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Most of the major clinical signs and consequences of eosinophilic esophagitis seem to be related to tissue remodeling. Important data on remodeling activity in patients with eosinophilic esophagitis are provided by a range of current and new biologic markers and diagnostics. To completely clarify the possible advantages and restrictions of therapeutic approaches, clinical studies should take into consideration the existence and reversibility of esophageal remodeling. The degree of mucosal or submucosal disease activity may not be reflected by epithelial eosinophilic inflammation, which is used to define one criterion of disease activity".
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Enteritis , Eosinofilia , Esofagitis Eosinofílica , Gastritis , Humanos , Esofagitis Eosinofílica/diagnóstico , Esofagitis Eosinofílica/terapia , FibrosisRESUMEN
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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Duodenitis , Eosinofilia , Gastritis , Humanos , Masculino , Niño , Femenino , Eosinofilia/epidemiología , Gastritis/epidemiología , Gastritis/complicaciones , Gastritis/patología , Duodenitis/epidemiología , Duodenitis/patología , Adolescente , Preescolar , Enteritis/epidemiología , Enteritis/complicaciones , Enteritis/diagnóstico , Recurrencia , Estudios Retrospectivos , Endoscopía GastrointestinalRESUMEN
INTRODUCTION: Eosinophilic gastrointestinal disorders beyond eosinophilic esophagitis (non-EoE EGIDs) are rare chronic inflammatory disorders of the gastrointestinal (GI) tract. Diagnosis is based on clinical symptoms and histologic findings of eosinophilic inflammation after exclusion of a secondary cause or systemic disease. Currently, no guidelines exist for the evaluation of non-EoE EGIDs. Therefore, the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) formed a task force group to provide consensus guidelines for childhood non-EoE EGIDs. METHODS: The working group was composed of pediatric gastroenterologists, adult gastroenterologists, allergists/immunologists, and pathologists. An extensive electronic literature search of the MEDLINE, EMBASE, and Cochrane databases was conducted up to February 2022. General methodology was used in the formulation of recommendations according to the Appraisal of Guidelines for Research and Evaluation (AGREE) II and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to meet current standards of evidence assessment. RESULTS: The guidelines provide information on the current concept of non-EoE EGIDs, disease pathogenesis, epidemiology, clinical manifestations, diagnostic and disease surveillance procedures, and current treatment options. Thirty-four statements based on available evidence and 41 recommendations based on expert opinion and best clinical practices were developed. CONCLUSION: Non-EoE EGIDs literature is limited in scope and depth, making clear recommendations difficult. These consensus-based clinical practice guidelines are intended to assist clinicians caring for children affected by non-EoE EGIDs and to facilitate high-quality randomized controlled trials of various treatment modalities using standardized, uniform disease definitions.
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Enteritis , Eosinofilia , Esofagitis Eosinofílica , Gastritis , Gastroenterología , Niño , Humanos , Esofagitis Eosinofílica/terapia , Esofagitis Eosinofílica/tratamiento farmacológico , Enteritis/diagnóstico , Gastritis/diagnóstico , Gastritis/terapiaRESUMEN
MicroRNA (miRNA)-mediated mRNA regulation directs many homeostatic and pathological processes, but how miRNAs coordinate aberrant esophageal inflammation during eosinophilic esophagitis (EoE) is poorly understood. Here, we report a deregulatory axis where microRNA-155 (miR-155) regulates epithelial barrier dysfunction by selectively constraining tight junction CLDN7 (claudin-7). MiR-155 is elevated in the esophageal epithelium of biopsies from patients with active EoE and in cell culture models. MiR-155 localization using in situ hybridization (ISH) in patient biopsies and intra-epithelial compartmentalization of miR-155 show expression predominantly within the basal epithelia. Epithelial miR-155 activity was evident through diminished target gene expression in 3D organotypic cultures, particularly in relatively undifferentiated basal cell states. Mechanistically, generation of a novel cell line with enhanced epithelial miR-155 stable overexpression induced a functionally deficient epithelial barrier in 3D air-liquid interface epithelial cultures measured by transepithelial electrical resistance (TEER). Histological assessment of 3D esophageal organoid cultures overexpressing miR-155 showed notable dilated intra-epithelial spaces. Unbiased RNA-sequencing analysis and immunofluorescence determined a defect in epithelial barrier tight junctions and revealed a selective reduction in the expression of critical esophageal tight junction molecule, claudin-7. Together, our data reveal a previously unappreciated role for miR-155 in mediating epithelial barrier dysfunction in esophageal inflammation.
