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Lucendo AJ, Gutiérrez-Ramírez L, Tejera-Muñoz A, Molina-Infante J, Arias Á. Proton Pump Inhibitors for Inducing and Maintaining Remission in Eosinophilic Esophagitis: An Updated Systematic Review and Meta-Analysis. Clin Gastroenterol Hepatol 2025:S1542-3565(25)00188-0. [PMID: 40089255 DOI: 10.1016/j.cgh.2025.01.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Revised: 12/19/2024] [Accepted: 01/02/2025] [Indexed: 03/17/2025]
Abstract
BACKGROUND & AIMS Proton pump inhibitor (PPI) therapy results in clinical and histological remission in approximately 50% of eosinophilic esophagitis (EoE) patients. We aimed to systematically update this topic due to cumulative data from pediatric/adult populations in wider geographical settings. METHODS A search in MEDLINE, Embase, and Scopus databases was performed. Primary outcomes were clinical response and histological remission (<15 eosinophils per high-power field). Subgroup analyses included age group, PPI drug and dosage, study design, data origin, and risk of bias. Data were pooled using random-effects models. RESULTS Seventy-three studies comprising 7304 patients were included. PPI therapy led to clinical response in 65% (95% confidence interval [CI], 57.2-72.4; I2 = 0%) and histological remission in 45.4% (95% CI, 41.6%-49.3%) of patients, without differences between children and adults (41.2% vs 48%; P ••• .17). Overall, 34.1% (95% CI, 27.9%-40.5%) achieved <5 eosinophils per high-power field. Pooled effectiveness was significantly superior (P < .001) in Western Pacific areas, principally Japan (67.9%), compared with American and European areas (40.6% and 44.4%, respectively). Histological remission was significantly higher with double PPI doses compared with standard (51.7% vs 28.3%; P •••.005). Response was significantly higher in studies with lower risk of bias. Maintenance half-doses led to sustained histological remission in 68.2% (95% CI, 63.7%-72.6%; I2 = 0%) of patients. CONCLUSIONS PPI therapy induces clinic-histological remission in almost half of pediatric and adult EoE patients. Response to PPIs is significantly higher in Japan. Sustained remission is common on tapering PPI doses.
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Affiliation(s)
- Alfredo J Lucendo
- Department of Gastroenterology, Hospital General de Tomelloso, Tomelloso, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Toledo, Spain; Instituto de Investigación Sanitaria de Castilla-La Mancha, Toledo, Spain; Instituto de Investigación Sanitaria Princesa, Madrid, Spain.
| | - Lucía Gutiérrez-Ramírez
- Instituto de Investigación Sanitaria de Castilla-La Mancha, Toledo, Spain; Research Unit Complejo Hospitalario La Mancha Centro, Alcázar de San Juan, Spain; Fundación del Hospital Nacional de Parapléjicos para la Investigación y la Integración, Toledo, Spain
| | - Antonio Tejera-Muñoz
- Instituto de Investigación Sanitaria de Castilla-La Mancha, Toledo, Spain; Research Unit Complejo Hospitalario La Mancha Centro, Alcázar de San Juan, Spain
| | - Javier Molina-Infante
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Toledo, Spain; Department of Gastroenterology, Hospital Universitario de Cáceres, Cáceres, Spain
| | - Ángel Arias
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Toledo, Spain; Instituto de Investigación Sanitaria de Castilla-La Mancha, Toledo, Spain; Instituto de Investigación Sanitaria Princesa, Madrid, Spain; Research Unit Complejo Hospitalario La Mancha Centro, Alcázar de San Juan, Spain
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Dellon ES. Monitoring of Maintenance Therapy in Eosinophilic Esophagitis: Listen, Look, and Touch. Dig Dis Sci 2025; 70:882-884. [PMID: 39826070 DOI: 10.1007/s10620-024-08819-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2024] [Accepted: 12/19/2024] [Indexed: 01/20/2025]
Affiliation(s)
- Evan S Dellon
- Division of Gastroenterology and Hepatology, Department of Medicine, Center for Esophageal Diseases and Swallowing, and Center for Gastrointestinal Biology and Disease, University of North Carolina School of Medicine, 130 Mason Farm Rd, Chapel Hill, North Carolina, USA.
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Tsuzuki Y, Shiotani A, Miyaguchi K, Ono S, Saito Y, Sugimoto M, Naito Y, Nomura S, Handa O, Hisamatsu T, Fujishiro M, Matsuda T, Morita Y, Yahagi N, Chan FKL, Ang TL, Abdullah M, Tablante MC, Prachayakul V, Li B, Jung HY, Matsumoto H, Shiomi R, Imaeda H. Questionnaire Survey on the Diagnosis and Treatments of Eosinophilic Gastrointestinal Diseases in Asia. Digestion 2025; 106:153-164. [PMID: 39947169 DOI: 10.1159/000544725] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Accepted: 02/10/2025] [Indexed: 03/22/2025]
Abstract
INTRODUCTION Eosinophilic gastrointestinal disease (EGID) is divided into eosinophilic esophagitis (EoE) and non-eosinophilic esophagitis eosinophilic gastrointestinal disease (non-EoE-EGID), based on the involved gastrointestinal organs. The present survey was performed to provide an overview of the current status of the epidemiology, diagnosis, and treatment of EGID in Asia. METHODS Responses to the questionnaire were obtained from 228 doctors at various institutions in eight Asian countries. The questionnaire consisted of 52 questions on EoE and non-EoE EGID. RESULTS Responses to questionnaire were obtained from 228 doctors from eight countries. The most common participation facilities were university hospitals, followed by public hospitals, private hospitals, and private clinics. 1-10 were the most frequent patients per year in each institution for both EoE and non-EoE-EGID. The 30s and 40s are common age groups for both EoE and non-EoE-EGID. Although endoscopic findings vary among countries, 15 or more eosinophil infiltrations in high-power fields as a diagnostic criterion are used in all countries for EoE. As treatments, the prescription rates of Proton pump inhibitor, diet, topical and systemic steroids, and biologics were similar among the eight countries in EoE. Non-EoE-EGID showed a similar trend to EoE in epidemiology, symptoms, diagnosis, and treatment. CONCLUSION The questionnaire survey partially revealed the current status of the epidemiology, symptoms, diagnosis, and treatment of EGID in Asian countries.
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Affiliation(s)
- Yoshikazu Tsuzuki
- Department of Gastroenterology, Saitama Medical University, Saitama, Japan
| | - Akiko Shiotani
- Department of Gastroenterology and Hepatology, Kawasaki Medical School, Okayama, Japan
| | - Kazuya Miyaguchi
- Department of Gastroenterology, Saitama Medical University, Saitama, Japan
| | - Shouko Ono
- Department of Gastroenterology, Hokkaido University Hospital, Sapporo, Japan
| | - Yutaka Saito
- Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan
| | - Mitsushige Sugimoto
- Research Center for GLOBAL and LOCAL Infectious Disease, Oita University, Oita, Japan
| | - Yuji Naito
- Department of Human Immunology and Nutrition Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Sachiyo Nomura
- Department of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Osamu Handa
- Department of Gastroenterology, Kawasaki Medical School, Okayama, Japan
| | - Tadakazu Hisamatsu
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, Tokyo, Japan
| | - Mitsuhiro Fujishiro
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Takahisa Matsuda
- Division of Gastroenterology and Hepatology, Toho University Omori Medical Center, Tokyo, Japan
| | - Yoshinori Morita
- Department of Gastroenterology, Kobe University International Clinical Cancer Research Center, Hyogo, Japan
| | - Naohisa Yahagi
- Cancer Center, Keio University School of Medicine, Tokyo, Japan
| | - Francis K L Chan
- Department of Medicine & Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong Kong, China
| | - Tiing Leong Ang
- Department of Gastroenterology and Hepatology, Changi General Hospital, Sing Healh Duke-NUS Academic Medical Centre, YLL School of Medicine, NUS, Simei, Singapore, Singapore
| | - Murdani Abdullah
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia/Dr Cipto Mangunkusumo Hospital, Jakarta, Indonesia
| | - Maria Carla Tablante
- Department Internal Medicine, Section of Gastroenterology and Hepatology, University of Santo Tomas Hospital, Manila, Philippines
| | - Varayu Prachayakul
- Department Internal medicine, Faculty of Medicine Mahidol university Siriraj hospital Division of Gastroenterology, Bangkok, Thailand
| | - Baiwen Li
- Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Hwoon-Yong Jung
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Asan Digestive Disease Research Institute, Seoul, Republic of Korea
| | - Hisashi Matsumoto
- Department of Gastroenterology, Saitama Medical University, Saitama, Japan
| | - Rie Shiomi
- Department of Gastroenterology, Saitama Medical University, Saitama, Japan
| | - Hiroyuki Imaeda
- Department of Gastroenterology, Saitama Medical University, Saitama, Japan
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Lucendo AJ, Nantes‐Castillejo Ó, Straumann A, Biedermann L, Bredenoord AJ, Guagnozzi D, Blas‐Jhon L, Wiechowska‐Kozlowska A, Weidlich S, von Arnim U, Santander‐Vaquero C, Perelló A, Pérez‐Martínez I, Barrio J, Vieth M, Gouya G, Dellon ES. Clinical Trial: Safety and Efficacy of a Novel Oesophageal Delivery System for Topical Corticosteroids Versus Placebo in the Treatment of Eosinophilic Oesophagitis. Aliment Pharmacol Ther 2025; 61:444-455. [PMID: 39676687 PMCID: PMC11707640 DOI: 10.1111/apt.18443] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2024] [Revised: 11/27/2024] [Accepted: 12/04/2024] [Indexed: 12/17/2024]
Abstract
BACKGROUND EsoCap is a thin mucoadhesive film designed to target the oesophageal mucosa. The device loaded with mometasone furoate (ESO-101) is under investigation for the treatment of eosinophilic oesophagitis (EoE). AIMS To evaluate the efficacy, safety and tolerability of ESO-101 in patients with active EoE. METHODS We conducted a randomised, placebo-controlled, phase 2, proof-of-concept trial at 14 European sites in adults with EoE. Participants received placebo, uncoated EsoCap (n = 15), or EsoCap loaded with 800 μg of mometasone furoate (n = 28) once daily during 28 days. The primary outcome was the absolute change in the peak eosinophil count; secondary outcomes were histologic, clinical and endoscopic measures. RESULTS Treatment with ESO-101 resulted in reduction (mean ± SD) of 49.1 ± 88.4 eosinophils/high-power field from baseline, compared with 6.6 ± 65.1 with placebo (p = 0.03). With ESO-101, 48% and 44% of patients achieved < 15 and < 6 eosinophils/high-power field, respectively; these were 0% with placebo. EoE Endoscopic Reference Score reduced significantly in patients treated with ESO-101. In contrast, dysphagia and odynophagia severity decreased similarly in both groups. There were no serious treatment-emergent adverse events. Mean serum cortisol did not change significantly throughout the trial. Notably, no oropharyngeal or oesophageal candidiasis was documented. The device was well tolerated. CONCLUSIONS ESO-101 was superior to placebo in reducing oesophageal eosinophilia. The device was safe and well tolerated in adults with EoE, supporting the continued development of ESO-101 for the treatment of EoE (Trials.gov No.: NCT04849390; Eu-CT No.: 2020-000082-16).
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Affiliation(s)
- Alfredo J. Lucendo
- Department of GastroenterologyHospital General de TomellosoTomellosoSpain
- Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBEREHD)MadridSpain
- Instituto de Investigación Sanitaria de Castilla‐La Mancha (IDISCAM)ToledoSpain
- Instituto de Investigación Sanitaria PrincesaMadridSpain
| | - Óscar Nantes‐Castillejo
- Department of GastroenterologyComplejo Hospitalario de NavarraPamplonaSpain
- IdiSNA. Instituto de Investigación Sanitaria de NavarraPamplonaSpain
| | - Alex Straumann
- Department of Gastroenterology & HepatologyUniversitäty Hospital ZurichZurichSwitzerland
| | - Luc Biedermann
- Department of Gastroenterology & HepatologyUniversitäty Hospital ZurichZurichSwitzerland
| | - Albert J. Bredenoord
- Department of GastroenterologyAmsterdam University Medical CenterAmsterdamThe Netherlands
| | - Danila Guagnozzi
- Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBEREHD)MadridSpain
- Department of GastroenterologyHospital Universitario Vall d'HebrónBarcelonaSpain
| | | | | | - Simon Weidlich
- Department of Internal Medicine II, School of Medicine and Health, University Hospital Rechts der IsarTechnical University of MunichMunichGermany
| | - Ulrike von Arnim
- Department of Gastroenterology, Hepatology and Infectious DiseasesUniversitätsklinikum Magdeburg AöRMagdeburgGermany
| | - Cecilio Santander‐Vaquero
- Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBEREHD)MadridSpain
- Instituto de Investigación Sanitaria PrincesaMadridSpain
- Department of GastroenterologyHospital Universitario de La PrincesaMadridSpain
| | - Antonia Perelló
- Department of GastroenterologyHospital de ViladecansViladecansSpain
| | - Isabel Pérez‐Martínez
- Department of GastroenterologyHospital Universitario Central de AsturiasOviedoSpain
- Diet, Microbiota and Health GroupInstituto de Investigación Sanitaria del Principado de Asturias (ISPA)OviedoSpain
| | - Jesús Barrio
- Department of GastroenterologyHospital Universitario Río Hortega. Gerencia Regional de Salud de Castilla y León (SACYL)ValladolidSpain
| | - Michael Vieth
- Institut für PathologieFriedrich‐Alexander‐Universität Erlangen‐Nürnberg, Klinikum BayreuthBayreuthGermany
| | | | - Evan S. Dellon
- Department of Medicine, Division of Gastroenterology and Hepatology, School of MedicineUniversity of North Carolina at Chapel HillChapel HillUSA
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Beveridge CA, Hermanns C, Thanawala S, Chatterjee A, Sharma N, Vura NVRK, Yang Q, Qin Y, Thota P, Hoscheit M, Brown JM, Ivanov AI, Lembo A, Gabbard S, Rieder F. Predictors of persistent symptoms in eosinophilic esophagitis after remission: fibrostenosis, eosinophilia, anxiety, and depression. Dis Esophagus 2025; 38:doae110. [PMID: 39673363 DOI: 10.1093/dote/doae110] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2024] [Revised: 10/21/2024] [Accepted: 11/14/2024] [Indexed: 12/16/2024]
Abstract
Eosinophilic Esophagitis (EoE) is a chronic inflammatory esophageal disorder, often associated with dysphagia, chest discomfort, and heartburn. There is limited information on persistent esophageal symptoms despite histologic remission (HR). We aimed to assess the prevalence and predictors of persistent esophageal symptoms in adult patients with EoE in HR. We performed a retrospective cohort study of adult EoE patients in HR (<15 eosinophils per high power field [eos/hpf]). Exclusion criteria included: no available data on symptoms, chronic opiate use, disorders of esophagogastric junction outflow on Chicago Classification version 4 diagnosis, esophageal candidiasis, erosive esophagitis, or other known cause of esophageal dysphagia besides EoE. Based on prior literature, definitions include: complete HR (<5 eos/hpf), partial HR (5-14 eos/hpf), and endoscopic fibrostenosis (rings and/or stricture). Esophageal symptoms were assessed within 2 weeks of HR and categorized into the major symptoms of dysphagia, chest pain, and heartburn. Given the retrospective nature of the study, a global symptom response (absence or presence) was used. Demographics, disease history, endoscopy reports, EoE endoscopic reference score, and histology were recorded. Univariate and multivariable logistic regression analyses were performed. Eosinophil thresholds for persistent symptoms were determined using receiver operating characteristics analyses. Of 289 EoE patients in HR, 133 (46%) had esophageal symptoms: dysphagia (N = 119; 41.2%), heartburn (N = 28; 20.8%), and chest pain (N = 10; 7.5%). Significant predictors for persistent dysphagia were anxiety (adjusted odds ratio [aOR] 3.77) and endoscopic fibrostenosis (aOR 3.87). Significant predictors for persistent heartburn with or without chest pain were anxiety or depression (aOR 12.2 and aOR 11.0) and partial HR (aOR 1.17 and aOR 1.18). Threshold eosinophil counts for persistent heartburn and chest pain were 2.5 and 3.5 eos/hpf, respectively (AUC 0.71 and 0.69). We report a high prevalence of persistent esophageal symptoms in EoE patients who are in HR. Risk factors include anxiety, depression, endoscopic fibrostenosis, and partial HR. These findings can help direct patient care, including endoscopic dilation and managing psychiatric comorbidities. Targeting less than 2.5 and 3.5 eos/hpf for heartburn and chest pain may be warranted.
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Affiliation(s)
- Claire A Beveridge
- Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Christina Hermanns
- Department of Internal Medicine, Community Care Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Shivani Thanawala
- Department of Medicine, Division of Gastroenterology, University of Pennsylvania, Philadelphia, PA, USA
| | - Arjun Chatterjee
- Department of Internal Medicine, Community Care Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Neha Sharma
- Department of Medicine, Division of Hospital Medicine, University of Texas Health Science Center, San Antonio, TX, USA
| | | | - Qijun Yang
- Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USA
| | - Yi Qin
- Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Prashanthi Thota
- Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Matthew Hoscheit
- Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases Institute, Cleveland Clinic, Cleveland, OH, USA
| | - J Mark Brown
- Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
- Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, OH, USA
| | - Andrei I Ivanov
- Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
| | - Anthony Lembo
- Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Scott Gabbard
- Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Florian Rieder
- Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases Institute, Cleveland Clinic, Cleveland, OH, USA
- Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
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Bose P, Zhang W, Mehrpouya-Bahrami P, Collins K, Zhao J, Cannon AM, Albright E, Idrees MT, Perkins A, Gupta SK, Hon EC, Kaplan MH. Increased expression of proton pump and allergic inflammation genes predicts PPI failure in pediatric eosinophilic esophagitis. Dis Esophagus 2025; 38:doae071. [PMID: 39237116 DOI: 10.1093/dote/doae071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Revised: 08/05/2024] [Accepted: 08/19/2024] [Indexed: 09/07/2024]
Abstract
Proton pump inhibitors (PPIs) are one of the standards of care of eosinophilic esophagitis (EoE) treatment, though PPI response rates are variable ranging from 23 to 63% in pediatric studies. We sought to determine if expression of select genes in esophageal mucosa can predict PPI responsiveness in EoE. Children with a new diagnosis of EoE (15 or more eosinophils/hpf on esophageal biopsy) were prospectively treated with 8 weeks of PPI therapy before follow-up esophagogastroduodenoscopy (EGD). Children with <15 eosinophils/hpf on follow-up were classified as having PPI-Responsive EoE (PPI-R) and ≥ 15 eosinophils/hpf as PPI-Nonresponsive EoE (PPI-NR). Using the Nanostring nCounter Analysis System, mRNA expression of a custom panel of genes was measured in esophageal biopsies. Immunohistochemical staining of biopsies was performed. Among children with EoE, 32% (8/25) had PPI-R EoE. ATP12A, ATP4A, tryptase-beta 2 (TPSB2), CLC and IL13 had higher expression in PPI-NR EoE compared to PPI-R EoE or controls. Immunohistochemical staining of ATP12A was higher among PPI-R EoE and PPI-NR EoE, compared to non-EoE controls. In this study, PPI-NR EoE had significantly higher baseline gene expression of mast cell, cytokine, proton pump, and eosinophil genes compared to PPI-R EoE. PPIs may be involved in an inflammatory cascade of mast cell activation that stimulates IL-13 release, which upregulates ATP12A and ATP4A that leads to eosinophil recruitment. Histologic PPI failure may occur when increased gene expression of these components is high and cannot be overcome pharmacologically, especially in the case of proton pump genes.
