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Ketchem CJ, Starling AS. Insights into the natural history and disease course of eosinophilic esophagitis. Ann Allergy Asthma Immunol 2025:S1081-1206(25)00154-1. [PMID: 40164282 DOI: 10.1016/j.anai.2025.03.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2025] [Revised: 03/20/2025] [Accepted: 03/21/2025] [Indexed: 04/02/2025]
Abstract
Eosinophilic esophagitis (EoE) is a chronic, immune-mediated disease marked by eosinophilic inflammation and esophageal dysfunction, with a significant impact on morbidity, quality of life, and health care utilization. Once considered rare, EoE has become increasingly prevalent, with global estimates exceeding 140 cases per 100,000 individuals. This rise highlights the need to better understand the natural history and disease course to inform diagnosis and management strategies. Evidence suggests that EoE is a progressive condition, such that untreated inflammation contributes to esophageal remodeling and fibrotic complications over years to decades. Patients can develop esophageal food impactions, leading to emergency department utilization and the need for emergent endoscopy. In addition, patients with fibrostenotic disease can require serial dilations. Long-term management, including dietary therapy, proton pump inhibitors, topical corticosteroids, and newer therapies such as dupilumab, demonstrate promise in altering the disease course. However, variability exists in the strength of evidence regarding each therapy's ability to halt or reverse fibrosis. Knowledge gaps persist, particularly in defining fibrosis, identifying phenotypes prone to progression, and tailoring therapies to individual patients. Addressing these gaps will require continued research into understanding fibrosis progression and how therapies alter this trajectory. These efforts are poised to significantly improve clinical care and enhance outcomes for patients with EoE.
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Affiliation(s)
- Corey J Ketchem
- Division of Gastroenterology and Hepatology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Alexandra Strauss Starling
- Division of Gastroenterology and Hepatology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
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2
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Erdle SC, Carr S, Chan ES, Robertson K, Watson W. Eosinophilic esophagitis. ALLERGY, ASTHMA, AND CLINICAL IMMUNOLOGY : OFFICIAL JOURNAL OF THE CANADIAN SOCIETY OF ALLERGY AND CLINICAL IMMUNOLOGY 2024; 20:72. [PMID: 39702284 PMCID: PMC11660462 DOI: 10.1186/s13223-024-00929-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/24/2024] [Accepted: 11/13/2024] [Indexed: 12/21/2024]
Abstract
Eosinophilic esophagitis (EoE) is an atopic condition of the esophagus that has become increasingly recognized. Diagnosis of the disorder is dependent on the patient's clinical manifestations and must be confirmed by histologic findings on esophageal mucosal biopsies. The epidemiology, pathophysiology, diagnosis, treatment, and prognosis of EoE are discussed in this review.
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Affiliation(s)
- Stephanie C Erdle
- Division of Allergy, Department of Pediatrics, University of British Columbia, BC Children's Hospital, Vancouver, BC, Canada.
| | - Stuart Carr
- Snö Asthma & Allergy, Abu Dhabi, United Arab Emirates
| | - Edmond S Chan
- Division of Allergy, Department of Pediatrics, University of British Columbia, BC Children's Hospital, Vancouver, BC, Canada
| | - Kara Robertson
- Division of Allergy & Immunology, Department of Internal Medicine, Western University, London, ON, Canada
| | - Wade Watson
- Division of Allergy, Department of Pediatrics, Dalhousie University, IWK Health Centre, Halifax, NS, Canada
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3
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Haber C, Al-Shaikhly T, Jhaveri P. Milk or egg allergy diagnosis increases the risk of eosinophilic esophagitis diagnosis. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. IN PRACTICE 2024; 12:3150-3152.e1. [PMID: 39151688 PMCID: PMC11560657 DOI: 10.1016/j.jaip.2024.08.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/26/2024] [Revised: 07/18/2024] [Accepted: 08/07/2024] [Indexed: 08/19/2024]
Affiliation(s)
- Catherine Haber
- Department of Pediatrics, Pennsylvania State College of Medicine, Hershey, Pa.
| | - Taha Al-Shaikhly
- Department of Medicine, Section of Allergy, Asthma and Immunology, Pennsylvania State College of Medicine, Hershey, Pa
| | - Pooja Jhaveri
- Department of Pediatrics, Division of Allergy, Asthma and Immunology, Pennsylvania State College of Medicine, Hershey, Pa
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Authors, Collaborators. S2k guideline Gastroesophageal reflux disease and eosinophilic esophagitis of the German Society of Gastroenterology, Digestive and Metabolic Diseases (DGVS). ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:1786-1852. [PMID: 39389106 DOI: 10.1055/a-2344-6282] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/12/2024]
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Schlager H, Baumann-Durchschein F, Steidl K, Häfner M, Dinkhauser P, Weitersberger M, Holzinger J, Mader M, Gröchenig HP, Madl C, Schreiner P. Diagnosis and management of eosinophilic esophagitis and esophageal food impaction in adults : A position paper issued by the Austrian Society of Gastroenterology and Hepatology (ÖGGH). Wien Klin Wochenschr 2024; 136:479-499. [PMID: 39230674 PMCID: PMC11387459 DOI: 10.1007/s00508-024-02401-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2024] [Accepted: 06/21/2024] [Indexed: 09/05/2024]
Abstract
This position paper deals with an expert consensus on diagnosis and management of eosinophilic esophagitis and esophageal food impaction issued by the Austrian Eosinophilic Esophagitis Network, a working group under the patronage of the Austrian Society of Gastroenterology and Hepatology (ÖGGH). In need of a standardized approach on the management of EoE, recommendations were made based on international guidelines and landmark studies.
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Affiliation(s)
- Hansjörg Schlager
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, University Hospital Graz, Auenbruggerplatz 15, 8036, Graz, Austria.
| | - Franziska Baumann-Durchschein
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, University Hospital Graz, Auenbruggerplatz 15, 8036, Graz, Austria
| | - Karin Steidl
- Department of Internal Medicine, Barmherzige Brüder St. Veit/Glan, St. Veit, Austria
| | - Michael Häfner
- 2nd Medical Department, Barmherzige Schwestern Krankenhaus, Vienna, Austria
| | - Patrick Dinkhauser
- Department of Internal Medicine I, Division of Gastroenterology and Hepatology, Endocrinology and Rheumatology, Klinikum Wels-Grieskirchen, Wels, Austria
| | - Michael Weitersberger
- Department of Gastroenterology and Hepatology, Ordensklinikum Linz Barmherzige Schwestern, Linz, Austria
| | - Josef Holzinger
- Department of Surgery, Paracelsus Medical University/Salzburger Landeskliniken (SALK), Salzburg, Austria
| | - Markus Mader
- Department of Internal Medicine II, Universitätsklinikum St. Pölten-Karl Landsteiner Privatuniversität, St. Pölten, Austria
| | - Hans Peter Gröchenig
- Department of Internal Medicine, Barmherzige Brüder St. Veit/Glan, St. Veit, Austria
| | - Christian Madl
- Division of Gastroenterology and Hepatology, Krankenanstalt Rudolfstiftung, Krankenanstaltenverbund Wien (KAV), Vienna, Austria
| | - Philipp Schreiner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
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Abonia JP, Rudman Spergel AK, Hirano I, Shoda T, Zhang X, Martin LJ, Mukkada VA, Putnam PE, Blacklidge M, Neilson D, Collins MH, Yang GY, Capocelli KE, Foote H, Eby M, Dong S, Aceves SS, Rothenberg ME. Losartan Treatment Reduces Esophageal Eosinophilic Inflammation in a Subset of Eosinophilic Esophagitis. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. IN PRACTICE 2024; 12:2427-2438.e3. [PMID: 39059581 PMCID: PMC11552403 DOI: 10.1016/j.jaip.2024.07.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Revised: 07/08/2024] [Accepted: 07/11/2024] [Indexed: 07/28/2024]
Abstract
BACKGROUND Eosinophilic esophagitis (EoE) is a chronic, food antigen-driven esophageal disorder. Connective tissue disorders (CTDs) and esophageal connective tissue alterations are associated with EoE. Therefore, angiotensin II type 1 receptor blockade with losartan, an accepted CTD treatment, is a potential EoE treatment. OBJECTIVE We evaluated losartan's effects on esophageal pathology, symptoms, and safety in patients with EoE with and without a CTD in an open-label, non-placebo controlled multisite study. METHODS Fifteen participants with EoE, aged 5 to 23 years, underwent treatment with per-protocol titrated doses of losartan in an open-label, 16-week pilot trial. Losartan was added to standard of care therapy and 14 patients completed the study. Eosinophil counts served as the primary end point, whereas we also assessed the EoE Histology Scoring System, Endoscopic Reference Scores, EoE Diagnostic Panel, and patient-reported outcomes. RESULTS Esophageal eosinophilia was not reduced after losartan. The peak eosinophil count was not reduced for the proximal (median [interquartile range]: -3 [-22 to 3]; P = .49) and distal esophagus (median [interquartile range]: -18 [-39 to -1]; P = .23). There were no differences in losartan response in EoE with or without CTD (n = 7 and 8, respectively). Regardless, in a small subset of four participants esophageal eosinophilia was resolved with a concomitant reduction in EoE Histology Scoring System score and Endoscopic Reference Score. Across all subjects, the Pediatric EoE Symptom Score, Pediatric Quality of Life Inventory EoE Module, and EoE Diagnostic Panel improved after losartan (P < .05). CONCLUSIONS Losartan treatment was associated with improved patient-reported outcome scores and EoE Diagnostic Panel biomarkers although without a reduction in esophageal eosinophilia overall. A subset of patients demonstrated improved histopathologic and endoscopic features that could not be tied to a specific feature predicting response to treatment.
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Affiliation(s)
- J Pablo Abonia
- Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio
| | - Amanda K Rudman Spergel
- Division of Allergy, Immunology, and Transplantation, National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethesda, Md
| | - Ikuo Hirano
- Division of Gastroenterology and Hepatology, Northwestern University, Feinberg School of Medicine, Chicago, Ill
| | - Tetsuo Shoda
- Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio
| | - Xue Zhang
- Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio
| | - Lisa J Martin
- Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio
| | - Vincent A Mukkada
- Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio
| | - Philip E Putnam
- Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio
| | - Melodie Blacklidge
- Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio
| | - Derek Neilson
- Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio
| | - Margaret H Collins
- Division of Pathology and Laboratory Medicine, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio
| | - Guang-Yu Yang
- Division of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, Ill
| | | | - Heather Foote
- Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio
| | - Mike Eby
- Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio
| | - Stephanie Dong
- Division of Allergy Immunology, Rady Children's Hospital, University of California, San Diego, San Diego, Calif
| | - Seema S Aceves
- Division of Allergy Immunology, Rady Children's Hospital, University of California, San Diego, San Diego, Calif.
| | - Marc E Rothenberg
- Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio
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Chehade M, Hiremath GS, Zevit N, Oliva S, Pela T, Khodzhayev A, Jacob-Nara J, Radwan A. Disease Burden and Spectrum of Symptoms that Impact Quality of Life in Pediatric Patients with Eosinophilic Esophagitis. GASTRO HEP ADVANCES 2024; 3:1054-1068. [PMID: 39529644 PMCID: PMC11550740 DOI: 10.1016/j.gastha.2024.08.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/15/2024] [Accepted: 08/05/2024] [Indexed: 11/16/2024]
Abstract
Eosinophilic esophagitis (EoE) is a progressive type 2 inflammatory disease characterized by symptoms related to esophageal dysfunction and significant esophageal eosinophilic infiltration. It can affect patients from infancy through adulthood. Pediatric EoE has a multidimensional impact on the quality of life of both patients and their families. Nonspecific symptoms mimicking other gastrointestinal conditions, such as food refusal, failure to thrive, and feeding difficulties, may profoundly affect young children's eating skills, growth, and psychosocial status, as well as impact family financial conditions. In adolescence, dysphagia and esophageal food impactions often lead to feeding-related anxiety and influence social lives. Delays in diagnosis, arising from lack of awareness among families and clinicians and compensatory eating behaviors, could increase the risk of fibrostenotic complications, which may ultimately add to the symptom burden. Currently available treatment options include proton pump inhibitors, dietary therapies, swallowed topical steroids, esophageal dilation, and biologic therapy. Despite the efficacy of these approaches, disease burden may be further impacted by their limitations, including poor adherence rates, refractory disease, potential long-term safety concerns, and high costs for care. Thus, there is a need for more timely diagnosis in clinical practice and novel targeted disease-modifying therapies better tailored to treat various phenotypes of EoE, aimed at reducing the physical and psychosocial burdens on patients and their caregivers.