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Claudinas , Esofagitis Eosinofílica , MicroARNs , Humanos , Claudinas/genética , Esofagitis Eosinofílica/genética , Esofagitis Eosinofílica/metabolismo , Esofagitis Eosinofílica/patología , Células Epiteliales/metabolismo , Hipoxia/metabolismo , Inflamación/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Uniones Estrechas/metabolismoRESUMEN
In 2022, the US Food and Drug Administration approved dupilumab for treatment of eosinophilic esophagitis (EoE). The aims of this study were to report physician and patient perspectives on initiating dupilumab. A 2-pronged approach was used: (1) data on physician prescribing practices was gathered via retrospective chart review of EoE patients prescribed dupilumab and (2) pediatric patients on dupilumab were approached to complete a questionnaire regarding reasons for initiation. During this time, 42 patients were prescribed dupilumab. From the physician's perspective, the primary reasons for dupilumab included nonresponse to topical corticosteroids (TCS) (52%), nonadherence (28%), adverse effects (10%), or to treat multiple atopic diseases (5%). The median dupilumab initiation time, from day prescribed to first injection, was 37 days [interquartile range (IQR) 37]. Almost all required prior authorization (PA) (98%), while 17% required letter of appeal and 2% required peer-to-peer. Fifteen patients (36%) completed the questionnaire portion of the study. From the patient's perspective, the primary reasons for dupilumab initiation included nonresponse to TCS (27%), nonadherence to TCS (27%), concern about adverse effects of TCS (7%), and treatment of multiple atopic diseases (33%). In conclusion, physicians are prescribing dupilumab primarily for nonresponse to TCS and almost all required PA with a long delay to starting dupilumab.
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Fármacos Dermatológicos , Esofagitis Eosinofílica , Humanos , Niño , Esofagitis Eosinofílica/tratamiento farmacológico , Estudios Retrospectivos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Glucocorticoides/uso terapéutico , Fármacos Dermatológicos/efectos adversos , Evaluación del Resultado de la Atención al Paciente , Resultado del TratamientoRESUMEN
INTRODUCTION: Eosinophilic Gastrointestinal Disorders beyond Eosinophilic Esophagitis (non-EoE EGIDs) are rare chronic inflammatory disorders of the gastrointestinal (GI) tract. Diagnosis is based on clinical symptoms and histologic findings of eosinophilic inflammation after exclusion of a secondary cause or systemic disease. Currently, no guidelines exist for the evaluation of non-EoE EGIDs. Therefore, the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) formed a task force group to provide consensus guidelines for childhood non-EoE EGIDs. METHODS: The working group was composed of pediatric gastroenterologists, adult gastroenterologists, allergists/immunologists, and pathologists. An extensive electronic literature search of the MEDLINE, EMBASE, and Cochrane databases was conducted up to February 2022. General methodology was used in the formulation of recommendations according to the Appraisal of Guidelines for Research and Evaluation (AGREE) II and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to meet current standards of evidence assessment. RESULTS: The guidelines provide information on the current concept of non-EoE EGIDs, disease pathogenesis, epidemiology, clinical manifestations, diagnostic and disease surveillance procedures, and current treatment options. Thirty-four statements based on available evidence and 41 recommendations based on expert opinion and best clinical practices were developed. CONCLUSION: Non-EoE EGIDs literature is limited in scope and depth, making clear recommendations difficult. These consensus-based clinical practice guidelines are intended to assist clinicians caring for children affected by non-EoE EGIDs and to facilitate high-quality randomized controlled trials of various treatment modalities using standardized, uniform disease definitions.
