Endoscopic Features of Eosinophilic Esophagitis.

Edema, rings, exudates, furrows, and strictures (EREFS) represent the major endoscopic features of eosinophilic esophagitis (EoE). The Endoscopic Reference System (EREFS) grading system is easy to learn and apply during daily clinical practice in the diagnosis and follow-up of EoE patients. When endoscopy is performed by an EoE-experienced physician, the EREFS criteria will identify the majority of EoE patients. The EREFS score from the area of greatest involvement of the esophagus should be reported. The EREFS grading system was formally validated as an endoscopy score and several randomized placebo-controlled trials have shown responsiveness of the EREFS score to therapeutic interventions.

Pediatric Patients with Eosinophilic Esophagitis and Their Parents Identify Symptoms as the Most Important Treatment Outcome.

INTRODUCTION: Given the lack of data, we aimed to explore which therapeutic endpoints pediatric patients with eosinophilic esophagitis (EoE) and their parents consider to be relevant. METHODS: We created an educational brochure on EoE and a questionnaire, both of which were content-validated by pediatric patients and parents. Validated documents were sent to 112 patients and parents. They ranked the importance (5 levels) of short (during next 3 months) and long-term (≥1 year) treatment effect on symptoms, quality of life, endoscopic inflammation, stricture formation, histological inflammation, and fibrosis. RESULTS: A total of 45 parents and 30 pediatric patients ≥11 years completed the questionnaires. Pediatric patients identified improvement in the following domains as most important in the short- and long-term, respectively: symptoms (73% vs. 77%), QoL (53% vs. 57%), histologic inflammation (47% vs. 50%), histologic fibrosis (40% vs. 33%), endoscopic inflammation (47% vs. 40%), and strictures (33% vs. 40%). Parents of children ≥11 years old classified improvement in the following domains as most important in the short- and long-term, respectively: symptoms (70% vs. 83%), QoL (63% vs. 80%), histologic inflammation (67% vs. 77%), histologic fibrosis (47% vs. 63%), endoscopic inflammation (77% vs. 80%), and strictures (40% vs. 53%). Agreement between caregiver and children on the short-term importance of treatment outcomes was as follows: symptoms (77%), QoL (40%), histologic inflammation and fibrosis (47% and 43%), endoscopic inflammation and strictures (50% and 40%). CONCLUSION: Pediatric patients and parents attributed most importance to improvement in symptoms and QoL. Agreement between parents and patients regarding therapy goals is limited.

A Multicenter Long-Term Cohort Study of Eosinophilic Esophagitis Variants and Their Progression to Eosinophilic Esophagitis Over Time.

INTRODUCTION: Eosinophilic esophagitis (EoE) variants have been recently characterized as conditions with symptoms of esophageal dysfunction resembling EoE, but absence of significant esophageal eosinophilia. Their disease course and severity have yet to be determined. METHODS: Patients from 6 EoE centers with symptoms of esophageal dysfunction, but peak eosinophil counts of <15/hpf in esophageal biopsies and absence of gastroesophageal reflux disease with at least one follow-up visit were included. Clinical, (immuno)histological, and molecular features were determined and compared with EoE and healthy controls. RESULTS: We included 54 patients with EoE variants (EoE-like esophagitis 53.7%; lymphocytic esophagitis 13.0%; and nonspecific esophagitis 33.3%). In 8 EoE-like esophagitis patients, EoE developed after a median of 14 months (interquartile range 3.6-37.6). Such progression increased over time (17.6% year 1, 32.0% year 3, and 62.2% year 6). Sequential RNA sequencing analyses revealed only 7 genes associated with this progression (with TSG6 and ALOX15 among the top 3 upregulated genes) with upregulation of a previously attenuated Th2 pathway. Immunostaining confirmed the involvement of eosinophil-associated proteins (TSG6 and ALOX15) and revealed a significantly increased number of GATA3-positive cells during progression, indicating a Th1/Th2 switch. Transition from one EoE variant (baseline) to another variant (during follow-up) was seen in 35.2% (median observation time of 17.3 months). DISCUSSION: Transition of EoE variants to EoE suggests the presence of a disease spectrum. Few genes seem to be associated with the progression to EoE with upregulation of a previously attenuated Th2 signal. These genes, including GATA3 as a Th1/Th2 switch regulator, may represent potential therapeutic targets in early disease pathogenesis.

Histological Phenotyping in Eosinophilic Esophagitis: Localized Proximal Disease Is Infrequent but Associated with Less Severe Disease and Better Disease Outcome.

