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Wickramasinghe N, Devanarayana NM. Insight into global burden of gastroesophageal reflux disease: Understanding its reach and impact. World J Gastrointest Pharmacol Ther 2025; 16:97918. [PMID: 40094147 PMCID: PMC11907340 DOI: 10.4292/wjgpt.v16.i1.97918] [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: 06/12/2024] [Revised: 10/29/2024] [Accepted: 12/10/2024] [Indexed: 03/03/2025] Open
Abstract
The exact worldwide prevalence of gastroesophageal reflux disease (GERD) remains uncertain, despite its recognition as a common condition. This conundrum arises primarily from the lack of a standardized definition for GERD. The gold standard diagnostic tests for GERD, such as pH impedance testing and endoscopy, are cumbersome and impractical for assessing community prevalence. Consequently, most epidemiological studies rely on symptom-based screening tools. GERD symptoms can be both esophageal and extraesophageal, varying widely among individuals. This variability has led to multiple symptom-based definitions of GERD, with no consensus, resulting in prevalence estimates ranging from 5% to 25% worldwide. Most systematic reviews define GERD as experiencing heartburn and/or regurgitation at least once weekly, yielding a calculated prevalence of 13.98%. In 2017, the global age-standardized prevalence of GERD was estimated at 8819 per 100000 people (95% confidence interval: 7781-9863), a figure that has remained stable from 1990 to 2017. Prevalence increases with age, leading to more years lived with disability. GERD significantly impairs quality of life and can lead to multiple complications. Additionally, it imposes a severe economic burden, with the United States alone estimated to spend around 10 billion dollars annually on diagnosis and treatment. In summary, GERD prevalence varies greatly by region and even within different areas of the same province. Determining the exact prevalence is challenging due to inconsistent diagnostic criteria. However, it is well-documented that GERD poses a significant global burden, affecting the quality of life of individuals and creating a substantial healthcare cost.
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Affiliation(s)
- Nilanka Wickramasinghe
- Department of Physiology, Faculty of Medicine, University of Colombo, Colombo 00800, Western Province, Sri Lanka
| | - Niranga Manjuri Devanarayana
- Department of Physiology, Faculty of Medicine, University of Kelaniya, Ragama 11010, Western Province, Sri Lanka
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García-Compeán D, Jiménez-Rodríguez AR, González-Martínez CE. Eosinophilic esophagitis: Current concepts of pathophysiology, diagnosis, and treatment. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2025; 90:63-76. [PMID: 40307156 DOI: 10.1016/j.rgmxen.2024.09.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/10/2024] [Accepted: 09/26/2024] [Indexed: 05/02/2025]
Abstract
Eosinophilic esophagitis (EoE) is a chronic, immune-mediated disease characterized by the infiltration of eosinophils into the esophageal mucosa. It is the most frequent cause of dysphagia and food impaction in adults. Due to its similar pathophysiology to allergic rhinitis, asthma, and atopic dermatitis, it has been considered the esophageal manifestation of allergy. It is more frequently seen in the United States, Europe, and Australia. Incidence and prevalence have increased significantly in those countries over the past three decades, to such a degree that some consider it an epidemic. The disease is infrequently diagnosed in Mexico and Latin America, and so little information on this disease is produced in our region of the world. The precise factors explaining this low incidence are unknown. On the other hand, there has been intense research on EoE in other parts of the world in recent years. Its pathophysiology has been better understood and endoscopic and clinical procedures have been refined for making the diagnosis. In addition, new drugs and special formulations of existing ones have been introduced for treating the disease. Simpler and more effective dietary treatment strategies have also been evaluated. The aim of the present work was to review the current status of EoE globally and in Mexico, emphasizing the probable factors (environmental and technical) that intervene in the low incidence recorded in our country. In addition, we conducted a review of the advances in research on the different aspects of EoE carried out in recent years.
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Affiliation(s)
- D García-Compeán
- Servicio de Gastroenterología, Hospital Universitario «Dr. José Eleuterio González», Facultad de Medicina, Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, Mexico.
| | - A R Jiménez-Rodríguez
- Servicio de Gastroenterología, Hospital Universitario «Dr. José Eleuterio González», Facultad de Medicina, Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, Mexico
| | - C E González-Martínez
- Servicio de Gastroenterología, Hospital Universitario «Dr. José Eleuterio González», Facultad de Medicina, Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, Mexico
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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; 90:63-76. [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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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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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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Chang JW, Jensen ET. Epidemiologic and Clinical Clues to the Etiology of Eosinophilic Esophagitis. Immunol Allergy Clin North Am 2024; 44:145-155. [PMID: 38575214 PMCID: PMC11003716 DOI: 10.1016/j.iac.2023.12.003] [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] [Indexed: 04/06/2024]
Abstract
Despite the rising prevalence and incidence of eosinophilic esophagitis (EoE), the etiology and pathophysiology remain unknown. Studies to date suggest that complex interactions between genetic and environmental risk factors result in the development and presentation of disease. Examining environmental factors both in the early life and later life exposures offers potential clues for the development of EoE, although challenges exist in making causal inferences due to diagnostic delay and access, ascertainment biases, and misclassification of cases. The authors review studies supporting early life factors as etiologic factors in the development of EoE.
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Affiliation(s)
- Joy W Chang
- Division of Gastroenterology, Department of Internal Medicine, 3912 Taubman Center, 1500 East Medical Center Drive, SPC 5362, Ann Arbor, MI 48109, USA.
| | - Elizabeth T Jensen
- Department of Epidemiology and Prevention, Wake Forest University School of Medicine, 475 Vine Street, Winston-Salem, NC 27101, USA
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Ding J, Garber JJ, Uchida A, Lefkovith A, Carter GT, Vimalathas P, Canha L, Dougan M, Staller K, Yarze J, Delorey TM, Rozenblatt-Rosen O, Ashenberg O, Graham DB, Deguine J, Regev A, Xavier RJ. An esophagus cell atlas reveals dynamic rewiring during active eosinophilic esophagitis and remission. Nat Commun 2024; 15:3344. [PMID: 38637492 PMCID: PMC11026436 DOI: 10.1038/s41467-024-47647-0] [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: 09/08/2023] [Accepted: 04/09/2024] [Indexed: 04/20/2024] Open
Abstract
Coordinated cell interactions within the esophagus maintain homeostasis, and disruption can lead to eosinophilic esophagitis (EoE), a chronic inflammatory disease with poorly understood pathogenesis. We profile 421,312 individual cells from the esophageal mucosa of 7 healthy and 15 EoE participants, revealing 60 cell subsets and functional alterations in cell states, compositions, and interactions that highlight previously unclear features of EoE. Active disease displays enrichment of ALOX15+ macrophages, PRDM16+ dendritic cells expressing the EoE risk gene ATP10A, and cycling mast cells, with concomitant reduction of TH17 cells. Ligand-receptor expression uncovers eosinophil recruitment programs, increased fibroblast interactions in disease, and IL-9+IL-4+IL-13+ TH2 and endothelial cells as potential mast cell interactors. Resolution of inflammation-associated signatures includes mast and CD4+ TRM cell contraction and cell type-specific downregulation of eosinophil chemoattractant, growth, and survival factors. These cellular alterations in EoE and remission advance our understanding of eosinophilic inflammation and opportunities for therapeutic intervention.
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Affiliation(s)
- Jiarui Ding
- Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA
- Department of Computer Science, University of British Columbia, Vancouver, BC, V6T 1Z4, Canada
| | - John J Garber
- Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA.
- Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.
| | - Amiko Uchida
- Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA
| | - Ariel Lefkovith
- Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA
| | - Grace T Carter
- Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA
| | - Praveen Vimalathas
- Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA
- Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA
| | - Lauren Canha
- Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA
| | - Michael Dougan
- Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA
| | - Kyle Staller
- Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA
| | - Joseph Yarze
- Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA
| | - Toni M Delorey
- Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA
| | - Orit Rozenblatt-Rosen
- Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA
- Genentech, South San Francisco, CA, 94080, USA
| | - Orr Ashenberg
- Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA
| | - Daniel B Graham
- Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA
- Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA
- Center for Computational and Integrative Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA
- Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA
| | - Jacques Deguine
- Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA
| | - Aviv Regev
- Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
- Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, 02142, USA.
- Genentech, South San Francisco, CA, 94080, USA.
| | - Ramnik J Xavier
- Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
- Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.
- Center for Computational and Integrative Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.
- Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.
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Nanda N, Chhetri D. Eosinophilic Esophagitis: What the Otolaryngologist Needs to Know. Otolaryngol Clin North Am 2024; 57:343-352. [PMID: 37951721 DOI: 10.1016/j.otc.2023.10.004] [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: 11/14/2023]
Abstract
Eosinophilic esophagitis is a male-predominant disease with presentations ranging from nonspecific feeding issues to dysphagia and food impaction. The currently proposed pathophysiology is a combination of genetics, allergens, and epithelial barrier impairment. Diagnosis is reliant on history, endoscopic examination, and biopsy. Recent guidelines recognize the role of concurrent gastroesophageal reflux disease. Treatment is based on 3 paradigms: diet, drugs, and dilation. Drug therapy has historically focused on topical corticosteroids; as of 2022, dupilumab was approved for targeted biologic therapy. Dilation is reserved for symptomatic and anatomic management. As this clinical entity is better understood, additional therapies will hopefully be developed.
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Affiliation(s)
- Nainika Nanda
- Department of Head & Neck Surgery, University of California Los Angeles, 200 UCLA Medical Plaza, Suite 550, Los Angeles, CA 90024, USA
| | - Dinesh Chhetri
- Department of Head & Neck Surgery, University of California Los Angeles, 200 UCLA Medical Plaza, Suite 550, Los Angeles, CA 90024, USA.
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Wu J, Duan C, Han C, Hou X. Identification of CXC Chemokine Receptor 2 (CXCR2) as a Novel Eosinophils-Independent Diagnostic Biomarker of Pediatric Eosinophilic Esophagitis by Integrated Bioinformatic and Machine-Learning Analysis. Immunotargets Ther 2024; 13:55-74. [PMID: 38328342 PMCID: PMC10849108 DOI: 10.2147/itt.s439289] [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: 09/08/2023] [Accepted: 01/17/2024] [Indexed: 02/09/2024] Open
Abstract
Background Eosinophilic esophagitis (EoE) is a complex allergic condition frequently accompanied by various atopic comorbidities in children, which significantly affects their life qualities. Therefore, this study aimed to evaluate pivotal molecular markers that may facilitate the diagnosis of EoE in pediatric patients. Methods Three available EoE-associated gene expression datasets in children: GSE184182, GSE 197702, GSE55794, along with GSE173895 were downloaded from the GEO database. Differentially expressed genes (DEGs) identified by "limma" were intersected with key module genes identified by weighted gene co-expression network analysis (WGCNA), and the shared genes went through functional enrichment analysis. The protein-protein interaction (PPI) network and the machine learning algorithms: least absolute shrinkage and selection operator (LASSO), random forest (RF), and XGBoost were used to reveal candidate diagnostic markers for EoE. The receiver operating characteristic (ROC) curve showed the efficacy of differential diagnosis of this marker, along with online databases predicting its molecular regulatory network. Finally, we performed gene set enrichment analysis (GSEA) and assessed immune cell infiltration of EoE/control samples by using the CIBERSORT algorithm. The correlations between the key diagnostic biomarker and immune cells were also investigated. Results The intersection of 936 DEGs and 1446 key module genes in EoE generated 567 genes, which were primarily enriched in immune regulation. Following the construction of the PPI network and filtration by machine learning, CXCR2 served as a potential diagnostic biomarker of pediatric EoE with a perfect diagnostic efficacy (AUC = ~1.00) in regional tissue/peripheral whole blood samples. Multiple infiltrated immune cells were observed to participate in disrupting the homeostasis of esophageal epithelium to varying degrees. Conclusion The immune-correlated CXCR2 gene was proved to be a promising diagnostic indicator for EoE, and dysregulated regulatory T cells (Tregs)/neutrophils might play a crucial role in the pathogenesis of EoE in children.