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BACKGROUND: Little is known regarding the impact of race, ethnicity, and socioeconomic status on the health outcomes of children with eosinophilic esophagitis (EoE). OBJECTIVE: To (1) identify demographic characteristics of children diagnosed with EoE in a large tertiary care center, and (2) determine associations between a patient's demographics and depth of evaluation or treatment choices. METHODS: This retrospective cohort study included children 0 to 18 years old seen in Children's Hospital Colorado between January 1, 2009, and December 31, 2020. Demographics were extracted from the electronic medical record. Rural-Urban Commuting Area taxonomy codes were used to classify urbanization. Area Deprivation Index (ADI) scores were used to categorize neighborhood advantage/disadvantage. Data were analyzed using descriptive statistics and regression analysis. RESULTS: The study included 2,117 children with EoE. Children with higher state ADI scores (greater neighborhood disadvantage) had less radiographic evaluation of their disease (odds ratio [95% CI] per unit increase in state ADI = 0.93 [0.89-0.97]; P = .0002) and had esophageal dilations at younger ages (r = -0.24; P = .007). Black children compared with White children were younger at diagnosis (8.3 y vs 10.0 y; P = .002). Children from rural areas were seen less by feeding therapy (3.9% vs 9.9%; P = .02), but were younger at their visits (2.3 y vs 4.3 y; P < .001). CONCLUSIONS: In this study of children with EoE cared for in a large tertiary care center, we found differences in presentation and care depending on race, urbanization, and socioeconomic status.
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Esofagitis Eosinofílica , Niño , Humanos , Recién Nacido , Lactante , Preescolar , Adolescente , Esofagitis Eosinofílica/diagnóstico , Esofagitis Eosinofílica/epidemiología , Esofagitis Eosinofílica/terapia , Estudios Retrospectivos , Endoscopía , EtnicidadRESUMEN
INTRODUCTION: Inflammation in eosinophilic esophagitis (EoE) often leads to esophageal strictures. Evaluating esophageal narrowing is clinically challenging. We evaluated esophageal distensibility as related to disease activity, fibrosis, and dysphagia. METHODS: Adult patients with and without EoE underwent endoscopy and distensibility measurements. Histology, distensibility, and symptoms were analyzed. RESULTS: Patients with EoE had significantly lower distensibilities than controls. We found a cohort with esophageal diameter under 15 mm despite lack of dysphagia. DISCUSSION: This study raises concern that current assessments of fibrostenosis are suboptimal. We describe a cohort with unrecognized slender esophagus that were identified through impedance planimetry measurements. This tool provides additional information beyond symptomatic, histologic, and endoscopic assessments.
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Trastornos de Deglución , Esofagitis Eosinofílica , Estenosis Esofágica , Adulto , Humanos , Esofagitis Eosinofílica/complicaciones , Esofagitis Eosinofílica/diagnóstico , Esofagitis Eosinofílica/patología , Trastornos de Deglución/diagnóstico , Trastornos de Deglución/etiología , Estenosis Esofágica/diagnóstico , Estenosis Esofágica/etiología , Estenosis Esofágica/patología , Endoscopía GastrointestinalRESUMEN
BACKGROUND: Recent studies have shown that IgG4 is increased in the esophageal tissue of eosinophilic esophagitis patients, including the presence of IgG4+ plasma cells. AIMS: Our aim was to determine whether IgG4 is elevated in the gastric or duodenal tissue of pediatric patients with eosinophilic gastritis or duodenitis (EoG or EoD). METHODS: This was a retrospective single center study. Pediatric patients were characterized as having active EoG, EoD, or as controls based on clinical symptoms and histologic features. Immunohistochemistry for IgG4 was performed in gastric and duodenal tissue, and peak IgG4+ cells were compared between groups and after treatment. RESULTS: The frequency of IgG4+ cells was significantly higher in patients with EoG and EoD compared to controls in the stomach [EoG 6.5 cells/hpf (3.6-10.9), control 0 cells/hpf (0-0.7), p<0.0001] and duodenum [EoD 7.5 cells/hpf (2.8-37), control 0.5 cells/hpf (0.3-1.3), p<0.001)] respectively, and positively correlated with eosinophil counts (stomach: r 0.74, p<0.0001; duodenum: r 0.57, p<0.0001). The amount of tissue IgG4 was significantly decreased in patients in remission but not in persistently active disease. CONCLUSIONS: These data suggest local tissue production of IgG4 may be a universal feature of eosinophilic gastrointestinal disease that tracks with disease activity.
