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BACKGROUND: Because young children cannot self-report symptoms, there is a need for parent surrogate reports. While early work suggested parent child alignment for eosinophil esophagitis (EoE) patient reported outcomes (PROs), the longitudinal alignment is unclear. OBJECTIVE: To assess the agreement and longitudinal stability of PROs between children with EoE and their parents. METHODS: 292 parent-child respondents completed 723 completed questionnaires over 5 years in an observational trial in the Consortium of Eosinophilic Gastrointestinal Disease Researchers. The change in and agreement between parent and child Pediatric Eosinophilic Esophagitis Symptom Score version 2 (PEESSv2.0) and Pediatric Quality of Life Eosinophilic Esophagitis Module (PedsQL-EoE) PROs over time were assessed using Pearson correlation and Bland-Altman analyses. Clinical factors influencing PROs and their agreement were evaluated using linear mixed models. RESULTS: The cohort had a median disease duration equalling 3.7 years and was predominantly male (73.6%) and white (85.3%). Child and parent PEESSv2.0 response groups were identified and were stable over time. There was strong correlation between child and parent report (PEESSv2.0 0.83, PedsQL-EoE 0.74) with minimal pairwise differences for symptoms. Longitudinally, parent-reported PedsQL-EoE scores were stable (p ≥ 0.32), whereas child-reported PedsQL-EoE scores improved (p = 0.026). A larger difference in parent and child PedsQL-EoE reports was associated with younger age (p < 0.001) and differences were driven by psychosocial PRO domains. CONCLUSION: There is strong longitudinal alignment between child and parent report using EoE PROs. These data provide evidence that parent report is a stable proxy for objective EoE symptoms in their children.
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BACKGROUND: The Index of Severity for Eosinophilic Esophagitis (I-SEE) is a new expert-defined clinical tool that classifies disease severity of eosinophilic esophagitis (EoE). OBJECTIVE: We aimed to determine whether I-SEE is associated with patient characteristics, molecular features of EoE, or both. METHODS: We analyzed a prospective cohort of patients with EoE from the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR). Associations between I-SEE and clinical and molecular features (assessed by an EoE diagnostic panel [EDP]) were assessed. RESULTS: In 318 patients with chronic EoE (209 adults, 109 children), median total I-SEE score was 7.0, with a higher symptoms and complications score in children than adults (4.0 vs 1.0; P < .001) and higher inflammatory and fibrostenotic features scores in adults than children (3.0 vs 1.0 and 3.0 vs 0, respectively; both P < .001). Total I-SEE score had a bimodal distribution with the inactive to moderate categories and severe category. EDP score correlated with total I-SEE score (r = -0.352, P < .001) and both inflammatory and fibrostenotic features scores (r = -0.665, P < .001; r = -0.446, P < .001, respectively), but not with symptoms and complications scores (r = 0.047, P = .408). Molecular severity increased from inactive to mild and moderate, but not severe, categories. Longitudinal changes of modified I-SEE scores and inflammatory and fibrostenotic features scores reflected histologic and molecular activity. CONCLUSIONS: I-SEE score is associated with select clinical features across severity categories and with EoE molecular features for nonsevere categories, warranting further validation.
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Esofagitis Eosinofílica , Índice de Severidad de la Enfermedad , Humanos , Esofagitis Eosinofílica/diagnóstico , Masculino , Femenino , Niño , Adulto , Adolescente , Preescolar , Persona de Mediana Edad , Estudios Prospectivos , Adulto JovenRESUMEN
Background: The demographic characteristics of patients with eosinophilic gastrointestinal diseases (EGIDs) are poorly understood. Population-based assessments of EGID demographics may indicate health disparities in diagnosis. Objectives: We aimed to characterize the demographic distribution of EGIDs and evaluate the potential for bias in reporting patient characteristics. Methods: We conducted a systematic review, extracting data on age, sex, gender, race, ethnicity, body mass index, insurance, and urban/rural residence on EGID patients and the source population. Differences in proportions were assessed by chi-square tests. Demographic reporting was compared to recent guidelines. Results: Among 50 studies that met inclusion/exclusion criteria, 12 reported ≥1 demographic feature in both EGID and source populations. Except for age and sex or gender, demographics were rarely described (race = 4, ethnicity = 1, insurance = 1) or were not described (body mass index, urban/rural residence). A higher proportion of male subjects was observed for EoE or esophageal eosinophilia relative to the source population, but no difference in gender or sex distribution was observed for other EGIDs. "Sex" and "gender" were used interchangeably, and frequently only the male proportion was reported. Reporting of race and ethnicity was inconsistent with guidelines. Conclusion: Current data support a male predominance for EoE only. Evidence was insufficient to support enrichment of EGIDs in any particular racial, ethnic, or other demographic group. Population-based studies presenting demographics on both cases and source populations are needed. Implementation of guidelines for more inclusive reporting of demographic characteristics is crucial to prevent disparities in timely diagnosis and management of patients with EGIDs.
