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Borrelli O, Ruggiero C, Alfano G, Jackman L, Russo G, Volpe D, Gaynor E, Goh L, Oliva S. Eosinophilic esophagitis in children: new kids on the block. Expert Opin Pharmacother 2025. [PMID: 40490426 DOI: 10.1080/14656566.2025.2517801] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2025] [Revised: 06/03/2025] [Accepted: 06/05/2025] [Indexed: 06/11/2025]
Abstract
INTRODUCTION Eosinophilic esophagitis (EoE) is an immune-mediated disease characterized by esophageal dysfunction and eosinophil rich inflammatory infiltrate. Its incidence is rising globally due to increased awareness, improved diagnostics, and environmental and genetic factors. EoE is driven by a Th2-mediated immune response to food and environmental allergens, leading to chronic inflammation, epithelial barrier dysfunction and progressive esophageal remodeling. AREAS COVERED This review explores pediatric EoE, focusing on epidemiology, pathogenesis, clinical presentation, diagnosis, and both standard and new treatment strategies. Symptoms vary by age, from feeding difficulties in infants to dysphagia and food impaction in older children. Diagnosis relies on clinical symptoms, endoscopic findings and histologic assessment. Standard treatments include dietary elimination, proton pump inhibitors and topical corticosteroids, while biologic therapies such as dupilumab offer targeted alternatives for refractory cases. EXPERT OPINION Future research focuses on optimizing treatment sequencing (step-up and step-down approach), exploring non-eosinophil-mediated inflammation, and enhancing noninvasive test to predict disease severity and phenotypes for better long-term management.
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Affiliation(s)
- Osvaldo Borrelli
- Department of Pediatric Gastroenterology, Great Ormond Street Hospital, London, UK
| | - Cosimo Ruggiero
- Pediatric Gastroenterology and Liver Unit, Maternal and Child Health Department, Sapienza University of Rome, Italy
| | - Giovanna Alfano
- Department of Pediatric Gastroenterology, Great Ormond Street Hospital, London, UK
| | - Lucy Jackman
- Dietetics Department, Great Ormond Street Hospital, Great Ormond Street Hospital, London, UK
| | - Giusy Russo
- Pediatric Gastroenterology and Liver Unit, Maternal and Child Health Department, Sapienza University of Rome, Italy
| | - Danila Volpe
- Pediatric Gastroenterology and Liver Unit, Maternal and Child Health Department, Sapienza University of Rome, Italy
| | - Edward Gaynor
- Department of Pediatric Gastroenterology, Great Ormond Street Hospital, London, UK
| | - Leanne Goh
- Department of Pediatric Gastroenterology, Great Ormond Street Hospital, London, UK
| | - Salvatore Oliva
- Pediatric Gastroenterology and Liver Unit, Maternal and Child Health Department, Sapienza University of Rome, Italy
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Dellon ES, Collins MH, Bredenoord AJ, Philpott H, Biedermann L, Dulcine M, Nguyen-Cleary T, Su C, Yu J, Tan H, Cataldi F, Wu J, Wang W, Clax P, Woolcott JC, Hirano I. Etrasimod as a treatment for eosinophilic oesophagitis (VOYAGE): a double-blind, placebo-controlled, randomised, phase 2 trial. Lancet Gastroenterol Hepatol 2025:S2468-1253(25)00062-7. [PMID: 40381637 DOI: 10.1016/s2468-1253(25)00062-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2024] [Revised: 02/19/2025] [Accepted: 02/20/2025] [Indexed: 05/20/2025]
Abstract
BACKGROUND Novel treatments are needed for eosinophilic oesophagitis. Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator in development for the treatment of immune-mediated inflammatory diseases. We assessed efficacy and safety of etrasimod versus placebo in adults with eosinophilic oesophagitis. METHODS In this double-blind, randomised, phase 2 trial, patients aged 18-65 years with a previous diagnosis of eosinophilic oesophagitis and histologically active disease from 64 clinical sites (in Australia, Belgium, Spain, Switzerland, and the USA) were randomly assigned (3:3:2) using an interactive web response system to receive oral etrasimod 2 mg or 1 mg or matching placebo for 24 weeks (centrally randomly assigned and double-blind; placebo-controlled period); they continued assigned etrasimod doses or were randomly assigned (1:1) from placebo to etrasimod 2 mg or 1 mg for 28 weeks (extension period). Randomisation was stratified by history of oesophageal dilation and concurrent proton pump inhibitor therapy. The full analysis set and safety set consisted of all randomly assigned patients who received at least one study treatment dose. The primary endpoint was percentage change from baseline in oesophageal peak eosinophil count (PEC) at week 16. Safety was assessed up to week 52. Patients were analysed according to treatment received in the placebo-controlled period and extension period. The trial was registered with ClinicalTrials.gov, NCT04682639, and EudraCT, 2020-003226-23; completed on June 30, 2023. FINDINGS Between Dec 15, 2020, and May 27, 2022, 41 patients were randomly assigned to etrasimod 2 mg (20 [49%] females and 21 [51%] males), 39 to etrasimod 1 mg (17 [44%] females and 22 [56%] males), and 28 to placebo (14 [50%] females and 14 [50%] males). 85 (79%) of 108 patients completed the double-blind period, entering the extension period. Median percentage changes from baseline in PEC at week 16 were -58·4% (IQR -86·2 to -26·3) for etrasimod 2 mg (p=0·010 vs placebo), -39·4% (-71·1 to 79·0) for etrasimod 1 mg (p=0·29 vs placebo) and -21·5% (-57·2 to 55·4) for placebo. In the placebo-controlled period, the most common treatment-emergent adverse events were gastrointestinal disorders (11 [27%] of 41 patients in the etrasimod 2 mg group, 13 [33%] of 39 patients in the etrasimod 1 mg group, and 14 [50%] of 28 patients in the placebo group). Bradycardia events, reported by three patients (two [5%] patients in the etrasimod 2 mg group and one [4%] in the placebo group) in the placebo-controlled period, were mild or moderate in severity. No serious treatment-emergent adverse events or deaths occurred. INTERPRETATION Etrasimod led to sustained histological and endoscopic improvements in eosinophilic oesophagitis over 52 weeks, symptom improvement in patients without dilation, and was well tolerated. This trial provides the first evidence that targeting the S1P pathway can improve disease activity in patients with eosinophilic oesophagitis and that S1P receptor modulation is a viable treatment target for this disease. FUNDING Pfizer.
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Affiliation(s)
- Evan S Dellon
- Center for Esophageal Diseases and Swallowing, and Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
| | - 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, OH, USA
| | - Albert J Bredenoord
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Center, Amsterdam, Netherlands
| | - Hamish Philpott
- Northern Adelaide Local Health Network, Department of Gastroenterology Lyell McEwin and Modbury Hospitals, University of Adelaide, Adelaide, SA, Australia
| | - Luc Biedermann
- Department of Gastroenterology and Hepatology, University Hospital Zürich, Zürich, Switzerland
| | | | | | | | - Jin Yu
- Pfizer, Collegeville, PA, USA
| | | | | | | | | | | | | | - Ikuo Hirano
- Kenneth C Griffin Esophageal Center, Division of Gastroenterology and Hepatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
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Min S, Chang JW. From Past to Present: The Evolution of Pharmacologic Therapies for Eosinophilic Esophagitis. Gastroenterol Hepatol (N Y) 2025; 21:298-303. [PMID: 40416916 PMCID: PMC12100528] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/27/2025]
Abstract
Within the evolving landscape of eosinophilic esophagitis (EoE) management are multiple pharmacologic treatment modalities, including proton pump inhibitors (PPIs), swallowed topical corticosteroids, and novel biologic agents. Studies to date on PPIs and corticosteroids have provided valuable insights into how to define the disease, and recently approved biologic therapies are heralding a new era of EoE management. Although progress has been made in treating this complex inflammatory, fibrostenotic disease and in understanding its pathophysiology, several knowledge gaps persist and continue to be investigated. In addition, unknowns exist regarding the long-term safety and efficacy of new EoE treatments and how to position therapies in diverse patient populations. This article aims to provide historical context for the current landscape of pharmacologic treatments in EoE and perspectives on how future development may improve understanding and management of this complex disease.
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Affiliation(s)
- Susie Min
- Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan
| | - Joy W. Chang
- Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan
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Canonica GW, Mazziotti G, Repici A, Povero M, Castello L, Pradelli L, Dobreva M, Fanelli F, Saab JP, Savarino EV. The clinical impact of conventional therapies for adults and adolescents suffering from eosinophilic esophagitis, a type 2 inflammatory chronic disease, and their economic consequences in Italy: Systematic literature review and meta-analysis. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. GLOBAL 2025; 4:100383. [PMID: 39877128 PMCID: PMC11773236 DOI: 10.1016/j.jacig.2024.100383] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/18/2024] [Revised: 10/02/2024] [Accepted: 10/06/2024] [Indexed: 01/31/2025]
Abstract
Background Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder marked by eosinophilic infiltration of the esophageal mucosa. Despite advances in understanding and management, optimal therapeutic strategies remain unclear, with conflicting guidelines. Objective We sought to evaluate effectiveness and safety of topical corticosteroids (TCSs) and proton pump inhibitors (PPIs) in managing EoE and their economic implications in Italy. Methods MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched up to December 2023 and 78 publications were included, covering treatment outcomes and adverse events. Meta-analyses were performed to evaluate treatment efficacy and safety across various patient populations and study designs. Results TCSs showed superior efficacy over PPIs in achieving histologic, endoscopic, and partial clinical responses. Older patients responded better to both treatments. Treatment outcomes varied by sex and presence of atopic conditions. TCSs discontinuation increased the risk of clinical relapse (0.70 cases per person-year), whereas continuous use was linked to a rise in nonserious adverse events (dilation, infections, upper respiratory tract infections, and skin disorders). Economic analysis indicated cost variations based on treatment regimens and follow-up protocols, with dilation and relapse being significant cost drivers in Italy. Conclusions This review provides insights into efficacy, safety, and economic impact of TCSs and PPIs in managing EoE. TCSs were more effective in achieving histologic and endoscopic responses, whereas PPIs were effective in reducing symptoms. Standardized treatment guidelines are needed because of varied treatment efficacy across studies. Future research and new therapies may enhance outcomes and reduce health care costs, improving patient quality of life.
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Affiliation(s)
- Giorgio Walter Canonica
- Department of Biomedical Sciences, Humanitas University of Milan, Pieve Emanuele, Milan, Italy
- Personalized Medicine Asthma & Allergy Clinic Humanitas Research Hospital—IRCCS, Rozzano, Milan, Italy
| | - Gherardo Mazziotti
- Department of Biomedical Sciences, Humanitas University of Milan, Pieve Emanuele, Milan, Italy
- Endocrinology, Diabetology and Medical Andrology Unit, Metabolic Bone Diseases and Osteoporosis Section, IRCCS Humanitas Research Hospital, Milan, Italy
| | - Alessandro Repici
- Department of Gastroenterology Humanitas University & Humanitas Research Hospital, Rozzano, Milan, Italy
| | | | | | | | | | | | | | - Edoardo Vincenzo Savarino
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
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Chang JW, Dellon ES, Mukkada V. Budesonide Oral Suspension: Expanding the Toolkit for Eosinophilic Esophagitis. Am J Gastroenterol 2025; 120:16-19. [PMID: 39311427 PMCID: PMC11695148 DOI: 10.14309/ajg.0000000000003090] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2024] [Accepted: 09/18/2024] [Indexed: 10/13/2024]
Affiliation(s)
- Joy W. Chang
- Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI
| | - Evan S. Dellon
- Division of Gastroenterology, Center for Esophageal and Swallowing Disorders, University of North Carolina, Chapel Hill, NC
| | - Vincent Mukkada
- Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH
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McCallen JD, Dave M, LaFata S, Cameron BA, Xue AZ, Kiran A, Ocampo AA, Lee CJ, Borinsky SA, Redd WD, Cotton CC, Eluri S, Reed CC, Dellon ES. Topical Steroids Are Effective and Safe in Patients With Eosinophilic Esophagitis Over a Median of 6.5 Years of Chronic Use. J Clin Gastroenterol 2024:00004836-990000000-00355. [PMID: 39365834 PMCID: PMC11973234 DOI: 10.1097/mcg.0000000000002081] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2024] [Accepted: 09/12/2024] [Indexed: 10/06/2024]
Abstract
GOALS To determine long-term efficacy and safety of tCS for treatment of EoE. BACKGROUND Maintenance therapy with topical corticosteroids (tCS) is recommended for eosinophilic esophagitis (EoE), but data for long-term use are still needed. STUDY This retrospective cohort study assessed newly diagnosed patients with EoE who were treated with a tCS and had a follow-up endoscopy with biopsy after at least 5 years. Histologic symptomatic and endoscopic responses were extracted from medical records. Patients who did and did not have long-term tCS treatment were compared at baseline, and outcomes for patients were assessed at their last endoscopy while on tCS. RESULTS Of 431 patients with EoE treated with tCS, 104 met inclusion criteria for long-term use. For patients with long-term tCS use, the median time (IQR) on tCS was 6.5 years (5.4 to 8.8 y). At the last endoscopy, 54% had histologic response (<15 eos/hpf), but those with excellent adherence had a histologic response of 64%. Endoscopic severity also decreased with improved adherence which was strongly associated with EREFS (1.7 vs. 2.8 vs. 4.0 for excellent, good, and poor adherence; P<0.001). Symptomatic response was 68% overall, but only 40% in those with poor adherence (P=0.07). Complications of taking tCS were uncommon (adrenal insufficiency: 1%; osteopenia: 1%; and esophageal candidiasis: 4% at final endoscopy). CONCLUSIONS Long-term tCS (median 6.5 y) were generally effective, especially with better adherence, and also safe, with only rare serious complications. These data can be used to help patients make clinical decisions about chronic tCS use in EoE.
