. Elemental diets (exclusive feeding with amino acid-based formulas) and empiric 6-food elimination diets (withdrawing milk, wheat, egg, soy, nuts, and fish/seafood for 6 weeks) have consistently shown the best efficacy rates. However, their high level of restriction and need for multiple endoscopies have hampered their implementation in clinical practice. Currently, milk, wheat/gluten, and egg are the most common food triggers in children and adults from the United States, Spain, and Australia. Hence less restrictive empiric schemes, such as a 4-food elimination diet (dairy, gluten-containing cereals, egg, and legumes) or a 2-food elimination diet (dairy and gluten-containing cereals) have been lately developed with good efficacy rates (2-food elimination diet, 43%; 4-food elimination diet in adults, 54%; and 4-food elimination diet in children, 64%). A step-up approach (2-4-6) might result in prompt recognition of a majority of responders with few food triggers, reducing the number of endoscopies and costs and shortening the diagnostic process. Standardization of food reintroduction, novel food allergy testing, and studies evaluating a milk elimination diet in children and the long-term outcomes of dietary interventions are warranted., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Numerous dietary restrictions and endoscopies limit the implementation of empiric elimination diets in patients with eosinophilic esophagitis (EoE). Milk and wheat/gluten are the most common food triggers., Objective: We sought to assess the effectiveness of a step-up dietary strategy for EoE., Methods: We performed a prospective study conducted in 14 centers. Patients underwent a 6-week 2-food-group elimination diet (TFGED; milk and gluten-containing cereals). Remission was defined by symptom improvement and less than 15 eosinophils/high-power field. Nonresponders were gradually offered a 4-food-group elimination diet (FFGED; TFGED plus egg and legumes) and a 6-food-group elimination diet (SFGED; FFGED plus nuts and fish/seafood). In responders eliminated food groups were reintroduced individually, followed by endoscopy., Results: One hundred thirty patients (25 pediatric patients) were enrolled, with 97 completing all phases of the study. A TFGED achieved EoE remission in 56 (43%) patients, with no differences between ages. Food triggers in TFGED responders were milk (52%), gluten-containing grains (16%), and both (28%). EoE induced only by milk was present in 18% and 33% of adults and children, respectively. Remission rates with FFGEDs and SFGEDs were 60% and 79%, with increasing food triggers, especially after an SFGED. Overall, 55 (91.6%) of 60 of the TFGED/FFGED responders had 1 or 2 food triggers. Compared with the initial SFGED, a step-up strategy reduced endoscopic procedures and diagnostic process time by 20%., Conclusions: A TFGED diet achieves EoE remission in 43% of children and adults. A step-up approach results in early identification of a majority of responders to an empiric diet with few food triggers, avoiding unnecessary dietary restrictions, saving endoscopies, and shortening the diagnostic process., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Introduction: Eosinophilic esophagitis (EoE) is a chronic inflammatory esophageal disease triggered predominantly, but not excusively, by food antigens. Elimination diet thus remains the only therapy targeting the cause of the disease. Importantly, EoE is a unique form of non-IgE mediated food allergy, largely dependant upon delayed, cell-mediated hypersensitivity. Areas covered: A comprehensive review of literature to summarize and update the most relevant advances on dietary therapy for pediatric and adult EoE patients is conducted. Expert commentary: None of the currently available food allergy tests adequately predict food triggers for EoE, especially in adults. Elemental diet (exclusive feeding with aminoacid-based formulas) and empiric six-food elimination diet, withdrawing cow´s milk, wheat, egg, soy, nuts and fish/seafood for 6 weeks, have consistently shown the best cure rates. However, their high level of restriction and need for multiple endoscopies (top-down approach) have been a deterrent for patients and physicians. Less restrictive empiric schemes, like a four-food (animal milk, gluten-containing cereals, egg, legumes) or a two-food (animal milk and gluten-containing cereals) elimination diet have lately shown encouraging results. Therefore, a novel step-up strategy (2-4-6) may enhance patient uptake and promptly identify most responders to empiric diets with few food triggers, besides saving unnecessary dietary restrictions and endoscopic procedures.