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BACKGROUND: The mechanistic basis of the variable symptomatology seen in eosinophilic esophagitis (EoE) remains poorly understood. OBJECTIVE: We examined the correlation of a validated, patient-reported outcome metric with a broad spectrum of esophageal transcripts to uncover potential symptom pathogenesis. METHODS: We extracted data from 146 adults with EoE through the Consortium of Eosinophilic Gastrointestinal Disease Researchers. Patients were subgrouped by esophageal dilation history. We compared a validated patient-reported outcome metric, the EoE Activity Index (EEsAI), with a set of transcripts expressed in the esophagus of patients with EoE, the EoE Diagnostic Panel (EDP). We used single-cell RNA sequencing data to identify the cellular source of EEsAI-related EDP genes and further analyzed patients with mild and severe symptoms. RESULTS: The EEsAI correlated with the EDP total score, especially in patients without recent esophageal dilation (r = -0.31; P = .003). We identified 14 EDP genes that correlated with EEsAI scores (r ≥ 0.3; P < .05). Of these, 11 were expressed in nonepithelial cells and three in epithelial cells. During histologic remission, only four of 11 nonepithelial genes (36%) versus all three epithelial genes (100%) had decreased expression to less than 50% of that in active EoE. Fibroblasts expressed five of 11 nonepithelial EEsAI-associated EDP genes (45%). A subset of nonepithelial genes (eight of 11; 73%), but not EoE-representative genes (none of four; 0%; CCL26, CAPN14, DSG1, and SPINK7), was upregulated in patients with EoE with the highest versus lowest symptom burden. CONCLUSION: The correlation of symptoms and nonepithelial esophageal gene expression substantiates that nonepithelial cells (eg, fibroblasts) likely contribute to symptom severity.
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The Human Epidemiology and Response to SARS-CoV-2 (HEROS) is a prospective multi-city 6-month incidence study which was conducted from May 2020-February 2021. The objectives were to identify risk factors for SARS-CoV-2 infection and household transmission among children and people with asthma and allergic diseases, and to use the host nasal transcriptome sampled longitudinally to understand infection risk and sequelae at the molecular level. To overcome challenges of clinical study implementation due to the coronavirus pandemic, this surveillance study used direct-to-participant methods to remotely enroll and prospectively follow eligible children who are participants in other NIH-funded pediatric research studies and their household members. Households participated in weekly surveys and biweekly nasal sampling regardless of symptoms. The aim of this report is to widely share the methods and study instruments and to describe the rationale, design, execution, logistics and characteristics of a large, observational, household-based, remote cohort study of SARS-CoV-2 infection and transmission in households with children. The study enrolled a total of 5,598 individuals, including 1,913 principal participants (children), 1,913 primary caregivers, 729 secondary caregivers and 1,043 other household children. This study was successfully implemented without necessitating any in-person research visits and provides an approach for rapid execution of clinical research.
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PURPOSE OF REVIEW: This review seeks to understand novel avenues for eosinophilic GI disease management. Biomarkers offer a unique and non-invasive approach to tracking EoE disease progression. While no biomarkers have definitively met the diagnostic criteria for eosinophilic GI diseases, some biomarkers have been shown to be associated with disease activity. Here, we examine the potential of recently studied biomarkers. RECENT FINDINGS: Current research shows advancements in blood, luminal fluid, and breath testing. Particular areas of interest include mRNA analyses, protein fingerprinting, amplicon sequence variants (ASVs), T cells and IgE receptors, eosinophilic cationic proteins, cytokines, and nitric oxide exhalation. Preliminary results showed that mucosal biomarkers, directly captured from the esophagus, may reflect the best representation of biopsy-based results, in contrast to biomarkers obtained from indirect or peripheral (blood, breath) methods. However, this is based on limited clinical studies without sufficient numbers to evaluate true diagnostic accuracy. Large-scale randomized trials are needed to fully ascertain both the optimal sampling technique and the specific biomarkers that reflect diagnostic status of the disease.