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Affiliation(s)
- Mirna Chehade
- Department of Pediatrics and Medicine, Mount Sinai Center for Eosinophilic Disorders, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Girish S. Hiremath
- Department of Pediatrics, Monroe Carell Jr Children’s Hospital at Vanderbilt, Nashville, Tennessee
| | - Noam Zevit
- Institute of Gastroenterology, Hepatology and Nutrition, Schneider Children's Medical Center of Israel, Petach-Tikva, Israel
- Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Salvatore Oliva
- Pediatric Gastroenterology and Liver Unit, Maternal and Child Health Department, Sapienza University of Rome, Rome, Italy
| | | | | | | | - Amr Radwan
- Regeneron Pharmaceuticals Inc, Tarrytown, New York
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Lucendo A, Groetch M, Gonsalves N. Dietary Management of Eosinophilic Esophagitis. Immunol Allergy Clin North Am 2024; 44:223-244. [PMID: 38575220 DOI: 10.1016/j.iac.2023.12.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/06/2024]
Abstract
Eosinophilic esophagitis (EoE) is a chronic immune-mediated food allergy-driven disease characterized by eosinophilic inflammation of the esophagus leading to symptoms of esophageal dysfunction. Prior studies have supported the key role of food allergen exposure as the main driver behind the etiopathogenesis showing that removal of food antigens can result in disease remission in both children and adults. These landmark studies serve as the basis for the rising interest and evolution of dietary therapy in EoE. This article will focus on the rationale for dietary therapy in EoE and provide helpful tools for the implementation of dietary therapy in practice.
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Affiliation(s)
- Alfredo Lucendo
- Department of Gastroenterology, Hospital General de Tomelloso, Tomelloso, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd); Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), Tomelloso, Ciudad Real 13700, Spain
| | - Marion Groetch
- Department of Pediatric Allergy & Immunology, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA
| | - Nirmala Gonsalves
- Division of Gastroenterology and Hepatology, Northwestern University-Feinberg School of Medicine, 676 North St. Claire, Suite 1400, Chicago, IL 60611, USA.
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Borinsky SA, Cameron BA, Xue Z, LaFata S, Kiran A, Ocampo AA, McCallen J, Lee CJ, Redd WD, Cotton CC, Eluri S, Reed CC, Dellon ES. Feeding Tube Placement, Complications, and Treatment Responses in a Large Eosinophilic Esophagitis Patient Population. J Pediatr Gastroenterol Nutr 2023; 77:753-759. [PMID: 37697476 PMCID: PMC11213236 DOI: 10.1097/mpg.0000000000003941] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/13/2023]
Abstract
OBJECTIVES Feeding tubes can provide a temporary or long-term solution for nutritional therapy. Little is known regarding the use of feeding tubes in patients with eosinophilic esophagitis (EoE). We sought to describe the characteristics and outcomes in EoE patients requiring tube feeding. METHODS This was a retrospective cohort study of EoE patients at a large tertiary care health system. Demographics, clinical characteristics, and endoscopic findings were extracted from medical records, and patients who had a feeding tube were identified. Patients with and without a feeding tube were compared. Details about the tube, complications, and treatment were extracted. Growth, global symptomatic, endoscopic, and histopathologic (<15 eos/hpf) responses were compared before and after the initiation of feeding tube therapy. RESULTS We identified 39 of 1216 EoE patients who had a feeding tube (3%). Feeding tube patients were younger (mean age 6.3 years), reported more vomiting, and had a lower total endoscopic reference score than non-feeding tube patients ( P < 0.01 for all). Tubes were used for therapy for an average of 6.8 years, with most patients (95%) receiving both pharmacologic and formula treatment for EoE. An emergency department visit for a tube complication was required in 26%. Tube feeding improved body mass index z score ( P < 0.01), symptomatic response (42%), endoscopic response (53%), and histologic response (71%). CONCLUSIONS Among EoE patients, only a small subset required a feeding tube and predominantly were young children with failure to thrive. Feeding tubes significantly improved growth and, when used in combination with other treatments, led to reduced esophageal eosinophilic inflammation.
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Affiliation(s)
- Stephanie A Borinsky
- From the Pediatric Gastroenterology, Department of Pediatrics, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Brenderia A Cameron
- the Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Zeyun Xue
- the Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Sean LaFata
- the Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Akshatha Kiran
- the Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Adolfo A Ocampo
- the Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Justin McCallen
- the Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Christopher J Lee
- the Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Walker D Redd
- the Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Cary C Cotton
- the Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Swathi Eluri
- the Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Craig C Reed
- the Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Evan S Dellon
- the Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC
- the Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC
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Votto M, De Filippo M, Caimmi S, Indolfi C, Raffaele A, Tosca MA, Marseglia GL, Licari A. A Practical Update on Pediatric Eosinophilic Esophagitis. CHILDREN (BASEL, SWITZERLAND) 2023; 10:1620. [PMID: 37892285 PMCID: PMC10605219 DOI: 10.3390/children10101620] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/26/2023] [Revised: 09/14/2023] [Accepted: 09/26/2023] [Indexed: 10/29/2023]
Abstract
Eosinophilic esophagitis (EoE) is an emerging atopic disease of unknown etiology limited to the esophagus. The pathogenesis is still understood and is likely characterized by type 2 inflammation. Food allergens are the primary triggers of EoE that stimulate inflammatory cells through an impaired esophageal barrier. In children and adolescents, clinical presentation varies with age and mainly includes food refusal, recurrent vomiting, failure to thrive, abdominal/epigastric pain, dysphagia, and food impaction. Upper-gastrointestinal endoscopy is the gold standard for diagnosing and monitoring EoE. EoE therapy aims to achieve clinical, endoscopic, and histological ("deep") remission; prevent esophageal fibrosis; and improve quality of life. In pediatrics, the cornerstones of therapy are proton pump inhibitors, topical steroids (swallowed fluticasone and viscous budesonide), and food elimination diets. In recent years, much progress has been made in understanding EoE pathogenesis, characterizing the clinical and molecular heterogeneity, and identifying new therapeutic approaches. Notably, clinical, molecular, endoscopic, and histological features reflect and influence the evolution of inflammation over time and the response to currently available treatments. Therefore, different EoE phenotypes and endotypes have recently been recognized. Dupilumab recently was approved by FDA and EMA as the first biological therapy for adolescents (≥12 years) and adults with active EoE, but other biologics are still under consideration. Due to its chronic course, EoE management requires long-term therapy, a multidisciplinary approach, and regular follow-ups.
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Affiliation(s)
- Martina Votto
- Pediatric Unit, Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, 27100 Pavia, Italy; (M.V.); (M.D.F.); (G.L.M.)
- Pediatric Clinic, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy;
| | - Maria De Filippo
- Pediatric Unit, Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, 27100 Pavia, Italy; (M.V.); (M.D.F.); (G.L.M.)
- Pediatric Clinic, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy;
| | - Silvia Caimmi
- Pediatric Clinic, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy;
| | - Cristiana Indolfi
- Department of Woman, Child and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy;
| | - Alessandro Raffaele
- Pediatric Surgery Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy;
| | | | - Gian Luigi Marseglia
- Pediatric Unit, Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, 27100 Pavia, Italy; (M.V.); (M.D.F.); (G.L.M.)
- Pediatric Clinic, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy;
| | - Amelia Licari
- Pediatric Unit, Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, 27100 Pavia, Italy; (M.V.); (M.D.F.); (G.L.M.)
- Pediatric Clinic, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy;
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11
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Nistel M, Andrews R, Furuta GT, Atkins D. Elimination Diet or Swallowed Topical Steroid Treatment of Pediatric Eosinophilic Esophagitis: Five-Year Outcomes. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. IN PRACTICE 2023; 11:2516-2523.e2. [PMID: 37263351 PMCID: PMC10525024 DOI: 10.1016/j.jaip.2023.05.036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Revised: 05/02/2023] [Accepted: 05/23/2023] [Indexed: 06/03/2023]
Abstract
BACKGROUND Eosinophilic esophagitis (EoE) is a chronic, antigen-mediated disease of the esophagus commonly treated with swallowed topical steroids (STS) or elimination diets (EDs). Evidence of a long-term response to EDs in pediatric patients is sparse. OBJECTIVE Our study sought to understand the natural history of pediatric EoE treated exclusively with EDs and to examine a similar population of STS-treated EoE subjects. We hypothesized that long-term adherence to an effective ED would result in ongoing EoE disease remission. METHODS We conducted a retrospective study of pediatric EoE subjects who had at least 2 visits to a multidisciplinary clinic. Subjects were identified who had (1) a new referral with a suspected diagnosis of EoE; (2) received either EDs or STS alone, and (3) completed both a diagnostic and a posttreatment endoscopy. Concomitant proton-pump inhibitor use was allowed. We collected demographics, clinical features, treatment plans, and associated side effects on each subject. Remission was defined as fewer than 15 eosinophils/high-powered field. RESULTS We screened the electronic medical record from 2015 to 2016 for subjects cared for in the Gastrointestinal Eosinophilic Diseases Program who fit criteria for inclusion in this analysis. One hundred ninety-nine subjects were identified, 16 who received exclusive EDs and 15 who were treated with STS. Treatment of these subjects was documented for 4.8 and 5.2 years, respectively (P = .51). Significant differences between the groups were observed in average age at EoE diagnosis (3.5 y ED vs 7.8 y STS; P = .002) and in number of endoscopies (6.6 in ED vs 4.5 in STS; P = .03). Fifteen of 16 subjects treated with ED attained histological remission. The initial effective ED removed a mean of 7.7 foods and the final ED removed a mean of 4 foods. No food impactions or esophageal dilations occurred in the ED group. The STS group required an average of 3.7 dose/formulation changes, 4 subjects required 1 or more dilations, 1 subject had 2 food impactions, and 2 were diagnosed with adrenal insufficiency. CONCLUSIONS Treatment with either ED or STS can lead to long-term remission of EoE. In this study, fewer side effects developed in the ED group than the STS group, but the validity of this conclusion is limited by the small sample size and reinforces the need for prospective study to explore these initial findings.
