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Background: The effectiveness of dietary therapy to induce remission of eosinophilic esophagitis (EoE) has been evaluated over the last decades and summarized in meta-analyses. Choosing the dietary modality, identifying the most suitable patients, and implementing specific prerequisites are essential to ensure long-term success. Summary: Impractical exclusive elemental diets provided the highest remission rates in EoE; however, they are not recommended due to their numerous disadvantages and detrimental effects on patient quality of life. Allergy testing-guided diets for EoE are limited; their insufficient effectiveness and low reproducibility are due to poor accuracy of skin or serum test results in identifying EoE food triggers. Initial experiences with a six-food elimination diet have provided evidence of high and predictive effectiveness rates and paved the way for less restrictive and more efficient step-up approaches, including four-food, two-food, and most recently, milk elimination diets. Dietary treatment for EoE is challenging for patients and families and requires certain skills to ensure success in the short and long term. Key Messages: The selection of appropriate patients is essential to ensure the success of and long-term adherence to dietary treatment of EoE. As normal triggers for EoE are commonly found in the staple diet, it is important to ensure adequate nutritional substitutes to avoid nutrient deficiency risks when long-lasting feeding difficulties or extensive restrictions are present. Specialized facilities in dietary therapy should adopt patient-centered and personalized approaches in order to provide timely monitoring and support for complex cases.

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BACKGROUND: Nearly 80% of patients with eosinophilic esophagitis (EoE) have coexisting atopic disease, yet a subset do not. It is unclear if this lack of atopy impacts presentation or response to therapy. OBJECTIVES: To characterize the presentation and response to therapy in atopic versus nonatopic pediatric patients with EoE. METHODS: A case-control study of patients with EoE aged 6 months to 18 years (between 2018 and 2021) was performed. Patients were eligible if they had allergy testing, assessment of atopic history, and at least 1 endoscopy after initiation of treatment. Patients were considered nonatopic if they had negative allergy testing and no history of significant atopy. Response to therapy was classified as complete (peak eosinophils [eos] <15/high power field [hpf]), partial (≥15 eos/hpf but at least a 50% reduction in peak eos), or nonresponse. RESULTS: A total of 168 participants were enrolled. The majority were White (n = 141, 84%), male (n = 124, 74%), and non-Hispanic (n = 158, 95%). The mean age at diagnosis was 9.4 years (standard deviation: ±4.8 years). A total of 123 participants (73.2%) were atopic, and 45 (26.8%) were nonatopic. There was no significant difference between atopic and nonatopic for most demographics or presenting symptoms. Nonatopic participants were younger than atopic participants (8.14 vs 9.8 years, P = .046). Swallowed topical corticosteroids (STC) and food elimination diets (FED) were used at a similar rate. There were no differences in treatment response between atopic/nonatopic participants in regard to STC, FED, or STC+FED. CONCLUSIONS: Atopic status does not significantly impact presentation or response to treatment in pediatric EoE, but a lack of atopy may be a risk for earlier onset of disease.

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Eosinophilic esophagitis (EoE) is an emerging atopic disease of unknown etiology limited to the esophagus. The pathogenesis is still understood and is likely characterized by type 2 inflammation. Food allergens are the primary triggers of EoE that stimulate inflammatory cells through an impaired esophageal barrier. In children and adolescents, clinical presentation varies with age and mainly includes food refusal, recurrent vomiting, failure to thrive, abdominal/epigastric pain, dysphagia, and food impaction. Upper-gastrointestinal endoscopy is the gold standard for diagnosing and monitoring EoE. EoE therapy aims to achieve clinical, endoscopic, and histological ("deep") remission; prevent esophageal fibrosis; and improve quality of life. In pediatrics, the cornerstones of therapy are proton pump inhibitors, topical steroids (swallowed fluticasone and viscous budesonide), and food elimination diets. In recent years, much progress has been made in understanding EoE pathogenesis, characterizing the clinical and molecular heterogeneity, and identifying new therapeutic approaches. Notably, clinical, molecular, endoscopic, and histological features reflect and influence the evolution of inflammation over time and the response to currently available treatments. Therefore, different EoE phenotypes and endotypes have recently been recognized. Dupilumab recently was approved by FDA and EMA as the first biological therapy for adolescents (≥12 years) and adults with active EoE, but other biologics are still under consideration. Due to its chronic course, EoE management requires long-term therapy, a multidisciplinary approach, and regular follow-ups.