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Affiliation(s)
- Junhao Wu
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China
| | - Caihan Duan
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China
| | - Chaoqun Han
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China
| | - Xiaohua Hou
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China
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10
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Low EE, Dellon ES. Review article: Emerging insights into the epidemiology, pathophysiology, diagnostic and therapeutic aspects of eosinophilic oesophagitis and other eosinophilic gastrointestinal diseases. Aliment Pharmacol Ther 2024; 59:322-340. [PMID: 38135920 PMCID: PMC10843587 DOI: 10.1111/apt.17845] [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: 07/21/2023] [Revised: 09/08/2023] [Accepted: 12/13/2023] [Indexed: 12/24/2023]
Abstract
BACKGROUND Eosinophilic gastrointestinal diseases (EGIDs) are chronic, immune-mediated disorders characterised clinically by gastrointestinal symptoms and histologically by a pathologic increase in eosinophil-predominant inflammation in the gastrointestinal tract, in the absence of secondary causes of eosinophilia. AIMS To highlight emerging insights and research efforts into the epidemiology, pathophysiology, diagnostic and therapeutic aspects of eosinophilic oesophagitis (EoE) and non-EoE EGIDs, and discuss key remaining knowledge gaps. METHODS We selected and reviewed original research, retrospective studies, case series, randomised controlled trials, and meta-analyses. RESULTS Standardised nomenclature classifies EGIDs as EoE, eosinophilic gastritis (EoG), eosinophilic enteritis (EoN), and eosinophilic colitis (EoC). Incidence and prevalence of EoE are rising, emphasising the need to better understand how environmental risk factors and genetic features interact. Advances in understanding EoE pathophysiology have led to clinical trials of targeted therapy and the approval (in the United States) of dupilumab for EoE. Several therapies that are under investigation hope to satisfy both histologic and clinical targets. For non-EoE EGIDs, efforts are focused on better defining clinical and histopathologic disease determinants and natural history, as well as establishing new therapies. CONCLUSIONS Unmet needs for research are dramatically different for EoE and non-EoE EGIDs. In EoE, non-invasive diagnostic tests, clinicopathologic models that determine the risk of disease progression and therapeutic failure, and novel biologic therapies are emerging. In contrast, in non-EoE EGIDs, epidemiologic trends, diagnostic histopathologic thresholds, and natural history models are still developing for these more rare disorders.
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Affiliation(s)
- Eric E. Low
- Division of Gastroenterology and Hepatology, University of California San Diego, San Diego, CA, USA
| | - Evan S. Dellon
- Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, NC, USA
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11
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Ketchem CJ, Ocampo AA, Xue Z, Chang NC, Thakkar KP, Reddy S, Greenberg SB, Lee CJ, Redd WD, Eluri S, Reed CC, Dellon ES. Higher Body Mass Index Is Associated With Decreased Treatment Response to Topical Steroids in Eosinophilic Esophagitis. Clin Gastroenterol Hepatol 2023; 21:2252-2259.e3. [PMID: 36410644 PMCID: PMC11508185 DOI: 10.1016/j.cgh.2022.11.004] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2022] [Revised: 11/01/2022] [Accepted: 11/04/2022] [Indexed: 11/21/2022]
Abstract
BACKGROUND & AIMS Understanding which eosinophilic esophagitis (EoE) patients will respond to treatment with topical corticosteroids (tCS) remains challenging, and it is unknown whether obesity impacts treatment response. This study aimed to determine whether treatment outcomes to tCS in EoE patients vary by body mass index (BMI). METHODS This retrospective cohort study of the University of North Carolina EoE Clinicopathologic database assessed subjects age 14 years or older with a new diagnosis of EoE. Their BMI was calculated and histologic, symptom, and endoscopic responses were recorded after tCS treatment. The treatment response of obese (BMI, ≥30 kg/m2) and nonobese EoE status was compared using bivariate and multivariate analyses. RESULTS We identified 296 EoE patients treated with tCS. Baseline characteristics were similar, although obese EoE patients had more heartburn and hiatal hernias. Histologic response was higher for those who were nonobese compared with obese at fewer than 15 (61% vs 47%; P = .049) and 6 or fewer (54% vs 38%; P = .02) eosinophils per high-power field, respectively. In addition, nonobese patients had significantly greater endoscopic and symptomatic responses. On multivariate analysis, increasing BMI was associated independently with decreased histologic response after accounting for age, heartburn, dilation, and hiatal hernia whether BMI was assessed as a continuous variable (adjusted odds ratio [aOR], 0.93; 95% CI, 0.89-0.98), as nonobese vs obese (aOR, 0.38; 95% CI, 0.21-0.68), or in 4 categories (overweight vs normal [aOR, 0.46; 95% CI, 0.26-0.84] or obese vs normal [aOR, 0.26; 95% CI, 0.13-0.51]). CONCLUSIONS As BMI increases in EoE patients, the odds of histologic, symptomatic, and endoscopic responses to tCS decreases, with obese patients having an approximately 40% decrease in odds of response.
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Affiliation(s)
- Corey J Ketchem
- Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina
| | - Adolfo A Ocampo
- Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina
| | - Zeyun Xue
- Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina
| | - Nicole C Chang
- Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina
| | - Kisan P Thakkar
- Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina
| | - Sumana Reddy
- Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina
| | - Sydney B Greenberg
- Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina
| | - Christopher J Lee
- Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina
| | - Walker D Redd
- Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina
| | - Swathi Eluri
- Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina
| | - Craig C Reed
- Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina
| | - Evan S Dellon
- Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina; Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
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12
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Scherer R, Schreiner P, Rossel JB, Greuter T, Burri E, Saner C, Schlag C, Safroneeva E, Schoepfer A, Straumann A, Biedermann L. Barrett's Esophagus in Eosinophilic Esophagitis in Swiss Eosinophilic Esophagitis Cohort Study (SEECS). Dig Dis 2023; 41:695-707. [PMID: 37231862 DOI: 10.1159/000531060] [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: 11/18/2022] [Accepted: 05/04/2023] [Indexed: 05/27/2023]
Abstract
INTRODUCTION There is a complex interrelationship between gastroesophageal reflux disease (GERD) and eosinophilic esophagitis (EoE) potentially promoting the occurrence and modulating severity of each other reciprocally. Presence of Barrett's esophagus (BE) is a defining factor for the diagnosis of GERD. While several studies investigated the potential impact of concomitant GERD on the presentation and course of EoE, little was known with regards to BE in EoE patients. METHODS We analyzed prospectively collected clinical, endoscopic, and histological data from patients enrolled in the Swiss Eosinophilic Esophagitis Cohort Study (SEECS) regarding differences between EoE patients with (EoE/BE+) versus without BE (EoE/BE-) and determined the prevalence of BE in EoE patients. RESULTS Among a total of 509 EoE patients included in our analysis, 24 (4.7%) had concomitant BE with a high male preponderance (EoE/BE+ 83.3% vs. EoE/BE- 74.4%). While there were no differences in dysphagia, odynophagia was significantly (12.5 vs. 3.1%, p = 0.047) more common in EoE/BE+ versus EoE/BE-. General well-being at last follow-up was significantly lower in EoE/BE+. Endoscopically, we observed an increased incidence of fixed rings in the proximal esophagus in EoE/BE+ (70.8 vs. 46.3% in EoE/BE-, p = 0.019) and a higher fraction of patients with a severe fibrosis in the proximal histological specimen (8.7 vs. 1.6% in EoE/BE, p = 0.017). CONCLUSION Our study reveals that BE is twice as frequent in EoE patients compared to general population. Despite many similarities between EoE patients with and without BE, the finding of a more pronounced remodeling in EoE patients with Barrett is noteworthy.
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Affiliation(s)
- Roger Scherer
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Philipp Schreiner
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | | | - Thomas Greuter
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Emanuel Burri
- Department of Gastroenterology and Hepatology, Cantonal Hospital Liestal, Liestal, Switzerland
| | - Catherine Saner
- Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne, Switzerland
| | - Christoph Schlag
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Ekaterina Safroneeva
- Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland
| | - Alain Schoepfer
- Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne, Switzerland
| | - Alex Straumann
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Luc Biedermann
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
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Tasaki Y, Obata M, Inoue M, Sakazume S, Ohta K. Eosinophilic esophagitis with donut-shaped thickened esophageal mucosa on computed tomography. Pediatr Int 2023; 65:e15639. [PMID: 37804049 DOI: 10.1111/ped.15639] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Revised: 07/03/2023] [Accepted: 07/27/2023] [Indexed: 10/08/2023]
Affiliation(s)
- Yuko Tasaki
- Department of Pediatrics, National Hospital Organization, Kanazawa Medical Center, Kanazawa, Ishikawa, Japan
| | - Misato Obata
- Department of Pediatrics, National Hospital Organization, Kanazawa Medical Center, Kanazawa, Ishikawa, Japan
| | - Mika Inoue
- Department of Pediatrics, National Hospital Organization, Kanazawa Medical Center, Kanazawa, Ishikawa, Japan
| | - Sinobu Sakazume
- Department of Pediatrics, National Hospital Organization, Kanazawa Medical Center, Kanazawa, Ishikawa, Japan
| | - Kazuhide Ohta
- Department of Pediatrics, National Hospital Organization, Kanazawa Medical Center, Kanazawa, Ishikawa, Japan
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14
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Abe Y, Sasaki Y, Yagi M, Mizumoto N, Onozato Y, Umehara M, Ueno Y. Endoscopic Diagnosis of Eosinophilic Esophagitis: Basics and Recent Advances. Diagnostics (Basel) 2022; 12:diagnostics12123202. [PMID: 36553209 PMCID: PMC9777529 DOI: 10.3390/diagnostics12123202] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2022] [Accepted: 12/14/2022] [Indexed: 12/24/2022] Open
Abstract
Eosinophilic esophagitis (EoE) is a chronic, immune-mediated inflammatory disease, characterized by esophageal dysfunction and intense eosinophil infiltration localized in the esophagus. In recent decades, EoE has become a growing concern as a major cause of dysphagia and food impaction in adolescents and adults. EoE is a clinicopathological disease for which the histological demonstration of esophageal eosinophilia is essential for diagnosis. Therefore, the recognition of the characteristic endoscopic features with subsequent biopsy are critical for early definitive diagnosis and treatment, in order to prevent complications. Accumulating reports have revealed that EoE has several non-specific characteristic endoscopic findings, such as rings, furrows, white exudates, stricture/narrowing, edema, and crepe-paper esophagus. These findings were recently unified under the EoE endoscopic reference score (EREFS), which has been widely used as an objective, standard measurement for endoscopic EoE assessment. However, the diagnostic consistency of those findings among endoscopists is still inadequate, leading to underdiagnosis or misdiagnosis. Some endoscopic findings suggestive of EoE, such as multiple polypoid lesions, caterpillar sign, ankylosaurus back sign, and tug sign/pull sign, will aid the diagnosis. In addition, image-enhanced endoscopy represented by narrow band imaging, endocytoscopy, and artificial intelligence are expected to render endoscopic diagnosis more efficient and less invasive. This review focuses on suggestions for endoscopic assessment and biopsy, including recent advances in optical technology which may improve the diagnosis of EoE.
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Affiliation(s)
- Yasuhiko Abe
- Division of Endoscopy, Yamagata University Hospital, Yamagata 990-2321, Japan
- Correspondence:
| | - Yu Sasaki
- Department of Gastroenterology, Faculty of Medicine, Yamagata University, Yamagata 990-2321, Japan
| | - Makoto Yagi
- Division of Endoscopy, Yamagata University Hospital, Yamagata 990-2321, Japan
| | - Naoko Mizumoto
- Department of Gastroenterology, Faculty of Medicine, Yamagata University, Yamagata 990-2321, Japan
| | - Yusuke Onozato
- Department of Gastroenterology, Faculty of Medicine, Yamagata University, Yamagata 990-2321, Japan
| | - Matsuki Umehara
- Department of Gastroenterology, Faculty of Medicine, Yamagata University, Yamagata 990-2321, Japan
| | - Yoshiyuki Ueno
- Department of Gastroenterology, Faculty of Medicine, Yamagata University, Yamagata 990-2321, Japan
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15
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Liu X, Xiao X, Liu D, Tan C. A meta-analysis on randomized controlled trials of treating eosinophilic esophagitis with budesonide. Ann Med 2022; 54:2078-2088. [PMID: 35862288 PMCID: PMC9310820 DOI: 10.1080/07853890.2022.2101689] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
OBJECTIVE Eosinophilic esophagitis (EoE) is a chronic, local immune-mediated inflammatory oesophageal disease. Although Budesonide is recommended as one of the first-line drugs for EoE treatment, its efficacy is still controversial in multiple studies. Due to the continuous emergence of new and reliable research evidence in recent years, we updated the meta-analysis using RCT trial results to evaluate the efficacy and safety of budesonide. MATERIALS AND METHOD Retrieve the data of the randomised controlled trial literature from 2000 to June 20, 2021, on using Budesonide in the treatment of eosinophilic esophagitis from the three major databases. Based on the results achieved with the Cochrane risk assessment tool, evaluate the quality of the included literature to extract the data, and perform the Meta-analysis with RevMan5.4 and Stata15.0. RESULTS A total of 958 articles were retrieved, with 10 articles finally included, thus forming a sample size of 712 cases. The main outcome indicators of the meta-analysis are as follows: (1) Histological remission: the Budesonide group performs better than the placebo control group when it comes to histological remission of injuries [RR = 23.82, 95%CI = (13.46, 42.21), p < .001]; (2) Eosinophil count: the Budesonide group is superior to the control group in terms of reduced eosinophil count [SMD = -1.34, 95%CI = (-1.52, -1.15), p < .001]. CONCLUSION More and more high-quality randomised controlled trials show that oral budesonide in the treatment of eosinophils esophagitis was better than the placebo group. Mounting high-quality RCTs have confirmed the efficacy of oral budesonide in the treatment of eosinophilic esophagitis and that the effects of this drug may not be so dose-dependent. It is safe to take budesonide for a long time, and this drug is a relatively ideal option for drug treatment of eosinophilic esophagitis at present, so it is worthy of clinical application.Key MessagesWe used high-quality randomised controlled trials to meta-update the previous results to further confirm the clinical efficacy and safety of budesonide.Oral budesonide in the treatment of eosinophilic esophagitis is significantly better than the placebo control group. We have confirmed the value of its clinical application and promotion by including more high-quality randomised controlled trials.We also found that the efficacy of budesonide in patients is not dose-dependent, and more research is needed to confirm this.