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Affiliation(s)
- Mason Nistel
- Department of Pediatrics, Gastrointestinal Eosinophilic Diseases Program, Section of Pediatric Gastroenterology, Hepatology and Nutrition, University of Colorado School of Medicine; Digestive Health Institute, Children's Hospital Colorado; Mucosal Inflammation Program, University of Colorado School of Medicine, Aurora, Colo.
| | - Rachel Andrews
- Department of Pediatrics, Gastrointestinal Eosinophilic Diseases Program, Section of Pediatric Gastroenterology, Hepatology and Nutrition, University of Colorado School of Medicine; Digestive Health Institute, Children's Hospital Colorado; Mucosal Inflammation Program, University of Colorado School of Medicine, Aurora, Colo
| | - Glenn T Furuta
- Department of Pediatrics, Gastrointestinal Eosinophilic Diseases Program, Section of Pediatric Gastroenterology, Hepatology and Nutrition, University of Colorado School of Medicine; Digestive Health Institute, Children's Hospital Colorado; Mucosal Inflammation Program, University of Colorado School of Medicine, Aurora, Colo
| | - Dan Atkins
- Department of Pediatrics, Gastrointestinal Eosinophilic Diseases Program, Section of Pediatric Gastroenterology, Hepatology and Nutrition, University of Colorado School of Medicine; Digestive Health Institute, Children's Hospital Colorado; Mucosal Inflammation Program, University of Colorado School of Medicine, Aurora, Colo
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Franciosi JP, Gordon M, Sinopoulou V, Dellon ES, Gupta SK, Reed CC, Gutiérrez-Junquera C, Venkatesh RD, Erwin EA, Egiz A, Elleithy A, Mougey EB. Medical treatment of eosinophilic esophagitis. Cochrane Database Syst Rev 2023; 7:CD004065. [PMID: 37470293 PMCID: PMC10358040 DOI: 10.1002/14651858.cd004065.pub4] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/21/2023]
Abstract
BACKGROUND Eosinophilic esophagitis (EoE) is a chronic antigen-mediated eosinophilic inflammatory disease isolated to the esophagus. As a clinicopathologic disorder, a diagnosis of EoE requires a constellation of clinical symptoms of esophageal dysfunction and histologic findings (at least 15 eosinophils/high-powered microscope field (eos/hpf)). Current guidelines no longer require the failure of response to proton pump inhibitor medications to establish a diagnosis of EoE, but continue to suggest the exclusion of other etiologies of esophageal eosinophilia. The treatment goals for EoE are improvement in clinical symptoms, resolution of esophageal eosinophilia and other histologic abnormalities, endoscopic improvement, improved quality of life, improved esophageal function, minimized adverse effects of treatment, and prevention of disease progression and subsequent complications. Currently, there is no cure for EoE, making long-term treatment necessary. Standard treatment modalities include dietary modifications, esophageal dilation, and pharmacologic therapy. Effective pharmacologic therapies include corticosteroids, rapidly emerging biological therapies, and proton pump inhibitor medications. OBJECTIVES To evaluate the efficacy and safety of medical interventions for people with eosinophilic esophagitis. SEARCH METHODS We searched CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, and WHO ICTRP to 3 March 2023. SELECTION CRITERIA Randomized controlled trials (RCTs) comparing any medical intervention or food elimination diet for the treatment of eosinophilic esophagitis, either alone or in combination, to any other intervention (including placebo). DATA COLLECTION AND ANALYSIS Pairs of review authors independently selected studies and conducted data extraction and risk of bias assessment. We expressed outcomes as a risk ratio (RR) and as the mean or standardized mean difference (MD/SMD) with 95% confidence interval (CI). We assessed the certainty of the evidence using GRADE. Our primary outcomes were: clinical, histological, and endoscopic improvement, and withdrawals due to adverse events. Secondary outcomes were: serious and total adverse events, and quality of life. MAIN RESULTS We included 41 RCTs with 3253 participants. Eleven studies included pediatric patients while the rest recruited both children and adults. Four studies were in patients with inactive disease while the rest were in patients with active disease. We identified 19 intervention comparisons. In this abstract we present the results of the primary outcomes for the two main comparisons: corticosteroids versus placebo and biologics versus placebo, based on the prespecified outcomes defined of the primary studies. Fourteen studies compared corticosteroids to placebo for induction of remission and the risk of bias for these studies was mostly low. Corticosteroids may lead to slightly better clinical improvement (20% higher), measured dichotomously (risk ratio (RR) 1.74, 95% CI 1.08 to 2.80; 6 studies, 583 participants; number needed to treat for an additional beneficial outcome (NNTB) = 4; low certainty), and may lead to slightly better clinical improvement, measured continuously (standard mean difference (SMD) 0.51, 95% CI 0.17 to 0.85; 5 studies, 475 participants; low certainty). Corticosteroids lead to a large histological improvement (63% higher), measured dichotomously (RR 11.94, 95% CI 6.56 to 21.75; 12 studies, 978 participants; NNTB = 3; high certainty), and may lead to histological improvement, measured continuously (SMD 1.42, 95% CI 1.02 to 1.82; 5 studies, 449 participants; low certainty). Corticosteroids may lead to little to no endoscopic improvement, measured dichotomously (RR 2.60, 95% CI 0.82 to 8.19; 5 studies, 596 participants; low certainty), and may lead to endoscopic improvement, measured continuously (SMD 1.33, 95% CI 0.59 to 2.08; 5 studies, 596 participants; low certainty). Corticosteroids may lead to slightly fewer withdrawals due to adverse events (RR 0.64, 95% CI 0.43 to 0.96; 14 studies, 1032 participants; low certainty). Nine studies compared biologics to placebo for induction of remission. Biologics may result in little to no difference in clinical improvement, measured dichotomously (RR 1.14, 95% CI 0.85 to 1.52; 5 studies, 410 participants; low certainty), and may result in better clinical improvement, measured continuously (SMD 0.50, 95% CI 0.22 to 0.78; 7 studies, 387 participants; moderate certainty). Biologics result in better histological improvement (55% higher), measured dichotomously (RR 6.73, 95% CI 2.58 to 17.52; 8 studies, 925 participants; NNTB = 2; moderate certainty). We could not draw conclusions for this outcome when measured continuously (SMD 1.01, 95% CI 0.36 to 1.66; 6 studies, 370 participants; very low certainty). Biologics may result in little to no difference in endoscopic improvement, measured dichotomously (effect not estimable, low certainty). We cannot draw conclusions for this outcome when measured continuously (SMD 2.79, 95% CI 0.36 to 5.22; 1 study, 11 participants; very low certainty). There may be no difference in withdrawals due to adverse events (RR 1.55, 95% CI 0.88 to 2.74; 8 studies, 792 participants; low certainty). AUTHORS' CONCLUSIONS Corticosteroids (as compared to placebo) may lead to clinical symptom improvement when reported both as dichotomous and continuous outcomes, from the primary study definitions. Corticosteroids lead to a large increase in histological improvement (dichotomous outcome) and may increase histological improvement (continuous outcome) when compared to placebo. Corticosteroids may or may not increase endoscopic improvement (depending on whether the outcome is measured dichotomously or continuously). Withdrawals due to adverse events (dichotomous outcome) may occur less frequently when corticosteroids are compared to placebo. Biologics (as compared to placebo) may not lead to clinical symptom improvement when reported as a dichotomous outcome and may lead to an increase in clinical symptom improvement (as a continuous outcome), from the primary study definitions. Biologics lead to a large increase in histological improvement when reported as a dichotomous outcome, but this is uncertain when reported as a continuous outcome, as compared to placebo. Biologics may not increase endoscopic improvement (dichotomous outcome), but this is uncertain when measured as a continuous outcome. Withdrawals due to adverse events as a dichotomous outcome may occur as frequently when biologics are compared to placebo.
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Affiliation(s)
- James P Franciosi
- Division of Gastroenterology, Hepatology, and Nutrition, Nemours Children's Hospital, Orlando, FL, USA
- College of Medicine, University of Central Florida, Orlando, USA
| | - Morris Gordon
- School of Medicine, University of Central Lancashire, Preston, UK
| | | | - Evan S Dellon
- Department of Medicine, Division of Gastroenterology and Hepatology, Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, NC, USA
| | - Sandeep K Gupta
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, University of Illinois College of Medicine at Peoria and Children's Hospital of Illinois, Peoria, IN, USA
| | - Craig C Reed
- Department of Medicine, Division of Gastroenterology and Hepatology, Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, NC, USA
| | - Carolina Gutiérrez-Junquera
- Pediatric Gastroenterology, University Hospital Puerta de Hierro Majadahonda. Autonomous University of Madrid, Madrid, Spain
| | - Rajitha D Venkatesh
- Pediatrics, Gastroenterology & Hepatology & Nutrition, Nationwide Children's Hospital, Columbus, OH, USA
| | - Elizabeth A Erwin
- Pediatric Allergy, Nationwide Children's Hospital, Columbus, OH, USA
| | - Abdullah Egiz
- School of Medicine, University of Central Lancashire, Preston, UK
| | - Assem Elleithy
- School of Medicine, University of Central Lancashire, Preston, UK
| | - Edward B Mougey
- Clinical Pharmacogenomics and Translational Research, Nemours Children's Health System, Jacksonville, FL, USA
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Redd WD, Ocampo AA, Xue Z, Chang NC, Thakkar KP, Reddy SB, Greenberg SB, Lee CJ, Ketchem CJ, Eluri S, Reed CC, Dellon ES. Eosinophilic esophagitis patients with multiple atopic conditions: Clinical characteristics and treatment response to topical steroids. Ann Allergy Asthma Immunol 2023; 131:109-115.e2. [PMID: 37100277 PMCID: PMC10330289 DOI: 10.1016/j.anai.2023.04.026] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 04/12/2023] [Accepted: 04/17/2023] [Indexed: 04/28/2023]
Abstract
BACKGROUND Patients with eosinophilic esophagitis (EoE) typically have concomitant atopic conditions, but whether there are differences in presentation or treatment response by the number of atopic diseases is unknown. OBJECTIVE To determine whether patients with EoE having multiple atopic conditions have differences in presentation or response to topical corticosteroid (TCS) treatment. METHODS We performed a retrospective cohort study of adults and children with newly diagnosed EoE. The total number of atopic comorbidities (allergic rhinitis, asthma, eczema, food allergy) was calculated. Patients with at least 2 atopic conditions other than allergic rhinitis were defined as having multiple atopic conditions and their baseline characteristics were compared with those with less than 2 atopic conditions. Histologic, symptom, and endoscopic responses to TCS treatment were also compared with bivariable and multivariable analyses. RESULTS Of the 1020 patients with EoE having atopic disease information, 235 (23%) had 1 atopic comorbidity, 211 (21%) had 2, 113 (11%) had 3, and 34 (3%) had 4. At baseline, the 180 (18%) patients with 2 or more atopic diseases were younger and had more vomiting, less abdominal pain, more exudates and edema on endoscopy, and higher peak eosinophil counts. Among those treated with TCS, there was a trend toward better global symptom response in patients with less than 2 atopic conditions, but there was no difference in histologic or endoscopic response compared with those with 2 or more atopic conditions. CONCLUSION There were differences in the initial presentation of EoE between those with and without multiple atopic conditions, but there were no major differences in histologic treatment response to corticosteroids by atopic status.
