One-food versus 4-food elimination diet for pediatric eosinophilic esophagitis: A multisite randomized trial.

Background: A 6-food elimination diet in pediatric eosinophilic esophagitis (EoE) is difficult to implement and may negatively affect quality of life (QoL). Less restrictive elimination diets may balance QoL and efficacy.

Objective: We performed a multisite, randomized comparative efficacy trial of a 1-food (milk) elimination diet (1FED) versus 4-food (milk, egg, wheat, soy) elimination diet (4FED) in pediatric EoE.

Losartan Treatment Reduces Esophageal Eosinophilic Inflammation in a Subset of Eosinophilic Esophagitis.

Background: Eosinophilic esophagitis (EoE) is a chronic, food antigen-driven esophageal disorder. Connective tissue disorders (CTDs) and esophageal connective tissue alterations are associated with EoE. Therefore, angiotensin II type 1 receptor blockade with losartan, an accepted CTD treatment, is a potential EoE treatment.

Mast cell activation syndrome: Current understanding and research needs.

Mast cell activation syndrome (MCAS) is a term applied to several clinical entities that have gained increased attention from patients and medical providers. Although several descriptive publications about MCAS exist, there are many gaps in knowledge, resulting in confusion about this clinical syndrome. Whether MCAS is a primary syndrome or exists as a constellation of symptoms in the context of known inflammatory, allergic, or clonal disorders associated with systemic mast cell activation is not well understood.

Single-cell RNA sequencing of mast cells in eosinophilic esophagitis reveals heterogeneity, local proliferation, and activation that persists in remission.

Background: Mast cells (MCs) are pleiotropic cells that accumulate in the esophagus of patients with eosinophilic esophagitis (EoE) and are thought to contribute to disease pathogenesis, yet their properties and functions in this organ are largely unknown.

Objectives: This study aimed to perform a comprehensive molecular and spatial characterization of esophageal MCs in EoE.

Methods: Esophageal biopsies obtained from patients with active EoE, patients with EoE in histologic remission, and individuals with histologically normal esophageal biopsies and no history of esophageal disease (ie, control individuals) were subject to single-cell RNA sequencing, flow cytometry, and immunofluorescence analyses.

International Consensus Recommendations for Eosinophilic Gastrointestinal Disease Nomenclature.

Background & Aims: Substantial heterogeneity in terminology used for eosinophilic gastrointestinal diseases (EGIDs), particularly the catchall term "eosinophilic gastroenteritis," limits clinical and research advances. We aimed to achieve an international consensus for standardized EGID nomenclature.

Methods: This consensus process utilized Delphi methodology.

Prospective Endoscopic Activity Assessment for Eosinophilic Gastritis in a Multisite Cohort.

Introduction: Eosinophilic gastritis (EG) is a chronic inflammatory disease of the stomach characterized by eosinophil-predominant gastric mucosal inflammation and gastrointestinal symptoms. The aim of this study was to prospectively evaluate endoscopic features in a large series of children and adults with EG to better understand the endoscopic manifestations and develop a standardized instrument for investigations.

Methods: Data were prospectively collected as part of the Consortium for Eosinophilic Gastrointestinal Disease Researchers, a national collaborative network.

Desmoplakin and periplakin genetically and functionally contribute to eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is a chronic allergic inflammatory disease with a complex underlying genetic etiology. Herein, we conduct whole-exome sequencing of a multigeneration EoE pedigree (discovery set) and 61 additional multiplex families with EoE (replication set). A series of rare, heterozygous, missense variants are identified in the genes encoding the desmosome-associated proteins DSP and PPL in 21% of the multiplex families.

Loss of Endothelial TSPAN12 Promotes Fibrostenotic Eosinophilic Esophagitis via Endothelial Cell-Fibroblast Crosstalk.

Background & Aims: Eosinophilic esophagitis (EoE) can progress to fibrostenosis by unclear mechanisms. Herein, we investigated gene dysregulation in fibrostenotic EoE, its association with clinical parameters and specific pathways, and the functional consequences.

Methods: Esophageal biopsies from subjects with EoE were collected across 11 Consortium of Eosinophilic Gastrointestinal Disease Researchers sites (n = 311) and 2 independent replication cohorts (n = 83).

Developing a standardized approach for assessing mast cells and eosinophils on tissue biopsies: A Work Group Report of the AAAAI Allergic Skin Diseases Committee.

Mast cells and eosinophils are commonly found, expectedly or unexpectedly, in human tissue biopsies. Although the clinical significance of their presence, absence, quantity, and quality continues to be investigated in homeostasis and disease, there are currently gaps in knowledge related to what constitutes quantitatively relevant increases in mast cell and eosinophil number in tissue specimens for several clinical conditions. Diagnostically relevant thresholds of mast cell and eosinophil numbers have been proposed and generally accepted by the medical community for a few conditions, such as systemic mastocytosis and eosinophilic esophagitis.

Long-Lasting Dissociation of Esophageal Eosinophilia and Symptoms After Dilation in Adults With Eosinophilic Esophagitis.

Background & Aims: Esophageal dilation improves dysphagia but not inflammation in eosinophilic esophagitis (EoE) patients. We investigated if dilation modifies the association between symptoms and peak esophageal eosinophils per high-power field (eos/hpf).