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Duodenitis , Esofagitis Eosinofílica , Humanos , Niño , Estudios Retrospectivos , Inmunoglobulina G , Esofagitis Eosinofílica/diagnósticoRESUMEN
BACKGROUND & AIMS: Disease activity and severity of eosinophilic esophagitis (EoE) dictate therapeutic options and management, but the decision-making process for determining severity varies among practitioners. To reduce variability in practice patterns and help clinicians monitor the clinical course of the disease in an office setting, we aimed to create an international consensus severity scoring index for EoE. METHODS: A multidisciplinary international group of adult and pediatric EoE researchers and clinicians, as well as non-EoE allergy immunology and gastroenterology experts, formed 3 teams to review the existing literature on histology, endoscopy, and symptoms of EoE in the context of progression and severity. A steering committee convened a 1-day virtual meeting to reach consensus on each team's opinion on salient features of severity across key clinicopathologic domains and distill features that would allow providers to categorize disease severity. RESULTS: Symptom features and complications and inflammatory and fibrostenotic features on both endoscopic and histologic examination were collated into a simplified scoring system-the Index of Severity for Eosinophilic Esophagitis (I-SEE)-that can be completed at routine clinic visits to assess disease severity using a point scale of 0-6 for mild, 7-14 for moderate, and ≥15 for severe EoE. CONCLUSIONS: A multidisciplinary team of experts iteratively created a clinically usable EoE severity scoring system denominated "I-SEE" to guide practitioners in EoE management by standardizing disease components reflecting disease severity beyond eosinophil counts. I-SEE should be validated and refined using data from future clinical trials and routine clinical practice to increase its utilization and functionality.
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Esofagitis Eosinofílica , Adulto , Niño , Consenso , Endoscopía Gastrointestinal , Enteritis , Eosinofilia , Esofagitis Eosinofílica/tratamiento farmacológico , Esofagitis Eosinofílica/terapia , Gastritis , Humanos , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND & AIMS: Disease activity and severity of eosinophilic esophagitis (EoE) dictate therapeutic options and management, but the decision-making process for determining severity varies among practitioners. To reduce variability in practice patterns and help clinicians monitor the clinical course of the disease in an office setting, we aimed to create an international consensus severity scoring index for EoE. METHODS: A multidisciplinary international group of adult and pediatric EoE researchers and clinicians, as well as non-EoE allergy immunology and gastroenterology experts, formed 3 teams to review the existing literature on histology, endoscopy, and symptoms of EoE in the context of progression and severity. A steering committee convened a 1-day virtual meeting to reach consensus on each team's opinion on salient features of severity across key clinicopathologic domains and distill features that would allow providers to categorize disease severity. RESULTS: Symptom features and complications and inflammatory and fibrostenotic features on both endoscopic and histologic examination were collated into a simplified scoring system-the Index of Severity for Eosinophilic Esophagitis (I-SEE)-that can be completed at routine clinic visits to assess disease severity using a point scale of 0-6 for mild, 7-14 for moderate, and ≥15 for severe EoE. CONCLUSIONS: A multidisciplinary team of experts iteratively created a clinically usable EoE severity scoring system denominated "I-SEE" to guide practitioners in EoE management by standardizing disease components reflecting disease severity beyond eosinophil counts. I-SEE should be validated and refined using data from future clinical trials and routine clinical practice to increase its utilization and functionality.