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BACKGROUND: The eosinophilic esophagitis histologic scoring system (EoEHSS) was developed to enhance the diagnostic standard of peak eosinophil count (PEC) in evaluating disease activity in EoE. AIMS: (1) Correlate the EoEHSS and PEC to measures of symptomatic and endoscopic disease activity, (2) Correlate EoEHSS grade and stage subcomponents to clinical, radiology, and endoscopic markers of fibrotic disease, (3) Evaluate EoEHSS remission in asymptomatic patients with PEC < 15 eosinophils per high powered field (eos/hpf). METHODS: Secondary analysis of prospective cohort data of 22 patients with EoE that underwent dietary therapy and endoscopy at 3 time points. Active disease was defined by EoEHSS grade or stage > 0.125, symptomatic disease by EoE symptom activity index > 20, endoscopic disease by endoscopic reference score > 2, and histologic disease by PEC ≥ 15 eos/hpf. EoEHSS remission was defined by esophageal inflammation (EI) grade of 0-1, EI stage of 0, total grade ≤ 3, and total stage ≤ 3. RESULTS: EoEHSS grade and stage did not correlate with symptomatic disease but did with endoscopic and histologic disease. PEC showed similar correlation pattern. Abnormal grade and stage had strong sensitivity (87-100%) but poor specificity (11-36%) to detect symptomatic, endoscopic, and histologic disease activity. Lamina propria fibrosis was evaluated in 36% of biopsies and did not correlate with minimum esophageal diameter. Out of 14 patients who were in complete symptomatic, endoscopic, and histologic remission, 8 met criteria for EoEHSS remission. CONCLUSION: The positive and negative correlations of EoEHSS to specific measures of symptomatic, histologic, and endoscopic activity suggest that it provides complementary information in EoE.

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Eosinophilic esophagitis (EoE) is a chronic immune-mediated food antigen-driven disease characterized by tissue eosinophilia and clinical symptoms of esophageal dysfunction. Medical and dietary therapies can be offered as treatment options in both pediatric and adult populations. Advances in nutritional research in EoE have produced different levels of dietary restriction, ranging from elimination of a single food group to more extensive restriction such as the two-food elimination diet, four-food elimination diet, or six-food elimination diet. Efficacy and outcomes vary for each level of restriction. The option of using dietary therapy allows clinicians to partner with patients in shared decision-making to balance the right level of food antigen restriction for the desired outcome. Key considerations when choosing dietary therapy hinge on patient preference and resources, food-related quality of life, and the ability to provide nutritional diversity and maintain nutritional parameters. This article highlights these considerations and offers clinical pearls to guide clinicians who wish to incorporate dietary therapy of EoE into their practice.

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INTRODUCTION: Dietary and pharmacological (proton pump inhibitors, swallowed topical corticosteroids) therapies are effective for induction of clinical and histological remission of eosinophilic esophagitis. However, data evaluating their long-term efficacy and safety is limited. AREAS COVERED: Since eosinophilic esophagitis is chronic, clinical, endoscopic, and histological features usually recur when successful treatments are stopped. In untreated patients, persistent esophageal eosinophilic inflammation may progress to fibrostenosis over time, giving place to strictures and narrow-caliber esophagi. This article comprehensively reviews available data on long-term maintenance of eosinophilic esophagitis with pharmacological and dietary treatment. It also discusses limitations re: available literature and outlines data gaps on adherence to therapy and monitoring disease activity in the long-term. EXPERT OPINION: Evidence indicates that long-term maintenance therapy may decrease the risk of esophageal stricture, food bolus impaction, and need for dilation in patients with eosinophilic esophagitis. Further knowledge on eosinophilic esophagitis phenotypes is needed to ascertain who will benefit best from sustained therapy. Unanswered questions include an adequate definition for sustained remission, best strategies for maintenance drugs and diets, enhancement of treatment adherence, and proper monitoring for long-term surveillance.