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Affiliation(s)
- Justin D. McCallen
- Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Mili Dave
- Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Sean LaFata
- Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Brenderia A. Cameron
- Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Angela Z. Xue
- Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Akshatha Kiran
- Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Adolfo A. Ocampo
- Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Christopher J. Lee
- Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Stephanie A. Borinsky
- Pediatric Gastroenterology, Department of Pediatrics; University of North Carolina School of Medicine, Chapel Hill, NC
| | - Walker D. Redd
- Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Cary C. Cotton
- Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Swathi Eluri
- Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, NC
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL
| | - Craig C. Reed
- Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Evan S. Dellon
- Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, NC
- 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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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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Amil-Dias J, Oliva S, Papadopoulou A, Thomson M, Gutiérrez-Junquera C, Kalach N, Orel R, Auth MKH, Nijenhuis-Hendriks D, Strisciuglio C, Bauraind O, Chong S, Ortega GD, Férnandez SF, Furman M, Garcia-Puig R, Gottrand F, Homan M, Huysentruyt K, Kostovski A, Otte S, Rea F, Roma E, Romano C, Tzivinikos C, Urbonas V, Velde SV, Zangen T, Zevit N. Diagnosis and management of eosinophilic esophagitis in children: An update from the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN). J Pediatr Gastroenterol Nutr 2024; 79:394-437. [PMID: 38923067 DOI: 10.1002/jpn3.12188] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Revised: 08/17/2023] [Accepted: 09/04/2023] [Indexed: 06/28/2024]
Abstract
INTRODUCTION Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus characterized by symptoms of esophageal dysfunction and histologically by predominantly eosinophilic infiltration of the squamous epithelium. European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) published a guideline in 2014; however, the rapid evolution of knowledge about pathophysiology, diagnostic criteria, and therapeutic options have made an update necessary. METHODS A consensus group of pediatric gastroenterologists from the ESPGHAN Working Group on Eosinophilic Gastrointestinal Diseases (ESPGHAN EGID WG) reviewed the recent literature and proposed statements and recommendations on 28 relevant questions about EoE. A comprehensive electronic literature search was performed in MEDLINE, EMBASE, and Cochrane databases from 2014 to 2022. The Grading of Recommendations Assessment, Development and Evaluation system was used to assess the quality of evidence and formulate recommendations. RESULTS A total of 52 statements based on the available evidence and 44 consensus-based recommendations are available. A revision of the diagnostic protocol, options for initial drug treatment, and the new concept of simplified empiric elimination diets are now available. Biologics are becoming a part of the potential armamentarium for refractory EoE, and systemic steroids may be considered as the initial treatment for esophageal strictures before esophageal dilation. The importance and assessment of quality of life and a planned transition to adult medical care are new areas addressed in this guideline. CONCLUSION Research in recent years has led to a better understanding of childhood EoE. This guideline incorporates the new findings and provides a practical guide for clinicians treating children diagnosed with EoE.
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Affiliation(s)
- Jorge Amil-Dias
- Pediatric Gastroenterology, Hospital Lusíadas, Porto, Portugal
| | - Salvatore Oliva
- Maternal and Child Health Department, University Hospital - Umberto I, Sapienza - University of Rome, Rome, Italy
| | - Alexandra Papadopoulou
- Division of Gastroenterology and Hepatology, First Department of Pediatrics, Children's hospital Agia Sofia, University of Athens, Athens, Greece
| | - Mike Thomson
- Centre for Paediatric Gastroenterology, International Academy for Paediatric Endoscopy Training, Sheffield Children's Hospital, UK
| | - Carolina Gutiérrez-Junquera
- Pediatric Gastroenterology Unit, Hospital Universitario Puerta de Hierro Majadahonda, Universidad Autónoma de Madrid, Spain
| | - Nicolas Kalach
- Department of Pediatrics, Saint Vincent de Paul Hospital, Groupement des Hôpitaux de l'Institut Catholique de Lille (GHICL), Catholic University, Lille, France
| | - Rok Orel
- Department of Gastroenterology, Hepatology, and Nutrition, University Children's Hospital, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | | | | | - Caterina Strisciuglio
- Department of Woman, Child and General and Specialized Surgery of the University of Campania "Luigi Vanvitelli", Naples, Italy
| | | | - Sonny Chong
- Epsom and St Helier University Hospitals NHS Trust, UK
| | - Gloria Dominguez Ortega
- Pediatric Gastroenterology and Nutrition Department, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
| | - Sonia Férnandez Férnandez
- Pediatric Gastroenterology Unit, Department of Pediatrics, Severo Ochoa University Hospital, Madrid, Spain
| | - Mark Furman
- Royal Free London NHS Foundation Trust, London, UK
| | - Roger Garcia-Puig
- Pediatric Gastroenterology, Hepatology and Nutrition Unit, Pediatrics Department, Hospital Universitari MútuaTerrassa, Universitat de Barcelona, Barcelona, Spain
| | | | - Matjaz Homan
- Department of Gastroenterology, Hepatology, and Nutrition, University Children's Hospital, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Koen Huysentruyt
- Kindergastro-enterologie, hepatologie en nutritie, Brussels Centre for Intestinal Rehabilitation in Children (BCIRC), Belgium
| | - Aco Kostovski
- University Children's Hospital Skopje, Faculty of Medicine, University Ss Cyril and Methodius, Skopje, Republic of North Macedonia
| | - Sebastian Otte
- Childrens' Hospital, Helios Mariahilf Hospital, Hamburg, Germany
| | - Francesca Rea
- Endoscopy and Surgey Unit, Bambino Gesu Children's Hospital, Rome, Italy
| | - Eleftheria Roma
- First Department of Pediatrics, University of Athens and Pediatric Gastroenterology Unit Mitera Children's Hospital, Athens, Greece
| | - Claudio Romano
- Department of Human Pathology in Adulthood and Childhood "G. Barresi", University of Messina, Messina, Italy
| | - Christos Tzivinikos
- Paediatric Gastroenterology Department, Al Jalila Children's Specialty Hospital, Dubai, UAE
- Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, UAE
| | - Vaidotas Urbonas
- Vilnius University Medical Faculty Clinic of Children's Diseases, Vilnius, Lithuania
| | | | - Tsili Zangen
- Pediatric Gastroenterology Unit, Wolfson Medical Center, Holon, Israel
| | - Noam Zevit
- Eosinophilic Gastrointestinal Disease Clinic, Institute of Gastroenterology, Hepatology, and Nutrition, Schneider Children's Medical Center of Israel, Israel
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Caminati M, Senna G, Maule M, Di Sabatino A, Rossi CM. Diagnosis, management and therapeutic options for eosinophilic esophagitis. Curr Opin Allergy Clin Immunol 2024; 24:122-128. [PMID: 38656287 DOI: 10.1097/aci.0000000000000982] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/26/2024]
Abstract
PURPOSE OF REVIEW Eosinophilic esophagitis is a chronic and commonly evolving condition leading to relevant and potentially irreversible burden in terms of tissue damage and related functional impairment, thus significantly impacting on quality of life. The aim of the present review is to summarize the recent advances in terms of diagnostic work-up and pharmacological and nonpharmacological management of the disease, under the broader perspective of type 2 inflammation. RECENT FINDINGS Two major novelties have prompted an innovative approach to EoE. In terms of diagnosis, it has been proposed to dissect the disease heterogeneity in three endotypes, independent from tissue eosinophil number: EoEe1, characterized by normal appearing oesophagus; EoEe2, associated with type 2 inflammation and steroid-refractoriness; EoEe3, whose features include adult onset, a more fibro-stenotic aspect and loss of epithelial gene expression. Concerning treatment, two recently licensed drugs for EoE, oro-dispersible budesonide and dupilumab represent the first treatment options specifically developed for EoE and addressing EoE-related peculiar pathobiological features. SUMMARY In the era of precision medicine, managing EoE according to a phenotype-driven approach might be helpful in defining the best treatment options in the different disease forms or stages. In addition, exploring the coexistence or the previous occurrence of other type 2 conditions may suggest the opportunity to specifically target type 2 inflammation through biologic therapy. The complex EoE pathobiology combining inflammatory and functional features, both at organ and systemic level, requires a multidimensional approach relying on the strict integration of gastroenterologists and allergist-immunologists.
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Affiliation(s)
- Marco Caminati
- Asthma Center and Allergy Unit, Center for Hyper-eosinophilic dysimmune conditions, Integrated University Hospital of Verona
- Department of Medicine, University of Verona, Verona
| | - Gianenrico Senna
- Asthma Center and Allergy Unit, Center for Hyper-eosinophilic dysimmune conditions, Integrated University Hospital of Verona
- Department of Medicine, University of Verona, Verona
| | - Matteo Maule
- Asthma Center and Allergy Unit, Center for Hyper-eosinophilic dysimmune conditions, Integrated University Hospital of Verona
- Department of Medicine, University of Verona, Verona
| | - Antonio Di Sabatino
- Department of Medicine and Medical Therapeutics, University of Pavia
- Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Carlo Maria Rossi
- Department of Medicine and Medical Therapeutics, University of Pavia
- Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
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Chan J, Flynn DM, Gordon M, Parmar R, Moolenschot K, Jackman L, Gaynor E, Epstein J, Cordell A, Kannappan H, Furman M, Thompson J, Gasparetto M, Auth MKH. Swallowed topical steroid therapy for eosinophilic oesophagitis in children: practical, evidence-based guidance by the BSPGHAN Eosinophilic Oesophagitis Working Group. BMJ Paediatr Open 2024; 8:e002467. [PMID: 38782481 PMCID: PMC11116858 DOI: 10.1136/bmjpo-2023-002467] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Accepted: 05/12/2024] [Indexed: 05/25/2024] Open
Abstract
OBJECTIVE To develop evidence-based guidance for topical steroid use in paediatric eosinophilic oesophagitis (pEoE) in the UK for both induction and maintenance treatment. METHODS A systematic literature review using Cochrane guidance was carried out by the British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) Eosinophilic Oesophagitis (EoE) Working Group (WG) and research leads to determine the evidence base for preparation, dosing and duration of use of swallowed topical steroid (STS) formulations in EoE. Seven themes relating to pEoE were reviewed by the WG, alongside the Cochrane review this formed the evidence base for consensus recommendations for pEoE in the UK. We provide an overview of practical considerations including treatment regimen and dosing. Oral viscous budesonide (OVB) and, if agreed by local regulatory committees, orodispersible budesonide (budesonide 1 mg tablets) were selected for ease of use and with most improvement in histology. A practical 'how to prepare and use' OVB appendix is included. Side effects identified included candidiasis and adrenal gland suppression. The use of oral systemic steroids in strictures is discussed briefly. RESULTS 2638 citations were identified and 18 randomised controlled trials were included. Evidence exists for the use of STS for induction and maintenance therapy in EoE, especially regarding histological improvement. Using the Appraisal of Guidelines, Research and Evaluation criteria, dosing of steroids by age (0.5 mg two times per day <10 years and 1 mg two times per day ≥10 years) for induction of at least 3 months was suggested based on evidence and practical consideration. Once histological remission is achieved, maintenance dosing of steroids appears to reduce the frequency and severity of relapse, as such a maintenance weaning regimen is proposed. CONCLUSION A practical, evidence-based flow chart and guidance recommendations with consensus from the EoE WG and education and research representatives of BSPGHAN were developed with detailed practical considerations for use in the UK.