Eosinophilic esophagitis (EoE) is a chronic disease characterized clinically by symptoms of esophageal dysfunction and histologically by eosinophil-predominant inflammation. EoE is frequently associated with concomitant atopic diseases and immunoglobulin E (IgE) sensitization to food allergens in children as well as to aeroallergens and cross-reactive plant allergen components in adults. Patients with EoE respond well to elemental and empirical food elimination diets. Recent research has, however, indicated that the pathogenesis of EoE is distinct from IgE-mediated food allergy. In this review, we discuss the individual roles of epithelial barrier defects, dysregulated innate and adaptive immune responses, and of microbiota in the pathogenesis of EoE. Although food has been recognized as a trigger factor of EoE, the mechanism by which it initiates or facilitates eosinophilic inflammation appears to be largely independent of IgE and needs to be further investigated. Understanding the pathogenic role of food in EoE is a prerequisite for the development of specific diagnostic tools and targeted therapeutic procedures., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

In recent years, several randomized controlled trials and meta-analyses have evaluated the efficacy of the various therapeutic options available for treating patients with eosinophilic esophagitis, including dietary modifications, proton pump inhibitors, topical corticosteroids, and endoscopic esophageal dilation. Proton pump inhibitors are currently considered the first-line treatment for eosinophilic esophagitis, achieving histological remission and improvement of symptoms in 50.5% and 60.8% of patients, respectively. The efficacy of topical corticosteroids in eosinophilic esophagitis has been assessed in several trials. Meta-analyses summarizing results indicate that budesonide and fluticasone propionate are significantly superior to placebo, both in decreasing eosinophil densities in the esophageal mucosa and in relieving symptoms. However, owing to differences in drug delivery, viscous budesonide seems to be the best pharmacological therapy for eosinophilic esophagitis. Results for dietary modifications have been mixed depending on the type of diet prescribed. Thus, while exclusive amino acid-based elemental diets are the most effective in inducing histological remission of eosinophilic esophagitis (90.8%), their severe drawbacks limit their implementation in clinical practice. Allergy testing-based food elimination provides a suboptimal remission rate of 45.5%, although this is lower in adults than in children (32.2% vs 47.9%, respectively). In addition, the various available studies are highly heterogeneous. Empirical 6-food elimination diets were shown to be the best diet-based therapy, with a homogeneous remission rate of 72%. Simpler, more convenient empirical schemes have also been evaluated. The aim of this review is to provide an evidence-based overview on the efficacy of the options available for treatment of eosinophilic esophagitis along with a practical management algorithm.

Background: Eosinophilic esophagitis (EoE) is an esophageal disorder predominantly triggered by food antigens. A six-food group elimination diet (SFGED) achieves remission in more than 70% of adult patients with EoE. After individual food reintroduction, just 1 or 2 food triggers for EoE can be identified in 65% to 85% of the patients, so some dietary restrictions and endoscopies after food challenge may be unnecessary., Objective: To evaluate the efficacy of a four-food group elimination diet (FFGED) (dairy products, wheat, egg, and legumes) for adult patients with EoE., Methods: Prospective multicenter study. All patients were reevaluated after 6 weeks on an FFGED. Response to the FFGED was defined by clinical and histologic (<15 eos/hpf) remission. Responders underwent reintroduction of each individual food over 6 weeks followed by endoscopy and esophageal biopsies. Nonresponders were offered a rescue SFGED., Results: A total of 52 adult patients were included, of whom 12 patients (23%) had previous failure to topical steroid therapy. Twenty-eight of the 52 patients (54%) achieved clinicopathologic remission on the FFGED and 6 of the 19 (31%) nonresponders to the FFGED were successfully rescued with the SFGED. Twenty-two of 28 responders to the FFGED (78%) finished the individual food reintroduction challenge. Milk was identified as an EoE trigger in 11 patients (50%), egg in 8 (36%), wheat in 7 (31%), and legumes in 4 (18%). All patients had just 1 or 2 food triggers, with milk being the only causative food in 27% of the patients., Conclusions: An FFGED achieved clinicopathologic remission in 54% of adult patients with EoE. An SFGED was effective in almost a third of FFGED nonresponders, resulting in a combined efficacy of 72% of both