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Affiliation(s)
- Walker D Redd
- Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, North Carolina
| | - Adolfo A Ocampo
- Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, North Carolina
| | - Zeyun Xue
- Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, North Carolina
| | - Nicole C Chang
- Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, North Carolina
| | - Kisan P Thakkar
- Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, North Carolina
| | - Sumana B Reddy
- Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, North Carolina
| | - Sydney B Greenberg
- Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, North Carolina
| | - Christopher J Lee
- Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, North Carolina
| | - Corey J Ketchem
- Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, North Carolina
| | - Swathi Eluri
- Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, North Carolina
| | - Craig C Reed
- Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, North Carolina
| | - Evan S Dellon
- Center for Esophageal Diseases and Swallowing, 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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Autorinnen/Autoren, Collaborators:. S2k-Leitlinie Gastroösophageale Refluxkrankheit und eosinophile Ösophagitis der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) – März 2023 – AWMF-Registernummer: 021–013. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2023; 61:862-933. [PMID: 37494073 DOI: 10.1055/a-2060-1069] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/28/2023]
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Chang JW, Kliewer K, Haller E, Lynett A, Doerfler B, Katzka DA, Peterson KA, Dellon ES, Gonsalves N. Development of a Practical Guide to Implement and Monitor Diet Therapy for Eosinophilic Esophagitis. Clin Gastroenterol Hepatol 2023; 21:1690-1698. [PMID: 36933603 PMCID: PMC10293042 DOI: 10.1016/j.cgh.2023.03.006] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Revised: 03/02/2023] [Accepted: 03/07/2023] [Indexed: 03/20/2023]
Abstract
Dietary therapy for short- and long-term management of eosinophilic esophagitis is an effective yet poorly understood and underutilized treatment strategy. Despite several prospective trials demonstrating the efficacy of dietary therapies, successful clinical implementation is hampered by the need for a multidisciplinary approach including dietitian support and provider expertise. The availability of these resources is not readily available to most gastroenterologists. Without standardized guidance on starting or completing the diet for gastrointestinal providers and/or consulting dietitians, provider attitudes toward dietary therapy vary greatly depending on familiarity and knowledge gaps in using diet therapy. This review aims to summarize evidence in support of dietary therapy in eosinophilic esophagitis while providing guidance on initiation and implementation of dietary therapy for providers.
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Affiliation(s)
- Joy W Chang
- Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.
| | - Kara Kliewer
- Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Emily Haller
- Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan
| | - Amanda Lynett
- Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan
| | - Bethany Doerfler
- Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - David A Katzka
- Division of Digestive and Liver Diseases, Columbia University, New York, New York
| | - Kathryn A Peterson
- Division of Gastroenterology, University of Utah School of Medicine, Salt Lake City, Utah
| | - 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
| | - Nirmala Gonsalves
- Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois
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Oh TY, Hofmekler T, Freeman AJ. Update in Pediatric Gastroenterology and Nutrition. UPDATE IN PEDIATRICS 2023:369-398. [DOI: 10.1007/978-3-031-41542-5_15] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Tolerability and safety of a new elimination diet for pediatric eosinophilic gastritis and duodenitis. Allergol Int 2022; 72:306-315. [PMID: 36414511 DOI: 10.1016/j.alit.2022.11.001] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Revised: 10/22/2022] [Accepted: 10/23/2022] [Indexed: 11/21/2022] Open
Abstract
BACKGROUND Non-esophageal eosinophilic gastrointestinal disorders (non-EoE EGIDs) are chronic inflammatory disorders with massive infiltration of eosinophils into the gastrointestinal tract. Food elimination diets are potentially effective treatments. But the existing dietary therapies have various weak points. We developed a new regimen to compensate for the shortcomings of the elemental diet and 6-food elimination diet. The new regimen consists of an amino-acid-based formula, potatoes, vegetables, fruits and restricted seasonings. We named it the "Rainbow Elimination Diet (ED)." The aims of this study were to evaluate the tolerability and safety of this diet. METHODS A retrospective medical record examination was conducted at the National Center for Child Health and Development covering the period from January 2010 through December 2018. The medical records of patients (age 2-17 y) with histologically diagnosed non-EoE EGIDs were reviewed. The tolerability, nutritional intake, symptoms, and blood test findings were evaluated. RESULTS Nineteen patients were offered several kinds of food-elimination diets. Seven patients (eosinophilic gastritis: 5; gastroenteritis: 1; duodenitis: 1) were treated with Rainbow ED. Six patients were compliant with this diet. The median duration of the diet induction phase was 15 days (range 14-30). All 5 patients who had had symptoms just before the induction phase became symptom-free. The body weight decreased in 5 patients (median -0.6 kg), probably because the serum protein increased, resulting in reduced edema. All 5 patients with hypoproteinemia had elevated serum albumin (median 2.9-3.5 g/dL). The ingested nutritional elements were calculated, and most of them were sufficient, except for fat and selenium. CONCLUSIONS The Rainbow ED was well-tolerated and safe for pediatric non-EoE EGIDs.
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Wechsler JB, Schwartz S, Arva NC, Kim KYA, Chen L, Makhija M, Amsden K, Keeley K, Mohammed S, Dellon ES, Kagalwalla AF. A Single-Food Milk Elimination Diet Is Effective for Treatment of Eosinophilic Esophagitis in Children. Clin Gastroenterol Hepatol 2022; 20:1748-1756.e11. [PMID: 33823291 PMCID: PMC10123872 DOI: 10.1016/j.cgh.2021.03.049] [Citation(s) in RCA: 45] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Revised: 03/25/2021] [Accepted: 03/29/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Cow's milk protein (CMP) is the most common trigger of inflammation in children and adults with eosinophilic esophagitis (EoE). We sought to assess the clinical, endoscopic, and histologic efficacy of dietary elimination of all CMP-containing foods in EoE. METHODS We performed a prospective observational study in children with EoE treated with the 1-food elimination diet (1FED), excluding all CMP. Children and their caretakers were educated by a registered dietitian regarding dietary elimination of all CMP-containing foods, with substitutions to meet nutritional needs for optimal growth and development, and daily meal planning. Upper endoscopy with biopsies was performed after 8 to 12 weeks of treatment. The primary end point was histologic remission, defined as fewer than 15 eosinophils per high-power field. Secondary end points were symptomatic, endoscopic, and quality-of-life (QOL) improvements. RESULTS Forty-one children (76% male; ages, 9 ± 4 years; 88% white) underwent 1FED education and post-treatment endoscopy with biopsies. Histologic remission occurred in 21 (51%) children, with a decrease in peak eosinophils per high-power field from a median of 50 (interquartile range, 35-70) to a median of 1 (interquartile range, 0-6; P < .0001). Endoscopic abnormalities improved in 24 (59%) patients, while symptoms improved in 25 (61%). Improved symptoms included chest pain, dysphagia, and pocketing/spitting out food. Parents perceived worse QOL, while children perceived improved QOL with the 1FED. CONCLUSIONS One-food elimination of CMP-containing foods from the diet induced histologic remission in more than 50% of children with EoE and led to significant improvement in symptoms and endoscopic abnormalities. The ease of implementation and adherence supports the 1FED as first-line dietary treatment.
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Affiliation(s)
- Joshua B Wechsler
- Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois; Eosinophilic Gastrointestinal Diseases Program, Division of Gastroenterology, Hepatology, and Nutrition
| | - Sally Schwartz
- Eosinophilic Gastrointestinal Diseases Program, Division of Gastroenterology, Hepatology, and Nutrition
| | - Nicoleta C Arva
- Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois; Department of Pathology and Laboratory Medicine, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois
| | - Kwang-Youn A Kim
- Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois; Department of Preventive Medicine
| | - Liqi Chen
- Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois; Department of Preventive Medicine
| | - Melanie Makhija
- Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois; Division of Allergy and Clinical Immunology, Department of Pediatrics
| | - Katie Amsden
- Eosinophilic Gastrointestinal Diseases Program, Division of Gastroenterology, Hepatology, and Nutrition
| | - Kaitlin Keeley
- Eosinophilic Gastrointestinal Diseases Program, Division of Gastroenterology, Hepatology, and Nutrition
| | - Saeed Mohammed
- Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - Evan S Dellon
- Division of Gastroenterology and Hepatology, Department of Medicine, Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, North Carolina
| | - Amir F Kagalwalla
- Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois; Eosinophilic Gastrointestinal Diseases Program, Division of Gastroenterology, Hepatology, and Nutrition; Department of Pediatrics, John H Stroger Hospital of Cook County, Chicago, Illinois.
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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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Ruffner MA, Juste L, Muir AB. Medical Management of Eosinophilic Esophagitis in Pediatric Patients. Pediatr Clin North Am 2021; 68:1191-1204. [PMID: 34736584 DOI: 10.1016/j.pcl.2021.07.014] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Eosinophilic esophagitis is an immune-mediated allergic disease of the esophagus that affects pediatric patients of all ages. The diagnosis is made by esophagogastroduodenoscopy demonstrating eosinophilic infiltrate of the esophagus. Approaches to treatment involve proton pump inhibitors (PPIs), swallowed topical steroid preparations, as well as dietary elimination. In this review we discuss the evidence and efficacy of each of these approaches.
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Affiliation(s)
- Melanie A Ruffner
- Division of Allergy and Immunology, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, 34th and Civic Center Boulevard, Wood Building 3rd Floor, Philadelphia, PA 19104, USA
| | - Linola Juste
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Abramson Research Center 902E, 3615 Civic Center Boulevard, Philadelphia, PA 19104, USA
| | - Amanda B Muir
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Abramson Research Center 902E, 3615 Civic Center Boulevard, Philadelphia, PA 19104, USA.
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Treatment of Eosinophilic Esophagitis: Diet or Medication? THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE 2021; 9:3249-3256. [DOI: 10.1016/j.jaip.2021.07.029] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Revised: 07/22/2021] [Accepted: 07/22/2021] [Indexed: 12/11/2022]
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Kaymak T, Hruz P, Niess JH. Immune system and microbiome in the esophagus: implications for understanding inflammatory diseases. FEBS J 2021; 289:4758-4772. [PMID: 34213831 PMCID: PMC9542113 DOI: 10.1111/febs.16103] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2021] [Revised: 05/20/2021] [Accepted: 07/01/2021] [Indexed: 12/15/2022]
Abstract
The gastrointestinal tract is the largest compartment of the body's immune system exposed to microorganisms, structural components and metabolites, antigens derived from the diet, and pathogens. Most studies have focused on immune responses in the stomach, the small intestine, and the colon, but the esophagus has remained an understudied anatomic immune segment. Here, we discuss the esophagus' anatomical and physiological distinctions that may account for inflammatory esophageal diseases.
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Affiliation(s)
- Tanay Kaymak
- Department of Biomedicine, University of Basel, Switzerland
| | - Petr Hruz
- Clarunis - University Center for Gastrointestinal and Liver Diseases Basel, Switzerland
| | - Jan Hendrik Niess
- Department of Biomedicine, University of Basel, Switzerland.,Clarunis - University Center for Gastrointestinal and Liver Diseases Basel, Switzerland
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23
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De Vlieger L, Smolders L, Nuyttens L, Verelst S, Breynaert C, Vanuytsel T, Hoffman I, Bullens DMA. A Clinical Perspective on the Dietary Therapies for Pediatric Eosinophilic Esophagitis: The Gap Between Research and Daily Practice. Front Immunol 2021; 12:677859. [PMID: 34093578 PMCID: PMC8171264 DOI: 10.3389/fimmu.2021.677859] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2021] [Accepted: 05/05/2021] [Indexed: 12/21/2022] Open
Abstract
Pediatric eosinophilic esophagitis (ped-EoE) is an immune-mediated pathology affecting 34 per 100.000 children. It is characterized by an esophageal inflammation caused by an immune response towards food antigens that come into contact with the esophageal lining. Depending on the age of the child, symptoms can vary from abdominal pain, vomiting and failure to thrive to dysphagia and food impaction. The diagnosis of this chronic disease is based on the symptoms of esophageal dysfunction combined with an infiltration of more than 15 eosinophils per high-power field and the exclusion of secondary causes. The treatment modalities include the 3Ds: Drugs, allergen avoidance by Diet and/or esophageal Dilation. In this review we focused on the efficacy of dietary approaches in ped-EoE, which currently include the elemental diet (amino acid-based diet), the empiric elimination diet and the allergy test-directed elimination diet. Although several reviews have summarized these dietary approaches, a lack of consistency between and within the elimination diets hampers its clinical use and differences in subsequent reintroduction phases present a barrier for dietary advice in daily clinical practice. We therefore conducted an analysis driven from a clinician's perspective on these dietary therapies in the management of ped-EoE, whereby we examined whether these variations within dietary approaches, yet considered to be similar, could result in significant differences in dietary counseling.