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Affiliation(s)
- Joseph Chan
- Paediatric Gastroenterology, University Hospital of Wales, Cardiff, UK
| | - Diana M Flynn
- Paediatric Gastroenterology, Royal Hospital for Children, Glasgow, UK
| | | | - Raj Parmar
- Paediatric Gastroenterology, Alder Hey Children's Hospital, Liverpool, UK
| | | | - Lucy Jackman
- Specialist Paediatric Dietitian, Great Ormond Street Hospital for Children, London, UK
| | - Ed Gaynor
- Paediatric Gastroenterology/Mucosal Immunology, Great Ormond Street Hospital for Children, London, UK
| | - Jenny Epstein
- Paediatric Gastroenterology, Chelsea and Westminster Hospital, London, UK
| | | | - Hema Kannappan
- General Paediatrics, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK
| | - Mark Furman
- Paediatric Gastroenterology, Royal Free Hospital, London, UK
| | | | - Marco Gasparetto
- Paediatric Gastroenterology, Norfolk and Norwich University Hospital, Norwich, UK
| | - Marcus K H Auth
- Gastroenterology, Hepatology and Nutrition, Alder Hey Children's NHS Foundation Trust, Liverpool, UK
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11
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Falk GW, Pesek R. Pharmacologic Management of Eosinophilic Esophagitis. Immunol Allergy Clin North Am 2024; 44:245-264. [PMID: 38575221 DOI: 10.1016/j.iac.2023.12.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/06/2024]
Abstract
Proton pump inhibitors (PPIs), swallowed topical corticosteroids (STSs), and dupilumab are highly effective therapies for the treatment of eosinophilic esophagitis. Shared decision-making informs the choice of therapy and factors such as ease of use, safety, cost, and efficacy should be addressed. PPIs are the most common medication utilized early in the disease course; however, for nonresponders, STSs are an excellent alternative. Dupilumab is unlikely to replace PPIs or STSs as first-line therapy, except in highly specific circumstances. Identification of novel biologic pathways and the development of small molecules may lead to a wider range of treatment options in the future.
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Affiliation(s)
- Gary W Falk
- Division of Gastroenterology & Hepatology, Department of Medicine, Hospital of the University of Pennsylvania, University of Pennsylvania Perelman School of Medicine, 7th Floor South Pavilion PCAM, 3400 Civic Center Boulevard, Philadelphia, PA 19104, USA
| | - Robbie Pesek
- Division of Allergy and Immunology, Department of Pediatrics, Arkansas Children's Hospital, University of Arkansas for Medical Sciences, 13 Children's Way, Slot 512-13, Little Rock, AR 72202, USA.
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12
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Venter C, Meyer R, Bauer M, Bird JA, Fleischer DM, Nowak-Wegrzyn A, Anagnostou A, Vickery BP, Wang J, Groetch M. Identifying Children at Risk of Growth and Nutrient Deficiencies in the Food Allergy Clinic. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. IN PRACTICE 2024; 12:579-589. [PMID: 38280452 DOI: 10.1016/j.jaip.2024.01.027] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Revised: 01/16/2024] [Accepted: 01/19/2024] [Indexed: 01/29/2024]
Abstract
BACKGROUND Food allergies affect growth in children by decreasing the availability of nutrients through decreased dietary intake, increased dietary needs, food-medication interactions, and psychosocial burden. Guidelines on food allergy management frequently recommend nutrition counseling and growth monitoring of children with food allergies. OBJECTIVE To provide clear guidance for clinicians to identify children with food allergies who are at nutritional risk and ensure prompt intervention. METHODS We provide a narrative review summarizing information from national and international guidelines, retrospective studies, population studies, review articles, case reports, and case series to identify those with food allergy at greatest nutritional risk, determine the impact of nutritional interventions on growth, and develop guidance for risk reduction in children with food allergies. RESULTS Children with food allergies are at increased risk of nutritional deficiencies and poor growth. Nutritional assessment and intervention can improve outcomes. Identifying poor growth is an important step in the nutrition assessment. Therefore, growth should be assessed at each allergy evaluation. Interventions to ensure adequate dietary intake for growth include appropriately prescribed elimination diets, breast-feeding support and assessment, supplemental formula, vitamin and/or mineral supplementation, appropriate milk substitutes, and timely introduction of nutrient-dense complementary foods. Access to foods of appropriate nutritional value is an ongoing concern. CONCLUSION Nutrition intervention or referral to registered dietitian nutritionists with additional training and/or experience in food allergy may result in improved growth and nutrition outcomes.
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Affiliation(s)
- Carina Venter
- Section of Pediatric Allergy and Immunology, Children's Hospital Colorado, University of Colorado, Aurora, Colo.
| | - Rosan Meyer
- Department of Medicine, Imperial College London, London, United Kingdom; Department of Nutrition and Dietetics, University of Winchester, Winchester, United Kingdom; Department of Medicine, KU Leuven, Leuven, Belgium
| | - Maureen Bauer
- Section of Pediatric Allergy and Immunology, Children's Hospital Colorado, University of Colorado, Aurora, Colo
| | - J Andrew Bird
- Department of Pediatrics, Division of Allergy and Immunology, UT Southwestern Medical Center, Dallas, Texas
| | - David M Fleischer
- Section of Pediatric Allergy and Immunology, Children's Hospital Colorado, University of Colorado, Aurora, Colo
| | - Anna Nowak-Wegrzyn
- Hassenfeld Children's Hospital, Department of Pediatrics, NYU Grossman School of Medicine, New York, NY; Department of Pediatrics, Gastroenterology and Nutrition, Collegium Medicum, University of Warmia and Mazury, Olsztyn, Poland
| | - Aikaterini Anagnostou
- Section of Allergy and Immunology, Baylor College of Medicine, Houston, Texas; Section of Allergy and Immunology, Department of Pediatrics, Texas Children's Hospital, Houston, Texas
| | - Brian P Vickery
- Children's Healthcare of Atlanta, Atlanta, Ga; Department of Pediatrics, Emory University, Atlanta, Ga
| | - Julie Wang
- Division of Pediatric Allergy and Immunology, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Marion Groetch
- Division of Pediatric Allergy and Immunology, Icahn School of Medicine at Mount Sinai, New York, NY
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13
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Bredenoord AJ, Dellon ES, Hirano I, Lucendo AJ, Schlag C, Sun X, Glotfelty L, Mannent L, Maloney J, Laws E, Mortensen E, Shabbir A. Dupilumab demonstrated efficacy and was well tolerated regardless of prior use of swallowed topical corticosteroids in adolescent and adult patients with eosinophilic oesophagitis: a subgroup analysis of the phase 3 LIBERTY EoE TREET study. Gut 2024; 73:398-406. [PMID: 38050037 PMCID: PMC10894847 DOI: 10.1136/gutjnl-2023-330220] [Citation(s) in RCA: 6] [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: 05/09/2023] [Accepted: 10/24/2023] [Indexed: 12/06/2023]
Abstract
OBJECTIVE To assess the effect of long-term dupilumab on histological, symptomatic and endoscopic aspects of eosinophilic oesophagitis (EoE) in adolescent and adult patients with and without prior use of swallowed topical corticosteroids (STC) or prior inadequate response, intolerance or contraindication to STC. DESIGN Pre-specified analysis of data from the phase 3 LIBERTY EoE TREET study on patients who received dupilumab 300 mg once a week or placebo for 24 weeks (W24) in parts A and B, and an additional 28 weeks (W52) in part C. Patients were categorised as with/without prior STC use and with/without inadequate/intolerance/contraindication to STC. The proportion of patients achieving ≤6 eosinophils per high-power field (eos/hpf), absolute change in Dysphagia Symptom Questionnaire (DSQ) score, mean change in Endoscopic Reference Score and Histologic Scoring System grade/stage scores were assessed for each subgroup. RESULTS Regardless of prior STC use, dupilumab increased the proportion of patients achieving ≤6 eos/hpf and improved DSQ score versus placebo at W24, with improvements maintained or improved at W52. The DSQ score and the proportion of patients achieving ≤6 eos/hpf after switching from placebo to dupilumab at W24 were similar to those observed in the dupilumab group at W24, regardless of prior STC use or inadequate/intolerance/contraindication to STC. Improvements in other outcomes with dupilumab were similar in patients with/without prior STC use or inadequate/intolerance/contraindication to STC. CONCLUSION Dupilumab 300 mg once a week demonstrated efficacy and was well tolerated in patients with EoE regardless of prior STC use or inadequate response, intolerance and/or contraindication to STC. TRIAL REGISTRATION NUMBER NCT03633617.
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Affiliation(s)
- Albert J Bredenoord
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, Amsterdam, The Netherlands
| | - Evan S Dellon
- Department of Medicine, Division of Gastroenterology and Hepatology, The University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA
| | - Ikuo Hirano
- Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Alfredo J Lucendo
- Instituto de Investigación Sanitaria Princesa, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), Hospital General Tomelloso, Tomelloso, Spain
| | - Christoph Schlag
- Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany
| | - Xian Sun
- Regeneron Pharmaceuticals Inc, Tarrytown, New York, USA
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14
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Mukkada VA, Gupta SK, Gold BD, Dellon ES, Collins MH, Katzka DA, Falk GW, Williams J, Zhang W, Boules M, Hirano I, Desai NK. Pooled Phase 2 and 3 Efficacy and Safety Data on Budesonide Oral Suspension in Adolescents with Eosinophilic Esophagitis. J Pediatr Gastroenterol Nutr 2023; 77:760-768. [PMID: 37718471 PMCID: PMC10642696 DOI: 10.1097/mpg.0000000000003948] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2023] [Accepted: 08/07/2023] [Indexed: 09/19/2023]
Abstract
OBJECTIVES The objective of this study was to evaluate the efficacy and safety of budesonide oral suspension (BOS) in adolescents with eosinophilic esophagitis (EoE). METHODS This post hoc analysis pooled data from two 12-week, randomized, double-blind, placebo-controlled studies of BOS 2.0 mg twice daily (b.i.d.) (phase 2, NCT01642212; phase 3, NCT02605837) in patients aged 11-17 years with EoE and dysphagia. Efficacy endpoints included histologic (≤6, ≤1, and <15 eosinophils per high-power field [eos/hpf]), dysphagia symptom (≥30% reduction in Dysphagia Symptom Questionnaire [DSQ] scores from baseline), and clinicopathologic (≤6 eos/hpf and ≥30% reduction in DSQ scores from baseline) responses at week 12. Change from baseline to week 12 in peak eosinophil counts, DSQ scores, EoE Histology Scoring System (EoEHSS) grade (severity) and stage (extent) total score ratios (TSRs), and total EoE Endoscopic Reference Scores (EREFS) were assessed. Safety outcomes were also examined. RESULTS Overall, 76 adolescents were included (BOS, n = 45; placebo, n = 31). Significantly more patients who received BOS than placebo achieved histologic responses (≤6 eos/hpf: 46.7% vs 6.5%; ≤1 eos/hpf: 42.2% vs 0.0%; <15 eos/hpf: 53.3% vs 9.7%; P < 0.001) and a clinicopathologic response (31.1% vs 3.2%; P = 0.003) at week 12. More BOS-treated than placebo-treated patients achieved a dysphagia symptom response at week 12 (68.9% vs 58.1%; not statistically significant P = 0.314). BOS-treated patients had significantly greater reductions in EoEHSS grade and stage TSRs ( P < 0.001) and total EREFS ( P = 0.021) from baseline to week 12 than placebo-treated patients. BOS was well tolerated, with no clinically meaningful differences in adverse events versus placebo. CONCLUSIONS BOS 2.0 mg b.i.d. significantly improved most efficacy outcomes in adolescents with EoE versus placebo.
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Affiliation(s)
- Vincent A Mukkada
- From the Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH
| | - Sandeep K Gupta
- the Section of Pediatric Gastroenterology, Hepatology and Nutrition, Indiana University School of Medicine, Riley Hospital for Children at Indiana University Health, Indianapolis, IN
- the Community Health Network, Indianapolis, IN
| | - Benjamin D Gold
- the GI Care for Kids, LLC, Children's Center for Digestive Healthcare, Atlanta, GA
| | - Evan S Dellon
- the Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC
| | - Margaret H Collins
- the Department of Pathology and Laboratory Medicine, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH
| | - David A Katzka
- the Division of Digestive and Liver Diseases, NewYork-Presbyterian/Columbia University Irving Medical Center, New York, NY
| | - Gary W Falk
- the Division of Gastroenterology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - James Williams
- the Takeda Development Center Americas, Inc., Cambridge, MA
| | - Wenwen Zhang
- the Takeda Development Center Americas, Inc., Cambridge, MA
| | - Mena Boules
- the Takeda Pharmaceuticals USA, Inc., Lexington, MA
| | - Ikuo Hirano
- the Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL
| | - Nirav K Desai
- the Takeda Development Center Americas, Inc., Cambridge, MA
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15
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Sharlin CS, Mukkada VA, Putnam PE, Bolton SM. Treatment of Pediatric Eosinophilic Esophagitis: Traditional and Novel Therapies. Curr Gastroenterol Rep 2023; 25:289-298. [PMID: 37658151 DOI: 10.1007/s11894-023-00893-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/17/2023] [Indexed: 09/03/2023]
Abstract
PURPOSE OF REVIEW This review presents and summarizes the existing studies on the treatment goals and options for pediatric eosinophilic esophagitis utilizing rigorous peer-reviewed literature. RECENT FINDINGS In addition to traditional treatments, emerging biologic therapies continue to evolve the approach to treating pediatric eosinophilic esophagitis. Well defined treatment goals will aid the continued development of new therapies. Further, innovative assessment tools have changed how the clinician is able to assess the effectiveness of therapies with a trend toward less invasive options. The management of pediatric eosinophilic esophagitis continues to evolve with the advent of both novel treatment options and assessment tools. Treatment choices, with benefits and risks involved, should be presented to families upon diagnosis and tailored towards the individual patient and likelihood of adherence and success. Biologic therapy for EoE presents an exciting option for both first line therapy and escalation for those with severe or unresponsive disease.