Methods: Adults enrolled in a multisite prospective Consortium of Gastrointestinal Eosinophilic Disease Researchers Outcome Measures for Eosinophilic Gastrointestinal Diseases Across Ages observational study (NCT02523118) completed the symptom-based EoE activity index (EEsAI) patient-reported outcome instrument and underwent endoscopy with biopsy specimens.

Replication and meta-analyses nominate numerous eosinophilic esophagitis risk genes.

Background: Eosinophilic esophagitis (EoE) is an emerging, chronic, rare allergic disease associated with marked eosinophil accumulation in the esophagus. Previous genome-wide association studies have provided strong evidence for 3 genome-wide susceptibility loci.

Objective: We sought to replicate known and suggestive EoE genetic risk loci and conduct a meta-analysis of previously reported data sets.

Type 2 Immunity and Age Modify Gene Expression of Coronavirus-induced Disease 2019 Receptors in Eosinophilic Gastrointestinal Disorders.

Infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can lead to coronavirus-induced disease 2019 (COVID-19). The gastrointestinal (GI) tract is now an appreciated portal of infection. SARS-CoV-2 enters host cells via angiotensin-converting enzyme-2 (ACE2) and the serine protease TMPRSS2.

High Patient Disease Burden in a Cross-sectional, Multicenter Contact Registry Study of Eosinophilic Gastrointestinal Diseases.

Objectives: Clinical features of eosinophilic esophagitis (EoE) have been well-described in the literature, however, characterization of features experienced by patients with other eosinophilic gastrointestinal diseases (EGIDs) is lacking. Using data collected from a patient contact registry, we sought to characterize and contrast patient-reported gastrointestinal and extragastrointestinal symptoms and comorbidities in non-EoE EGIDs, including eosinophilic gastritis, gastroenteritis and colitis, relative to EoE.

Methods: We conducted a cross-sectional study of contact registry data collected from 2015 to 2018.

Eosinophilic Esophagitis: Existing and Upcoming Therapies in an Age of Emerging Molecular and Personalized Medicine.

Purpose Of Review: Recent research efforts have spurred great progress in the diagnosis and management of eosinophilic esophagitis (EoE). Nonetheless, challenges remain in addressing disease burden and impairment in the growing EoE population. We highlight work from the Cincinnati Center for Eosinophilic Disorders, the Consortium of Eosinophilic Gastrointestinal Disease Researchers, and others that address these ongoing challenges.

Functional role of kallikrein 5 and proteinase-activated receptor 2 in eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is a chronic, food antigen-driven, inflammatory disease of the esophagus and is associated with impaired barrier function. Evidence is emerging that loss of esophageal expression of the serine peptidase inhibitor, kazal type 7 (SPINK7), is an upstream event in EoE pathogenesis. Here, we provide evidence that loss of mediates its pro-EoE effects via kallikrein 5 (KLK5) and its substrate, protease-activated receptor 2 (PAR2).

Monitoring Eosinophilic Esophagitis Disease Activity With Blood Eosinophil Progenitor Levels.

Objectives: A minimally invasive biomarker to monitor disease activity is one of the greatest unmet clinical needs of the pediatric eosinophilic esophagitis (EoE) population. We aimed to determine whether circulating eosinophil progenitors (EoPs) could be used as a biomarker to identify pediatric patients with active EoE.

Methods: In a prospective observational study, peripheral blood samples, symptom history, and laboratory data were collected from pediatric patients undergoing endoscopy for evaluation of EoE on dietary therapy at Cincinnati Children's Hospital.

Pediatric Hypereosinophilia: Characteristics, Clinical Manifestations, and Diagnoses.

Background: Eosinophilia is associated with various conditions, including allergic, infectious, and neoplastic disorders. The diagnostic differential is broad, and data on hypereosinophilia in pediatric patients are limited.

Objective: The objectives of this study were to identify cases of hypereosinophilia in a tertiary pediatric medical center, determine clinical characteristics and disease associations, and estimate the incidence of hypereosinophilia in the hospital and geographic populations.

Phenotypic Characterization of Eosinophilic Esophagitis in a Large Multicenter Patient Population from the Consortium for Food Allergy Research.

Background: Eosinophilic esophagitis (EoE) is increasingly common, but data on phenotypic aspects are still incomplete.

Objectives: To describe the clinical, endoscopic, and histopathologic features of a large number of children and adults with EoE across the United States.

Methods: This was a multisite single visit registry enrolling subjects aged 6 months to 65 years with EoE.

Genetic variants at the 16p13 locus confer risk for eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus triggered by immune hypersensitivity to food. Herein, we tested whether genetic risk factors for known, non-allergic, immune-mediated diseases, particularly those involving autoimmunity, were associated with EoE risk. We used the high-density Immunochip platform, encoding 200,000 genetic variants for major auto-immune disease.

Alignment of parent- and child-reported outcomes and histology in eosinophilic esophagitis across multiple CEGIR sites.

Background: Patient-reported outcome metrics for eosinophilic esophagitis (EoE) have been developed and validated but not used in a multicenter pediatric population or systematically aligned with histology.

Objective: We sought to understand (1) the potential of caregiver report to predict patient self-reported symptoms and (2) the correlation of patient-reported outcome domains with histology.

Methods: Patients with EoE (n = 310) and their parents participating in the Consortium of Gastrointestinal Eosinophilic Disease Researchers (CEGIR) observational clinical trial were queried for baseline patient symptoms and quality of life (QOL) by using the Pediatric Eosinophilic Esophagitis Symptom Score, version 2 (PEESSv2.