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This position paper deals with an expert consensus on diagnosis and management of eosinophilic esophagitis and esophageal food impaction issued by the Austrian Eosinophilic Esophagitis Network, a working group under the patronage of the Austrian Society of Gastroenterology and Hepatology (ÖGGH). In need of a standardized approach on the management of EoE, recommendations were made based on international guidelines and landmark studies., (© 2024. The Author(s).)

The present document constitutes Part 2 of the EoETALY Consensus Statements guideline on the diagnosis and management of eosinophilic esophagitis (EoE) developed by experts in the field of EoE across Italy (i.e., EoETALY Consensus Group). Part 1 was published as a different document, and included three chapters discussing 1) definition, epidemiology, and pathogenesis; 2) clinical presentation and natural history and 3) diagnosis of EoE. The present work provides guidelines on the management of EoE in two final chapters: 4) treatment and 5) monitoring and follow-up, and also includes considerations on knowledge gaps and a proposed research agenda for the coming years. The guideline was developed through a Delphi process, with grading of the strength and quality of the evidence of the recommendations performed according to accepted GRADE criteria.This document has received the endorsement of three Italian national societies including the Italian Society of Gastroenterology (SIGE), the Italian Society of Neurogastroenterology and Motility (SINGEM), and the Italian Society of Allergology, Asthma, and Clinical Immunology (SIAAIC). The guidelines also involved the contribution of members of ESEO Italia, the Italian Association of Families Against EoE., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Eosinophilic oesophagitis (EoE) is a chronic, immune-mediated disease of the oesophagus. Eosinophilic oesophagitis is associated with a substantial disease burden affecting the quality of life and affecting mental health. There are limited data describing the incidence of psychiatric disorders and the use of psychotropic drugs (PDs) in EoE patients., Objectives: The aim was to investigate whether EoE patients in Denmark have higher use of PDs, contacts with the department of psychiatry, and attempts of suicide or intentional self-harm compared with the general population after being diagnosed with EoE., Methods: This study was a nationwide, population-based register study including 3367 EoE patients and 16,835 age- and sex-matched comparators. A register-based EoE definition was used to identify cases. Incident PD use was extracted from the prescription register and information regarding psychiatric contacts was retrieved from the Danish Psychiatric Central Research Register., Results: The 5-year incidence of PD use in EoE patients was 13.8% compared to 7.1% of the matched comparators (Hazard ratio 1.83; confidence interval 1.6-2.0; p ≤ 0.001). Antidepressants were the most frequently prescribed PD, whereas antipsychotics were the least prescribed PD. Increasing age, lower educational level, and comorbidity (Charlson Comorbidity Index score ≥1) were associated with the prescription of PDs. The risk of PD use was lower in men than in women with EoE., Conclusion: Treatment with PDs were more common in EoE patients after they were diagnosed than in the general Danish population, indicating that EoE patients have an increased risk of psychiatric disorders., (© 2024 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Eosinophilic esophagitis (EoE) is a chronic type 2-mediated inflammatory disease of the esophagus that represents the most common eosinophilic gastrointestinal disease. Experts in the field of EoE across Italy (i.e., EoETALY Consensus Group) including gastroenterologists, endoscopists, allergologists/immunologists, and paediatricians conducted a Delphi process to develop updated consensus statements for the management of patients with EoE and update the previous position paper of the Italian Society of Gastroenterology (SIGE) in light of recent evidence. Grading of the strength and quality of the evidence of the recommendations was performed using accepted GRADE criteria. The guideline is divided in two documents: Part 