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Affiliation(s)
- Colby S Sharlin
- Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - Vincent A Mukkada
- Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Philip E Putnam
- Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Scott M Bolton
- Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
- Cincinnati Children's Hospital, 3333 Burnet Ave, Cincinnati, OH, 45229, USA.
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16
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Hirano I, Dellon ES, Gupta SK, Katzka DA, Collins MH, Wojtowicz AM, Terreri B, Zhang W, Boules M, Bhatia S, Desai NK. Safety of an investigational formulation of budesonide (budesonide oral suspension) for eosinophilic oesophagitis: an integrated safety analysis of six phase 1-3 clinical trials. Aliment Pharmacol Ther 2023; 57:1117-1130. [PMID: 36890134 DOI: 10.1111/apt.17430] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Revised: 10/05/2022] [Accepted: 02/12/2023] [Indexed: 03/10/2023]
Abstract
BACKGROUND Questions remain regarding the safety of swallowed topical corticosteroids in eosinophilic oesophagitis (EoE). AIM To assess the safety of an investigational formulation of budesonide (budesonide oral suspension; BOS) from six trials. METHODS Safety data were integrated from six trials (healthy adults: SHP621-101 [phase 1]; patients with EoE: MPI 101-01 and MPI 101-06 [phase 2]; SHP621-301, SHP621-302 and SHP621-303 [phase 3]) for participants who received ≥1 dose of study drug (BOS 2.0 mg twice daily [b.i.d.], BOS any dose [including BOS 2.0 mg b.i.d.] and placebo). Adverse events (AEs), laboratory testing, bone density and adrenal AEs were assessed. Exposure-adjusted incidence rates were calculated for AEs and AEs of special interest (AESIs). RESULTS Overall, 514 unique participants were included (BOS 2.0 mg b.i.d., n = 292; BOS any dose, n = 448; placebo, n = 168). The BOS 2.0 mg b.i.d., BOS any dose and placebo groups totalled 93.7, 122.4 and 25.0 participant-years of exposure (PY), respectively. Proportions of treatment-emergent AEs (TEAEs) and AESIs (any) reported were higher for BOS than placebo; however, most were mild/moderate in severity. The most commonly reported AESIs (exposure-adjusted incidence rates [per 100 PY]) in the BOS 2.0 mg b.i.d., BOS any dose and placebo groups were infections (133.5, 154.4 and 136.2, respectively) and gastrointestinal AEs (84.3, 80.9 and 92.1, respectively). Adrenal AEs were more frequent with BOS 2.0 mg b.i.d. and BOS any dose than placebo (44.8, 34.3 and 24.0, respectively). TEAEs and AESIs related to study drug or leading to discontinuation were infrequent. CONCLUSIONS BOS was well-tolerated; most TEAEs with BOS were mild/moderate in severity. CLINICALTRIALS GOV NUMBERS SHP621-101 (no clinical trials registration number), MPI 101-01 (NCT00762073), MPI 101-06 (NCT01642212), SHP621-301 (NCT02605837), SHP621-302 (NCT02736409) and SHP621-303 (NCT03245840).
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Affiliation(s)
- Ikuo Hirano
- Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Evan S Dellon
- Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Sandeep K Gupta
- Section of Pediatric Gastroenterology, Hepatology and Nutrition, Indiana University School of Medicine, Riley Hospital for Children at Indiana University Health, Indianapolis, Indiana, USA.,Community Health Network, Indianapolis, Indiana, USA
| | - David A Katzka
- Division of Gastroenterology, Columbia University Medical Center, New York, New York, USA
| | - Margaret H Collins
- Department of Pathology and Laboratory Medicine, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
| | | | - Brian Terreri
- Takeda Pharmaceuticals USA, Inc., Lexington, Massachusetts, USA
| | - Wenwen Zhang
- Takeda Development Center Americas, Inc., Cambridge, Massachusetts, USA
| | - Mena Boules
- Takeda Pharmaceuticals USA, Inc., Lexington, Massachusetts, USA
| | - Siddharth Bhatia
- Takeda Pharmaceuticals International Co., Cambridge, Massachusetts, USA
| | - Nirav K Desai
- Takeda Development Center Americas, Inc., Cambridge, Massachusetts, USA
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17
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A New Viscous Budesonide Formulation for the Treatment of Eosinophilic Esophagitis in Children: A Preliminary Experience and Review of the Literature. J Clin Med 2022; 11:jcm11226730. [PMID: 36431208 PMCID: PMC9694526 DOI: 10.3390/jcm11226730] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Revised: 11/08/2022] [Accepted: 11/10/2022] [Indexed: 11/16/2022] Open
Abstract
Eosinophilic esophagitis (EoE) is a chronic disease, characterized clinically by esophageal disfunction. Topical corticosteroids (tCS), predominantly fluticasone and budesonide, are considered the effective first line treatment, as well as an option of maintenance therapy in EoE. The way that tCS are administered significantly affects their effectiveness. There is still no ready-to-use steroid drug to be applied topically to the esophagus in children-a few experimental viscous slurries (mainly of budesonide) have been shown in trials to be more effective than steroids administered via metered dose inhalers (MDIs) and swallowed. The best examined steroid solvent of all is sucralose, a high-intensity artificial sweetener. Although it has been shown in a critical review that it is non-toxic and safe for all consumers, there are still some concerns among patients about its potential adverse effect on humans. Due to that fact, we developed a new viscous formulation and evaluated its effectiveness in the treatment of children with EoE. In an open, prospective, single-center study, we administered our new formulation of viscous budesonide twice daily for 8 weeks in patients with an active EoE. After treatment, we performed a control gastroscopy with the collection and evaluation of histopathological samples. We have proven our formulation effectiveness at 64%, as far as histological remission is concerned. We have also shown a reduction in the mean endoscopic reference score (EREFS) from 3.1 points at the beginning of the study to 1.6 points at the end of the study. Bearing in mind how important the acceptance of the solvent is for long-time compliance, especially among children, we also decided to assess the taste of the formulation. Therefore, we asked 46 adults and 10 children to swallow a sample of the solvent and fill in a short anonymous questionnaire about its taste, smell, consistency and easiness of swallowing. General acceptance for the proprietary solvent was high, reaching 7.5/10 among adults and 6.5/10 in children. To be able to compare the results of our preliminary experience, we reviewed the studies which evaluated substances that have been used so far as steroid solvents for the treatment of EoE. The overall effectiveness of the oral viscous budesonide (OVB) ranged from 65% to 90%, which is consistent with the results obtained in our study. Unfortunately, the high heterogeneity of the studies did not allow us to draw reliable conclusions.
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18
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Dellon ES, Lucendo AJ, Schlag C, Schoepfer AM, Falk GW, Eagle G, Nezamis J, Comer GM, Knoop K, Hirano I. Fluticasone Propionate Orally Disintegrating Tablet (APT-1011) for Eosinophilic Esophagitis: Randomized Controlled Trial. Clin Gastroenterol Hepatol 2022; 20:2485-2494.e15. [PMID: 35181572 DOI: 10.1016/j.cgh.2022.02.013] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2021] [Revised: 02/04/2022] [Accepted: 02/09/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Topical steroids are effective treatments for eosinophilic esophagitis (EoE). The FLUTE (Fluticasone in EoE) trial evaluated safety and efficacy of APT-1011 (fluticasone propionate oral disintegrating tablet) vs placebo for treatment of EoE. METHODS In this randomized, double-blind, placebo-controlled, dose-finding, phase 2b trial, 106 adults with EoE received 1 of 4 APT-1011 doses or placebo for a 12-week induction period and 40 weeks of maintenance. Primary outcome was histologic response (≤6 eosinophils per high-power field) at Week 12. Secondary outcomes included endoscopic features and dysphagia frequency. RESULTS Histologic response rates were 0% for placebo, 80% for APT-1011 3 mg twice daily (BID), 67% for 3 mg at bedtime (HS), 86% for 1.5 mg BID, 48% for 1.5 mg HS (P < .001 for all groups vs placebo). At Week 12, mean Edema/Rings/Exudates/Furrows/Strictures (EoE Endoscopic Reference Score) total score (max, 9.0) improved from 4.5 to 2.3 for 3 mg BID, 5.3 to 2.1 for 3 mg HS, 4.6 to 1.7 for 1.5 mg BID, 5.3 to 2.9 for 1.5 mg HS vs 5.2 to 4.5 for placebo. Mean dysphagia frequency over 14 days improved from baseline to Week 12 with all active groups improving more than placebo. Improvements were sustained to Week 52. APT-1011 was safe and well-tolerated, with higher incidence of candidiasis noted at the higher twice daily doses. CONCLUSION APT-1011 dosing regimens were superior for histologic and endoscopic responses, and for reduction in dysphagia frequency vs placebo. Based on the symptom improvement and assessment of adverse events together with the histologic response rate, 3 mg once daily at bedtime dose showed the most favorable risk-benefit profile. CLINICALTRIALS gov, Number: NCT03191864.
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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.
| | - Alfredo J Lucendo
- Division of Gastroenterology, General Hospital Tomelloso, Ciudad Real, Spain
| | - Christoph Schlag
- Second Medical Department, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
| | - Alain M Schoepfer
- Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland
| | - Gary W Falk
- Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Gina Eagle
- Ellodi Pharmaceuticals, Lawrenceville, New Jersey
| | | | - Gail M Comer
- Ellodi Pharmaceuticals, Lawrenceville, New Jersey
| | - Karol Knoop
- Ellodi Pharmaceuticals, Lawrenceville, New Jersey
| | - Ikuo Hirano
- Department of Gastroenterology and Hepatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
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Lucendo AJ, Molina-Infante J. Current treatment options and long-term outcomes in patients with eosinophilic esophagitis. Expert Rev Clin Immunol 2022; 18:859-872. [PMID: 35770955 DOI: 10.1080/1744666x.2022.2096591] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
INTRODUCTION Dietary and pharmacological (proton pump inhibitors, swallowed topical corticosteroids) therapies are effective for induction of clinical and histological remission of eosinophilic esophagitis. However, data evaluating their long-term efficacy and safety is limited. AREAS COVERED Since eosinophilic esophagitis is chronic, clinical, endoscopic, and histological features usually recur when successful treatments are stopped. In untreated patients, persistent esophageal eosinophilic inflammation may progress to fibrostenosis over time, giving place to strictures and narrow-caliber esophagi. This article comprehensively reviews available data on long-term maintenance of eosinophilic esophagitis with pharmacological and dietary treatment. It also discusses limitations re: available literature and outlines data gaps on adherence to therapy and monitoring disease activity in the long-term. EXPERT OPINION Evidence indicates that long-term maintenance therapy may decrease the risk of esophageal stricture, food bolus impaction, and need for dilation in patients with eosinophilic esophagitis. Further knowledge on eosinophilic esophagitis phenotypes is needed to ascertain who will benefit best from sustained therapy. Unanswered questions include an adequate definition for sustained remission, best strategies for maintenance drugs and diets, enhancement of treatment adherence, and proper monitoring for long-term surveillance.