INTRODUCTION: It is still unknown whether eosinophilic esophagitis (EoE) patients with localized disease are different from those with extended disease. METHODS: We evaluated prospectively included patients in the Swiss EoE cohort. Data on all patients with active disease at baseline, no concomitant gastroesophageal reflux disease, no strictures at baseline, and at least one follow-up visit were analyzed. We compared patients with histologically localized proximal versus distal versus extended (=proximal and distal) disease with regard to patient, disease characteristics, disease presentation, and development of complications. RESULTS: We included 124 patients with a median of 2.5 years of follow-up (73.4% males, median age 35.0 years). Ten patients had proximal (8.1%), 46 patients had distal (37.1%), and 68 patients had extended disease (54.8%). Patients with proximal disease were significantly more often females (80%) compared with patients with distal (26.1%, p = 0.002) or extended disease (19.1%, p < 0.001) and reported less severe symptoms (VAS 0 vs. VAS 1, p = 0.001). Endoscopic and histological disease was less pronounced in the proximal esophagus of proximal EoE compared to extended disease (EREFS 1.0 vs. 3.0, p = 0.001; 27.0 eos/hpf vs. 52.5 eos/hpf, p = 0.008). Patients with proximal disease were less likely to undergo dilation compared to patients with distal disease in the follow-up (3.3% vs. 23.3%, p = 0.010). In a multivariate Cox regression model, proximal eosinophilia was less likely to be associated with treatment failure compared to distal eosinophilia. CONCLUSION: Although isolated proximal EoE is infrequent, it is associated with less severe disease and better disease outcome. Proximal disease appears to present a unique EoE phenotype.

Assessing the Clinical and Endoscopic Efficacy of Extended Treatment Duration with Different Doses of Mesalazine for Mild-to-Moderate Ulcerative Colitis beyond 8 Weeks of Induction.

Introduction: High-strength mesalazine formulations play an important role in providing a convenient option to increase the dose in ulcerative colitis (UC) patients and therefore avoiding the switch to another therapeutic class. Higher doses of mesalazine may be required during periods of remission in order to prevent relapse. Aim: The aim of the study was to investigate clinical outcomes of three mesalazine maintenance doses adapted for post induction response. Methods: In this post hoc analysis, 675 UC patients entered an open-label extension study for a total of 38 weeks (including 8-12 week induction period with 3.2 g/day mesalazine). After the induction period, they were separated into three groups: remitters (in clinical and endoscopic remission), responders (decrease in Partial Mayo Clinic Score of ≥2 points and ≥30% from week 0), and nonresponders (failed to achieve endoscopic or clinical response at week 8) and received 1.6 g/day, 3.2 g/day, or 4.8 g/day of mesalazine (using a new 1,600 mg mesalazine tablet), respectively. Results: 133/202 (65.8%), 108/274 (39.4%), and 59/199 (29.6%) patients achieved clinical and endoscopic remission at week 38 with 1.6 g/day, 3.2 g/day, and 4.8 g/day, respectively. At week 38, 142/202 (70.3%), 93/274 (33.9%), and 61/199 (30.7%) patients achieved clinical remission (stool score of 0 and rectal bleeding score of 0) with 1.6 g/day, 3.2 g/day, and 4.8 g/day, respectively. Conclusions: Patients partially responding or not responding to an initial induction dose of 3.2 g/day mesalazine could benefit from an extended treatment period at the same dose, or an increase to 4.8 g/day in an attempt to achieve combined clinical and endoscopic remission.

Lack of Benefit for Early Escalation to Advanced Therapies in Ulcerative Colitis: Critical Appraisal of Current Evidence.

Although ulcerative colitis [UC] shares many common pathways and therapeutic options with Crohn's disease [CD], CD patients are four times more likely to undergo surgery 10 years into their disease in the biological era and are more likely to have extraintestinal manifestations than UC patients. Early treatment in CD has been demonstrated to modify the natural history of the disease and potentially delay surgery. Previous reviews on this topic have borrowed their evidence from CD to make UC-specific recommendations. This review highlights the emergence of UC-specific data from larger cohort studies and a comprehensive individual patient data systemic review and meta-analysis to critically appraise evidence on the utility of early escalation to advanced therapies with respect to short-, medium-, and long-term outcomes. In UC, the utility of the early escalation concept for the purposes of changing the natural history, including reducing colectomy and hospitalizations, is not supported by the available data. Data on targeting clinical, biochemical, endoscopic, and histological outcomes are needed to demonstrate that they are meaningful with regard to achieving reductions in hospitalization and surgery, improving quality of life, and minimizing disability. Analyses of different populations of UC patients, such as those with 'relapsing & remitting' disease or with severe or complicated disease course, are urgently needed. The costs and risk/benefit profile of some of the newer advanced therapies should be carefully considered. In this clinical landscape, it appears premature to advocate an indiscriminate 'one size fits all' approach to escalating to advanced therapies early during the course of UC.