1 includes three chapters, namely 1) definition, epidemiology, and pathogenesis; 2) clinical presentation and natural history, and 3) diagnosis, while Part 2 includes two chapters: 4) treatment and 5) monitoring and follow-up. This document has received the endorsement of three Italian national societies including the SIGE, the Italian Society of Neurogastroenterology and Motility (SINGEM), and the Italian Society of Allergology, Asthma, and Clinical Immunology (SIAAIC). With regards to patients' involvement, these guidelines involved the contribution of members of ESEO Italia, the Italian Association of Families Against EoE., Competing Interests: Declaration of competing interest Nicola de Bortoli: Advisory board member for: AlfaSigma, Sanofi Genzyme, Dr Falk; Lecture grants from Reckitt-Benkiser, Malesci, Dr. Flak, Sofar, Alfa-Sigma, Pharma-Line. Pierfrancesco Visaggi: Has served as speaker for Dr Falk, JB Pharmaceuticals, Malesci. Roberto Penagini: Has served as speaker for Dr Falk, Sanofi. Edda Battaglia: has served as consultant for NZP, GUNA Gaia Pellegatta has served as speaker for Dr Falk, Sanofi Genzyme, Malesci. Paola Iovino: Has served as consultant for Dr Falk Giovanni Marasco: Served as an advisory board member for AlfaSigma, EG Pharma, Monteresearch srl, Recordati, Cineca. Received lecture grants from Agave, AlfaSigma, Bromatech, Clorofilla, Echosens, Ferring, Mayoly Spindler, Menarini and Schwabe Pharma. Salvatore Oliva: Has served as speaker for Sanofi, Medtronic; Has served as consultant for: Sanofi, Medtronic, Brystol; Has received research support from Alfa Sigma, Medtronic. Francesca Racca: has served as speaker for Sanofi; has served as consultant for Dr Falk, Sanofi, GSK Erminia Ridolo: has served as consultant for Dr Falk Edoardo Vincenzo Savarino: has served as speaker for Abbvie, Agave, AGPharma, Alfasigma, Aurora Pharma, CaDiGroup, Celltrion, Dr Falk, EG Stada Group, Fenix Pharma, Fresenius Kabi, Galapagos, Janssen, JB Pharmaceuticals, Innovamedica/Adacyte, Malesci, Mayoly Biohealth, Omega Pharma, Pfizer, Reckitt Benckiser, Sandoz, SILA, Sofar, Takeda, Tillots, Unifarco; has served as consultant for Abbvie, Agave, Alfasigma, Biogen, Bristol-Myers Squibb, Celltrion, Diadema Farmaceutici, Dr. Falk, Fenix Pharma, Fresenius Kabi, Janssen, JB Pharmaceuticals, Merck & Co, Nestlè, Reckitt Benckiser, Regeneron, Sanofi, SILA, Sofar, Synformulas GmbH, Tssakeda, Unifarco; he received research support from Pfizer, Reckitt Benckiser, SILA, Sofar, Unifarco, Zeta Farmaceutici. Bruno Annibale, Federica Baiano Svizzero, Giovanni Barbara, Brigida Barberio, Ottavia Bartolo, Antonio Di Sabatino, Ludovico Docimo, Marzio Frazzoni, Manuele Furnari, Matteo Ghisa, Andrea Iori, Marco Vincenzo Lenti, Elisa Marabotto, Aurelio Mauro, Marcella Pesce, Antonino Carlo Privitera, Ilaria Puxeddu, Mentore Ribolsi, Salvatore Russo, Giovanni Sarnelli, Salvatore Tolone, Patrizia Zentilin, Fabiana Zingone: None., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background and Aims: Ultrasonography has shown that eosinophils accumulate in each segment of the esophageal mucosa in human EoE, ultimately promoting esophageal motility dysfunction; however, no mechanistic evidence explains how or why this accumulation occurs., Methods: Quantitative PCR, ELISA, flow cytometry, immunostaining, and immunofluorescence analyses were performed using antibodies specific to the related antigens and receptors., Results: In deep esophageal biopsies of EoE patients, eosinophils and mast cells accumulate adjacent to nerve cell-derived VIP in each esophageal segment. qRT -PCR analysis revealed five- to sixfold increases in expression levels of VIP , CRTH2 , and VAPC2 receptors and proteins in human blood- and tissue-accumulated eosinophils and mast cells. We also observed a significant correlation between mRNA CRTH2 levels and eosinophil- and nerve cell-derived VIP s in human EoE ( p < 0.05). We provide evidence that eosinophil and mast cell deficiency following CRTH2 antagonist treatment improves motility dysfunction in a chronic DOX-inducible CC10-IL-13 murine model of experimental EoE., Conclusions: CRTH2 antagonist treatment is a novel therapeutic strategy for inflammatory cell-induced esophageal motility dysfunction in IL-13-induced chronic experimental EoE.