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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 de Castilla-La Mancha (IDISCAM), 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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20
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Tamarit-Sebastian S, Ferrer-Soler FM, Lucendo AJ. Current options and investigational drugs for the treatment of eosinophilic esophagitis. Expert Opin Investig Drugs 2022; 31:193-210. [DOI: 10.1080/13543784.2022.2033207] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- Sonsoles Tamarit-Sebastian
- Department of Gastroenterology, Hospital General de Tomelloso
- Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM)
| | - Francisco Miguel Ferrer-Soler
- Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM)
- Hospital Pharmacy, Hospital General de Tomelloso
| | - Alfredo J Lucendo
- Department of Gastroenterology, Hospital General de Tomelloso
- Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM)
- Hospital Pharmacy, Hospital General de Tomelloso
- Instituto de Investigación Sanitaria Princesa (IIS-IP)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD)
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21
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Feo-Ortega S, Lucendo AJ. Evidence-based treatments for eosinophilic esophagitis: insights for the clinician. Therap Adv Gastroenterol 2022; 15:17562848211068665. [PMID: 35069803 PMCID: PMC8777364 DOI: 10.1177/17562848211068665] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Accepted: 12/03/2021] [Indexed: 02/04/2023] Open
Abstract
Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder characterized by symptoms of esophageal dysfunction and eosinophil-predominant inflammation. Left untreated, EoE progresses to fibrous remodeling and stricture formation that impairs quality of life. Therefore, EoE requires either repeated treatments or maintenance therapy. Current guidelines recommend swallowed topical corticosteroids (STCs), proton-pump inhibitors (PPIs), or dietary intervention as initial options to induce and maintain long-term disease remission. Impractical exclusive elemental diets and suboptimal allergy testing-directed food avoidance paved the way for empirical elimination diets. These are moderately effective and highly reproducible in inducing EoE remission and allow for identification of specific food triggers. Step-up strategies, including two- and four-food rather than six-food elimination diets, should be considered as initial approaches for dietary treatment in patients of all ages, as they reduce the need for endoscopic procedures, shorten diagnostic processing time, and avoid unnecessary restrictions. Formulations of STC originally designed for asthma therapy are suboptimal for EoE treatment, with new effervescent orodispersible tablets and viscose formulations designed to coat the esophageal mucosa providing increased effectiveness at reduced doses. The anti-inflammatory effects of PPI in EoE are independent from gastric acid secretion inhibition; despite evidence from observational research, PPIs are the most commonly prescribed first-line therapy for EoE due to their accessibility, low cost, and safety profile. Double doses of PPI only induce remission in half of EoE patients, irrespective of the drug used or patients' age. Inflammatory rather than stricturing EoE phenotype and treatment duration up to 12 weeks increase chances of achieving EoE remission. Most responders effectively maintain long-term remission with standard PPI doses. Finally, endoscopic dilation should be considered in patients with reduced esophageal caliber or persistent dysphagia despite histological remission. This article provides a state-of-the-art review and updated discussion of current therapies and newly developed options for EoE.
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Affiliation(s)
- Sara Feo-Ortega
- Pediatric Gastroenterology Unit, Hospital
General de Tomelloso, Tomelloso, Spain, and Instituto de Investigación
Sanitaria de Castilla-La Mancha (IDISCAM)
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22
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Zevit N, Chehade M, Leung J, Marderfeld L, Dellon ES. Eosinophilic Esophagitis Patients Are Not at Increased Risk of Severe COVID-19: A Report From a Global Registry. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. IN PRACTICE 2022; 10:143-149.e9. [PMID: 34688963 PMCID: PMC8530774 DOI: 10.1016/j.jaip.2021.10.019] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Revised: 09/29/2021] [Accepted: 10/06/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUND The impact of coronavirus disease 2019 (COVID-19) on eosinophilic esophagitis (EoE) and eosinophilic gastrointestinal diseases (EGIDs) is unknown. OBJECTIVE We aimed to characterize patients with EoE and EGIDs who had COVID-19, assess severity of COVID-19 in the EoE/EGID population, and evaluate for COVID-19-induced EoE/EGID flares. METHODS We established an online global registry collecting physician entered, deidentified data related to patient demographics, EoE/EGID disease features, comorbidities, and treatments, COVID-19 source of exposure, symptoms, illness severity, hospitalizations, and deaths. RESULTS Ninety-four cases were reported between March 2020 and April 2021 (median age, 21 years; range, 1.5-53 years; 73% male). Most had atopy (73%), and 80% had isolated EoE. Before COVID-19, the EoE/EGID activity was reported as clinical remission in 51 (54%) and moderate in 20 (21%). EoE/EGID treatments at the time of COVID-19 included proton pump inhibitors 49 (52%), swallowed/topical steroids 48 (51%), and dietary elimination 34 (36%). COVID-19 symptoms included cough (56%), fever (49%), anosmia (21%), and ageusia (22%). Most patients with COVID-19 had a mild course (70%), with 15% asymptomatic, 12% moderate, and 2% severe. Three patients were hospitalized, and no intensive care unit admissions or deaths were reported. Mean time from first symptoms to resolution in symptomatic patients was 10 days (range, 1-90 days). A single EGID flare was reported during COVID-19. CONCLUSIONS In a global EoE/EGID registry, relatively few COVID-19 cases have been reported. COVID-19 severity was comparable to the general population. Based on this registry, it does not appear that patients with EoE are at increased risk for severe COVID-19 infection or that COVID-19 leads to EGID flares.
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Affiliation(s)
- Noam Zevit
- Institute of Gastroenterology, Hepatology and Nutrition, Schneider Children's Medical Center of Israel, Petach Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
| | - Mirna Chehade
- Mount Sinai Center for Eosinophilic Disorders, Icahn School of Medicine at Mount Sinai, New York, NY
| | - John Leung
- Boston Specialists LLC, Boston, Mass; Department of Gastroenterology, Tufts Medical Center, Boston, Mass
| | - Luba Marderfeld
- Division of Gastroenterology, The Ottawa Hospital IBD Centre, Ottawa, Ontario, Canada
| | - Evan S Dellon
- Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC; 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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23
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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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24
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Fernandez-Becker NQ. Eosinophilic Esophagitis: Incidence, Diagnosis, Management, and Future Directions. Gastroenterol Clin North Am 2021; 50:825-841. [PMID: 34717873 DOI: 10.1016/j.gtc.2021.08.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/21/2023]
Abstract
Eosinophilic esophagitis (EoE) is an antigen-mediated esophageal disease defined by the presence of esophageal eosinophilia and symptoms of esophageal dysfunction. The pathophysiology involves an allergen-driven Th2 T cell response that triggers infiltration of eosinophils into the esophagus leading to inflammation, remodeling, and fibrosis. This results in disruption of esophageal function and accompanying symptoms - most notably dysphagia. Effective therapies target inflammation or fibrostenotic complications and include proton pump inhibitors, swallowed topical steroids, dietary exclusion, and dilation. Clinical trials testing promising biologic therapies are ongoing.
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25
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Barni S, Arasi S, Mastrorilli C, Pecoraro L, Giovannini M, Mori F, Liotti L, Saretta F, Castagnoli R, Caminiti L, Cianferoni A, Novembre E. Pediatric eosinophilic esophagitis: a review for the clinician. Ital J Pediatr 2021; 47:230. [PMID: 34809686 PMCID: PMC8609874 DOI: 10.1186/s13052-021-01178-2] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Accepted: 10/27/2021] [Indexed: 12/16/2022] Open
Abstract
Eosinophilic esophagitis (EoE) is a chronic clinical-pathologic disease characterized by eosinophilic infiltration of the esophageal epithelium with esophageal dysfunction symptoms.EoE can occur at any age and has different clinical manifestations depending on the age onset.To date, esophago-gastroduodenal endoscopy (EGD) with biopsy is the gold-standard for EoE diagnosis.According to the recent consensus guidelines, proton pump inhibitors, corticosteroids and elimination diets could be a first-line therapy option. The aim of the treatment is clinical and histological remission for preventing long-lasting untreatable fibrosis.A multidisciplinary approach (allergist, gastroenterology, dietitian, and pathologist) is recommended for managing patients affected by EoE, given the complexity of its treatment.This review will provide a practical guide to assist pediatricians treating children with EoE.Moreover, it highlights the unmet needs in diagnosis and treatment that require urgent attention from the scientific community in the aim of improving the management of patients with EoE.
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Affiliation(s)
- Simona Barni
- Allergy Unit, Department of Pediatrics, Meyer Children’s University Hospital, Florence, Italy
| | - Stefania Arasi
- Predictive and Preventive Medicine Research Unit, Multifactorial and Systemic Diseases Research Area, Pediatric Allergy Unit, Bambino Gesù Children’s Hospital IRCCS, Rome, Italy
| | - Carla Mastrorilli
- Pediatric Unit and Emergency, University Hospital Consortium Corporation Polyclinic of Bari, Pediatric Hospital Giovanni XXIII, Bari, Italy
- Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Luca Pecoraro
- Department of Medicine, University of Verona, Policlinico GB Rossi, Verona, Italy
- Pediatric Unit, ASST Mantua, Mantua, Italy
| | - Mattia Giovannini
- Allergy Unit, Department of Pediatrics, Meyer Children’s University Hospital, Florence, Italy
| | - Francesca Mori
- Allergy Unit, Department of Pediatrics, Meyer Children’s University Hospital, Florence, Italy
| | - Lucia Liotti
- Pediatric Unit, Senigallia Hospital, Senigallia, Italy
| | - Francesca Saretta
- Pediatric Department, Latisana-Palmanova Hospital, Azienda Sanitaria Universitaria Friuli Centrale, Udine, Italy
| | - Riccardo Castagnoli
- Department of Pediatrics, Pediatric Clinic, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy
| | - Lucia Caminiti
- Department of Human Pathology in Adult and Development Age “Gaetano Barresi”, Allergy Unit, Department of Pediatrics, AOU Policlinico Gaetano Martino, Messina, Italy
| | - Antonella Cianferoni
- Pediatrics Department, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA
- Allergy and Immunology Division, The Children’s Hospital of Philadelphia, Philadelphia, USA
| | - Elio Novembre
- Allergy Unit, Department of Pediatrics, Meyer Children’s University Hospital, Florence, Italy
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Abstract
Importance Eosinophilic esophagitis (EoE) is a chronic immune-mediated inflammatory disease of the esophagus that affects an estimated 34.4/100 000 people in Europe and North America. EoE affects both children and adults, and causes dysphagia, food impaction of the esophagus, and esophageal strictures. Observations EoE is defined by symptoms of esophageal dysfunction, such as vomiting, dysphagia, or feeding difficulties, in a patient with an esophageal biopsy demonstrating at least 15 eosinophils per high-power field in the absence of other conditions associated with esophageal eosinophilia such as gastroesophageal reflux disease or achalasia. Genetic factors and environmental factors, such as exposure to antibiotics early in life, are associated with EoE. Current therapies include proton pump inhibitors; topical steroid preparations, such as fluticasone and budesonide; dietary therapy with amino acid formula or empirical food elimination; and endoscopic dilation. In a systematic review of observational studies that included 1051 patients with EoE, proton pump inhibitor therapy was associated with a histologic response, defined as less than 15 eosinophils per high-power field on endoscopic biopsy, in 41.7% of patients, while placebo was associated with a 13.3% response rate. In a systematic review of 8 randomized trials of 437 patients with EoE, topical corticosteroid treatment was associated with histologic remission in 64.9% of patients compared with 13.3% for placebo. Patients with esophageal narrowing may require dilation. Objective assessment of therapeutic response typically requires endoscopy with biopsy. Conclusions and Relevance EoE has a prevalence of approximately 34.4/100 000 worldwide. Treatments consist of proton pump inhibitors, topical steroids, elemental diet, and empirical food elimination, with esophageal dilation reserved for patients with symptomatic esophageal narrowing.
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Affiliation(s)
- Amanda Muir
- Division of Gastroenterology, Hepatology, and Nutrition, Children’s Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104
| | - Gary W. Falk
- Division of Gastroenterology, Hospital of the University of Pennsylvania, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104
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27
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Alexander R, Alexander JA, Akambase J, Harmsen WS, Geno D, Tholen C, Katzka DA, Ravi K. Proton Pump Inhibitor Therapy in Eosinophilic Esophagitis: Predictors of Nonresponse. Dig Dis Sci 2021; 66:3096-3104. [PMID: 32995996 DOI: 10.1007/s10620-020-06633-4] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2020] [Accepted: 09/20/2020] [Indexed: 12/19/2022]
Abstract
BACKGROUND Identification of clinical predictors of response to first-line therapies for EoE is needed to guide initial medical management. STUDY DESIGN A retrospective analysis of patients diagnosed with EoE from 2011 to 2018 was conducted. Clinical and diagnostic variables including demographics, endoscopic, and esophagram findings were compared between PPI responders and PPI nonresponders. All patients underwent a standard 8-week twice-daily PPI trial, with PPI responsiveness defined as < 15 eos/hpf on repeat EGD. Univariate and multivariable analyses were conducted to identify risk factors for nonresponse, and ROC curves were created to identify cutoff values. RESULTS A total of 223 EoE patients (135 male, median age 39 (29-51)) were identified, with PPI nonresponse (PPI-NR) in 71% of patients. PPI-NR was seen in all 10 patients with failure of scope passage, with an OR of 9.06 by univariate analysis (P = 0.1485). In a multivariable model, age per 10 years (OR 0.71; P = 0.007), BMI per 1 kg/m2 (OR 0.94; P = 0.03), and peripheral eosinophil count per 100 per mm3 (OR 1.37; P = 0.003) were independent risk factors. Dichotomization to maximize sensitivity and specificity identified age ≤ 36 years old, BMI ≤ 25.2 kg/m2, and peripheral eos > 460 per mm3 as predictive thresholds for PPI-NR. The probability of PPI-NR was 72.4-84.5% with 1 risk factor, 87.9-93.8% with 2 risk factors, and 97.2% with all 3 risk factors. CONCLUSIONS Young age, reduced BMI, elevated peripheral eosinophil count, and likely inability to pass an endoscope predict lack of response to PPIs in patients with EoE.