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INTRODUCTION: Eosinophilic esophagitis (EoE) is a clinical and pathological disorder, characterized by symptoms of esophageal dysfunction, and eosinophil-predominant inflammation restricted to the esophagus. Treatment outcomes include symptomatic remission, histological and endoscopic normalization and improving quality of life. Besides dietary modifications and endoscopic dilation, drugs available are swallowed topical corticosteroids (STCs) with reduced bioavailability and proton pump inhibitors (PPI). AREAS COVERED: Herein, the authors review the current treatment strategies for EoE in adults, providing the reader with their expert perspectives. The authors give discussion to the value of PPIs as a first-line therapy for EoE, in addition to the use of STCs. The current development of new formulations of STCs targeting the esophagus and novel therapies aimed at blocking molecular pathways are also discussed. Finally, the authors briefly look at the value of monoclonal antibodies targeting IL-5RA, IL-13, IL-4 or Siglec8, and oral S1PR agonists to the treatment of EoE. EXPERT OPINION: Viscose formulations of STC designed to coat the esophagus and new effervescent orodispersible tablets provide increased effectiveness at low doses. Investigational therapies that target several Th2-associated diseases seem useful in EoE. Comparative effectiveness and cost-utility analyses will help to position them in a complex therapeutic scenario.

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AIM: Paediatric eosinophilic gastritis (EG) is a rare disorder and existing literature on diagnostic criteria and management remains lacking. We aim to describe the clinical spectrum and assess the efficacy of dietary elimination and proton-pump inhibitor (PPI) therapy, with particular emphasis on histologic remission in children with primary EG. METHODS: We performed a retrospective study of patients aged 0-18 years diagnosed with EG at a single centre in Singapore from 2013 to 2021. EG was diagnosed based on histological criteria of infiltration of >30 eosinophils per high-power film (HPF) in >5 separate HPFs from gastric biopsies, in the absence of other causes. First-line treatment consisted of PPI therapy and empiric 1-6 food elimination diet (FED). Outcomes measured were clinical, endoscopic and histological remission (defined as eosinophil count <20/HPF in gastric biopsies). RESULTS: Twenty-one (66.7% females) patients were included with median age at diagnosis of 15 months (range:3-192). Majority presented with vomiting (76.2%) and gastrointestinal bleeding (71.4%). Twenty patients were initiated on FED+PPI and 16 had post-treatment biopsies. Clinical, endoscopic and histologic remissions were achieved in 94.7%, 81.3% and 68.8% respectively following FED+PPI. Histologic remission was significantly associated with younger age (9 vs. 132 months; P = 0.026). Four patients who did not respond to FED+PPI were started on oral viscous budesonide, of whom one achieved histological remission and two had clinical improvement. CONCLUSIONS: FED+PPI is effective as first-line treatment in achieving histological remission in paediatric EG particularly in younger patients. Topical corticosteroids can be considered for those who have failed FED+PPI therapy.