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Affiliation(s)
- Paroma Bose
- Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Indiana University School of Medicine/Riley Hospital for Children, Indianapolis, IN, USA
| | - Wenwu Zhang
- Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Pegah Mehrpouya-Bahrami
- Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA
- Labcorp Biomarker Solution Center, Indianapolis, IN, USA
| | - Katrina Collins
- Department of Clinical Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Jennifer Zhao
- Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Anthony M Cannon
- Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Eric Albright
- Department of Clinical Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Muhammad T Idrees
- Department of Clinical Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Anthony Perkins
- Department of Biostatistics and Health Data Science, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Sandeep K Gupta
- Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Indiana University School of Medicine/Riley Hospital for Children, Indianapolis, IN, USA
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, The University of Alabama at Birmingham, Birmingham, AL, USA
| | - Emily C Hon
- Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Indiana University School of Medicine/Riley Hospital for Children, Indianapolis, IN, USA
- Medical Gastroenterology, Eli Lilly and Company, Indianapolis, IN, USA
| | - Mark H Kaplan
- Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA
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García-Compeán D, Jiménez-Rodríguez A, González-Martínez C. La esofagitis eosinofílica. Conceptos actuales de la fisiopatología, del diagnóstico y del tratamiento. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO 2025. [DOI: 10.1016/j.rgmx.2024.09.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/02/2025]
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Visaggi P, Del Corso G, Solinas I, Ovidi F, Adamo G, Dulmin I, Baiano Svizzero F, Bellini M, Savarino EV, de Bortoli N. Adaptive Behaviors, Esophageal Anxiety, and Hypervigilance Modify the Association Between Dysphagia Perception and Histological Disease Activity in Eosinophilic Esophagitis. Am J Gastroenterol 2024:00000434-990000000-01505. [PMID: 39787341 DOI: 10.14309/ajg.0000000000003272] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2024] [Accepted: 12/12/2024] [Indexed: 01/12/2025]
Abstract
INTRODUCTION Adaptive behaviors at mealtime, esophageal symptom-specific anxiety and hypervigilance may affect dysphagia reporting in patients with eosinophilic esophagitis (EoE), but this has not been investigated. Moreover, the relationship between such confounding factors and histological disease activity (HDA) is unclear. METHODS This was a prospective study on adults with EoE. Dysphagia, anxiety, and hypervigilance were assessed using specific questionnaires (i.e., modified dysphagia symptom questionnaire [mDSQ], Dysphagia Symptom Score [DSS], and Esophageal Hypervigilance and Anxiety Scale). Adaptive behaviors were assessed using the Pisa EoE Adaptation Questionnaire. Appropriate statistics was used to investigate correlation between dysphagia, anxiety, hypervigilance, adaptive behaviors, and HDA. RESULTS Ninety-five patients were included. Esophageal anxiety, hypervigilance, and use of adaptive behaviors were found in about 50% of patients with EoE. Esophageal anxiety and hypervigilance were significantly higher ( P = 0.03 for both), and adaptive behaviors were significantly more prevalent in histologically active EoE compared with EoE in remission (76.8% vs 25.6%, P < 0.001). As a standalone measurement, mDSQ and DSS had area under the receiver operating characteristic curve of 77.7% and 75.3% for predicting HDA. Adjustments of mDSQ and DSS based on individual Esophageal Hypervigilance and Anxiety Scale scores and adaptive behaviors at mealtime significantly improved the area under the receiver operating characteristic curve of mDSQ and DSS to 86.6% and 84.3%, respectively ( P < 0.05 for both). DISCUSSION Use of adaptive behaviors, higher esophageal anxiety and hypervigilance are associated with active EoE and represent clinical markers of HDA. Adaptive behaviors provide complementary clinical information that is not detected by symptoms alone. The assessment of adaptive behaviors, anxiety, and hypervigilance improves the correlation between clinical and HDA in EoE.
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Affiliation(s)
- Pierfrancesco Visaggi
- Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Giulio Del Corso
- Institute of Information Science and Technologies "A. Faedo", National Research Council of Italy (CNR), Pisa, Italy
| | - Irene Solinas
- Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Filippo Ovidi
- Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Giulia Adamo
- Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Isabella Dulmin
- Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Federica Baiano Svizzero
- Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Massimo Bellini
- Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Edoardo V Savarino
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Nicola de Bortoli
- Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
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Laserna‐Mendieta EJ, Casabona‐Francés S, Amorena E, Savarino EV, Pérez‐Martínez I, Blas‐Jhon L, Guardiola‐Arévalo A, Coletta M, Pellegatta G, Guagnozzi D, Barrio J, Perello A, Betoré E, Krarup AL, Votto M, Gutiérrez‐Junquera C, Naves JE, Oliva S, Teruel Sánchez‐Vegazo C, Carrión S, de la Riva S, Espina‐Cadenas S, Fernández‐Fernández S, Llorente‐Barrio M, Pascual‐Lopez I, Masiques‐Mas ML, Honrubia‐López R, Dainese R, García‐Morales N, Cobian J, Bisso‐Zein JK, Roales V, Juan‐Juan A, Rodríguez‐Sánchez A, Feo‐Ortega S, Martín‐Domínguez V, Nantes‐Castillejo Ó, Nicolay‐Maneru J, Ghisa M, Maniero D, Suarez A, Maray I, Álvarez‐García M, Granja‐Navacerrada A, Penagini R, Racca F, Llerena‐Castro R, Santander C, Arias Á, Lucendo AJ. Sex-related differences in the presentation, management and response to treatment of eosinophilic esophagitis: Cross sectional analysis of EoE CONNECT registry. United European Gastroenterol J 2024; 12:1388-1398. [PMID: 39513462 PMCID: PMC11652331 DOI: 10.1002/ueg2.12699] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2024] [Accepted: 10/02/2024] [Indexed: 11/15/2024] Open
Abstract
BACKGROUND Eosinophilic esophagitis (EoE) predominantly affects males across all ages; however, little is known about sex differences for other aspects of EoE. OBJECTIVE To investigate associations between sex and clinical presentation, endoscopic features, treatment choice and response in EoE patients in real-world practice. METHODS Cross-sectional analysis of the multicenter EoE CONNECT registry. The independent contribution of patients' sex and other relevant variables were statistically assessed by multivariate models. RESULTS A total of 2976 patients (76% male) were evaluated. Males were diagnosed at a younger age compared to females (32.7 ± 14.8 vs. 34.8 ± 15.6 years, respectively; p = 0.002) with similar diagnostic delay. EoE symptoms varied significantly between sexes, with food impaction predominating in males and dysphagia, heartburn, regurgitation and abdominal and epigastric pain in females. However, female sex contributed to higher symptom severity at diagnosis as measured with Dysphagia Symptom Score (R2 = 0.57; p = 0.013) and presented higher peak eosinophil count in esophageal biopsies (p = 0.005). Males showed increased risk of stricturing or mixed phenotypes (adjusted OR 1.43, 95%CI:1.05-1.96; p = 0.024). No association was found between patients' sex and first-line treatment modality: proton pump inhibitors (PPI) were preferred over topical corticosteroids in patients with inflammatory phenotypes instead of stricturing or mixed phenotypes, and in patients who did not present food impaction. Both topical corticosteroids and dietary interventions were preferred over PPI in pediatric patients regardless of sex. CONCLUSIONS Sex is associated with clinical and phenotypical presentation of EoE at diagnosis, with more fibrotic findings in males but higher symptom score in females.
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Affiliation(s)
- Emilio J. Laserna‐Mendieta
- Department of GastroenterologyHospital General de TomellosoTomellosoSpain
- Instituto de Investigación Sanitaria La PrincesaMadridSpain
- Instituto de Investigación Sanitaria de Castilla‐La Mancha (IDISCAM)MadridSpain
- Centro de Investigación Biomédica en Red Enfermedades Hepáticas y DigestivasMadridSpain
| | - Sergio Casabona‐Francés
- Instituto de Investigación Sanitaria La PrincesaMadridSpain
- Department of GastroenterologyHospital Universitario de La PrincesaMadridSpain
| | - Edurne Amorena
- Department of GastroenterologyComplejo Universitario de NavarraPamplonaSpain
| | - Edoardo V. Savarino
- Surgery, Oncology and Gastroenterology, Gastroenterology UnitAzienza Ospedaliera di PadovaPadovaItaly
| | - Isabel Pérez‐Martínez
- Department of GastroenterologyHospital Universitario Central de AsturiasOviedoSpain
- Diet, Microbiota and Health GroupInstituto de Investigación Sanitaria del Principado de Asturias (ISPA)OviedoSpain
| | | | | | - Marina Coletta
- Department of GastroenterologyFondazione IRCCS Cà Granda Ospedale Maggiore PoliclinicoMilanItaly
| | - Gaia Pellegatta
- Endoscopy UnitDepartment of GastroenterologyIRCCS Humanitas Research HospitalMilanItaly
| | - Danila Guagnozzi
- Centro de Investigación Biomédica en Red Enfermedades Hepáticas y DigestivasMadridSpain
- Department of GastroenterologyHospital Universitario Vall d’HebrónBarcelonaSpain
| | - Jesús Barrio
- Department of GastroenterologyHospital Universitario Rio HortegaValladolidSpain
| | - Antonia Perello
- Department of GastroenterologyHospital Universitari Son EspasesPalma de MallorcaSpain
| | - Elena Betoré
- Department of GastroenterologyHospital Universitario Miguel ServetZaragozaSpain
| | - Anne Lund Krarup
- Department of Emergency Medicine and Trauma CenterDepartment of Gastroenterology and HepatologyAalborg University Hospital and Institute of Clinical Medicine Aalborg UniversityAalborgDenmark
| | - Martina Votto
- Pediatric UnitDepartment of Clinical, Surgical, Diagnostic and Pediatric SciencesUniversity of PaviaPaviaItaly
| | | | | | - Salvatore Oliva
- Department of Pediatric Digestive EndoscopyUniversity Hospital Umberto I & Sapienza University of RomeRomeItaly
| | | | - Silvia Carrión
- Centro de Investigación Biomédica en Red Enfermedades Hepáticas y DigestivasMadridSpain
- Department of GastroenterologyHospital de MataróMataróSpain
| | - Susana de la Riva
- Department of GastroenterologyClínica Universidad de NavarraPamplonaSpain
| | | | | | | | - Irene Pascual‐Lopez
- Department of GastroenterologyHospital Universitario Arnau de Vilanova & Hospital Universitario Santa MaríaLéridaSpain
| | | | - Raúl Honrubia‐López
- Department of GastroenterologyHospital Universitario Infanta SofíaSan Sebastián de los ReyesSpain
| | - Raffaella Dainese
- Department of GastroenterologyCentre Hospitalier d'Antibes Juan‐les‐PinsAntibesFrance
| | | | - Julyssa Cobian
- Department of GastroenterologyHospital DonostiaSan SebastiánSpain
| | | | - Valentín Roales
- Department of GastroenterologyHospital Clínico Universitario San CarlosMadridSpain
| | - Alba Juan‐Juan
- Department of GastroenterologyHospital Sant Joan Despí Moisès BroggiBarcelonaSpain
| | | | - Sara Feo‐Ortega
- Instituto de Investigación Sanitaria de Castilla‐La Mancha (IDISCAM)MadridSpain
- Department of PediatricsHospital General de TomellosoTomellosoSpain
| | - Verónica Martín‐Domínguez
- Instituto de Investigación Sanitaria La PrincesaMadridSpain
- Department of GastroenterologyHospital Universitario de La PrincesaMadridSpain
| | - Óscar Nantes‐Castillejo
- Department of GastroenterologyComplejo Universitario de NavarraPamplonaSpain
- Instituto de Investigación Sanitaria de Navarra (IdiSNA)PamplonaSpain
| | | | - Matteo Ghisa
- Surgery, Oncology and Gastroenterology, Gastroenterology UnitAzienza Ospedaliera di PadovaPadovaItaly
| | - Daria Maniero
- Surgery, Oncology and Gastroenterology, Gastroenterology UnitAzienza Ospedaliera di PadovaPadovaItaly
| | - Adolfo Suarez
- Department of GastroenterologyHospital Universitario Central de AsturiasOviedoSpain
- Diet, Microbiota and Health GroupInstituto de Investigación Sanitaria del Principado de Asturias (ISPA)OviedoSpain
| | - Iván Maray
- Diet, Microbiota and Health GroupInstituto de Investigación Sanitaria del Principado de Asturias (ISPA)OviedoSpain
- Department of PharmacyHospital Universitario Central de AsturiasOviedoSpain
| | | | | | - Roberto Penagini
- Department of GastroenterologyFondazione IRCCS Cà Granda Ospedale Maggiore PoliclinicoMilanItaly
| | - Francesca Racca
- Personalized Medicine, Asthma and Allergy ClinicIRCCS Humanitas Research HospitalRozzano ‐ MilanItaly
| | | | - Cecilio Santander
- Instituto de Investigación Sanitaria La PrincesaMadridSpain
- Centro de Investigación Biomédica en Red Enfermedades Hepáticas y DigestivasMadridSpain
- Department of GastroenterologyHospital Universitario de La PrincesaMadridSpain
| | - Ángel Arias
- Instituto de Investigación Sanitaria La PrincesaMadridSpain
- Instituto de Investigación Sanitaria de Castilla‐La Mancha (IDISCAM)MadridSpain
- Centro de Investigación Biomédica en Red Enfermedades Hepáticas y DigestivasMadridSpain
- Research Support UnitHospital General La Mancha CentroAlcázar de San JuanSpain
| | - Alfredo J. Lucendo
- Department of GastroenterologyHospital General de TomellosoTomellosoSpain
- Instituto de Investigación Sanitaria La PrincesaMadridSpain
- Instituto de Investigación Sanitaria de Castilla‐La Mancha (IDISCAM)MadridSpain
- Centro de Investigación Biomédica en Red Enfermedades Hepáticas y DigestivasMadridSpain
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10
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Molina‐Jiménez F, Ugalde‐Triviño L, Arias‐González L, Armenteros E, Relaño‐Rupérez C, Casabona S, Moreno‐Monteagudo JA, Pérez‐Fernández MT, Martín‐Domínguez V, Fernández‐Pacheco J, Laserna‐Mendieta EJ, Muñoz‐Hernández P, García‐Martínez J, Muñoz J, Lucendo AJ, Santander C, Majano P. Proton pump inhibitor effect on esophageal protein signature of eosinophilic esophagitis, prediction, and evaluation of treatment response. Allergy 2024; 79:3448-3463. [PMID: 39092539 PMCID: PMC11657045 DOI: 10.1111/all.16261] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2023] [Revised: 07/04/2024] [Accepted: 07/21/2024] [Indexed: 08/04/2024]
Abstract
BACKGROUND Recently, we have identified a dysregulated protein signature in the esophageal epithelium of eosinophilic esophagitis (EoE) patients including proteins associated with inflammation and epithelial barrier function; however, the effect of proton pump inhibitor (PPI) treatment on this signature is unknown. Herein, we used a proteomic approach to investigate: (1) whether PPI treatment alters the esophageal epithelium protein profile observed in EoE patients and (2) whether the protein signature at baseline predicts PPI response. METHODS We evaluated the protein signature of esophageal biopsies using a cohort of adult EoE (n = 25) patients and healthy controls (C) (n = 10). In EoE patients, esophageal biopsies were taken before (pre) and after (post) an 8-week PPI treatment, determining the histologic response. Eosinophil count PostPPI was used to classify the patients: ≥15 eosinophils/hpf as non-responders (non-responder) and < 15 eosinophils/hpf as responders (R). Protein signature was determined and differentially accumulated proteins were characterized to identify altered biological processes and signaling pathways. RESULTS Comparative analysis of differentially accumulated proteins between groups revealed common signatures between three groups of patients with inflammation (responder-PrePPI, non-responder-PrePPI, and non-responder-PostPPI) and without inflammation (controls and responder-PostPPI). PPI therapy almost reversed the EoE specific esophageal protein signature, which is enriched in pathways associated with inflammation and epithelial barrier function, in responder-PostPPI. Furthermore, we identified a set of candidate proteins to differentiate responder-PrePPI and non-responder-PrePPI EoE patients before treatment. CONCLUSION These findings provide evidence that PPI therapy reverses the alterations in esophageal inflammatory and epithelial proteins characterizing EoE, thereby providing new insights into the mechanism of PPI clinical response. Interestingly, our results also suggest that PPI response could be predicted at baseline in EoE.