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Affiliation(s)
- Ryan Alexander
- Department of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street, SW, Rochester, MN, 55905, USA
| | - Jeffrey A Alexander
- Department of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street, SW, Rochester, MN, 55905, USA
| | - Joseph Akambase
- Department of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street, SW, Rochester, MN, 55905, USA
| | - William Scott Harmsen
- Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA
| | - Debra Geno
- Department of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street, SW, Rochester, MN, 55905, USA
| | - Crystal Tholen
- Department of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street, SW, Rochester, MN, 55905, USA
| | - David A Katzka
- Department of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street, SW, Rochester, MN, 55905, USA
| | - Karthik Ravi
- Department of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street, SW, Rochester, MN, 55905, USA.
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28
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Kwon J, Koop A, Meek S, Francis D. A case series of eosinophilic esophagitis and primary adrenal insufficiency. Clin Res Hepatol Gastroenterol 2021; 45:101699. [PMID: 33892157 DOI: 10.1016/j.clinre.2021.101699] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2021] [Accepted: 03/31/2021] [Indexed: 02/04/2023]
Abstract
Although previously associated with secondary adrenal insufficiency and other autoimmune diseases, eosinophilic esophagitis has not been described in patients with primary adrenal insufficiency. In this case series, we describe three patients with eosinophilic esophagitis and primary adrenal insufficiency, including two patients with polyglandular autoimmune syndrome type 1. All patients experienced improvement in esophageal symptoms with treatment of eosinophilic esophagitis. The association between eosinophilic esophagitis and primary adrenal insufficiency is unclear, but may include underlying genetic predisposition and/or immune system dysregulation.
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Affiliation(s)
- Josh Kwon
- Division of Community Internal Medicine, Department of Internal Medicine, Mayo Clinic Jacksonville, FL, United States.
| | - Andree Koop
- Division of Gastroenterology, Department of Internal Medicine, Mayo Clinic Jacksonville, FL, United States.
| | - Shon Meek
- Division of Endocrinology, Department of Internal Medicine, Mayo Clinic Jacksonville, FL, United States.
| | - Dawn Francis
- Division of Gastroenterology, Department of Internal Medicine, Mayo Clinic Jacksonville, FL, United States.
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29
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Kochis SR, Cooke DW, Dantzer J, Wood R, Keet C. Low detection of adrenal suppression secondary to swallowed steroids for eosinophilic esophagitis in a quality improvement project. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. IN PRACTICE 2020; 8:3647-3649.e3. [PMID: 32668294 PMCID: PMC7655671 DOI: 10.1016/j.jaip.2020.06.050] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/20/2020] [Revised: 04/30/2020] [Accepted: 06/16/2020] [Indexed: 01/07/2023]
Affiliation(s)
- Suzanne R Kochis
- Division of Pediatric Allergy/Immunology, Johns Hopkins School of Medicine, Baltimore, Md.
| | - David W Cooke
- Division of Pediatric Endocrinology, Johns Hopkins School of Medicine, Baltimore, Md
| | - Jennifer Dantzer
- Division of Pediatric Allergy/Immunology, Johns Hopkins School of Medicine, Baltimore, Md
| | - Robert Wood
- Division of Pediatric Allergy/Immunology, Johns Hopkins School of Medicine, Baltimore, Md
| | - Corinne Keet
- Division of Pediatric Allergy/Immunology, Johns Hopkins School of Medicine, Baltimore, Md
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30
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Reddy A, Ashat D, Murali AR. Recent insights on the use of topical steroids in eosinophilic esophagitis. Expert Rev Gastroenterol Hepatol 2020; 14:953-963. [PMID: 32567417 DOI: 10.1080/17474124.2020.1785869] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
INTRODUCTION Eosinophilic Esophagitis (EoE) is an immune-mediated, chronic inflammatory disorder of the esophagus. Topical steroids have been used in the management of EoE for over 15 years. However, there are no Food and Drug Administration (FDA) approved drug therapies for EoE. AREAS COVERED This review discusses the current understanding of EoE and the role of topical steroids in the induction and maintenance of remission in patients with EoE. We performed a comprehensive review of the literature, summarized randomized control trials from 2006 to 2020, and provided a simplified management algorithm for EoE. EXPERT OPINION In patients with EoE, topical steroids are effective in inducing clinical and histologic remission. Formulations of topical steroids that maximize the exposure to esophageal mucosa have the highest efficacy. A majority of patients who achieve remission with topical steroids develop clinical and histologic relapse off therapy within a year. Current evidence suggests that maintenance therapy with long-term topical steroids decreases the risk of relapse and progression to fibrostenotic disease. While uncertainty over the dose and duration of maintenance topical steroids and their potential side effects exists, long-term maintenance therapy with topical steroids appears to be the way forward to improve long-term outcomes in patients with EoE.
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Affiliation(s)
- Aditi Reddy
- Department of Internal Medicine, University of Iowa Hospitals and Clinics , Iowa City, IA, USA
| | - Divya Ashat
- Department of Internal Medicine, University of Iowa Hospitals and Clinics , Iowa City, IA, USA.,Division of Gastroenterology & Hepatology, University of Iowa Hospitals and Clinics , Iowa City, IA, USA
| | - Arvind R Murali
- Department of Internal Medicine, University of Iowa Hospitals and Clinics , Iowa City, IA, USA.,Division of Gastroenterology & Hepatology, University of Iowa Hospitals and Clinics , Iowa City, IA, USA
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31
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Fernandez-Becker NQ, Raja S, Scarpignato C, Lynch KL, Ahuja NK, Horsley-Silva JL. Eosinophilic esophagitis: updates on key unanswered questions. Ann N Y Acad Sci 2020; 1481:30-42. [PMID: 32762154 DOI: 10.1111/nyas.14421] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Revised: 05/25/2020] [Accepted: 06/05/2020] [Indexed: 12/20/2022]
Abstract
Eosinophilic esophagitis (EoE) is a clinicopathologic disease characterized by symptoms of esophageal dysfunction and esophageal eosinophilia. In the last decade, there has been a dramatic increase in its prevalence for reasons that are not completely understood. The underlying pathophysiology involves an antigen-mediated TH 2 immune response that draws eosinophils to the esophagus, causing mucosal inflammation, esophageal remodeling, and fibrosis. This ultimately leads to esophageal dysfunction that most commonly manifests as dysphagia. In this review, we will discuss updates on key questions regarding the diagnosis and treatment of EoE.
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Affiliation(s)
| | - Shreya Raja
- Department of Medicine, Emory University, Atlanta, Georgia
| | - Carmelo Scarpignato
- Department of Health Sciences, United Campus of Malta, Msida, Malta.,Faculty of Medicine, Chinese University of Hong Kong, Sha Tin, Hong Kong
| | - Kristle L Lynch
- Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Nitin K Ahuja
- Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
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32
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Rossetti D, Isoldi S, Oliva S. Eosinophilic Esophagitis: Update on Diagnosis and Treatment in Pediatric Patients. Paediatr Drugs 2020; 22:343-356. [PMID: 32519266 DOI: 10.1007/s40272-020-00398-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Eosinophilic esophagitis (EoE) is a chronic immune-mediated inflammatory disorder characterized by symptomatic esophageal dysfunction and an eosinophil-predominant inflammation of the esophagus. EoE arises from interaction between genetic and environmental factors. In pediatric patients, clinical manifestations vary depending on age, from a gastroesophageal reflux disease (GERD)-like condition to severe dysphagic symptoms. Upper endoscopy is considered the gold standard for diagnosis and monitoring of EoE; however, significant efforts are underway to identify noninvasive diagnostic tools and biomarkers to avoid repetitive invasive procedures. Therapeutic first-line options currently available for EoE are elimination diets, proton pump inhibitors (PPIs), and steroids. The aim of treatment is to improve clinical symptoms while obtaining mucosal healing and avoiding long-term complications. Dietary treatment options comprise different empiric diets or an exclusively amino acid formula. Despite the efficacy of diets, compliance is often challenging. PPIs and topical steroids represent the main pharmacological options for EoE, and both can induce and maintain remission. Topical steroids have been reported as more effective, but data on long-term safety remain insufficient for both these and PPIs. Endoscopic dilations are currently reserved for severe untreated fibrostenotic disease unresponsive to medical therapies. Several biologic agents are available but not yet approved for EoE.
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Affiliation(s)
- Danilo Rossetti
- Pediatric Gastroenterology and Liver Unit, Maternal and Child Health Department, Sapienza University of Rome, viale Regina Elena, 324-00161, Rome, Italy
| | - Sara Isoldi
- Pediatric Gastroenterology and Liver Unit, Maternal and Child Health Department, Sapienza University of Rome, viale Regina Elena, 324-00161, Rome, Italy
| | - Salvatore Oliva
- Pediatric Gastroenterology and Liver Unit, Maternal and Child Health Department, Sapienza University of Rome, viale Regina Elena, 324-00161, Rome, Italy.
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Gutiérrez Junquera C, Fernández Fernández S, Domínguez-Ortega G, Vila Miravet V, García Puig R, García Romero R, Fernández de Valderrama A, Andradas Rivas R, Alonso Vicente C, Álvarez Beltrán M, Barrio Torres J, Barros García P, Colomé Rivero G, Javier Eizaguirre Arocena F, Fernández Caamaño B, Orden Izquierdo EL, Leis Trabazo R, Lorenzo Garrido H, Medina Benítez E, Montraveta Querol M, Vecino López R. Recommendations for the diagnosis and practical management of paediatric eosinophilic oesophagitis. ANALES DE PEDIATRÍA (ENGLISH EDITION) 2020. [DOI: 10.1016/j.anpede.2020.04.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022] Open
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Beveridge C, Falk GW. Novel Therapeutic Approaches to Eosinophilic Esophagitis. Gastroenterol Hepatol (N Y) 2020; 16:294-301. [PMID: 34035732 PMCID: PMC8132706] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/12/2023]
Abstract
Eosinophilic esophagitis is a chronic inflammatory condition that requires treatment to improve symptoms and prevent complications of esophageal remodeling, such as strictures and narrow-caliber esophagus. First-line treatments include proton pump inhibitors, topical corticosteroids, elimination or elemental diets, and esophageal dilation. Topical corticosteroids have typically required repurposing inhaled asthma medications by swallowing an aerosolized medication or mixing a nebulizer solution into a slurry. New topical corticosteroid formulations undergoing investigation include a premade budesonide oral suspension and disintegrating budesonide and fluticasone propionate tablets. The approach to an elimination diet is also changing, with an emphasis on patient preference when considering a traditional 6-food elimination diet compared with a step-up approach. This approach involves eliminating only 2 or 4 foods initially and expanding if necessary. While this method can be initially less effective for some patients, it generally involves fewer endoscopies and minimizes diet restriction. Beyond conventional therapies, a number of novel biologic agents are also under investigation. These include weekly subcutaneous injections or monthly intravenous infusions of RPC4046, dupilumab, antolimab, and benralizumab. The increasing number of approaches under development as well as anticipated submissions to the US Food and Drug Administration offer the potential of multiple specific therapies becoming available in the near future.
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Affiliation(s)
- Claire Beveridge
- Dr Beveridge is a gastroenterology and hepatology fellow and Dr Falk is a professor of medicine in the Division of Gastroenterology and Hepatology at the University of Pennsylvania Perelman School of Medicine in Philadelphia, Pennsylvania
| | - Gary W Falk
- Dr Beveridge is a gastroenterology and hepatology fellow and Dr Falk is a professor of medicine in the Division of Gastroenterology and Hepatology at the University of Pennsylvania Perelman School of Medicine in Philadelphia, Pennsylvania
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Comer GM, Bush MA, Dellon ES, Marino MT. Effect of Food Intake and Body Position on the Pharmacokinetics of Swallowed APT-1011, a Fluticasone Orally Disintegrating Tablet, in Healthy Adult Volunteers. J Clin Pharmacol 2020; 60:734-743. [PMID: 31943257 DOI: 10.1002/jcph.1572] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2019] [Accepted: 12/02/2019] [Indexed: 12/20/2022]
Abstract
Eosinophilic esophagitis is a common atopic disease of the esophagus. APT-1011 is an orally disintegrating tablet formulation of fluticasone propionate under development for the treatment of eosinophilic esophagitis. The objective of this study was to evaluate the pharmacokinetics, safety, and tolerability of APT-1011 under fed or fasted conditions in the morning (am) or at bedtime (hs) in the supine position. The study was a randomized, single-dose, 3-way, crossover design in healthy adult volunteers. In each study period participants received 2 3-mg orally disintegrating APT-1011 tablets. Serial plasma samples were collected before dosing and up to 72 hours after each dose. Twenty-two participants completed the study. The fluticasone propionate peak concentration (Cmax ) ranged from 5.97 to 200 pg/mL. Compared with am-fasted dosing, am-fed dosing was associated with a modestly higher Cmax (∼21%) but lower net exposure (area under the concentration-time curve ∼56% difference) and shorter time to reach Cmax (Tmax ) (Tmax fasted = 10 hours, fed = 5 hours). Dosing at hs resulted in an 18% and 32% decrease in Cmax relative to am-fasted and am-fed conditions, respectively. Dosing at hs led to an exposure that was higher than am-fed but lower than am-fasted dosing. Tmax with hs dosing (14 hours) was later than that with am dosing (Tmax fasted = 10 hours, fed = 5 hours). Adverse events were mild. There is low systemic exposure of fluticasone propionate with APT-1011. The rate of absorption was increased with a high-fat meal but decreased with hs dosing, suggesting the potential for longer dwell times in the esophagus.