Barrett's Esophagus in Eosinophilic Esophagitis in Swiss Eosinophilic Esophagitis Cohort Study (SEECS).

INTRODUCTION: There is a complex interrelationship between gastroesophageal reflux disease (GERD) and eosinophilic esophagitis (EoE) potentially promoting the occurrence and modulating severity of each other reciprocally. Presence of Barrett's esophagus (BE) is a defining factor for the diagnosis of GERD. While several studies investigated the potential impact of concomitant GERD on the presentation and course of EoE, little was known with regards to BE in EoE patients. METHODS: We analyzed prospectively collected clinical, endoscopic, and histological data from patients enrolled in the Swiss Eosinophilic Esophagitis Cohort Study (SEECS) regarding differences between EoE patients with (EoE/BE+) versus without BE (EoE/BE-) and determined the prevalence of BE in EoE patients. RESULTS: Among a total of 509 EoE patients included in our analysis, 24 (4.7%) had concomitant BE with a high male preponderance (EoE/BE+ 83.3% vs. EoE/BE- 74.4%). While there were no differences in dysphagia, odynophagia was significantly (12.5 vs. 3.1%, p = 0.047) more common in EoE/BE+ versus EoE/BE-. General well-being at last follow-up was significantly lower in EoE/BE+. Endoscopically, we observed an increased incidence of fixed rings in the proximal esophagus in EoE/BE+ (70.8 vs. 46.3% in EoE/BE-, p = 0.019) and a higher fraction of patients with a severe fibrosis in the proximal histological specimen (8.7 vs. 1.6% in EoE/BE, p = 0.017). CONCLUSION: Our study reveals that BE is twice as frequent in EoE patients compared to general population. Despite many similarities between EoE patients with and without BE, the finding of a more pronounced remodeling in EoE patients with Barrett is noteworthy.

Impact of Diagnostic Delay on Disease Course in Pediatric- versus Adult-Onset Patients with Ulcerative Colitis: Data from the Swiss IBD Cohort.

Introduction: Given the lack of data, we aimed to assess the impact of the length of diagnostic delay on the natural history of ulcerative colitis (UC) in pediatric (diagnosed <18 years) and adult patients (diagnosed ≥18 years). Methods: Data from the Swiss Inflammatory Bowel Disease Cohort Study were analyzed. Diagnostic delay was defined as the interval between the first appearance of UC-related symptoms until diagnosis. Logistic regression modeling evaluated the appearance of the following complications in the long term according to the length of diagnostic delay: colonic dysplasia, colorectal cancer, UC-related hospitalization, colectomy, and extraintestinal manifestations (EIMs). Results: A total of 184 pediatric and 846 adult patients were included. The median diagnostic delay was 4 [IQR 2-7.5] months for the pediatric-onset group and 3 [IQR 2-10] months for the adult-onset group (p = 0.873). In both, pediatric- and adult-onset groups, the length of diagnostic delay at UC diagnosis was not associated with colectomy, UC-related hospitalization, colon dysplasia, and colorectal cancer. EIMs were significantly more prevalent at UC diagnosis in the adult-onset group with long diagnostic delay than in the adult-onset group with short diagnostic delay (p = 0.022). In the long term, the length of diagnostic delay was associated in the adult-onset group with colorectal dysplasia (p = 0.023), EIMs (p < 0.001), and more specifically arthritis/arthralgias (p < 0.001) and ankylosing spondylitis/sacroiliitis (p < 0.001). In the pediatric-onset UC group, the length of diagnostic delay in the long term was associated with arthritis/arthralgias (p = 0.017); however, it was not predictive for colectomy and UC-related hospitalization. Conclusions: As colorectal cancer and EIMs are associated with considerable morbidity and costs, every effort should be made to reduce diagnostic delay in UC patients.

Diagnostic Delay in Patients With Eosinophilic Esophagitis Has Not Changed Since the First Description 30 Years Ago: Diagnostic Delay in Eosinophilic Esophagitis.

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.

A Clinical Severity Index for Eosinophilic Esophagitis: Development, Consensus, and Future Directions.