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Affiliation(s)
- Francisca Molina‐Jiménez
- Molecular Biology UnitHospital Universitario de la PrincesaMadridSpain
- Instituto de Investigación Sanitaria Hospital Universitario de La Princesa (IIS‐IP)MadridSpain
| | - Lola Ugalde‐Triviño
- Molecular Biology UnitHospital Universitario de la PrincesaMadridSpain
- Instituto de Investigación Sanitaria Hospital Universitario de La Princesa (IIS‐IP)MadridSpain
| | - Laura Arias‐González
- Instituto de Investigación Sanitaria Hospital Universitario de La Princesa (IIS‐IP)MadridSpain
- Department of Gastroenterology, Hospital General de TomellosoCiudad RealSpain
- Instituto de Investigación Sanitaria de Castilla‐La Mancha (IDISCAM)Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd)MadridSpain
| | - Elisa Armenteros
- Molecular Biology UnitHospital Universitario de la PrincesaMadridSpain
- Instituto de Investigación Sanitaria Hospital Universitario de La Princesa (IIS‐IP)MadridSpain
| | - Carlos Relaño‐Rupérez
- Molecular Biology UnitHospital Universitario de la PrincesaMadridSpain
- Instituto de Investigación Sanitaria Hospital Universitario de La Princesa (IIS‐IP)MadridSpain
- Department of GastroenterologyHospital Universitario de La PrincesaMadridSpain
| | - Sergio Casabona
- Instituto de Investigación Sanitaria Hospital Universitario de La Princesa (IIS‐IP)MadridSpain
- Department of GastroenterologyHospital Universitario de La PrincesaMadridSpain
| | - José Andrés Moreno‐Monteagudo
- Instituto de Investigación Sanitaria Hospital Universitario de La Princesa (IIS‐IP)MadridSpain
- Department of GastroenterologyHospital Universitario de La PrincesaMadridSpain
| | - María Teresa Pérez‐Fernández
- Instituto de Investigación Sanitaria Hospital Universitario de La Princesa (IIS‐IP)MadridSpain
- Department of GastroenterologyHospital Universitario de La PrincesaMadridSpain
| | - Verónica Martín‐Domínguez
- Instituto de Investigación Sanitaria Hospital Universitario de La Princesa (IIS‐IP)MadridSpain
- Department of GastroenterologyHospital Universitario de La PrincesaMadridSpain
| | - Jennifer Fernández‐Pacheco
- Instituto de Investigación Sanitaria Hospital Universitario de La Princesa (IIS‐IP)MadridSpain
- Department of GastroenterologyHospital Universitario de La PrincesaMadridSpain
| | - Emilio José Laserna‐Mendieta
- Instituto de Investigación Sanitaria Hospital Universitario de La Princesa (IIS‐IP)MadridSpain
- Department of Gastroenterology, Hospital General de TomellosoCiudad RealSpain
- Clinical LaboratoryHospital Universitario de La PrincesaMadridSpain
| | | | - Jorge García‐Martínez
- Instituto de Investigación Sanitaria Hospital Universitario de La Princesa (IIS‐IP)MadridSpain
- Department of Pediatric Hematology and OncologyHospital Infantil Universitario Niño JesúsMadridSpain
| | - Javier Muñoz
- Cell Signalling and Clinical Proteomics GroupBiocruces Bizkaia Health Research InstituteBarakaldoSpain
- Ikerbasque, Basque Foundation for ScienceBilbaoSpain
| | - Alfredo J. Lucendo
- Instituto de Investigación Sanitaria Hospital Universitario de La Princesa (IIS‐IP)MadridSpain
- Department of Gastroenterology, Hospital General de TomellosoCiudad RealSpain
- Instituto de Investigación Sanitaria de Castilla‐La Mancha (IDISCAM)Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd)MadridSpain
| | - Cecilio Santander
- Instituto de Investigación Sanitaria Hospital Universitario de La Princesa (IIS‐IP)MadridSpain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd)MadridSpain
- Department of GastroenterologyHospital Universitario de La PrincesaMadridSpain
| | - Pedro Majano
- Molecular Biology UnitHospital Universitario de la PrincesaMadridSpain
- Instituto de Investigación Sanitaria Hospital Universitario de La Princesa (IIS‐IP)MadridSpain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd)MadridSpain
- Department of Cellular Biology, Faculty of BiologyUniversidad Complutense de MadridMadridSpain
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11
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Sawada A, Ihara Y, Imai T, Tanaka F, Fujiwara Y. Real world treatment patterns in patients with eosinophilic esophagitis in Japan. Sci Rep 2024; 14:27490. [PMID: 39528636 PMCID: PMC11555047 DOI: 10.1038/s41598-024-78868-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2024] [Accepted: 11/04/2024] [Indexed: 11/16/2024] Open
Abstract
The management of eosinophilic esophagitis (EoE) has not been completely established yet. There is a controversy over the universal maintenance therapy for EoE to prevent esophageal fibrostenotic complications. Using an employer-based insurance claim database from January 2005 to September 2022, we investigated the treatment patterns of EoE and the occurrence of esophageal complications. The treatment patterns were analyzed at a 6-month interval from the diagnosis of EoE. The time to treatment discontinuation of proton pump inhibitor (PPI)/potassium-competitive acid blocker (P-CAB) was evaluated by the Kaplan-Meier method. Of 15,200,895 individuals, 615 patients with EoE were ultimately analyzed with the median follow-up time from the index date of 700 days. PPI/P-CAB and swallowed topical steroids accounted for 80% and 4.6% of the initial therapy, respectively. PPI/P-CAB use rapidly decreased by 40% in the first 6 months and afterwards reinitiation was rarely seen. The median time to treatment discontinuation were 172 days (95% CI 147-206 days) for PPI/P-CAB. Only 1 EoE patient developed esophageal fibrostenotic complications after the diagnosis. With the low incidence of esophageal complications, the universal maintenance therapy may not be necessary for mild EoE patients often seen in Japan.
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Affiliation(s)
- Akinari Sawada
- Department of Gastroenterology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan.
| | - Yasutaka Ihara
- Department of Medical Statistics, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Takumi Imai
- Department of Medical Statistics, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Fumio Tanaka
- Department of Gastroenterology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Yasuhiro Fujiwara
- Department of Gastroenterology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
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Alexander R, Kassmeyer B, Lennon R, Alexander J, Snyder D, Ravi K. EoE Recurrence on PPI Maintenance Therapy: You Do Not Know if You Do Not Look! Dig Dis Sci 2024; 69:4048-4052. [PMID: 39407083 DOI: 10.1007/s10620-024-08676-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Accepted: 09/28/2024] [Indexed: 11/16/2024]
Abstract
BACKGROUND AND AIMS Data regarding histologic recurrence of EoE on PPI maintenance therapy are lacking. METHODS Retrospective review of 101 patients with histologic PPI-responsive EoE. RESULTS 52/101 (51%) patients underwent follow-up EGD with biopsies. Of the 52 patients, 29 (56%) maintained histologic remission and 23 (44%) had histologic recurrence. 21 (40%) patients maintained BID PPI, 20 (39%) tapered to QD, and 11 (21%) had discontinued PPI. Of the 21 patients on BID PPI, 7 (33%) had histologic recurrence, of which 6 (86%) were asymptomatic. CONCLUSIONS Patients on PPI therapy for EoE benefit from serial clinical, endoscopic, and histologic surveillance.
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Affiliation(s)
- Ryan Alexander
- Department of Internal Medicine, Mayo Clinic Rochester, Rochester, USA.
- Community Internal Medicine, Baldwin Building, 221 Fourth Ave SW, Rochester, MN, 55905, USA.
| | - Blake Kassmeyer
- Department of Quantitative Health Sciences, Mayo Clinic Rochester, Rochester, USA
| | - Ryan Lennon
- Department of Quantitative Health Sciences, Mayo Clinic Rochester, Rochester, USA
| | - Jeffrey Alexander
- Department of Gastroenterology and Hepatology, Mayo Clinic Rochester, Rochester, USA
| | - Diana Snyder
- Department of Gastroenterology and Hepatology, Mayo Clinic Rochester, Rochester, USA
| | - Karthik Ravi
- Department of Gastroenterology and Hepatology, Mayo Clinic Rochester, Rochester, USA
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Keske Ş, Güdücüoğlu H, Ergönül Ö. The Mpox 2024 Outbreak: The Main Challenges. Balkan Med J 2024; 41:416-418. [PMID: 39484798 PMCID: PMC11589207 DOI: 10.4274/balkanmedj.galenos.2024.2024-240924] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2024] Open
Affiliation(s)
- Şiran Keske
- Department of Infectious Diseases and Clinical Microbiology, Koç University School of Medicine, İstanbul, Türkiye
- Koc University İşbank Center for Infectious Diseases (KUISCID), İstanbul, Türkiye
| | - Hüseyin Güdücüoğlu
- Department of Medical Microbiology, Trakya University Faculty of Medicine, Edirne, Türkiye
| | - Önder Ergönül
- Department of Infectious Diseases and Clinical Microbiology, Koç University School of Medicine, İstanbul, Türkiye
- Koc University İşbank Center for Infectious Diseases (KUISCID), İstanbul, Türkiye
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Frandsen LT, Melgaard D, Hansen SK, Mørk K, Krarup AL. Effectiveness of treatment with budesonide orodispersible tablets in 76 patients with eosinophilic oesophagitis - real-life experience from the population-based DanEoE cohort. Scand J Gastroenterol 2024; 59:1137-1143. [PMID: 39267404 DOI: 10.1080/00365521.2024.2395865] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Revised: 08/02/2024] [Accepted: 08/10/2024] [Indexed: 09/17/2024]
Abstract
BACKGROUND Eosinophilic oesophagitis (EoE) is a chronic immune-mediated disease. In Denmark, the budesonide orodispersible tablet (BOT) is recommended as a second-line treatment for proton pump inhibitor-refractory EoE patients. AIMS To evaluate the effectiveness of treatment with BOT in adult EoE patients in a population-based setting in Denmark. METHODS This was a retrospective, registry-based, DanEoE cohort study of all 76 adult EoE patients treated with BOT and diagnosed between 2007 and 2021 in the North Denmark Region. After medical record revision, the EoE diagnosis was defined according to the AGREE consensus. Symptomatic response was based on the information found in the patients' medical reports and histologic remission was defined as <15 eosinophils per high-power field (eos/hpf). RESULTS Histologic remission was achieved in 89% of the patients treated with BOT who underwent histologic evaluation. Clinicohistologic remission was achieved in 71% of the patients who underwent both symptomatic and histologic evaluation. Despite histologic remission, 18% of patients still experienced symptoms. Non-responders were found in 7% of the patients. Complications were rare, with dilation of strictures performed in 7% and food bolus obstruction (FBO) occurring in 3%. Discontinuation of the treatment due to unacceptable side effects was observed in 11% of the treated patients. CONCLUSIONS Treatment with BOT effectively induced histologic remission in most of the EoE patients. Despite achieving histologic remission, approximately 1/5 of the patients were still symptomatic. Complications were rare. In non-responders and those with unacceptable side effects, alternative treatment options such as biologic agents might be needed.
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Affiliation(s)
- Line Tegtmeier Frandsen
- Department of Gastroenterology, North Denmark Regional Hospital, Hjørring, Denmark
- Department of Emergency Medicine and Trauma Center, Aalborg University Hospital, Aalborg, Denmark
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Dorte Melgaard
- Department of Emergency Medicine and Trauma Center, Aalborg University Hospital, Aalborg, Denmark
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Stine Kjærsgaard Hansen
- Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark
| | - Kasper Mørk
- Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark
| | - Anne Lund Krarup
- Department of Emergency Medicine and Trauma Center, Aalborg University Hospital, Aalborg, Denmark
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
- Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark
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15
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S2k guideline Gastroesophageal reflux disease and eosinophilic esophagitis of the German Society of Gastroenterology, Digestive and Metabolic Diseases (DGVS). ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:1786-1852. [PMID: 39389106 DOI: 10.1055/a-2344-6282] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/12/2024]
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16
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Fortunato A, Antonini D, Savarino EV, Racca F, Penagini R, Fanelli F, Saab JP, Cipriani F, Giodice R, Rumi F, Cicchetti A. A cost-of-illness study of eosinophilic esophagitis in Italy: assessing direct and indirect costs. FRONTIERS IN GASTROENTEROLOGY 2024; 3. [DOI: 10.3389/fgstr.2024.1414251] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
Abstract
BackgroundEosinophilic esophagitis (EoE) is a chronic and progressive type 2 inflammatory disease affecting the esophagus. Its prevalence has increased in recent years due to increased awareness, evolving clinical guidelines, and heightened sensitivity among healthcare professionals managing the condition. The exact causes behind EoE’s development remain unknown, and its clinical presentation varies, often leading to significant diagnostic delays depending on the age at which symptoms manifest. Consequently, achieving long-term disease control through heightened awareness becomes imperative. EoE generates a significant clinical burden, resulting in substantial economic consequences for patients, healthcare systems, and society. This study aimed to assess the economic and social impacts on EoE patients within the Italian context.MethodsA cost-of-illness analysis was conducted from two perspectives: the National Health System (NHS) and the societal perspective. This analysis encompassed direct healthcare, indirect healthcare, and non-healthcare costs. Data were collected and assessed through a survey administered to a panel of expert clinicians and EoE-affected patients.ResultsManaging EoE incurs a significant burden on healthcare systems, amounting to €6,852.28 per patient per year. The primary cost component appears to be direct costs, comprising 60.73% of the total cost per patient for this condition, while indirect costs contribute to 29.68% of the overall management expenses.ConclusionThis analysis underscores a substantial financial burden on both the healthcare system and patients affected by eosinophilic esophagitis. It emphasizes the imperative need for a continuous and combined effort from clinicians, patients, and families to promptly recognize symptoms and adaptive behavior to mitigate diagnostic delays.
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17
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Schlager H, Baumann-Durchschein F, Steidl K, Häfner M, Dinkhauser P, Weitersberger M, Holzinger J, Mader M, Gröchenig HP, Madl C, Schreiner P. Diagnosis and management of eosinophilic esophagitis and esophageal food impaction in adults : A position paper issued by the Austrian Society of Gastroenterology and Hepatology (ÖGGH). Wien Klin Wochenschr 2024; 136:479-499. [PMID: 39230674 PMCID: PMC11387459 DOI: 10.1007/s00508-024-02401-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2024] [Accepted: 06/21/2024] [Indexed: 09/05/2024]
Abstract
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.
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Affiliation(s)
- Hansjörg Schlager
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, University Hospital Graz, Auenbruggerplatz 15, 8036, Graz, Austria.
| | - Franziska Baumann-Durchschein
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, University Hospital Graz, Auenbruggerplatz 15, 8036, Graz, Austria
| | - Karin Steidl
- Department of Internal Medicine, Barmherzige Brüder St. Veit/Glan, St. Veit, Austria
| | - Michael Häfner
- 2nd Medical Department, Barmherzige Schwestern Krankenhaus, Vienna, Austria
| | - Patrick Dinkhauser
- Department of Internal Medicine I, Division of Gastroenterology and Hepatology, Endocrinology and Rheumatology, Klinikum Wels-Grieskirchen, Wels, Austria
| | - Michael Weitersberger
- Department of Gastroenterology and Hepatology, Ordensklinikum Linz Barmherzige Schwestern, Linz, Austria
| | - Josef Holzinger
- Department of Surgery, Paracelsus Medical University/Salzburger Landeskliniken (SALK), Salzburg, Austria
| | - Markus Mader
- Department of Internal Medicine II, Universitätsklinikum St. Pölten-Karl Landsteiner Privatuniversität, St. Pölten, Austria
| | - Hans Peter Gröchenig
- Department of Internal Medicine, Barmherzige Brüder St. Veit/Glan, St. Veit, Austria
| | - Christian Madl
- Division of Gastroenterology and Hepatology, Krankenanstalt Rudolfstiftung, Krankenanstaltenverbund Wien (KAV), Vienna, Austria
| | - Philipp Schreiner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
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Amil-Dias J, Oliva S, Papadopoulou A, Thomson M, Gutiérrez-Junquera C, Kalach N, Orel R, Auth MKH, Nijenhuis-Hendriks D, Strisciuglio C, Bauraind O, Chong S, Ortega GD, Férnandez SF, Furman M, Garcia-Puig R, Gottrand F, Homan M, Huysentruyt K, Kostovski A, Otte S, Rea F, Roma E, Romano C, Tzivinikos C, Urbonas V, Velde SV, Zangen T, Zevit N. Diagnosis and management of eosinophilic esophagitis in children: An update from the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN). J Pediatr Gastroenterol Nutr 2024; 79:394-437. [PMID: 38923067 DOI: 10.1002/jpn3.12188] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Revised: 08/17/2023] [Accepted: 09/04/2023] [Indexed: 06/28/2024]
Abstract
INTRODUCTION Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus characterized by symptoms of esophageal dysfunction and histologically by predominantly eosinophilic infiltration of the squamous epithelium. European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) published a guideline in 2014; however, the rapid evolution of knowledge about pathophysiology, diagnostic criteria, and therapeutic options have made an update necessary. METHODS A consensus group of pediatric gastroenterologists from the ESPGHAN Working Group on Eosinophilic Gastrointestinal Diseases (ESPGHAN EGID WG) reviewed the recent literature and proposed statements and recommendations on 28 relevant questions about EoE. A comprehensive electronic literature search was performed in MEDLINE, EMBASE, and Cochrane databases from 2014 to 2022. The Grading of Recommendations Assessment, Development and Evaluation system was used to assess the quality of evidence and formulate recommendations. RESULTS A total of 52 statements based on the available evidence and 44 consensus-based recommendations are available. A revision of the diagnostic protocol, options for initial drug treatment, and the new concept of simplified empiric elimination diets are now available. Biologics are becoming a part of the potential armamentarium for refractory EoE, and systemic steroids may be considered as the initial treatment for esophageal strictures before esophageal dilation. The importance and assessment of quality of life and a planned transition to adult medical care are new areas addressed in this guideline. CONCLUSION Research in recent years has led to a better understanding of childhood EoE. This guideline incorporates the new findings and provides a practical guide for clinicians treating children diagnosed with EoE.
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Affiliation(s)
- Jorge Amil-Dias
- Pediatric Gastroenterology, Hospital Lusíadas, Porto, Portugal
| | - Salvatore Oliva
- Maternal and Child Health Department, University Hospital - Umberto I, Sapienza - University of Rome, Rome, Italy
| | - Alexandra Papadopoulou
- Division of Gastroenterology and Hepatology, First Department of Pediatrics, Children's hospital Agia Sofia, University of Athens, Athens, Greece
| | - Mike Thomson
- Centre for Paediatric Gastroenterology, International Academy for Paediatric Endoscopy Training, Sheffield Children's Hospital, UK
| | - Carolina Gutiérrez-Junquera
- Pediatric Gastroenterology Unit, Hospital Universitario Puerta de Hierro Majadahonda, Universidad Autónoma de Madrid, Spain
| | - Nicolas Kalach
- Department of Pediatrics, Saint Vincent de Paul Hospital, Groupement des Hôpitaux de l'Institut Catholique de Lille (GHICL), Catholic University, Lille, France
| | - Rok Orel
- Department of Gastroenterology, Hepatology, and Nutrition, University Children's Hospital, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | | | | | - Caterina Strisciuglio
- Department of Woman, Child and General and Specialized Surgery of the University of Campania "Luigi Vanvitelli", Naples, Italy
| | | | - Sonny Chong
- Epsom and St Helier University Hospitals NHS Trust, UK
| | - Gloria Dominguez Ortega
- Pediatric Gastroenterology and Nutrition Department, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
| | - Sonia Férnandez Férnandez
- Pediatric Gastroenterology Unit, Department of Pediatrics, Severo Ochoa University Hospital, Madrid, Spain
| | - Mark Furman
- Royal Free London NHS Foundation Trust, London, UK
| | - Roger Garcia-Puig
- Pediatric Gastroenterology, Hepatology and Nutrition Unit, Pediatrics Department, Hospital Universitari MútuaTerrassa, Universitat de Barcelona, Barcelona, Spain
| | | | - Matjaz Homan
- Department of Gastroenterology, Hepatology, and Nutrition, University Children's Hospital, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Koen Huysentruyt
- Kindergastro-enterologie, hepatologie en nutritie, Brussels Centre for Intestinal Rehabilitation in Children (BCIRC), Belgium
| | - Aco Kostovski
- University Children's Hospital Skopje, Faculty of Medicine, University Ss Cyril and Methodius, Skopje, Republic of North Macedonia
| | - Sebastian Otte
- Childrens' Hospital, Helios Mariahilf Hospital, Hamburg, Germany
| | - Francesca Rea
- Endoscopy and Surgey Unit, Bambino Gesu Children's Hospital, Rome, Italy
| | - Eleftheria Roma
- First Department of Pediatrics, University of Athens and Pediatric Gastroenterology Unit Mitera Children's Hospital, Athens, Greece
| | - Claudio Romano
- Department of Human Pathology in Adulthood and Childhood "G. Barresi", University of Messina, Messina, Italy
| | - Christos Tzivinikos
- Paediatric Gastroenterology Department, Al Jalila Children's Specialty Hospital, Dubai, UAE
- Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, UAE
| | - Vaidotas Urbonas
- Vilnius University Medical Faculty Clinic of Children's Diseases, Vilnius, Lithuania
| | | | - Tsili Zangen
- Pediatric Gastroenterology Unit, Wolfson Medical Center, Holon, Israel
| | - Noam Zevit
- Eosinophilic Gastrointestinal Disease Clinic, Institute of Gastroenterology, Hepatology, and Nutrition, Schneider Children's Medical Center of Israel, Israel
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19
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Navarro P, Feo-Ortega S, Casabona-Francés S, Gutiérrez-Junquera C, Savarino EV, Amorena E, Fernández-Fernández S, Pérez-Martínez I, Oliva S, Barrio J, Masiques-Mas ML, Guardiola-Arévalo A, Guagnozzi D, Racca F, Betoré E, Votto M, Rodríguez-Sánchez A, Barrio ML, Blas-Jhon L, Sánchez-Vegazo CT, García-Morales N, Krarup AL, Dainese R, Martín-Dominguez V, García-Díaz A, Maniero D, Santander C, Arias Á, Laserna-Mendieta EJ, Lucendo AJ. Determinant factors for first-line treatment choice and effectiveness in pediatric eosinophilic esophagitis: an analysis of the EUREOS EoE CONNECT registry. Eur J Pediatr 2024; 183:3567-3578. [PMID: 38819501 PMCID: PMC11263422 DOI: 10.1007/s00431-024-05618-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2024] [Revised: 05/03/2024] [Accepted: 05/17/2024] [Indexed: 06/01/2024]
Abstract
This study compared short-term effectiveness of proton pump inhibitors (PPI), swallowed topical corticosteroids (STC), and dietary therapies in reversing clinical and histological features in pediatric patients with eosinophilic esophagitits (EoE). Determinants for treatment choice and PPI therapy effectiveness were also assessed. A cross-sectional study analysis of patients under 18 years old recruited onto the multicenter EoE CONNECT registry was performed. Clinico-histological response was defined as symptomatic improvement plus a peak eosinophil count below 15 per high-power field after treatment. Effectiveness of first-line options used in monotherapy was compared. Overall, 393 patients (64% adolescents) receiving PPI, STC, or dietary monotherapy to induce EoE remission were identified. PPI was the preferred option (71.5%), despite STC providing the highest clinico-histological response rates (66%) compared to PPI (44%) and diet (42%). Logistic regression identified fibrotic features and recruitment at Italian sites independently associated to first-line STC treatment; age under 12 associated to dietary therapy over other options. Analysis of 262 patients in whom PPI effectiveness was evaluated after median (IQR) 96 (70-145) days showed that this effectiveness was significantly associated with management at pediatric facilities and use of high PPI doses. Among PPI responders, decrease in rings and structures in endoscopy from baseline was documented, with EREFS fibrotic subscore for rings also decreasing among responders (0.27 ± 0.63 vs. 0.05 ± 0.22, p < 0.001). Conclusion: Initial therapy choice for EoE depends on endoscopic phenotype, patient's age, and patients' origin. High PPI doses and treatment in pediatric facilities significantly determined effectiveness, and reversed fibrotic endoscopic features among responders. What is Known: • Proton pump inhibitors are widely used to induce and maintain remission in EoE in real practice, despite other first-line alternative therapies possibly providing higher effectiveness. What is New: • Proton pump inhibitors represent up to two-thirds of first-line monotherapies used to induce EoE remission in pediatric and adolescent patients with EoE. The choice of STC as first-line treatment for EoE was significantly associated with fibrotic features at baseline endoscopy and recruitment in Italian centers; age less than 12 years was associated with dietary therapy. • PPI effectiveness was found to be determined by use of high doses, attendance at pediatric facilities, presenting inflammatory instead of fibrotic or mixed phenotypes, and younger age. Among responders, PPI therapy reversed both inflammatory and fibrotic features of EoE after short-term treatment.