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Affiliation(s)
- Liselot De Vlieger
- Allergy and Immunology Research Group, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
| | | | - Lisa Nuyttens
- Allergy and Immunology Research Group, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
- Clinical Division of Pediatrics, UZ Leuven, Leuven, Belgium
| | - Sophie Verelst
- Clinical Division of Pediatrics, UZ Leuven, Leuven, Belgium
| | - Christine Breynaert
- Allergy and Immunology Research Group, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
- Department of General Internal Medicine, UZ Leuven, Leuven, Belgium
| | - Tim Vanuytsel
- Gastroenterology and Hepatology, UZ Leuven, Leuven, Belgium
| | - Ilse Hoffman
- Pediatric Gastroenterology, Hepatology and Nutrition, UZ Leuven, Leuven, Belgium
| | - Dominique MA Bullens
- Allergy and Immunology Research Group, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
- Clinical Division of Pediatrics, UZ Leuven, Leuven, Belgium
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24
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Gargano D, Appanna R, Santonicola A, De Bartolomeis F, Stellato C, Cianferoni A, Casolaro V, Iovino P. Food Allergy and Intolerance: A Narrative Review on Nutritional Concerns. Nutrients 2021; 13:1638. [PMID: 34068047 PMCID: PMC8152468 DOI: 10.3390/nu13051638] [Citation(s) in RCA: 84] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Revised: 05/05/2021] [Accepted: 05/10/2021] [Indexed: 02/07/2023] Open
Abstract
Adverse food reactions include immune-mediated food allergies and non-immune-mediated intolerances. However, this distinction and the involvement of different pathogenetic mechanisms are often confused. Furthermore, there is a discrepancy between the perceived vs. actual prevalence of immune-mediated food allergies and non-immune reactions to food that are extremely common. The risk of an inappropriate approach to their correct identification can lead to inappropriate diets with severe nutritional deficiencies. This narrative review provides an outline of the pathophysiologic and clinical features of immune and non-immune adverse reactions to food-along with general diagnostic and therapeutic strategies. Special emphasis is placed on specific nutritional concerns for each of these conditions from the combined point of view of gastroenterology and immunology, in an attempt to offer a useful tool to practicing physicians in discriminating these diverging disease entities and planning their correct management. We conclude that a correct diagnostic approach and dietary control of both immune- and non-immune-mediated food-induced diseases might minimize the nutritional gaps in these patients, thus helping to improve their quality of life and reduce the economic costs of their management.
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Affiliation(s)
- Domenico Gargano
- Allergy and Clinical Immunology Unit, San Giuseppe Moscati Hospital, 83100 Avellino, Italy; (D.G.); (F.D.B.)
| | - Ramapraba Appanna
- Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, 84081 Baronissi, Italy; (R.A.); (A.S.); (C.S.); (V.C.)
| | - Antonella Santonicola
- Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, 84081 Baronissi, Italy; (R.A.); (A.S.); (C.S.); (V.C.)
| | - Fabio De Bartolomeis
- Allergy and Clinical Immunology Unit, San Giuseppe Moscati Hospital, 83100 Avellino, Italy; (D.G.); (F.D.B.)
| | - Cristiana Stellato
- Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, 84081 Baronissi, Italy; (R.A.); (A.S.); (C.S.); (V.C.)
| | - Antonella Cianferoni
- Division of Allergy and Immunology, The Children’s Hospital of Philadelphia, Perelman School of Medicine at University of Pennsylvania, Philadelphia, PA 19104, USA;
| | - Vincenzo Casolaro
- Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, 84081 Baronissi, Italy; (R.A.); (A.S.); (C.S.); (V.C.)
| | - Paola Iovino
- Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, 84081 Baronissi, Italy; (R.A.); (A.S.); (C.S.); (V.C.)
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25
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Classification of patients with esophageal eosinophilia by patterns of sensitization revealed by a diagnostic assay for multiple allergen-specific IgEs. J Gastroenterol 2021; 56:422-433. [PMID: 33591429 DOI: 10.1007/s00535-021-01766-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Accepted: 01/25/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND Eosinophilic esophagitis (EoE) is considered to be an immunoglobulin E (IgE)-mediated allergic disorder. Our goal was to examine IgE-mediated allergic sensitization patterns in patients with esophageal eosinophilia (EE). METHODS We enrolled subjects with EE who underwent evaluation with a diagnostic panel to document multiple allergen-specific IgEs. Statistically significant groups were identified by cluster analysis. We also defined allergens based on their characteristics including outdoor, indoor, plant, and animal allergens. RESULTS We classified patients with EE into 3 distinct groups, including cluster 1 (n = 62) who were minimally sensitized to most allergens except pollen and house dust, cluster 2 (n = 30) who were hypersensitized to outdoor and plant allergens, and cluster 3 (n = 15) who were hypersensitized to most allergens, most notably to indoor and animal allergens. Dysphagia reported among those in clusters 1, 2, and 3 at 35.5%, 46.7%, and 73.3%, respectively, (p = 0.028) and EoE endoscopic reference scores (EREFS) at 3.0, 6.0, and 8.0, respectively, (p < 0.001) differed significantly between the 3 clusters. Those in cluster 3 had a significantly higher prevalence of dysphagia (35.5% vs. 73.3%, p = 0.030), and higher EREFS with respect to rings (0.3 vs. 0.9, p = 0.003) and strictures (0.0 vs. 0.13, p = 0.011) compared to those in cluster 1. CONCLUSIONS IgE-mediated allergic sensitization patterns are associated with clinical features of patients with EE. Use of a diagnostic panel that detects multiple allergen-specific IgEs can help to explain the heterogeneous phenotype of this patient cohort.
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26
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Chang JW, Haller E, Dellon ES. Dietary Management of Eosinophilic Esophagitis: Man Versus Food or Food Versus Man? Gastroenterol Clin North Am 2021; 50:59-75. [PMID: 33518169 DOI: 10.1016/j.gtc.2020.10.009] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
An alternative to pharmacologic management of eosinophilic esophagitis, elimination of food antigens for diet therapy is an effective first-line treatment strategy to induce and maintain symptomatic, histologic, and endoscopic disease remission. The 3 dietary strategies for eosinophilic esophagitis include elemental diet, empiric elimination diet, and targeted elimination diet. We review the studies supporting various diet therapy strategies, practical considerations and challenges for applying an elimination diet, and novel testing to identify triggers and optimize food reintroduction.
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Affiliation(s)
- Joy W Chang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, 3912 Taubman Center, 1500 E. Medical Center Drive, SPC 5362, Ann Arbor, MI 48109, USA.
| | - Emily Haller
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, 3912 Taubman Center, 1500 E. Medical Center Drive, SPC 5362, Ann Arbor, MI 48109, USA
| | - Evan S Dellon
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, CB #7080, Bioinformatics Building, 130 Mason Farm Road, Chapel Hill, NC 27599, USA
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27
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Votto M, De Filippo M, Lenti MV, Rossi CM, Di Sabatino A, Marseglia GL, Licari A. Diet Therapy in Eosinophilic Esophagitis. Focus on a Personalized Approach. Front Pediatr 2021; 9:820192. [PMID: 35127602 PMCID: PMC8812465 DOI: 10.3389/fped.2021.820192] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Accepted: 12/27/2021] [Indexed: 12/11/2022] Open
Abstract
Eosinophilic esophagitis (EoE) is a chronic allergic disease defined by a marked eosinophilic inflammation and symptoms of esophageal dysfunction. EoE is a heterogeneous disease and severely impacts the quality of life of affected patients. The current therapeutic management of EoE is based on two cornerstones: medication and diet therapy, both effective but limited by several critical issues. The choice of one or the other therapy might depend on the different disease phenotypes (allergic vs. non-allergic, inflammatory vs. fibro-stenotic), patient's age (adult vs. childhood-onset), food habits, patient/family preference, and familiar financial resource. Diet therapy is a successful treatment but limited by low patient adherence, the need for several endoscopies, food restrictions, psychosocial impact, and potential nutritional deficiencies. All these limitations could be effectively overcome with multidisciplinary and personalized management. This review summarizes the most recent evidence on the dietary elimination approaches and will provide a practical guide to clinicians in managing and implementing dietary therapy for patients with EoE.
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Affiliation(s)
- Martina Votto
- Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy
| | - Maria De Filippo
- Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy
| | - Marco Vincenzo Lenti
- Department of Internal Medicine, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy
| | - Carlo Maria Rossi
- Department of Internal Medicine, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy
| | - Antonio Di Sabatino
- Department of Internal Medicine, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy
| | - Gian Luigi Marseglia
- Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy
- Pediatric Clinic, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Amelia Licari
- Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy
- Pediatric Clinic, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
- *Correspondence: Amelia Licari
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28
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Lucendo AJ. Nutritional approach to eosinophilic esophagitis: which diet and when. Minerva Gastroenterol (Torino) 2020; 68:49-59. [PMID: 33267566 DOI: 10.23736/s2724-5985.20.02797-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Dietary elimination therapy has been for a long time an option for patients with eosinophilic esophagitis (EoE) and remains the only therapy targeting the cause of the disease. Different dietary approaches have been described along the last 3 decades, and cumulative evidence has defined the effectiveness and usefulness of each approach. Elemental diets are highly effective to induce EoE remission, but unpractical in most patients. Allergy testing-directed food restrictions resulted inefficient to induce remission in a significant proportion of patients (especially adults) and show a low concordance with the dietary causes of EoE. Empiric elimination diets are currently considered the most effective drug-free treatment for patients of all ages with EoE, after widely providing reproducible results. Highly restrictive empiric six-food elimination diets have paved the way to most efficient and less restrictive step-up approaches, which now include four-food and two-food elimination diets. The potential role of milk-elimination, especially in children, should be also considered. Multiple factors including demographics, nutritional status, patient and family lifestyles, social and financial support, and acceptance of repeated endoscopies influence the results of dietary therapy. Dietary therapy in EoE should be patient centered, and the patients and/or their families together with the medical provider should participate in the decision to set up this treatment. This article updates recent knowledge on dietary therapy for EoE and provides guideline to choose the most suitable alternative for patients with EoE, as well as practical tips to achieve the best results in clinical practice.
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Affiliation(s)
- Alfredo J Lucendo
- Department of Gastroenterology, General Hospital of Tomelloso, Tomelloso, Spain - .,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain - .,Instituto de Investigación Sanitaria La Princesa, Madrid, Spain -
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29
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Doyle AD, Masuda MY, Kita H, Wright BL. Eosinophils in Eosinophilic Esophagitis: The Road to Fibrostenosis is Paved With Good Intentions. Front Immunol 2020; 11:603295. [PMID: 33335531 PMCID: PMC7736408 DOI: 10.3389/fimmu.2020.603295] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2020] [Accepted: 11/03/2020] [Indexed: 12/15/2022] Open
Abstract
Eosinophilic esophagitis (EoE) is an antigen-driven disease associated with epithelial barrier dysfunction and chronic type 2 inflammation. Eosinophils are the defining feature of EoE histopathology but relatively little is known about their role in disease onset and progression. Classically defined as destructive, end-stage effector cells, eosinophils (a resident leukocyte in most of the GI tract) are increasingly understood to play roles in local immunity, tissue homeostasis, remodeling, and repair. Indeed, asymptomatic esophageal eosinophilia is observed in IgE-mediated food allergy. Interestingly, EoE is a potential complication of oral immunotherapy (OIT) for food allergy. However, we recently found that patients with peanut allergy may have asymptomatic esophageal eosinophilia at baseline and that peanut OIT induces transient esophageal eosinophilia in most subjects. This is seemingly at odds with multiple studies which have shown that EoE disease severity correlates with tissue eosinophilia. Herein, we review the potential role of eosinophils in EoE at different stages of disease pathogenesis. Based on current literature we suggest the following: (1) eosinophils are recruited to the esophagus as a homeostatic response to epithelial barrier disruption; (2) eosinophils mediate barrier-protective activities including local antibody production, mucus production and epithelial turnover; and (3) when type 2 inflammation persists, eosinophils promote fibrosis.