strategies., (Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Eosinophilic esophagitis is usually triggered by foods, by unclear mechanisms. We evaluated the roles of IgE and IgG4 in the development of eosinophilic esophagitis., Methods: We performed a prospective, randomized, double-blind, placebo-controlled trial of adults with eosinophilic esophagitis given an antibody against IgE (omalizumab, n = 16) or placebo (n = 14) every 2-4 weeks for 16 weeks, based on weight and serum level of IgE. Endoscopy was performed, esophageal biopsy specimens were collected, and symptoms were assessed at baseline and at 16 weeks. Maximum numbers of eosinophils/high-power field were determined. Homogenates of esophageal biopsy specimens from 11 subjects with eosinophilic esophagitis and 8 without (controls) were assessed for IgM, IgA, and IgG subclasses. In a retrospective analysis, we performed immunofluorescence analysis of IgG4 in fixed esophageal tissues from 2 patients with eosinophilic esophagitis who underwent esophagectomy and 47 consecutive autopsies (controls). We also performed immunofluorescence analysis of IgG4 in esophageal mucosal biopsy specimens from 24 subjects with eosinophilic esophagitis and 9 without (controls). Finally, sera were collected from 15 subjects with eosinophilic esophagitis and from 41 without (controls), and assayed for total and food-reactive IgG4., Results: Omalizumab did not alter symptoms of eosinophilic esophagitis or eosinophil counts in biopsy samples compared with placebo. Homogenates of esophageal tissues from patients with eosinophilic esophagitis had a 45-fold increase in IgG4 compared with controls (P < 3 × 10(-5)), but no significant increases in other IgG subclasses, IgM, or IgA. Sparse stromal deposits resembling immune complexes were found in 2 of 5 eosinophilic esophagitis biopsy specimens based on ultrastructural analysis. Esophagectomy samples from 2 patients with eosinophilic esophagitis contained 180 and 300 IgG4 plasma cells/maximal high-power field, mainly in the deep lamina propria; these levels were greater than in tissues from controls. Fibrosis essentially was exclusive to the lamina propria. Granular extracellular IgG4 was detected in biopsy specimens from 21 of 24 patients with eosinophilic esophagitis, but in none of the specimens from 9 controls (P = 6 × 10(-6)). The total serum level of IgG4 increased only slightly in patients with eosinophilic esophagitis, compared with controls. Subjects with eosinophilic esophagitis had increased serum levels of IgG4 that reacted with milk, wheat, egg, and nuts-the 4 foods that most commonly trigger this condition (P ≤ 3 × 10(-4) for each food)., Conclusions: In a prospective trial, omalizumab did not reduce symptoms of eosinophilic esophagitis or tissue eosinophil counts compared with placebo. This finding, along with observed granular deposits of IgG4, abundant IgG4-containing plasma cells, and serum levels of IgG4 reactive to specific foods, indicate that, in adults, eosinophilic esophagitis is IgG4-associated, and not an IgE-induced allergy. ClinicalTrials.gov number: NCT 00123630., (Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Sedation might improve tolerability and adherence to endoscopic procedures in patients with eosinophilic esophagitis (EoE). Propofol administration is often contraindicated in patients with hypersensitivity to egg, soy, or peanut., Objective: To investigate the safety of propofol administration for procedural sedation in EoE patients sensitized/allergic to egg, soy, peanut., Methods: A retrospective observational study in adult EoE patients undergoing esophagogastroduodenoscopy with propofol sedation was conducted between January 2009 and March 2013. Food-specific serum IgE and skin prick tests for egg, soy, peanut, and cross-reactant foods were performed in all patients., Results: Sixty EoE adult patients, mostly on food elimination diets (91%), were evaluated (age: 28 years (14-56), male gender (90%)). Atopy was present in 88% of patients, being the most prevalent comorbidities rhinoconjunctivitis (78%) and asthma (67%). Fifty-two patients (86%) were sensitized to either egg, soy, or peanut. Eighteen patients (28%) had a history of allergic reactions to egg, legumes, and nuts and strictly avoided these foods. A total of 404 upper endoscopies were performed under propofol sedation. No allergic adverse events were reported, except a transient bronchospasm after orotracheal intubation in an asthmatic adolescent receiving multiple drugs for anesthesia, in whom no sensitization to either propofol or its lipid vehicle was confirmed., Conclusions: Propofol was safely administered for procedural sedation in a large series of adult EoE patients multisensitized to egg, soy, peanut, showing one-third clinical allergy to these foods., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Although