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Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder characterized by symptoms of esophageal dysfunction and eosinophil-predominant inflammation. Left untreated, EoE progresses to fibrous remodeling and stricture formation that impairs quality of life. Therefore, EoE requires either repeated treatments or maintenance therapy. Current guidelines recommend swallowed topical corticosteroids (STCs), proton-pump inhibitors (PPIs), or dietary intervention as initial options to induce and maintain long-term disease remission. Impractical exclusive elemental diets and suboptimal allergy testing-directed food avoidance paved the way for empirical elimination diets. These are moderately effective and highly reproducible in inducing EoE remission and allow for identification of specific food triggers. Step-up strategies, including two- and four-food rather than six-food elimination diets, should be considered as initial approaches for dietary treatment in patients of all ages, as they reduce the need for endoscopic procedures, shorten diagnostic processing time, and avoid unnecessary restrictions. Formulations of STC originally designed for asthma therapy are suboptimal for EoE treatment, with new effervescent orodispersible tablets and viscose formulations designed to coat the esophageal mucosa providing increased effectiveness at reduced doses. The anti-inflammatory effects of PPI in EoE are independent from gastric acid secretion inhibition; despite evidence from observational research, PPIs are the most commonly prescribed first-line therapy for EoE due to their accessibility, low cost, and safety profile. Double doses of PPI only induce remission in half of EoE patients, irrespective of the drug used or patients' age. Inflammatory rather than stricturing EoE phenotype and treatment duration up to 12 weeks increase chances of achieving EoE remission. Most responders effectively maintain long-term remission with standard PPI doses. Finally, endoscopic dilation should be considered in patients with reduced esophageal caliber or persistent dysphagia despite histological remission. This article provides a state-of-the-art review and updated discussion of current therapies and newly developed options for EoE.

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INTRODUCTION: Current treatments of eosinophilic esophagitis (EoE) induce symptomatic and histological remission in a proportion of patients. However, they do not fully meet patients' needs and limitations should be acknowledged. The growing epidemiology of EoE has generated a great interest for research into novel therapeutic approaches. AREAS COVERED: This article discusses current therapies available for EoE, those under investigation and presents potential additional ones. Established anti-inflammatory treatments for EoE include dietary therapy, proton pump inhibitors, and swallowed topical corticosteroids, which are combined with endoscopic dilation in cases of strictures. Refractoriness, recurrence after treatment-cessation, and need for long-term therapies have encouraged investigation of novel, esophageal-targeted formulas of topical corticosteroids and of new therapeutic approaches directed at blocking the molecular pathways that lead to inflammation in EoE. These include monoclonal antibodies (including mepolizumab, reslizumab, benralizumab, dectrekumab, cendakimab, and dupilumab), JAK-STAT blockers, and S1PR agonists, among others. Some have provided evidence of effectiveness and safeness in the short-term use. EXPERT OPINION: Therapies under investigation potentially can target multiple Th2-associated diseases that converge in EoE patients. Therapeutic strategies require a personalized and patient-centered approach to reduce the burden of the disease, and cost-effectiveness analysis to position their use in a complex therapeutic landscape.

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Eosinophilic esophagitis (EoE) is a unique form of non-immunoglobulin E-mediated food allergy, restricted to the esophagus, characterized by esophageal eosinophil-predominant inflammation and dysfunction. The diagnosis requires an esophago-gastroduodenoscopy with esophageal biopsies demonstrating active eosinophilic inflammation with 15 or more eosinophils/high-power field, following the exclusion of alternative causes of eosinophilia. Food allergens trigger the disease, withdairy/milk, wheat/gluten, egg, soy/legumes, and seafood the most common. Therapeutic strategies comprise dietary restrictions, proton pump inhibitors, topical corticosteroids, biologic agents, and esophageal dilation when strictures are present. However, avoidance of trigger foods remains the only option targeting the cause, and not the effect, of the disease. Because EoE relapses when treatment is withdrawn, dietary therapy offers a long-term, drug-free alternative to patients who wish to remain off drugs and still be in remission. There are currently multiple dietary management strategies to choose from, each having its specific efficacy, advantages, and disadvantages that both clinicians and patients should acknowledge. In addition, dietary regimens should be tailored around each individual patient to increase the chance of tolerability and long-term adherence. In general, liquid elemental diets devoid of antigens and elimination diets restricting causative foods are valuable options. Designing diets on the basis of food allergy skin tests results is not reliable and should be avoided. This review summarizes the most recent knowledge regarding the clinical use of dietary measures in EoE. We discussed endpoints, rationale, advantages and disadvantages, and tailoring of diets, as well as currently available dietary regimens for EoE.