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.

A Clinical Severity Index for Eosinophilic Esophagitis: Development, Consensus, and Future Directions.

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.

Close follow-up is associated with fewer stricture formation and results in earlier detection of histological relapse in the long-term management of eosinophilic esophagitis.

BACKGROUND AND AIMS: No recommendations exist regarding optimal follow-up schedule in patients with eosinophilic esophagitis (EoE) under maintenance treatment. METHODS: We retrospectively evaluated a long-term surveillance concept at the Swiss EoE clinic, where clinical, endoscopic and histological disease activity is assessed annually regardless of EoE symptoms. Data on 159 adult patients under maintenance steroid treatment with available follow-up were analyzed. Patients were classified as having close (duration between visits <18 months) or non-close follow-up (≥18 months). RESULTS: We analyzed a total of 309 follow-up visits of 159 patients (123 males, age at diagnosis 38.9 ± 15.4 years). 157 (51%) visits were within a close follow-up schedule (median duration between visits of 1.0 years (interquartile range (IQR) 0.9-1.2)), while 152 visits (49%) were not (median duration between visits 2.9 years (IQR 2.0-4.1)). There was no difference regarding ongoing clinical, endoscopic, and histological disease activity, and adherence to prescribed steroid treatment between the two groups. However, stricture formation was significantly less frequently observed at visits within a close follow-up schedule (22.9 vs. 33.6%, p = 0.038). Absence of close follow-up was a significant risk factor for stricture development in a multivariate regression model. Patients who achieved histological remission and were followed within a close-follow-up schedule had significantly earlier detection of histological relapse compared to patients not within such close follow-up. CONCLUSION: Close follow-up is associated with fewer stricture formation and appears to result in earlier detection of histological relapse in patients with eosinophilic esophagitis. We advocate for regular assessment of disease activity (every 12-18 months) in order to detect relapsing disease as early as possible, and therefore potentially minimize the risk for EoE complications.

Management of eosinophilic esophagitis associated food impaction in Europe and the United States.

Eosinophilic esophagitis (EoE) is the most common cause of esophageal food impaction (EFI). Approaches to management of EFI due to EoE have not been well characterized. We conducted a web-based survey to understand approaches to management of EFI due to EoE among endoscopists. Questions focused on management of patients from presentation to post-endoscopy follow-up. The survey was administered to a list of eligible candidates provided by societies of gastroenterology. A total of 308 endoscopists completed the questionnaire. The majority (83%) practiced in Europe and treated adults (78%). Most agreed patients should be advised to seek emergency care (66%) within 1 to 2 hours (41% agreement). There was agreement that medications to induce vomiting should be avoided (84%) and that blood tests or imaging studies were usually not required before endoscopy. By contrast, there was more variability in the type of sedation recommended and the need for endotracheal intubation, especially when comparing more experienced with less experienced EoE-endoscopists. Overall, fewer than half (43%) respondents recommended obtaining esophageal biopsies during the initial endoscopy. However, there were significant differences in the proportion who recommended biopsies based on level of EoE-experience (25, 52, 77%, P < 0.001; less vs. moderate vs. very experienced) and comparing pediatric and adult endoscopists (32, vs. 79%, P < 0.001; adult vs. pediatric). There exists heterogeneity among endoscopists in recommendations to manage EFI in patients with EoE. These findings support development of clinical guidelines and new studies to clarify the rationale for best practices. Key summary: Established knowledge-The optimal management of patients with esophageal food impaction due to eosinophilic esophagitis from presentation at the emergency department to postendoscopy care is unclear. New findings-Considerable recommendation variation exists in the management of EFI in patients with EoE. Our findings provide a rationale for the creation of consensus practice guidelines and further study into best practices.

Characterization of eosinophilic esophagitis variants by clinical, histological, and molecular analyses: A cross-sectional multi-center study.

