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Olsson N, Bergman D, Sun J, Carlson M, Uchida AM, Ludvigsson JF. Incidence of non-esophageal eosinophilic gastrointestinal disease in Sweden 1990-2015. Scand J Gastroenterol 2025; 60:343-348. [PMID: 40069573 DOI: 10.1080/00365521.2025.2475093] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Revised: 02/17/2025] [Accepted: 02/26/2025] [Indexed: 04/02/2025]
Abstract
BACKGROUND Data on the incidence of Eosinophilic gastrointestinal disease (EGID) distal to the esophagus are scarce. This study aimed to examine the incidence of non-eosinophilic esophagitis (EoE) EGID in Sweden, as well as its three entities; eosinophilic gastritis (EoG), eosinophilic enteritis (EoN), and eosinophilic colitis (EoC). METHODS We performed a nationwide population-based cohort study of individuals with incident biopsy-confirmed non-EoE EGID in Sweden from 1990 to 2015. Age-standardized and age-specific incidence rates (IRs) were calculated. RESULTS We identified 1882 individuals with incident non-EoE EGID. Females constituted 58% and the mean age at diagnosis was 45 years. EoC was the most common subtype (62%). From 1990 to 2015, the mean age-standardized IR was approximately 0.8 per 100,000 person-years (IR = 0.79; 95%CI = 0.64-0.93), but with higher IRs in recent years (2013-2015: IR = 1.51; 95%CI = 1.09-1.93). The incidence increased especially during the 1990s, with a 27% annual increase before 2000, compared to a 3% annual increase thereafter. The incidence rate ratio (IRR) between females and males was 1.38 (95%CI = 1.26-1.51), but no evidence was found to suggest that the IRR varied across calendar periods or by age. The lifetime risk of diagnosed non-EoE EGID was 0.08% (1 in 1250) in females and 0.06% (1 in 1667) in males. CONCLUSION The incidence of non-EoE EGID in Sweden increased between 1990 and 2015. This may reflect a higher disease awareness in recent years.
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Affiliation(s)
- Natasha Olsson
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
- Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
| | - David Bergman
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Jiangwei Sun
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Marie Carlson
- Department of Medical Sciences, Gastroenterology Research Group, Uppsala University, Uppsala, Sweden
| | - Amiko M Uchida
- Division of Gastroenterology, Hepatology and Nutrition, Salt Lake City, University of Utah School of Medicine, USA
| | - Jonas F Ludvigsson
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
- Department of Pediatrics, Örebro University Hospital, Örebro, Sweden
- Celiac Disease Center, Department of Medicine, Columbia University College of Physicians and Surgeons, NY, USA
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Wang Y, Huang Y, Yeo YH, Pang S, Ramai D, Zheng T, Wang Y, Yan Y, DeVault KR, Francis D, Antwi SO, Pang M. Eosinophilic Esophagitis-Related Food Impaction: Distinct Demographics, Interventions, and Promising Predictive Models. Dig Dis Sci 2025; 70:675-684. [PMID: 39779592 DOI: 10.1007/s10620-024-08823-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2024] [Accepted: 12/22/2024] [Indexed: 01/11/2025]
Abstract
BACKGROUND Eosinophilic esophagitis (EoE) is an increasingly common cause of food impaction. AIMS This study aims to provide a nationwide analysis of food impaction in patients with or without EoE diagnosis, concentrating on patient demographics, interventions, outcomes, and development of predictive machine-learning models. METHODS A retrospective assessment was conducted using Nationwide Emergency Department Sample data from January 1, 2018, to December 31, 2019. We compared patients with food impaction with an associated EoE diagnosis to those without EoE and derived machine-learning models to predict EoE using International Classification of Diseases codes at discharge for identification. RESULTS Of 286,886,714 emergency department visits, 146,084 were for food impaction, with 7093 cases coinciding with an EoE diagnosis (4.9%). Patients with EoE were more commonly young men with fewer overall comorbidities but higher incidences of obesity, asthma, gastritis, and allergic rhinitis. A significantly larger proportion in the EoE group (89.6%) underwent esophagogastroduodenoscopy compared to the non-EoE group (51.1%; P < 0.001) and had a higher rate of biopsy during esophagogastroduodenoscopy in the emergency department (54.9% vs 13.4%; P < 0.001). Our machine-learning models, incorporating patient demographics, hospital attributes, and comorbidities, had a sensitivity of 86.1% and an area under the receiver operating characteristic curve of 0.828. CONCLUSIONS This nationwide study demonstrates that EoE in food impaction is associated with specific patient demographics, comorbidities, and elevated interventions. Our machine-learning models hold promise as screening tools for EoE, aiding medical practitioners in determining the need for biopsy.
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Affiliation(s)
- Yichen Wang
- Division of Hospital Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
| | - Yuting Huang
- Division of Gastroenterology and Hepatology, Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL, USA
| | - Yee Hui Yeo
- Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Songhan Pang
- University of Virginia College of Arts and Sciences, Charlottesville, VA, USA
| | - Daryl Ramai
- Division of Gastroenterology and Hepatology, University of Utah, Salt Lake City, UT, USA
| | - Ting Zheng
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Yiming Wang
- Department of Computing, Xi'an Jiaotong-Liverpool University, Suzhou, China
| | - Yan Yan
- Division of Gastroenterology and Hepatology, Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL, USA
| | - Kenneth R DeVault
- Division of Gastroenterology and Hepatology, Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL, USA
| | - Dawn Francis
- Division of Gastroenterology and Hepatology, Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL, USA
| | - Samuel O Antwi
- Department of Quantitative Health Sciences, Mayo Clinic, Jacksonville, FL, USA
| | - Maoyin Pang
- Division of Gastroenterology and Hepatology, Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL, USA.
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Ben-Tov A, Melzer-Cohen C, Yahalom R, Yarden A, Livnat I, Patalon T, Gazit S. Increase Incidence and Prevalence of Eosinophilic Gastrointestinal Disorders in Israel During the Last Decade. J Gastroenterol Hepatol 2025; 40:413-420. [PMID: 39631438 DOI: 10.1111/jgh.16829] [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: 03/22/2024] [Revised: 09/17/2024] [Accepted: 11/09/2024] [Indexed: 12/07/2024]
Abstract
BACKGROUND Eosinophilic gastrointestinal disorders (EGIDs) are primary immune-mediated disorders, with significant morbidity and long-term sequelae. Temporal trends in incidence and prevalence are on the rise, but studies outside Europe and North America are sparse. METHODS Based on retrospective Electronic Medical Records (EMR) data, we studied a large population cohort during the years 2014-2021 of all patients diagnosed with EGIDs. Incidence rate and prevalence were calculated for each year during the study cohort stratified by disease location, age, and sex. RESULTS Between 2014 and 2021, among a population of 2.4 million persons, the incidence rate of EGIDs tripled from 2.51 (95% CI: 1.78-3.23) to 7.88 (95% CI: 6.75-9.01) per 100 000 person-years. Most (85.1%) were patients with eosinophilic esophagitis (EoE). The increased temporal trend was almost identical among all subgroups, including patients with EoE, patients with non-EoE EGIDs, and patients with EGIDs with esophageal involvement. The prevalence of EGIDs increased from 14.53 (95% CI: 12.80-16.26) to 51.43 (95% CI: 48.60-54.26) per 100 000 persons. In 2021, at the end of the study, the prevalence of EoE was 39.54 (95% CI: 37.05-42.02) per 100 000 persons, and the prevalence of non-EoE EGID was 11.89 (95% CI: 10.53-13.26) per 100 000 persons. CONCLUSIONS The incidence and prevalence of EGIDs in Israel have risen steeply during the last decade. The main contribution came from the increased incidence rate of patients with EoE. By the end of the surveillance period, the increased temporal trends did not reach a plateau.
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Affiliation(s)
- Amir Ben-Tov
- Kahn Sagol Maccabi (KSM) Research & Innovation Center, Maccabi Healthcare Services, Tel Aviv, Israel
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Cheli Melzer-Cohen
- Maccabitech Institute for Research and Innovation, Maccabi Healthcare Services, Tel Aviv, Israel
| | - Roni Yahalom
- Medical Affairs, BioPharmaceuticals Medical, AstraZeneca, Kfar-Saba, Israel
| | - Adva Yarden
- Medical Affairs, BioPharmaceuticals Medical, AstraZeneca, Kfar-Saba, Israel
| | - Idit Livnat
- Medical Affairs, BioPharmaceuticals Medical, AstraZeneca, Kfar-Saba, Israel
| | - Tal Patalon
- Kahn Sagol Maccabi (KSM) Research & Innovation Center, Maccabi Healthcare Services, Tel Aviv, Israel
- Maccabitech Institute for Research and Innovation, Maccabi Healthcare Services, Tel Aviv, Israel
| | - Sivan Gazit
- Kahn Sagol Maccabi (KSM) Research & Innovation Center, Maccabi Healthcare Services, Tel Aviv, Israel
- Maccabitech Institute for Research and Innovation, Maccabi Healthcare Services, Tel Aviv, Israel
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4
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Dlugosz A, Berglund A, Uhde M. The epidemiology of eosinophilic esophagitis in Sweden - a nationwide population-based study. Scand J Gastroenterol 2025; 60:1-9. [PMID: 39697135 DOI: 10.1080/00365521.2024.2440787] [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: 09/28/2024] [Revised: 11/12/2024] [Accepted: 12/06/2024] [Indexed: 12/20/2024]
Abstract
INTRODUCTION Eosinophilic esophagitis (EoE) is a chronic inflammatory condition that affects the esophagus. Previous studies have indicated a substantial increase of EoE over the last decades. The aim of the current study was to describe the incidence and prevalence of EoE over time and by geographical regions in Sweden, utilizing nationwide population-based registries. MATERIAL AND METHODS The number of hospital admissions (in-patient and out-patient) for patients were identified using ICD-10-SE code K20.9A from the National Patient Registry between 1st January 2011 and 31st December 2021. Crude incidence and prevalence numbers were presented per 100,000 person years and persons, respectively. RESULTS In 2011, no hospital visits of EoE were recorded. A total of 3,243 incident patients (2,379 (73.4%) men and 864 (26.6%) women) had a record of EoE between 2012 and 2021. The incidence increased over calendar year in where the incidence was from 1.59 per 100,000 person years in 2012 to 5.34 per 100,000 person years in 2021. The prevalence was 1.29 per 100,000 person years and 31.02 per 100,000 person years in 2012 and 2021, respectively. Major differences in the prevalence between geographical regions in Sweden were observed, e.g. in 2021, the prevalence was 12.24 in Västernorrland compared to 43.26 in Västra Götaland per 100,000 person years, which is similar to the prevalence in the Stockholm region. CONCLUSION The incidence and prevalence of eosinophilic esophagitis has significantly increased over calendar year but differs between geographical regions in Sweden. These differences should be further investigated.
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Affiliation(s)
- Aldona Dlugosz
- H7 Department of Medicine, Huddinge, Karolinska institutet, Stockholm, Sweden
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Pitsios C, Rossi CM. Allergen immunotherapy and eosinophilic esophagitis: friends or foes? Curr Opin Allergy Clin Immunol 2024; 24:504-509. [PMID: 39270037 DOI: 10.1097/aci.0000000000001029] [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: 09/15/2024]
Abstract
PURPOSE OF REVIEW The connection between eosinophilic esophagitis (EoE) and food and airborne allergens is complex. Exposure to allergens (mainly food) is often the trigger for EoE flares. The development of EoE has been described as a side effect of allergen immunotherapy, especially oral immunotherapy (OIT, with food allergens), while isolated cases of EoE have been reported during sublingual immunotherapy (SLIT, with extracts of aeroallergens). RECENT FINDINGS EoE is currently recognized as a common side effect of OIT, while a solid correlation between SLIT and EoE is missing. Animal models have been developed to study the pathophysiological link between sensitization to aeroallergens and the induction of EoE and will probably provide an interpretation of why there are cases of EoE developed during SLIT. Recent findings in animal models suggest a genetic connection to EoE development after sensitization and re-exposure to airborne allergens. Subcutaneous allergen immunotherapy does not have a causative effect on EoE; on the contrary, a beneficial effect on EoE has been reported. Moreover, epicutaneous immunotherapy with a vector containing milk has also been used to treat children with milk-induced EoE. SUMMARY Discovering the immune links between allergens and EoE will further guide the proper use of allergen immunotherapy and help define future strategies for the management of EoE.
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Affiliation(s)
- Constantinos Pitsios
- Medical School, University of Cyprus
- Allergy Outpatient Clinic, General Hospital of Nicosia, Nicosia, Cyprus
| | - Carlo Maria Rossi
- Department of Internal Medicine, IRCCS San Matteo Hospital Foundation
- Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy
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Karpf J, Safroneeva E, Rossel JB, Hildenbrand F, Saner C, Greuter T, Rogler G, Straumann A, Schoepfer A, Biedermann L, Murray FR, Schreiner P. Odynophagia and Retrosternal Pain Are Common in Eosinophilic Esophagitis and Associated with an Increased Overall Symptom Severity. Dig Dis Sci 2024; 69:3853-3862. [PMID: 39115646 PMCID: PMC11489245 DOI: 10.1007/s10620-024-08586-4] [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: 02/02/2024] [Accepted: 08/01/2024] [Indexed: 10/20/2024]
Abstract
BACKGROUND AND AIMS Dysphagia is the hallmark symptom in eosinophilic esophagitis (EoE). However, data are limited regarding the overall prevalence and potential implications of atypical symptoms like odynophagia and retrosternal pain. METHODS Patients enrolled into the Swiss EoE cohort study (SEECS) were analyzed regarding the presence of odynophagia and retrosternal pain. Demographics, other EoE-related symptoms, histologic and endoscopic activity were compared between EoE-patients with vs. without odynophagia and/or retrosternal pain. RESULTS 474 patients (75.2% male) were analyzed. In their individual course of disease 110 (23.2%) patients stated to have ever experienced odynophagia and 64 (13.5%) retrosternal pain independent of food intake, 24 (5%) patients complained about both symptoms. Patients with odynophagia consistently scored higher in symptom severity (p < 0.001), EREFS score (median 3.0 vs. 2.0, p = 0.006), histologic activity and a lower quality of life (p = 0.001) compared to patients without odynophagia. Sex, age at diagnosis, EoE-specific treatment, complications such as candida or viral esophagitis and disease duration were similar in patients with vs. without odynophagia. Also patients with retrosternal pain scored higher in symptom severity (2.0 vs. 1.0, p = 0.001 and 2.0 vs. 1.0, p < 0.001 in physician and patient questionnaire assessment, respectively). However, there was neither a difference in endoscopic/histologic disease activity nor in quality of life according to presence or absence of retrosternal pain. Due to logistic reasons, a stratification regarding the presence of concomitant dysphagia was not possible. CONCLUSION Odynophagia and swallowing-independent retrosternal pain are common symptoms in patients with EoE, associate with an overall higher EoE-related symptom severity and for the case of odynophagia lower quality of life. However, the influence of concomitant dysphagia and its severity remains unclear and needs to be included in future analyses.