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Affiliation(s)
- Pilar Navarro
- Department of Gastroenterology, Hospital General de Tomelloso, Vereda de Socuéllamos s/n, 13700, Tomelloso, Spain
- Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), Toledo, Spain
- Instituto de Investigación Sanitaria La Princesa, Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, CIBERehd, Madrid, Spain
| | - Sara Feo-Ortega
- Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), Toledo, Spain
- Department of Pediatrics, Hospital General de Tomelloso, Tomelloso, Spain
| | - Sergio Casabona-Francés
- Instituto de Investigación Sanitaria La Princesa, Madrid, Spain
- Department of Gastroenterology, Hospital Universitario de La Princesa, Madrid, Spain
| | - Carolina Gutiérrez-Junquera
- Pediatric Gastroenterology Unit, Hospital Universitario Puerta de Hierro, Majadahonda, Spain
- Universidad Autónoma de Madrid, Madrid, Spain
| | - Edoardo V Savarino
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
- Gastroenterology Unit, Azienza Ospedaliera di Padova, Padua, Italy
| | - Edurne Amorena
- Department of Gastroenterology, Hospital Universitario de Navarra, Pamplona, Spain
| | | | - Isabel Pérez-Martínez
- Department of Gastroenterology, Hospital Universitario Central de Asturias, Oviedo, Spain
- Diet, Microbiota and Health Group, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain
| | - Salvatore Oliva
- Pediatric Gastroenterology and Liver Unit, Maternal and Child Health Department, Sapienza-University of Rome, Rome, Italy
| | - Jesús Barrio
- Department of Gastroenterology, Hospital Universitario Rio Hortega, Valladolid, Spain
| | | | | | - Danila Guagnozzi
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, CIBERehd, Madrid, Spain
- Department of Gastroenterology, Hospital Universitario Vall d'Hebrón, Barcelona, Spain
| | - Francesca Racca
- Personalized Medicine, Asthma and Allergy Clinic, IRCCS Humanitas Research Hospital, Rozzano - Milan, Italy
| | - Elena Betoré
- Department of Gastroenterology, Hospital Universitario Miguel Servet, Zaragoza, Spain
| | - Martina Votto
- Pediatric Unit, Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia; and Pediatric Clinic, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | | | | | | | | | | | - Anne Lund Krarup
- Department of Emergency Medicine and Trauma Center, Aalborg University Hospital, Aalborg, Denmark
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Raffaella Dainese
- Department of Gastroenterology, Centre Hospitalier d'Antibes Juan-les Pins, Antibes, France
| | - Verónica Martín-Dominguez
- Instituto de Investigación Sanitaria La Princesa, Madrid, Spain
- Department of Gastroenterology, Hospital Universitario de La Princesa, Madrid, Spain
| | - Alejandro García-Díaz
- Pediatric Gastroenterology Unit, Hospital Universitario Puerta de Hierro, Majadahonda, Spain
| | - Daria Maniero
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Cecilio Santander
- Instituto de Investigación Sanitaria La Princesa, Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, CIBERehd, Madrid, Spain
- Department of Gastroenterology, Hospital Universitario de La Princesa, Madrid, Spain
- Department of Medicine, Universidad Autónoma de Madrid, Madrid, Spain
| | - Ángel Arias
- Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), Toledo, Spain
- Instituto de Investigación Sanitaria La Princesa, Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, CIBERehd, Madrid, Spain
- Research Unit, Hospital General Mancha-Centro, Alcázar de San Juan, Spain
| | - Emilio J Laserna-Mendieta
- Department of Gastroenterology, Hospital General de Tomelloso, Vereda de Socuéllamos s/n, 13700, Tomelloso, Spain
- Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), Toledo, Spain
- Instituto de Investigación Sanitaria La Princesa, Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, CIBERehd, Madrid, Spain
| | - Alfredo J Lucendo
- Department of Gastroenterology, Hospital General de Tomelloso, Vereda de Socuéllamos s/n, 13700, Tomelloso, Spain.
- Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), Toledo, Spain.
- Instituto de Investigación Sanitaria La Princesa, Madrid, Spain.
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, CIBERehd, Madrid, Spain.
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Visaggi P, Ghisa M, Vespa E, Barchi A, Mari A, Pasta A, Marabotto E, de Bortoli N, Savarino EV. Optimal Assessment, Treatment, and Monitoring of Adults with Eosinophilic Esophagitis: Strategies to Improve Outcomes. Immunotargets Ther 2024; 13:367-383. [PMID: 39071859 PMCID: PMC11283784 DOI: 10.2147/itt.s276869] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2024] [Accepted: 07/20/2024] [Indexed: 07/30/2024] Open
Abstract
Eosinophilic esophagitis (EoE) is a chronic type 2 inflammation-mediated disease characterized by an eosinophil-predominant inflammation of the esophagus and symptoms of esophageal dysfunction. Relevant treatment outcomes in the setting of EoE include the improvement of histology, symptoms, and endoscopy findings, quality of life (QoL), and the psychological burden of the disease. Established validated tools for the assessment of EoE include questionnaires on dysphagia and QoL (ie, DSQ, EEsAI, and EoE-IQ). More recently, esophageal symptom-specific anxiety and hypervigilance, assessed using the esophageal hypervigilance and anxiety scale (EHAS), have emerged as contributors to disease burden, confirming the importance of psychological aspects in EoE patients. The EoE endoscopic reference score (EREFS) is the only validated endoscopy score in EoE and can quantify mucosal disease burden. However, esophageal panometry using the functional lumen imaging probe (FLIP) and high-resolution manometry (HRM) have shown potential to optimize the assessment of fibrostenotic features of EoE, providing novel insights into the pathophysiology of symptoms. There is a growing number of licenced and off-label therapeutic options in EoE, with various randomized controlled trials demonstrating the efficacy of proton pump inhibitors, topical steroids, food elimination diets, biological drugs, and esophageal dilatation. However, standardized optimal management strategies of EoE are currently lacking. In this review, we provide an overview of established and novel assessment tools in EoE including patient reported outcomes, FLIP panometry, HRM, endoscopy, and histology outcome measures to improve the outcomes of EoE patients. In addition, we summarize available therapeutic options for EoE based on the most recent evidence.
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Affiliation(s)
- Pierfrancesco Visaggi
- Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Matteo Ghisa
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Edoardo Vespa
- Gastroenterology and Digestive Endoscopy, IRCCS Ospedale San Raffaele, Milan, 20132, Italy
| | - Alberto Barchi
- Gastroenterology and Digestive Endoscopy, IRCCS Ospedale San Raffaele, Milan, 20132, Italy
| | - Amir Mari
- Gastroenterology Unit, Nazareth Hospital EMMS, Azrieli Faculty of Medicine, Bar Ilan University, Ramat Gan, Israel
| | - Andrea Pasta
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Elisa Marabotto
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
- IRCCS Policlinico San Martino, Genoa, Italy
| | - Nicola de Bortoli
- Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Edoardo Vincenzo Savarino
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
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21
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de Bortoli N, Visaggi P, Penagini R, Annibale B, Baiano Svizzero F, Barbara G, Bartolo O, Battaglia E, Di Sabatino A, De Angelis P, Docimo L, Frazzoni M, Furnari M, Iori A, Iovino P, Lenti MV, Marabotto E, Marasco G, Mauro A, Oliva S, Pellegatta G, Pesce M, Privitera AC, Puxeddu I, Racca F, Ribolsi M, Ridolo E, Russo S, Sarnelli G, Tolone S, Zentilin P, Zingone F, Barberio B, Ghisa M, Savarino EV. The 1st EoETALY Consensus on the Diagnosis and Management of Eosinophilic Esophagitis-Current Treatment and Monitoring. Dig Liver Dis 2024; 56:1173-1184. [PMID: 38521670 DOI: 10.1016/j.dld.2024.02.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2024] [Revised: 02/11/2024] [Accepted: 02/28/2024] [Indexed: 03/25/2024]
Abstract
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.
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Affiliation(s)
- Nicola de Bortoli
- Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Pierfrancesco Visaggi
- Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Roberto Penagini
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Bruno Annibale
- Department of Medical-Surgical Sciences and Translational Medicine, Sant'Andrea Hospital, Sapienza University of Rome, 00189, Rome, Italy
| | - Federica Baiano Svizzero
- Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Giovanni Barbara
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy; IRCCS Azienda Ospedaliero Universitaria di Bologna, Bologna, Italy
| | | | - Edda Battaglia
- Gastroenterology Unit ASLTO4, Chivasso - Ciriè - Ivrea, Italy
| | - Antonio Di Sabatino
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, 27100, Pavia, Italy; First Department of Internal Medicine, IRCCS San Matteo Hospital Foundation, 27100, Pavia, Italy
| | - Paola De Angelis
- Digestive Endoscopy Unit - Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Ludovico Docimo
- Department of Advanced Medical and Surgical Sciences, University of Campania "L. Vanvitelli", Naples, Italy
| | - Marzio Frazzoni
- Digestive Pathophysiology Unit and Digestive Endoscopy Unit, Azienda Ospedaliero Universitaria di Modena, Ospedale Civile di Baggiovara, Modena, Italy
| | - Manuele Furnari
- Division of Gastroenterology, Department of Internal Medicine, University of Genoa,Genoa,Italy, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Andrea Iori
- Gastroenterology and Digestive Endoscopy Unit, 'Santa Chiara' Hospital, Trento, Italy
| | - Paola Iovino
- Gastrointestinal Unit, Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, 84084, Baronissi, Italy
| | - Marco Vincenzo Lenti
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, 27100, Pavia, Italy
| | - Elisa Marabotto
- Division of Gastroenterology, Department of Internal Medicine, University of Genoa,Genoa,Italy, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Giovanni Marasco
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy; IRCCS Azienda Ospedaliero Universitaria di Bologna, Bologna, Italy
| | - Aurelio Mauro
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Policlinico San Matteo, 27100, Pavia, Italy
| | - Salvatore Oliva
- Maternal and Child Health Department, Pediatric Gastroenterology and Liver Unit, Sapienza - University of Rome, Italy
| | - Gaia Pellegatta
- Endoscopic Unit, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Milan, Italy; Humanitas University, Department of Biomedical Sciences, Via Rita Levi Montalcini 4, 20090, Pieve Emanuele, Milan, Italy
| | - Marcella Pesce
- Department of clinical medicine and surgery, University of Naples Federico II, Naples, Italy
| | | | - Ilaria Puxeddu
- Immunoallergology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Italy
| | - Francesca Racca
- Personalized Medicine, Asthma and Allergy Clinic, IRCCS Humanitas Research Hospital, Rozzano - Milan, Italy
| | - Mentore Ribolsi
- Unit of Gastroenterology and Digestive Endoscopy, Campus Bio Medico University, Rome, Italy
| | - Erminia Ridolo
- Allergy Unit, Department of Internal Medicine, University Hospital of Parma, Parma, Italy
| | - Salvatore Russo
- Gastroenterology and Digestive Endoscopy Unit, Azienda Ospedaliera Universitaria of Modena, Modena, Italy
| | - Giovanni Sarnelli
- Department of clinical medicine and surgery, University of Naples Federico II, Naples, Italy
| | - Salvatore Tolone
- Division of General, Oncological, Mini-Invasive and Obesity Surgery, University of Campania "Luigi Vanvitelli", 80131, Naples, Italy
| | - Patrizia Zentilin
- Division of Gastroenterology, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Fabiana Zingone
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Brigida Barberio
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Matteo Ghisa
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Edoardo Vincenzo Savarino
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy.
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Quinn LA, Burger C, Nguyen B, Arnold MA, Pan Z, Furuta GT, Bauer ME, Menard-Katcher C. Natural Histories and Disease Complications in a Cohort of 151 Children With Gastric or Duodenal Eosinophilia. Am J Gastroenterol 2024; 119:1298-1308. [PMID: 38174865 PMCID: PMC11222049 DOI: 10.14309/ajg.0000000000002644] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Accepted: 12/20/2023] [Indexed: 01/05/2024]
Abstract
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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Affiliation(s)
- Laura A Quinn
- Digestive Health Institute, Children's Hospital Colorado, Gastrointestinal Eosinophilic Diseases Program, Section of Pediatric Gastroenterology, Hepatology and Nutrition, University of Colorado School of Medicine, Aurora, Colorado, USA
| | - Cassandra Burger
- Digestive Health Institute, Children's Hospital Colorado, Gastrointestinal Eosinophilic Diseases Program, Section of Pediatric Gastroenterology, Hepatology and Nutrition, University of Colorado School of Medicine, Aurora, Colorado, USA
| | - Brian Nguyen
- Department of Pathology, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA
| | - Michael A Arnold
- Department of Pathology, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA
- Department of Pathology and Laboratory Medicine, Children's Hospital Colorado, Aurora, Colorado, USA
| | - Zhaoxing Pan
- Child Health Biostatistics Core, Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA
| | - Glenn T Furuta
- Digestive Health Institute, Children's Hospital Colorado, Gastrointestinal Eosinophilic Diseases Program, Section of Pediatric Gastroenterology, Hepatology and Nutrition, University of Colorado School of Medicine, Aurora, Colorado, USA
| | - Maureen E Bauer
- Gastrointestinal Eosinophilic Diseases Program, Section of Allergy and Immunology, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, Colorado, USA
| | - Calies Menard-Katcher
- Digestive Health Institute, Children's Hospital Colorado, Gastrointestinal Eosinophilic Diseases Program, Section of Pediatric Gastroenterology, Hepatology and Nutrition, University of Colorado School of Medicine, Aurora, Colorado, USA
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Laserna‐Mendieta EJ, Navarro P, Casabona‐Francés S, Savarino EV, Amorena E, Pérez‐Martínez I, Guagnozzi D, Blas‐Jhon L, Betoré E, Guardiola‐Arévalo A, Pellegatta G, Krarup AL, Perello A, Barrio J, Gutiérrez‐Junquera C, Teruel Sánchez‐Vegazo C, Fernández‐Fernández S, Naves JE, Oliva S, Rodríguez‐Oballe JA, Carrión S, Espina S, Llorente Barrio M, Masiques‐Mas ML, Dainese R, Feo‐Ortega S, Martín‐Dominguez V, Fernández‐Pacheco J, Pérez‐Fernández MT, Ghisa M, Maniero D, Nantes‐Castillejo Ó, Nicolay‐Maneru J, Suárez A, Maray I, Llerena‐Castro R, Ortega‐Larrodé A, Alcedo J, Granja Navacerrada A, Racca F, Santander C, Arias Á, Lucendo AJ. Swallowed topical corticosteroids for eosinophilic esophagitis: Utilization and real-world efficacy from the EoE CONNECT registry. United European Gastroenterol J 2024; 12:585-595. [PMID: 38284792 PMCID: PMC11176909 DOI: 10.1002/ueg2.12533] [Citation(s) in RCA: 11] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Accepted: 11/25/2023] [Indexed: 01/30/2024] Open
Abstract
BACKGROUND Swallowed topical corticosteroids (tC) are common therapy for patients with eosinophilic esophagitis (EoE). Widely heterogeneous results have occurred due to their active ingredients, formulations and doses. OBJECTIVE To assess the effectiveness of topical corticosteroid therapy for EoE in real-world practice. METHODS Cross-sectional study analysis of the multicentre EoE CONNECT registry. Clinical remission was defined as a decrease of ≥50% in dysphagia symptom scores; histological remission was defined as a peak eosinophil count below 15 per high-power field. The effectiveness in achieving clinico-histological remission (CHR) was compared for the main tC formulations. RESULTS Overall, data on 1456 prescriptions of tC in monotherapy used in 866 individual patients were assessed. Of those, 904 prescriptions with data on formulation were employed for the induction of remission; 234 reduced a previously effective dose for maintenance. Fluticasone propionate formulations dominated the first-line treatment, while budesonide was more common in later therapies. A swallowed nasal drop suspension was the most common formulation of fluticasone propionate. Doses ≥0.8 mg/day provided a 65% CHR rate and were superior to lower doses. Oral viscous solution prepared by a pharmacist was the most common prescription of budesonide; 4 mg/day provided no benefit over 2 mg/day (CHR rated being 72% and 80%, respectively). A multivariate analysis revealed budesonide orodispersible tablets as the most effective therapy (OR 18.9, p < 0.001); use of higher doses (OR 4.3, p = 0.03) and lower symptom scores (OR 0.9, p = 0.01) were also determinants of effectiveness. CONCLUSION Reduced symptom severity, use of high doses, and use of budesonide orodispersible tablets particularly were all independent predictors of tC effectiveness.