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Affiliation(s)
- Xiaopei Liu
- School of Basic Medicine, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, China
| | - Xue Xiao
- School of Basic Medicine, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, China
| | - Dan Liu
- Department of Anorectal, Xi'an Hospital of Traditional Chinese Medicine, Xi'an, Shaanxi, China
| | - Cong'e Tan
- School of Basic Medicine, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, China
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16
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Diagnostic Delay in Patients With Eosinophilic Esophagitis Has Not Changed Since the First Description 30 Years Ago: Diagnostic Delay in Eosinophilic Esophagitis. Am J Gastroenterol 2022; 117:1772-1779. [PMID: 35971224 DOI: 10.14309/ajg.0000000000001950] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2022] [Accepted: 08/01/2022] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Eosinophilic esophagitis (EoE) is a chronic progressive disease. Diagnostic delay (DD) is associated with increased risk of esophageal strictures and food impactions. We aimed to assess the evolution of DD since the first description of EoE in 1993 until 2021. METHODS We analyzed data from patients prospectively included in the Swiss EoE database. DD was calculated as the time interval between the first occurrence of EoE symptoms and the confirmed diagnosis. DD was analyzed annually over time (1989-2021) and according to milestone publications in the field (1993: first description; 2007: first consensus recommendations; and 2011: updated consensus recommendations). In addition, a Cox proportional hazards model has been used to describe the relation between DD and covariates. RESULTS Complete data of 1,152 patients (857 male [74%]; median age at diagnosis: 38 years, interquartile range: 28-49, range: 1-86) were analyzed. Overall, median DD was 4 years (interquartile range: 1-11, range, 0-56), with DD ≥ 10 years in 32% of the population. Over time, DD did not significantly change, neither annually nor according to release dates of milestone publications with a persistently stable fraction of roughly one-third of all patients with a DD of ≥10 years. Both ages at diagnosis ( P < 0.001, with an increase in DD up to the age of 31-40 years) and at symptom onset (younger patients had a longer DD; P < 0.001) were significantly associated with DD. DISCUSSION DD has not changed since the first description of EoE almost 30 years ago and remains substantial. Even today, one-third of patients have a persistently high DD of ≥10 years. Substantial efforts are warranted to increase awareness for EoE and its hallmark symptom, solid food dysphagia, as an age-independent red-flag symptom among healthcare professionals and presumably the general population alike to lower risk of long-term complications.
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17
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Suda T, Shirota Y, Hodo Y, Sato K, Wakabayashi T. Mucosal color changes on narrow-band imaging in esophageal eosinophilic infiltration. Medicine (Baltimore) 2022; 101:e29891. [PMID: 36197201 PMCID: PMC9509114 DOI: 10.1097/md.0000000000029891] [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: 11/29/2022] Open
Abstract
This study aimed to examine the range of beige colored mucosa (BCM) in patients with esophageal eosinophilic infiltration (EEI) using narrow-band imaging (NBI). In this retrospective study, EEI was confirmed histologically in 12 consecutive patients from January 2014 to December 2017. The BCM tone on NBI without magnifying endoscopy was evaluated, and red, green, and blue (RGB) values of BCM and normal mucosa were measured. BCM was macroscopically classified into 2 groups (bright and dark) using cluster analysis. Histopathological analysis was performed in 1 patient who underwent biopsy for both normal mucosa and BCM. All 12 patients presented with BCM. Endoscopy revealed fixed rings, longitudinal furrows, mucosal edema, and exudate in 3, 12, 10, and 8 patients, respectively. Strictures were absent. Five patients had findings suggestive of gastroesophageal reflux disease. In the cluster analysis, 5 and 7 patients had bright and dark BCM, respectively. Consistent results were noted when we categorized patients according to their macroscopic characteristics. RGB values of the BCM and normal mucosa were measured-normal mucosa: R: 99.8 ± 16.5, G: 121.7 ± 23.1, and B: 93.4 ± 19.2; BCM: R: 152.0 ± 31.3, G: 123.9 ± 35.0, and B: 97.5 ± 29.5. BCM had significantly higher R values than normal mucosa (P = .0001). All parameters were significantly lower in the dark BCM group than in the bright BCM group (P < .001). Histopathological analysis revealed expansion of the epithelial intercellular space, eosinophilic infiltration, and basal cell hyperplasia at the BCM sites. BCM was observed in all cases of EEI. RGB values differed between bright and dark BCM. Assessing BCM tone using NBI is a potentially novel diagnostic method for EEI.
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Affiliation(s)
- Tsuyoshi Suda
- Department of Gastroenterology, Saiseikai Kanazawa Hospital, Ishikawa, Japan
- *Correspondence: Tsuyoshi Suda, MD, Department of Gastroenterology, Saiseikai Kanazawa Hospital, Ni 13-6, Akatsuchimachi, Kanazawa, Ishikawa 920-0353, Japan (e-mail: )
| | - Yukihiro Shirota
- Department of Gastroenterology, Saiseikai Kanazawa Hospital, Ishikawa, Japan
| | - Yuji Hodo
- Department of Gastroenterology, Saiseikai Kanazawa Hospital, Ishikawa, Japan
| | - Katsuaki Sato
- Department of Pathology II, Kanazawa Medical University, Ishikawa, Japan
| | - Tokio Wakabayashi
- Department of Gastroenterology, Saiseikai Kanazawa Hospital, Ishikawa, Japan
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Abstract
INTRODUCTION Eosinophilic esophagitis (EoE) is a clinical and pathological disorder, characterized by symptoms of esophageal dysfunction, and eosinophil-predominant inflammation restricted to the esophagus. Treatment outcomes include symptomatic remission, histological and endoscopic normalization and improving quality of life. Besides dietary modifications and endoscopic dilation, drugs available are swallowed topical corticosteroids (STCs) with reduced bioavailability and proton pump inhibitors (PPI). AREAS COVERED Herein, the authors review the current treatment strategies for EoE in adults, providing the reader with their expert perspectives. The authors give discussion to the value of PPIs as a first-line therapy for EoE, in addition to the use of STCs. The current development of new formulations of STCs targeting the esophagus and novel therapies aimed at blocking molecular pathways are also discussed. Finally, the authors briefly look at the value of monoclonal antibodies targeting IL-5RA, IL-13, IL-4 or Siglec8, and oral S1PR agonists to the treatment of EoE. EXPERT OPINION Viscose formulations of STC designed to coat the esophagus and new effervescent orodispersible tablets provide increased effectiveness at low doses. Investigational therapies that target several Th2-associated diseases seem useful in EoE. Comparative effectiveness and cost-utility analyses will help to position them in a complex therapeutic scenario.
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Affiliation(s)
- Alfredo J Lucendo
- Department of Gastroenterology. Hospital General de Tomelloso, Tomelloso, Spain.,Instituto de Investigación Sanitaria La Princesa, Spain.,Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM).,Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBERehd), Spain
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19
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Lam AY, Ma C, Lee JK, Bredenoord AJ. Eosinophilic esophagitis: New molecules, better life? Curr Opin Pharmacol 2022; 63:102183. [PMID: 35176546 DOI: 10.1016/j.coph.2022.102183] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Revised: 01/10/2022] [Accepted: 01/12/2022] [Indexed: 11/03/2022]
Abstract
Eosinophilic esophagitis (EoE) is an antigen-mediated chronic T helper type 2 (Th2)-associated inflammatory disorder that has emerged in the last three decades as an increasingly common cause of esophageal symptoms. Despite rising incidence and prevalence, there are currently no approved therapies for EoE in the United States and only one oral topical corticosteroid approved in Europe and Canada. Current management relies on labor- and endoscopy-intensive dietary elimination, proton-pump inhibitors (PPIs) with only moderate efficacy, and use of inhaled or nebulized topical corticosteroids designed for asthma and limited by accessibility. Fortunately, progress in elucidating the underlying pathophysiology of EoE has led to the development of new therapies derived from molecular targets necessary for disease pathogenesis. We summarize established and emerging medical therapies for EoE, with a focus on new treatments with specific molecular targets that are likely to change EoE management paradigms in the next decade.
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Affiliation(s)
- Angela Y Lam
- Department of Gastroenterology, Kaiser Permanente San Francisco, San Francisco, CA, USA
| | - Christopher Ma
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada; Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
| | - Jeffrey K Lee
- Department of Gastroenterology, Kaiser Permanente San Francisco, San Francisco, CA, USA; Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA
| | - Albert J Bredenoord
- Department of Gastroenterology and Hepatology, Academic Medical Centre, Amsterdam, the Netherlands.
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20
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Franciosi JP, Mougey EB, Dellon ES, Gutierrez-Junquera C, Fernandez-Fernandez S, Venkatesh RD, Gupta SK. Proton Pump Inhibitor Therapy for Eosinophilic Esophagitis: History, Mechanisms, Efficacy, and Future Directions. J Asthma Allergy 2022; 15:281-302. [PMID: 35250281 PMCID: PMC8892718 DOI: 10.2147/jaa.s274524] [Citation(s) in RCA: 35] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2021] [Accepted: 01/14/2022] [Indexed: 12/11/2022] Open
Abstract
Over the past decade, the role of proton pump inhibitor (PPI) medication has evolved from a diagnostic tool for Eosinophilic Esophagitis (EoE), by excluding patients with PPI responsive esophageal eosinophilia (PPI-REE), to a therapy for EoE. This transition resulted from the Updated International Consensus Diagnostic Criteria for Eosinophilic Esophagitis: Proceedings of the Appraisal of Guidelines for Research and Evaluation II (AGREE) Conference to support PPI therapy for EoE in children and adults. Additional recent advances have suggested a role for genetic variations that might impact response to PPI therapy for EoE. This review article will explore a brief background of EoE, the evolution of PPI therapy for EoE and its proposed mechanisms, efficacy and safety in children and adults, and considerations for future PPI precision medicine in patients with EoE.
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Affiliation(s)
- James P Franciosi
- Division of Gastroenterology, Nemours Children’s Hospital, Orlando, FL, USA
- College of Medicine, University of Central Florida, Orlando, FL, USA
- Correspondence: James P Franciosi, Division of Gastroenterology, Nemours Children’s Hospital, 6535 Nemours Parkway, Orlando, FL, 32827, USA, Email
| | - Edward B Mougey
- Center for Pharmacogenomics and Translational Research, Nemours Children’s Health System, Jacksonville, FL, USA
| | - Evan S Dellon
- Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, NC, USA
| | - Carolina Gutierrez-Junquera
- Pediatric Gastroenterology Unit, Hospital Universitario Puerta de Hierro-Majadahonda, Autonomous University of Madrid, Madrid, Spain
| | | | - Rajitha D Venkatesh
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Nationwide Children’s Hospital, Columbus, OH, USA
| | - Sandeep K Gupta
- Section of Pediatric Gastroenterology, Hepatology and Nutrition, Riley Hospital for Children, Indiana University School of Medicine and Community Health Network, Indianapolis, IN, USA
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21
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Racca F, Pellegatta G, Cataldo G, Vespa E, Carlani E, Pelaia C, Paoletti G, Messina MR, Nappi E, Canonica GW, Repici A, Heffler E. Type 2 Inflammation in Eosinophilic Esophagitis: From Pathophysiology to Therapeutic Targets. Front Physiol 2022; 12:815842. [PMID: 35095572 PMCID: PMC8790151 DOI: 10.3389/fphys.2021.815842] [Citation(s) in RCA: 41] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2021] [Accepted: 12/09/2021] [Indexed: 12/11/2022] Open
Abstract
Eosinophilic esophagitis (EoE) is a chronic immune-mediated disease of the esophagus characterized clinically by symptoms related to esophageal dysfunction and histologically by eosinophil-predominant inflammation, whose incidence is rising. It significantly affects patients’ quality of life and, if left untreated, results in fibrotic complications. Although broad consensus has been achieved on first-line therapy, a subset of patients remains non-responder to standard therapy. The pathogenesis of EoE is multifactorial and results from the complex, still mostly undefined, interaction between genetics and intrinsic factors, environment, and antigenic stimuli. A deep understanding of the pathophysiology of this disease is pivotal for the development of new therapies. This review provides a comprehensive description of the pathophysiology of EoE, starting from major pathogenic mechanisms (genetics, type 2 inflammation, epithelial barrier dysfunction, gastroesophageal reflux, allergens, infections and microbiota) and subsequently focusing on the single protagonists of type 2 inflammation (involved cells, cytokines, soluble effectors, surface proteins and transcription factors) that could represent present and future therapeutic targets, while summarizing previous therapeutic approaches in literature.