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Affiliation(s)
- Gail M Comer
- Adare Pharmaceuticals, Lawrence Township, New Jersey, USA
| | - Mark A Bush
- Nuventra Pharma Sciences, Durham, North Carolina, USA
| | - 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, USA
| | - Mark T Marino
- Mark T. Marino, Consulting, LLC, Carlsbad, California, USA
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Gutiérrez Junquera C, Fernández Fernández S, Domínguez-Ortega G, Vila Miravet V, García Puig R, García Romero R, Fernández de Valderrama A, Andradas Rivas R. [Recommendations for the diagnosis and practical management of paediatric eosinophilic oesophagitis]. An Pediatr (Barc) 2020; 92:376.e1-376.e10. [PMID: 32471747 DOI: 10.1016/j.anpedi.2020.04.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2020] [Revised: 04/05/2020] [Accepted: 04/06/2020] [Indexed: 11/26/2022] Open
Abstract
Eosinophilic oesophagitis is an emerging and chronic disorder mediated by the immune system, and is characterised by symptoms of oesophageal dysfunction and inflammation with isolated eosinophil infiltration in the oesophagus. It is more common in males and in atopic subjects, and the symptoms vary with age. In younger children, there is vomiting, abdominal pain and dietary problems, with dysphagia and food impaction in older children and adolescents. The diagnosis is based on the presence of symptoms and oesophageal inflammation with ≥ 15 eosinophils / high power field, and after ruling out other causes of oesophageal eosinophilia. Without treatment, the disease usually persists and can progress to fibrostenotic forms more common in adults. The treatment options included proton pump inhibitors, empirical elimination diets, and swallowed topical corticosteroids. Maintenance therapy is advisable after the induction treatment. Diet is the only treatment that is directed at the cause of the disease, on identifying the triggering food or foods. The response to the treatments requires a histological assessment due to the poor agreement between the symptoms and the oesophageal inflammation. The practical management of Eosinophilic oesophagitis presents with challenges, due to, among other causes, the current lack of availability of specific drugs, and to its approach with, occasionally complex, diet treatments. The present document, prepared by the Working Group on Eosinophilic Gastrointestinal Disorders of the Spanish Society of Paediatric Gastroenterology, Hepatology and Nutrition, has as its objective to help in the diagnostic and therapeutic approach to paediatric eosinophilic oesophagitis, based on the recent evidence-based consensus guidelines.
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Affiliation(s)
| | | | | | - Víctor Vila Miravet
- Gastroenterología Pediátrica, Hospital Universitario Maternoinfantil San Joan de Deu, Barcelona, España
| | - Roger García Puig
- Gastroenterología Pediátrica, Hospital Universitario Mutua Terrassa, Barcelona, España
| | - Ruth García Romero
- Gastroenterología Pediátrica, Hospital Infantil Universitario Miguel Servet, Zaragoza, España
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Rank MA, Sharaf RN, Furuta GT, Aceves SS, Greenhawt M, Spergel JM, Falck-Ytter YT, Dellon ES. Technical review on the management of eosinophilic esophagitis: a report from the AGA institute and the joint task force on allergy-immunology practice parameters. Ann Allergy Asthma Immunol 2020; 124:424-440.e17. [PMID: 32336463 PMCID: PMC8171057 DOI: 10.1016/j.anai.2020.03.021] [Citation(s) in RCA: 58] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Eosinophilic esophagitis (EoE) is a chronic inflammatory condition of the esophagus. Many new studies have been reported recently that describe EoE management. An expert panel was convened by the American Gastroenterological Association Institute and the Joint Task Force on Allergy-Immunology Practice Parameters to provide a technical review to be used as the basis for an updated clinical guideline. This technical review was developed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. Eighteen focused EoE management questions were considered, with 15 answered using the GRADE framework and 3 with a narrative summary. There is moderate certainty in the evidence that topical glucocorticosteroids effectively reduce esophageal eosinophil counts to <15 per high-power field over a short-term treatment period of 4-12 weeks, but very low certainty about the effects of using topical glucocorticosteroids as maintenance therapy. Multiple dietary strategies may be effective in reducing esophageal eosinophil counts to <15 per high-power field over a short-term treatment period, with moderate certainty for elemental diets, low certainty for empiric 2-, 4-, and 6-food elimination diets, and very low certainty that allergy-based testing dietary eliminations have a higher failure rate compared to empiric diet elimination. There is very low certainty for the effect of proton pump inhibitors in patients with esophageal eosinophilia. Although esophageal dilation appears to be relatively safe, there is no evidence that it reduces esophageal eosinophil counts. There is very low certainty in the effects of multiple other medical treatments for EoE: anti-interleukin-5 therapy, anti-interleukin-13 therapy, anti-IgE therapy, montelukast, cromolyn, and anti-TNF therapy.
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Affiliation(s)
- Matthew A Rank
- Division of Allergy, Asthma, and Clinical Immunology, Mayo Clinic, Scottsdale, Arizona
| | - Rajiv N Sharaf
- Division of Gastroenterology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Manhasset, New York
| | - Glenn T Furuta
- Digestive Health Institute, Children's Hospital Colorado, Gastrointestinal Eosinophilic Diseases Program, University of Colorado School of Medicine, Aurora, Colorado
| | - Seema S Aceves
- Division of Allergy Immunology Center for Immunity, Infection, and Inflammation, University of California, San Diego Rady Children's Hospital, San Diego, California
| | - Matthew Greenhawt
- Section of Allergy/Immunology, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, Colorado
| | - Jonathan M Spergel
- Division of Allergy-Immunology, Children's Hospital of Philadelphia, Perelman School of Medicine at University of Pennsylvania, Philadelphia, Pennsylvania
| | - Yngve T Falck-Ytter
- Division of Gastroenterology and Hepatology, Cleveland Veterans Affairs Medical Center and University Hospitals, Case Western Reserve University School of Medicine, Cleveland, Ohio
| | - Evan S Dellon
- Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, North Carolina
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38
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Rank MA, Sharaf RN, Furuta GT, Aceves SS, Greenhawt M, Spergel JM, Falck-Ytter YT, Dellon ES. Technical Review on the Management of Eosinophilic Esophagitis: A Report From the AGA Institute and the Joint Task Force on Allergy-Immunology Practice Parameters. Gastroenterology 2020; 158:1789-1810.e15. [PMID: 32359563 PMCID: PMC9473155 DOI: 10.1053/j.gastro.2020.02.039] [Citation(s) in RCA: 98] [Impact Index Per Article: 19.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Eosinophilic esophagitis (EoE) is a chronic inflammatory condition of the esophagus. Many new studies have been reported recently that describe EoE management. An expert panel was convened by the American Gastroenterological Association Institute and the Joint Task Force on Allergy-Immunology Practice Parameters to provide a technical review to be used as the basis for an updated clinical guideline. This technical review was developed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. Eighteen focused EoE management questions were considered, with 15 answered using the GRADE framework and 3 with a narrative summary. There is moderate certainty in the evidence that topical glucocorticosteroids effectively reduce esophageal eosinophil counts to <15 per high-power field over a short-term treatment period of 4-12 weeks, but very low certainty about the effects of using topical glucocorticosteroids as maintenance therapy. Multiple dietary strategies may be effective in reducing esophageal eosinophil counts to <15 per high-power field over a short-term treatment period, with moderate certainty for elemental diets, low certainty for empiric 2-, 4-, and 6-food elimination diets, and very low certainty that allergy-based testing dietary eliminations have a higher failure rate compared to empiric diet elimination. There is very low certainty for the effect of proton pump inhibitors in patients with esophageal eosinophilia. Although esophageal dilation appears to be relatively safe, there is no evidence that it reduces esophageal eosinophil counts. There is very low certainty in the effects of multiple other medical treatments for EoE: anti-interleukin-5 therapy, anti-interleukin-13 therapy, anti-IgE therapy, montelukast, cromolyn, and anti-TNF therapy.
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Affiliation(s)
- Matthew A. Rank
- Division of Allergy, Asthma, and Clinical Immunology, Mayo
Clinic, Scottsdale, Arizona
| | - Ravi N. Sharaf
- Division of Gastroenterology, Donald and Barbara
Zucker School of Medicine at Hofstra/Northwell, Manhasset, New York
| | - Glenn T. Furuta
- Digestive Health Institute, Children’s
Hospital Colorado, Gastrointestinal Eosinophilic Diseases Program, University of
Colorado School of Medicine, Aurora, Colorado
| | - Seema S. Aceves
- Division of Allergy Immunology Center for Immunity,
Infection, and Inflammation, University of California, San Diego Rady
Children’s Hospital, San Diego, California
| | - Matthew Greenhawt
- Section of Allergy/Immunology, Children’s
Hospital Colorado, University of Colorado School of Medicine, Aurora, Colorado
| | - Jonathan M. Spergel
- Division of Allergy-Immunology, Children’s
Hospital of Philadelphia, Perelman School of Medicine at University of Pennsylvania,
Philadelphia, Pennsylvania
| | - Yngve T. Falck-Ytter
- Division of Gastroenterology and Hepatology, Cleveland
Veterans Affairs Medical Center and University Hospitals, Case Western Reserve
University School of Medicine, Cleveland, Ohio
| | - Evan S. Dellon
- Center for Esophageal Diseases and Swallowing, Division of
Gastroenterology and Hepatology, University of North Carolina School of Medicine,
Chapel Hill, North Carolina
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Richter JE. Editorial: fluticasone propionate orally disintegrating tablets-interesting concept but is it going anywhere? Aliment Pharmacol Ther 2020; 51:989-990. [PMID: 32338782 DOI: 10.1111/apt.15694] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Affiliation(s)
- Joel E Richter
- Joy McCann Culverhouse Center for Swallowing Disorders, Division of Digestive Diseases and Nutrition, University of South Florida Morsani College of Medicine, Tampa, FL, USA
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40
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Lucendo AJ. Pharmacological treatments for eosinophilic esophagitis: current options and emerging therapies. Expert Rev Clin Immunol 2020; 16:63-77. [PMID: 31842634 DOI: 10.1080/1744666x.2019.1705784] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Introduction: The epidemiology of eosinophilic esophagitis (EoE) has increased rapidly to represent a common cause of chronic and recurrent esophageal symptoms. Current treatment options have limitations so the development of novel therapies is a matter of growing interest.Areas covered: This article provides an up-to-date discussion of current therapies and investigational options for EoE. Established anti-inflammatory treatments for EoE at present include dietary therapy, proton pump inhibitors and swallowed topic steroids, which should be combined with endoscopic dilation in case of strictures. Refractoriness, high recurrence rates, and need for long-term therapies have promoted the investigation of novel, esophageal-targeted formulas of topic corticosteroids, and monoclonal antibodies (including mepolizumab, reslizumab, QAX576, RPC4046, dupilumab, omalizumab, infliximab, and vedolizumab) for EoE, with some having been demonstrated as effective and safe in the short term. Several additional promising therapies are also discussed.Expert opinion: Several therapeutic targets have shown efficacy and will be approved to treat EoE, especially corticosteroid-sparing options and those for patients with multiple Th2-associated diseases. Personalized therapeutic strategies for initial and maintenance treatments of EoE must be rationally designed, to reduce the burden of disease and answer meaningfully the needs of all stakeholders involved in EoE.
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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), Spain.,Instituto de Investigación Sanitaria La Princesa, Madrid, Spain
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41
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Diagnostic and Therapeutic Long-term Management of Eosinophilic Esophagitis- Current Concepts and Perspectives for Steroid Use. Clin Transl Gastroenterol 2019; 9:e212. [PMID: 30802222 PMCID: PMC6303250 DOI: 10.1038/s41424-018-0074-8] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus, which requires short- and long-term treatment. In addition, patients under long-term treatment for any chronic condition should have a structured follow-up. The mainstays in EoE treatment are drugs (such as swallowed topical corticosteroids [STC] and proton pump inhibitors), dietary exclusions, and endoscopic dilations. STC are the most widely used treatment and have proven efficacy in inducing clinical, endoscopic and histological remission in active EoE. However, data regarding maintaining disease remission and long-term management are limited. Ongoing disease activity and relapses despite STC treatment are frequently observed. This sheds light on the urgent need for adequate maintenance strategies, which have not been well defined. In terms of follow-up concepts, to date neither guidelines nor consensus recommendations have been published. To summarize the current knowledge on long-term diagnostic and therapeutic STC management of EoE, we conducted a literature search using PubMed and Embase applying the following key search items: Eosinophilic esophagitis, eosinophils, esophagus, swallowed topical corticosteroids, fluticasone, budesonide, long-term, treatment, therapy, and follow-up. In addition, we present empirically developed long-term management concepts applied at two large EoE centers, with a special focus on STC treatments. Finally, we highlight areas of future research and perspectives regarding the long-term management of EoE.