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24
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de Bortoli N, Visaggi P, Penagini R, Annibale B, Baiano Svizzero F, Barbara G, Bartolo O, Battaglia E, Di Sabatino A, De Angelis P, Docimo L, Frazzoni M, Furnari M, Iori A, Iovino P, Lenti MV, Marabotto E, Marasco G, Mauro A, Oliva S, Pellegatta G, Pesce M, Privitera AC, Puxeddu I, Racca F, Ribolsi M, Ridolo E, Russo S, Sarnelli G, Tolone S, Zentilin P, Zingone F, Barberio B, Ghisa M, Savarino EV. The 1st EoETALY Consensus on the Diagnosis and Management of Eosinophilic Esophagitis - Definition, Clinical Presentation and Diagnosis. Dig Liver Dis 2024; 56:951-963. [PMID: 38423918 DOI: 10.1016/j.dld.2024.02.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2024] [Revised: 01/26/2024] [Accepted: 02/09/2024] [Indexed: 03/02/2024]
Abstract
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.
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Affiliation(s)
- Nicola de Bortoli
- Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Pierfrancesco Visaggi
- Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Roberto Penagini
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Bruno Annibale
- Department of Medical-Surgical Sciences and Translational Medicine, Sant'Andrea Hospital, Sapienza University of Rome, Rome 00189, Italy
| | - Federica Baiano Svizzero
- Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Giovanni Barbara
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | | | - Edda Battaglia
- Gastroenterology Unit ASLTO4, Chivasso - Ciriè - Ivrea, Italy
| | - Antonio Di Sabatino
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, Pavia 27100, Italy; First Department of Internal Medicine, IRCCS San Matteo Hospital Foundation, Pavia 27100, Italy
| | - Paola De Angelis
- Digestive Endoscopy Unit - Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Ludovico Docimo
- Department of Advanced Medical and Surgical Sciences, University of Campania "L. Vanvitelli", Naples, Italy
| | - Marzio Frazzoni
- Digestive Pathophysiology Unit and Digestive Endoscopy Unit, Azienda Ospedaliero Universitaria di Modena, Ospedale Civile di Baggiovara, Modena, Italy
| | - Manuele Furnari
- Division of Gastroenterology, Department of Internal Medicine, University of Genoa, Genoa, Italy; IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Andrea Iori
- Gastroenterology and Digestive Endoscopy Unit,' Santa Chiara' Hospital, Trento, Italy
| | - Paola Iovino
- Gastrointestinal Unit, Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, Baronissi 84084, Italy
| | - Marco Vincenzo Lenti
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, Pavia 27100, Italy
| | - Elisa Marabotto
- Division of Gastroenterology, Department of Internal Medicine, University of Genoa, Genoa, Italy; IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Giovanni Marasco
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Aurelio Mauro
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Policlinico San Matteo, Pavia 27100, Italy
| | - Salvatore Oliva
- Maternal and Child Health Department, Pediatric Gastroenterology and Liver Unit, Sapienza - University of Rome, Italy
| | - Gaia Pellegatta
- Endoscopic Unit, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Milan, Italy; Department of Biomedical Sciences, Humanitas University, Humanitas University, Via Rita Levi Montalcini 4, 20090 Pieve Emanuele, Milan, Italy
| | - Marcella Pesce
- Department of clinical medicine and surgery, University of Naples Federico II, Naples, Italy
| | | | - Ilaria Puxeddu
- Immunoallergology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Italy
| | - Francesca Racca
- Personalized Medicine, Asthma and Allergy Clinic, IRCCS Humanitas Research Hospital, Rozzano - Milan, Italy
| | - Mentore Ribolsi
- Unit of Gastroenterology and Digestive Endoscopy, Campus Bio Medico University, Rome, Italy
| | - Erminia Ridolo
- Allergy Unit, Department of Internal Medicine, University Hospital of Parma, Parma, Italy
| | - Salvatore Russo
- Gastroenterology and Digestive Endoscopy Unit, Azienda Ospedaliera Universitaria of Modena, Modena, Italy
| | - Giovanni Sarnelli
- Department of clinical medicine and surgery, University of Naples Federico II, Naples, Italy
| | - Salvatore Tolone
- Division of General, Oncological, Mini-Invasive and Obesity Surgery, University of Campania "Luigi Vanvitelli", Naples 80131, Italy
| | - Patrizia Zentilin
- Division of Gastroenterology, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Fabiana Zingone
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Via Giustiniani 2, Padua 35128, Italy
| | - Brigida Barberio
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Via Giustiniani 2, Padua 35128, Italy
| | - Matteo Ghisa
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Via Giustiniani 2, Padua 35128, Italy
| | - Edoardo Vincenzo Savarino
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Via Giustiniani 2, Padua 35128, Italy.
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25
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Falk GW, Pesek R. Pharmacologic Management of Eosinophilic Esophagitis. Immunol Allergy Clin North Am 2024; 44:245-264. [PMID: 38575221 DOI: 10.1016/j.iac.2023.12.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/06/2024]
Abstract
Proton pump inhibitors (PPIs), swallowed topical corticosteroids (STSs), and dupilumab are highly effective therapies for the treatment of eosinophilic esophagitis. Shared decision-making informs the choice of therapy and factors such as ease of use, safety, cost, and efficacy should be addressed. PPIs are the most common medication utilized early in the disease course; however, for nonresponders, STSs are an excellent alternative. Dupilumab is unlikely to replace PPIs or STSs as first-line therapy, except in highly specific circumstances. Identification of novel biologic pathways and the development of small molecules may lead to a wider range of treatment options in the future.
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Affiliation(s)
- Gary W Falk
- Division of Gastroenterology & Hepatology, Department of Medicine, Hospital of the University of Pennsylvania, University of Pennsylvania Perelman School of Medicine, 7th Floor South Pavilion PCAM, 3400 Civic Center Boulevard, Philadelphia, PA 19104, USA
| | - Robbie Pesek
- Division of Allergy and Immunology, Department of Pediatrics, Arkansas Children's Hospital, University of Arkansas for Medical Sciences, 13 Children's Way, Slot 512-13, Little Rock, AR 72202, USA.
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26
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Nader LS, Epifanio M, Coelho MG, Steinhaus C, Melere M, da Silva CS, Ferreira CT. High prevalence of response to PPI treatment in children and adolescents with eosinophilic esophagitis in southern Brazil. FRONTIERS IN ALLERGY 2024; 5:1346843. [PMID: 38650863 PMCID: PMC11033356 DOI: 10.3389/falgy.2024.1346843] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Accepted: 03/21/2024] [Indexed: 04/25/2024] Open
Abstract
Introduction Eosinophilic esophagitis is a newly recognized entity, in which there is significant evidence available that clearly demonstrates the positive impact of PPIs on reducing esophageal eosinophilia in individuals across different age groups, including children, adolescents, and adults. Multiple mechanisms have been proposed to explain how this treatment effect occurs. In Brazil, there seems to be a lack of studies that have prospectively assessed the clinical and therapeutic response rate in pediatric patients with EoE. The objective of this study was to prospectively evaluate the clinical and therapeutic response of pediatric patients with EoE in a medical center located in southern Brazil, by investigating the effectiveness of PPI treatment. Methods This study is a clinical, prospective, open trial that took place in a pediatric hospital located in southern Brazil. The focus of the study was on patients diagnosed with Eosinophilic Esophagitis (EoE) who were given treatment using omeprazole/esomeprazole at a dosage of 1 mg.kg per dose, twice daily, for a period of 8-12 weeks. Following the treatment period, the patients underwent another endoscopy. Patients who exhibited 15 or less eosinophils in the biopsy conducted after the treatment were considered as responders. Results A total of 27 patients was evaluated (74.1% boys). The average age (± standard deviation) was 8 years (±4). Nineteen patients (70.3%) were considered as responders to PPI treatment: 6 patients-22.2%-exhibited a complete response (defined as having 5 or fewer eosinophil per high power field. Additionally, 13 patients-48.1%-demonstrated a partial response, characterized by eosinophil counts exceeding 5 but less than 15 eos/hpf. When comparing the responder and non-responder groups at presentation, a statistical difference was observed in the prevalence of food refusal as a presenting symptom. Food refusal was found to be more prevalent in the non-responder group (87.5% vs. 26.3%, P = 0.008). No differences were observed in terms of atopy history and endoscopic scores. Upon comparing the histological findings from the post-treatment endoscopy of the two groups, it was observed that PPI responders exhibited a greater tendency to decrease basal cell hyperplasia (P = 0.06) and intercellular edema (P = 0.08). Conclusion In this group of pediatric patients with EoE in Southern Brazil most patients showed a high prevalence of histological, endoscopic, and clinical response to PPI treatment. PPIs showed efficacy in Brazilian patients with EoE, most of whom would probably not be able to adequately undergo other treatments. Clinical Trial Registration https://ensaiosclinicos.gov.br/rg/RBR-2ntbth9, identifier (U1111-1301-1842).
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Affiliation(s)
- Luiza Salgado Nader
- Division of Pediatric Gastroenterology Unit, Santa Casa de Porto Alegre, Porto Alegre, Brazil
- Graduate Program in Pediatrics, Federal University of Health Sciences of Porto Alegre, Porto Alegre, Brazil
| | - Matias Epifanio
- Division of Pediatric Gastroenterology Unit, Santa Casa de Porto Alegre, Porto Alegre, Brazil
| | | | - Cintia Steinhaus
- Division of Pediatric Gastroenterology Unit, Santa Casa de Porto Alegre, Porto Alegre, Brazil
- Graduate Program in Pediatrics, Federal University of Health Sciences of Porto Alegre, Porto Alegre, Brazil
| | - Melina Melere
- Division of Pediatric Gastroenterology Unit, Santa Casa de Porto Alegre, Porto Alegre, Brazil
- Graduate Program in Pediatrics, Federal University of Health Sciences of Porto Alegre, Porto Alegre, Brazil
| | - Carolina Soares da Silva
- Division of Pediatric Gastroenterology Unit, Santa Casa de Porto Alegre, Porto Alegre, Brazil
- Graduate Program in Pediatrics, Federal University of Health Sciences of Porto Alegre, Porto Alegre, Brazil
| | - Cristina Targa Ferreira
- Division of Pediatric Gastroenterology Unit, Santa Casa de Porto Alegre, Porto Alegre, Brazil
- Graduate Program in Pediatrics, Federal University of Health Sciences of Porto Alegre, Porto Alegre, Brazil
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27
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Ugalde-Triviño L, Molina-Jiménez F, H-Vázquez J, Relaño-Rupérez C, Arias-González L, Casabona S, Pérez-Fernández MT, Martín-Domínguez V, Fernández-Pacheco J, Lucendo AJ, Bernardo D, Santander C, Majano P. Circulating immunome fingerprint in eosinophilic esophagitis is associated with clinical response to proton pump inhibitor treatment. Front Immunol 2024; 15:1374611. [PMID: 38646544 PMCID: PMC11026586 DOI: 10.3389/fimmu.2024.1374611] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2024] [Accepted: 03/25/2024] [Indexed: 04/23/2024] Open
Abstract
Objectives The aim of the study was to characterize the circulating immunome of patients with EoE before and after proton pump inhibitor (PPI) treatment in order to identify potential non-invasive biomarkers of treatment response. Methods PBMCs from 19 healthy controls and 24 EoE patients were studied using a 39-plex spectral cytometry panel. The plasmacytoid dendritic cell (pDC) population was differentially characterized by spectral cytometry analysis and immunofluorescence assays in esophageal biopsies from 7 healthy controls and 13 EoE patients. Results Interestingly, EoE patients at baseline had lower levels of circulating pDC compared with controls. Before treatment, patients with EoE who responded to PPI therapy had higher levels of circulating pDC and classical monocytes, compared with non-responders. Moreover, following PPI therapy pDC levels were increased in all EoE patients, while normal levels were only restored in PPI-responding patients. Finally, circulating pDC levels inversely correlated with peak eosinophil count and pDC count in esophageal biopsies. The number of tissue pDCs significantly increased during active EoE, being even higher in non-responder patients when compared to responder patients pre-PPI. pDC levels decreased after PPI intake, being further restored almost to control levels in responder patients post-PPI. Conclusions We hereby describe a unique immune fingerprint of EoE patients at diagnosis. Moreover, circulating pDC may be also used as a novel non-invasive biomarker to predict subsequent response to PPI treatment.
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Affiliation(s)
- Lola Ugalde-Triviño
- Molecular Biology Unit, Hospital Universitario de la Princesa, Madrid, Spain
- Department of Molecular Biology, Instituto de Investigación Sanitaria Hospital Universitario de La Princesa (IIS-Princesa), Madrid, Spain
| | - Francisca Molina-Jiménez
- Molecular Biology Unit, Hospital Universitario de la Princesa, Madrid, Spain
- Department of Molecular Biology, Instituto de Investigación Sanitaria Hospital Universitario de La Princesa (IIS-Princesa), Madrid, Spain
| | - Juan H-Vázquez
- Mucosal Immunology Lab, Unit of Excellence Institute of Biomedicine and Molecular Genetics (IBGM), University of Valladolid and CSIC, Valladolid, Spain
| | - Carlos Relaño-Rupérez
- Molecular Biology Unit, Hospital Universitario de la Princesa, Madrid, Spain
- Department of Molecular Biology, Instituto de Investigación Sanitaria Hospital Universitario de La Princesa (IIS-Princesa), Madrid, Spain
- Bioinformatics Unit, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain
| | - Laura Arias-González
- Department of Molecular Biology, Instituto de Investigación Sanitaria Hospital Universitario de La Princesa (IIS-Princesa), Madrid, Spain
- Department of Gastroenterology, Hospital General de Tomelloso, Tomelloso, Ciudad Real, Spain
- Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), Toledo, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
| | - Sergio Casabona
- Department of Molecular Biology, Instituto de Investigación Sanitaria Hospital Universitario de La Princesa (IIS-Princesa), Madrid, Spain
- Department of Gastroenterology, Hospital Universitario de La Princesa, Madrid, Spain
| | - María Teresa Pérez-Fernández
- Department of Molecular Biology, Instituto de Investigación Sanitaria Hospital Universitario de La Princesa (IIS-Princesa), Madrid, Spain
- Department of Gastroenterology, Hospital Universitario de La Princesa, Madrid, Spain
| | - Verónica Martín-Domínguez
- Department of Molecular Biology, Instituto de Investigación Sanitaria Hospital Universitario de La Princesa (IIS-Princesa), Madrid, Spain
- Department of Gastroenterology, Hospital Universitario de La Princesa, Madrid, Spain
| | - Jennifer Fernández-Pacheco
- Department of Molecular Biology, Instituto de Investigación Sanitaria Hospital Universitario de La Princesa (IIS-Princesa), Madrid, Spain
- Department of Gastroenterology, Hospital Universitario de La Princesa, Madrid, Spain
| | - Alfredo J. Lucendo
- Department of Molecular Biology, Instituto de Investigación Sanitaria Hospital Universitario de La Princesa (IIS-Princesa), Madrid, Spain
- Department of Gastroenterology, Hospital General de Tomelloso, Tomelloso, Ciudad Real, Spain
- Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), Toledo, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
| | - David Bernardo
- Mucosal Immunology Lab, Unit of Excellence Institute of Biomedicine and Molecular Genetics (IBGM), University of Valladolid and CSIC, Valladolid, Spain
- Centro de Investigaciones Biomedicas en Red de Enfermedades Infecciosas (CIBERINFEC), Madrid, Spain
| | - Cecilio Santander
- Department of Molecular Biology, Instituto de Investigación Sanitaria Hospital Universitario de La Princesa (IIS-Princesa), Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
- Department of Gastroenterology, Hospital Universitario de La Princesa, Madrid, Spain
| | - Pedro Majano
- Molecular Biology Unit, Hospital Universitario de la Princesa, Madrid, Spain
- Department of Molecular Biology, Instituto de Investigación Sanitaria Hospital Universitario de La Princesa (IIS-Princesa), Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
- Department of Cellular Biology, Faculty of Biology, Universidad Complutense de Madrid, Madrid, Spain
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28
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Rodríguez-Alcolado L, Navarro P, Arias-González L, Grueso-Navarro E, Lucendo AJ, Laserna-Mendieta EJ. Proton-Pump Inhibitors in Eosinophilic Esophagitis: A Review Focused on the Role of Pharmacogenetics. Pharmaceutics 2024; 16:487. [PMID: 38675148 PMCID: PMC11054109 DOI: 10.3390/pharmaceutics16040487] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2024] [Revised: 03/22/2024] [Accepted: 03/25/2024] [Indexed: 04/28/2024] Open
Abstract
Proton-pump inhibitors (PPIs) are the most administered first-line treatment for eosinophilic esophagitis (EoE). However, only around half of EoE patients respond histologically to a double dosage of PPI. In addition, 70% of responders maintain EoE in remission after tapering the PPI dose. In order to avoid endoscopy with biopsies-the only accurate method of assessing PPI response-efforts have been made to identify PPI responder patients. The clinical or endoscopic features and biomarkers evaluated so far, however, have not proven to be sufficient in predicting PPI response. Although new approaches based on omics technologies have uncovered promising biomarkers, the specialized and complex procedures required are difficult to implement in clinical settings. Alternatively, PPI pharmacogenetics based on identifying variations in CYP2C19 and STAT6 genes have shown promising results in EoE, and could easily be performed in most laboratories. Other genetic variations have also been associated with PPI response and may explain those cases not related to CYP2C19 or STAT6. Here, we provide an overview of PPI treatment in EoE and evidence of how genetic variations in CYP2C19 and other genes could affect PPI effectiveness, and also discuss studies evaluating the role of pharmacogenetics in predicting PPI response in patients with EoE.
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Affiliation(s)
- Leticia Rodríguez-Alcolado
- Department of Gastroenterology, Hospital General de Tomelloso, 13700 Tomelloso, Spain; (L.R.-A.); (P.N.); (L.A.-G.); (E.G.-N.)
- Department of Surgery, Medical and Social Sciences, Universidad de Alcalá, 28805 Alcalá de Henares, Spain
| | - Pilar Navarro
- Department of Gastroenterology, Hospital General de Tomelloso, 13700 Tomelloso, Spain; (L.R.-A.); (P.N.); (L.A.-G.); (E.G.-N.)
- Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), 45071 Toledo, Spain
- Instituto de Investigación Sanitaria La Princesa, 28006 Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 28029 Madrid, Spain
| | - Laura Arias-González
- Department of Gastroenterology, Hospital General de Tomelloso, 13700 Tomelloso, Spain; (L.R.-A.); (P.N.); (L.A.-G.); (E.G.-N.)
- Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), 45071 Toledo, Spain
- Instituto de Investigación Sanitaria La Princesa, 28006 Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 28029 Madrid, Spain
| | - Elena Grueso-Navarro
- Department of Gastroenterology, Hospital General de Tomelloso, 13700 Tomelloso, Spain; (L.R.-A.); (P.N.); (L.A.-G.); (E.G.-N.)
- Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), 45071 Toledo, Spain
- Instituto de Investigación Sanitaria La Princesa, 28006 Madrid, Spain
| | - Alfredo J. Lucendo
- Department of Gastroenterology, Hospital General de Tomelloso, 13700 Tomelloso, Spain; (L.R.-A.); (P.N.); (L.A.-G.); (E.G.-N.)
- Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), 45071 Toledo, Spain
- Instituto de Investigación Sanitaria La Princesa, 28006 Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 28029 Madrid, Spain
| | - Emilio J. Laserna-Mendieta
- Department of Gastroenterology, Hospital General de Tomelloso, 13700 Tomelloso, Spain; (L.R.-A.); (P.N.); (L.A.-G.); (E.G.-N.)
- Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), 45071 Toledo, Spain
- Instituto de Investigación Sanitaria La Princesa, 28006 Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 28029 Madrid, Spain
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Goyal R, Kamboj AK, Snyder DL. Eosinophilic Esophagitis: Clinical Pearls for Primary Care Providers and Gastroenterologists. Mayo Clin Proc 2024; 99:640-648. [PMID: 38569813 DOI: 10.1016/j.mayocp.2023.12.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Revised: 12/10/2023] [Accepted: 12/28/2023] [Indexed: 04/05/2024]
Abstract
Eosinophilic esophagitis (EoE) is a chronic and progressive immune-mediated esophageal disorder. Given its increasing incidence, it is now a leading cause of dysphagia and food impaction in the United States. Eosinophilic esophagitis is most common in adult White men and has a high concurrence rate with other atopic conditions like allergic rhinitis, bronchial asthma, and eczema. The initial presentation includes symptoms of esophageal dysfunction, classically solid-food dysphagia. Without treatment, inflammation can progress to fibrosis with the formation of strictures, leading to complications such as food impaction. It is a clinicopathologic disease requiring compatible clinical symptoms and histologic evidence of eosinophil-predominant inflammation of the esophageal epithelium with more than 15 eosinophils per high-power field. The mainstay of management includes the 3 d's (diet, drugs, dilation): dietary modifications to eliminate trigger food groups; medications including proton pump inhibitors, swallowed topical glucocorticoids, and dupilumab; and esophageal dilation to manage strictures. Various elimination diets have been found to be effective, including 1-food, 2-food, 4-food, and 6-food elimination diets. Dupilumab, a humanized monoclonal antibody that regulates interleukin 4 and 13 signaling pathways, has shown promising results in clinical trials and was approved by the Food and Drug Administration in 2022 for use in EoE. Symptom alleviation, although important, is not the sole end point of treatment in EoE as persistent inflammation, even in the absence of symptoms, can lead to esophageal fibrosis and stricture formation over time. The chronic nature and high recurrence rates of EoE warrant maintenance therapy in patients with EoE after initial remission is achieved.
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Affiliation(s)
- Rohit Goyal
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | - Amrit K Kamboj
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | - Diana L Snyder
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN.
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Soria-Chacartegui P, Navares-Gómez M, Molina-Jiménez F, Laserna-Mendieta EJ, Arias-González L, Majano P, Casabona S, Lucendo AJ, Abad-Santos F, Santander C, Zubiaur P. Impact of STAT6 Variants on the Response to Proton Pump Inhibitors and Comorbidities in Patients with Eosinophilic Esophagitis. Int J Mol Sci 2024; 25:3685. [PMID: 38612496 PMCID: PMC11011338 DOI: 10.3390/ijms25073685] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2024] [Revised: 03/20/2024] [Accepted: 03/22/2024] [Indexed: 04/14/2024] Open
Abstract
Proton pump inhibitors (PPIs) are the first-line drug for eosinophilic esophagitis (EoE), although it is estimated that there is a lack of histological remission in 50% of patients. This research aimed to identify pharmacogenetic biomarkers predictive of PPI effectiveness and to study their association with disease features. Peak eosinophil count (PEC) and the endoscopic reference score (EREFS) were determined before and after an eight-week PPI course in 28 EoE patients. The impact of the signal transducer and activator of transcription 6 (STAT6), CYP2C19, CYP3A4, CYP3A5, and ABCB1 genetic variations on baseline PEC and EREFS, their reduction and histological response, and on EoE symptoms and comorbidities was analyzed. PEC reduction was higher in omeprazole-treated patients (92.5%) compared to other PPIs (57.9%, p = 0.003). STAT6 rs12368672 (g.18453G>C) G/G genotype showed higher baseline PEC values compared to G/C and C/C genotypes (83.2 vs. 52.9, p = 0.027). EREFS reduction in STAT6 rs12368672 G/G and G/C genotypes was higher than in the C/C genotype (36.7% vs. -75.0% p = 0.011). However, significance was lost after Bonferroni correction. Heartburn incidence was higher in STAT6 rs167769 (g.27148G>A) G/G patients compared to G/A (54.55% vs. 11.77%, p = 0.030). STAT6 rs12368672G>C and rs167769G>A variants might have a relevant impact on EoE status and PPI response. Further research is warranted to clarify the clinical relevance of these variants.
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Affiliation(s)
- Paula Soria-Chacartegui
- Clinical Pharmacology Department, Hospital Universitario de La Princesa, Faculty of Medicine, Universidad Autónoma de Madrid (UAM), 28006 Madrid, Spain
- Instituto de Investigación Sanitaria La Princesa (IIS-IP), 28006 Madrid, Spain (A.J.L.)
| | - Marcos Navares-Gómez
- Clinical Pharmacology Department, Hospital Universitario de La Princesa, Faculty of Medicine, Universidad Autónoma de Madrid (UAM), 28006 Madrid, Spain
- Instituto de Investigación Sanitaria La Princesa (IIS-IP), 28006 Madrid, Spain (A.J.L.)
| | - Francisca Molina-Jiménez
- Instituto de Investigación Sanitaria La Princesa (IIS-IP), 28006 Madrid, Spain (A.J.L.)
- Gastroenterology Department, Hospital Universitario de La Princesa, Faculty of Medicine, Universidad Autónoma de Madrid (UAM), 28006 Madrid, Spain
| | - Emilio J. Laserna-Mendieta
- Instituto de Investigación Sanitaria La Princesa (IIS-IP), 28006 Madrid, Spain (A.J.L.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain
- Gastroenterology Department, Hospital General de Tomelloso, 13700 Ciudad Real, Spain
- Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), 45071 Toledo, Spain
| | - Laura Arias-González
- Instituto de Investigación Sanitaria La Princesa (IIS-IP), 28006 Madrid, Spain (A.J.L.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain
- Gastroenterology Department, Hospital General de Tomelloso, 13700 Ciudad Real, Spain
- Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), 45071 Toledo, Spain
| | - Pedro Majano
- Instituto de Investigación Sanitaria La Princesa (IIS-IP), 28006 Madrid, Spain (A.J.L.)
- Gastroenterology Department, Hospital Universitario de La Princesa, Faculty of Medicine, Universidad Autónoma de Madrid (UAM), 28006 Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain
- Cellular Biology Department, Faculty of Biology, Universidad Complutense de Madrid, 28040 Madrid, Spain
| | - Sergio Casabona
- Instituto de Investigación Sanitaria La Princesa (IIS-IP), 28006 Madrid, Spain (A.J.L.)
- Gastroenterology Department, Hospital Universitario de La Princesa, Faculty of Medicine, Universidad Autónoma de Madrid (UAM), 28006 Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Alfredo J. Lucendo
- Instituto de Investigación Sanitaria La Princesa (IIS-IP), 28006 Madrid, Spain (A.J.L.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain
- Gastroenterology Department, Hospital General de Tomelloso, 13700 Ciudad Real, Spain
- Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), 45071 Toledo, Spain
| | - Francisco Abad-Santos
- Clinical Pharmacology Department, Hospital Universitario de La Princesa, Faculty of Medicine, Universidad Autónoma de Madrid (UAM), 28006 Madrid, Spain
- Instituto de Investigación Sanitaria La Princesa (IIS-IP), 28006 Madrid, Spain (A.J.L.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Cecilio Santander
- Instituto de Investigación Sanitaria La Princesa (IIS-IP), 28006 Madrid, Spain (A.J.L.)
- Gastroenterology Department, Hospital Universitario de La Princesa, Faculty of Medicine, Universidad Autónoma de Madrid (UAM), 28006 Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Pablo Zubiaur
- Clinical Pharmacology Department, Hospital Universitario de La Princesa, Faculty of Medicine, Universidad Autónoma de Madrid (UAM), 28006 Madrid, Spain
- Instituto de Investigación Sanitaria La Princesa (IIS-IP), 28006 Madrid, Spain (A.J.L.)
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Elghoudi A, Zourob D, Al Atrash E, Alshamsi F, Alkatheeri M, Narchi H, Bitar R. Evolving strategies: Enhancements in managing eosinophilic esophagitis in pediatric patients. World J Clin Pediatr 2024; 13:89580. [PMID: 38596434 PMCID: PMC11000055 DOI: 10.5409/wjcp.v13.i1.89580] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Revised: 12/26/2023] [Accepted: 01/16/2024] [Indexed: 03/06/2024] Open
Abstract
Eosinophilic esophagitis is a newly recognized disease first described about 50 years ago. The definition, diagnosis, and management have evolved with new published consensus guidelines and newly approved treatment available to pediatricians, enabling a better understanding of this disease and more targeted treatment for patients. We describe the definition, presentation, and diagnosis of eosinophilic esophagitis including management, challenges, and future directions in children. The definition, diagnosis, and management of eosinophilic esophagitis have evolved over the last 50 years. Consensus guidelines and newly approved biologic treatment have enabled pediatricians to better understand this disease and allow for more targeted treatment for patients. We describe the definition, presentation, diagnosis, management, and treatment in addition to the challenges and future directions of eosinophilic esophagitis management in children.
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Affiliation(s)
- Ahmed Elghoudi
- Department of Pediatric, Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates
| | - Doaa Zourob
- Division of Pediatric Gastroenterology, Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates
| | - Eman Al Atrash
- Division of Pediatric Gastroenterology, Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates
| | - Fatima Alshamsi
- Pediatric Residency Program, Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates
| | - Manal Alkatheeri
- Division of Pediatric Gastroenterology, Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates
| | - Hassib Narchi
- College of Medicine and Health Sciences, United Arab Emirates University, Alain, Abu Dhabi, United Arab Emirates
| | - Rana Bitar
- Division of Pediatric Gastroenterology, Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates
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32
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Shalem T, Cohen DL, Epstein-Rigbi N, Elizur A, Eindor-Abarbanel A, Broide E, Richter V. Proton pump inhibitors in eosinophilic esophagitis (EoE) related to oral immunotherapy: is it as effective as in other EoE? Eur J Pediatr 2023; 182:5409-5416. [PMID: 37750913 DOI: 10.1007/s00431-023-05228-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2023] [Revised: 09/07/2023] [Accepted: 09/17/2023] [Indexed: 09/27/2023]
Abstract
Oral immunotherapy (OIT) may induce eosinophilic esophagitis (EoE). Proton pump inhibitors (PPIs) are an effective treatment for EoE. However, the effect of PPI treatment is not well established in patients with EoE induced by OIT. Our primary aim was to compare the clinical, endoscopic, and histological response rates to PPIs in children with EoE induced by OIT (EoE+OIT) versus EoE patients without OIT (EoE-OIT). The secondary aims are to describe the clinical and histological features of EoE+OIT. Demographic, clinical, endoscopic, and histological findings of patients with EoE in the gastroenterology clinic at Shamir Medical Center between March 2015 and December 2022 were collected. Comparisons were performed between EoE+OIT and EoE-OIT patients. The study included 42 children (74% male, mean age 11.2), of whom 31 had EoE-OIT and 11 had EoE+OIT. There were no significant differences between groups regarding sex, comorbidities, symptoms, or endoscopic and histological characteristics at diagnosis. All 42 children were treated with PPIs after diagnosis with or without diet changes. The rates of any clinical response were 83.9% and 90.1% in the EoE-OIT group and EoE+OIT group, respectively (p = 1.0). The rate of any endoscopic response was 74.2% for EoE-OIT and 81.8% for EoE+OIT (p = 0.54). Histologically, PPIs were even more effective in the EoE+OIT group, where only 18.2% had no histological response at all compared to 51.6% in the EoE-OIT group (p = 0.1). CONCLUSION PPI treatment is as effective in EoE with OIT as it is in EoE due to other etiologies. WHAT IS KNOWN • Proton pump inhibitor (PPI) treatment is effective for achieving clinical response and histologic remission in some patients with eosinophilic esophagitis (EoE). • EoE has also been reported to be triggered by oral immunotherapy (OIT). WHAT IS NEW • PPI treatment in EoE with OIT is as effective as treatment for EoE due to other etiologies.
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Affiliation(s)
- Tzippora Shalem
- The Jecheskiel Sigi Gonczarowski Pediatric Gastroenterology Unit, Shamir (Assaf Harofeh) Medical Center, Zerifin, 70300, Israel
| | - Daniel L Cohen
- The Gonczarowski Family Institute of Gastroenterology and Liver Disease, Shamir (Assaf Harofeh) Medical Center, Zerifin, 70300, Israel
| | - Na'ama Epstein-Rigbi
- Institute of Allergy, Immunology and Pediatric Pulmonology, Shamir (Assaf Harofeh) Medical Center, Zerifin, Israel
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Arnon Elizur
- Institute of Allergy, Immunology and Pediatric Pulmonology, Shamir (Assaf Harofeh) Medical Center, Zerifin, Israel
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Adi Eindor-Abarbanel
- The Jecheskiel Sigi Gonczarowski Pediatric Gastroenterology Unit, Shamir (Assaf Harofeh) Medical Center, Zerifin, 70300, Israel
| | - Efrat Broide
- The Jecheskiel Sigi Gonczarowski Pediatric Gastroenterology Unit, Shamir (Assaf Harofeh) Medical Center, Zerifin, 70300, Israel
- The Gonczarowski Family Institute of Gastroenterology and Liver Disease, Shamir (Assaf Harofeh) Medical Center, Zerifin, 70300, Israel
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Vered Richter
- The Gonczarowski Family Institute of Gastroenterology and Liver Disease, Shamir (Assaf Harofeh) Medical Center, Zerifin, 70300, Israel.
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
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33
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Casabona Francés S, Ruiz de León San Juan A, Sanz García A, Ortega Rabbione GJ, Majano P, Pérez Fernández MT, Lucendo AJ, Santander C. Esophageal biomechanics assessed by impedance planimetry (EndoFLIPTM) in healthy subjects and in patients with eosinophilic esophagitis. Normality values. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2023; 115:693-699. [PMID: 37449498 DOI: 10.17235/reed.2023.9560/2023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/18/2023]
Abstract
BACKGROUND active eosinophilic esophagitis is associated with esophageal caliber, distensibility and motility changes that may be reversed with treatment. OBJECTIVES to study esophageal diameter, distensibility and contractility in healthy subjects compared to patients with eosinophilic esophagitis, both before and after treatment. METHODS a quasi-experimental study, EndoFLIP™, was used to analyze the esophageal body and esophago-gastric junction (EGJ) in all three groups, and a program was designed to obtain esophageal diameter, distensibility and contractility values. RESULTS ten healthy volunteers (24-61 years, six men) and nine patients with eosinophilic esophagitis (21-52 years, seven men) were included. The esophagogastric junction distensibility index was 5.07 mm2/Hg in the control subjects, 2.40 mm2/Hg in the subjects with eosinophilic esophagitis before treatment and 2.46 mm2/Hg after treatment. The distensibility plateau was 20.02 mm, 15.43 mm and 17.41 mm, respectively, and the diameter was 21.90 mm, 17.73 mm and 18.30 mm, showing significant differences (p < 0.05), except between control subjects and patients after treatment (p = 0.079). Repetitive antegrade contractions developed in 90 % of control subjects, 66.7 % of eosinophilic esophagitis patients before treatment and 88.9 % of the latter after treatment (p > 0.05). CONCLUSIONS esophago-gastric junction distensibility index, distensibility plateau and diameter values were higher in controls than in patients, although six weeks of treatment seems a short period to observe significant changes in esophageal biomechanics. Repetitive antegrade contractions are the predominant pattern in healthy subjects and eosinophilic esophagitis. We provide normality values for esophageal biomechanics, measured by impedance planimetry in our setting.
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Affiliation(s)
| | | | - Ancor Sanz García
- Unidad de Análisis de Datos, Instituto de Investigación Sanitaria Princesa (IIS-IP)
| | | | - Pedro Majano
- Aparato Digestivo, Hospital Universitario de La Princesa
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Marasco G, Visaggi P, Vassallo M, Fiocca M, Cremon C, Barbaro MR, De Bortoli N, Bellini M, Stanghellini V, Savarino EV, Barbara G. Current and Novel Therapies for Eosinophilic Gastrointestinal Diseases. Int J Mol Sci 2023; 24:15165. [PMID: 37894846 PMCID: PMC10607071 DOI: 10.3390/ijms242015165] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2023] [Revised: 10/01/2023] [Accepted: 10/02/2023] [Indexed: 10/29/2023] Open
Abstract
Eosinophilic gastrointestinal diseases (EGIDs) are an emerging group of pathological entities characterized by an eosinophil-predominant infiltration of different tracts of the gut in the absence of secondary causes of eosinophilia. According to the specific tract of the gut involved, EGIDs can be classified into eosinophilic esophagitis (EoE), eosinophilic gastritis (EoG), eosinophilic enteritis (EoN), and eosinophilic colitis (EoC). The epidemiology of EGIDs is evolving rapidly. EoE, once considered a rare disease, now has an incidence and prevalence of 7.7 new cases per 100,000 inhabitants per years and 34.4 cases per 100,000 inhabitants per year, respectively. Fewer data are available regarding non-EoE EGIDs, whose prevalence are estimated to range between 2.1 and 17.6 in 100,000 individuals, depending on age, sex, and ethnicity. Diagnosis requires the presence of suggestive symptoms, endoscopic biopsies showing abnormal values of eosinophils infiltrating the gut, and exclusion of secondary causes of eosinophilia. EoE typically presents with dysphagia and episodes of food bolus impactions, while EoG, EoN, and EoC may all present with abdominal pain and diarrhea, with or without other non-specific symptoms. In addition, although different EGIDs are currently classified as different entities, there may be overlap between different diseases in the same patient. Despite EGIDs being relatively novel pathological entities, the research on possible treatments is rapidly growing. In this regard, several randomized controlled trials are currently ongoing to investigate novel molecules, including ad-hoc steroid formulations, immunosuppressants, and mostly monoclonal antibodies that target the specific molecular mediators of EGIDs. This narrative review provides an up-to-date overview of available and investigational drugs for different EGIDs.
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Affiliation(s)
- Giovanni Marasco
- IRCCS Azienda Ospedaliero, Universitaria di Bologna, Via Massarenti 9, 40138 Bologna, Italy; (G.M.); (M.V.); (M.F.); (C.C.); (M.R.B.); (V.S.)
- Department of Medical and Surgical Sciences, University of Bologna, Via Massarenti, 9, 40138 Bologna, Italy
| | - Pierfrancesco Visaggi
- Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Risorgimento 36, 56126 Pisa, Italy; (P.V.); (N.D.B.); (M.B.)
| | - Mariagiulia Vassallo
- IRCCS Azienda Ospedaliero, Universitaria di Bologna, Via Massarenti 9, 40138 Bologna, Italy; (G.M.); (M.V.); (M.F.); (C.C.); (M.R.B.); (V.S.)
- Department of Medical and Surgical Sciences, University of Bologna, Via Massarenti, 9, 40138 Bologna, Italy
| | - Miriam Fiocca
- IRCCS Azienda Ospedaliero, Universitaria di Bologna, Via Massarenti 9, 40138 Bologna, Italy; (G.M.); (M.V.); (M.F.); (C.C.); (M.R.B.); (V.S.)