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Affiliation(s)
- Jeanine Karpf
- Department of Gastroenterology, Stadtspital Zurich, Birmensdorferstrasse 497, 8063, Zurich, Switzerland
| | - Ekaterina Safroneeva
- Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland
| | | | - Florian Hildenbrand
- Department of Gastroenterology, Stadtspital Zurich, Birmensdorferstrasse 497, 8063, Zurich, Switzerland
| | - Catherine Saner
- Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne, Switzerland
| | - Thomas Greuter
- Department of Internal Medicine, GZO - Zurich Regional Health Center, Wetzikon, Switzerland
- Department of Gastroenterology, University Hospital Zurich, Raemistrasse 100, 8091, Zurich, Switzerland
| | - Gerhard Rogler
- Department of Gastroenterology, University Hospital Zurich, Raemistrasse 100, 8091, Zurich, Switzerland
| | - Alex Straumann
- Department of Gastroenterology, University Hospital Zurich, Raemistrasse 100, 8091, Zurich, Switzerland
| | - Alain Schoepfer
- Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne, Switzerland
| | - Luc Biedermann
- Department of Gastroenterology, University Hospital Zurich, Raemistrasse 100, 8091, Zurich, Switzerland
| | - Fritz R Murray
- Department of Gastroenterology, Stadtspital Zurich, Birmensdorferstrasse 497, 8063, Zurich, Switzerland
| | - Philipp Schreiner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
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S2k guideline Gastroesophageal reflux disease and eosinophilic esophagitis of the German Society of Gastroenterology, Digestive and Metabolic Diseases (DGVS). ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:1786-1852. [PMID: 39389106 DOI: 10.1055/a-2344-6282] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/12/2024]
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Tadros M, Trovato A, Manem N, Donovan K, Nudelman N, Dellon ES, Gemoets DE, Ashley C. Epidemiology and Racial Differences of EoE Patients in a U.S. Veterans Population. Dig Dis Sci 2024; 69:2315-2323. [PMID: 38761307 DOI: 10.1007/s10620-024-08400-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2023] [Accepted: 03/19/2024] [Indexed: 05/20/2024]
Abstract
BACKGROUND Eosinophilic esophagitis (EoE) is increasing in prevalence but there is a lack of population-based studies. We sought to determine the prevalence, demographics, and associated atopic diseases in the Veterans Affairs (VA) population. METHODS A nationwide analysis of data from the VA patient population was done using a Veterans Health Administration database. EoE was identified using ICD9 (530.13) and ICD10 (K20.0) codes from October 2008 to June 2020. Demographic data, smoking status, BMI, treatment, and ICD codes for atopic diagnoses were collected. Two sample proportion z-tests, Chi-square tests, two-sample t tests, and one-way ANOVA were used to assess associations across demographic categories. RESULTS We identified a total of 11,775 patients with an EoE diagnosis: 91% male, 83% White, 8.6% Black, and 5% were of Hispanic ethnicity. The prevalence of EoE increased over time. At diagnosis, the mean age was 48.5 years overall, 51.6 years for Black patients, 45.3 years for Hispanic patients, and 48.2 years for Whites. Dysphagia was the most common symptom overall, but a higher percentage of Blacks and females were found to report chest pain (p < 0.0001, h = 0.32). With the exception of urticaria and atopic dermatitis, both Blacks and Hispanics had a higher incidence of atopic conditions compared to other races and ethnicities (p < 0.0001). CONCLUSION While EoE is seen primarily in White males, our study shows that a notable percentage of patients were Black or Hispanic, suggesting that EoE should be considered in non-white patients. The later age of diagnosis in this group could represent a lack of awareness about EoE among non-white patients. More research is needed to study these associations.
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Affiliation(s)
- Micheal Tadros
- Albany Medical Center, 43 New Scotland Ave, Albany, NY, 12208, USA.
| | - Alexa Trovato
- Boston Medical Center, 72 East Concord Street, Evans 124, Boston, MA, 02118, USA
| | - Nihita Manem
- Albany Medical College, 43 New Scotland Ave, Albany, NY, 12208, USA
| | | | - Nicole Nudelman
- Albany Medical College, 43 New Scotland Ave, Albany, NY, 12208, USA
| | - Evan S Dellon
- Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, 130 Mason Farm Rd, Chapel Hill, NC, 27599-7080, USA
| | - Darren E Gemoets
- Albany Stratton VA Medical Center, 113 Holland Ave, Albany, NY, 12208, USA
| | - Christopher Ashley
- Albany Stratton VA Medical Center, 113 Holland Ave, Albany, NY, 12208, USA
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Quinn LA, Burger C, Nguyen B, Arnold MA, Pan Z, Furuta GT, Bauer ME, Menard-Katcher C. Natural Histories and Disease Complications in a Cohort of 151 Children With Gastric or Duodenal Eosinophilia. Am J Gastroenterol 2024; 119:1298-1308. [PMID: 38174865 PMCID: PMC11222049 DOI: 10.14309/ajg.0000000000002644] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Accepted: 12/20/2023] [Indexed: 01/05/2024]
Abstract
INTRODUCTION Eosinophilic gastritis (EoG) and duodenitis (EoD) are rare conditions that are poorly understood. Our aim was to describe the natural history of children with varying degrees of gastric or duodenal eosinophilia with respect to disease complications and histologic and endoscopic longitudinal trajectories. METHODS The electronic medical record at a tertiary children's hospital was queried to identify patients with EoG, EoD, or EoG + EoD who were cared for between January 2010 and 2022. Multiple logistic regression was performed to explore associations between baseline features and persistence/recurrence of eosinophilia or complications remote from diagnosis. RESULTS We identified 151 patients: 92 with EoG, 24 with EoD, 12 with EoG + EoD, and 23 with tissue eosinophilia but did not meet histologic criteria for EoG or EoD (low grade). The average age at diagnosis was 10.6 years, and average follow-up was 5.8 years. Twenty-five percent of patients with EoG or EoD had persistence/recurrence of eosinophilia; this was associated with increases in the EoG Endoscopic Reference Score (adjusted odds ratio [aOR] 1.34, confidence interval [CI] 1.03-1.74) on diagnostic endoscopy. Eighteen percent suffered from disease complications, and development of late complications was associated with presenting with a complication (aOR 9.63, CI 1.09-85.20), severity of duodenal endoscopic abnormalities (aOR 8.74, CI 1.67-45.60), and increases in the EoG Endoscopic Reference Score (aOR 1.70, CI 1.11-2.63). DISCUSSION Patients with gastric and duodenal eosinophilia should be followed closely to monitor for recurrence and complications, especially those presenting with endoscopic abnormalities or complications.
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Affiliation(s)
- Laura A Quinn
- Digestive Health Institute, Children's Hospital Colorado, Gastrointestinal Eosinophilic Diseases Program, Section of Pediatric Gastroenterology, Hepatology and Nutrition, University of Colorado School of Medicine, Aurora, Colorado, USA
| | - Cassandra Burger
- Digestive Health Institute, Children's Hospital Colorado, Gastrointestinal Eosinophilic Diseases Program, Section of Pediatric Gastroenterology, Hepatology and Nutrition, University of Colorado School of Medicine, Aurora, Colorado, USA
| | - Brian Nguyen
- Department of Pathology, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA
| | - Michael A Arnold
- Department of Pathology, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA
- Department of Pathology and Laboratory Medicine, Children's Hospital Colorado, Aurora, Colorado, USA
| | - Zhaoxing Pan
- Child Health Biostatistics Core, Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA
| | - Glenn T Furuta
- Digestive Health Institute, Children's Hospital Colorado, Gastrointestinal Eosinophilic Diseases Program, Section of Pediatric Gastroenterology, Hepatology and Nutrition, University of Colorado School of Medicine, Aurora, Colorado, USA
| | - Maureen E Bauer
- Gastrointestinal Eosinophilic Diseases Program, Section of Allergy and Immunology, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, Colorado, USA
| | - Calies Menard-Katcher
- Digestive Health Institute, Children's Hospital Colorado, Gastrointestinal Eosinophilic Diseases Program, Section of Pediatric Gastroenterology, Hepatology and Nutrition, University of Colorado School of Medicine, Aurora, Colorado, USA
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Alsohaibani FI, Peedikayil MC, Alzahrani MA, Azzam NA, Almadi MA, Dellon ES, Al-Hussaini AA. Eosinophilic esophagitis: Current concepts in diagnosis and management. Saudi J Gastroenterol 2024; 30:210-227. [PMID: 38752302 PMCID: PMC11379248 DOI: 10.4103/sjg.sjg_50_24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2024] [Revised: 04/19/2024] [Accepted: 04/21/2024] [Indexed: 07/30/2024] Open
Abstract
ABSTRACT Eosinophilic esophagitis is an antigen-mediated chronic inflammatory disorder that has risen in incidence and prevalence over the past 2 decades. The clinical presentation is variable and consists of mainly esophageal symptoms such as dysphagia, heartburn, food impaction, and vomiting. Current management relies on dietary elimination, proton-pump inhibitors, and topical corticosteroids with different response rates and relapses after treatment discontinuation. With a better understanding of the underlying pathophysiology, many molecules emerged recently as targeted treatment including dupilumab (IL4/IL13 blocker), as the first FDA-approved biological treatment, which has changed the management paradigm.
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Affiliation(s)
- Fahad I. Alsohaibani
- Department of Medicine, Section of Gastroenterology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - Musthafa C. Peedikayil
- Department of Medicine, Section of Gastroenterology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | | | - Nahla A. Azzam
- Division of Gastroenterology, Department of Medicine, College of Medicine, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia
| | - Majid A. Almadi
- Division of Gastroenterology, Department of Medicine, College of Medicine, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia
| | - Evan S. Dellon
- Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, USA
| | - Abdulrahman A. Al-Hussaini
- Division of Pediatric Gastroenterology, Children’s Specialized Hospital, King Fahad Medical City, Riyadh, Saudi Arabia
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de Bortoli N, Visaggi P, Penagini R, Annibale B, Baiano Svizzero F, Barbara G, Bartolo O, Battaglia E, Di Sabatino A, De Angelis P, Docimo L, Frazzoni M, Furnari M, Iori A, Iovino P, Lenti MV, Marabotto E, Marasco G, Mauro A, Oliva S, Pellegatta G, Pesce M, Privitera AC, Puxeddu I, Racca F, Ribolsi M, Ridolo E, Russo S, Sarnelli G, Tolone S, Zentilin P, Zingone F, Barberio B, Ghisa M, Savarino EV. The 1st EoETALY Consensus on the Diagnosis and Management of Eosinophilic Esophagitis - Definition, Clinical Presentation and Diagnosis. Dig Liver Dis 2024; 56:951-963. [PMID: 38423918 DOI: 10.1016/j.dld.2024.02.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2024] [Revised: 01/26/2024] [Accepted: 02/09/2024] [Indexed: 03/02/2024]
Abstract
Eosinophilic esophagitis (EoE) is a chronic type 2-mediated inflammatory disease of the esophagus that represents the most common eosinophilic gastrointestinal disease. Experts in the field of EoE across Italy (i.e., EoETALY Consensus Group) including gastroenterologists, endoscopists, allergologists/immunologists, and paediatricians conducted a Delphi process to develop updated consensus statements for the management of patients with EoE and update the previous position paper of the Italian Society of Gastroenterology (SIGE) in light of recent evidence. Grading of the strength and quality of the evidence of the recommendations was performed using accepted GRADE criteria. The guideline is divided in two documents: Part 1 includes three chapters, namely 1) definition, epidemiology, and pathogenesis; 2) clinical presentation and natural history, and 3) diagnosis, while Part 2 includes two chapters: 4) treatment and 5) monitoring and follow-up. This document has received the endorsement of three Italian national societies including the SIGE, the Italian Society of Neurogastroenterology and Motility (SINGEM), and the Italian Society of Allergology, Asthma, and Clinical Immunology (SIAAIC). With regards to patients' involvement, these guidelines involved the contribution of members of ESEO Italia, the Italian Association of Families Against EoE.
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Affiliation(s)
- Nicola de Bortoli
- Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Pierfrancesco Visaggi
- Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Roberto Penagini
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Bruno Annibale
- Department of Medical-Surgical Sciences and Translational Medicine, Sant'Andrea Hospital, Sapienza University of Rome, Rome 00189, Italy
| | - Federica Baiano Svizzero
- Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Giovanni Barbara
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | | | - Edda Battaglia
- Gastroenterology Unit ASLTO4, Chivasso - Ciriè - Ivrea, Italy
| | - Antonio Di Sabatino
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, Pavia 27100, Italy; First Department of Internal Medicine, IRCCS San Matteo Hospital Foundation, Pavia 27100, Italy
| | - Paola De Angelis
- Digestive Endoscopy Unit - Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Ludovico Docimo
- Department of Advanced Medical and Surgical Sciences, University of Campania "L. Vanvitelli", Naples, Italy
| | - Marzio Frazzoni
- Digestive Pathophysiology Unit and Digestive Endoscopy Unit, Azienda Ospedaliero Universitaria di Modena, Ospedale Civile di Baggiovara, Modena, Italy
| | - Manuele Furnari
- Division of Gastroenterology, Department of Internal Medicine, University of Genoa, Genoa, Italy; IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Andrea Iori
- Gastroenterology and Digestive Endoscopy Unit,' Santa Chiara' Hospital, Trento, Italy
| | - Paola Iovino
- Gastrointestinal Unit, Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, Baronissi 84084, Italy
| | - Marco Vincenzo Lenti
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, Pavia 27100, Italy
| | - Elisa Marabotto
- Division of Gastroenterology, Department of Internal Medicine, University of Genoa, Genoa, Italy; IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Giovanni Marasco
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Aurelio Mauro
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Policlinico San Matteo, Pavia 27100, Italy
| | - Salvatore Oliva
- Maternal and Child Health Department, Pediatric Gastroenterology and Liver Unit, Sapienza - University of Rome, Italy
| | - Gaia Pellegatta
- Endoscopic Unit, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Milan, Italy; Department of Biomedical Sciences, Humanitas University, Humanitas University, Via Rita Levi Montalcini 4, 20090 Pieve Emanuele, Milan, Italy
| | - Marcella Pesce
- Department of clinical medicine and surgery, University of Naples Federico II, Naples, Italy
| | | | - Ilaria Puxeddu
- Immunoallergology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Italy
| | - Francesca Racca
- Personalized Medicine, Asthma and Allergy Clinic, IRCCS Humanitas Research Hospital, Rozzano - Milan, Italy
| | - Mentore Ribolsi
- Unit of Gastroenterology and Digestive Endoscopy, Campus Bio Medico University, Rome, Italy
| | - Erminia Ridolo
- Allergy Unit, Department of Internal Medicine, University Hospital of Parma, Parma, Italy
| | - Salvatore Russo
- Gastroenterology and Digestive Endoscopy Unit, Azienda Ospedaliera Universitaria of Modena, Modena, Italy
| | - Giovanni Sarnelli
- Department of clinical medicine and surgery, University of Naples Federico II, Naples, Italy
| | - Salvatore Tolone
- Division of General, Oncological, Mini-Invasive and Obesity Surgery, University of Campania "Luigi Vanvitelli", Naples 80131, Italy
| | - Patrizia Zentilin
- Division of Gastroenterology, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Fabiana Zingone
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Via Giustiniani 2, Padua 35128, Italy
| | - Brigida Barberio
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Via Giustiniani 2, Padua 35128, Italy
| | - Matteo Ghisa
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Via Giustiniani 2, Padua 35128, Italy
| | - Edoardo Vincenzo Savarino
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Via Giustiniani 2, Padua 35128, Italy.
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12
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Chang JW, Jensen ET. Epidemiologic and Clinical Clues to the Etiology of Eosinophilic Esophagitis. Immunol Allergy Clin North Am 2024; 44:145-155. [PMID: 38575214 PMCID: PMC11003716 DOI: 10.1016/j.iac.2023.12.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/06/2024]
Abstract
Despite the rising prevalence and incidence of eosinophilic esophagitis (EoE), the etiology and pathophysiology remain unknown. Studies to date suggest that complex interactions between genetic and environmental risk factors result in the development and presentation of disease. Examining environmental factors both in the early life and later life exposures offers potential clues for the development of EoE, although challenges exist in making causal inferences due to diagnostic delay and access, ascertainment biases, and misclassification of cases. The authors review studies supporting early life factors as etiologic factors in the development of EoE.
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Affiliation(s)
- Joy W Chang
- Division of Gastroenterology, Department of Internal Medicine, 3912 Taubman Center, 1500 East Medical Center Drive, SPC 5362, Ann Arbor, MI 48109, USA.
| | - Elizabeth T Jensen
- Department of Epidemiology and Prevention, Wake Forest University School of Medicine, 475 Vine Street, Winston-Salem, NC 27101, USA
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13
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Muir AB, Bailey DD, Mehta P. Embracing Diversity, Equity, Inclusion, and Accessibility in Eosinophilic Gastrointestinal Diseases. Immunol Allergy Clin North Am 2024; 44:293-298. [PMID: 38575224 DOI: 10.1016/j.iac.2024.01.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/06/2024]
Abstract
Eosinophilic gastrointestinal diseases (EGIDs) including eosinophilic esophagitis (EoE) are rare diseases in which eosinophils abnormally infiltrate the gastrointestinal tract. Because these are rare diseases, there is limited information regarding race and ethnicity in EGIDs and even less is known about the impact of socioeconomic factors. There is some evidence that access to care in rural settings may be affecting epidemiologic understanding of EGIDs in the pediatric populations. Future work should try to evaluate bias in research and strive for representation in clinical trials and medicine.
