Summary of the updated international consensus diagnostic criteria for eosinophilic esophagitis: AGREE conference

Basal zone hyperplasia (BZH) and dilated intercellular spaces (DISs) are thought to contribute to the clinical manifestations of eosinophilic esophagitis (EoE); however, the molecular pathways that drive BZH remain largely unexplored.

We sought to define the role of IL-13–induced transcriptional programs in esophageal epithelial proliferation in EoE.

We performed RNA sequencing, bioinformatics, Western blot, reverse transcriptase quantitative PCR, and histologic analyses on esophageal biopsies from healthy control and patients with EoE, primary esophageal cells derived from patients with EoE, and IL-13–stimulated esophageal epithelial keratinocytes grown at the air-liquid interface (EPC2-ALI). Genetic (shRNA) and pharmacologic (proteolysis-targeting chimera degrader) approaches and in vivo model of IL-13–induced esophageal epithelial remodeling (Krt5-rtTA x tetO-IL-13Tg) were used to define the role of signal transducer and activator of transcription 3 (STAT3) and STAT6 and secreted frizzled-related protein 1 (SFRP1) in esophageal epithelial proliferation.

RNA-sequencing analysis of esophageal biopsies (healthy control vs EoE) and EPC2-ALI revealed 82 common differentially expressed genes that were enriched for putative STAT3 target genes. In vitro and in vivo analyses revealed a link between IL-13–induced STAT3 and STAT6 phosphorylation, SFRP1 mRNA expression, and esophageal epithelial proliferation. In vitro studies showed that IL-13–induced esophageal epithelial proliferation was STAT3-dependent and regulated by the STAT3 target SFRP1. SFRP1 mRNA is increased in esophageal biopsies from patients with active EoE compared with healthy controls or patients in remission and identifies an esophageal suprabasal epithelial cell subpopulation that uniquely expressed the core EoE proinflammatory transcriptome genes (CCL26, ALOX15, CAPN14, ANO1, and TNFAIP6).

These studies identify SFRP1 as a key regulator of IL-13–induced and STAT3-dependent esophageal proliferation and BZH in EoE and link SFRP1⁺ esophageal epithelial cells with the proinflammatory and epithelial remodeling response in EoE.

Eosinophilic esophagitis (EoE), a chronic allergic inflammatory disease, is linked to multiple genetic risk factors, but studies have focused on populations of European ancestry. Few studies have assessed Black or African American (AA) populations for loci involved in EoE susceptibility.

We performed admixture mapping (AM) and genome-wide association study (GWAS) of EoE using participants from AA populations.

We conducted AM and GWAS of EoE using 137 EoE cases and 1465 healthy controls from the AA population. Samples were genotyped using molecular evolutionary genetics analysis (MEGA). Genotype imputation was carried out with the Consortium on Asthma Among African-Ancestry Populations in the Americas (CAAPA) reference panel using the Michigan Imputation Server. Global and local ancestry inference was carried out, followed by fine mapping and RNA sequencing. After quality control filtering, over 6,000,000 variants were tested by logistic regression adjusted for sex, age, and global ancestry.

The global African ancestry proportion was found to be significantly lower among cases than controls (0.751 vs 0.786, P = .012). Case-only AM identified 3 significant loci (9p13.3, 12q24.22-23, and 15q11.2) associated with EoE, of which 12q24.22-23 and 9p13.3 were further replicated in the case–control analysis, with associations observed with African ancestry. Fine mapping and multiomic functional annotations prioritized the variants rs11068264 (FBXW8) and rs7307331 (VSIG10) at 12q24.23 and rs2297879 (ARHGEF39) at 9p13.3. GWAS identified 1 genome-wide significant locus at chromosome 1p22.3 (rs17131726, DDAH1) and 10 other suggestive loci. Most GWAS variants were low-frequency African ancestry–specific variants. RNA sequencing revealed that esophageal DDAH1 and VSIG10 were downregulated and ARHGEF39 upregulated among EoE cases.