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Affiliation(s)
- Francesca Racca
- Personalized Medicine, Asthma and Allergy, IRCCS Humanitas Research Hospital, Rozzano, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
- *Correspondence: Francesca Racca,
| | - Gaia Pellegatta
- Digestive Endoscopy Unit, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano, Italy
| | - Giuseppe Cataldo
- Personalized Medicine, Asthma and Allergy, IRCCS Humanitas Research Hospital, Rozzano, Italy
| | - Edoardo Vespa
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
- Digestive Endoscopy Unit, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano, Italy
| | - Elisa Carlani
- Digestive Endoscopy Unit, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano, Italy
| | - Corrado Pelaia
- Department of Medical and Surgical Sciences, University “Magna Graecia” of Catanzaro, Catanzaro, Italy
| | - Giovanni Paoletti
- Personalized Medicine, Asthma and Allergy, IRCCS Humanitas Research Hospital, Rozzano, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
| | - Maria Rita Messina
- Personalized Medicine, Asthma and Allergy, IRCCS Humanitas Research Hospital, Rozzano, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
| | - Emanuele Nappi
- Personalized Medicine, Asthma and Allergy, IRCCS Humanitas Research Hospital, Rozzano, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
| | - Giorgio Walter Canonica
- Personalized Medicine, Asthma and Allergy, IRCCS Humanitas Research Hospital, Rozzano, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
| | - Alessandro Repici
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
- Digestive Endoscopy Unit, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano, Italy
| | - Enrico Heffler
- Personalized Medicine, Asthma and Allergy, IRCCS Humanitas Research Hospital, Rozzano, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
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22
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Montoya-Cerrillo D, Bernieh A, Saad AG. Critical diagnoses in paediatric gastrointestinal diseases. Pathology 2022; 54:195-206. [PMID: 35033374 DOI: 10.1016/j.pathol.2021.09.023] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Revised: 09/26/2021] [Accepted: 09/30/2021] [Indexed: 12/11/2022]
Abstract
Gastrointestinal biopsies represent an increasing proportion of the paediatric pathologist's workload, an increase fundamentally due to an expansion of the understanding of the basic clinical, molecular, genetic, and histopathological features of paediatric gastrointestinal disorders. The histological interpretation of endoscopically retrieved gastrointestinal biopsies in children requires a unique set of diagnostic expertise and detailed knowledge of various gastrointestinal disorders that have a predilection for the paediatric population. This article's major role is to highlight the unique problems inherent to paediatric gastrointestinal disorders that require immediate communication with the paediatric surgeon or the gastroenterologist. For this, we tried to cover the most important diseases that a paediatric pathologist might encounter in daily practice. Some of these diseases are relatively rare, such as microvillous inclusion disease and tufting enteropathy, but some are more common such as eosinophilic disorders and inflammatory bowel disease. Awareness of the histopathological features of these diseases, particularly those that are relatively uncommon, is crucial to spare the patient a lengthy and costly evaluation. We made a particular effort to abundantly reference this article should the reader wish to expand on the content of any section.
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Affiliation(s)
| | - Anas Bernieh
- Division of Pathology, Cincinnati Children's Hospital, Cincinnati, OH, USA
| | - Ali G Saad
- Department of Pathology, University of Miami Miller School of Medicine, Miami, FL, USA.
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23
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Esophageal Motility Disorders in the Natural History of Acid-Dependent Causes of Dysphagia and Their Influence on Patients' Quality of Life-A Prospective Cohort Study. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:ijerph182111138. [PMID: 34769657 PMCID: PMC8583542 DOI: 10.3390/ijerph182111138] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Revised: 10/20/2021] [Accepted: 10/20/2021] [Indexed: 12/12/2022]
Abstract
Background: Esophageal dysmotility may be the cause or a secondary effect of gastric acid-dependent diseases: erosive reflux disease (ERD), Schatzki ring (SR) and eosinophilic esophagitis (EoE). Methods: This study aims to compare concomitant dysphagia with ERD, SR and EoE, considering manometric patterns, their role in the natural history and their impact on assessing quality of life. Fifty-eight patients with dysphagia underwent high-resolution manometry and esophago-gastro-duodenoscopy (EGD) with an assessment of SR, ERD and sampling for EoE, completed a questionnaire with the Eating Assessment Tool (EAT-10) and the Gastrointestinal Quality of Life Index. Based on endoscopic images and the histopathological criterion of EoE (≥15 eosinophils/high-power field), patients were assigned to groups with ERD, EoE, SR and with normal endoscopic and histopathological images. In the data analysis, p ≤ 0.05 was considered statistically significant. This trial was registered with ClinicalTrials.gov (no. NCT04803162). Results: Both EoE, SR and ERD correlate with ineffective motility. In ERD, normal peristalsis precedes the development of the disease, unlike EoE, which develops later and leads to absent contractility. The development of SR is associated with disorders of the upper esophageal sphincter (UES). In the group with SR and ERD, UES insufficiency significantly reduces the quality of life. Patients with normal esophagus in EGD scored the lowest quality of life and those with SR had the most severe dysphagia. Conclusion: The esophageal motility disorders co-occurring with endoscopic and histological anomalies do not significantly affect the severity of dysphagia, however, in the case of patients with ERD and SR and concomitant UES insufficiency, this motor dysfunction has a significant impact on the reduction in the patients’ quality of life. Although no specific esophageal motility pattern typical of EoE, ERD and SR has been identified, comparative assessment of manometric features may have a potential role in differential diagnosis.
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24
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Eke R, Dellon ES. Hospitalization trends and determinants of inpatient costs for eosinophilic esophagitis patients in the United States: results from the Nationwide Inpatient Sample analysis. Ann Gastroenterol 2021; 34:643-650. [PMID: 34475734 PMCID: PMC8375654 DOI: 10.20524/aog.2021.0638] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2020] [Accepted: 03/16/2021] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Inpatient care for patients with eosinophilic esophagitis (EoE) is thought to be uncommon, there are few data on inpatient care costs for individuals with EoE. The purpose of this study was to assess trends in inpatient admissions for EoE and examine factors that drive hospitalization costs. METHODS We examined EoE hospitalizations using ICD-9/10 codes, from 2010-2016 in the National Inpatient Sample. We also identified the diagnosis-related group codes, current procedural terminology codes, and common symptom codes documented during admission. We conducted 2 main analyses, primary (all EoE-related hospitalizations) and secondary (hospitalization with a primary diagnosis for EoE), and a sensitivity analysis using only hospitalizations with the secondary diagnosis for EoE, to determine the trend and cost of EoE-related hospitalizations. We used univariate and multivariate models to evaluate the effect of factors that drive hospitalization on total costs. RESULTS Our primary analysis showed that an estimated total of 33,467 EoE-related hospitalizations occurred in the US between 2010 and 2016, representing approximately 13 per 100,000 hospitalizations in the US. The admission rate increased by approximately 70% from 2010-2016 (9.26 to 15.75 per 100,000 hospitalizations), while the total annual and mean inflation-adjusted per-patient costs for EoE-related admissions were $24 million per year and $5135 (standard deviation $153), respectively. Patients and hospital characteristics were independently associated with cost of hospitalization. CONCLUSION The rate of hospital admission for EoE has markedly increased in the US, as has the mean cost for EoE-related hospitalization, at a rate tenfold that of inflation from 2010-2016.
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Affiliation(s)
- Ransome Eke
- Department of Health Science, College of Human Environmental Sciences, The University of Alabama, Tuscaloosa, AL (Ransome Eke)
- Correspondence to: Ransome Eke, MD, PhD, Department of Health Science, College of Human, Environmental Sciences, The University of Alabama, 105 Russell Hall, Tuscaloosa, AL 35487, USA, e-mail:
| | - Evan S. Dellon
- Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, NC (Evan S. Dellon)
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25
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Ghoz H, Stancampiano FF, Valery JR, Nordelo K, Malviya B, Lacy BE, Francis D, DeVault K, Bouras E, Krishna M, Palmer WC. Extent of eosinophilic esophagitis predicts response to treatment. Endosc Int Open 2021; 9:E1234-E1242. [PMID: 34447870 PMCID: PMC8383079 DOI: 10.1055/a-1492-2650] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Accepted: 03/15/2021] [Indexed: 11/13/2022] Open
Abstract
Background and study aim The clinical impact of eosinophilic esophagitis (EoE) limited to the distal esophagus (Lim-EE) vs. diffuse involvement (Dif-EE) is unknown. This study compared clinical characteristics and outcomes of Lim-EE vs. Dif-EE. Patients and methods This retrospective, single-center study of patients with EoE between December 2011 and December 2019 evaluated treatment response based on repeated pathology and/or clinical improvement using comparative statistics. Results 479 patients were identified (126 Lim-EE, 353 Dif-EE). Lim-EE patients had a higher incidence of endoscopically identified esophagitis (23.0 % vs. 14.7 %; P = 0.04), were older (50.8 [SD 16.2] vs. 46.4 [SD 15.3] years; P = 0.007), and were more likely to present with iron deficiency anemia (5.6 % vs. 1.7 %; P = 0.05), dyspepsia (15.1 % vs. 8.8 %; P = 0.06) or for Barrett's surveillance (10.3 % vs. 3.7 %; P = 0.02). Patients with Dif-EE presented more frequently with dysphagia (57.2 % vs. 45.2 %; P = 0.02). Both groups had similar proton pump inhibitor (87.2 % vs. 83.3 %; P = 0.37) and steroid (12.8 % vs. 21.4 %; P = 0.14) use. Patients with Lim-EE had a better clinicopathologic response (61.5 % vs. 44.8 %; P = 0.009). On multivariate analysis, EoE extent predicted treatment response with an odds ratio of 1.89 (95 % confidence interval 1.13-3.20; P = 0.02). However, treatment response based only on repeat biopsy results showed no statistical difference between Lim-EE (52.5 %) and Dif-EE (39.7 %; P = 0.15). Conclusions Lim-EE may represent a distinct phenotype separate from Dif-EE, with more overlap with gastroesophageal reflux disease and better treatment response.
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Affiliation(s)
- Hassan Ghoz
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, United States
| | | | - Jose R. Valery
- Division of Internal Medicine, Mayo Clinic, Jacksonville, Florida, United States
| | - Katie Nordelo
- Clinical Research Internship Study Program (CRISP), Mayo Clinic, Jacksonville, Florida, United States
| | - Balkishan Malviya
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, United States
| | - Brian E. Lacy
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, United States
| | - Dawn Francis
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, United States
| | - Kenneth DeVault
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, United States
| | - Ernest Bouras
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, United States
| | - Murli Krishna
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Jacksonville, Florida, United States
| | - William C. Palmer
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, United States
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26
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Biedermann L, Straumann A, Greuter T, Schreiner P. Eosinophilic esophagitis-established facts and new horizons. Semin Immunopathol 2021; 43:319-335. [PMID: 34097125 PMCID: PMC8241662 DOI: 10.1007/s00281-021-00855-y] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2020] [Accepted: 03/23/2021] [Indexed: 12/13/2022]
Abstract
Despite dramatic advances in our understanding of the pathogenesis and course of disease in the relatively short timeframe since the discovery and first description of eosinophilic esophagitis (EoE) less than three decades ago, many open questions remain to be elucidated. For instance, we will need to better characterize atypical clinical presentations of EoE and other forms of esophageal inflammatory conditions with often similar clinical presentations, nut fulfilling current diagnostic criteria for EoE and to determine their significance and interrelationship with genuine EoE. In addition, the interrelationship of EoE with other immune-mediated diseases remains to be clarified. Hopefully, a closer look at the role of environmental factors and their interaction with genetic susceptibility often in context of atopic predisposition may enable identifying the candidate substances/agents/allergens and potentially earlier (childhood) events to trigger the condition. It appears plausible to assume that in the end—comparable to current concepts in other immune-mediated chronic diseases, such as for instance inflammatory bowel disease or asthma bronchiale—we will not be rewarded with the identification of a “one-and-only” underlying pathogenetic trigger factor, with causal responsibility for the disease in each and every EoE patient. Rather, the relative contribution and importance of intrinsic susceptibility, i.e., patient-driven factors (genetics, aberrant immune response) and external trigger factors, such as food (or aero-) allergens as well as early childhood events (e.g., infection and exposure to antibiotics and other drugs) may substantially differ among given individuals with EoE. Accordingly, selection and treatment duration of medical therapy, success rates and extent of required restriction in dietary treatment, and the need for mechanical treatment to address strictures and stenosis require an individualized approach, tailored to each patient. With the advances of emerging treatment options, the importance of such an individualized and patient-centered assessment will increase even further.