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Affiliation(s)
- Amanda B Muir
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Children's Hospital of Philadelphia, 2057 Lombard Street, Philadelphia, PA 19146, USA
| | - Dominique D Bailey
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons/New York-Presbyterian Morgan Stanley Children's Hospital, 3959 Broadway, New York, NY 10032, USA
| | - Pooja Mehta
- Section of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Children's Hospital Colorado, University of Colorado School of Medicine, 13123 East 16th Avenue, B290, Aurora, CO 80045, USA.
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Gupta M, Grinman M. Diagnostic et prise en charge de l’œsophagite à éosinophiles. CMAJ 2024; 196:E568-E576. [PMID: 38684286 PMCID: PMC11057888 DOI: 10.1503/cmaj.230378-f] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/02/2024] Open
Affiliation(s)
- Milli Gupta
- Divisions de gastroentérologie et d'hépatologie (Gupta) et de médecine interne générale (Grinman), Département de médecine, École de médecine Cumming, Université de Calgary, Calgary, Alb.
| | - Michelle Grinman
- Divisions de gastroentérologie et d'hépatologie (Gupta) et de médecine interne générale (Grinman), Département de médecine, École de médecine Cumming, Université de Calgary, Calgary, Alb
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15
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Goyal R, Kamboj AK, Snyder DL. Eosinophilic Esophagitis: Clinical Pearls for Primary Care Providers and Gastroenterologists. Mayo Clin Proc 2024; 99:640-648. [PMID: 38569813 DOI: 10.1016/j.mayocp.2023.12.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Revised: 12/10/2023] [Accepted: 12/28/2023] [Indexed: 04/05/2024]
Abstract
Eosinophilic esophagitis (EoE) is a chronic and progressive immune-mediated esophageal disorder. Given its increasing incidence, it is now a leading cause of dysphagia and food impaction in the United States. Eosinophilic esophagitis is most common in adult White men and has a high concurrence rate with other atopic conditions like allergic rhinitis, bronchial asthma, and eczema. The initial presentation includes symptoms of esophageal dysfunction, classically solid-food dysphagia. Without treatment, inflammation can progress to fibrosis with the formation of strictures, leading to complications such as food impaction. It is a clinicopathologic disease requiring compatible clinical symptoms and histologic evidence of eosinophil-predominant inflammation of the esophageal epithelium with more than 15 eosinophils per high-power field. The mainstay of management includes the 3 d's (diet, drugs, dilation): dietary modifications to eliminate trigger food groups; medications including proton pump inhibitors, swallowed topical glucocorticoids, and dupilumab; and esophageal dilation to manage strictures. Various elimination diets have been found to be effective, including 1-food, 2-food, 4-food, and 6-food elimination diets. Dupilumab, a humanized monoclonal antibody that regulates interleukin 4 and 13 signaling pathways, has shown promising results in clinical trials and was approved by the Food and Drug Administration in 2022 for use in EoE. Symptom alleviation, although important, is not the sole end point of treatment in EoE as persistent inflammation, even in the absence of symptoms, can lead to esophageal fibrosis and stricture formation over time. The chronic nature and high recurrence rates of EoE warrant maintenance therapy in patients with EoE after initial remission is achieved.
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Affiliation(s)
- Rohit Goyal
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | - Amrit K Kamboj
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | - Diana L Snyder
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN.
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Cameron BA, Anderson CW, Jensen ET, Dellon ES. Vitamin D Levels as a Potential Modifier of Eosinophilic Esophagitis Severity in Adults. Dig Dis Sci 2024; 69:1287-1292. [PMID: 38183560 DOI: 10.1007/s10620-023-08264-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2023] [Accepted: 11/27/2023] [Indexed: 01/08/2024]
Abstract
BACKGROUND Vitamin D deficiency is associated with atopic and immune-mediated diseases but has not been extensively assessed in eosinophilic esophagitis (EoE). We aimed to assess if vitamin D levels in newly diagnosed EoE patients were lower than in non-EoE controls and examine levels in relation to EoE clinical features. METHODS This secondary analysis of a prospective cohort study used data and biosamples from adults who underwent outpatient esophagogastroduodenoscopy. Before each procedure, blood was obtained and stored at -80oC. Serum 25-hydroxy-vitamin D3 (25(OH)D3) was measured by ELISA. Levels for cases and controls were compared at baseline. Within cases, 25(OH)D3 levels were compared for clinical, endoscopic, and histologic measures. RESULTS We analyzed 40 EoE and 40 non-EoE controls. Mean serum 25(OH)D3 level was slightly lower in EoE patients than controls (30.9 ± 15.3 ng/mL vs. 35.9 ± 15.4; p = 0.15). After controlling for age, sex, and race, adjusted levels were 10.8 ng/mL lower in EoE patients (95% CI: -19.0, -2.5), but 25(OH)D3 deficiency (< 20ng/mL) was similar in cases and controls (20% vs. 15%; p = 0.56). Levels of 25(OH)D3 were not associated with differences in clinical or endoscopic features of EoE, and EREFS and eosinophil counts did not significantly correlate with 25(OH)D3 levels (R of -0.28 [p = 0.08] and - 0.01 [p = 0.93], respectively). 25(OH)D3 levels were lower in EoE cases with lamina propria fibrosis (23.2 ± 9.6 vs. 45.0 ± 17.7; p = 0.03). CONCLUSIONS After adjusting for age, sex, and race, 25(OH)D3 levels were lower in EoE cases than controls, but deficiency was not common. 25(OH)D3 levels were generally similar across most EoE disease features.
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Affiliation(s)
- Brenderia A Cameron
- Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, CB#7080 Bioinformatics Building 130 Mason Farm Rd. UNC-CH, Chapel Hill, NC, 27599-7080, USA
| | - Carlton W Anderson
- 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
| | - Elizabeth T Jensen
- Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, CB#7080 Bioinformatics Building 130 Mason Farm Rd. UNC-CH, Chapel Hill, NC, 27599-7080, USA
- Department of Epidemiology and Prevention, Wake Forest University School of Medicine, Winston-Salem, NC, USA
- Department of Internal Medicine, Gastroenterology Section, Wake Forest University School of Medicine, Winston-Salem, NC, USA
| | - Evan S Dellon
- Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, CB#7080 Bioinformatics Building 130 Mason Farm Rd. UNC-CH, Chapel Hill, NC, 27599-7080, USA.
- 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.
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Elghoudi A, Zourob D, Al Atrash E, Alshamsi F, Alkatheeri M, Narchi H, Bitar R. Evolving strategies: Enhancements in managing eosinophilic esophagitis in pediatric patients. World J Clin Pediatr 2024; 13:89580. [PMID: 38596434 PMCID: PMC11000055 DOI: 10.5409/wjcp.v13.i1.89580] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Revised: 12/26/2023] [Accepted: 01/16/2024] [Indexed: 03/06/2024] Open
Abstract
Eosinophilic esophagitis is a newly recognized disease first described about 50 years ago. The definition, diagnosis, and management have evolved with new published consensus guidelines and newly approved treatment available to pediatricians, enabling a better understanding of this disease and more targeted treatment for patients. We describe the definition, presentation, and diagnosis of eosinophilic esophagitis including management, challenges, and future directions in children. The definition, diagnosis, and management of eosinophilic esophagitis have evolved over the last 50 years. Consensus guidelines and newly approved biologic treatment have enabled pediatricians to better understand this disease and allow for more targeted treatment for patients. We describe the definition, presentation, diagnosis, management, and treatment in addition to the challenges and future directions of eosinophilic esophagitis management in children.
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Affiliation(s)
- Ahmed Elghoudi
- Department of Pediatric, Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates
| | - Doaa Zourob
- Division of Pediatric Gastroenterology, Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates
| | - Eman Al Atrash
- Division of Pediatric Gastroenterology, Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates
| | - Fatima Alshamsi
- Pediatric Residency Program, Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates
| | - Manal Alkatheeri
- Division of Pediatric Gastroenterology, Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates
| | - Hassib Narchi
- College of Medicine and Health Sciences, United Arab Emirates University, Alain, Abu Dhabi, United Arab Emirates
| | - Rana Bitar
- Division of Pediatric Gastroenterology, Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates
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18
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Eussen SRBM, Wielders S, de Rooij WE, Van Ampting MTJ, Van Esch BCAM, de Vries JHM, Bredenoord AJ, Vlieg‐Boerstra B. Dietary composition of adult eosinophilic esophagitis patients is related to disease severity. Immun Inflamm Dis 2024; 12:e1206. [PMID: 38456617 PMCID: PMC10921897 DOI: 10.1002/iid3.1206] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2023] [Revised: 02/07/2024] [Accepted: 02/15/2024] [Indexed: 03/09/2024] Open
Abstract
BACKGROUND In addition to the elimination diet, dietary composition may influence disease severity in patients with eosinophilic esophagitis (EoE) through modulation of the immune response. AIM To explore the immunomodulatory role of nutrition before and during elimination diet in adult EoE patients. METHODS Nutritional intake was assessed in 39 Dutch adult EoE patients participating in the Supplemental Elemental Trial (Dutch trial registry NL6014, NTR6778) using 3-day food diaries. In this randomized controlled trial, diagnosed patients received either a four-food elimination diet alone (FFED) or FFED with addition of an amino acid-based formula for 6 weeks. Multiple linear regression analyses were performed to assess associations between the intake of nutrients and food groups per 1000 kCal and peak eosinophil count/high power field (PEC), both at baseline and after 6 weeks. RESULTS At baseline, we found a statistically significant negative (thus favorable) relationship between the intake of protein, total fat, phosphorus, zinc, vitamin B12, folate, and milk products and PEC (p < .05), while calcium (p = .058) and full-fat cheese/curd (p = .056) were borderline (favorably) significant. In contrast, total carbohydrates, prepacked fruit juice, and white bread were significantly positively (unfavorable) related to PEC (p < .05), while ultra-processed meals (p = .059) were borderline (unfavorably) significant. After dietary intervention, coffee/tea were significantly negatively (favorably) related to PEC, hummus/legumes were significantly positively (unfavorably) related with PEC, while peanuts were borderline significantly positively related (p = .058). CONCLUSION Dietary composition may be related to inflammation in adult EoE patients. High-quality and anti-inflammatory diets may be a promising adjuvant therapy in the dietary management of EoE.
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Affiliation(s)
| | - Sanne Wielders
- Division of Human NutritionWageningen UniversityWageningenThe Netherlands
| | - Willemijn E. de Rooij
- Department of Gastroenterology & HepatologyAmsterdam University Medical CenterAmsterdamThe Netherlands
| | | | - Betty C. A. M. Van Esch
- Danone Nutricia ResearchUtrechtThe Netherlands
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of ScienceUtrecht UniversityUtrechtThe Netherlands
| | | | - Albert J. Bredenoord
- Department of Gastroenterology & HepatologyAmsterdam University Medical CenterAmsterdamThe Netherlands
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Affiliation(s)
- Milli Gupta
- Divisions of Gastroenterology and Hepatology (Gupta), and General Internal Medicine (Grinman), Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alta.
| | - Michelle Grinman
- Divisions of Gastroenterology and Hepatology (Gupta), and General Internal Medicine (Grinman), Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alta
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20
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Roberts SE, Morrison‐Rees S, Thapar N, Williams JG. Incidence and prevalence of eosinophilic oesophagitis across Europe: A systematic review and meta-analysis. United European Gastroenterol J 2024; 12:89-102. [PMID: 37921701 PMCID: PMC10859717 DOI: 10.1002/ueg2.12465] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2023] [Accepted: 08/15/2023] [Indexed: 11/04/2023] Open
Abstract
BACKGROUND Several studies have reported large increases in the incidence of eosinophilic oesophagitis (EoE) in the last 20 years. We aimed to systematically review the incidence and prevalence of EoE, focused on all European countries. METHODS Systematic review and meta-analysis up to 31 December 2022, based on PubMed, CINAHL and extensive hand searching of reference lists. Twenty-five eligible studies were identified and included. RESULTS For both adults and children, the highest EoE incidence and prevalence have been reported from regional studies in Spain. EoE incidence for both adults and children was significantly lower (p < 0.001) in nationwide studies (meta-analysis = 3.64 per 100,000 person-years overall) compared with regional or centre-based studies (7.16). EoE incidence and prevalence were significantly higher (p < 0.001) in adults than children. All studies that reported on longitudinal trends in EoE incidence showed increases over time, more markedly during more recent years. Larger increases in incidence tend to refer to regional rather than nationwide studies; from Spain, Switzerland and Denmark, both for paediatric and adult age groups. Increases in EoE incidence 100,000 person-years were larger than for incidence per number of diagnostic endoscopies. The most frequently reported co-morbidities in adults were rhinitis, followed by asthma, food allergy and gastroesophageal reflux disease, and in children, erosive oesophagitis, asthma, food allergy and rhinitis. CONCLUSIONS The incidence of EoE has increased in Europe over the last 30 years, exceeding increases in the volume of oesophago-gastro-duodenoscopies performed. The patchy and low incidence and prevalence of EoE generally in Europe and compared with North America, may reflect a lack of clinical awareness and research focus rather than a genuinely low incidence of EoE. A co-ordinated Europe-wide study that uses standardised methodology is urgently needed to provide a comprehensive picture of EoE incidence and prevalence across Europe.
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Affiliation(s)
| | | | - Nikhil Thapar
- Department of Paediatric GastroenterologyQueensland Children's HospitalBrisbaneAustralia
- School of MedicineUniversity of QueenslandSt Lucia, BrisbaneAustralia
- Stem Cells and Regenerative MedicineUCL Great Ormond Street Institute of Child HealthLondonUK
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Low EE, Dellon ES. Review article: Emerging insights into the epidemiology, pathophysiology, diagnostic and therapeutic aspects of eosinophilic oesophagitis and other eosinophilic gastrointestinal diseases. Aliment Pharmacol Ther 2024; 59:322-340. [PMID: 38135920 PMCID: PMC10843587 DOI: 10.1111/apt.17845] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2023] [Revised: 09/08/2023] [Accepted: 12/13/2023] [Indexed: 12/24/2023]
Abstract
BACKGROUND Eosinophilic gastrointestinal diseases (EGIDs) are chronic, immune-mediated disorders characterised clinically by gastrointestinal symptoms and histologically by a pathologic increase in eosinophil-predominant inflammation in the gastrointestinal tract, in the absence of secondary causes of eosinophilia. AIMS To highlight emerging insights and research efforts into the epidemiology, pathophysiology, diagnostic and therapeutic aspects of eosinophilic oesophagitis (EoE) and non-EoE EGIDs, and discuss key remaining knowledge gaps. METHODS We selected and reviewed original research, retrospective studies, case series, randomised controlled trials, and meta-analyses. RESULTS Standardised nomenclature classifies EGIDs as EoE, eosinophilic gastritis (EoG), eosinophilic enteritis (EoN), and eosinophilic colitis (EoC). Incidence and prevalence of EoE are rising, emphasising the need to better understand how environmental risk factors and genetic features interact. Advances in understanding EoE pathophysiology have led to clinical trials of targeted therapy and the approval (in the United States) of dupilumab for EoE. Several therapies that are under investigation hope to satisfy both histologic and clinical targets. For non-EoE EGIDs, efforts are focused on better defining clinical and histopathologic disease determinants and natural history, as well as establishing new therapies. CONCLUSIONS Unmet needs for research are dramatically different for EoE and non-EoE EGIDs. In EoE, non-invasive diagnostic tests, clinicopathologic models that determine the risk of disease progression and therapeutic failure, and novel biologic therapies are emerging. In contrast, in non-EoE EGIDs, epidemiologic trends, diagnostic histopathologic thresholds, and natural history models are still developing for these more rare disorders.