OBJECTIVE: Physicians are increasingly confronted with patients presenting with symptoms of esophageal dysfunction resembling eosinophilic esophagitis (EoE), but absence of significant esophageal eosinophilia. The purpose of this study was to characterize and classify this group of EoE variants. DESIGN: Patients from six EoE-centers with symptoms of esophageal dysfunction, but peak eosinophil counts of <60/mm2 (<15/hpf) in esophageal biopsies and absence of gastro-esophageal reflux disease (GERD) were included. Clinical, endoscopic, (immuno)-histological, and molecular features were determined and compared with EoE, GERD, and healthy controls. RESULTS: We included 69 patients with EoE variants. Endoscopic abnormalities were found in 53.6%. We identified three histological subtypes: EoE-like esophagitis (36/69, 52.2%), lymphocytic esophagitis (14/69, 20.3%), and non-specific esophagitis (19/69, 27.5%). Immunohistochemistry revealed-in contrast to EoE-no significant increase in inflammatory cell infiltrates compared with GERD and healthy controls, except for lymphocytes in lymphocytic esophagitis. EoE-typical Th2-response was absent in all EoE variants. However, considerable structural changes were detected based on histology and protein expression. Using next generation mRNA sequencing, we found the three EoE variants to have distinct molecular fingerprints partially sharing pronounced traits of EoE. Hierarchical sample clustering of RNA sequencing data confirmed the presence of an EoE-like (characterized by eotaxin-3 expression), non-specific, and lymphocytic variant cluster (characterized by CD3 cells and TSLP expression). CONCLUSION: All EoE variants are clinically and histologically active conditions despite the absence of esophageal eosinophilia. EoE variants appear to be part of a disease spectrum, where classical EoE represents the most common and apparent phenotype.

Impact of Overweight and Obesity on Disease Outcome in the Pediatric Swiss Inflammatory Bowel Disease Cohort.

Given the paucity of data, we aimed to assess the impact of obesity on disease activity, complications, and quality of life (QoL) in pediatric inflammatory bowel disease (IBD) patients. Methods: Prospective analysis of pediatric IBD patients. Patients were categorized into 4 groups according to the World Health Organization (WHO) child growth standards: obese, overweight, normal weight, and underweight. Results: Three hundred twenty-seven pediatric patients were included (146 with Crohn's disease [CD], 181 with ulcerative colitis of whom 13 [4%] were underweight, 272 [83.2%] had normal weight, 22 [6.7%] were overweight, and 20 [6.1%] were obese). Compared with normal weight patients, obese ulcerative colitis had a significantly higher clinical but not biological disease activity nor severity. Compared with normal weight patients, overweight/obese CD patients did not have higher clinical or biological disease activity nor severity. Perianal abscesses and surgery for this purpose were more frequently observed in overweight/obese CD patients compared with normal weight controls. Overweight/obese IBD patients were similarly hospitalized in the last 12 months compared with normal weight controls. Conclusions: Prevalence of overweight/obesity was 12.8% in pediatric IBD patients. Obesity was not associated with a decrease in disease remission rates nor an increase in the risk of complicated disease progression in IBD pediatric patients, except for the occurrence of perianal abscesses and related surgery in CD patients.

Sex Impacts Disease Activity But Not Symptoms or Quality of Life in Adults With Eosinophilic Esophagitis.

BACKGROUND: Eosinophilic esophagitis has a strong male predominance that appears at least partially due to genetic susceptibility. However, data regarding sex-related differences in patients with EoE are scarce. METHODS: We analyzed prospectively collected data from adults enrolled into the Swiss Eosinophilic Esophagitis Cohort Study. Patients with and without dilation in the past 12 months completed patient-reported Eosinophilic Esophagitis Activity Index (EEsAI) and EoE-specific quality of life in adults (EoE-QoL-A) and underwent endoscopy with biopsies. We used linear regression with EEsAI or EoE-QoL-A as the outcome, eosinophils per high power field, rings and strictures, current therapy use, and disease duration as predictors. RESULTS: A total of 266 patients (77% male, median age at diagnosis 35.8 years, median disease duration 10.4 years) were seen during 408 visits. Men had a longer diagnostic delay (62 months vs 36 months; P = .022), higher endoscopic disease activity (median endoscopic reference score 3.0 [interquartile range, 1.0-6.0] vs 2.0 [interquartile range, 0.0-4.0]; P = .010), more microabscesses (25% vs 13%; P = .025), and more often fibrosis of the lamina propria (mild/moderate 74.7% vs 61.5%, severe 9.1% vs 5.8%; P = .047) than women. When adjusting for objective measures of disease activity, disease duration, and current therapy use, we did not observe differences in EEsAI or EoE-QoL-A between women and men. CONCLUSIONS: Male EoE patients had higher endoscopic and histologic disease activity than female patients. When adjusting for biologic activity and therapy use, we did not identify differences in symptom severity or EoE-QoL between male and female eosinophilic esophagitis patients.

Long-Lasting Dissociation of Esophageal Eosinophilia and Symptoms After Dilation in Adults With Eosinophilic Esophagitis.