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Affiliation(s)
- Luc Biedermann
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.
| | - Alex Straumann
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Thomas Greuter
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.,Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne, Switzerland
| | - Philipp Schreiner
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
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27
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Wright BL, Fernandez-Becker NQ, Kambham N, Purington N, Cao S, Tupa D, Zhang W, Sindher SB, Rank MA, Kita H, Katzka DA, Shim KP, Bunning BJ, Doyle AD, Jacobsen EA, Tsai M, Boyd SD, Manohar M, Chinthrajah RS. Gastrointestinal Eosinophil Responses in a Longitudinal, Randomized Trial of Peanut Oral Immunotherapy. Clin Gastroenterol Hepatol 2021; 19:1151-1159.e14. [PMID: 32434067 PMCID: PMC8445108 DOI: 10.1016/j.cgh.2020.05.019] [Citation(s) in RCA: 44] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2020] [Accepted: 05/01/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS Gastrointestinal side effects are common during oral immunotherapy (OIT) and eosinophilic esophagitis (EoE) is a potential complication. We aimed to characterize eosinophilic gastrointestinal responses to peanut OIT, in which peanut protein is given orally, with incremental increases in dose over time. METHODS Twenty adults with IgE-mediated peanut allergy were randomly assigned to groups given peanut OIT (n = 15) or placebo (n = 5); 1 additional subject withdrew before randomization. Serial gastrointestinal biopsies were collected at baseline (n = 21, 0 weeks), following dose escalation (n = 10, 52 weeks), and during the maintenance phase (n = 11, 104 weeks). Endoscopic findings were characterized using the EoE endoscopic reference score. Biopsies were assessed for eosinophils per high-power field (eos/hpf) and other pathology features using EoE histologic scoring system scores. We performed immunohistochemical analyses of eosinophil peroxidase deposition, quantified using automated image analysis. RESULTS At baseline, no subjects reported current gastrointestinal symptoms. However, 3 of the 21 subjects (14%) had esophageal peak eosinophil counts ≥15 eos/hpf and all subjects had dilated intercellular spaces (DIS). OIT induced or exacerbated esophageal eosinophilia (EE) at 52 weeks in most subjects (peak eosinophil counts >5 eos/hpf in 6 of 7 patients [86%]; peak eosinophil counts ≥15 eos/hpf in 4 of 7 patients [57%]). One subject met clinicopathologic criteria for EoE and withdrew; no significant changes in esophageal peak eosinophil counts were observed in the placebo group. EE in the OIT group corresponded with significant increases in EoE histologic scoring system scores and deposition of eosinophil peroxidase. In 4 of 6 participants (67%), OIT-induced EE and gastrointestinal eosinophilia resolved by the end of the maintenance phase. Gastrointestinal symptoms were not clearly associated with EE or gastrointestinal eosinophilia. CONCLUSIONS In this pilot study, we found that peanut OIT-induced EE and gastrointestinal eosinophilia are usually transient and are not always associated with gastrointestinal symptoms. Clinicaltrials.gov no: NCT02103270.
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Affiliation(s)
- Benjamin L. Wright
- Division of Allergy, Asthma, and Clinical Immunology, Department of Medicine, Mayo Clinic Arizona, Scottsdale, AZ, United States,Division of Pulmonology, Phoenix Children’s Hospital, Phoenix, AZ, United States
| | - Nielsen Q. Fernandez-Becker
- Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, CA, United States
| | - Neeraja Kambham
- Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, CA, United States,Department of Pathology, Stanford University School of Medicine, Stanford, CA, United States
| | - Natasha Purington
- Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, CA, United States
| | - Shu Cao
- Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, CA, United States
| | - Dana Tupa
- Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, CA, United States
| | - Wenming Zhang
- Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, CA, United States
| | - Sayantani B. Sindher
- Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, CA, United States
| | - Matthew A. Rank
- Division of Allergy, Asthma, and Clinical Immunology, Department of Medicine, Mayo Clinic Arizona, Scottsdale, AZ, United States,Division of Pulmonology, Phoenix Children’s Hospital, Phoenix, AZ, United States
| | - Hirohito Kita
- Division of Allergy, Asthma, and Clinical Immunology, Department of Medicine, Mayo Clinic Arizona, Scottsdale, AZ, United States,Department of Immunology, Mayo Clinic Arizona, Scottsdale, AZ, United States
| | - David A. Katzka
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN. United States
| | - Kelly P. Shim
- Division of Allergy, Asthma, and Clinical Immunology, Department of Medicine, Mayo Clinic Arizona, Scottsdale, AZ, United States,Division of Pulmonology, Phoenix Children’s Hospital, Phoenix, AZ, United States
| | - Bryan J. Bunning
- Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, CA, United States
| | - Alfred D. Doyle
- Division of Allergy, Asthma, and Clinical Immunology, Department of Medicine, Mayo Clinic Arizona, Scottsdale, AZ, United States
| | - Elizabeth A. Jacobsen
- Division of Allergy, Asthma, and Clinical Immunology, Department of Medicine, Mayo Clinic Arizona, Scottsdale, AZ, United States,Department of Immunology, Mayo Clinic Arizona, Scottsdale, AZ, United States
| | - Mindy Tsai
- Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, CA, United States,Department of Pathology, Stanford University School of Medicine, Stanford, CA, United States
| | - Scott D. Boyd
- Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, CA, United States,Department of Pathology, Stanford University School of Medicine, Stanford, CA, United States
| | - Monali Manohar
- Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, CA, United States
| | - R. Sharon Chinthrajah
- Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, CA, United States
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28
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Fabian E, Gröchenig HP, Bauer PK, Eherer AJ, Gugatschka M, Binder L, Langner C, Fickert P, Krejs GJ. Clinical-Pathological Conference Series from the Medical University of Graz : Case No 171: A 37-year-old engineer with bolus hold-up (esophageal food impaction). Wien Klin Wochenschr 2021; 132:551-559. [PMID: 32601726 PMCID: PMC7518999 DOI: 10.1007/s00508-020-01694-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Affiliation(s)
- Elisabeth Fabian
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Hans Peter Gröchenig
- Department of Internal Medicine, Hospital Brothers of St. John of God, Sankt Veit an der Glan, Austria
| | - Philipp K Bauer
- Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria
| | - Andreas J Eherer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Austria
| | - Markus Gugatschka
- Division of Phoniatrics, Department of Otorhinolaryngology, Medical University of Graz, Graz, Austria
| | - Lukas Binder
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Austria
| | - Cord Langner
- Department of Pathology, Medical University of Graz, Graz, Austria
| | - Peter Fickert
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Austria
| | - Guenter J Krejs
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Austria.
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29
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Visaggi P, Savarino E, Sciume G, Chio TD, Bronzini F, Tolone S, Frazzoni M, Pugno C, Ghisa M, Bertani L, Bellini M, Savarino V, Peroni D, Marchi S, de Bortoli N. Eosinophilic esophagitis: clinical, endoscopic, histologic and therapeutic differences and similarities between children and adults. Therap Adv Gastroenterol 2021; 14:1756284820980860. [PMID: 33613690 PMCID: PMC7871287 DOI: 10.1177/1756284820980860] [Citation(s) in RCA: 50] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Accepted: 11/20/2020] [Indexed: 02/04/2023] Open
Abstract
In the absence of secondary causes, eosinophilic esophagitis (EoE) is a chronic, local, progressive, T-helper type 2 immune-mediated disorder characterized by symptoms of esophageal dysfunction and eosinophil-predominant inflammation. In the last 20 years, the incidence and prevalence of EoE have risen sharply, and the chances of encountering affected patients in clinics and endoscopy rooms have increased. Nevertheless, it is estimated that the mean diagnostic delay of EoE is 4-6 years in both children and adults. Unfortunately, the longer the disease stays unrecognized, the likelier it is for the patient to have persistent or increased esophageal eosinophilic inflammation, to complain of non-resolving symptoms, and to develop fibrotic complications. Early detection depends on the recognition of initial clinical manifestations that vary from childhood to adulthood and even among patients of the same age. The disease phenotype also influences therapeutic approaches that include drugs, dietary interventions, and esophageal dilation. We have herein reviewed epidemiologic, clinical, endoscopic, and histologic features and therapeutic options of EoE focusing on differences and similarities between children and adults that may certainly serve in daily clinical practice.
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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
| | - Edoardo Savarino
- Division of Gastroenterology, Department of
Surgery, Oncology and Gastroenterology, University of Padua, Padua,
Italy
| | - Giusi Sciume
- Gastroenterology Unit, Department of
Translational Research and New Technologies in Medicine and Surgery,
University of Pisa, Pisa, Italy
| | - Teresa Di Chio
- Pediatric Institute of Italian Switzerland,
Bellinzona, Switzerland
| | - Francesco Bronzini
- Gastroenterology Unit, Department of
Translational Research and New Technologies in Medicine and Surgery,
University of Pisa, Pisa, Italy
| | - Salvatore Tolone
- Division of Surgery, Department of Surgery,
University of Campania, Naples, Italy
| | - Marzio Frazzoni
- Gastroenterology Digestive Pathophysiology Unit,
Baggiovara Hospital, Modena, Italy
| | - Camilla Pugno
- 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
| | - Lorenzo Bertani
- 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
| | - Vincenzo Savarino
- Gastroenterology Unit, Department of Internal
Medicine, University of Genoa, Genoa, Italy
| | - Diego Peroni
- Pediatric Unit, Department of Clinical and
Experimental Medicine, University of Pisa, Pisa, Italy
| | - Santino Marchi
- Gastroenterology Unit, Department of
Translational Research and New Technologies in Medicine and Surgery,
University of Pisa, Pisa, Italy
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30
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Krarup AL, Drewes AM, Ejstrud P, Laurberg PT, Vyberg M. Implementation of a biopsy protocol to improve detection of esophageal eosinophilia: a Danish registry-based study. Endoscopy 2021; 53:15-24. [PMID: 32757199 DOI: 10.1055/a-1206-0852] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND : In the North Denmark Region (580 272 inhabitants), only 0-4 cases of possible eosinophilic esophagitis (EoE) were identified annually in 1999-2010, suggesting underdiagnosis. This study aimed to increase the diagnosis of EoE by introducing a regional biopsy protocol for patients with dysphagia. METHODS : In 2011, leaders of regional endoscopy units attended a consensus meeting where a biopsy protocol was proposed. The national pathology registry was used to identify patients with esophageal eosinophilic inflammation during 2007-2017. RESULTS : Discussion resulted in consensus on a protocol to take eight biopsy samples in dysphagia patients (four biopsies from 4 cm and 14 cm above the esophagogastric junction-"4-14-4 rule") regardless of the macroscopic appearance, and to code eosinophilia systematically in the pathology registry. A pictogram showing the 4-14-4 rule was sent to all endoscopy units. The number of patients with esophageal eosinophilia detected per year increased 50-fold after the protocol was implemented in 2011 (median of 1 [interquartile range 0-3] vs. 52 [47-56]; P < 0.001), and the number of biopsy samples per patient doubled (median 4 [4-5] vs. 8 [6-9]; P < 0.04). Of 309 patients diagnosed with esophageal eosinophilia in 2007-2017, 24 % had erosive esophagitis or Barrett's esophagus, and 74 % had EoE. CONCLUSIONS : A consensus-based biopsy protocol and improved coding of eosinophilia in the pathology registry resulted in a 50-fold increase in patients diagnosed with esophageal eosinophilia/year. These patients can now receive treatment. The effort to establish the protocol and change the culture of endoscopists and pathologists was minimal.
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Affiliation(s)
- Anne Lund Krarup
- Department of Neurogastroenterological Research, Department of Medicine and Centre for Clinical Research, North Denmark Regional Hospital, Hjørring, Denmark.,Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Asbjørn Mohr Drewes
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.,MechSense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark
| | - Per Ejstrud
- Department of Surgery, Aalborg University Hospital, Aalborg, Denmark
| | - Peter Thaysen Laurberg
- Department of Neurogastroenterological Research, Department of Medicine and Centre for Clinical Research, North Denmark Regional Hospital, Hjørring, Denmark
| | - Mogens Vyberg
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.,Institute of Pathology, Aalborg University Hospital, Aalborg, Denmark
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31
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Kon T, Abe Y, Sasaki Y, Kikuchi R, Uchiyama S, Kusaka G, Yaoita T, Yagi M, Shoji M, Onozato Y, Mizumoto N, Ueno Y. Clinical Features of Esophageal Eosinophilia According to Endoscopic Phenotypes. Intern Med 2020; 59:2971-2979. [PMID: 32759578 PMCID: PMC7759713 DOI: 10.2169/internalmedicine.4447-20] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Objective Esophageal eosinophilia (EE), a histological hallmark of eosinophilic esophagitis, is classified into two endoscopic phenotypes: localized and diffuse EE. Our aim was to determine the prevalence of EE localized in the lower esophagus and to describe its clinical features in comparison with diffuse EE. Methods Data from 81 consecutive patients with EE were retrospectively investigated. EE was histologically defined as ≥15 eosinophils per high-power field. Based on the endoscopic appearance with a histological assessment, EE was classified as either diffuse or localized type. We compared the clinical features, including the medical treatment and natural course, between the two types. Results Of the 81 patients, 52 (64.2%) had diffuse EE, and 29 (35.8%) had localized EE. Among men patients, localized EE was significantly more common than diffuse EE. In localized EE, dysphagia and food impaction were less prevalent, and the presence of rings was significantly less common than in diffuse EE. Acid-suppressive therapy was administered to only 3 of the 29 patients with localized EE. In asymptomatic patients, especially those with localized EE, endoscopic abnormalities did not worsen but rather improved in some findings, such as with regard to furrows or exudate, during the natural course of three years without medical treatment. Conclusion Localized EE has a strong predilection for men patients and accounted for more than one third of all cases of EE. This condition appears to be less symptomatic and necessitates milder medical treatment than diffuse EE and might not worsen progressively.