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Esofagitis Eosinofílica , Adulto , Niño , Consenso , Endoscopía Gastrointestinal , Enteritis , Eosinofilia , Esofagitis Eosinofílica/tratamiento farmacológico , Esofagitis Eosinofílica/terapia , Gastritis , Humanos , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Esophageal remodeling is a factor in disease progression and symptom severity for patients with eosinophilic esophagitis (EoE). Remodeling can begin early in children, resulting in stricture and food impaction. Detection of esophageal remodeling often depends on endoscopy and is appreciated only in its later stages. OBJECTIVE: We sought to determine whether luminal eosinophil-associated and remodeling proteins captured by the esophageal string test (EST) correlate with measures of esophageal remodeling and biomarkers of the epithelial-mesenchymal transition (EMT). METHODS: Patients with EoE (7-18 years old) were enrolled from 2 pediatric hospitals. Participants performed the EST and underwent endoscopy. Histology, distensibility measured by endoluminal functional lumen imaging probe, and symptoms were assessed. Protein quantitation by ELISA was performed on mucosal biopsy and EST samples. Tissue sections were evaluated for EMT. Outcome measures were summarized, and Spearman ρ was used to assess bivariate correlations. RESULTS: Forty patients (68% male) were enrolled (mean age, 12.5 years). Twenty-four (60%) had active disease (≥15 eosinophils per high-power field). EST-captured eotaxin-3, major basic protein 1, EDN, eosinophil peroxidase, and Charcot-Leyden crystal protein/galectin-10 showed significant correlations with peak eosinophils per high-power field (ρ 0.53-0.68, P < .001). Luminal proteins positively correlated with endoscopic features and markers of EMT, and negatively with esophageal distensibility. Periostin was captured by the EST and correlated with eosinophil density, basal zone hyperplasia, endoscopic appearance, and markers of EMT. CONCLUSION: Luminal markers of esophageal remodeling in addition to biomarkers of eosinophilic inflammation correlate with epithelial and functional remodeling in EoE.
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Esofagitis Eosinofílica , Adolescente , Biomarcadores/metabolismo , Niño , Enteritis , Eosinofilia , Esofagitis Eosinofílica/patología , Eosinófilos/patología , Femenino , Gastritis , Humanos , Inflamación/patología , MasculinoRESUMEN
BACKGROUND & AIMS: Substantial heterogeneity in terminology used for eosinophilic gastrointestinal diseases (EGIDs), particularly the catchall term "eosinophilic gastroenteritis," limits clinical and research advances. We aimed to achieve an international consensus for standardized EGID nomenclature. METHODS: This consensus process utilized Delphi methodology. An initial naming framework was proposed and refined in iterative fashion, then assessed in a first round of Delphi voting. Results were discussed in 2 consensus meetings, and the framework was updated and reassessed in a second Delphi vote, with a 70% threshold set for agreement. RESULTS: Of 91 experts participating, 85 (93%) completed the first and 82 (90%) completed the second Delphi surveys. Consensus was reached on all but 2 statements. "EGID" was the preferred umbrella term for disorders of gastrointestinal (GI) tract eosinophilic inflammation in the absence of secondary causes (100% agreement). Involved GI tract segments will be named specifically and use an "Eo" abbreviation convention: eosinophilic gastritis (now abbreviated EoG), eosinophilic enteritis (EoN), and eosinophilic colitis (EoC). The term "eosinophilic gastroenteritis" is no longer preferred as the overall name (96% agreement). When >2 GI tract areas are involved, the name should reflect all of the involved areas. CONCLUSIONS: This international process resulted in consensus for updated EGID nomenclature for both clinical and research use. EGID will be the umbrella term, rather than "eosinophilic gastroenteritis," and specific naming conventions by location of GI tract involvement are recommended. As more data are developed, this framework can be updated to reflect best practices and the underlying science.