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42
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Gómez-Aldana A, Jaramillo-Santos M, Delgado A, Jaramillo C, Lúquez-Mindiola A. Eosinophilic esophagitis: Current concepts in diagnosis and treatment. World J Gastroenterol 2019; 25:4598-4613. [PMID: 31528089 PMCID: PMC6718043 DOI: 10.3748/wjg.v25.i32.4598] [Citation(s) in RCA: 43] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2019] [Revised: 07/13/2019] [Accepted: 07/19/2019] [Indexed: 02/06/2023] Open
Abstract
Eosinophilic esophagitis is an immune-allergic pathology of multifactorial etiology (genetic and environmental) that affects both pediatric and adult patients. Its symptoms, which include heartburn, regurgitation, and esophageal stenosis (with dysphagia being more frequent in eosinophilic esophagitis in young adults and children), are similar to those of gastroesophageal reflux disease, causing delays in diagnosis and treatment. Although endoscopic findings such as furrows, esophageal mucosa trachealization, and whitish exudates may suggest its presence, this diagnosis should be confirmed histologically based on the presence of more than 15 eosinophils per high-power field and the exclusion of other causes of eosinophilia (parasitic infections, hypereosinophilic syndrome, inflammatory bowel disease, among others) for which treatment could be initiated. Currently, the 3 "D"s ("Drugs, Diet, and Dilation") are considered the fundamental components of treatment. The first 2 components, which involve the use of proton pump inhibitors, corticosteroids, immunosuppressants and empirical diets or guided food elimination based on allergy tests, are more useful in the initial phases, whereas endoscopic dilation is reserved for esophageal strictures. Herein, the most important aspects of eosinophilic esophagitis pathophysiology will be reviewed, in addition to evidence for the various treatments.
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Affiliation(s)
- Andrés Gómez-Aldana
- Departament of Internal Medicine, Section of Gastroenterology, Santa Fe Foundation of Bogotá (Fundación Santa Fe de Bogotá), Bogotá 220246, Colombia
- University of Los Andes, Bogotá 111711, Colombia
| | - Mario Jaramillo-Santos
- Department of Endoscopy, Caldas University, Manizales 275, Colombia
- Department of Endoscopy, Surgeons’ Union SAS (Joint stock company) (Union de cirujanos SAS), Manizales 170001661, Colombia
| | - Andrés Delgado
- Departament of Internal Medicine, Section of Gastroenterology, Santa Fe Foundation of Bogotá (Fundación Santa Fe de Bogotá), Bogotá 220246, Colombia
| | - Carlos Jaramillo
- Department of Endoscopy, Caldas University, Manizales 275, Colombia
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43
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Zheng P, Tan HY. New developments in diagnosis and treatment of eosinophilic esophagitis. Shijie Huaren Xiaohua Zazhi 2019; 27:828-834. [DOI: 10.11569/wcjd.v27.i13.828] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Affiliation(s)
- Pu Zheng
- Department of Emergency Medicine, Beijing Hospital, Beijing 100005, China
| | - Huang-Ying Tan
- Department of Integrative Oncology, China-Japan Friendship Hospital, Beijing 100029, China
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44
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Pérez-Martínez I, Rodrigo L, Lucendo AJ. Esofagitis eosinofílica: aproximación al diagnóstico y tratamiento desde la evidencia. Med Clin (Barc) 2019; 152:444-449. [DOI: 10.1016/j.medcli.2018.10.022] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2018] [Revised: 10/12/2018] [Accepted: 10/16/2018] [Indexed: 01/07/2023]
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45
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Rodríguez Manchón S, Domínguez Ortega G, Bacelo Ruano I, Martínez Ibeas MA, Pozo Román J, Cañedo Villarroya E, Muñoz Codoceo RA. Letter: reassuringly normal response to ACTH in children treated with swallowed topical corticosteroids for eosinophilic oesophagitis. Aliment Pharmacol Ther 2019; 49:1537-1538. [PMID: 31134648 DOI: 10.1111/apt.15243] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Affiliation(s)
- Silvia Rodríguez Manchón
- Department of Paediatrics, Section of Gastroenterology and Nutrition, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
| | - Gloria Domínguez Ortega
- Department of Paediatrics, Section of Gastroenterology and Nutrition, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
| | - Irene Bacelo Ruano
- Department of Paediatrics, Section of Gastroenterology and Nutrition, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
| | - María Angeles Martínez Ibeas
- Department of Paediatrics, Section of Gastroenterology and Nutrition, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
| | - Jesús Pozo Román
- Paediatric Endocrinology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
| | - Elvira Cañedo Villarroya
- Department of Paediatrics, Section of Gastroenterology and Nutrition, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
| | - Rosa Ana Muñoz Codoceo
- Department of Paediatrics, Section of Gastroenterology and Nutrition, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
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46
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Philpott H, Dougherty M, Torpy D, Dellon E. Letter: reassuringly normal response to ACTH in children treated with swallowed topical corticosteroids for eosinophilic oesophagitis - authors' reply. Aliment Pharmacol Ther 2019; 49:1539. [PMID: 31134652 DOI: 10.1111/apt.15292] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Affiliation(s)
- Hamish Philpott
- Department of Gastroenterology, Northern Adelaide Local Health Network, Adelaide, SA, Australia.,Faculty of Sciences, University of Adelaide, Adelaide, SA, Australia
| | - Michael Dougherty
- Department of Gastroenterology, Center for Digestive Disease and Swallowing, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - David Torpy
- Faculty of Sciences, University of Adelaide, Adelaide, SA, Australia.,Division of Endocrinology and Metabolism, University of Adelaide, Adelaide, SA, Australia
| | - Evan Dellon
- Department of Gastroenterology, Center for Digestive Disease and Swallowing, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
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47
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Cost-effective care in eosinophilic esophagitis. Ann Allergy Asthma Immunol 2019; 123:166-172. [PMID: 31009702 DOI: 10.1016/j.anai.2019.04.010] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2019] [Revised: 04/05/2019] [Accepted: 04/11/2019] [Indexed: 12/11/2022]
Abstract
OBJECTIVE To examine costs related to eosinophilic esophagitis (EoE), understand the source of these costs, discuss a possible approach for cost-effective care in EoE, and identify areas for future research in this topic. DATA SOURCES/STUDY SELECTIONS Narrative review of the literature from 1977 (first description of EoE) to March 2019, focusing on costs and cost-effectiveness analyses in EoE. RESULTS High costs in EoE can be related to diagnostic delays, requirement for upper endoscopy with biopsy for diagnosis and monitoring of disease activity, expensive medications currently used off-label, increased food costs related to dietary elimination treatment, frequent doctor visits with subspecialists, and complications or disease exacerbations. Provision of cost-effective care in EoE is an understudied area, and a patient-centric approach is key. There are multiple areas in which future research can make an impact. These include determining predictors of treatment response, minimally or noninvasive methods to monitor disease activity, and validation of the use of multidisciplinary care. CONCLUSION Eosinophilic esophagitis (EoE) is considered to be a rare disease, but the costs of care and burden of disease attributed to EoE are substantial. However, few studies examine either the costs related to EoE or the approach to cost-effective care for the EoE patient. To provide cost-effective care, a patient-centric approach and shared decision-making model are optimal. In addition, a rational strategy for EoE diagnosis and initial treatment, effective maintenance therapy for disease control and ideally to prevent complications, and appropriate long-term monitoring are all required.
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48
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Nhu QM, Moawad FJ. New Developments in the Diagnosis and Treatment of Eosinophilic Esophagitis. CURRENT TREATMENT OPTIONS IN GASTROENTEROLOGY 2019; 17:48-62. [PMID: 30707411 PMCID: PMC6519728 DOI: 10.1007/s11938-019-00216-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
PURPOSE OF REVIEW Eosinophilic esophagitis (EoE) is a chronic, allergen-driven, immune-mediated disease of the esophagus that progresses to esophageal fibrostenosis if left untreated. The aim of this review is to provide a concise update on recent clinically relevant advances in the development of diagnostic and therapeutic approaches for EoE. RECENT FINDINGS Current diagnostic and disease monitoring protocols for EoE rely on repetitive endoscopic evaluations and esophageal tissue acquisition for histopathologic analysis. Recent advancements in EoE diagnosis include endoscopic functional lumen imaging probe (FLIP), transnasal endoscopy (TNE), and the emergence of non-invasive diagnostic tools including cytosponge, esophageal string test, and mucosal impedance probe. Biomarkers for EoE have not yet proven their clinical utility. No Food and Drug Administration (FDA)-approved drugs currently exist for the treatment of EoE. Topical corticosteroid, proton-pump inhibitors (PPI), elimination diet, and dilation are the current treatment modalities for confirmed EoE. Promising results from clinical trials are emerging for biologic agents that target the interleukin (IL)-13 and the IL-4/IL-13 receptor, specifically, RPC4046 and dupilumab, respectively. New diagnostic algorithms, non-invasive diagnostic strategies, and treatment modalities for EoE are emerging. Patients with EoE continue to require a multimodal and multi-disciplinary management approach.
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Affiliation(s)
- Quan M Nhu
- Division of Gastroenterology & Hepatology, Scripps Clinic, 10666 N. Torrey Pines Road, Suite 203N, La Jolla, CA, 92037, USA.
- Scripps Research Translational Institute, The Scripps Research Institute, La Jolla, CA, USA.
| | - Fouad J Moawad
- Division of Gastroenterology & Hepatology, Scripps Clinic, 10666 N. Torrey Pines Road, Suite 203N, La Jolla, CA, 92037, USA.
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Cianferoni A, Shuker M, Brown-Whitehorn T, Hunter H, Venter C, Spergel JM. Food avoidance strategies in eosinophilic oesophagitis. Clin Exp Allergy 2019; 49:269-284. [DOI: 10.1111/cea.13360] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2018] [Revised: 01/02/2019] [Accepted: 01/03/2019] [Indexed: 12/21/2022]
Affiliation(s)
- Antonella Cianferoni
- Division of Allergy and Immunology; The Children’s Hospital of Phialdelphia; Phialdelphia Pennsylvania
- Department of Pediatrics; Perelman School of Medicine; University of Pennsylvania
| | - Michelle Shuker
- Division of Allergy and Immunology; The Children’s Hospital of Phialdelphia; Phialdelphia Pennsylvania
| | - Terri Brown-Whitehorn
- Division of Allergy and Immunology; The Children’s Hospital of Phialdelphia; Phialdelphia Pennsylvania
- Department of Pediatrics; Perelman School of Medicine; University of Pennsylvania
| | - Hannah Hunter
- Allergy; Guy's and Saint Thomas’ NHS Foundation Trust; London UK
| | - Carina Venter
- Allergy and Immunology; Children's Hospital Colorado; Aurora Colorado
| | - Jonathan M. Spergel
- Division of Allergy and Immunology; The Children’s Hospital of Phialdelphia; Phialdelphia Pennsylvania
- Department of Pediatrics; Perelman School of Medicine; University of Pennsylvania
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Abstract
Eosinophilic esophagitis (EoE) is a chronic disorder characterized by symptoms of esophageal dysfunction and esophageal inflammation with intraepithelial eosinophils. EoE represents an important cause of upper gastrointestinal morbidity. Primary care providers are pivotal for timely and accurate recognition of symptoms of eosinophilic esophagitis, for facilitating diagnoses through specialist referrals, and for understanding management strategies. This process begins with a thorough understanding of the clinical features of EoE, its associated atopic conditions, and its evolving epidemiology.
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Affiliation(s)
- Craig C Reed
- Division of Gastroenterology and Hepatology, Department of Medicine, Center for Esophageal Diseases and Swallowing, Center for Gastrointestinal Biology and Disease, University of North Carolina School of Medicine, 130 Mason Farm Road, Chapel Hill, NC 27599-7080, USA
| | - Evan S Dellon
- Division of Gastroenterology and Hepatology, Department of Medicine, Center for Esophageal Diseases and Swallowing, Center for Gastrointestinal Biology and Disease, University of North Carolina School of Medicine, CB #7080, Room 4140, Bioinformatics Building, 130 Mason Farm Road, Chapel Hill, NC 27599-7080, USA.
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