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Biomarcadores , Eosinofilia , Humanos , Eosinofilia/diagnóstico , Eosinofilia/inmunología , Esofagitis Eosinofílica/diagnóstico , Esofagitis Eosinofílica/inmunología , Pruebas Respiratorias/métodos , Gastritis/diagnóstico , Gastritis/inmunología , Enteritis/diagnóstico , Enteritis/inmunologíaRESUMEN
INTRODUCTION: Eosinophilic esophagitis (EoE) variants have been recently characterized as conditions with symptoms of esophageal dysfunction resembling EoE, but absence of significant esophageal eosinophilia. Their disease course and severity have yet to be determined. METHODS: Patients from 6 EoE centers with symptoms of esophageal dysfunction, but peak eosinophil counts of <15/hpf in esophageal biopsies and absence of gastroesophageal reflux disease with at least one follow-up visit were included. Clinical, (immuno)histological, and molecular features were determined and compared with EoE and healthy controls. RESULTS: We included 54 patients with EoE variants (EoE-like esophagitis 53.7%; lymphocytic esophagitis 13.0%; and nonspecific esophagitis 33.3%). In 8 EoE-like esophagitis patients, EoE developed after a median of 14 months (interquartile range 3.6-37.6). Such progression increased over time (17.6% year 1, 32.0% year 3, and 62.2% year 6). Sequential RNA sequencing analyses revealed only 7 genes associated with this progression (with TSG6 and ALOX15 among the top 3 upregulated genes) with upregulation of a previously attenuated Th2 pathway. Immunostaining confirmed the involvement of eosinophil-associated proteins (TSG6 and ALOX15) and revealed a significantly increased number of GATA3-positive cells during progression, indicating a Th1/Th2 switch. Transition from one EoE variant (baseline) to another variant (during follow-up) was seen in 35.2% (median observation time of 17.3 months). DISCUSSION: Transition of EoE variants to EoE suggests the presence of a disease spectrum. Few genes seem to be associated with the progression to EoE with upregulation of a previously attenuated Th2 signal. These genes, including GATA3 as a Th1/Th2 switch regulator, may represent potential therapeutic targets in early disease pathogenesis.
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Progresión de la Enfermedad , Esofagitis Eosinofílica , Esófago , Humanos , Esofagitis Eosinofílica/genética , Esofagitis Eosinofílica/patología , Esofagitis Eosinofílica/diagnóstico , Femenino , Masculino , Adulto , Esófago/patología , Araquidonato 15-Lipooxigenasa/genética , Araquidonato 15-Lipooxigenasa/metabolismo , Adolescente , Eosinófilos/patología , Eosinófilos/inmunología , Adulto Joven , Factor de Transcripción GATA3/genética , Moléculas de Adhesión Celular/genética , Moléculas de Adhesión Celular/metabolismo , Niño , Biopsia , Células Th2/inmunología , Persona de Mediana Edad , Estudios de Casos y Controles , Recuento de LeucocitosRESUMEN
INTRODUCTION: Eosinophilic gastrointestinal disorders beyond eosinophilic esophagitis (non-EoE EGIDs) are rare chronic inflammatory disorders of the gastrointestinal (GI) tract. Diagnosis is based on clinical symptoms and histologic findings of eosinophilic inflammation after exclusion of a secondary cause or systemic disease. Currently, no guidelines exist for the evaluation of non-EoE EGIDs. Therefore, the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) formed a task force group to provide consensus guidelines for childhood non-EoE EGIDs. METHODS: The working group was composed of pediatric gastroenterologists, adult gastroenterologists, allergists/immunologists, and pathologists. An extensive electronic literature search of the MEDLINE, EMBASE, and Cochrane databases was conducted up to February 2022. General methodology was used in the formulation of recommendations according to the Appraisal of Guidelines for Research and Evaluation (AGREE) II and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to meet current standards of evidence assessment. RESULTS: The guidelines provide information on the current concept of non-EoE EGIDs, disease pathogenesis, epidemiology, clinical manifestations, diagnostic and disease surveillance procedures, and current treatment options. Thirty-four statements based on available evidence and 41 recommendations based on expert opinion and best clinical practices were developed. CONCLUSION: Non-EoE EGIDs literature is limited in scope and depth, making clear recommendations difficult. These consensus-based clinical practice guidelines are intended to assist clinicians caring for children affected by non-EoE EGIDs and to facilitate high-quality randomized controlled trials of various treatment modalities using standardized, uniform disease definitions.