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Affiliation(s)
- Eric E. Low
- Division of Gastroenterology and Hepatology, University of California San Diego, San Diego, CA, USA
| | - Evan S. Dellon
- Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, NC, USA
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22
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Ocampo AA, Xue Z, Chang NC, Thakkar KP, Reddy SB, Greenberg SB, Lee CJ, Ketchem CJ, Redd WD, Eluri S, Reed CC, Dellon ES. Clinical Features and Treatment Response to Topical Steroids in Ethnic and Racial Minority Patients With Eosinophilic Esophagitis. Am J Gastroenterol 2024; 119:262-269. [PMID: 37782465 PMCID: PMC10872844 DOI: 10.14309/ajg.0000000000002532] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Accepted: 09/05/2023] [Indexed: 10/03/2023]
Abstract
INTRODUCTION Differences in eosinophilic esophagitis (EoE) presentation and outcomes by ethnicity or race remain understudied. We aimed to determine whether EoE patients of Hispanic/Latinx ethnicity or non-White race have differences in presentation at diagnosis or response to topical corticosteroid (tCS) treatment. METHODS This retrospective cohort study included subjects of any age with a new diagnosis of EoE and documentation of ethnicity or race. For those who had treatment with tCS and follow-up endoscopy/biopsy, we assessed histologic response (<15 eosinophils/hpf), global symptom response, and endoscopic response. Hispanic EoE patients were compared with non-Hispanics at baseline and before and after treatment. The same analyses were repeated for White vs non-Whites. RESULTS Of 1,026 EoE patients with ethnicity data, just 23 (2%) were Hispanic. Most clinical features at presentation were similar to non-Hispanic EoE patients but histologic response to tCS was numerically lower (38% vs 57%). Non-White EoE patients (13%) were younger at diagnosis and had less insurance, lower zip code-level income, shorter symptom duration, more vomiting, less dysphagia and food impaction, fewer typical endoscopic features, and less dilation. Of 475 patients with race data treated with tCS, non-Whites had a significantly lower histologic response rate (41% vs 59%; P = 0.01), and odds of histologic response remained lower after controlling for potential confounders (adjusted odds ratio 0.40, 95% confidence intervals: 0.19-0.87). DISCUSSION Few EoE patients at our center were Hispanic, and they had similar clinical presentations as non-Hispanics. The non-White EoE group was larger, and presentation was less dysphagia-specific. Non-White patients were also less than half as likely to respond to tCS.
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Affiliation(s)
- Adolfo A. Ocampo
- Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Department of Medicine; University of North Carolina School of Medicine, Chapel Hill, NC
| | - Zeyun Xue
- Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Department of Medicine; University of North Carolina School of Medicine, Chapel Hill, NC
| | - Nicole C. Chang
- Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Department of Medicine; University of North Carolina School of Medicine, Chapel Hill, NC
| | - Kisan P. Thakkar
- Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Department of Medicine; University of North Carolina School of Medicine, Chapel Hill, NC
| | - Sumana B. Reddy
- Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Department of Medicine; University of North Carolina School of Medicine, Chapel Hill, NC
| | - Sydney B. Greenberg
- Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Department of Medicine; University of North Carolina School of Medicine, Chapel Hill, NC
| | - Christopher J. Lee
- Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Department of Medicine; University of North Carolina School of Medicine, Chapel Hill, NC
| | - Corey J. Ketchem
- Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Department of Medicine; University of North Carolina School of Medicine, Chapel Hill, NC
| | - Walker D. Redd
- Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Department of Medicine; University of North Carolina School of Medicine, Chapel Hill, NC
| | - Swathi Eluri
- Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Department of Medicine; University of North Carolina School of Medicine, Chapel Hill, NC
| | - Craig C. Reed
- Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Department of Medicine; University of North Carolina School of Medicine, Chapel Hill, NC
| | - 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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Kiran A, Dellon ES, Reed CC. Retrospective cohort study: Effect of age as a barrier to diagnosis of eosinophilic oesophagitis. Aliment Pharmacol Ther 2024; 59:260-268. [PMID: 37877160 DOI: 10.1111/apt.17781] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2023] [Revised: 07/18/2023] [Accepted: 10/13/2023] [Indexed: 10/26/2023]
Abstract
BACKGROUND Prior work suggests eosinophilic oesophagitis (EoE) is rare in those aged over 65 years. However, elderly patients with EoE experience a substantial diagnostic delay from symptom onset to diagnosis. AIMS To assess if age predicted whether oesophageal biopsies were obtained in patients with EoE symptoms, what clinical features predict EoE in the elderly, and if EoE phenotype differs between elderly and non-elderly patients. METHODS We conducted a retrospective cohort study utilising the University of North Carolina (UNC) electronic medical record, EoE clinicopathologic database and UNC endoscopy software from July 2008 to April 2021. A sample of 193 elderly and non-elderly patients with dysphagia, chest pain and/or heartburn were assembled. Patients with EoE were newly diagnosed per contemporaneous guidelines. Patient demographics, clinical characteristics and procedural data were extracted. Summary statistics, bivariate and multivariate analyses were performed. RESULTS Of 193 patients, we included 91 elderly (47%) and 102 non-elderly (53%). Age independently predicted the odds of biopsies (adjusted odds ratio (aOR): 0.44 elderly vs. non-elderly; 95% CI: 0.21-0.92). Endoscopic features of EoE, but not symptoms, were more common in elderly than non-EoE elderly patients. Elderly patients with EoE differed from non-elderly only by time to diagnosis (aOR per year of symptoms preceding diagnosis: 1.08, 95% CI: 1.04-1.11). CONCLUSIONS Elderly patients with EoE have <50% the odds of oesophageal biopsies. There were no significant differences between elderly and non-elderly EoE patients, although endoscopic features helped discriminate the two groups. Our findings suggest that older age represents a barrier to EoE diagnosis.
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Affiliation(s)
- Akshatha Kiran
- Center for Esophageal Diseases and Swallowing, 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
| | - Evan S Dellon
- Center for Esophageal Diseases and Swallowing, 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
| | - Craig C Reed
- Center for Esophageal Diseases and Swallowing, 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
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24
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El-Khoury JW, Safroneeva E, Saner C, Rossel JB, Trelle S, Zwahlen M, Biedermann L, Kreienbuehl A, Greuter T, Schreiner P, Netzer P, Franke A, Brand S, Hasler C, Aepli P, Burri E, Weber A, Sempoux C, Biral R, Jochum W, Diebold J, Willi N, Straumann A, Schoepfer AM. Cohort Profile Update: The Swiss Eosinophilic Esophagitis Cohort Study (SEECS). Inflamm Intest Dis 2024; 9:165-173. [PMID: 39144837 PMCID: PMC11324224 DOI: 10.1159/000539713] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Accepted: 05/28/2024] [Indexed: 08/16/2024] Open
Abstract
Introduction The Swiss Eosinophilic Esophagitis Cohort Study (SEECS) is a national cohort that was established in 2015 with the aim of improving quality of care of affected adults with eosinophilic esophagitis (EoE). Between 2020 and 2022, paper questionnaires were gradually replaced by fully electronic data capture using Research Electronic Data Capture (REDCap®) software. We aim to provide an update of the SEECS 8 years after its launch. Methods The SEECS prospectively includes adults (≥18 years of age) with EoE as well as patients with gastroesophageal reflux disease (GERD) and healthy control subjects (HC). Upon inclusion and follow-up (typically once every 12-18 months), patients and physicians complete REDCap® questionnaires, which are available in German, French, and English. Patient-reported outcomes (PROs) and biologic findings are assessed on the same day using validated instruments (EEsAI PRO for symptoms; EoE-QoL-A for QoL; EREFS for endoscopic activity; modified EoE-HSS for histologic activity). The SEECS biobank includes biosamples from patients with EoE, GERD, and HC. Results As of July 2023, the SEECS included 778 patients (716 [92%] with EoE, 29 [3.8%] with GERD, and 33 [4.2%] HC; 559/778 [71.9%] were male). Mean age ± SD (years) at enrollment according to diagnosis was as follows: EoE 41.9 ± 12.9, GERD 53.6 ± 16.4, HC 51.7 ± 17.2. Concomitant GERD was found in 200 patients (27.9%) of the EoE cohort. Concomitant allergic disorders (asthma, rhinoconjunctivitis, eczema) were present in 500 EoE patients (74.4%). At inclusion, 686 (95.8%) of EoE patients were on ongoing treatment (orodispersible budesonide tablet [Jorveza®] in 281 patients [41%]; budesonide or fluticasone syrup or swallowed powder in 290 patients [42.3%]; proton-pump inhibitors in 162 patients [23.6%]; elimination diets in 103 patients [15%]; and esophageal dilation at last visit in 166 patients [24.2%]). A total of 8,698 biosamples were collected, of which 1,395 (16%) were used in the framework of translational research projects. Conclusion SEECS continuously grows and is operational using fully electronic data capture. SEECS offers up-to-date epidemiologic and real-world clinical efficacy data on EoE and promotes clinical and translational research.
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Affiliation(s)
- Jeanine Wakim El-Khoury
- Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne, Switzerland
| | - Ekaterina Safroneeva
- Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland
| | - Catherine Saner
- Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne, Switzerland
| | | | - Sven Trelle
- Department of Clinical Research, University of Bern, Bern, Switzerland
| | - Marcel Zwahlen
- Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland
| | - Luc Biedermann
- Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Andrea Kreienbuehl
- Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Thomas Greuter
- Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
- Division of Gastroenterology and Hepatology, Spital Wetzikon, Wetzikon, Switzerland
| | - Philipp Schreiner
- Division of Gastroenterology and Hepatology, University Hospital AKH Vienna, Vienna, Austria
| | - Peter Netzer
- GastroZentrum Netzer AG, Lindenhofspital, Bern, Switzerland
| | - Annett Franke
- Division of Gastroenterology and Hepatology, Kantonsspital St. Gallen, St. Gallen, Switzerland
| | - Stephan Brand
- Division of Gastroenterology and Hepatology, Kantonsspital St. Gallen, St. Gallen, Switzerland
| | - Chantal Hasler
- Division of Gastroenterology and Hepatology, Kantonsspital Lucerne, Lucerne, Switzerland
| | - Patrick Aepli
- Division of Gastroenterology and Hepatology, Kantonsspital Lucerne, Lucerne, Switzerland
| | - Emanuel Burri
- Division of Gastroenterology and Hepatology, University Hospital Basel, Liestal, Switzerland
| | - Achim Weber
- Division of Pathology, University Hospital Zurich, Zurich, Switzerland
| | - Christine Sempoux
- Institute of Pathology, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne, Switzerland
| | | | - Wolfram Jochum
- Institute of Pathology, Kantonsspital St. Gallen, St. Gallen, Switzerland
| | - Joachim Diebold
- Division of Pathology, Kantonsspital Luzern, Luzern, Switzerland
| | - Niels Willi
- Division of Pathology, Kantonsspital Liestal, Liestal, Switzerland
| | - Alex Straumann
- Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Alain M. Schoepfer
- Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne, Switzerland
| | - on behalf of the Swiss EoE Cohort Study Group
- Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne, Switzerland
- Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland
- Department of Clinical Research, University of Bern, Bern, Switzerland
- Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
- Division of Gastroenterology and Hepatology, Spital Wetzikon, Wetzikon, Switzerland
- Division of Gastroenterology and Hepatology, University Hospital AKH Vienna, Vienna, Austria
- GastroZentrum Netzer AG, Lindenhofspital, Bern, Switzerland
- Division of Gastroenterology and Hepatology, Kantonsspital St. Gallen, St. Gallen, Switzerland
- Division of Gastroenterology and Hepatology, Kantonsspital Lucerne, Lucerne, Switzerland
- Division of Gastroenterology and Hepatology, University Hospital Basel, Liestal, Switzerland
- Division of Pathology, University Hospital Zurich, Zurich, Switzerland
- Institute of Pathology, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne, Switzerland
- Pathologie Länggasse, Bern, Switzerland
- Institute of Pathology, Kantonsspital St. Gallen, St. Gallen, Switzerland
- Division of Pathology, Kantonsspital Luzern, Luzern, Switzerland
- Division of Pathology, Kantonsspital Liestal, Liestal, Switzerland
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25
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Samanta A, Poddar U, Kumari N, Sen Sarma M, Srivastava A, Mishra P. Eosinophilic esophagitis in children: A cross-sectional study from a tertiary care center. JGH Open 2024; 8:e13024. [PMID: 38268956 PMCID: PMC10805495 DOI: 10.1002/jgh3.13024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Revised: 11/28/2023] [Accepted: 12/03/2023] [Indexed: 01/26/2024]
Abstract
Background and Aim The prevalence of eosinophilic esophagitis (EoE) is rising in the West. However, data from the Indian subcontinent is limited. In this prospective cross-sectional study, we estimated the prevalence of EoE among children undergoing elective upper gastrointestinal endoscopy (UGIE). Methods We enrolled 200 consecutive children (123 boys, median age 10.25 years [interquartile range 8.25-14.5]) between March 2020 and November 2022 at our center. Clinical characteristics, endoscopic findings, and laboratory parameters were noted. A total of 12 mucosal biopsies (3 each from the middle and lower third of the esophagus, stomach, and duodenum) were obtained. EoE was diagnosed if the peak eosinophil count was ≥15/high-power field (HPF) in absence of gastric and duodenal eosinophilia. Results The commonest indications for UGIE were gastroesophageal reflux disease-like symptoms (29%), inflammatory bowel disease (22.5%), celiac disease (15%), and abdominal pain (13%). EoE was detected in seven children, suggesting an overall prevalence of 3.5%. Of the 20 children evaluated for dysphagia, 4 (20%) had EoE. Also, two of three (67%) children presented with food bolus impaction along with dysphagia had EoE. Of the seven children with EoE, three (43%) had bronchial asthma, two (28.5%) had peripheral eosinophilia, and one (14%) had elevated serum IgE. Trachealization and linear furrows were found in 57% and 71% cases, respectively. Four children received high-dose proton pump inhibitor (PPI) for 12 weeks, two received PPI+ stricture dilatation, and one received systemic steroids. All achieved clinical, endoscopic, and histopathological remission. Conclusion Hospital-based prevalence of EoE among children undergoing elective UGIE was 3.5%. EoE patients had favorable outcomes with PPI.
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Affiliation(s)
- Arghya Samanta
- Department of Pediatric GastroenterologySanjay Gandhi Postgraduate Institute of Medical SciencesLucknowIndia
| | - Ujjal Poddar
- Department of Pediatric GastroenterologySanjay Gandhi Postgraduate Institute of Medical SciencesLucknowIndia
| | - Niraj Kumari
- Department of PathologySanjay Gandhi Postgraduate Institute of Medical SciencesLucknowIndia
| | - Moinak Sen Sarma
- Department of Pediatric GastroenterologySanjay Gandhi Postgraduate Institute of Medical SciencesLucknowIndia
| | - Anshu Srivastava
- Department of Pediatric GastroenterologySanjay Gandhi Postgraduate Institute of Medical SciencesLucknowIndia
| | - Prabhakar Mishra
- Department of Biostatistics and Health InformaticsSanjay Gandhi Postgraduate Institute of Medical SciencesLucknowIndia
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26
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O'Connor HJ. Forty years of Helicobacter pylori infection and changes in findings at esophagogastroduodenoscopy. Helicobacter 2023; 28:e13026. [PMID: 37818739 DOI: 10.1111/hel.13026] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Revised: 09/24/2023] [Accepted: 09/26/2023] [Indexed: 10/13/2023]
Abstract
BACKGROUND It is 40 years since the discovery of Helicobacter pylori infection. Over that time major changes have occurred in esophagogastroduodenoscopy (EGD) findings. The aim of this review is to describe these changes, and the important role H. pylori infection has played in their evolution. METHODS References were identified through searches of PubMed using the search terms-endoscopy time trends, peptic ulcer disease, gastroesophageal reflux disease, upper gastrointestinal cancer, gastric polyps, H. pylori, eosinophilic gastrointestinal disorders, and celiac disease, from 1970 through December 2021. RESULTS The prevalence of H. pylori infection has fallen and consequently, H. pylori-positive peptic ulcer disease has become rare. Gastroesophageal reflux disease is now the commonest disorder diagnosed at EGD, and Barrett's esophagus has increased in parallel. Cancer of the distal stomach has fallen while esophageal adenocarcinoma and reflux-related cardia cancer have risen. Gastric polyps have changed from hyperplastic and adenomas to sporadic fundic gland polyps. Antimicrobial resistance has made H. pylori infection more difficult to eradicate. Eosinophilic gastrointestinal disorders, particularly eosinophilic esophagitis, have emerged as important new allergic disorders. Celiac disease has changed and increased. CONCLUSIONS EGD findings appear to have changed from features suggesting a H. pylori-positive "phenotype" 40 years ago to a H. pylori-negative "phenotype" today. These changes have major implications for the management of gastrointestinal disorders.