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Affiliation(s)
- Takashi Kon
- Department of Gastroenterology, Faculty of Medicine, Yamagata University, Japan
| | - Yasuhiko Abe
- Division of Endoscopy, Yamagata University Hospital, Japan
- Internal Medicine, Shinoda General Hospital, Japan
| | - Yu Sasaki
- Department of Gastroenterology, Faculty of Medicine, Yamagata University, Japan
| | | | - Shiho Uchiyama
- Department of Gastroenterology, JR Sendai Hospital, Japan
| | - Gen Kusaka
- Department of Gastroenterology, JR Sendai Hospital, Japan
| | - Takao Yaoita
- Department of Gastroenterology, Faculty of Medicine, Yamagata University, Japan
| | - Makoto Yagi
- Division of Endoscopy, Yamagata University Hospital, Japan
| | - Masakuni Shoji
- Department of Gastroenterology, Faculty of Medicine, Yamagata University, Japan
| | - Yusuke Onozato
- Department of Gastroenterology, Faculty of Medicine, Yamagata University, Japan
| | - Naoko Mizumoto
- Department of Gastroenterology, Faculty of Medicine, Yamagata University, Japan
| | - Yoshiyuki Ueno
- Department of Gastroenterology, Faculty of Medicine, Yamagata University, Japan
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32
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Red Between the Lines: Evolution of Eosinophilic Esophagitis as a Distinct Clinicopathologic Syndrome. Dig Dis Sci 2020; 65:3434-3447. [PMID: 33052498 PMCID: PMC7669680 DOI: 10.1007/s10620-020-06642-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/25/2020] [Indexed: 12/09/2022]
Abstract
Eosinophilic esophagitis (EoE) is characterized by eosinophilic infiltration of the esophageal mucosa and symptoms of esophageal dysfunction, including dysphagia. While EoE is still considered a rare disease, in practice it seems that more and more cases are diagnosed every week, research in the field is exploding, and the pipeline for treatments contains multiple agents, some of which are quite far along the development pathway. After only scattered cases and small series were published in the late 1970s and 1980, Stephen Attwood, Thomas Smyrk, Tom DeMeester, and James Jones, published in Digestive Diseases and Sciences in 1993 a seminal report that described a clinicopathologic syndrome of esophageal eosinophilia with dysphagia. This review details the origins of this paper and compares and contrast what was observed then and what is known now about multiple aspects of EoE, including the clinical presentation, diagnosis, epidemiology, natural history, and treatments and outcomes. Moreover, it will highlight how the paper presaged a number of controversies in the field that have yet to be resolved, as well as foreshadowed the collaborative, multidisciplinary approach that has led to rapid advances.
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33
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DeLay K, Tappata M, Huang KZ, Koutlas NT, Robey BS, Fan C, Eluri S, Menard-Katcher P, Dellon ES. Long-term Continued Proton Pump Inhibitor Use is Common in Patients Diagnosed with Eosinophilic Esophagitis Despite Failure of Histologic Response: Data from a two-centre study: Long-term PPI Use in Patients with EoE. GASTROHEP 2020; 2:281-287. [PMID: 35356404 PMCID: PMC8963175 DOI: 10.1002/ygh2.432] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
BACKGROUND AND AIMS Treatment paradigms for proton pump inhibitors (PPIs) in eosinophilic esophagitis (EoE) are evolving. We aimed to determine patterns of long-term PPI use after EoE diagnosis in PPI histologic non-responders. METHODS We conducted a retrospective review at University of Colorado (UCH) and University of North Carolina (UNC) of EoE patients who were histologic non-responders to PPIs. Data were extracted from electronic medical records related to demographics, PPI use, and reasons for continuing or stopping PPI. RESULTS Of 67 patients in the UCH cohort, PPIs were initially discontinued in 9 (13%). Of 58 remaining on PPI, 48% were not instructed to discontinue therapy and 26% continued for symptom improvement. Of 675 patients at UNC, PPI was stopped in 185 (27%). Of patients remaining on PPI, 15% were not told to discontinue therapy and 62% were continued for symptom improvement. At last contact, >50% of patients remained on PPI at both centres with most common reasons for continuation being symptom improvement and not telling patients to discontinue. In the UNC cohort, clinical features associated with remaining on PPI included children younger than 18 years (p=0.01), males (p<0.001), heartburn symptoms (p<0.001) and hiatal hernia (p=0.004). Patients with dysphagia were less likely to remain on PPIs (p<0.001). CONCLUSIONS Long-term PPI use is common in EoE patients even without histologic response. Failure to instruct patients to discontinue therapy was a common reason for long-term use, thus PPI use should be revisited in all EoE patients to confirm clinical benefit.
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Affiliation(s)
- Kelli DeLay
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora, CO, United States
| | - Manaswita Tappata
- Division of Gastroenterology and Hepatology, Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, NC, United States
| | - Kevin Z. Huang
- Division of Gastroenterology and Hepatology, Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, NC, United States
| | - Nathaniel T. Koutlas
- Division of Gastroenterology and Hepatology, Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, NC, United States
| | - Benjamin S. Robey
- Division of Gastroenterology and Hepatology, Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, NC, United States
| | - Claire Fan
- Division of Gastroenterology and Hepatology, Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, NC, United States
| | - Swathi Eluri
- Division of Gastroenterology and Hepatology, Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, NC, United States
| | - Paul Menard-Katcher
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora, CO, United States
| | - Evan S. Dellon
- Division of Gastroenterology and Hepatology, Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, NC, United States
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34
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Arias Á, Lucendo AJ. Epidemiology and risk factors for eosinophilic esophagitis: lessons for clinicians. Expert Rev Gastroenterol Hepatol 2020; 14:1069-1082. [PMID: 32749898 DOI: 10.1080/17474124.2020.1806054] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
INTRODUCTION The rapid expansion in the epidemiology of eosinophilic esophagitis (EoE) is being documented, along with cumulative research assessing environmental exposures associated with EoE and susceptibility due to genetic variants. AREAS COVERED Incidence rates for EoE of 5-10 new cases per 100,000 inhabitants annually have shown an increase in recent reports of up to 20 in some countries; the highest prevalence being reported for Europe and North America, where EoE now affects more than 1 out of 1,000 people. EoE has been shown to be associated with several disorders, Th2-mediated atopies being the most common. Patients with EoE exhibit increased frequency of asthma, allergic rhinitis and eczema, and EoE has been considered as a late component of the atopic march. Risk variants in TSLP, CAPN14 and LRCC32 genes, among others, have all been related to EoE, and interact with prenatal and early life exposure potentially modifying abundance and composition of gut microbiome. Dysregulated interactions between bacteria and mucosal immunity emerge as leading causes of EoE. EXPERT OPINION The expanding epidemiology of EoE, the resources needed and subsequent increasing healthcare costs require additional effort to optimize cost-effective management and unveil mechanisms that enhance the development of future preventive strategies.
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Affiliation(s)
- Ángel Arias
- Research Unit, Hospital General Mancha Centro , Alcázar De San Juan, Spain.,Centro De Investigación Biomédica En Red De Enfermedades Hepáticas Y Digestivas (Ciberehd) , Madrid, Spain.,Instituto De Investigación Sanitaria La Princesa , Madrid, Spain
| | - Alfredo J Lucendo
- Centro De Investigación Biomédica En Red De Enfermedades Hepáticas Y Digestivas (Ciberehd) , Madrid, Spain.,Instituto De Investigación Sanitaria La Princesa , Madrid, Spain.,Department of Gastroenterology, Hospital General De Tomelloso , Ciudad Real, Spain
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35
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Katzka DA, Falck-Ytter Y. AGA Commentary on Eosinophilic Esophagitis Guidelines. Gastroenterology 2020; 159:813-815. [PMID: 32492376 DOI: 10.1053/j.gastro.2020.05.070] [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: 05/27/2020] [Indexed: 12/02/2022]
Affiliation(s)
- David A Katzka
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Yngve Falck-Ytter
- Division of Gastroenterology and Hepatology, VA Northeast Ohio Healthcare System, Case Western Reserve University School of Medicine, Cleveland, Ohio
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36
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Abstract
The evaluation of gastrointestinal pathology in children often requires a different approach from that in adults. In this concise review, the authors outline 3 diagnostic challenges that are often encountered in daily practice; these include eosinophilic diseases, duodenal intraepithelial lymphocytosis with preserved villous architecture, and terminal ileal inflammation in the setting of idiopathic inflammatory bowel disease.
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Affiliation(s)
- Juan Putra
- Department of Laboratory Medicine and Pathobiology, University of Toronto, 555 University Avenue, Toronto, Ontario M5G1X8, Canada; Division of Pathology, Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G1X8, Canada
| | - Jeffrey D Goldsmith
- Department of Pathology, Boston Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
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37
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Fernandez-Becker NQ, Raja S, Scarpignato C, Lynch KL, Ahuja NK, Horsley-Silva JL. Eosinophilic esophagitis: updates on key unanswered questions. Ann N Y Acad Sci 2020; 1481:30-42. [PMID: 32762154 DOI: 10.1111/nyas.14421] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Revised: 05/25/2020] [Accepted: 06/05/2020] [Indexed: 12/20/2022]
Abstract
Eosinophilic esophagitis (EoE) is a clinicopathologic disease characterized by symptoms of esophageal dysfunction and esophageal eosinophilia. In the last decade, there has been a dramatic increase in its prevalence for reasons that are not completely understood. The underlying pathophysiology involves an antigen-mediated TH 2 immune response that draws eosinophils to the esophagus, causing mucosal inflammation, esophageal remodeling, and fibrosis. This ultimately leads to esophageal dysfunction that most commonly manifests as dysphagia. In this review, we will discuss updates on key questions regarding the diagnosis and treatment of EoE.
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Affiliation(s)
| | - Shreya Raja
- Department of Medicine, Emory University, Atlanta, Georgia
| | - Carmelo Scarpignato
- Department of Health Sciences, United Campus of Malta, Msida, Malta.,Faculty of Medicine, Chinese University of Hong Kong, Sha Tin, Hong Kong
| | - Kristle L Lynch
- Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Nitin K Ahuja
- Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
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38
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Lottrup C, Khan A, Rangan V, Clarke JO. Esophageal physiology-an overview of esophageal disorders from a pathophysiological point of view. Ann N Y Acad Sci 2020; 1481:182-197. [PMID: 32648992 DOI: 10.1111/nyas.14417] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Revised: 05/25/2020] [Accepted: 06/03/2020] [Indexed: 11/30/2022]
Abstract
The esophagus serves the principal purpose of transporting food from the pharynx into the stomach. A complex interplay between nerves and muscle fibers ensures that swallowing takes place as a finely coordinated event. Esophageal function can be tested by a variety of methods, endoscopy, manometry, and reflux monitoring being some of the most important. Regarding pathophysiology, motor disorders, such as achalasia, often cause dysphagia and/or chest pain. Functional esophageal disorders are a heterogeneous group with hypersensitivity as a dominant pathophysiological factor. Gastroesophageal reflux disease often causes symptoms, such as heartburn and regurgitation, and a spectrum of disease, ranging from minimal mucosal damage visible only in the microscope to esophageal ulcers and strictures in the most severe cases. Eosinophilic esophagitis is an immune-mediated condition that can result in significant dysphagia and associated luminal narrowing. In the following, we will provide an overview of the most common esophageal disorders from a combined pathophysiological and clinical view.