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Enteritis , Eosinofilia , Esofagitis Eosinofílica , Gastritis , Gastroenterología , Niño , Humanos , Esofagitis Eosinofílica/terapia , Esofagitis Eosinofílica/tratamiento farmacológico , Enteritis/diagnóstico , Gastritis/diagnóstico , Gastritis/terapiaRESUMEN
INTRODUCTION: Eosinophilic gastritis (EoG) and duodenitis (EoD) are rare conditions that are poorly understood. Our aim was to describe the natural history of children with varying degrees of gastric or duodenal eosinophilia with respect to disease complications and histologic and endoscopic longitudinal trajectories. METHODS: The electronic medical record at a tertiary children's hospital was queried to identify patients with EoG, EoD, or EoG + EoD who were cared for between January 2010 and 2022. Multiple logistic regression was performed to explore associations between baseline features and persistence/recurrence of eosinophilia or complications remote from diagnosis. RESULTS: We identified 151 patients: 92 with EoG, 24 with EoD, 12 with EoG + EoD, and 23 with tissue eosinophilia but did not meet histologic criteria for EoG or EoD (low grade). The average age at diagnosis was 10.6 years, and average follow-up was 5.8 years. Twenty-five percent of patients with EoG or EoD had persistence/recurrence of eosinophilia; this was associated with increases in the EoG Endoscopic Reference Score (adjusted odds ratio [aOR] 1.34, confidence interval [CI] 1.03-1.74) on diagnostic endoscopy. Eighteen percent suffered from disease complications, and development of late complications was associated with presenting with a complication (aOR 9.63, CI 1.09-85.20), severity of duodenal endoscopic abnormalities (aOR 8.74, CI 1.67-45.60), and increases in the EoG Endoscopic Reference Score (aOR 1.70, CI 1.11-2.63). DISCUSSION: Patients with gastric and duodenal eosinophilia should be followed closely to monitor for recurrence and complications, especially those presenting with endoscopic abnormalities or complications.
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Duodenitis , Eosinofilia , Gastritis , Humanos , Masculino , Niño , Femenino , Eosinofilia/epidemiología , Gastritis/epidemiología , Gastritis/complicaciones , Gastritis/patología , Duodenitis/epidemiología , Duodenitis/patología , Adolescente , Preescolar , Enteritis/epidemiología , Enteritis/complicaciones , Enteritis/diagnóstico , Recurrencia , Estudios Retrospectivos , Endoscopía GastrointestinalRESUMEN
BACKGROUND AND AIMS: The Index of Severity for Eosinophilic Esophagitis (I-SEE) was recently developed. We aimed to understand I-SEE scores in a longitudinal pediatric cohort and to determine the relationship between I-SEE and clinical features in children. METHODS: We performed a retrospective analysis on a prospectively enrolled cohort of children at a single center who were treated as part of routine clinical care. I-SEE was calculated at the diagnostic and follow-up endoscopies over a mean of 6.6 years. Scoring was 0 for inactive, 1-6 for mild, 7-14 for moderate, and ≥15 for severe eosinophilic esophagitis (EoE). We analyzed clinical, endoscopic, and histologic features at each instance. Symptoms were analyzed at the baseline, first follow-up, and last endoscopic instance. RESULTS: Of 67 children who met study criteria of at least 3 endoscopies over at least 2 years of follow-up time, 43%, 36%, and 21% had mild, moderate, and severe I-SEE scores at baseline, respectively. Between the first and second endoscopic instances, there was a decrease in the group mean I-SEE from 9.7 ± 7.2 to 6.1 ± 5.9 (P < .001). By the last instance, the overall I-SEE score dropped to 3.9 (P < .001). Body mass index <5% and poor feeding were more common in the children with severe I-SEE scores at baseline, and both improved by the last instance. Fibrosis was improved by the last instance biopsy (P < .01). CONCLUSIONS: I-SEE is a responsive severity metric in children treated long term during routine clinical care. Baseline low body mass index and poor feeding were more common in children with severe I-SEE scores.