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Affiliation(s)
- Humphrey J O'Connor
- Trinity Academic Gastroenterology Group, Trinity Centre for Health Sciences, The University of Dublin, Tallaght University Hospital, Dublin, Ireland
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27
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Hahn JW, Lee K, Shin JI, Cho SH, Turner S, Shin JU, Yeniova AÖ, Koyanagi A, Jacob L, Smith L, Fond G, Boyer L, Lee SW, Kwon R, Kim S, Shin YH, Rhee SY, Moon JS, Ko JS, Yon DK, Papadopoulos NG. Global Incidence and Prevalence of Eosinophilic Esophagitis, 1976-2022: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol 2023; 21:3270-3284.e77. [PMID: 37331411 DOI: 10.1016/j.cgh.2023.06.005] [Citation(s) in RCA: 65] [Impact Index Per Article: 32.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Revised: 05/07/2023] [Accepted: 06/02/2023] [Indexed: 06/20/2023]
Abstract
BACKGROUND AND AIMS Owing to 2018 expanded diagnostic criteria for eosinophilic esophagitis (EoE) and thus a possible increase in diagnosis, previous studies on the global incidence and prevalence of EoE may need to be updated. We aimed to describe global, regional, and national trends in the incidence and prevalence of EoE from 1976 to 2022 and analyze their associations with geographic, demographic, and social factors through a systematic review. METHODS We searched the PubMed/MEDLINE, Embase, CINAHL, Google Scholar, and Cochrane databases from their inception dates to December 20, 2022, for studies that reported the incidence or prevalence of EoE in the general population. We calculated the global incidence and prevalence of EoE using pooled estimates with 95% confidence intervals (CIs) and performed subgroup analysis based on age, sex, race, geographical area, World Bank income group, and diagnostic criteria of EoE. RESULTS Forty studies met the eligibility criteria, including over 288 million participants and 147,668 patients with EoE from 15 countries across the five continents. The global pooled incidence and prevalence of EoE were 5.31 cases per 100,000 inhabitant-years (95% CI, 3.98-6.63; number of studies, 27; sample population, 42,191,506) and 40.04 cases per 100,000 inhabitant-years (95% CI, 31.10-48.98; number of studies, 20; sample population, 30,467,177), respectively. The pooled incidence of EoE was higher in high-income countries (vs low- or middle-income countries), males, and North America (vs Europe and Asia). The global prevalence of EoE followed a similar pattern. The pooled prevalence of EoE gradually increased from 1976 to 2022 (1976-2001; 8.18; 95% CI, 3.67-12.69 vs 2017-2022; 74.42; 95% CI, 39.66-109.19 cases per 100,000 inhabitant-years). CONCLUSIONS The incidence and prevalence of EoE have increased substantially and vary widely across the world. Further research is needed to evaluate the incidence and prevalence of EoE in Asia, South America, and Africa.
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Affiliation(s)
- Jong Woo Hahn
- Department of Pediatrics, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Pediatrics, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Kwanjoo Lee
- Digestive Disease Center, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Republic of Korea
| | - Jae Il Shin
- Department of Pediatrics, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Seong Ho Cho
- Division of Allergy-Immunology, University of South Florida Morsani College of Medicine, Tampa, Florida
| | - Stephen Turner
- Maternity and Child Health Division, NHS Grampian Aberdeen, United Kingdom
| | - Jung U Shin
- Department of Dermatology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Republic of Korea
| | - Abdullah Özgür Yeniova
- Division of Gastroenterology, Department of Internal Medicine, Tokat Gaziosmanpaşa University Faculty of Medicine, Tokat, Turkey
| | - Ai Koyanagi
- Research and Development Unit, Parc Sanitari Sant Joan de Deu, CIBERSAM, ISCIII, Barcelona, Spain; Catalan Institute for Research and Advanced Studies (ICREA), Pg. Lluis Companys, Barcelona, Spain
| | - Louis Jacob
- Research and Development Unit, Parc Sanitari Sant Joan de Deu, CIBERSAM, ISCIII, Barcelona, Spain; Faculty of Medicine, University of Versailles Saint-Quentin-en-Yvelines, Montigny-le-Bretonneux, France
| | - Lee Smith
- Centre for Health, Performance and Wellbeing, Anglia Ruskin University, Cambridge, United Kingdom
| | - Guillaume Fond
- AP-HM, Aix-Marseille University, CEReSS, Health Service Research and Quality of Life Center, Marseille, France; FondaMental Foundation, Creteil, France
| | - Laurent Boyer
- AP-HM, Aix-Marseille University, CEReSS, Health Service Research and Quality of Life Center, Marseille, France; FondaMental Foundation, Creteil, France
| | - Seung Won Lee
- Department of Precision Medicine, Sungkyunkwan University College of Medicine, Suwon, Republic of Korea
| | - Rosie Kwon
- Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan; Center for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Center, Kyung Hee University College of Medicine, Seoul, Republic of Korea
| | - Soeun Kim
- Center for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Center, Kyung Hee University College of Medicine, Seoul, Republic of Korea
| | - Youn Ho Shin
- Department of Pediatrics, The Catholic University of Korea, Yeouido St. Mary's Hospital, Seoul, Republic of Korea
| | - Sang Youl Rhee
- Center for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Center, Kyung Hee University College of Medicine, Seoul, Republic of Korea; Department of Endocrinology and Metabolism, Kyung Hee University College of Medicine, Seoul, Republic of Korea
| | - Jin Soo Moon
- Department of Pediatrics, Seoul National University College of Medicine, Seoul, Republic of Korea.
| | - Jae Sung Ko
- Department of Pediatrics, Seoul National University College of Medicine, Seoul, Republic of Korea.
| | - Dong Keon Yon
- Center for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Center, Kyung Hee University College of Medicine, Seoul, Republic of Korea; Department of Pediatrics, Kyung Hee University College of Medicine, Seoul, Republic of Korea.
| | - Nikolaos G Papadopoulos
- Allergy Department, 2nd Paediatric Clinic, National and Kapodistrian University of Athens, Athens, Greece; Division of Immunology, Immunity to Infection and Respiratory Medicine, Faculty or Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom
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28
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Jevtić J, Ristić N, Pavlović V, Svorcan J, Milovanovich I, Radusinović M, Popovac N, Simić L, Ćirović A, Đuknić M, Životić M, Poljašević N, Obradović D, Filipović J, Janković R. The Usefulness of the Eosinophilic Esophagitis Histology Scoring System in Predicting Response to Proton Pump Inhibitor Monotherapy in Children with Eosinophilic Esophagitis. Diagnostics (Basel) 2023; 13:3445. [PMID: 37998581 PMCID: PMC10670290 DOI: 10.3390/diagnostics13223445] [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: 10/07/2023] [Revised: 11/08/2023] [Accepted: 11/12/2023] [Indexed: 11/25/2023] Open
Abstract
BACKGROUND Eosinophilic esophagitis (EoE) is an immune-mediated esophageal disease with rising incidence. While proton pump inhibitors (PPIs) are the first-line treatment, a significant proportion of patients do not respond. This study aimed to determine if the EoE Histology Scoring System (EoEHSS) can predict PPI responsiveness. METHODS A cross-sectional study was conducted on 89 pediatric patients diagnosed with EoE between 2016 and 2022. Patients were categorized into PPI responders (PPIREoE) and non-responders (PPINREoE) based on post-treatment biopsies. EoEHSS values from biopsies of the esophagus (distal, middle, and proximal segments) were compared between the two groups. RESULTS No significant differences in EoEHSS scores were observed for the distal and proximal esophagus between the groups. However, the middle esophagus showed a significantly higher EoEHSS grade score in the PPINREoE group, indicating a more pronounced disease severity. Specific histological features, particularly eosinophilic abscesses and surface layering of the middle segment of the esophagus, were significantly different between the groups. CONCLUSIONS Performing a biopsy of each esophageal segment, particularly the middle, is crucial for diagnostic precision and predicting PPI responsiveness. The EoEHSS can serve as a valuable tool in predicting therapy response, emphasizing the need for personalized therapeutic approaches in EoE management.
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Affiliation(s)
- Jovan Jevtić
- Institute of Pathology, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (L.S.); (M.Đ.); (M.Ž.); (D.O.); (J.F.)
| | - Nina Ristić
- Department of Gastroenterology, Hepatology and GI Endoscopy, University Children’s Hospital, 11000 Belgrade, Serbia; (N.R.); (J.S.); (I.M.); (M.R.); (N.P.)
| | - Vedrana Pavlović
- Institute of Medical Statistics and Informatics, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia;
| | - Jovana Svorcan
- Department of Gastroenterology, Hepatology and GI Endoscopy, University Children’s Hospital, 11000 Belgrade, Serbia; (N.R.); (J.S.); (I.M.); (M.R.); (N.P.)
| | - Ivan Milovanovich
- Department of Gastroenterology, Hepatology and GI Endoscopy, University Children’s Hospital, 11000 Belgrade, Serbia; (N.R.); (J.S.); (I.M.); (M.R.); (N.P.)
| | - Milica Radusinović
- Department of Gastroenterology, Hepatology and GI Endoscopy, University Children’s Hospital, 11000 Belgrade, Serbia; (N.R.); (J.S.); (I.M.); (M.R.); (N.P.)
| | - Nevena Popovac
- Department of Gastroenterology, Hepatology and GI Endoscopy, University Children’s Hospital, 11000 Belgrade, Serbia; (N.R.); (J.S.); (I.M.); (M.R.); (N.P.)
| | - Ljubica Simić
- Institute of Pathology, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (L.S.); (M.Đ.); (M.Ž.); (D.O.); (J.F.)
| | - Aleksandar Ćirović
- Institute of Anatomy, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia;
| | - Miloš Đuknić
- Institute of Pathology, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (L.S.); (M.Đ.); (M.Ž.); (D.O.); (J.F.)
| | - Maja Životić
- Institute of Pathology, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (L.S.); (M.Đ.); (M.Ž.); (D.O.); (J.F.)
| | - Nevena Poljašević
- Department of Pathology, University Clinical Center Tuzla, 75000 Tuzla, Bosnia and Herzegovina;
| | - Danilo Obradović
- Institute of Pathology, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (L.S.); (M.Đ.); (M.Ž.); (D.O.); (J.F.)
| | - Jelena Filipović
- Institute of Pathology, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (L.S.); (M.Đ.); (M.Ž.); (D.O.); (J.F.)
| | - Radmila Janković
- Institute of Pathology, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (L.S.); (M.Đ.); (M.Ž.); (D.O.); (J.F.)
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Low EE, Song Q, Yadlapati R, Dellon ES, Aceves S, Liu L, Gupta S, Choksi YA, Shah SC. Development and Validation of the Veterans Affairs Eosinophilic Esophagitis Cohort. Clin Gastroenterol Hepatol 2023; 21:3030-3040.e4. [PMID: 37031716 PMCID: PMC10558623 DOI: 10.1016/j.cgh.2023.03.033] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Revised: 03/08/2023] [Accepted: 03/23/2023] [Indexed: 04/11/2023]
Abstract
BACKGROUND & AIMS Gaps remain in understanding the epidemiology of eosinophilic esophagitis (EoE). Our aim was to identify and validate a national cohort of individuals with EoE using Veterans Health Administration (VHA) data. METHODS We used 2 validation strategies to develop algorithms that identified adults with EoE between 1999 and 2020. The first validation strategy applied International Classification of Diseases (ICD) code algorithms to a base cohort of individuals who underwent esophagogastroduodenoscopy with esophageal biopsy specimens. The second applied ICD code algorithms to a base cohort of all individuals in the VHA. For each ICD algorithm applied, a random sample of candidate EoE cases and non-EoE controls were selected and the charts were reviewed manually by a blinded reviewer. Each algorithm was modified iteratively until the prespecified diagnostic accuracy end point (95% confidence lower bound for a positive predictive value [PPV], >88%) was achieved. We compiled individuals from each strategy's maximum performance algorithm to construct the Veterans Affairs Eosinophilic Esophagitis Cohort. RESULTS The maximum performance algorithm from the first validation strategy included 2 or more ICD code encounters for EoE separated by more than 30 days and achieved a 93.3% PPV (lower bound, 88.1%) for identifying true EoE cases. The maximum performance algorithm from the second validation strategy included 4 or more ICD code encounters for EoE in which 2 codes were separated by at least 30 days, and similarly achieved a 93.3% PPV (lower bound, 88.1%). Combining both strategies yielded 6637 individuals, which comprised the Veterans Affairs Eosinophilic Esophagitis Cohort. CONCLUSIONS We developed and validated 2 highly accurate coding algorithms for EoE and established a nationwide VHA cohort of adults with EoE for future studies.
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Affiliation(s)
- Eric E Low
- Jennifer Moreno Department of Veteran Affairs Medical Center, San Diego Healthcare System, San Diego, California; Division of Gastroenterology, University of California San Diego, San Diego, California
| | - Qingyuan Song
- Veterans Affairs Tennessee Valley Health Care System, Nashville, Tennessee
| | - Rena Yadlapati
- Division of Gastroenterology, University of California San Diego, San Diego, California
| | - 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
| | - Seema Aceves
- Division of Allergy and Immunology, Department of Pediatrics, Rady Children's Hospital, University of California San Diego, San Diego, California
| | - Lin Liu
- Jennifer Moreno Department of Veteran Affairs Medical Center, San Diego Healthcare System, San Diego, California; Division of Biostatistics and Bioinformatics, Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, San Diego, California
| | - Samir Gupta
- Jennifer Moreno Department of Veteran Affairs Medical Center, San Diego Healthcare System, San Diego, California; Division of Gastroenterology, University of California San Diego, San Diego, California
| | - Yash A Choksi
- Veterans Affairs Tennessee Valley Health Care System, Nashville, Tennessee; Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University, Nashville, Tennessee
| | - Shailja C Shah
- Jennifer Moreno Department of Veteran Affairs Medical Center, San Diego Healthcare System, San Diego, California; Division of Gastroenterology, University of California San Diego, San Diego, California.
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Pehrsson M, de Rooij WE, Bay-Jensen AC, Karsdal MA, Mortensen JH, Bredenoord AJ. Extracellular matrix remodeling proteins as biomarkers for clinical assessment and treatment outcomes in eosinophilic esophagitis. BMC Gastroenterol 2023; 23:357. [PMID: 37845632 PMCID: PMC10577915 DOI: 10.1186/s12876-023-02977-z] [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: 06/29/2022] [Accepted: 09/26/2023] [Indexed: 10/18/2023] Open
Abstract
BACKGROUND Eosinophilic esophagitis (EoE) is a chronic progressive inflammatory disease of the esophagus, characterized by extracellular matrix remodeling and fibrotic stricture formation. Disease monitoring requires multiple re-endoscopies with esophageal biopsies. Hence non-invasive methods for determining tissue fibrosis and treatment efficacy are warranted. AIMS To investigate the ability of extracellular matrix proteins in serum as potential biomarkers of tissue remodeling and clinical, endoscopic, and histological disease outcomes in adult EoE patients. METHODS Protein-fingerprint assays were used to measure neo-epitope specific fragments of collagen remodeling, human-neutrophil elastase degraded calprotectin, and citrullinated or non-citrullinated vimentin in the serum of an adult EoE-cohort. Biomarker analysis, symptoms, endoscopic features and histological disease activity (eosinophils(eos) per high-power-field(hpf)) were evaluated at baseline and after six weeks of dietary intervention. RESULTS Patients with a baseline (Endoscopic Reference score) EREFS fibrosis subscore ≥ 2 presented with increased fibrolysis of cross-linked type III collagen (CTX-III) (p < 0.01), whereas low CTX-III levels were observed in patients achieving histological remission (< 15 eos/hpf) (vs. no histological remission (p < 0.05). Progression of endoscopic fibrosis after intervention was associated with increased levels of type-III (PRO-C3) and -VI collagen (PRO-C6) formation (all; p < 0.05). A baseline EREFS inflammatory subscore ≥ 2 correlated with higher neutrophilic activity (Cpa9-HNE) at week 6 (p < 0.05). Moreover, increased degradation of type-III (C3M) and -IV (C4M/PRO-C4) collagens were associated with remission of food impaction after intervention (all; p < 0.05). CONCLUSION Serum extracellular matrix remodeling proteins demonstrated potential as surrogate biomarkers for assessing histological disease remission, endoscopic fibrosis, and remission of symptoms of food impaction after diet intervention in adult EoE patients.