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Enteritis , Eosinofilia , Esofagitis Eosinofílica , Gastritis , Humanos , Consenso , Enteritis/diagnóstico , Enteritis/complicaciones , Gastritis/diagnóstico , Gastritis/complicaciones , Eosinofilia/diagnóstico , Eosinofilia/complicaciones , Esofagitis Eosinofílica/complicacionesRESUMEN
BACKGROUND & AIMS: Colonic eosinophilia, an enigmatic finding often referred to as eosinophilic colitis (EoC), is a poorly understood condition. Whether EoC is a distinct disease or a colonic manifestation of eosinophilic gastrointestinal diseases (EGIDs) or inflammatory bowel disease (IBD) is undetermined. METHODS: Subjects with EoC (n = 27) and controls (normal [NL, n = 20], Crohn's disease [CD, n = 14]) were enrolled across sites associated with the Consortium of Eosinophilic Gastrointestinal Disease Researchers. EoC was diagnosed as colonic eosinophilia (ascending ≥100, descending ≥85, sigmoid ≥65 eosinophils/high-power field) with related symptoms. Colon biopsies were subjected to RNA sequencing. Associations between gene expression and histologic features were analyzed with Spearman correlation; operational pathways and cellular constituents were computationally derived. RESULTS: We identified 987 differentially expressed genes (EoC transcriptome) between EoC and NL (>1.5-fold change, P < .05). Colonic eosinophil count correlated with 31% of EoC transcriptome, most notably with CCL11 and CLC (r = 0.78 and 0.77, P < .0001). Among EoC and other EGIDs, there was minimal transcriptomic overlap and minimal evidence of a strong allergic type 2 immune response in EoC compared with other EGIDs. Decreased cell cycle and increased apoptosis in EoC compared with NL were identified by functional enrichment analysis and immunostaining using Ki-67 and cleaved caspase-3. Pericryptal circumferential eosinophil collars were associated with the EoC transcriptome (P < .001). EoC transcriptome-based scores were reversible with disease remission and differentiated EoC from IBD, even after controlling for colonic eosinophil levels (P < .0001). CONCLUSIONS: We established EoC transcriptomic profiles, identified mechanistic pathways, and integrated findings with parallel IBD and EGID data. These findings establish EoC as a distinct disease compared with other EGIDs and IBD, thereby providing a basis for improving diagnosis and treatment.
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Colitis Microscópica , Eosinofilia , Enfermedades Inflamatorias del Intestino , Enteritis , Eosinofilia/diagnóstico , Eosinofilia/genética , Gastritis , HumanosRESUMEN
The US Food and Drug Administration hosted a workshop on July 21, 2021, to discuss the disease characteristics, natural history, and end points to assess treatment benefit in patients with eosinophilic gastrointestinal disorders (EGIDs) beyond eosinophilic esophagitis (EoE). Notably, EGIDs beyond EoE, such as eosinophilic gastritis, eosinophilic enteritis, and eosinophilic colitis, herein referred to as non-EoE EGIDs, are understudied relative to EoE. This workshop provided a forum for open discussion among stakeholders-medical professionals (including their societies and research groups), Food and Drug Administration representatives, an industry representative, and a patient representative-to facilitate drug development. Experts in many disciplines related to EGIDs, including allergy, immunology, epidemiology, gastroenterology, and pathology, and both adult and pediatric clinicians contributed. Herein, we discuss some of the insights of the material presented at the meeting and present perspectives on moving the field forward toward drug approval.