- Department of Medical and Surgical Sciences, University of Bologna, Via Massarenti, 9, 40138 Bologna, Italy
| | - Cesare Cremon
- IRCCS Azienda Ospedaliero, Universitaria di Bologna, Via Massarenti 9, 40138 Bologna, Italy; (G.M.); (M.V.); (M.F.); (C.C.); (M.R.B.); (V.S.)
- Department of Medical and Surgical Sciences, University of Bologna, Via Massarenti, 9, 40138 Bologna, Italy
| | - Maria Raffaella Barbaro
- IRCCS Azienda Ospedaliero, Universitaria di Bologna, Via Massarenti 9, 40138 Bologna, Italy; (G.M.); (M.V.); (M.F.); (C.C.); (M.R.B.); (V.S.)
- Department of Medical and Surgical Sciences, University of Bologna, Via Massarenti, 9, 40138 Bologna, Italy
| | - Nicola De Bortoli
- Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Risorgimento 36, 56126 Pisa, Italy; (P.V.); (N.D.B.); (M.B.)
| | - Massimo Bellini
- Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Risorgimento 36, 56126 Pisa, Italy; (P.V.); (N.D.B.); (M.B.)
| | - Vincenzo Stanghellini
- IRCCS Azienda Ospedaliero, Universitaria di Bologna, Via Massarenti 9, 40138 Bologna, Italy; (G.M.); (M.V.); (M.F.); (C.C.); (M.R.B.); (V.S.)
- Department of Medical and Surgical Sciences, University of Bologna, Via Massarenti, 9, 40138 Bologna, Italy
| | - Edoardo Vincenzo Savarino
- Gastroenterology Unit, Azienda Ospedale Università of Padua, Via Giustiniani 2, 35128 Padua, Italy;
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Via Giustiniani 2, 35128 Padua, Italy
| | - Giovanni Barbara
- IRCCS Azienda Ospedaliero, Universitaria di Bologna, Via Massarenti 9, 40138 Bologna, Italy; (G.M.); (M.V.); (M.F.); (C.C.); (M.R.B.); (V.S.)
- Department of Medical and Surgical Sciences, University of Bologna, Via Massarenti, 9, 40138 Bologna, Italy
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35
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Dutta AK, Jain A, Jearth V, Mahajan R, Panigrahi MK, Sharma V, Goenka MK, Kochhar R, Makharia G, Reddy DN, Kirubakaran R, Ahuja V, Berry N, Bhat N, Dutta U, Ghoshal UC, Jain A, Jalihal U, Jayanthi V, Kumar A, Nijhawan S, Poddar U, Ramesh GN, Singh SP, Zargar S, Bhatia S. Guidelines on optimizing the use of proton pump inhibitors: PPI stewardship. Indian J Gastroenterol 2023; 42:601-628. [PMID: 37698821 DOI: 10.1007/s12664-023-01428-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2023] [Accepted: 07/10/2023] [Indexed: 09/13/2023]
Abstract
Proton pump inhibitors (PPIs) have been available for over three decades and are among the most commonly prescribed medications. They are effective in treating a variety of gastric acid-related disorders. They are freely available and based on current evidence, use of PPIs for inappropriate indications and duration appears to be common. Over the years, concerns have been raised on the safety of PPIs as they have been associated with several adverse effects. Hence, there is a need for PPI stewardship to promote the use of PPIs for appropriate indication and duration. With this objective, the Indian Society of Gastroenterology has formulated guidelines on the rational use of PPIs. The guidelines were developed using a modified Delphi process. This paper presents these guidelines in detail, including the statements, review of literature, level of evidence and recommendations. This would help the clinicians in optimizing the use of PPIs in their practice and promote PPI stewardship.
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Affiliation(s)
- Amit Kumar Dutta
- Department of Gastroenterology, Christian Medical College and Hospital, Vellore, 632 004, India.
| | | | - Vaneet Jearth
- Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India
| | - Ramit Mahajan
- Dayanand Medical College and Hospital, Ludhiana, 141 001, India
| | | | - Vishal Sharma
- Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India
| | | | | | - Govind Makharia
- All India Institute of Medical Sciences, New Delhi, 110 029, India
| | | | - Richard Kirubakaran
- Center of Biostatistics and Evidence Based Medicine, Vellore, 632 004, India
| | - Vineet Ahuja
- All India Institute of Medical Sciences, New Delhi, 110 029, India
| | - Neha Berry
- BLK Institute of Digestive and Liver Disease, New Delhi, 201 012, India
| | - Naresh Bhat
- Aster CMI Hospital, Bengaluru, 560 092, India
| | - Usha Dutta
- Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India
| | - Uday Chand Ghoshal
- Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, 226 014, India
| | - Ajay Jain
- Choithram Hospital and Research Center, Indore, 452 014, India
| | | | - V Jayanthi
- Sri Ramachandra Medical College, Chennai, 600 116, India
| | - Ajay Kumar
- Institute of Digestive and Liver Diseases, BLK - Max Superspeciality Hospital, New Delhi, 201 012, India
| | | | - Ujjal Poddar
- Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, 226 014, India
| | | | - Shivram P Singh
- Kalinga Gastroenterology Foundation, Cuttack, 753 001, India
| | - Showkat Zargar
- Department of Gastroenterology, Sher-i-Kashmir Institute of Medical Sciences, Kashmir, 190 011, India
| | - Shobna Bhatia
- Sir H N Reliance Foundation Hospital, Mumbai, 400 004, India
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Molina-Jiménez F, Ugalde-Triviño L, Arias-González L, Relaño-Rupérez C, Casabona S, Pérez-Fernández MT, Martín-Domínguez V, Fernández-Pacheco J, Laserna-Mendieta EJ, Muñoz-Hernández P, Arias-Arias Á, Cano A, Muñoz J, Lucendo AJ, Santander C, Majano P. Proteomic analysis of the esophageal epithelium reveals key features of eosinophilic esophagitis pathophysiology. Allergy 2023; 78:2732-2744. [PMID: 37287363 DOI: 10.1111/all.15779] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2023] [Revised: 04/27/2023] [Accepted: 05/03/2023] [Indexed: 06/09/2023]
Abstract
BACKGROUND Eosinophilic esophagitis (EoE) is a chronic non-IgE-mediated allergic disease of the esophagus. An unbiased proteomics approach was performed to investigate pathophysiological changes in esophageal epithelium. Additionally, an RNAseq-based transcriptomic analysis in paired samples was also carried out. METHODS Total proteins were purified from esophageal endoscopic biopsies in a cohort of adult EoE patients (n = 25) and healthy esophagus controls (n = 10). Differentially accumulated (DA) proteins in EoE patients compared to control tissues were characterized to identify altered biological processes and signaling pathways. Results were also compared with a quantitative proteome dataset of the human esophageal mucosa. Next, results were contrasted with those obtained after RNAseq analysis in paired samples. Finally, we matched up protein expression with two EoE-specific mRNA panels (EDP and Eso-EoE panel). RESULTS A total of 1667 proteins were identified, of which 363 were DA in EoE. RNA sequencing in paired samples identified 1993 differentially expressed (DE) genes. Total RNA and protein levels positively correlated, especially in DE mRNA-proteins pairs. Pathway analysis of these proteins in EoE showed alterations in immune and inflammatory responses for the upregulated proteins, and in epithelial differentiation, cornification and keratinization in those downregulated. Interestingly, a set of DA proteins, including eosinophil-related and secreted proteins, were not detected at the mRNA level. Protein expression positively correlated with EDP and Eso-EoE, and corresponded with the most abundant proteins of the human esophageal proteome. CONCLUSIONS We unraveled for the first time key proteomic features involved in EoE pathogenesis. An integrative analysis of transcriptomic and proteomic datasets provides a deeper insight than transcriptomic alone into understanding complex disease mechanisms.
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Affiliation(s)
- Francisca Molina-Jiménez
- Molecular Biology Unit, Hospital Universitario de la Princesa, Madrid, Spain
- Instituto de Investigación Sanitaria Hospital Universitario de La Princesa (IIS-Princesa), Madrid, Spain
| | - Lola Ugalde-Triviño
- Molecular Biology Unit, Hospital Universitario de la Princesa, Madrid, Spain
- Instituto de Investigación Sanitaria Hospital Universitario de La Princesa (IIS-Princesa), Madrid, Spain
| | - Laura Arias-González
- Instituto de Investigación Sanitaria Hospital Universitario de La Princesa (IIS-Princesa), Madrid, Spain
- Department of Gastroenterology, Hospital General de Tomelloso, Ciudad Real, Spain
- Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), Toledo, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
| | - Carlos Relaño-Rupérez
- Molecular Biology Unit, Hospital Universitario de la Princesa, Madrid, Spain
- Instituto de Investigación Sanitaria Hospital Universitario de La Princesa (IIS-Princesa), Madrid, Spain
| | - Sergio Casabona
- Instituto de Investigación Sanitaria Hospital Universitario de La Princesa (IIS-Princesa), Madrid, Spain
- Department of Gastroenterology, Hospital Universitario de La Princesa, Madrid, Spain
| | - María Teresa Pérez-Fernández
- Instituto de Investigación Sanitaria Hospital Universitario de La Princesa (IIS-Princesa), Madrid, Spain
- Department of Gastroenterology, Hospital Universitario de La Princesa, Madrid, Spain
| | - Verónica Martín-Domínguez
- Instituto de Investigación Sanitaria Hospital Universitario de La Princesa (IIS-Princesa), Madrid, Spain
- Department of Gastroenterology, Hospital Universitario de La Princesa, Madrid, Spain
| | - Jennifer Fernández-Pacheco
- Instituto de Investigación Sanitaria Hospital Universitario de La Princesa (IIS-Princesa), Madrid, Spain
- Department of Gastroenterology, Hospital Universitario de La Princesa, Madrid, Spain
| | - Emilio José Laserna-Mendieta
- Instituto de Investigación Sanitaria Hospital Universitario de La Princesa (IIS-Princesa), Madrid, Spain
- Department of Gastroenterology, Hospital General de Tomelloso, Ciudad Real, Spain
- Clinical Laboratory, Hospital Universitario de La Princesa, Madrid, Spain
| | | | - Ángel Arias-Arias
- Instituto de Investigación Sanitaria Hospital Universitario de La Princesa (IIS-Princesa), Madrid, Spain
- Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), Toledo, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
- Research Unit, Hospital General La Mancha Centro, Alcázar de San Juan, Spain
| | - Ainara Cano
- Food Research, AZTI, Basque Research and Technology Alliance (BRTA), Parque Tecnológico de Bizkaia, Derio, Spain
| | - Javier Muñoz
- Cell Signalling and Clinical Proteomics Group, Biocruces Bizkaia Health Research Institute, Barakaldo, Spain
- Ikerbasque, Basque Foundation for Science, Bilbao, Spain
| | - Alfredo J Lucendo
- Instituto de Investigación Sanitaria Hospital Universitario de La Princesa (IIS-Princesa), Madrid, Spain
- Department of Gastroenterology, Hospital General de Tomelloso, Ciudad Real, Spain
- Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), Toledo, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
| | - Cecilio Santander
- Instituto de Investigación Sanitaria Hospital Universitario de La Princesa (IIS-Princesa), Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
- Department of Gastroenterology, Hospital Universitario de La Princesa, Madrid, Spain
| | - Pedro Majano
- Molecular Biology Unit, Hospital Universitario de la Princesa, Madrid, Spain
- Instituto de Investigación Sanitaria Hospital Universitario de La Princesa (IIS-Princesa), Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
- Department of Cellular Biology, Faculty of Biology, Universidad Complutense de Madrid, Madrid, Spain
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Attwood SE. Multiple inflammatory mechanisms in eosinophilic oesophagitis make it unlikely that single pathway inhibition by monoclonal biological therapies would succeed. Gut 2023; 72:1806-1807. [PMID: 37640444 DOI: 10.1136/gutjnl-2023-330590] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2023] [Accepted: 08/16/2023] [Indexed: 08/31/2023]
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Zhang X, Zhang N, Wang Z. Eosinophilic esophagitis and esophageal microbiota. Front Cell Infect Microbiol 2023; 13:1206343. [PMID: 37600943 PMCID: PMC10434796 DOI: 10.3389/fcimb.2023.1206343] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2023] [Accepted: 07/20/2023] [Indexed: 08/22/2023] Open
Abstract
Eosinophilic esophagitis (EoE) is an antigen-mediated chronic inflammatory disease of the esophagus, the prevalence of which has steadily increased in recent years. The pathogenesis of EoE is not yet well-defined; however, recent studies have demonstrated that the esophageal microbiota is an essential regulator of physiological and pathological processes of EoE. Currently, research on EoE and microbiota is an emerging field of study that is receiving increasing attention. Here, we review existing EoE-related esophageal microbiota studies to explore the potential mechanisms underlying esophageal microbiota-mediated EoE. The esophageal microbiome is altered in patients with EoE. Although α diversity is usually not significantly different, an increase in Haemophilus and a decrease in Firmicutes were observed in EoE patients. The role of microbiota in initiating and perpetuating inflammation is not fully understood. Current evidence suggests that the penetration of microbiota leads to the activation of epithelial cells as well as innate and adaptive immune cells, with the subsequent release of cytokines, leading to immune responses and inflammation. The involvement of toll-like receptors in EoE also supports the potential role of the microbiota in the progression of this disease. While EoE-induced inflammation can also lead to alterations in the local microbiome. Moreover, dietary modifications, proton pump inhibitors, and corticosteroids can modulate the esophageal microbiota; however, definitive conclusions about the alterations of microbes after treatment cannot be drawn. These findings provide promising avenues for future studies.
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Affiliation(s)
- Xiaohan Zhang
- Microbiota Division, Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
- Medical School, Nankai University, Tianjin, China
| | - Nana Zhang
- Microbiota Division, Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Zikai Wang
- Microbiota Division, Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
- National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China
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Henriksen SD, Hansen SK, Heinesen M, Terkelsen JH, Hollænder M, Bredal K, Melgaard D, Krarup AL. The phenotype of adults with complicated eosinophilic esophagitis is dominated by a 5-year longer diagnostic delay: A population-based study of the DanEoE cohort. JGH Open 2023; 7:553-558. [PMID: 37649863 PMCID: PMC10463020 DOI: 10.1002/jgh3.12947] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Revised: 06/04/2023] [Accepted: 07/05/2023] [Indexed: 09/01/2023]
Abstract
Background and Aim The DanEoE is a previously described population- and register-based cohort of 236 adult patients with eosinophilic esophagitis (EoE) in a well-defined Danish region with a population of 580 000 and free medical treatment. The aim of the study was to compare the phenotype and treatment response between EoE patients with complications to patients without complications at diagnosis. Methods A retrospective cross-sectional study of the DanEoE cohort's 236 adult EoE patients diagnosed between 2007 and 2017 in the North Denmark Region. Patients were divided into a group who had had complications (dilated or food bolus obstruction [FBO]) before or at the diagnosis, and a group without. Results At the diagnostic endoscopy, 61% had never had a complication, and 39% had either had FBO (n = 77) or been dilated (n = 15). The complicated group had the same mean age at symptom debut (37 [SD = 16] vs 37 [SD = 17] years, P = 1.0), but were diagnosed significantly later with a resulting longer diagnostic delay (13 [SD = 13] vs 7.9 [SD = 11] years, P = 0.01). Almost half of all patients were never treated to symptomatic remission (uncomplicated 40%, complicated 49%). The histological remission was not secured in the majority (uncomplicated 68%, complicated 70%). Despite this, <15% of patients with previous FBO experienced this after the diagnosis. Conclusion In the population-based DanEoE cohort, results indicated that the complicated EoE phenotype was a patient with a 5-year longer diagnostic delay. In the current study, the complication status did not predict the treatment response.
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Affiliation(s)
- Stine D Henriksen
- Department of Gastrointestinal SurgeryAalborg University HospitalAalborgDenmark
- Department of Clinical MedicineAalborg UniversityAalborgDenmark
- Clinical Cancer Research CenterAalborg University HospitalAalborgDenmark
| | - Stine K Hansen
- Department of Gastroenterology and HepatologyAalborg University HospitalAalborgDenmark
| | - Mia Heinesen
- Department of Emergency Medicine and Trauma CenterAalborg University HospitalAalborgDenmark
| | - Jacob H Terkelsen
- Department of Clinical MedicineAalborg UniversityAalborgDenmark
- Department of Emergency Medicine and Trauma CenterAalborg University HospitalAalborgDenmark
| | - Martin Hollænder
- Department of Clinical MedicineAalborg UniversityAalborgDenmark
- Department of Emergency Medicine and Trauma CenterAalborg University HospitalAalborgDenmark
| | - Kasper Bredal
- Department of Clinical MedicineAalborg UniversityAalborgDenmark
- Department of Emergency Medicine and Trauma CenterAalborg University HospitalAalborgDenmark
| | - Dorte Melgaard
- Department of Clinical MedicineAalborg UniversityAalborgDenmark
- North Denmark Regional HospitalHjørringDenmark
- Mech‐Sense, Department of Gastroenterology and HepatologyAalborg University HospitalAalborgDenmark
| | - Anne L Krarup
- Department of Clinical MedicineAalborg UniversityAalborgDenmark
- Department of Gastroenterology and HepatologyAalborg University HospitalAalborgDenmark
- Department of Emergency Medicine and Trauma CenterAalborg University HospitalAalborgDenmark
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Melgaard D, Hansen AB, Pedersen C, Sandholm E, Hansen TB, Frandsen LT, Krarup AL. An improved guideline adherence and PPI efficacy has been accompanied by a decrease in diagnostic delay, and strictures before diagnosis of eosinophilic esophagitis in the North Denmark Region - a retrospective registry study of the DanEoE cohorts. Clin Res Hepatol Gastroenterol 2023; 47:102159. [PMID: 37307949 DOI: 10.1016/j.clinre.2023.102159] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2023] [Revised: 06/07/2023] [Accepted: 06/09/2023] [Indexed: 06/14/2023]
Abstract
BACKGROUND In the North Denmark Region an increased awareness of eosinophilic esophagitis (EoE) was observed after 2011 where a regional biopsy guideline was implemented. This resulted in an increased awareness of EoE and a 50-fold increase in the incidence of EoE patients between 2007-2017. AIMS The aims of this study were to examine the progress in diagnostic delay, complications, PPI treatment, and follow up since 2017 in Danish patients with eosinophilic esophagitis. MATERIALS AND METHODS This was a retrospective registry- and population-based cohort study (DanEoE2 cohort) including 346 adult patients with esophageal eosinophilia diagnosed between 2018-2021 in the North Denmark Region. The DanEoE2 cohort included all possible EoE patients by using the Danish Patho-histology registry based on the SNOMED-system. The data was analyzed and compared to the DanEoE cohort (2007-2017). RESULTS The diagnostic delay of EoE patients diagnosed between 2018-2021 in the North Denmark Region had decreased with a median of 1.5 years (5.5 (2.0;12) years versus 4.0 (1.0;12) years, p=0.03). Strictures before diagnosis had decreased 8.4 % (11.6% versus 3.2%, p=0.003). The number of patients started on high-dose PPI increased (56% versus 88%, p<0.001). An intensified awareness regarding national guidelines and follow-up was observed as an increase in the number of histological follow up (67% versus 74%, p=0.05). CONCLUSIONS Comparisons of the DanEoE cohorts showed a decrease in diagnostic delay, a decrease in stricture formation before diagnosis, and an improved guideline adherence after 2017. Future studies are needed to assess if symptomatic or histological remission on PPI treatment is more capable of predicting a patient's risk of developing complications.