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Affiliation(s)
- Martin Pehrsson
- Biomarkers and Research, Nordic Bioscience A/S, Herlev, Denmark
| | - Willemijn E de Rooij
- Department of Gastroenterology & Hepatology, Amsterdam University Medical Center, Amsterdam, Netherlands.
| | | | | | | | - Albert Jan Bredenoord
- Department of Gastroenterology & Hepatology, Amsterdam University Medical Center, Amsterdam, Netherlands
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Dellon ES, Peterson KA, Mitlyng BL, Iuga A, Bookhout CE, Cortright LM, Walker KB, Gee TS, McGee SJ, Cameron BA, Galanko JA, Woosley JT, Eluri S, Moist SE, Hirano I. Mepolizumab for treatment of adolescents and adults with eosinophilic oesophagitis: a multicentre, randomised, double-blind, placebo-controlled clinical trial. Gut 2023; 72:1828-1837. [PMID: 37423717 PMCID: PMC11315207 DOI: 10.1136/gutjnl-2023-330337] [Citation(s) in RCA: 42] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2023] [Accepted: 06/28/2023] [Indexed: 07/11/2023]
Abstract
OBJECTIVE We aimed to determine whether mepolizumab, an anti-IL-5 antibody, was more effective than placebo for improving dysphagia symptoms and decreasing oesophageal eosinophil counts in eosinophilic oesophagitis (EoE). METHODS We conducted a multicentre, randomised, double-blind, placebo-controlled, trial. In the first part, patients aged 16-75 with EoE and dysphagia symptoms (per EoE Symptom Activity Index (EEsAI)) were randomised 1:1 to 3 months of mepolizumab 300 mg monthly or placebo. Primary outcome was change in EEsAI from baseline to month 3 (M3). Secondary outcomes included histological, endoscopic and safety metrics. In part 2, patients initially randomised to mepolizumab continued 300 mg monthly for 3 additional months (mepo/mepo), placebo patients started mepolizumab 100 mg monthly (pbo/mepo), and outcomes were reassessed at month 6 (M6). RESULTS Of 66 patients randomised, 64 completed M3, and 56 completed M6. At M3, EEsAI decreased 15.4±18.1 with mepolizumab and 8.3±18.0 with placebo (p=0.14). Peak eosinophil counts decreased more with mepolizumab (113±77 to 36±43) than placebo (146±94 to 160±133) (p<0.001). With mepolizumab, 42% and 34% achieved histological responses of <15 and ≤6 eos/hpf compared with 3% and 3% with placebo (p<0.001 and 0.02). The change in EoE Endoscopic Reference Score at M3 was also larger with mepolizumab. At M6, EEsAI decreased 18.3±18.1 points for mepo/mepo and 18.6±19.2 for pbo/mepo (p=0.85). The most common adverse events were injection-site reactions. CONCLUSIONS Mepolizumab did not achieve the primary endpoint of improving dysphagia symptoms compared with placebo. While eosinophil counts and endoscopic severity improved with mepolizumab at 3 months, longer treatment did not yield additional improvement. TRIAL REGISTRATION NUMBER NCT03656380.
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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, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA
| | - Kathryn A Peterson
- Department of Internal Medicine, Division of Gastroenterology, University of Utah, Salt Lake City, Utah, USA
| | | | - Alina Iuga
- Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, North Carolina, USA
| | - Christine E Bookhout
- Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, North Carolina, USA
| | - Lindsay M Cortright
- Center for Esophageal Diseases and Swallowing, and Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA
| | - Kacie B Walker
- Center for Esophageal Diseases and Swallowing, and Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA
| | - Timothy S Gee
- Center for Esophageal Diseases and Swallowing, and Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA
| | - Sarah J McGee
- Center for Esophageal Diseases and Swallowing, and Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA
| | - Brenderia A Cameron
- Center for Esophageal Diseases and Swallowing, and Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA
| | - Joseph A Galanko
- Center for Esophageal Diseases and Swallowing, and Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA
| | - John T Woosley
- Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, North Carolina, USA
| | - Swathi Eluri
- Center for Esophageal Diseases and Swallowing, and Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA
| | - Susan E Moist
- Center for Esophageal Diseases and Swallowing, and Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA
| | - Ikuo Hirano
- Division of Gastroenterology and Hepatology, Northwestern University School of Medicine, Chicago, Illinois, USA
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Abramson L, Smeekens JM, Kulis MD, Dellon ES. Food-specific IgA levels in esophageal biopsies are not sufficiently high to predict food triggers in eosinophilic esophagitis. Immun Inflamm Dis 2023; 11:e1029. [PMID: 37773691 PMCID: PMC10523942 DOI: 10.1002/iid3.1029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Revised: 08/29/2023] [Accepted: 09/09/2023] [Indexed: 10/01/2023] Open
Abstract
BACKGROUND Eosinophilic esophagitis (EoE) is an immune-mediated disease, characterized by Th2-type inflammation linked to specific foods. No currently available allergy tests reliably identify food triggers in EoE, leading to empiric dietary elimination strategies. Recently, milk- and wheat-specific IgA in esophageal brushings were linked to clinical food triggers. In this study, we aimed to determine whether food-specific IgA from esophageal biopsies is associated with known food triggers. METHODS A prior cohort of 21 patients (median age 39 years) with confirmed EoE underwent empirical elimination diets and subsequent reintroduction of foods to determine triggers. Archived baseline biopsies were used to quantify levels of peanut-, milk-, soy-, egg-, wheat-specific and total IgA by enzyme-linked immunosorbent assay. RESULTS Overall, 13 patients (62%) responded to the dietary elimination as determined by histology (<15 eos/hpf), with milk and egg being the most common triggers. Biopsies had varying amounts of total IgA, while food-specific IgA was only detectable in 48 of 105 (46%) samples. Food-specific IgA was normalized to total IgA for each sample and stratified by whether a food was a known trigger. For all foods tested, there were no significant differences in IgA between positive and negative triggers. CONCLUSIONS Food-specific IgA in esophageal biopsies was not associated with previously identified food triggers in this cohort. Future studies comparing food-specific IgA in esophageal brushings, mucous scrapings, and biopsies from patients with known triggers will be critical to determining whether food-specific IgA may serve as a biomarker for identification of EoE triggers.
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Affiliation(s)
- Lior Abramson
- Division of Gastroenterology and Hepatology, Department of Medicine, Center for Esophageal Diseases and SwallowingUniversity of North CarolinaChapel HillNorth CarolinaUSA
| | - Johanna M. Smeekens
- Division of Allergy and Immunology, Department of PediatricsUNC School of MedicineChapel HillNorth CarolinaUSA
| | - Michael D. Kulis
- Division of Allergy and Immunology, Department of PediatricsUNC School of MedicineChapel HillNorth CarolinaUSA
| | - Evan S. Dellon
- Division of Gastroenterology and Hepatology, Department of Medicine, Center for Esophageal Diseases and SwallowingUniversity of North CarolinaChapel HillNorth CarolinaUSA
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Kurt G, Svane HML, Erichsen R, Heide-Jørgensen U, Sørensen HT, Dellon ES, Jensen ET. Prenatal, Intrapartum, and Neonatal Factors Increase the Risk of Eosinophilic Esophagitis. Am J Gastroenterol 2023; 118:1558-1565. [PMID: 37104675 PMCID: PMC10523886 DOI: 10.14309/ajg.0000000000002303] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Accepted: 04/04/2023] [Indexed: 04/29/2023]
Abstract
INTRODUCTION Early-life exposures have been associated with an increased risk of eosinophilic esophagitis (EoE); however, most studies to date have been conducted at referral centers and are subject to recall bias. By contrast, we conducted a nationwide, population-based and registry-based case-control study of prenatal, intrapartum, and neonatal exposures, using data collected prospectively through population-based Danish health and administrative registries. METHODS We ascertained all EoE cases in Denmark (birth years 1997-2018). Cases were sex and age matched to controls (1:10) using risk-set sampling. We obtained data on prenatal, intrapartum, and neonatal factors, i.e., pregnancy complications, mode of delivery, gestational age at delivery, birthweight (expressed as a z-score), and neonatal intensive care unit (NICU) admission. We used conditional logistic regression to compute the crude and adjusted odds ratios (aOR) of EoE in relation to each prenatal, intrapartum, and neonatal factor, thus providing an estimate of incidence density ratios with 95% confidence intervals (CI). RESULTS In the 393 cases and 3,659 population controls included (median age at index date, 11 years [interquartile range, 6-15]; 69% male), we observed an association between gestational age and EoE, peaking at 33 vs 40 weeks (aOR 3.6 [95% CI 1.8-7.4]), and between NICU admission and EoE (aOR 2.8 [95% CI 1.2-6.6], for a NICU hospitalization of 2-3 weeks vs no admission). In interaction analyses, we observed a stronger association between NICU admission and EoE in infants born at term than in preterm infants (aOR 2.0 [95% CI 1.4-2.9] for term infants and aOR 1.0 [95% CI 0.5-2.0] for preterm infants). We also observed an association between pregnancy complications and EoE (aOR 1.4 [95% CI 1.0-1.9]). Infants who were very growth restricted at birth had an increased rate of EoE (aOR 1.4 [95% CI: 1.0-1.9] for a z-score of -1.5 vs a z-score of 0). Mode of delivery was not associated with EoE. DISCUSSION Prenatal, intrapartum, and neonatal factors, particularly preterm birth and NICU admission, were associated with development of EoE. Further research is needed to elucidate the mechanisms underlying the observed associations.
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Affiliation(s)
- Gencer Kurt
- Department of Clinical Epidemiology, Aarhus University
| | | | - Rune Erichsen
- Department of Clinical Epidemiology, Aarhus University
| | | | - Henrik T. Sørensen
- Department of Clinical Epidemiology, Aarhus University
- Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, NC, USA
| | - Evan S. Dellon
- Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, NC, USA
| | - Elizabeth T. Jensen
- Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, NC, USA
- Department of Epidemiology and Prevention, Wake Forest University School of Medicine
- Gastroenterology, Department of Internal Medicine, Wake Forest University School of Medicine
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Jensen ET, Dai X, Kodroff E, Strobel MJ, Zicarelli A, Gray S, Cordell A, Anderson C, Hiremath G, Dellon ES. Early life exposures as risk factors for non-esophageal eosinophilic gastrointestinal diseases. Clin Res Hepatol Gastroenterol 2023; 47:102170. [PMID: 37352927 PMCID: PMC10529369 DOI: 10.1016/j.clinre.2023.102170] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Revised: 06/16/2023] [Accepted: 06/20/2023] [Indexed: 06/25/2023]
Abstract
OBJECTIVES Early life exposures increase risk of eosinophilic esophagitis (EoE), but it is unknown whether they contribute to increased risk for non-EoE eosinophilic gastrointestinal diseases (EGIDs). We aimed to assess the association between prenatal, antenatal, and early life factors and non-EoE EGIDs. METHODS We conducted a case-control study based in EGID Partners, an online patient-centered research network. Adults (≥18 years) with non-EoE EGIDs, caregivers of children <18 years of age with an EGID, and non-EGID adult controls were eligible. Subjects completed our Early Life Exposure Questionnaire, detailing maternal and early childhood exposures. We assessed for associations between non-EoE EGIDs and early life exposures, focusing on exposures previously evaluated in association with EoE. RESULTS We analyzed 61 non-EoE EGID cases and 20 controls. Of the EGID cases, 14 had eosinophilic gastritis, 19 had eosinophilic enteritis, 6 had eosinophilic colitis, and 22 had multiple areas affected; additionally, 30 had esophageal involvement. Relative to controls, EGID cases were more likely to have had antenatal/perinatal pregnancy-related complications (43% vs 13%; p = 0.02), NICU admission (20% vs 0%; p = 0.03), and antibiotics in infancy (43% vs 10%; p = 0.01). With adjustment for age at diagnosis, we observed increased odds of an EGID for pregnancy complications (aOR 3.83; 95% CI: 0.99-14.9) and antibiotic use in infancy (aOR 7.65; 95% CI: 1.28-45.7). CONCLUSIONS Early life factors, including pregnancy complications, NICU admission, and antibiotics in infancy, were associated with development of non-EoE EGIDs. The impact of early life exposures on non-EoE EGID pathogenic mechanisms should be investigated.
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Affiliation(s)
- Elizabeth T Jensen
- Department of Epidemiology and Prevention, Wake Forest University School of Medicine, Winston-Salem, NC, USA; Center for Gastrointestinal Biology and Disease, University of North Carolina School of Medicine, Chapel Hill, NC, USA
| | - Xiangfeng Dai
- Center for Gastrointestinal Biology and Disease, University of North Carolina School of Medicine, Chapel Hill, NC, USA
| | - Ellyn Kodroff
- Campaign Urging Research for Eosinophilic Disease (CURED), USA
| | - Mary Jo Strobel
- American Partnership for Eosinophilic Disorders (APFED), USA
| | | | | | | | - Chelsea Anderson
- Center for Gastrointestinal Biology and Disease, University of North Carolina School of Medicine, Chapel Hill, NC, USA
| | - Girish Hiremath
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Monroe Carell Jr. Children's Hospital at Vanderbilt, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Evan S Dellon
- Center for Gastrointestinal Biology and Disease, University of North Carolina School of Medicine, Chapel Hill, NC, USA; Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
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POLAT TERECE S, YAPAR D, ERTOY KARAGÖL Hİ, KÖKEN G, TEKER DÜZTAŞ D, EĞRİTAŞ GÜRKAN Ö, SARI S, DALGIÇ B, BAKIRTAŞ A. Is the Pediatric Eosinophilic Esophagitis Symptom Score v2.0 reliable for telemedicine? Turk J Med Sci 2023; 53:859-864. [PMID: 38031952 PMCID: PMC10760582 DOI: 10.55730/1300-0144.5649] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2022] [Revised: 08/18/2023] [Accepted: 05/25/2023] [Indexed: 12/01/2023] Open
Abstract
BACKGROUND Eosinophilic esophagitis (EoE) is a chronic immune-mediated disease. Telemedicine is a healthcare technology used when a patient is separated by distance. The reliability of the Pediatric Eosinophilic Esophagitis Symptom Score, version 2.0 (PEESS v2.0) for telemedicine applications, has not been studied yet. Therefore, we aimed to evaluate the reliability of PEESS v2.0 for telemedicine. METHODS We sent a telesurvey using questionnaires via electronic telecommunication as the telemedicine method. Children with EoE and their parents were asked to complete PEESS v2.0 with the telesurvey method (unsynchronized with the physician) and attend in-person visits one week apart. Intraclass correlation (ICC), Wilcoxon, and Bland-Altman tests were used as reliability analyses. Reliability was defined as a strong agreement between the measurements in ICC ≥ 0.8 and a p-value of ≤0.05 and no statistically significant difference between the scores of the two methods in the Wilcoxon and Bland-Altman analyses, i.e. a p-value of >0.05. RESULTS The total scores of children and parents were higher in in-person visits than in the telesurvey (Wilcoxon tests, p ≤ 0.05). Bland- Altman analysis showed that the mean difference in total scores between the two methods was significant for both children and parents (p ≤ 0.05). ICC levels for the children and parent scores for the entire group ranged from 0.595 to 0.763 (moderate agreement). DISCUSSION Unsynchronized telesurvey use of PEESS v2.0 is unreliable both for children and parents. We suggest testing the reliability of chosen telemedicine methods before using them in clinical and research practice.
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Affiliation(s)
- Sinem POLAT TERECE
- Division of Pediatric Allergy, Department of Pediatrics, Faculty of Medicine, Gazi University, Ankara,
Turkiye
| | - Dilek YAPAR
- Muratpaşa District Health Directorate, Antalya,
Turkiye
| | - Hacer İlbilge ERTOY KARAGÖL
- Division of Pediatric Allergy, Department of Pediatrics, Faculty of Medicine, Gazi University, Ankara,
Turkiye
| | - Gizem KÖKEN
- Division of Pediatric Allergy, Department of Pediatrics, Faculty of Medicine, Gazi University, Ankara,
Turkiye
| | - Demet TEKER DÜZTAŞ
- Division of Pediatric Gastroenterology, Department of Pediatrics, Faculty of Medicine, Gazi University, Ankara,
Turkiye
| | - Ödül EĞRİTAŞ GÜRKAN
- Division of Pediatric Gastroenterology, Department of Pediatrics, Faculty of Medicine, Gazi University, Ankara,
Turkiye
| | - Sinan SARI
- Division of Pediatric Gastroenterology, Department of Pediatrics, Faculty of Medicine, Gazi University, Ankara,
Turkiye
| | - Buket DALGIÇ
- Division of Pediatric Gastroenterology, Department of Pediatrics, Faculty of Medicine, Gazi University, Ankara,
Turkiye
| | - Arzu BAKIRTAŞ
- Division of Pediatric Allergy, Department of Pediatrics, Faculty of Medicine, Gazi University, Ankara,
Turkiye
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Gurtner A, Crepaz D, Arnold IC. Emerging functions of tissue-resident eosinophils. J Exp Med 2023; 220:e20221435. [PMID: 37326974 PMCID: PMC10276195 DOI: 10.1084/jem.20221435] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Revised: 05/12/2023] [Accepted: 05/25/2023] [Indexed: 06/17/2023] Open
Abstract
Eosinophils are typically considered tissue-damaging effector cells in type 2 immune-related diseases. However, they are also increasingly recognized as important modulators of various homeostatic processes, suggesting they retain the ability to adapt their function to different tissue contexts. In this review, we discuss recent progress in our understanding of eosinophil activities within tissues, with particular emphasis on the gastrointestinal tract, where a large population of these cells resides under non-inflammatory conditions. We further examine evidence of their transcriptional and functional heterogeneity and highlight environmental signals emerging as key regulators of their activities, beyond classical type 2 cytokines.