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Affiliation(s)
- Christian Lottrup
- Department of Medicine, Aalborg University Hospital, Hobro, Denmark.,Mech-Sense, Department of Gastroenterology & Hepatology, Aalborg University Hospital, Aalborg, Denmark
| | - Abraham Khan
- Department of Medicine, New York University School of Medicine, New York, New York
| | - Vikram Rangan
- Division of Gastroenterology and Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts
| | - John O Clarke
- Division of Gastroenterology, Department of Medicine, Stanford University, Stanford, California
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39
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Roh JH, Ryoo E, Tchah H. Clinical Manifestations of Eosinophilic Esophagitis in Children and Adolescents: A Single-Center, Matched Case-Control Study. Pediatr Gastroenterol Hepatol Nutr 2020; 23:319-328. [PMID: 32704493 PMCID: PMC7354874 DOI: 10.5223/pghn.2020.23.4.319] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2019] [Revised: 11/15/2019] [Accepted: 11/30/2019] [Indexed: 11/14/2022] Open
Abstract
PURPOSE To examine the prevalence and clinical manifestations of eosinophilic esophagitis (EoE) in Korea children. METHODS The study was designed as a 1:2 matching case-control study. Using information from the endoscopic database of a tertiary center, we retrospectively reviewed the medical records of patients aged 18 years or younger who underwent upper gastrointestinal endoscopy between January 2014 and December 2017. A total of 21 patients were diagnosed with EoE based on current diagnostic criteria. In addition, 42 controls with normal esophageal biopsy findings matched to each EoE case by sex, age (±1 months), and season were randomly selected during the study period. RESULTS The mean age of EoE diagnosis was 12.1±4.0 years and the male-to-female ratio was 2:1. The proportion of allergic diseases in patients with EoE (28.6%) was higher than that in the controls (6.8%) (p=0.04). Most EoE patients tested for allergy were positive for at least one antigen, which was significantly different to the controls (88.2% vs. 47.4%, p=0.01). Characteristic endoscopic findings of EoE were noted in 19 patients (90.5%), but 2 patients (9.5%) showed normal esophageal mucosa. The clinical symptoms of EoE were improved by a proton-pump inhibitor in 10 patients (50.0%), and by an H2 blocker in 9 patients (45.0%). Only one patient (5.0%) required inhaled steroids. CONCLUSION While EoE is rare in the Korean pediatric population, the results of this study will improve our understanding of the clinical manifestations of the disease.
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Affiliation(s)
- Ji Hyeon Roh
- Department of Pediatrics, Gachon University Gil Medical Center, Incheon, Korea
| | - Eell Ryoo
- Department of Pediatrics, Gachon University Gil Medical Center, Incheon, Korea
| | - Hann Tchah
- Department of Pediatrics, Gachon University Gil Medical Center, Incheon, Korea
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40
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Slack IF, Schwartz JT, Mukkada VA, Hottinger S, Abonia JP. Eosinophilic Esophagitis: Existing and Upcoming Therapies in an Age of Emerging Molecular and Personalized Medicine. Curr Allergy Asthma Rep 2020; 20:30. [PMID: 32506181 DOI: 10.1007/s11882-020-00928-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
PURPOSE OF REVIEW Recent research efforts have spurred great progress in the diagnosis and management of eosinophilic esophagitis (EoE). Nonetheless, challenges remain in addressing disease burden and impairment in the growing EoE population. We highlight work from the Cincinnati Center for Eosinophilic Disorders, the Consortium of Eosinophilic Gastrointestinal Disease Researchers, and others that address these ongoing challenges. RECENT FINDINGS New tools for characterizing EoE disease activity include the EoE Histology Scoring System (EoEHSS), endoscopic alternatives, validated patient-reported outcome (PRO) questionnaires, and investigational biomarkers. These diagnostic and monitoring strategies have been complemented by advances in EoE therapy. Treatment modalities have refined the traditional approaches of dietary elimination, swallowed steroids, and proton pump inhibitors (PPI), and biologics offer promise for future treatment. This review summarizes EoE advances in disease management and newly defined EoE endotypes that may serve as the foundation for EoE-personalized medicine.
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Affiliation(s)
- Ian F Slack
- Division of Allergy and Immunology, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC 7028, Cincinnati, OH, 45229, USA
| | - Justin T Schwartz
- Division of Allergy and Immunology, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC 7028, Cincinnati, OH, 45229, USA
| | - Vincent A Mukkada
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - Shawna Hottinger
- Division of Allergy and Immunology, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC 7028, Cincinnati, OH, 45229, USA
| | - J Pablo Abonia
- Division of Allergy and Immunology, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC 7028, Cincinnati, OH, 45229, USA.
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41
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Rank MA, Sharaf RN, Furuta GT, Aceves SS, Greenhawt M, Spergel JM, Falck-Ytter YT, Dellon ES. Technical review on the management of eosinophilic esophagitis: a report from the AGA institute and the joint task force on allergy-immunology practice parameters. Ann Allergy Asthma Immunol 2020; 124:424-440.e17. [PMID: 32336463 PMCID: PMC8171057 DOI: 10.1016/j.anai.2020.03.021] [Citation(s) in RCA: 58] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Eosinophilic esophagitis (EoE) is a chronic inflammatory condition of the esophagus. Many new studies have been reported recently that describe EoE management. An expert panel was convened by the American Gastroenterological Association Institute and the Joint Task Force on Allergy-Immunology Practice Parameters to provide a technical review to be used as the basis for an updated clinical guideline. This technical review was developed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. Eighteen focused EoE management questions were considered, with 15 answered using the GRADE framework and 3 with a narrative summary. There is moderate certainty in the evidence that topical glucocorticosteroids effectively reduce esophageal eosinophil counts to <15 per high-power field over a short-term treatment period of 4-12 weeks, but very low certainty about the effects of using topical glucocorticosteroids as maintenance therapy. Multiple dietary strategies may be effective in reducing esophageal eosinophil counts to <15 per high-power field over a short-term treatment period, with moderate certainty for elemental diets, low certainty for empiric 2-, 4-, and 6-food elimination diets, and very low certainty that allergy-based testing dietary eliminations have a higher failure rate compared to empiric diet elimination. There is very low certainty for the effect of proton pump inhibitors in patients with esophageal eosinophilia. Although esophageal dilation appears to be relatively safe, there is no evidence that it reduces esophageal eosinophil counts. There is very low certainty in the effects of multiple other medical treatments for EoE: anti-interleukin-5 therapy, anti-interleukin-13 therapy, anti-IgE therapy, montelukast, cromolyn, and anti-TNF therapy.
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Affiliation(s)
- Matthew A Rank
- Division of Allergy, Asthma, and Clinical Immunology, Mayo Clinic, Scottsdale, Arizona
| | - Rajiv N Sharaf
- Division of Gastroenterology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Manhasset, New York
| | - Glenn T Furuta
- Digestive Health Institute, Children's Hospital Colorado, Gastrointestinal Eosinophilic Diseases Program, University of Colorado School of Medicine, Aurora, Colorado
| | - Seema S Aceves
- Division of Allergy Immunology Center for Immunity, Infection, and Inflammation, University of California, San Diego Rady Children's Hospital, San Diego, California
| | - Matthew Greenhawt
- Section of Allergy/Immunology, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, Colorado
| | - Jonathan M Spergel
- Division of Allergy-Immunology, Children's Hospital of Philadelphia, Perelman School of Medicine at University of Pennsylvania, Philadelphia, Pennsylvania
| | - Yngve T Falck-Ytter
- Division of Gastroenterology and Hepatology, Cleveland Veterans Affairs Medical Center and University Hospitals, Case Western Reserve University School of Medicine, Cleveland, Ohio
| | - Evan S Dellon
- Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, North Carolina
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42
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Rank MA, Sharaf RN, Furuta GT, Aceves SS, Greenhawt M, Spergel JM, Falck-Ytter YT, Dellon ES. Technical Review on the Management of Eosinophilic Esophagitis: A Report From the AGA Institute and the Joint Task Force on Allergy-Immunology Practice Parameters. Gastroenterology 2020; 158:1789-1810.e15. [PMID: 32359563 PMCID: PMC9473155 DOI: 10.1053/j.gastro.2020.02.039] [Citation(s) in RCA: 98] [Impact Index Per Article: 19.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Eosinophilic esophagitis (EoE) is a chronic inflammatory condition of the esophagus. Many new studies have been reported recently that describe EoE management. An expert panel was convened by the American Gastroenterological Association Institute and the Joint Task Force on Allergy-Immunology Practice Parameters to provide a technical review to be used as the basis for an updated clinical guideline. This technical review was developed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. Eighteen focused EoE management questions were considered, with 15 answered using the GRADE framework and 3 with a narrative summary. There is moderate certainty in the evidence that topical glucocorticosteroids effectively reduce esophageal eosinophil counts to <15 per high-power field over a short-term treatment period of 4-12 weeks, but very low certainty about the effects of using topical glucocorticosteroids as maintenance therapy. Multiple dietary strategies may be effective in reducing esophageal eosinophil counts to <15 per high-power field over a short-term treatment period, with moderate certainty for elemental diets, low certainty for empiric 2-, 4-, and 6-food elimination diets, and very low certainty that allergy-based testing dietary eliminations have a higher failure rate compared to empiric diet elimination. There is very low certainty for the effect of proton pump inhibitors in patients with esophageal eosinophilia. Although esophageal dilation appears to be relatively safe, there is no evidence that it reduces esophageal eosinophil counts. There is very low certainty in the effects of multiple other medical treatments for EoE: anti-interleukin-5 therapy, anti-interleukin-13 therapy, anti-IgE therapy, montelukast, cromolyn, and anti-TNF therapy.
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Affiliation(s)
- Matthew A. Rank
- Division of Allergy, Asthma, and Clinical Immunology, Mayo
Clinic, Scottsdale, Arizona
| | - Ravi N. Sharaf
- Division of Gastroenterology, Donald and Barbara
Zucker School of Medicine at Hofstra/Northwell, Manhasset, New York
| | - Glenn T. Furuta
- Digestive Health Institute, Children’s
Hospital Colorado, Gastrointestinal Eosinophilic Diseases Program, University of
Colorado School of Medicine, Aurora, Colorado
| | - Seema S. Aceves
- Division of Allergy Immunology Center for Immunity,
Infection, and Inflammation, University of California, San Diego Rady
Children’s Hospital, San Diego, California
| | - Matthew Greenhawt
- Section of Allergy/Immunology, Children’s
Hospital Colorado, University of Colorado School of Medicine, Aurora, Colorado
| | - Jonathan M. Spergel
- Division of Allergy-Immunology, Children’s
Hospital of Philadelphia, Perelman School of Medicine at University of Pennsylvania,
Philadelphia, Pennsylvania
| | - Yngve T. Falck-Ytter
- Division of Gastroenterology and Hepatology, Cleveland
Veterans Affairs Medical Center and University Hospitals, Case Western Reserve
University School of Medicine, Cleveland, Ohio
| | - Evan S. Dellon
- Center for Esophageal Diseases and Swallowing, Division of
Gastroenterology and Hepatology, University of North Carolina School of Medicine,
Chapel Hill, North Carolina
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Mari A, Tsoukali E, Yaccob A. Eosinophilic Esophagitis in Adults: A Concise Overview of an Evolving Disease. Korean J Fam Med 2020; 41:75-83. [PMID: 32062959 PMCID: PMC7093678 DOI: 10.4082/kjfm.18.0162] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2018] [Accepted: 10/15/2018] [Indexed: 12/19/2022] Open
Abstract
Eosinophilic esophagitis (EoE) is a chronic inflammatory disease that encompasses esophageal symptoms along with eosinophilic infiltration of the esophageal epithelium. EoE is an evolving disease that has been a subject of interest to many researchers since the first studies recognized this condition as a new and distinct clinicopathological entity 25 years ago. Clinical presentation in adult patients may include dysphagia, food impaction, vomiting, and reflux symptoms. The diagnosis of EoE is based on the combination of clinical history suggestive of esophageal dysfunction, endoscopic features indicative of the disease, and histology revealing eosinophilic infiltration of the esophageal epithelium that persists after a trial of proton pump inhibitor therapy along with the exclusion of other disorders that may be associated with esophageal tissue eosinophilia. The interplay between EoE and gastroesophageal reflux disease (GERD) is complex, and differentiating these two conditions continues to be difficult and challenging in clinical practice. The mainstay treatment includes dietary modification, topical steroids, and/or endoscopic dilation. The primary care physician (PCP) plays an important role in improving patient care and quality of life by ensuring early referral and participating in management and follow-up. This article provides an overview of the current knowledge base regarding the disease including epidemiology, genetics, pathogenesis, common clinical presentations, the interplay between EoE and GERD, diagnostic approaches, and therapeutic options available to the PCP.