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Affiliation(s)
- Alfred D Doyle
- Division of Allergy, Asthma, and Clinical Immunology, Department of Medicine, Mayo Clinic Arizona, Scottsdale, AZ, United States
| | - Mia Y Masuda
- Division of Allergy, Asthma, and Clinical Immunology, Department of Medicine, Mayo Clinic Arizona, Scottsdale, 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
| | - 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
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30
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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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31
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Eosinophilic Esophagitis as a Side Effect of Food Oral Immunotherapy. ACTA ACUST UNITED AC 2020; 56:medicina56110618. [PMID: 33207848 PMCID: PMC7697667 DOI: 10.3390/medicina56110618] [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: 10/05/2020] [Revised: 10/29/2020] [Accepted: 10/30/2020] [Indexed: 02/06/2023]
Abstract
Food allergies (FAs) include a spectrum of immune-mediated serious and potentially life-threatening medical conditions with an overall estimated prevalence ranging from 4% to 8% in the U.S. and Europe. Significant progress in food allergen-specific immunotherapy has been accomplished over the past 10 years. The most studied strategy has been oral immunotherapy (OIT), also known as food desensitization, a treatment in which a child is slowly and deliberately given a small amount of the food to ingest (that previously was a food allergy trigger) with the ultimate goal of the child eating that food without a reaction. OIT is now recommended in the European guidelines for the treatment of milk, egg, and peanut allergies and was the first American Food Drug Administration (FDA) approved product for the prevention of severe reaction to peanuts in 4–17 year olds to be released on the market. The side effects associated with OIT treatment trials are mild to moderate, predominantly oropharyngeal, and easily treated. More severe reactions, such as generalized urticaria/angioedema, wheezing/respiratory distress, laryngeal edema, and repetitive emesis, have been reported. However systemic reactions are very rare. Low-dose immunotherapy is associated with significantly fewer side effects. Currently, its most limiting allergic side effect is that approximately 10–15% of subjects treated with OIT experience gastrointestinal symptoms, preventing the continuation of therapy. Eosinophilic esophagitis (EoE) has also been reported as a cause of persistent abdominal symptoms in OIT.
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Abstract
PURPOSE OF REVIEW To summarize current dietary and pharmacologic approaches in the treatment of eosinophilic esophagitis (EoE). RECENT FINDINGS Studies comparing dietary approaches in EoE treatment support empiric elimination diets as the preferred approach to dietary EoE treatment, with no data to support use of currently available allergy tests to guide specific food elimination diets. Swallowed topical corticosteroid therapy is the current standard of care in pharmacologic EoE treatment, with similar effectiveness of fluticasone and budesonide, but their discontinuation results in return of both EoE symptoms and disease. A number of nonsteroid-based therapies are currently under investigation for the treatment of EoE, which are focused on targeting disease at a cellular level. SUMMARY EoE can be treated with diet or medications. Empiric elimination is presently the preferred dietary approach. Swallowed steroids is the standard of care to treat EoE with medication; however, there are several promising drugs currently undergoing clinical trials.
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33
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Lucendo AJ, Molina-Infante J. Dietary therapy for eosinophilic esophagitis: chances and limitations in the clinical practice. Expert Rev Gastroenterol Hepatol 2020; 14:941-952. [PMID: 32614693 DOI: 10.1080/17474124.2020.1791084] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Eosinophilic esophagitis (EoE) is a non-Immunoglobulin E-mediated food allergy that currently represents the main cause of dysphagia and food impaction in children and young adults. Diet remains the only therapy targeting the cause of the disease. Relevant advances in recent years allow novel approaches to dietary therapy in EoE. AREAS COVERED An up-to-date review on dietary therapy for EoE is provided, as a potential first-line anti-inflammatory therapy able to induce and maintain remission in a significant proportion of patients. Unpractical elemental diets and suboptimal food allergy testing-directed food restrictions paved the way for empiric elimination diets, which currently are to be considered as the most effective drug-free treatment for EoE. After largely restrictive empiric six-food elimination diets, most efficient step-up approaches now include four-food and two-food elimination diets. The potential of milk-elimination is also discussed. EXPERT COMMENTARY An empiric elimination diet step-up strategy should be currently considered as the initial approach for dietary treatment in EoE patients of all ages. Compared to a top-down strategy, step-up diets reduce the need for endoscopic procedures, shorten diagnostic process times, and avoid unnecessary restrictions. Furthermore, early identification of responders with few food triggers may select best candidates for maintenance dietary therapy.
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Affiliation(s)
- Alfredo J Lucendo
- Department of Gastroenterology, Hospital General de Tomelloso , Tomelloso, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) , Madrid, Spain.,Instituto de Investigación Sanitaria La Princesa , Madrid, Spain
| | - Javier Molina-Infante
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) , Madrid, Spain.,Department of Gastroenterology, Hospital Universitario de Caceres , Caceres, Spain
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34
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A Novel Allergen-Specific Immune Signature-Directed Approach to Dietary Elimination in Eosinophilic Esophagitis. Clin Transl Gastroenterol 2020; 10:e00099. [PMID: 31789931 PMCID: PMC6970559 DOI: 10.14309/ctg.0000000000000099] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
OBJECTIVES: Dietary elimination for treatment of eosinophilic esophagitis (EoE) is limited by lack of accuracy in current allergy tests. We aimed to develop an immunologic approach to identify dietary triggers and prospectively test allergen-specific immune signature-guided dietary elimination therapy. METHODS: In the first phase, we developed and assessed 2 methods for determining selected food triggers using samples from 24 adults with EoE: a CD4+ T-cell proliferation assay in peripheral blood and food-specific tissue IgG4 levels in esophageal biopsies. In the second phase, we clinically tested elimination diets created from these methods in a prospective cohort treated for 6 weeks (NCT02722148). Outcomes included peak eosinophil counts (eos/hpf), endoscopic findings (measured by the EoE Endoscopic Reference Score), and symptoms (measured by the EoE Symptom Activity Index). RESULTS: Parameters were optimized with a positive test on either assay, yielding agreements of 60%, 75%, 53%, 58%, and 53% between predicted and known triggers of peanut, egg, soy, wheat, and milk, respectively. In clinical testing, the mean number of foods eliminated based on the assays was 3.4, and 19 of 22 subjects were compliant with treatment. After treatment, median peak eosinophil counts decreased from 75 to 35 (P = 0.007); there were 4 histologic responders (21%). The EoE Endoscopic Reference Score and EoE Symptom Activity Index score also decreased after treatment (4.6 vs 3.0; P = 0.002; and 32.5 vs 25.0; P = 0.06, respectively). DISCUSSION: We successfully developed a new testing approach using CD4+ T-cell proliferation and esophageal food-specific IgG4 levels, with promising accuracy rates. In clinical testing, this led to improvement in eosinophil counts, endoscopic severity, and symptoms of dysphagia, but a smaller than expected number of patients achieved histologic remission.
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35
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Kashyap PC, Johnson S, Geno DM, Lekatz HR, Lavey C, Alexander JA, Chen J, Katzka DA. A decreased abundance of clostridia characterizes the gut microbiota in eosinophilic esophagitis. Physiol Rep 2020; 7:e14261. [PMID: 31650712 PMCID: PMC6813259 DOI: 10.14814/phy2.14261] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2019] [Revised: 09/12/2019] [Accepted: 09/17/2019] [Indexed: 01/14/2023] Open
Abstract
Abnormalities in the gut microbiome are associated with suppressed Th2 response (Belizario et al., 2018 Mediators Inflamm. 2018:2037838) and predisposition to atopic disease such as asthma and eczema. We investigated if this applies to eosinophilic esophagitis (EoE). Stool bacterial DNA was extracted and followed by 16S rRNA amplification from 12 patients with eosinophilic esophagitis and 12 controls. Alpha‐ and beta‐diversity were analyzed. Only two patients had asthma or atopy and one patient was on budesonide. No patients were on PPIs. Patients with EoE had lower gut microbiota alpha diversity (species richness, P = 0.09; Shannon index, P = 0.01). The microbial composition was distinct as evidenced by significantly different beta diversity (P = 0.03) when compared to healthy controls. There were also significant differences in relative abundance at multiple taxonomic levels when comparing the two communities; at the phylum level, we observed a marked decrease in Firmicutes and increase in Bacteroidetes and at the order and family level there were significant decreases in Clostridia and Clostridiales in patients with EoE (q ≤ 0.1). We conclude that there are significant differences in microbial community structure, microbial richness, and evenness and a significant decrease in taxa within the Clostridia in patients with EoE. Our data suggest that Clostridia based interventions could be tested as adjuncts to current therapeutic strategies in EoE.
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Affiliation(s)
- Purna C Kashyap
- Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.,Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota
| | - Stephen Johnson
- Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota
| | - Debra M Geno
- Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Heather R Lekatz
- Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Crystal Lavey
- Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | | | - Jun Chen
- Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota
| | - David A Katzka
- Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
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36
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Chen JW. Management of Eosinophilic Esophagitis: Dietary and Nondietary Approaches. Nutr Clin Pract 2020; 35:835-847. [PMID: 32822071 DOI: 10.1002/ncp.10571] [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] [Indexed: 12/19/2022] Open
Abstract
Eosinophilic esophagitis (EoE) is an allergen-driven chronic inflammatory condition, characterized by symptoms related to esophageal dysfunction and confirmed histologically by esophageal mucosal eosinophilia. Since its first description in the 1990s, the incidence and prevalence of EoE have been on the rise. It is known to affect all ages of various ethnic backgrounds and both sexes; however, it is most seen in White males. Children with EoE often present with abdominal pain, nausea, vomiting, and failure to thrive, whereas adults with EoE typically present with dysphagia and food impaction. Diagnosis of EoE requires histologic confirmation of elevated esophageal eosinophils in a symptomatic patient, and only after secondary causes have been excluded. Because EoE is a chronic and progressively fibrostenotic disease, treatment goals include resolution of symptoms, induction and maintenance of disease remission, and prevention and possibly reversal of fibrostenotic complications, while minimizing treatment-related adverse effects and improving quality of life. Treatment strategies include the "3 D's"-drugs, diet, and dilation. Standard drug therapies include proton-pump inhibitors and topical corticosteroids. Dietary therapies include elemental diet, allergy testing-directed elimination diet, and empiric elimination diets. Endoscopic esophageal dilation for EoE strictures can alleviate esophageal symptoms but has no effect on mucosal inflammation. Recent progress in EoE research has made possible evidence-based clinical guidelines. Ongoing pharmacologic trials show promise for novel biologic agents in the treatment of refractory EoE.