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BACKGROUND: Eosinophilic esophagitis (EoE) and eosinophilic gastroenteritis (EGE), part of the spectrum of eosinophilic gastrointestinal disorders (EGID), share pathogenic similarities. We examined differences regarding clinical characteristics and treatment outcomes between EoE and EGE cases. METHODS: Two-hundred fifteen EGID patients, including 181 with EoE and 34 with EGE, diagnosed at Shimane University Hospital between February 2011 and March 2019 were enrolled. Information regarding clinical parameters and treatment outcomes was reviewed. RESULTS: EoE showed significant male predominance (82.3%) as compared with EGE (50.0%) (p < 0.001). Furthermore, patients with EoE were significantly older and had a higher body mass index (24.8 ± 4.0 vs. 22.2 ± 4.3, p < 0.05). Over 90% of the EoE patients were initially given proton pump inhibitor (PPI) treatment, of whom 73.2% showed clinical and histological remission. Vonoprazan, a more potent acid inhibitor than PPI, was effective in two-thirds of the nonresponsive EoE patients initially treated with a PPI. In contrast, oral glucocorticoid administration was mainly given to patients with EGE (58.8%). Of 13 EGE patients treated with a food-elimination diet, responsible foods were successfully identified in 9, with 7 controlled in a state of remission without glucocorticoid therapy. CONCLUSIONS: We found different clinical characteristics and treatment strategies in the present EoE and EGE cases. Most of the EoE patients responded to and were maintained by acid suppressive therapy, using PPI or vonoprazan. For EGE patients, glucocorticoid administration was mainly used though food-elimination diet therapy also showed beneficial effects.

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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.

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A 13-year-old boy presented to the hospital with a 3-month history of repeated vomiting and abdominal pain. Results of esophagogastroduodenoscopy revealed a diagnosis of eosinophilic gastroenteritis (EGE). We initiated a short-term six-food elimination diet (SFED) and reintroduction therapy over five days. On the third day of SFED, the patient's abdominal symptoms completely disappeared. However, he experienced unbearable abdominal pain six hours after the reintroduction of milk and peanuts. His symptoms remain completely controlled at present after eliminating milk and peanut products. The SFED and reintroduction therapy for EGE may be effective even for short-term treatments over a five-day period.

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Introduction: The epidemiology of eosinophilic esophagitis (EoE) has increased rapidly to represent a common cause of chronic and recurrent esophageal symptoms. Current treatment options have limitations so the development of novel therapies is a matter of growing interest.Areas covered: This article provides an up-to-date discussion of current therapies and investigational options for EoE. Established anti-inflammatory treatments for EoE at present include dietary therapy, proton pump inhibitors and swallowed topic steroids, which should be combined with endoscopic dilation in case of strictures. Refractoriness, high recurrence rates, and need for long-term therapies have promoted the investigation of novel, esophageal-targeted formulas of topic corticosteroids, and monoclonal antibodies (including mepolizumab, reslizumab, QAX576, RPC4046, dupilumab, omalizumab, infliximab, and vedolizumab) for EoE, with some having been demonstrated as effective and safe in the short term. Several additional promising therapies are also discussed.Expert opinion: Several therapeutic targets have shown efficacy and will be approved to treat EoE, especially corticosteroid-sparing options and those for patients with multiple Th2-associated diseases. Personalized therapeutic strategies for initial and maintenance treatments of EoE must be rationally designed, to reduce the burden of disease and answer meaningfully the needs of all stakeholders involved in EoE.