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Affiliation(s)
- Alessandra Gurtner
- Institute of Experimental Immunology, University of Zürich , Zürich, Switzerland
| | - Daniel Crepaz
- Institute of Experimental Immunology, University of Zürich , Zürich, Switzerland
| | - Isabelle C Arnold
- Institute of Experimental Immunology, University of Zürich , Zürich, Switzerland
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S2k-Leitlinie Gastroösophageale Refluxkrankheit und eosinophile Ösophagitis der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) – März 2023 – AWMF-Registernummer: 021–013. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2023; 61:862-933. [PMID: 37494073 DOI: 10.1055/a-2060-1069] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/28/2023]
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Dellon ES, Tsai YS, Coffey AR, Bodwin K, Sninsky JA, Mosso CN, He TM, O’Connor KA, Selitsky SR, Nobel AB, Parker JS. Pre-treatment differential correlation of gene expression and response to topical steroids in eosinophilic esophagitis. Dis Esophagus 2023; 36:doac071. [PMID: 36222072 PMCID: PMC11220672 DOI: 10.1093/dote/doac071] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Revised: 09/07/2022] [Accepted: 09/12/2022] [Indexed: 12/11/2022]
Abstract
Few predictors of response to topical corticosteroid (tCS) treatment have been identified in eosinophilic esophagitis (EoE). We aimed to determine whether baseline gene expression predicts histologic response to tCS treatment for EoE. We analyzed prospectively collected samples from incident EoE cases who were treated with tCS for 8 weeks in a development cohort (prospective study) or in an independent validation cohort (clinical trial). Whole transcriptome RNA expression was determined from a baseline (pre-treatment) RNA-later preserved esophageal biopsy. Baseline expression was compared between histologic responders (<15 eos/hpf) and non-responders (≥15 eos/hpf), and differential correlation was used to assess baseline gene expression by response status. In 87 EoE cases analyzed in the development set, there were no differentially expressed genes associated with treatment response (at false discovery rate = 0.1). However, differential correlation identified a module of 22 genes with statistically significantly high pairwise correlation in non-responders (mean correlation coefficient = 0.7) compared to low correlation in responders (coefficient = 0.3). When this 22-gene module was applied to the 89 EoE cases in the independent cohort, it was not validated to predict tCS response at the 15 eos/hpf threshold (mean correlation coefficient = 0.32 in responders and 0.25 in nonresponders). Exploration of other thresholds also did not validate any modules. Though we identified a 22 gene differential correlation module measured pre-treatment that was strongly associated with subsequent histologic response to tCS in EoE, this was not validated in an independent population. Alternative methods to predict steroid response should be explored.
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Affiliation(s)
- Evan S Dellon
- Department of Medicine, Division of Gastroenterology and Hepatology, Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, NC, USA
| | - Yihsuan S Tsai
- Department of Genetics, University of North Carolina, Chapel Hill, NC, USA
- Department of Medicine, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA
| | - Alisha R Coffey
- Department of Genetics, University of North Carolina, Chapel Hill, NC, USA
- Department of Medicine, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA
| | - Kelly Bodwin
- Department of Statistics and Operations Research, University of North Carolina, Chapel Hill, NC, USA
- Statistics Department, Cal Poly, Obispo, CA, USA
| | - Jared A Sninsky
- Department of Medicine, Division of Gastroenterology and Hepatology, Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, NC, USA
| | - Carson N Mosso
- Department of Statistics and Operations Research, University of North Carolina, Chapel Hill, NC, USA
| | - Tianshe M He
- Department of Statistics and Operations Research, University of North Carolina, Chapel Hill, NC, USA
| | - Kevin A O’Connor
- Department of Statistics and Operations Research, University of North Carolina, Chapel Hill, NC, USA
| | - Sara R Selitsky
- Department of Genetics, University of North Carolina, Chapel Hill, NC, USA
- Department of Medicine, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA
| | - Andrew B Nobel
- Department of Statistics and Operations Research, University of North Carolina, Chapel Hill, NC, USA
| | - Joel S Parker
- Department of Genetics, University of North Carolina, Chapel Hill, NC, USA
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Jhaveri PB, Lambert KA, Bogale K, Lehman E, Alexander C, Ishmael F, Jhaveri PN, Hicks SD. Salivary microRNAs in pediatric eosinophilic esophagitis. Allergy Asthma Proc 2023; 44:145-152. [PMID: 36872450 DOI: 10.2500/aap.2023.44.220102] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/07/2023]
Abstract
Background: Diagnosis and management of eosinophilic esophagitis (EoE) occur via esophagogastroduodenoscopy with tissue biopsy. Objective: We sought to determine if salivary microribonucleic acid (miRNA) levels could differentiate children with EoE, serving as a noninvasive biomarker. Methods: Saliva was collected from children undergoing esophagogastroduodenoscopy (N = 291). miRNA analysis was conducted on 150 samples: EoE (n = 50), no pathologic alteration (n = 100). RNA was quantified with high throughput sequencing and aligned to build hg38 of the human genome using sequencing and alignment software. Quantile normalized levels of robustly expressed miRNAs (raw counts > 10 in 10% of samples) were compared across EoE and non-EoE groups with Wilcoxon rank sum testing. miRNA biomarker candidates were selected based on variable importance projection (VIP) scoring with partial least squared discriminant analysis (VIP > 1.5). Ability of these miRNAs to differentiate EoE status was assessed via logistic regression. Putative biologic targets for the miRNA candidates were determined in miRNA pathway analysis software. Results: Of the 56 salivary miRNAs reliably detected, miR-205-5p displayed the largest difference between EoE and non-EoE groups (V = 1623, adjusted p = 0.029). Six miRNAs (miR-26b-5p, miR-27b-3p, Let-7i-5p, miR-142-5p, miR-30a-5p, miR-205-5p) displayed elevated VIP scores (>1.5) and were able to differentiate EoE samples on logistic regression analysis with 70% sensitivity and 68% specificity. These six miRNAs demonstrated significant enrichment for gene targets involved in valine, leucine, and isoleucine biosynthesis (p = 0.0012), 2-oxycarboxylic acid metabolism (p = 0.043), and steroid hormone biosynthesis (p = 0.048). Conclusions: Salivary miRNAs represent a noninvasive, biologically relevant measure that may aid disease monitoring of EoE.
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Affiliation(s)
- Pooja Bm Jhaveri
- From the Division of Allergy & Immunology, Department of Pediatrics, Penn State Children's Hospital, Hershey, Pennsylvania
| | - Kristin A Lambert
- Department of Pediatrics, Cincinnati Children's Hospital & Medical Center, Cincinnati, Ohio
| | - Kaleb Bogale
- Department of Medicine, Columbia University Irving Medical Center, New York, New York
| | - Erik Lehman
- Department of Public Health Sciences, Penn State University, Hershey, Pennsylvania
| | - Chandran Alexander
- Division of Gastroenterology, Department of Pediatrics, Penn State Children's Hospital, Hershey, Pennsylvania
| | - Faoud Ishmael
- Department of Allergy and Sleep Medicine, Mount Nittany Medical Group, State College, Pennsylvania, and
| | - Punit N Jhaveri
- Division of Gastroenterology, Department of Pediatrics, Penn State Children's Hospital, Hershey, Pennsylvania
| | - Steve D Hicks
- Division of Academic General Pediatrics, Department of Pediatrics, Penn State Children's Hospital, Hershey, Pennsylvania
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Lee CJ, McGill SK. Food Allergies and Alpha-gal Syndrome for the Gastroenterologist. Curr Gastroenterol Rep 2023; 25:21-30. [PMID: 36705797 DOI: 10.1007/s11894-022-00860-7] [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] [Accepted: 12/02/2022] [Indexed: 01/28/2023]
Abstract
PURPOSE OF REVIEW Food allergies are typically not considered as a cause of gastrointestinal (GI) distress without additional allergic symptoms, apart from celiac disease and eosinophilic esophagitis. However, recent reports of patients with alpha-gal syndrome who presented with GI-only symptoms like abdominal pain, vomiting, and diarrhea challenge this paradigm. Alpha-gal syndrome is an IgE-mediated allergy characterized by delayed reactions after eating mammalian meat or mammalian-derived products that contain galactose-alpha-1,3-galactose (alpha-gal). The purpose of this review is to discuss our current understanding of food allergies, GI illness, and the GI manifestations of alpha-gal syndrome. RECENT FINDINGS Among Southeastern U.S. GI clinic patients who screened positive for serum alpha-gal IgE, a majority of patients reported significant symptom improvement on an alpha-gal-avoidant diet, suggesting that the allergy had played a role in their GI symptoms. Diagnosis of alpha-gal syndrome is typically made with concerning allergic symptoms, elevated alpha-gal specific IgE in the serum, and symptom improvement on an alpha-gal avoidant diet. Alpha-gal syndrome can cause a delayed allergic response that is increasingly recognized worldwide, including among patients with predominant GI symptoms.
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Affiliation(s)
- Christopher J Lee
- Department of Internal Medicine, University of North Carolina at Chapel Hill, 130 Mason Farm Road, Chapel Hill, NC, 27514, USA
| | - Sarah K McGill
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of North Carolina at Chapel Hill, 130 Mason Farm Road, Chapel Hill, NC, 27514, USA.
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Mechanisms and clinical management of eosinophilic oesophagitis: an overview. Nat Rev Gastroenterol Hepatol 2023; 20:101-119. [PMID: 36253463 DOI: 10.1038/s41575-022-00691-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/14/2022] [Indexed: 02/03/2023]
Abstract
Since the first description of eosinophilic oesophagitis (EoE) less than three decades ago, we have observed a striking increase in the number of patients diagnosed with EoE and the understanding of its clinical and immunopathogenic background. Nonetheless, a plethora of open questions await elucidation. In this Review, we discuss the current state of knowledge regarding the underlying mechanisms, particularly environmental factors and their interaction with genetic susceptibility. Subsequently, we discuss how to translate these factors into the diagnostic and therapeutic management of this chronic, immune-mediated disorder. Finally, we dissect the still long list of unmet needs, such as reasons for and handling refractory EoE and atypical clinical presentations. These open questions can guide us through future research steps and potentially foster reconsideration of the diagnostic guidelines of EoE.
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Fenneman AC, Weidner M, Chen LA, Nieuwdorp M, Blaser MJ. Antibiotics in the pathogenesis of diabetes and inflammatory diseases of the gastrointestinal tract. Nat Rev Gastroenterol Hepatol 2023; 20:81-100. [PMID: 36258032 PMCID: PMC9898198 DOI: 10.1038/s41575-022-00685-9] [Citation(s) in RCA: 49] [Impact Index Per Article: 24.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/01/2022] [Indexed: 02/06/2023]
Abstract
Antibiotic use is increasing worldwide. However, the use of antibiotics is clearly associated with changes in gut microbiome composition and function, and perturbations have been identified as potential environmental risk factors for chronic inflammatory disorders of the gastrointestinal tract. In this Review, we examine the association between the use of antibiotics and the onset and development of both type 1 and type 2 diabetes, inflammatory bowel disease, including ulcerative colitis and Crohn's disease, as well as coeliac disease and eosinophilic oesophagitis. We discuss the key findings of epidemiological studies, provide mechanistic insights into the pathways by which the gut microbiota might contribute to these diseases, and assess clinical trials investigating the effects of antibiotics. Such studies indicate that antibiotic exposures, varying in type, timing and dosage, could explain differences in disease risk. There seems to be a critical window in early life in which perturbation of the microbiome has a substantial effect on disease development. Identifying the antibiotic-perturbed gut microbiota as a factor that contributes to the pathophysiology of these inflammatory disorders might stimulate new approaches to prevention, diagnosis and treatment.
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Affiliation(s)
- Aline C Fenneman
- Department of Clinical and Experimental Vascular Medicine, Amsterdam Cardiovascular Sciences (ACS), Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
- Department of Endocrinology and Metabolism, Amsterdam Gastroenterology Endocrinology Metabolism (AGEM), Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
| | - Melissa Weidner
- Department of Paediatrics, Rutgers University, New Brunswick, NJ, USA
| | - Lea Ann Chen
- Department of Medicine, Rutgers University, New Brunswick, NJ, USA
| | - Max Nieuwdorp
- Department of Clinical and Experimental Vascular Medicine, Amsterdam Cardiovascular Sciences (ACS), Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
- Department of Endocrinology and Metabolism, Amsterdam Gastroenterology Endocrinology Metabolism (AGEM), Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
| | - Martin J Blaser
- Department of Medicine, Rutgers University, New Brunswick, NJ, USA.
- Department of Pathology and Laboratory Medicine, Rutgers University, New Brunswick, NJ, USA.
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Doyle AD, Masuda MY, Pyon GC, Luo H, Putikova A, LeSuer WE, Flashner S, Rank MA, Nakagawa H, Kita H, Wright BL. Detergent exposure induces epithelial barrier dysfunction and eosinophilic inflammation in the esophagus. Allergy 2023; 78:192-201. [PMID: 35899466 PMCID: PMC9797443 DOI: 10.1111/all.15457] [Citation(s) in RCA: 49] [Impact Index Per Article: 24.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Revised: 07/07/2022] [Accepted: 07/12/2022] [Indexed: 01/21/2023]
Abstract
BACKGROUND Eosinophilic esophagitis (EoE) is a chronic allergic disease associated with type 2 inflammation and epithelial barrier dysfunction. The etiology is unknown, however, genetic heritability studies suggest environmental factors play a key role in pathogenesis. Detergents, such as sodium dodecyl sulfate (SDS), are common ingredients in household products such as dish soap and toothpaste. We hypothesized detergent exposure decreases epithelial barrier function and induces esophageal inflammation. METHODS Immortalized esophageal epithelial cells (EPC2) were cultured in air-liquid interface (ALI) and exposed to SDS. Barrier function/activity was assessed by transepithelial electrical resistance (TEER), FITC-dextran flux, and RT-PCR. Additionally, SDS-treated mouse esophageal organoids were evaluated for morphology. To investigate the effects of SDS in vivo, mice were treated with 0.5% SDS in drinking water for 14 days. Esophagi were assessed by gross morphology, histopathology, protein expression, and bulk RNA sequencing. RESULTS When EPC2 cells were exposed to SDS (5 μg/ml) for 96 h, TEER decreased (p = 0.03), and FITC-dextran flux increased (p = 0.0002). mRNA expression of IL-33 increased 4.5-fold (p = 0.02) at 6 h and DSG1 decreased (p < 0.0001) by 72 h. Disrupted epithelial integrity was noted in SDS-treated esophageal organoids. When mice were exposed to SDS, they showed increased esophageal width, chemokine, and metalloprotease levels. Mice treated with SDS also showed increased IL-33 protein expression, basal zone hyperplasia, CD4+ cell infiltration, and esophageal eosinophilia. RNA sequencing revealed upregulation of immune response pathway genes. CONCLUSION Exposure to SDS decreases esophageal barrier integrity, stimulates IL-33 production, and promotes epithelial hyperplasia and tissue eosinophilia. Detergents may be a key environmental trigger in EoE pathogenesis.