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Affiliation(s)
- Joan W Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
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Chehade M, Brown S. Elimination diets for eosinophilic esophagitis: making the best choice. Expert Rev Clin Immunol 2020; 16:679-687. [DOI: 10.1080/1744666x.2020.1801419] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
- Mirna Chehade
- Mount Sinai Center for Eosinophilic Disorders, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Shimron Brown
- Mount Sinai Center for Eosinophilic Disorders, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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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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Lucendo AJ, Molina-Infante J. Treatment of eosinophilic esophagitis with diets. MINERVA GASTROENTERO 2020; 66:124-135. [DOI: 10.23736/s1121-421x.19.02634-5] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
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Gutiérrez-Junquera C, Zevit N. Dietary treatment of eosinophilic gastrointestinal disorders in children. Curr Opin Clin Nutr Metab Care 2020; 23:210-216. [PMID: 32068545 DOI: 10.1097/mco.0000000000000643] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
PURPOSE OF REVIEW To provide an overview of recent developments on dietary treatment of eosinophilic gastrointestinal disorders (EGID) in children. RECENT FINDINGS Food antigens are the main triggers of eosinophilic esophagitis (EoE); however, currently available allergy tests cannot reliably identify eliciting antigens. Studies evaluating the six-food empiric elimination diet (6FED-milk, wheat/gluten, egg, soy/legumes, nuts and fish/seafood) have shown histological remission rates of 72%. Milk, egg, wheat/gluten, and, to a lesser extent, soy/legumes were the most frequent food triggers with only one or two culprit foods identified for most patients. A 4-food elimination strategy afforded a 64% remission rate. A step-up two-four-six food elimination diet generated a 43% remission rate at the two-food elimination stage, and similar reported rates for 4FED and 6FED. Endoscopic procedures were reduced by a 20% compared with 6FED. In a prospective study including 63 children, exclusive milk elimination has been effective in 44% of them. Controlled elimination and reintroduction with histological assessment is necessary. SUMMARY Dietary therapy of EoE has evolved from more restrictive to less restrictive diets to provide better balance between efficacy vs. nutritional deficiencies and quality of life. Data on efficacy of dietary therapy in other EGIDs are very scarce.
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Affiliation(s)
- Carolina Gutiérrez-Junquera
- Pediatric Gastroenterology Unit, University Hospital Puerta de Hierro Majadahonda, Autonomous University of Madrid, Madrid, Spain
| | - Noam Zevit
- Institute of Gastroenterology, Nutrition and Liver Diseases, Schneider Children's Medical Center of Israel, Petah Tikva
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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Abstract
Food allergies, defined as an immune response to food proteins, affect as many as 8% of young children and 2% of adults in western countries, and their prevalence appears to be rising like all allergic diseases. In addition to well-recognized urticaria and anaphylaxis triggered by IgE antibody- mediated immune responses, there is an increasing recognition of cell-mediated disorders, such as eosinophilic esophagitis and food protein-induced enterocolitis. Non-IgE-Mediated gastrointestinal food allergies are a heterogeneous group of food allergies in which there is an immune reaction against food but the primary pathogenesis is not a production of IgE and activation of mast cells and basophils. Those diseases tend to affect mainly the gastrointestinal tract and can present as acute (FPIES) or chronic reaction, such as Eosinophilic Esophagitis (EoE), Food Protein-Induced Allergic Proctocolitis (FPIAP). The role of food allergy in Non-EoE gastrointestinal Eosinophilic disorders (Non- EoE EGID) is poorly understood. In some diseases like EoE, T cell seems to play a major role in initiating the immunological reaction against food, however, in FPIES and FPIAP, the mechanism of sensitization is not clear. Diagnosis requires food challenges and/or endoscopies in most of the patients, as there are no validated biomarkers that can be used for monitoring or diagnosis of Non-IgE mediated food allergies. The treatment of Non-IgE food allergy is dependent on diet (FPIES, and EoE) and/or use of drugs (i.e. steroids, PPI) in EoE and Non-EoE EGID. Non-IgE mediated food allergies are being being investigated.
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Affiliation(s)
- Antonella Cianferoni
- Division of Allergy and Immunology, Department of Pediatrics, The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, United States
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Abstract
BACKGROUND For eosinophilic esophagitis (EoE) recently an association with immunoglobulin (Ig)G4 rather than IgE has been reported. Gastroesophageal reflux disease (GERD) is the most important differential diagnosis of EoE. We compared esophageal IgG4 plasma cell infiltration and serum IgG4 levels of EoE patients (before and after budesonide therapy) with GERD patients. METHODS Prospectively collected serum samples of 17 EoE patients before and after 8 weeks of therapy with budesonide (1 mg BID) were analyzed for total and antigen-specific IgG4 and IgE levels. Also, immunohistochemical analysis of total and IgG4-positive plasma cells was performed on esophageal biopsies of these patients. In total, 14 GERD patients without histologic proof of eosinophilic infiltration were taken as a control group. RESULTS Total IgG4 serum levels in EoE patients were significantly higher than in GERD patients (121.0 vs. 71.2 mg/dL; P=0.038) and decreased under budesonide therapy (121.0 vs. 104.2 mg/dL; P=0.019). IgE levels did not differ significantly between all groups. In EoE patients also a high number of esophageal IgG4-positive plasma cells was detected and significantly reduced under therapy (29.1 vs. 0.1 IgG4-positive cells; P<0.001). In GERD patients no relevant esophageal plasma cell infiltration could be seen. CONCLUSIONS In EoE patients elevated systemic IgG4 serum levels compared with GERD patients can be seen and decrease under topical steroid therapy. Also, local IgG4 plasma cells expression is high in EoE, but not in GERD patients and normalize under therapy. These findings are further proof for a possible association of EoE with IgG4.
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Wong J, Goodine S, Samela K, Vance KS, Chatfield B, Wang Z, Sayej WN. Efficacy of Dairy Free Diet and 6-Food Elimination Diet as Initial Therapy for Pediatric Eosinophilic Esophagitis: A Retrospective Single-Center Study. Pediatr Gastroenterol Hepatol Nutr 2020; 23:79-88. [PMID: 31988878 PMCID: PMC6966220 DOI: 10.5223/pghn.2020.23.1.79] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2019] [Accepted: 10/14/2019] [Indexed: 12/17/2022] Open
Abstract
PURPOSE Management of eosinophilic esophagitis (EoE) varies from center to center. In this study, we evaluated the effectiveness of a dairy-free diet (DFD) and the 6-Food Elimination Diet (SFED) as initial therapies for the treatment of EoE in our practice. METHODS This was a retrospective study of children who had been treated for EoE at Connecticut Children's Medical Center, Hartford, CT, USA. Pre- and post-treatment endoscopy findings and histology results of patients treated with DFD or SFED were examined. RESULTS One hundred fifty-two patients (age 9.2±5.2 years, 76.3% male, 69.7% caucasian) met the inclusion criteria for initial treatment with DFD (n=102) or SFED (n=50). Response for DFD was 56.9% and for SFED was 52.0%. Response based on treatment duration (<10, 10-12, and >12 weeks) were 81.8%, 50.0%, and 55.1% for DFD, and 68.8%, 50.0%, and 40.0% for SFED. Response based on age (<6, 6-12, and >12 years) were 59.3%, 42.9%, and 67.5% for DFD, and 36.4%, 58.8%, and 72.7% for SFED. In patients treated with DFD, concomitant proton pump inhibitor (PPI) administration resulted in improved outcomes (p=0.0177). Bivariate regression analysis showed that PPI with diet is the only predictor of response (p=0.0491), however, there were no significant predictors on multiple regression analysis. CONCLUSION DFD and SFED are effective first line therapies for EoE. DFD should be tried first before extensive elimination diets. Concomitant therapy with PPI's may be helpful.
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Affiliation(s)
- Jonathan Wong
- Department of Pediatrics, University of Connecticut School of Medicine, Farmington, CT, USA
| | - Sue Goodine
- Department of Pediatrics, Division of Digestive Diseases, Hepatology and Nutrition, Connecticut Children's Medical Center, Hartford, CT, USA
| | - Kate Samela
- Department of Pediatrics, Division of Digestive Diseases, Hepatology and Nutrition, Connecticut Children's Medical Center, Hartford, CT, USA
| | - Katherine S Vance
- Department of Pediatrics, Division of Digestive Diseases, Hepatology and Nutrition, Connecticut Children's Medical Center, Hartford, CT, USA
| | - Beth Chatfield
- Department of Pediatrics, Division of Digestive Diseases, Hepatology and Nutrition, Connecticut Children's Medical Center, Hartford, CT, USA
| | - Zhu Wang
- Department of Pediatrics, University of Connecticut School of Medicine, Farmington, CT, USA.,Department of Pediatric Research, Connecticut Children's Medical Center, Hartford, CT, USA
| | - Wael N Sayej
- Department of Pediatrics, University of Connecticut School of Medicine, Farmington, CT, USA.,Department of Pediatrics, Division of Digestive Diseases, Hepatology and Nutrition, Connecticut Children's Medical Center, Hartford, CT, USA
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De Matteis A, Pagliaro G, Corleto VD, Pacchiarotti C, Di Giulio E, Villa MP, Parisi P, Vassallo F, Ziparo C, Di Nardo G. Eosinophilic Esophagitis in Children: Clinical Findings and Diagnostic Approach. Curr Pediatr Rev 2020; 16:206-214. [PMID: 31584371 PMCID: PMC8193808 DOI: 10.2174/1573396315666191004110549] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2019] [Revised: 09/02/2019] [Accepted: 09/02/2019] [Indexed: 02/07/2023]
Abstract
Eosinophilic esophagitis (EoE) is an emerging chronic immune and antigen-mediated clinicopathologic disease. During the last 2 decades, the incidence of this condition in children has increased significantly, thanks to practitioners for creating the awareness and higher use of diagnostic endoscopy. We have analysed paediatric literature on EoE focusing on the epidemiology, pathophysiology, clinical findings and diagnostic approach. EoE is pathogenically related to a Th2 inflammation characterized by a mixed IgE and non-IgEmediated reaction to food and/or environmental agents. This leads to esophageal dysfunction and remodeling accompanied by subepithelial fibrosis. EoE can be presented with several range of gastrointestinal symptoms, including regurgitation, vomiting, feeding difficulties or feeding refusal in infants and toddlers, as well as heartburn, dysphagia and food bolus impaction in older children and adults. The diagnostic suspicion is based on the presence of chronic symptoms of esophgeal dysfunction and esophageal eosinophilia characterised histologically by a significant eosinophilic infiltration of the oesophageal mucosa (>15 eosinophils per high powered field). In this review, we will provide an update on clinical presentation and diagnostic approach to EoE in children. We emphasized on the relevant aspects of the new clinical condition termed "PPI responsive esophageal eosinophilia", as entities distinct from EoE and the role of PPI trial in the diagnostic workup, therefore we proposed a new diagnostic algorithm.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | - Giovanni Di Nardo
- Address correspondence to this author at the Chair of Pediatrics, NESMOS Department, School of Medicine and Psychology, Sapienza University of Rome, Sant’Andrea University Hospital, Via di Grottarossa 1035-1039, 00189 - Rome, Italy; Tel: +393397267637; E-mail:
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45
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Atwal K, Hubbard GP, Venter C, Stratton RJ. The use of amino acid-based nutritional feeds is effective in the dietary management of pediatric eosinophilic oesophagitis. Immun Inflamm Dis 2019; 7:292-303. [PMID: 31692292 PMCID: PMC6842817 DOI: 10.1002/iid3.273] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2019] [Revised: 09/12/2019] [Accepted: 09/13/2019] [Indexed: 01/07/2023] Open
Abstract
INTRODUCTION Eosinophilic oesophagitis (EoE) is an immune-mediated, chronic disease characterized by eosinophilic inflammation and esophageal dysfunction. Specific food allergens including cow's milk protein, are partially causative to disease progression, and dietary management forms three main options; the elemental diet (ED), the empirical elimination diet (EED), and the targeted elimination diet (TED). The dietary choice should be individualized, however, the European Society for Pediatric Gastroenterology, Hepatology and Nutrition guidelines recommend an ED for pediatric EoE with multiple food allergies, failure to thrive, unresponsive disease or unable to follow a highly restricted diet. The aim of this narrative review was to explore the effectiveness of the ED (using amino acid formula [AAF]), in the management of pediatric EoE. METHODS Literature searches were performed to identify eligible studies that described outcomes including eosinophil count, clinical symptoms, growth, and medications. RESULTS Overall, 10 eligible studies were found, with n = 462 patients assigned to receive AAF from a total of n = 748 (average age 6.7 years), for a duration of 4 to 8 weeks. The use of AAF reduced eosinophil levels and demonstrated remission (defined as ≤10 eosinophils per high power field) in 75%-100% of children with improvements, if not resolution, in clinical symptoms. AAF was more clinically effective than the use of the EED or TED, where remission rates were 75%-81% and 40%-69%, respectively. Few studies collected growth outcomes, however where documented these were positive for those on AAF. The long-term impacts of each diet were not thoroughly explored. CONCLUSIONS The use of AAF is a clinically effective management option for pediatric EoE, and further research is required to guide long-term management.