GWAS and AM for EoE in AA revealed that African ancestry–specific genetic susceptibility loci exist at 1p22.3, 9p13.3, and 12q24.23, providing evidence of ancestry-specific inheritance of EoE. More independent genetic studies of different ancestries for EoE are needed.

The Joint Task Force for the American Academy of Allergy Asthma Immunology and American College of Allergy Asthma Immunology and the American Gastroenterology Association recently published guidelines for the management of eosinophilic esophagitis (EoE). Because the guideline was published, dupilumab became the first and only medication to gain regulatory approval for the treatment of EoE. This expert opinion document provides a framework for how the clinician can consider using dupilumab in the treatment strategy for patients with EoE.

Eosinophilic esophagitis (EoE) is a relatively new disease characterized by clinical symptoms resulting from esophageal involvement and the presence of marked eosinophilic infiltrate in the esophageal wall. Its prevalence has grown and currently represents the second cause of chronic esophagitis, after gastroesophageal reflux disease, and the main cause of dysphagia in children and young adults. EoE is due to an aberrant Th2 immune response to specific food antigens. The clinical presentation is variable, manifesting with inflammatory symptoms at the beginning, and may evolve over time to a fibrostenosant form. Food impaction is a cause of morbidity due to the risk of bronchoaspiration and esophageal perforation. Treatment aims to control symptoms, prevent relapses, and avoid complications. Important in the future will be the characterization of different phenotypes, resulting from different pathogenetic pathways, with the objective of predicting future behavior of the disease, responses to existing therapies, and the need for aggressive treatment, thus individualizing its treatment.

Eosinophilic esophagitis (EoE) is a chronic, allergen-mediated, eosinophil-predominant, type 2 inflammatory disease that progresses to fibrostenosis of the esophagus if left untreated. This review focuses on biologics therapy in EoE.

Manuscripts on EoE treatments are identified on PubMed.

Original research, randomized controlled trials, retrospective studies, meta-analyses, case series, and case reports of high relevance are selected and reviewed.

Biologics have been used as investigational therapies for EoE in clinical studies over the years, based on earlier work that identified key cytokines and mediators of eosinophilic inflammation and, more recently, type 2 inflammation that underlie EoE pathogenesis. Dupilumab, a monoclonal antibody that targets the interleukin (IL)-4Rα chain, thereby interfering with IL-4 and IL-13 binding with the receptor, was recently approved by the Food and Drug Administration for EoE. Dupilumab improved clinical symptoms, endoscopic scores, histologic inflammation, and esophageal distensibility. Several clinical trials that target key cytokines such as IL-5, IL-13, and thymic stromal lymphopoietin in EoE are still ongoing.

Topical corticosteroid, proton pump inhibitor therapy, elimination diet, and dilation are widely accepted treatment modalities for EoE. Dupilumab is the first Food and Drug Administration–approved therapy for EoE. Other studies evaluating biologics that target eosinophils, key cytokines, and inflammatory pathways in EoE are ongoing. Treatment algorithms are needed to position EoE therapies as they emerge.

Eosinophilic oesophagitis (EoE) is a characterised by the presence of intraepithelial eosinophils in oesophageal biopsies and symptoms of oesophageal dysfunction. This is a retrospective review of patients diagnosed with EoE between January 2010 to April 2021 within our Paediatric Gastro- Intestinal and Allergy department. 70 children were identified with a diagnosis of EoE, with mean age of diagnosis 8 years (range 0 – 17). Our diagnoses of EoE have increased over this period from 0.08 diagnoses per month in 2010 to 2.25 diagnoses per month in 2021. Notably 14 (44%) of patients had a legume allergy. The initial treatment plan included a proton pump inhibitor (PPI) for 53 (76%) patients, of which 40 (75%) used a low dose (less than 40mg per day), most frequently omeprazole 20mg once daily (in 32 patients, 60%). This analysis demonstrates the increasing incidence of EoE at our centre, in keeping with data from other centres.