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Affiliation(s)
- Alfred D Doyle
- Division of Allergy, Asthma, and Clinical Immunology, Mayo Clinic Arizona, Scottsdale, Arizona, USA
| | - Mia Y Masuda
- Division of Allergy, Asthma, and Clinical Immunology, Mayo Clinic Arizona, Scottsdale, Arizona, USA
| | - Grace C Pyon
- Division of Allergy, Asthma, and Clinical Immunology, Mayo Clinic Arizona, Scottsdale, Arizona, USA
| | - Huijun Luo
- Division of Allergy, Asthma, and Clinical Immunology, Mayo Clinic Arizona, Scottsdale, Arizona, USA
| | - Arina Putikova
- Division of Allergy, Asthma, and Clinical Immunology, Mayo Clinic Arizona, Scottsdale, Arizona, USA
| | - William E LeSuer
- Division of Allergy, Asthma, and Clinical Immunology, Mayo Clinic Arizona, Scottsdale, Arizona, USA
| | - Samuel Flashner
- Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, New York, USA
| | - Matthew A Rank
- Division of Allergy, Asthma, and Clinical Immunology, Mayo Clinic Arizona, Scottsdale, Arizona, USA
- Division of Pulmonology, Section of Allergy and Immunology, Phoenix Children's Hospital, Phoenix, Arizona, USA
| | - Hiroshi Nakagawa
- Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, New York, USA
| | - Hirohito Kita
- Division of Allergy, Asthma, and Clinical Immunology, Mayo Clinic Arizona, Scottsdale, Arizona, USA
| | - Benjamin L Wright
- Division of Allergy, Asthma, and Clinical Immunology, Mayo Clinic Arizona, Scottsdale, Arizona, USA
- Division of Pulmonology, Section of Allergy and Immunology, Phoenix Children's Hospital, Phoenix, Arizona, USA
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Greenberg SB, Ocampo AA, Xue Z, Chang NC, Thakkar KP, Reddy SB, Lee CJ, Ketchem CJ, Redd WD, Eluri S, Reed CC, Dellon ES. Increasing Rates of Esophageal Stricture and Dilation Over 2 Decades in Eosinophilic Esophagitis. GASTRO HEP ADVANCES 2022; 2:521-523. [PMID: 37293573 PMCID: PMC10249492 DOI: 10.1016/j.gastha.2022.12.006] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/04/2022] [Accepted: 12/26/2022] [Indexed: 06/10/2023]
Affiliation(s)
- S B Greenberg
- Division of Gastroenterology and Hepatology, Department of Medicine, Center for Esophageal Diseases and Swallowing, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - A A Ocampo
- Division of Gastroenterology and Hepatology, Department of Medicine, Center for Esophageal Diseases and Swallowing, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Z Xue
- Division of Gastroenterology and Hepatology, Department of Medicine, Center for Esophageal Diseases and Swallowing, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - N C Chang
- Division of Gastroenterology and Hepatology, Department of Medicine, Center for Esophageal Diseases and Swallowing, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - K P Thakkar
- Division of Gastroenterology and Hepatology, Department of Medicine, Center for Esophageal Diseases and Swallowing, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - S B Reddy
- Division of Gastroenterology and Hepatology, Department of Medicine, Center for Esophageal Diseases and Swallowing, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - C J Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, Center for Esophageal Diseases and Swallowing, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - C J Ketchem
- Division of Gastroenterology and Hepatology, Department of Medicine, Center for Esophageal Diseases and Swallowing, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - W D Redd
- Division of Gastroenterology and Hepatology, Department of Medicine, Center for Esophageal Diseases and Swallowing, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - S Eluri
- Division of Gastroenterology and Hepatology, Department of Medicine, Center for Esophageal Diseases and Swallowing, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - C C Reed
- Division of Gastroenterology and Hepatology, Department of Medicine, Center for Esophageal Diseases and Swallowing, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - E S Dellon
- Division of Gastroenterology and Hepatology, Department of Medicine, Center for Esophageal Diseases and Swallowing, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
- Division of Gastroenterology and Hepatology, Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
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Chang JW, Jensen ET, Dellon ES. Nature with Nurture: the Role of Intrinsic Genetic and Extrinsic Environmental Factors on Eosinophilic Esophagitis. Curr Allergy Asthma Rep 2022; 22:163-170. [PMID: 36190688 PMCID: PMC10838151 DOI: 10.1007/s11882-022-01042-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/22/2022] [Indexed: 12/13/2022]
Abstract
PURPOSE OF REVIEW As the rising prevalence and incidence of eosinophilic esophagitis (EoE) has quickly outpaced the rate of esophageal biopsies, particularly in Westernized countries, several studies have suggested a link between intrinsic genetic and extrinsic environmental risk factors and the development, presentation, and diagnosis of EoE. This review aims to critically assess existing studies describing the role of the environment on the development, symptomatic presentation, and diagnosis of this recently recognized chronic immune-mediated disease. RECENT FINDINGS We present and critically evaluate the working hypotheses and supportive studies thus far on environmental factors on EoE, describe sources of potential bias in diagnosis due to socioeconomic factors and thus undermining studies of EoE etiology, and highlight opportunities for future research. As genetics alone do not explain the rapid rise of EoE, we must look to environmental, or extrinsic, factors both in the early-life period which shape the development of the gut microbiome, as well as later life contributing to diagnosis of this new disease. Future etiologic studies linking risk factors to EoE development in individual patients are needed.
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Affiliation(s)
- Joy W Chang
- Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
| | - Elizabeth T Jensen
- Department of Epidemiology and Prevention, Wake Forest University School of Medicine, Winston-Salem, NC, USA
- Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, NC, USA
| | - Evan S Dellon
- Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, NC, USA
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Diagnostic Delay in Patients With Eosinophilic Esophagitis Has Not Changed Since the First Description 30 Years Ago: Diagnostic Delay in Eosinophilic Esophagitis. Am J Gastroenterol 2022; 117:1772-1779. [PMID: 35971224 DOI: 10.14309/ajg.0000000000001950] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2022] [Accepted: 08/01/2022] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Eosinophilic esophagitis (EoE) is a chronic progressive disease. Diagnostic delay (DD) is associated with increased risk of esophageal strictures and food impactions. We aimed to assess the evolution of DD since the first description of EoE in 1993 until 2021. METHODS We analyzed data from patients prospectively included in the Swiss EoE database. DD was calculated as the time interval between the first occurrence of EoE symptoms and the confirmed diagnosis. DD was analyzed annually over time (1989-2021) and according to milestone publications in the field (1993: first description; 2007: first consensus recommendations; and 2011: updated consensus recommendations). In addition, a Cox proportional hazards model has been used to describe the relation between DD and covariates. RESULTS Complete data of 1,152 patients (857 male [74%]; median age at diagnosis: 38 years, interquartile range: 28-49, range: 1-86) were analyzed. Overall, median DD was 4 years (interquartile range: 1-11, range, 0-56), with DD ≥ 10 years in 32% of the population. Over time, DD did not significantly change, neither annually nor according to release dates of milestone publications with a persistently stable fraction of roughly one-third of all patients with a DD of ≥10 years. Both ages at diagnosis ( P < 0.001, with an increase in DD up to the age of 31-40 years) and at symptom onset (younger patients had a longer DD; P < 0.001) were significantly associated with DD. DISCUSSION DD has not changed since the first description of EoE almost 30 years ago and remains substantial. Even today, one-third of patients have a persistently high DD of ≥10 years. Substantial efforts are warranted to increase awareness for EoE and its hallmark symptom, solid food dysphagia, as an age-independent red-flag symptom among healthcare professionals and presumably the general population alike to lower risk of long-term complications.
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Khokhar D, Marella S, Idelman G, Chang JW, Chehade M, Hogan SP. Eosinophilic esophagitis: Immune mechanisms and therapeutic targets. Clin Exp Allergy 2022; 52:1142-1156. [PMID: 35778876 PMCID: PMC9547832 DOI: 10.1111/cea.14196] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Revised: 06/08/2022] [Accepted: 06/20/2022] [Indexed: 01/26/2023]
Abstract
Eosinophilic esophagitis (EoE) is an emerging chronic inflammatory disease of the oesophagus and is clinically characterized by upper gastrointestinal (GI) symptoms including dysphagia and esophageal food impaction. Histopathologic manifestations, which include intraepithelial eosinophilic inflammation and alterations of the esophageal squamous epithelium, such as basal zone hyperplasia (BZH) and dilated intercellular spaces (DIS), are thought to contribute to esophageal dysfunction and disease symptoms. Corroborative clinical and discovery science-based studies have established that EoE is characterized by an underlying allergic inflammatory response, in part, related to the IL-13/CCL26/eosinophil axis driving dysregulation of several key epithelial barrier and proliferative regulatory genes including kallikrein (KLK) serine proteases, calpain 14 (CAPN14) and anoctamin 1 (ANO1). The contribution of these inflammatory and proliferative processes to the clinical and histological manifestations of disease are not fully elucidated. Herein, we discuss the immune molecules and cells that are thought to underlie the clinical and pathologic manifestations of EoE and the emerging therapeutics targeting these processes for the treatment of EoE.
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Affiliation(s)
- Dilawar Khokhar
- Division of Allergy and ImmunologyUniversity of MichiganAnn ArborMichiganUSA
- Mary H Weiser Food Allergy CenterUniversity of MichiganAnn ArborMichiganUSA
| | - Sahiti Marella
- Mary H Weiser Food Allergy CenterUniversity of MichiganAnn ArborMichiganUSA
- Department of PathologyUniversity of MichiganAnn ArborMichiganUSA
| | - Gila Idelman
- Mary H Weiser Food Allergy CenterUniversity of MichiganAnn ArborMichiganUSA
| | - Joy W. Chang
- Division of Gastroenterology, Department of Internal MedicineUniversity of MichiganAnn ArborMichiganUSA
| | - Mirna Chehade
- Mount Sinai Center for Eosinophilic DisordersIcahn School of Medicine at Mount SinaiNew YorkNew YorkUSA
| | - Simon P. Hogan
- Mary H Weiser Food Allergy CenterUniversity of MichiganAnn ArborMichiganUSA
- Department of PathologyUniversity of MichiganAnn ArborMichiganUSA
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Increasing incidence of eosinophilic esophagitis in Sweden: a nationwide population study. Esophagus 2022; 19:535-541. [PMID: 35654916 DOI: 10.1007/s10388-022-00926-5] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Accepted: 05/06/2022] [Indexed: 02/03/2023]
Abstract
BACKGROUND Eosinophilic esophagitis (EoE) is a chronic inflammatory condition of the esophagus associated with dysphagia and esophageal fibrosis. The incidence of EoE is not precisely known, and significant heterogeneity in study design and disease definition have led to widely variable estimates. Through the ESPRESSO (Epidemiology Strengthened by histoPathology Reports in Sweden) study we performed a nationwide population-based study to estimate the incidence and temporal patterns of biopsy-verified EoE. METHODS Between October 2015 and April 2017, we contacted all pathology departments in Sweden (n = 28) to obtain biopsy report data on EoE. To assure a high degree of completeness, we restricted the study to 2004-2015. We then calculated age-specific and age-standardized incidence rates. RESULTS We identified 1412 incident EoE cases between 2004-2015. The overall age-standardized incidence rates of EoE in Sweden was 1.22 per 100,000 person-years. During the study period, there was a significant increase of 33% [95%CI = 31-36%] (P < 0.001) per year in EoE incidence, and in the last 3 years of follow-up (2013-2015) the incidence was 2.79 per 100,000 person-years. This corresponds to a lifetime risk of biopsy-verified EoE for men of 0.33% (1 in 295 men) and for women 0.12% (1 in 813 women). We observed an early peak of EoE disgnosed at age 15-19 years for both males and females, and a second peak in the late 30 s for males, and early 40 s for females. We noted a 3:1 male-to-female predominance, which did not significantly vary over time. CONCLUSIONS EoE seems to be increasing in Sweden, with an overall age-standardized incidence of EoE of 1.22 per 100,000 person-years in the last decade.
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Allin KH, Poulsen G, Melgaard D, Frandsen LT, Jess T, Krarup AL. Eosinophilic oesophagitis in Denmark: Population‐based incidence and prevalence in a nationwide study from 2008 to 2018. United European Gastroenterol J 2022; 10:640-650. [PMID: 36106558 PMCID: PMC9486498 DOI: 10.1002/ueg2.12273] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2022] [Accepted: 06/18/2022] [Indexed: 11/09/2022] Open
Abstract
Background Eosinophilic oesophagitis (EoE) is a chronic immune‐mediated or antigen‐mediated oesophageal disease characterised by symptoms related to oesophageal dysfunction and eosinophil‐predominant inflammation. Objective We aimed to estimate the incidence and prevalence of EoE in Denmark during the period 2008–2018. Methods Based on data from nationwide registers we identified cases of EoE using two definitions: a broad definition based solely on oesophageal biopsies registered in the Danish Pathology Register and a narrow definition also including symptoms of oesophageal dysfunction registered in the Danish National Patient Registry. The annual incidence and prevalence were standardised by sex and age in 5‐year intervals to the 2013 study population. Results From 2008 to 2011, the standardised incidence of EoE was stable, but from 2011 to 2018 it increased from 3.9 (95% CI 3.3–4.4) to 11.7 (95% CI 10.8–12.6) per 100,000 person‐years. Similar temporal trends were observed when using the narrow EoE definition. The increase in incidence was most pronounced in men and in individuals above 40 years of age. In children, the EoE incidence was a fourth of the incidence in adults aged 40–64 years: 4.4 (95% CI 3.2–5.6) versus 17.6 (95% CI 15.7–19.5) per 100,000 person‐years. The EoE incidence varied substantially across the five regions in Denmark. Overall, the biopsy rate as well as the proportion of oesophageal biopsies with detected eosinophilia increased during the study period. Conclusion This study of the entire population of Denmark during the period 2008 to 2018 shows that the incidence and prevalence of EoE is not yet plateauing and that EoE could be severely underdiagnosed, especially in children.
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Affiliation(s)
- Kristine Højgaard Allin
- Center for Molecular Prediction of Inflammatory Bowel Disease (PREDICT) Department of Clinical Medicine Aalborg University Copenhagen Denmark
- Department of Gastroenterology and Hepatology Aalborg University Hospital Aalborg Denmark
| | - Gry Poulsen
- Center for Molecular Prediction of Inflammatory Bowel Disease (PREDICT) Department of Clinical Medicine Aalborg University Copenhagen Denmark
| | - Dorte Melgaard
- Center of Clinical Research North Denmark Regional Hospital Hjørring Denmark
- Faculty of Clinical Medicine Aalborg University Aalborg Denmark
| | | | - Tine Jess
- Center for Molecular Prediction of Inflammatory Bowel Disease (PREDICT) Department of Clinical Medicine Aalborg University Copenhagen Denmark
- Department of Gastroenterology and Hepatology Aalborg University Hospital Aalborg Denmark
| | - Anne Lund Krarup
- Department of Gastroenterology and Hepatology Aalborg University Hospital Aalborg Denmark
- Faculty of Clinical Medicine Aalborg University Aalborg Denmark
- Department of Emergency Medicine and Trauma Care Aalborg University Hospital Aalborg Denmark
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Disease Burden and Unmet Need in Eosinophilic Esophagitis. Am J Gastroenterol 2022; 117:1231-1241. [PMID: 35417421 DOI: 10.14309/ajg.0000000000001777] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2021] [Accepted: 04/04/2022] [Indexed: 12/11/2022]
Abstract
Eosinophilic esophagitis (EoE) is a chronic, progressive, type 2 inflammatory disease of increasing prevalence, characterized by symptoms of dysphagia and reduced quality of life. A dysregulated type 2 immune response to food and aeroallergen leads to barrier dysfunction, chronic esophageal inflammation, remodeling, and fibrosis. Patients with EoE have impaired quality of life because of dysphagia and other symptoms. They may also suffer social and psychological implications of food-related illness and expensive out-of-pocket costs associated with treatment. Disease burden in EoE is often compounded by the presence of comorbid type 2 inflammatory diseases. Current conventional treatments include elimination diet, proton pump inhibitors, and swallowed topical corticosteroids, as well as esophageal dilation in patients who have developed strictures. These treatments demonstrate variable response rates and may not always provide long-term disease control. There is an unmet need for long-term histologic, endoscopic, and symptomatic disease control; for targeted therapies that can normalize the immune response to triggers, reduce chronic inflammation, and limit or prevent remodeling and fibrosis; and for earlier diagnosis, defined treatment outcomes, and a greater understanding of patient perspectives on treatment. In addition, healthcare professionals need a better understanding of the patient perspective on disease burden, the disconnect between symptoms and disease activity, and the progressive nature of EoE and the need for continuous monitoring and maintenance treatment. In this review, we explore the progression of disease over the patient's lifespan, highlight the patient perspective on disease, and discuss the unmet need for effective long-term treatments.
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