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Enteritis , Eosinofilia , Esofagitis Eosinofílica , Gastritis , Niño , Humanos , Esofagitis Eosinofílica/patología , Estudios Retrospectivos , Endoscopía , BiopsiaRESUMEN
Although eosinophilic gastrointestinal diseases, including eosinophilic esophagitis, have been described over the past 2 to 3 decades, barriers to diagnosis and treatment are common and compounded by issues related to social determinants of health, race, ethnicity, and access to care. These barriers contribute to delays in diagnosis, resulting in persistent inflammation in the gastrointestinal tract, which can have significant consequences, including fibrostenotic complications in adults, failure to thrive in children, and decreased quality of life in all affected patients. In this commentary, we summarize gaps in knowledge regarding the epidemiology of eosinophilic gastrointestinal diseases, highlight barriers to diagnosis, discuss potential approaches based on best practices in other atopic and chronic gastrointestinal diseases, and provide recommendations for reducing barriers to timely diagnosis of eosinophilic gastrointestinal diseases in underserved populations.
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Enteritis , Eosinofilia , Esofagitis Eosinofílica , Gastritis , Adulto , Niño , Humanos , Calidad de Vida , Enteritis/diagnóstico , Enteritis/epidemiología , Enteritis/terapia , Gastritis/diagnóstico , Gastritis/epidemiología , Gastritis/terapia , Esofagitis Eosinofílica/diagnóstico , Esofagitis Eosinofílica/epidemiología , Esofagitis Eosinofílica/terapiaRESUMEN
MicroRNA (miRNA)-mediated mRNA regulation directs many homeostatic and pathological processes, but how miRNAs coordinate aberrant esophageal inflammation during eosinophilic esophagitis (EoE) is poorly understood. Here, we report a deregulatory axis where microRNA-155 (miR-155) regulates epithelial barrier dysfunction by selectively constraining tight junction CLDN7 (claudin-7). MiR-155 is elevated in the esophageal epithelium of biopsies from patients with active EoE and in cell culture models. MiR-155 localization using in situ hybridization (ISH) in patient biopsies and intra-epithelial compartmentalization of miR-155 show expression predominantly within the basal epithelia. Epithelial miR-155 activity was evident through diminished target gene expression in 3D organotypic cultures, particularly in relatively undifferentiated basal cell states. Mechanistically, generation of a novel cell line with enhanced epithelial miR-155 stable overexpression induced a functionally deficient epithelial barrier in 3D air-liquid interface epithelial cultures measured by transepithelial electrical resistance (TEER). Histological assessment of 3D esophageal organoid cultures overexpressing miR-155 showed notable dilated intra-epithelial spaces. Unbiased RNA-sequencing analysis and immunofluorescence determined a defect in epithelial barrier tight junctions and revealed a selective reduction in the expression of critical esophageal tight junction molecule, claudin-7. Together, our data reveal a previously unappreciated role for miR-155 in mediating epithelial barrier dysfunction in esophageal inflammation.
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Claudinas , Esofagitis Eosinofílica , MicroARNs , Humanos , Claudinas/genética , Esofagitis Eosinofílica/genética , Esofagitis Eosinofílica/metabolismo , Esofagitis Eosinofílica/patología , Células Epiteliales/metabolismo , Hipoxia/metabolismo , Inflamación/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Uniones Estrechas/metabolismoRESUMEN
The Consortium of Eosinophilic Gastrointestinal Diseases and The International Gastrointestinal Eosinophil Researchers organized a day-long symposium at the 2022 Annual Meeting of the American Academy of Allergy, Asthma & Immunology. The symposium featured a review of recent discoveries in the basic biology and pathogenesis of eosinophilic gastrointestinal diseases (EGIDs) in addition to advances in our understanding of the clinical features of EGIDs. Diagnostic and management approaches were reviewed and debated, and clinical trials of emerging therapies were highlighted. Herein, we briefly summarize the breakthrough discoveries in EGIDs.