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Enteritis , Esofagitis Eosinofílica , Gastritis , Adulto , Niño , Enteritis/tratamiento farmacológico , Enteritis/patología , Eosinofilia , Esofagitis Eosinofílica/tratamiento farmacológico , Esofagitis Eosinofílica/epidemiología , Gastritis/tratamiento farmacológico , Gastritis/patología , Humanos , Estados Unidos , United States Food and Drug AdministrationRESUMEN
BACKGROUND: End points used to determine treatment efficacy in eosinophilic esophagitis (EoE) have evolved over time. With multiple novel therapies in development for EoE, harmonization of outcomes measures will facilitate evidence synthesis and appraisal when comparing different treatments. OBJECTIVE: We sought to develop a core outcome set (COS) for controlled and observational studies of pharmacologic and diet interventions in adult and pediatric patients with EoE. METHODS: Candidate outcomes were generated from systematic literature reviews and patient engagement interviews and surveys. Consensus was established using an iterative Delphi process, with items voted on using a 9-point Likert scale and with feedback from other participants to allow score refinement. Consensus meetings were held to ratify the outcome domains of importance and the core outcome measures. Stakeholders were recruited internationally and included adult and pediatric gastroenterologists, allergists, dieticians, pathologists, psychologists, researchers, and methodologists. RESULTS: The COS consists of 4 outcome domains for controlled and observational studies: histopathology, endoscopy, patient-reported symptoms, and EoE-specific quality of life. A total of 69 stakeholders (response rate 95.8%) prioritized 42 outcomes in a 2-round Delphi process, and the final ratification meeting generated consensus on 33 outcome measures. These included measurement of the peak eosinophil count, Eosinophilic Esophagitis Histology Scoring System, Eosinophilic Esophagitis Endoscopic Reference Score, and patient-reported measures of dysphagia and quality of life. CONCLUSIONS: This interdisciplinary collaboration involving global stakeholders has produced a COS that can be applied to adult and pediatric studies of pharmacologic and diet therapies for EoE and will facilitate meaningful treatment comparisons and improve the quality of data synthesis.
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Esofagitis Eosinofílica/terapia , Medición de Resultados Informados por el Paciente , Adulto , Anciano , Niño , Esofagitis Eosinofílica/patología , Esofagitis Eosinofílica/psicología , Femenino , Humanos , Cooperación Internacional , Masculino , Persona de Mediana Edad , Calidad de VidaRESUMEN
Endoscopy and mucosal biopsies are essential to the diagnosis of EoE. Together they either confirm or exclude mucosal eosinophilia and provide a visual inspection of the esophagus that may be consistent with EoE or suggest other underlying etiologies. Endoscopy also plays an important therapeutic role in the management of EoE including the assessment of treatment response and treatment of associated complications including esophageal stricture and food impaction. Assessment of treatment response largely depends on endoscopy and mucosal biopsies although less invasive strategies may eventually provide alternative means to assess mucosal inflammation. Herein we will review current use of endoscopy in EoE, including recently developed technologies and their role in the management of EoE.
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BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic allergen-mediated disease of the esophagus. Pharmacologic treatment has largely relied on repurposing corticosteroids. Ciclesonide (CIC) is a corticosteroid for the treatment of asthma with biochemical properties that improve topical potency. OBJECTIVE: To determine whether CIC decreased clinicopathological features of EoE. METHODS: We performed a retrospective cohort study of patients with EoE treated with CIC at a pediatric hospital from 2010 to 2019. Data were extracted from the electronic health record. Patients who were prescribed CIC with pre- and post-CIC endoscopic and histological data available were included for analysis. RESULTS: A total of 281 patients were treated with CIC and 81 met criteria for inclusion. Use of CIC was associated with reduced symptoms including dysphagia (P < .001), abdominal pain (P < .001), vomiting (P = .01), heartburn (P = .02), and behavior changes (P = .02). Average composite endoscopic reference scores decreased from 2.54 to 1.37 (P < .001), with improvement in exudates, edema, and furrows (all P < .001). Peak eosinophil counts decreased from 48 to 23 eosinophils/hpf (P < .001). Forty-three patients (53%) achieved remission (<15 eosinophils/hpf). Esophageal Candida was reported in 1 patient. Fasting morning cortisol concentrations were low in 10 of 31 patients tested. Six of these 10 patients had abnormal adrenocorticotropic hormone stimulation testing, 5 of 6 diagnosed with adrenal insufficiency before transition to CIC and 3 of 6 with subsequent normalization of adrenal function on CIC therapy. CONCLUSIONS: Patients with EoE treated with CIC experienced significant reductions in clinicopathological features of EoE. CIC can be considered an alternative therapy in patients with known adrenal insufficiency or at risk of developing adrenal insufficiency.