Background & Aims: Dupilumab is approved for treatment of eosinophilic esophagitis (EoE), but real-world data are lacking. We aimed to determine the real-world efficacy of dupilumab in patients with severe, treatment-refractory, and fibrostenotic EoE., Methods: We conducted a retrospective cohort study of EoE patients prescribed dupilumab and who were treatment-refractory to standard modalities. Patient demographics, clinical characteristics, EoE history, and procedural data (including the histologically worst, predupilumab, and postdupilumab endoscopies) were extracted from medical records. Symptomatic, endoscopic, and histologic responses were assessed for the worst and predupilumab endoscopies compared with the postdupilumab endoscopy., Results: We identified 46 patients with refractory fibrostenotic EoE who were treated with dupilumab. Patients showed endoscopic, histologic, and symptomatic improvement on dupilumab compared with both the worst and the predupilumab esophagogastroduodenoscopies. The peak eosinophil counts decreased markedly, and postdupilumab histologic response rates were 80% and 57% for fewer than 15 eosinophils per high-power field and 6 or fewer eosinophils per high-power field, respectively, and the Endoscopic Reference Score decreased from 5.01 to 1.89 (P < .001 for all). Although the proportion of strictures was stable, there was a significant increase in the predilation esophageal diameter (from 13.9 to 16.0 mm; P < .001). Global symptom improvement was reported in 91% (P < .001)., Conclusions: In this population of severe, refractory, and fibrostenotic EoE patients, most achieved histologic, endoscopic, and symptom improvement with a median of 6 months of dupilumab, and esophageal stricture diameter improved. Dupilumab has real-world efficacy for a severe EoE population, most of whom would not have qualified for prior clinical trials., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Earlier studies on the possible association between eosinophilic esophagitis (EoE) and inflammatory bowel disease (IBD) have been contradictory., Methods: Patients with biopsy-verified EoE diagnosed between 1990 and 2017 in Sweden (n = 1587) were age- and sex-matched with up to five general population reference individuals (n = 7808). EoE was defined using pathology reports from all 28 pathology centers in Sweden (the ESPRESSO study). Multivariate Cox regression then estimated hazard ratios for future IBD. IBD was defined based on the international classification of disease codes and histopathology codes. In secondary analyses, sibling comparators were used to further reduce potential familial confounding. Additionally, we performed logistic regression examining earlier IBD in EoE., Results: During follow-up until 2020, 16 (0.01%) EoE patients and 21 (0.003%) general population reference individuals diagnosed with IBD, corresponding to a 3.5-fold increased risk of future IBD (aHR = 3.56; 95% CI 1.79-7.11). EoE was linked to Crohn's disease (aHR = 3.39 [95% CI 1.02-9.60]) but not to ulcerative colitis (aHR = 1.37; 95% CI 0.38-4.86). Compared to their siblings, patients with EoE were at a 2.48-fold increased risk of IBD (aHR = 2.48; 95% CI 0.92-6.70). Earlier IBD was 15 times more likely in EoE patients than in matched reference individuals (odds ratio, 15.39; 95% CI 7.68-33.59)., Conclusion: In this nationwide cohort study, EoE was associated with a 3.5-fold increased risk of later IBD diagnosis. This risk increase may be due to shared genetic or early environmental risk factors, but also surveillance bias could play a role., (© 2023 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Eosinophilic esophagitis (EoE) is a rare atopic disorder associated with esophageal dysfunction, including difficulty swallowing, food impaction, and inflammation, that develops in a small subset of people with food allergies. Genome-wide association studies (GWASs) have identified 9 independent EoE risk loci reaching genome-wide significance (p < 5 × 10 -8 ) and 27 additional loci of suggestive significance (5 × 10 -8  < p < 1 × 10 -5 ). In the current study, we perform linkage disequilibrium (LD) expansion of these loci to nominate a set of 531 variants that are potentially causal. To systematically interrogate the gene regulatory activity of these variants, we designed a massively parallel reporter assay (MPRA) containing the alleles of each variant within their genomic sequence context cloned into a GFP reporter library. Analysis of reporter gene expression in TE-7, HaCaT, and Jurkat cells revealed cell-type-specific gene regulation. We identify 32 allelic enhancer variants, representing 6 genome-wide significant EoE loci and 7 suggestive EoE loci, that regulate reporter gene expression in a genotype-dependent manner in at least one cellular context. By annotating these variants with expression quantitative trait loci (eQTL) and chromatin looping data in related tissues and cell types, we identify putative target genes affected by genetic variation in individuals with EoE. Transcription factor enrichment analyses reveal possible roles for cell-type-specific regulators, including GATA3. Our approach reduces the large set of EoE-associated variants to a set of 32 with allelic regulatory activity, providing functional insights into the effects of genetic variation in this disease., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)