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Affiliation(s)
- Dorte Melgaard
- MechSense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Hobrovej 18-22, Aalborg 9000, Denmark; Department of Clinical Medicine, Aalborg University, Søndre Skovvej 15, Aalborg 9000, Denmark
| | - Amalie Byrholdt Hansen
- Department of Clinical Medicine, Aalborg University, Søndre Skovvej 15, Aalborg 9000, Denmark
| | - Camilla Pedersen
- Department of Clinical Medicine, Aalborg University, Søndre Skovvej 15, Aalborg 9000, Denmark
| | - Elise Sandholm
- Department of Clinical Medicine, Aalborg University, Søndre Skovvej 15, Aalborg 9000, Denmark
| | - Tanja Bech Hansen
- Department of Clinical Medicine, Aalborg University, Søndre Skovvej 15, Aalborg 9000, Denmark
| | - Line Tegtmeier Frandsen
- Department of Gastroenterology and Hepatology, Aalborg University Hospital, Hobrovej 18-22, Aalborg 9000, Denmark
| | - Anne Lund Krarup
- Department of Clinical Medicine, Aalborg University, Søndre Skovvej 15, Aalborg 9000, Denmark; Department of Gastroenterology and Hepatology, Aalborg University Hospital, Hobrovej 18-22, Aalborg 9000, Denmark; Department of Emergency Medicine and Trauma Center, Aalborg University Hospital, Hobrovej 18-22, Aalborg 9000, Denmark.
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41
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S2k-Leitlinie Gastroösophageale Refluxkrankheit und eosinophile Ösophagitis der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) – März 2023 – AWMF-Registernummer: 021–013. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2023; 61:862-933. [PMID: 37494073 DOI: 10.1055/a-2060-1069] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/28/2023]
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Molina-Infante J, Mata-Romero P, Martín-Holgado D. New approaches to diet therapy for eosinophilic esophagitis. Curr Opin Gastroenterol 2023; 39:315-319. [PMID: 37097832 DOI: 10.1097/mog.0000000000000940] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/26/2023]
Abstract
PURPOSE OF REVIEW An empiric step-up (2-4-6) elimination diet remains the most common dietary approach in clinical practice when treating eosinophilic esophagitis (EoE). However, research in this field has fallen behind pharmacological therapy. This review aims to summarize novel approaches to dietary therapy for EoE. RECENT FINDINGS A first prospective multicenter study in 41 pediatric patients (mean age 9 years) has evaluated the efficacy of a cow's milk elimination diet. This dietary approach led to histological remission in 51% of patients, albeit a caveat is that up to 80% of patients were receiving concomitant therapy with proton pump inhibitors. In a series of 18 adult patients with documented milk-induced EoE, ingestión of 400 ml of sterilized milk (boiled for up to 20 min) daily for 8 weeks did not induce histologic relapse in two-thirds of patients. SUMMARY Milk elimination diet is effective in one-half of pediatric EoE patients and should likely be the first choice in children with EoE (within a step-up dietary approach). Promising data on tolerance of sterilized milk in adults with milk-induced EoE (66%) merit further replication in children, which may radically improve quality of life for patients and their caregivers.
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Affiliation(s)
- Javier Molina-Infante
- Department of Gastroenterology, Hospital Universitario de Cáceres, Cáceres
- Centro de Investigacion Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Pilar Mata-Romero
- Department of Gastroenterology, Hospital Universitario de Cáceres, Cáceres
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Leiman DA, Kamal AN, Otaki F, Bredenoord AJ, Dellon ES, Falk GW, Fernandez-Becker NQ, Gonsalves N, Hirano I, Katzka DA, Peterson K, Yadlapati R, Kathpalia P. Quality Indicators for the Diagnosis and Management of Eosinophilic Esophagitis. Am J Gastroenterol 2023; 118:1091-1095. [PMID: 36599135 PMCID: PMC10392038 DOI: 10.14309/ajg.0000000000002138] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2022] [Accepted: 11/21/2022] [Indexed: 01/06/2023]
Abstract
INTRODUCTION Despite best practice recommendations for managing eosinophilic esophagitis (EoE), variation in care exists. METHODS We used established methodology for quality indicator development to identify metrics to define quality for the treatment of EoE. RESULTS Among 29 proposed quality indicator statements, 9 (31%) were adopted as highly valid across all categories. Two (22%) of these statements were identified as having existing or suspected quality gaps. DISCUSSION We identified highly valid EoE quality indicators for adult gastroenterologists, which can be used for quality improvement with resulting benefits for patient outcomes.
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Affiliation(s)
- David A. Leiman
- Division of Gastroenterology, Duke University School of Medicine, Durham, North Carolina, USA
- Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA
| | - Afrin N. Kamal
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California, USA
| | - Fouad Otaki
- Division of Gastroenterology and Hepatology, Oregon Health and Science University, Portland, Oregon, USA
| | - Albert J. Bredenoord
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centre, Amsterdam, the Netherlands
| | - Evan S. Dellon
- Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, University of North Carolina, North Carolina, USA
| | - Gary W. Falk
- Division of Gastroenterology, University of Pennsylvania Perelman School of Medicine Philadelphia, Pennsylvania, USA
| | - Nielsen Q. Fernandez-Becker
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California, USA
| | - Nirmala Gonsalves
- Division of Gastroenterology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
| | - Ikuo Hirano
- Division of Gastroenterology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
| | - David A. Katzka
- Division of Gastroenterology, Columbia University Medical Center, New York, New York, USA
| | | | - Rena Yadlapati
- Division of Gastroenterology, University of California, San Diego, California, USA
| | - Priya Kathpalia
- Division of Gastroenterology and Hepatology, University of California-San Francisco, San Francisco, California, USA
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Miehlke S, Arnim UV, Schlag C, Labenz J, Madisch A. [Treatment of eosinophilic esophagitis - advancements and perspectives]. Laryngorhinootologie 2023; 102:339-348. [PMID: 37141876 DOI: 10.1055/a-1861-7152] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/06/2023]
Abstract
In recent years significant progress has been made in the treatment of eosinophilic esophagitis (EoE), especially in the area of topical corticosteroids. Novel EoE-specific formulations have been developed and first approvals have been obtained for induction and maintenance of remission in adult EoE patients with the orodispersible budesonide tablet in Germany and other European and non-EU countries. A novel budesonide oral suspension is currently under priority review by the FDA for first approval in the U.S. In contrast, the scientific evidence on the efficacy of proton pump inhibitors remains limited. Moreover, new biologicals have been identified which showed promising results in phase 2 trials and are now being studied in phase 3. This article aims to summarize and discuss recent advances and perspectives in the treatment of EoE.
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Affiliation(s)
- Stephan Miehlke
- Magen-Darm-Zentrum, Facharztzentrum Eppendorf, Hamburg, Germany
- Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
| | - Ulrike von Arnim
- Department of Gastroenterology, Hepatology and Infectious diseases, Universitätsklinikum Magdeburg AöR, Magdeburg, Germany
| | - Christoph Schlag
- Second medical department, Klinikum rechts der Isar der Technischen Universität München, Munchen, Germany
| | - Joachim Labenz
- Medizinische Klinik, Ev. Jung-Stilling Krankenhaus, Siegen, Germany
| | - Ahmed Madisch
- Department of Internal Medicine, Siloah Hospital, Hannover, Germany
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Proton Pump Inhibitor Therapy in Pediatric Eosinophilic Esophagitis: Predictive Factors and Long-Term Step-Down Efficacy. J Pediatr Gastroenterol Nutr 2023; 76:191-198. [PMID: 36416845 DOI: 10.1097/mpg.0000000000003660] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
OBJECTIVES To assess the short- and long-term efficacy of proton pump inhibitor (PPI) therapy for pediatric eosinophilic esophagitis (EoE) in real-world practice with a step-down strategy, and to evaluate factors predictive of PPI responsiveness. METHODS We collected data regarding the efficacy of PPIs during this cross-sectional analysis of the prospective nationwide RENESE registry. Children with EoE treated with PPI monotherapy were included. Histological remission was defined as a peak eosinophilic count of <15 eosinophils (eos)/high-power field (hpf). Factors associated with PPI responsiveness were identified using multivariate logistic regression analysis. RESULTS After induction therapy, histological and clinico-histological remission were observed in 51.4% (n = 346) and 46.5% of children, respectively. Normal endoscopic appearance of the esophagus was associated with a higher possibility [odds ratio (OR), 9.20; 95% confidence interval (CI), 2.10-40.16], and fibrostenotic phenotype was associated with a lower possibility (OR, 0.36; 95% CI, 0.18-0.74) of histological remission. Long-term therapy with a step-down strategy effectively maintained histological remission in 68.5% and 85.3% of children at 7 months (n = 108) and 16 months (n = 34), respectively. Complete initial histological remission (≤5 eos/hpf) was associated with a higher possibility of sustained histological remission (OR, 5.08; 95% CI, 1.75-14.68). Adverse events were infrequent and mild. CONCLUSIONS We confirmed the efficacy of PPIs for a large cohort of children with EoE with sustained histological remission using a step-down strategy. Children with fibrostenotic phenotypes are less likely to respond to induction therapy. Furthermore, patients with complete initial histological remission are more likely to experience long-term histological remission.
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Visaggi P, Baiano Svizzero F, Savarino E. Food elimination diets in eosinophilic esophagitis: Practical tips in current management and future directions. Best Pract Res Clin Gastroenterol 2023; 62-63:101825. [PMID: 37094908 DOI: 10.1016/j.bpg.2023.101825] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2022] [Accepted: 01/16/2023] [Indexed: 04/26/2023]
Abstract
Eosinophilic esophagitis (EoE) is a chronic, antigen-mediated disease of the esophagus characterized by symptoms of esophageal dysfunction and an eosinophil-predominant inflammation. Seminal reports identified the role of food allergens in the pathogenesis of the disease by demonstrating that food avoidance could lead to the resolution of esophageal eosinophilia in EoE patients. Although pharmacological treatments for EoE are increasingly being investigated, the exclusion of trigger foods from the diet still represents a valuable option for patients to achieve and maintain disease remission without drugs. Food elimination diets are variegated, and one size does not fit all. Accordingly, before starting any elimination diet, patients' characteristics should be thoroughly evaluated, and a rigorous management plan should be defined. This review provides practical tips and considerations to succeed in the management of EoE patients undergoing food elimination diets, as well as recent advances and future perspectives on food avoidance strategies.
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Affiliation(s)
- Pierfrancesco Visaggi
- Division of Gastroenterology, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Paradisa 2, 56125, Pisa, Italy.
| | - Federica Baiano Svizzero
- Division of Gastroenterology, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Paradisa 2, 56125, Pisa, Italy.
| | - Edoardo Savarino
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy.
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47
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Mechanisms and clinical management of eosinophilic oesophagitis: an overview. Nat Rev Gastroenterol Hepatol 2023; 20:101-119. [PMID: 36253463 DOI: 10.1038/s41575-022-00691-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/14/2022] [Indexed: 02/03/2023]
Abstract
Since the first description of eosinophilic oesophagitis (EoE) less than three decades ago, we have observed a striking increase in the number of patients diagnosed with EoE and the understanding of its clinical and immunopathogenic background. Nonetheless, a plethora of open questions await elucidation. In this Review, we discuss the current state of knowledge regarding the underlying mechanisms, particularly environmental factors and their interaction with genetic susceptibility. Subsequently, we discuss how to translate these factors into the diagnostic and therapeutic management of this chronic, immune-mediated disorder. Finally, we dissect the still long list of unmet needs, such as reasons for and handling refractory EoE and atypical clinical presentations. These open questions can guide us through future research steps and potentially foster reconsideration of the diagnostic guidelines of EoE.
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48
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Alexander JA, Ravi K, Symrk TC, Wu TT, Lavey CJ, Geno D, Johnson AJ, Lennon RJ, Collins MH, Dellon ES, Katzka DA. Use of the Esophageal Sponge in Directing Food Reintroduction in Eosinophilic Esophagitis. Clin Gastroenterol Hepatol 2023; 21:299-306.e3. [PMID: 35697266 DOI: 10.1016/j.cgh.2022.05.029] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Revised: 05/18/2022] [Accepted: 05/26/2022] [Indexed: 02/01/2023]
Abstract
BACKGROUND & AIMS Dietary therapy is successful in eosinophilic esophagitis (EoE) but requires multiple upper endoscopies. The aim of this study was to determine if food reintroduction in EoE can be directed by minimally-invasive esophageal sponge cytology. METHODS In this prospective non-blinded trial, 22 responders to 6-food elimination diets underwent sequential food reintroduction guided by esophageal sponge cytology. Foods were reintroduced followed by unsedated esophageal sponge cytology assessment. A food trigger was defined by sponge cytology peak eosinophil count of ≥15 eos/high-powered field (hpf). Symptoms (EoE symptom activity index [EEsAI]), endoscopic score (EoE endoscopic reference score [EREFS]), and biopsy histology (peak eosinophil count) were collected pre-dietary therapy and post-dietary therapy, and then 4 weeks post food reintroduction. RESULTS The EEsAI and EREFS were similar post-dietary therapy to post-food reintroduction: 12.0 (interquartile range [IQR], 0.0-27.0) vs 16.5 (IQR, 9.0-28.8) (P = .265) and 1.5 (IQR, 0.2-3.0) vs 1.0 (IQR, 0.0-2.0) (P = .185). However, the peak eosinophil count was increased post-food reintroduction compared with post-dietary therapy: 20.0 (IQR, 5.0-51.5) vs 2.0 (IQR, 1.0-4.0) (P < .001), suggesting a failure of identification of all food triggers. The peak eosinophil count was lower post-food reintroduction compared with pre-dietary therapy: 20.0 (IQR, 5.0-51.5) vs 52.0 (IQR, 30.8-76.2) (P = .008). At the post food reintroduction evaluation, sponge cytology and biopsy histology were in agreement in 59% (13/22) of cases using a cutoff of <15 eos/hpf and 68% (15/22) of cases using a cutoff of <6 eos/hpf. CONCLUSIONS In the first study to evaluate a non-endoscopic technique in the clinical management of EoE, the esophageal sponge was moderately successful at guiding food reintroduction in EoE dietary responders in the outpatient setting. CLINICALTRIALS gov, Number NCT02599558.
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Affiliation(s)
- Jeffrey A Alexander
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
| | - Karthik Ravi
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Thomas C Symrk
- Department of Pathology, Mayo Clinic, Rochester, Minnesota
| | - Tsung-The Wu
- Department of Pathology, Mayo Clinic, Rochester, Minnesota
| | - Crystal J Lavey
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Debra Geno
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Alyssa J Johnson
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Ryan J Lennon
- Department of Biostatistics, Mayo Clinic, Rochester, Minnesota
| | - Margaret H Collins
- Division of Pathology and Laboratory Medicine, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio
| | - Evan S Dellon
- Department of Gastroenterology, University of North Carolina, Chapel Hill, North Carolina
| | - David A Katzka
- Department of Gastroenterology, Columbia University Medical Center, New York, New York
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Kinoshita Y, Yahata S, Oouchi S. Eosinophilic Gastrointestinal Diseases: The Pathogenesis, Diagnosis, and Treatment. Intern Med 2023; 62:1-10. [PMID: 34670903 PMCID: PMC9876718 DOI: 10.2169/internalmedicine.8417-21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Eosinophilic gastrointestinal diseases are delayed-type chronic allergic disorders that show gastrointestinal eosinophil dense infiltration, with an exaggerated Th2-type immune reaction considered to be an important mechanism. These diseases can be roughly divided into two types: eosinophilic esophagitis, mainly found in young and middle-aged men, and eosinophilic gastroenteritis, which is found in both genders equally. A diagnosis of eosinophilic esophagitis is suspected when characteristic endoscopic findings, including longitudinal furrows and rings, are noted. However, characteristic endoscopic abnormalities are rarely found in cases with eosinophilic gastroenteritis, so multiple biopsy sampling from the apparently normal gastrointestinal mucosal surface is important for making an accurate diagnosis. The administration of systemic glucocorticoid is the standard treatment for eosinophilic gastroenteritis, while acid inhibitors and topical glucocorticoid swallowing therapy are effective for eosinophilic esophagitis. Anti-cytokine therapies for eosinophilic gastrointestinal diseases are currently under development.
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Affiliation(s)
- Yoshikazu Kinoshita
- Department of Medicine, Hyogo-Brain and Heart Center at Himeji, Japan
- Department of Medicine, Steel Memorial Hirohata Hospital, Japan
| | - Shinsuke Yahata
- Department of Medicine, Steel Memorial Hirohata Hospital, Japan
| | - Sachiko Oouchi
- Department of Medicine, Steel Memorial Hirohata Hospital, Japan
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50
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Sykes C, Fairlamb G, Fox M, Sweis R. Assessment of Esophageal Motility in Patients With Eosinophilic Esophagitis: A Scoping Review. J Clin Gastroenterol 2023; 57:10-30. [PMID: 36504227 DOI: 10.1097/mcg.0000000000001792] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Accepted: 10/08/2022] [Indexed: 12/15/2022]
Abstract
Eosinophilic esophagitis (EoE) is a chronic, immune-mediated condition causing esophageal symptoms, particularly dysphagia. Despite the important progress in the treatment of EoE, a significant proportion of patients continue to report symptoms that negatively impact quality of life. Esophageal manometry is used to assess motility and function, but is not routinely used in EoE. We aimed to systematically review and describe current literature evaluating esophageal manometry in EoE. Forty-eight studies meeting the criteria were identified, describing 802 patients. Using standard water swallow protocols, the proportion of abnormalities detected was not dissimilar to other populations, apart from disorders of esophago-gastric outflow, which were found in 5%. Twelve studies described pretreatment and posttreatment manometry, with motility normalization after pharmacological therapy reported in 20%. Early, brief panesophageal pressurization was described in a number of studies and was more prevalent in the few studies utilizing additional provocation testing. Reports in the literature regarding temporal relationships between manometric findings and symptoms are variable. Esophageal manometry may be capable of detecting clinically relevant changes to esophageal function in EoE. Possible mechanisms are altered neuromuscular function because of secretory products of EoE and/or fibroinflammatory processes, manifesting as pressurization because of altered esophageal compliance. Some changes may be reversible with therapy. Drawing strong conclusions from the literature is difficult, with bias toward case reports and retrospective observation. Adaptations to assessment protocols to include provocation testing may provide more robust evaluation and detect clinically relevant, subtle changes in esophageal function, earlier within the patient pathway.
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Affiliation(s)
- Catherine Sykes
- Medical Physics Department, County Durham and Darlington NHS Foundation Trust, Durham, UK
- Medical Physics Department, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle, UK
| | - Grace Fairlamb
- Medical Physics Department, County Durham and Darlington NHS Foundation Trust, Durham, UK
- Medical Physics Department, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle, UK
| | - Mark Fox
- Department of Gastroenterology and Hepatology, University Hospital Zürich, Zürich, Switzerland
- Digestive Function: Basel, Department of Gastroenterology, Klinik Arlesheim, Arlesheim, Switzerland
| | - Rami Sweis
- GI Physiology Unit, University College London Hospitals NHS Foundation Trust, London, UK
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