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Affiliation(s)
| | | | - Carina Venter
- Section of Allergy and Immunology, Children's Hospital ColoradoUniversity of Colorado Denver School of MedicineColorado
| | - Rebecca J. Stratton
- Medical AffairsNutricia LtdTrowbridgeUnited Kingdom
- Faculty of MedicineUniversity of SouthamptonSouthamptonUnited Kingdom
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46
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Dellon ES, Gupta SK. A Conceptual Approach to Understanding Treatment Response in Eosinophilic Esophagitis. Clin Gastroenterol Hepatol 2019; 17:2149-2160. [PMID: 30710696 PMCID: PMC6667323 DOI: 10.1016/j.cgh.2019.01.030] [Citation(s) in RCA: 75] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2018] [Revised: 01/15/2019] [Accepted: 01/20/2019] [Indexed: 02/07/2023]
Abstract
While the diagnosis and initial treatment of eosinophilic esophagitis are becoming more standardized, there are still major gaps in knowledge related to measuring treatment response. One such question centers on how to measure treatment response and what treatment endpoints should be. This impacts not only patient care and engagement in decision-making, but also the field of drug development. In addition, studies so far have use a myriad of treatment endpoints including over a dozen histologic endpoint criteria. This review will discuss the various stakeholders involved in assessment of treatment endpoints of a complex condition, including patients, practitioners and regulatory agencies, and the care settings in which treatment response is assessed, including routine clinical care, clinical trials, and observational studies. Potential parameters or treatment endpoints such as histology, symptoms, patient-reported outcomes, endoscopy, and biomarkers are discussed along with associated challenges and opportunities. A framework on how to define treatment outcomes is discussed and a conceptual approach treatment response is proposed. This takes into account histology, symptoms, and endoscopic findings and harnesses existing, validated tools. It includes definitions of nonresponse, complete normalization, and a graded response category between these 2 extremes, and also permits flexibility and latitude for modifications as newer knowledge emerges. In addition, ways to position the pediatric population in these endeavors are discussed as are future research directions.
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Affiliation(s)
- 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; Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
| | - Sandeep K Gupta
- Division of Pediatric Gastroenterology, University of Illinois College of Medicine, Peoria, IL
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47
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Capucilli P, Hill DA. Allergic Comorbidity in Eosinophilic Esophagitis: Mechanistic Relevance and Clinical Implications. Clin Rev Allergy Immunol 2019; 57:111-127. [PMID: 30903437 PMCID: PMC6626558 DOI: 10.1007/s12016-019-08733-0] [Citation(s) in RCA: 67] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Allergic eosinophilic esophagitis (EoE) is a chronic, allergen-mediated inflammatory disease of the esophagus, and the most common cause of prolonged dysphagia in children and young adults in the developed world. While initially undistinguished from gastroesophageal reflux disease-associated esophageal eosinophilia, EoE is now recognized as a clinically distinct entity that shares fundamental inflammatory features of other allergic conditions and is similarly increasing in incidence and prevalence. The clinical and epidemiologic associations between EoE and other allergic manifestations are well established. In addition to exaggerated rates of atopic dermatitis, IgE-mediated food allergy, asthma, and allergic rhinitis in EoE patients, each of these allergic manifestations imparts individual and cumulative risk for subsequent EoE diagnosis. As such, EoE may be a member of the "allergic march"-the natural history of allergic manifestations during childhood. Several determinants likely contribute to the relationship between these conditions, including shared genetic, environmental, and immunologic factors. Herein, we present a comprehensive review of allergic comorbidity in EoE. We discuss areas of the genome associated with both EoE and other allergic diseases, including the well-studied variants encoding thymic stromal lymphopoietin and calpain 14, among other "atopic" regions. We summarize ways that environmental factors (such as microbiome-altering pressures and aeroallergen exposure) may predispose to multiple allergic conditions including EoE. Finally, we touch on some fundamental features of type 2 inflammation, and the resulting implications for the development of multiple allergic manifestations. We conclude with an analysis of the "type 2" biologics, and how mechanistic similarities between EoE and the other allergic manifestations have important implications for screening and treatment of the allergic patient.
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Affiliation(s)
- Peter Capucilli
- Division of Allergy and Immunology, Department of Pediatrics, Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Abramson Research Building, 3615 Civic Center Blvd, Philadelphia, PA, 19104, USA
| | - David A Hill
- Division of Allergy and Immunology, Department of Pediatrics, Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Abramson Research Building, 3615 Civic Center Blvd, Philadelphia, PA, 19104, USA.
- Institute for Immunology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
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48
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Lianto P, Zhang Y, Che H. Signals from the various immune cells in promoting food allergy-induced eosinophilic esophagitis like disease. Asia Pac Allergy 2019; 9:e28. [PMID: 31384583 PMCID: PMC6676061 DOI: 10.5415/apallergy.2019.9.e28] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2017] [Accepted: 07/26/2019] [Indexed: 12/21/2022] Open
Abstract
Eosinophilic esophagitis (EoE) is a recently recognized esophageal inflammatory disease with clinical manifestations arising from esophageal dysfunction. The etiology of EoE is currently being clarified and food allergy is evolving as the central cornerstone of EoE disease pathogenesis. Given the large number of eosinophils in the esophagus of people with EoE verified by data from murine models EoE is widely considered as the hallmark T-helper type 2 (Th2) disease of the esophagus. It is also known that some eosinophilic inflammation is controlled by other subsets of T cells such as Th9 or Th17 and control is also exerted by type 2 innate lymphoid cells acting together with basophils. In this paper we review results from molecular studies of mouse models in light of the results from the first clinical trials targeting key cytokines in humans and present in-depth molecular understanding of EoE.
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Affiliation(s)
- Priscilia Lianto
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
| | - Yani Zhang
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
| | - Huilian Che
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
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49
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Alterio T, Cardile S, Trayers C, Valenti S, Loddo I, Mardare R, Mosca A, Nobili V. Eosinophilic esophagitis in children: current knowledge to open new horizons. Scand J Gastroenterol 2019; 54:822-829. [PMID: 31535579 DOI: 10.1080/00365521.2019.1641214] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Eosinophilic Esophagitis (EoE) is a chronic immune/antigen-mediated condition which is also driven by genetic and environmental factors. It has been deeply investigated over the last years and its incidence is widely increasing in childhood. Although atopic diseases are closely linked with EoE, it does not recognize a classical IgE-mediate immune pathogenesis but it is rather a T helper type 2 inflammatory process. Familial clustering supports genetic predisposition in EoE and recent advances in understanding the genetic basis for EoE may eventually translate into targeted management of the disease. EoE diagnosis is based on clinical symptoms, micro, and macroscopic findings along with exclusion of gastroesophageal reflux disease (GERD) evidence. Management of the disease encompasses both dietary and pharmacological solutions that need to be specifically targeted on patients' history, clinical symptoms, and diagnostic evaluations. New therapies, currently not available in children, may represent the basis for future therapeutic options in the next years.
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Affiliation(s)
- Tommaso Alterio
- Hepatology, Gastroenterology and Nutrition Unit, IRCCS "Bambino Gesù" Children's Hospital , Rome , Italy
| | - Sabrina Cardile
- Hepatology, Gastroenterology and Nutrition Unit, IRCCS "Bambino Gesù" Children's Hospital , Rome , Italy
| | - Claire Trayers
- Department of Paediatric and Perinatal Pathology, Cambridge University Hospitals (CUH), Addenbrooke's Hospital , Cambridge , UK
| | - Simona Valenti
- Department of Pediatrics, University of Messina , Messina , Italy
| | - Italia Loddo
- Department of Laboratory Medicine and Advanced Biotechnologies, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT) - IRCCS , Palermo , Italy
| | - Roxana Mardare
- Department of Pediatrics, Cambridge University Hospitals (CUH), Addenbrookes Hospital , Cambridge , UK
| | - Antonella Mosca
- Hepatology, Gastroenterology and Nutrition Unit, IRCCS "Bambino Gesù" Children's Hospital , Rome , Italy
| | - Valerio Nobili
- Hepatology, Gastroenterology and Nutrition Unit, IRCCS "Bambino Gesù" Children's Hospital , Rome , Italy.,Department of Pediatrics, University "La Sapienza" , Rome , Italy
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50
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Obesity and hiatal hernia may be non-allergic risk factors for esophageal eosinophilia in Japanese adults. Esophagus 2019; 16:309-315. [PMID: 30927164 DOI: 10.1007/s10388-019-00662-3] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2018] [Accepted: 03/23/2019] [Indexed: 02/03/2023]
Abstract
BACKGROUND Esophageal eosinophilia (EE) is a basal condition of eosinophilic esophageal disorders including eosinophilic esophagitis (EoE) and asymptomatic EE. EoE is considered as an allergic disorder, while it is unclear whether other non-allergic conditions are involved in the pathophysiology of EE. The aim of this study is to investigate the non-allergic risk factors for EE. METHODS This cross-sectional study included subjects who underwent esophagogastroduodenoscopy on a medical health check-up. We compared clinical characteristics between subjects with EE (n = 27) and those without EE (n = 5937). RESULTS The detection rate of EE was 0.45% (27/5964 persons). Of 27 subjects with EE, 20 subjects were symptomatic and 7 were asymptomatic. On univariate analysis, subjects with EE significantly had higher body mass index (BMI) compared to those without EE; 23.4 (4.4) vs 22.3 (4.5) kg/m2, median (interquartile range), p = 0.005. Endoscopic findings revealed that subjects with EE had significantly higher proportion of hiatal hernia (29.6% vs 14.7%; p = 0.049). Subjects with EE were significantly younger and had higher proportion of bronchial asthma; 45 (11.5) vs 51 (18) years, p = 0.013; 25.9% vs 5.2%, p < 0.001, respectively. Multivariate analysis showed that subjects with EE were positively associated with BMI [odds ratio (OR) 1.11; 95% confidence interval (CI) 1.03-1.20; p = 0.010) and hiatal hernia (OR 2.63; 95% CI 1.12-6.18; p = 0.026) compared to those without EE. On trend test, advanced BMI classification had significant trend for increased prevalence of EE (p = 0.002). CONCLUSIONS Obesity and hiatal hernia may be non-allergic risk factors for EE in Japanese adults.
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