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OBJECTIVES: Cow's milk is a commonly implicated trigger in eosinophilic esophagitis (EoE). Exclusive cow's milk avoidance has been reported previously, but the degree of elimination required for remission is unclear. Strict food avoidance may confer a risk of developing immunoglobulin E (IgE)-mediated allergy. The goal of this study was to evaluate the effectiveness of cow's milk elimination (CME) in children with EoE and compare responses of strict and liberalized CME diets. METHODS: Children (≤16 years) diagnosed with EoE who were treated with exclusive CME diets were evaluated clinically and histologically. Strict diets eliminated all milk products, including 'may-contain' and baked milk goods. Liberalized diets eliminated obvious sources including milk, cheese, yogurt, cream-based products but permitted foods with traces of milk and baked goods. RESULTS: Cow's milk elimination induced histological remission of <15 eosinophils per high-powered field in 18 of 31 children (58%) and complete remission in 23%. Overall, 77% had decreased eosinophils with this single intervention. Symptoms were improved in 90% of patients, regardless of histologic response. A liberalized (n=7) CME diet was associated with a nonsignificantly lower response compared with strict (n=24) elimination (29% versus 67%, P=0.099). Eight responders to strict elimination were transitioned to a liberalized diet; 63% maintained remission. CONCLUSION: Cow's milk elimination induced clinicopathological remission in a majority of patients with EoE, supporting its use as a first-line intervention. Liberalized CME allows dietary freedom and may prevent subsequent development of anaphylactic milk allergy but may be inferior to strict CME for improving EoE.

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INTRODUCTION: Eosinophilic esophagitis (EoE) is rare but incidence and prevalence is increasing. EoE is characterized by eosinophilic inflammation of the esophagus causing gastrointestinal symptoms such as abdominal pain, vomiting, reflux, dysphagia, and food impactions. If untreated, remodeling and fibrosis of the esophagus can occur and stricture formation may result. Current treatment options are limited to food-restriction diets or medications including proton pump inhibitors (PPIs) or swallowed corticosteroids. Significant progress has been made in understanding the underlying mechanisms of EoE allowing for development of drugs that target specific points in EoE pathways. Investigation of these drugs is early with few controlled studies, but many show promise as future treatments. Areas covered: This review will provide an up to date discussion of current therapies and investigational drugs for EoE. Articles used in this review were retrieved from PubMed. Ongoing or completed clinical trials were obtained through clinicaltrials.gov and review of the PharmaProjects database. Expert Opinion: Multiple therapeutic targets have been identified and several have shown efficacy. Work is needed to define appropriate trial outcome measures. Collaboration between government agencies, patient advocacy groups, and investigator-led consortia is critical for completing new clinical trials which should pave the way for new therapies in clinical practice.

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BACKGROUND: Atopy patch testing (APT) has shown potential for predicting dietary food triggers in studies of children and adolescents with eosinophilic esophagitis (EoE). AIMS: To assess the efficacy of APT in adults with EoE. METHODS: We conducted a prospective open-label pilot study of patients ≥ 18 years old with diagnosis of EoE at Mayo Clinic in Rochester, Minnesota, from November 2014 to January 2016. All patients underwent patch testing using intact food products, followed by a six food elimination diet and stepwise food reintroduction. Response to elimination diet was assessed with serial endoscopy with biopsies as well as clinical symptoms. APT results were directly compared to elimination diet results for assessment of efficacy. Correlation between clinical symptoms, endoscopic score, and histology was also qualitatively evaluated. RESULTS: Fifty percent of the patients had a positive APT, while only 16% had an APT result confirmed histologically during food reintroduction. Sensitivity of APT was calculated to be 5.9%, with specificity of 92.0%. Furthermore, we found significant qualitative inter-patient heterogeneity in the correlation between clinical symptoms, EREFS score, and histology. CONCLUSIONS: APT does not reliably predict food triggers identified by food elimination diet in adult patients with EoE. As a result, APT does not have a clear role in the evaluation of patients with EoE.

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