empiric exclusion from the diet of the 6 food groups most likely to trigger allergies achieves eosinophilic esophagitis (EoE) remission in children, data on its prolonged efficacy and effects on adults are lacking., Objective: We sought to evaluate the efficacy of a 6-food elimination diet in inducing and maintaining prolonged remission in patients with adult EoE., Methods: Sixty-seven consecutive patients with adult EoE were prospectively recruited and treated exclusively with a diet avoiding cereals, milk, eggs, fish/seafood, legumes/peanuts, and soy for 6 weeks. Subsequent challenge was undertaken by sequentially reintroducing all excluded single foods, followed by endoscopy and biopsies, which were developed every 6 weeks in case of response (eosinophil peak count reduction to <15/high-power field [hpf]). A food was considered a trigger for EoE and removed from the diet if pathologic eosinophilic infiltration (≥15 eosinophils/hpf) reappeared. Food-specific serum IgE measurements and skin prick tests were performed before initiating the diet., Results: Forty-nine (73.1%) patients exhibited significantly reduced eosinophil peak counts (<15 eosinophils/hpf) before sequential single-food reintroduction. A single offending food antigen was identified in 35.71% of patients, 2 food triggers were identified in 30.95%, and 3 or more food triggers were identified in 33.3%. Cow's milk was the most common food antigen (61.9%), followed by wheat (28.6%), eggs (26.2%), and legumes (23.8%). Prior allergy tests showed no concordance with food-reintroduction challenge results. All patients who continued to avoid the offending foods maintained histopathologic and clinical EoE remission for up to 3 years., Conclusions: An empiric 6-food elimination diet effectively induced remission of active adult EoE, which was maintained for up to 3 years with individually tailored, limited exclusion diets., (Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Eosinophilic esophagitis (EoE) is a chronic, immune/antigen-mediated, esophageal disease characterized by esophageal dysfunction and eosinophilic inflammation, manifested mainly as dysphagia and frequent food impaction. EoE is recognized into the spectrum of food allergy, but food sensitization studies used not to be efficient to identify the triggering food, because of what patients are frequently treated with topic steroids or even endoscopic esophageal dilation. Herein, we describe 3 adult patients-all suffering from EoE, but with different sensitization patterns-who were treated successfully with elimination diets. Allergy tests indicated no food sensitization for patient 1, but challenge with milk and wheat were positive. Food IgE-mediated allergies were found in patients 2 and 3; inflammation was resolved with food elimination. Lack of food allergy sensitization does not exclude the possibility of food allergies as a cause of EoE; elimination diets must therefore be considered as an effective diagnostic and treatment tool.

Eosinophilic esophagitis (EE) is a clinical-pathological disorder which is being increasingly diagnosed. It is etiologically associated with hypersensitivity to airborne allergens and/or dietary components. However, immediate hypersensitivity to foods has rarely been proven as the etiologic cause of the disorder. Two patients are presented with a history of rhinoconjunctivitis, allergic asthma, atopic dermatitis and food allergies which are currently under control and who show specific IgE to pulses and chicken respectively. These patients developed acute dysphagia and vomiting immediately after ingesting these foods and following appropriate examination were diagnosed as suffering from EE. The study also showed signs of blood hypereosinophilia while the esophageal manometry revealed a motor disorder characterized by aperistalsis and non-propulsive simultaneous waves affecting the lower two-thirds of the organ composed of smooth muscle. Topical treatment with fluticasone propionate was administered over a period of 3 months, in addition to a diet abstaining from the aforementioned foods and this led to remission of dysphagia and normalization of the endoscopic, histological and manometric studies of the esophagus. This situation remained stable for a considerable length of time after steroid treatment was discontinued, which showed that exposure to foods seemed to be the cause of the esophageal disorder. Similarly, allergies to inhalants and other digestive symptoms which appear upon immediate ingestion of the foods involved would not justify the sudden onset of dysphagia. We offer a pathophysiological explanation for the mechanisms of the disease based on the activation of eosinophils and mast cells by IgE and their ability to disturb the dynamic behavior of the neural and muscle components of the esophageal wall.