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Asma , Enteritis , Eosinofilia , Esofagitis Eosinofílica , Gastritis , Humanos , Estados Unidos , Enteritis/diagnóstico , Enteritis/terapia , Asma/diagnóstico , Asma/terapiaRESUMEN
In response to the social inequities that exist in health care, the NIH-funded Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR) recently formed a diversity committee to examine systemic racism and implicit bias in the care and research of eosinophilic gastrointestinal diseases (EGIDs). Herein, we describe our process, highlighting milestones and issues addressed since the committee's inception, which we hope will inspire other researchers to enhance diversity, equity, inclusion, and accessibility (DEIA) in their fields. Our journey began by establishing mission and vision statements to define the purpose of the committee. Regular discussion of diversity-related topics was incorporated into existing meetings and web-based materials were shared. This was followed by educational initiatives, including establishing a library of relevant publications and a speaker series to address DEIA topics. We then established a research agenda focused on the following actionable items: (1) to define what is known about the demographics of EGIDs by systematic review of population-based studies; (2) to develop a practical tool for reporting participant demographics to reduce bias in EGID literature; (3) to examine health disparities in the care of individuals with eosinophilic esophagitis who present to the emergency department with an esophageal food impaction; (4) to examine how access to a gastroenterologist affects the conclusions of published research examining the prevalence of pediatric eosinophilic esophagitis; and (5) to develop a model for examining the dimensions of diversity, and provide a framework for CEGIR's ongoing projects and data capture. In addition to promoting consciousness of DEIA, this initiative has fostered inclusivity among CEGIR members and will continue to inspire positive changes in EGID care and research.
Diversity in Eosinophilic Gastrointestinal Disease Research To address systemic bias in patient care and research in eosinophilic gastrointestinal diseases, the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR) recently formed a diversity committee. The CEGIR diversity committee has defined its purpose through mission and vision statements and developed structured educational and research initiatives to enhance diversity, equity, inclusivity, and accessibility (DEIA) in all CEGIR activities. Here, we share the process of formation of our diversity committee, highlighting milestones achieved and summarizing future directions. We hope that this report will serve as a guide and an inspiration for other researchers to enhance DEIA in their fields.
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BACKGROUND: Eosinophilic gastritis/gastroenteritis (EoG/EoGE) are rare disorders with pathologic gastric and/or small intestinal eosinophilia lacking an approved therapy. An allergic mechanism is postulated but underexplored mechanistically and therapeutically. OBJECTIVE: We evaluated the effectiveness of a food allergen-free diet (elemental formula) in controlling gastrointestinal eosinophilia in adult EoG/EoGE. METHODS: Adults aged 18 to 65 years with histologically active EoG/EoGE (≥30 eosinophils per high-power field) in the stomach and/or duodenum and gastrointestinal symptoms within the month preceding enrollment were prospectively enrolled onto a single-arm clinical trial to receive elemental formula for 6 consecutive weeks. The primary end point was percentage of participants with complete histologic remission (<30 eosinophils per high-power field in both stomach and duodenum). Exploratory outcomes were improvement in symptoms, endoscopy results, blood eosinophilia, quality of life, Physician Global Assessment score, and EoG-relevant gastric transcriptome and microbiome. RESULTS: Fifteen adults (47% male, average age 37.7 years, average symptom duration 8.8 years) completed the trial. Multi-gastrointestinal segment involvement affected 87%. All subjects had complete histologic remission in the stomach (P = .002) and duodenum (P = .001). Scores improved in overall PhGA (P = .002); EGREFS (P = .003); EGDP (P = .002); SODA pain intensity (P = .044), non-pain (P = .039), and satisfaction (P = .0024); and PROMIS depression (P = .0078) and fatigue (P = .04). Food reintroduction reversed these improvements. The intervention was well tolerated in 14 subjects, with 1 serious adverse event reported in 1 subject. CONCLUSION: An amino acid-based elemental diet improves histologic, endoscopic, symptomatic, quality-of-life, and molecular parameters of EoG/EoGE; these findings and disease recurrence with food trigger reintroduction support a dominant role for food allergens in disease pathogenesis. CLINICALTRIALS: gov Identifier: NCT03320369.