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Affiliation(s)
- Amir Mari
- Gastroenterology Institute, Nazareth EMMS Hospital, Nazareth, Israel.,The Azrieli Faculty of Medicine, Bar-Ilan University, Ramat Gan, Israel
| | - Emmanouela Tsoukali
- Gastroenterology and Hepatology Department, Evangelismos General Hospital of Athens, Athens, Greece
| | - Afif Yaccob
- Gastroenterology and Liver Disease Department, Rambam Healthcare Campus, Haifa, Israel
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Mari A, Abu Baker F, Mahamid M, Khoury T, Sbeit W, Pellicano R. Eosinophilic esophagitis: pitfalls and controversies in diagnosis and management. Minerva Med 2020; 111:9-17. [PMID: 31755670 DOI: 10.23736/s0026-4806.19.06322-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Formerly considered a rare disorder, eosinophilic esophagitis (EoE) has emerged as a leading cause of feeding problems in children and an increasingly recognized cause of dysphagia and food impaction in adults. Our understanding of EoE and its complex interplay with gastro-esophageal reflux disease (GERD) has evolved over the past decade and culminated in the introduction of proton pump inhibitor (PPI) responsive EoE as a distinct entity which has added to this complexity. It is now clear that this entity is on the same spectrum as the original EoE, and that PPIs should be considered as part of treatment protocol and should not be recommended as a diagnostic tool. As such, removing the PPI trial from the diagnostic algorithm has been encouraged recently. Recent guidelines and reviews thoroughly address various aspects in EoE pathogenesis and diagnostic workup as well as management endpoints, treatment options and novel therapies. However, despite the recent extensive study and the advances in our knowledge of this disease, unmet needs and pitfalls in diagnostic workup and management of these patients are still to be clarified and will be under focus in this review.
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Affiliation(s)
- Amir Mari
- Gastroenterology Unit, Nazareth Hospital EMMS, Faculty of Medicine, Bar Ilan University, Safed, Israel -
| | - Fadi Abu Baker
- Gastroenterology Unit, Hillel Yaffe MC, Technion, Haifa, Israel
| | - Mahmud Mahamid
- Gastroenterology Unit, Nazareth Hospital EMMS, Faculty of Medicine, Bar Ilan University, Safed, Israel
| | - Tawfik Khoury
- Gastroenterology Unit, Nazareth Hospital EMMS, Faculty of Medicine, Bar Ilan University, Safed, Israel
- Department of Gastroenterology, Galilee MC, Faculty of Medicine, Bar Ilan University, Safed, Israel
| | - Wisam Sbeit
- Department of Gastroenterology, Galilee MC, Faculty of Medicine, Bar Ilan University, Safed, Israel
| | - Rinaldo Pellicano
- Gastroenterology Unit, Molinette-San Giovanni Antica Sede Hospitals, Turin, Italy
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Gómez-Aldana A, Jaramillo-Santos M, Delgado A, Jaramillo C, Lúquez-Mindiola A. Eosinophilic esophagitis: Current concepts in diagnosis and treatment. World J Gastroenterol 2019; 25:4598-4613. [PMID: 31528089 PMCID: PMC6718043 DOI: 10.3748/wjg.v25.i32.4598] [Citation(s) in RCA: 43] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2019] [Revised: 07/13/2019] [Accepted: 07/19/2019] [Indexed: 02/06/2023] Open
Abstract
Eosinophilic esophagitis is an immune-allergic pathology of multifactorial etiology (genetic and environmental) that affects both pediatric and adult patients. Its symptoms, which include heartburn, regurgitation, and esophageal stenosis (with dysphagia being more frequent in eosinophilic esophagitis in young adults and children), are similar to those of gastroesophageal reflux disease, causing delays in diagnosis and treatment. Although endoscopic findings such as furrows, esophageal mucosa trachealization, and whitish exudates may suggest its presence, this diagnosis should be confirmed histologically based on the presence of more than 15 eosinophils per high-power field and the exclusion of other causes of eosinophilia (parasitic infections, hypereosinophilic syndrome, inflammatory bowel disease, among others) for which treatment could be initiated. Currently, the 3 "D"s ("Drugs, Diet, and Dilation") are considered the fundamental components of treatment. The first 2 components, which involve the use of proton pump inhibitors, corticosteroids, immunosuppressants and empirical diets or guided food elimination based on allergy tests, are more useful in the initial phases, whereas endoscopic dilation is reserved for esophageal strictures. Herein, the most important aspects of eosinophilic esophagitis pathophysiology will be reviewed, in addition to evidence for the various treatments.
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Affiliation(s)
- Andrés Gómez-Aldana
- Departament of Internal Medicine, Section of Gastroenterology, Santa Fe Foundation of Bogotá (Fundación Santa Fe de Bogotá), Bogotá 220246, Colombia
- University of Los Andes, Bogotá 111711, Colombia
| | - Mario Jaramillo-Santos
- Department of Endoscopy, Caldas University, Manizales 275, Colombia
- Department of Endoscopy, Surgeons’ Union SAS (Joint stock company) (Union de cirujanos SAS), Manizales 170001661, Colombia
| | - Andrés Delgado
- Departament of Internal Medicine, Section of Gastroenterology, Santa Fe Foundation of Bogotá (Fundación Santa Fe de Bogotá), Bogotá 220246, Colombia
| | - Carlos Jaramillo
- Department of Endoscopy, Caldas University, Manizales 275, Colombia
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Pharmacotherapies for the Treatment of Eosinophilic Esophagitis: State of the Art Review. Drugs 2019; 79:1419-1434. [DOI: 10.1007/s40265-019-01173-2] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
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Chandan VS, Wu TT. Eosinophilic Esophagitis. AJSP: REVIEWS AND REPORTS 2019; 24:144-149. [DOI: 10.1097/pcr.0000000000000310] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
Abstract
Abstract
Eosinophilic esophagitis is an immune-mediated chronic disease of the esophagus. It is clinically characterized by symptoms related to esophageal dysfunction and histologically by eosinophil-rich inflammation with a peak intraepithelial eosinophil count of at least 15 eosinophils per high-power field. Both children and adults can be affected with a strong male predominance. Food appears to be the key trigger, although the exact mechanisms remain unclear. Treatment for eosinophilic esophagitis can be summarized as the 3 D's: dietary, drugs, and dilatation. The differential diagnosis includes gastroesophageal reflux disease, eosinophilic gastroenteritis, drug hypersensitivity, hypereosinophilic syndrome, infection, Crohn disease, connective tissue diseases, and vasculitis.
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Affiliation(s)
- Vishal S. Chandan
- Department of Pathology, University of California, Irvine, Orange, CA; and
| | - Tsung-Teh Wu
- Division of Anatomic Pathology, Mayo Clinic, Rochester, MN
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van Lennep M, Singendonk MMJ, Dall'Oglio L, Gottrand F, Krishnan U, Terheggen-Lagro SWJ, Omari TI, Benninga MA, van Wijk MP. Oesophageal atresia. Nat Rev Dis Primers 2019; 5:26. [PMID: 31000707 DOI: 10.1038/s41572-019-0077-0] [Citation(s) in RCA: 96] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Oesophageal atresia (EA) is a congenital abnormality of the oesophagus that is caused by incomplete embryonic compartmentalization of the foregut. EA commonly occurs with a tracheo-oesophageal fistula (TEF). Associated birth defects or anomalies, such as VACTERL association, trisomy 18 or 21 and CHARGE syndrome, occur in the majority of patients born with EA. Although several studies have revealed signalling pathways and genes potentially involved in the development of EA, our understanding of the pathophysiology of EA lags behind the improvements in surgical and clinical care of patients born with this anomaly. EA is treated surgically to restore the oesophageal interruption and, if present, ligate and divide the TEF. Survival is now ~90% in those born with EA with severe associated anomalies and even higher in those born with EA alone. Despite these achievements, long-term gastrointestinal and respiratory complications and comorbidities in patients born with EA are common and lead to decreased quality of life. Oesophageal motility disorders are probably ubiquitous in patients after undergoing EA repair and often underlie these complications and comorbidities. The implementation of several new diagnostic and screening tools in clinical care, including high-resolution impedance manometry, pH-multichannel intraluminal impedance testing and disease-specific quality of life questionnaires now provide better insight into these problems and may contribute to better long-term outcomes in the future.
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Affiliation(s)
- Marinde van Lennep
- Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Pediatric Gastroenterology and Nutrition, Amsterdam, The Netherlands
| | - Maartje M J Singendonk
- Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Pediatric Gastroenterology and Nutrition, Amsterdam, The Netherlands
| | - Luigi Dall'Oglio
- Digestive Endoscopy and Surgery Unit, Bambino Gesu Children's Hospital-IRCCS, Rome, Italy
| | - Fréderic Gottrand
- CHU Lille, University Lille, National Reference Center for Congenital Malformation of the Esophagus, Department of Pediatric Gastroenterology Hepatology and Nutrition, Lille, France
| | - Usha Krishnan
- Department of Paediatric Gastroenterology, Sydney Children's Hospital, Sydney, New South Wales, Australia
- Discipline of Paediatrics, School of Women's and Children's Health, University of New South Wales, Sydney, New South Wales, Australia
| | - Suzanne W J Terheggen-Lagro
- Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Pediatric Pulmonology, Amsterdam, The Netherlands
| | - Taher I Omari
- College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
- Center for Neuroscience, Flinders University, Adelaide, South Australia, Australia
| | - Marc A Benninga
- Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Pediatric Gastroenterology and Nutrition, Amsterdam, The Netherlands.
| | - Michiel P van Wijk
- Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Pediatric Gastroenterology and Nutrition, Amsterdam, The Netherlands
- Emma Children's Hospital, Amsterdam UMC, Vrije Universiteit, Pediatric Gastroenterology, Amsterdam, The Netherlands
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Sawada A, Hashimoto A, Uemura R, Otani K, Tanaka F, Nagami Y, Yamagami H, Tanigawa T, Watanabe T, Fujiwara Y. Association between endoscopic findings of eosinophilic esophagitis and responsiveness to proton pump inhibitors. Endosc Int Open 2019; 7:E433-E439. [PMID: 30931374 PMCID: PMC6428677 DOI: 10.1055/a-0859-7276] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2018] [Accepted: 01/29/2019] [Indexed: 02/08/2023] Open
Abstract
Background and study aims Endoscopic findings of esophageal eosinophilia sometimes localize to small areas of the esophagus. A previous study suggested that pathogenesis of localized-type eosinophilic esophagitis (LEoE) was associated with acid reflux. However, LEoE treatment outcomes have not been studied. We aimed to analyze the clinical and histologic significance of LEoE in comparison with diffuse-type eosinophilic esophagitis (DEoE). Patients and methods This study included 106 patients with esophageal eosinophilia. Esophageal eosinophilia was defined as a condition where the maximum number of intraepithelial eosinophils was ≥ 15 per high-power field. LEoE was defined as an endoscopic lesion confined to one-third of the esophagus: upper, middle, or lower. Esophageal eosinophilia encompassing more than two-thirds of the esophagus was defined as DEoE. We retrospectively compared LEoE and DEoE in terms of clinical characteristics, histologic findings, and proportion of proton pump inhibitor (PPI) responders. Results Of 106 patients, 12 were classified as having LEoE and 94 were classified as having DEoE. The proportion of asymptomatic patients was significantly higher in the LEoE group than the DEoE group (42 % vs 7 %, P < 0.01). In the LEoE group, 10 patients (84 %) had endoscopic lesions in the lower esophagus. The maximum number of eosinophils did not differ between the groups (54 [24 - 71] for LEoE, 40 [20 - 75] for DEoE, P = 0.65). The prevalence of PPI responders was significantly higher in the LEoE group than the DEoE group (100 % vs 63 %, P = 0.01). Conclusion LEoE can be a sign of good responsiveness to PPI therapy.
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Affiliation(s)
- Akinari Sawada
- Department of Gastroenterology, Osaka City University Graduate School of Medicine
| | - Atsushi Hashimoto
- Department of Gastroenterology, Osaka City University Graduate School of Medicine
| | - Risa Uemura
- Department of Gastroenterology, Osaka City University Graduate School of Medicine
| | - Koji Otani
- Department of Gastroenterology, Osaka City University Graduate School of Medicine
| | - Fumio Tanaka
- Department of Gastroenterology, Osaka City University Graduate School of Medicine
| | - Yasuaki Nagami
- Department of Gastroenterology, Osaka City University Graduate School of Medicine
| | - Hirokazu Yamagami
- Department of Gastroenterology, Osaka City University Graduate School of Medicine
| | - Tetsuya Tanigawa
- Department of Gastroenterology, Osaka City University Graduate School of Medicine
| | - Toshio Watanabe
- Department of Gastroenterology, Osaka City University Graduate School of Medicine
| | - Yasuhiro Fujiwara
- Department of Gastroenterology, Osaka City University Graduate School of Medicine
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Vinit C, Dieme A, Courbage S, Dehaine C, Dufeu C, Jacquemot S, Lajus M, Montigny L, Payen E, Yang D, Dupont C. Eosinophilic esophagitis: Pathophysiology, diagnosis, and management. Arch Pediatr 2019; 26:182-190. [DOI: 10.1016/j.arcped.2019.02.005] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2017] [Revised: 12/10/2018] [Accepted: 02/03/2019] [Indexed: 12/31/2022]
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