BACKGROUND & AIMS: Esophageal dilation improves dysphagia but not inflammation in eosinophilic esophagitis (EoE) patients. We investigated if dilation modifies the association between symptoms and peak esophageal eosinophils per high-power field (eos/hpf). METHODS: Adults enrolled in a multisite prospective Consortium of Gastrointestinal Eosinophilic Disease Researchers Outcome Measures for Eosinophilic Gastrointestinal Diseases Across Ages observational study (NCT02523118) completed the symptom-based EoE activity index (EEsAI) patient-reported outcome instrument and underwent endoscopy with biopsy specimens. Patients were stratified based on dilation status as absent, performed 1 year or less before endoscopy, and performed more than 1 year before endoscopy. Assessments included Spearman correlations of the relationship between symptoms and eos/hpf and linear regression with EEsAI as the outcome, eos/hpf as predictor, and interaction for dilation and eos/hpf. RESULTS: Among 100 patients (n = 61 males; median age, 37 y), 15 and 40 patients underwent dilation 1 year or less and more than 1 year before index endoscopy, respectively. In nondilated patients, the association between eos/hpf and symptoms was moderate (ρ = 0.49; P < .001); for a 10-eos/hpf increase, the predicted EEsAI increased by 2.69 (P = .002). In patients dilated 1 or less and more than 1 year before index endoscopy, this association was abolished (ρ = -0.38; P = .157 for ≤1 y and ρ = 0.02; P = .883 >1 y); for a 10-eos/hpf increase, the predicted EEsAI changed by -1.64 (P = .183) and 0.78 (P = .494), respectively. Dilation modified the association between symptoms and eos/hpf (P = .005 and P = .187 for interaction terms of eos/hpf and dilation 1 or less years before and more than 1 year before index endoscopy, respectively). CONCLUSIONS: In nondilated EoE adults, eos/hpf correlate modestly with symptoms; this correlation was no longer appreciated in dilated patients, and the dilation effects lasted longer than 1 year. Dilation status should be considered in studies evaluating EoE treatment and for clinical follow-up evaluation.

Systematic Review of Outcome Measures Used in Observational Studies of Adults with Eosinophilic Esophagitis.

BACKGROUND: Over the last 20 years, diverse outcome measures have been used to evaluate the effectiveness of therapies for eosinophilic esophagitis (EoE). This systematic review aims to identify the readouts used in observational studies of topical corticosteroids, diet, and dilation in adult EoE patients. METHODS: We searched MEDLINE and Embase for prospective and retrospective studies (cohorts/case series, randomized open-label, and case-control) evaluating the use of diets, dilation, and topical corticosteroids in adults with EoE. Two authors independently assessed the articles and extracted information about histologic, endoscopic, and patient-reported outcomes and tools used to assess treatment effects. RESULTS: We included 69 studies that met inclusion criteria. EoE-associated endoscopic findings (assessed either as absence/presence or using Endoscopic Reference Score) were evaluated in 24/35, 11/17, and 9/17 studies of topical corticosteroids, diet, and dilation, respectively. Esophageal eosinophil density was recorded in 32/35, 17/17, and 11/17 studies of topical corticosteroids, diet, and dilation, respectively. Patient-reported outcomes were not uniformly used (only in 14, 8, and 3 studies of topical corticosteroids, diet, and dilation, respectively), and most tools were not validated for use in adults with EoE. CONCLUSIONS: Despite the lack of an agreed set of core outcomes that should be recorded and reported in studies in adult EoE patients, endoscopic EoE-associated findings and esophageal eosinophil density are commonly used to assess disease activity in observational studies. Standardization of outcomes and data supporting the use of outcomes are needed to facilitate interpretation of evidence, its synthesis, and comparisons of interventions in meta-analyses of therapeutic trials in adults with EoE.

The impact of colectomy on the course of extraintestinal manifestations in Swiss inflammatory bowel disease cohort study patients.

BACKGROUND AND AIMS: Extraintestinal manifestations are reported to occur in up to 45% of inflammatory bowel disease (IBD) patients during the course of disease. It is unknown whether colectomy reduces the rate of de novo extraintestinal manifestations (EIMs) or impacts on severity of EIMs following a parallel versus independent disease course from underlying IBD. METHODS: Using data from the Swiss Inflammatory Bowel Disease Cohort Study we aimed to analyse the course of EIMs in ulcerative colitis (UC) and Crohn's disease (CD) patients undergoing colectomy during the cohort's prospective follow-up. RESULTS: One hundred and twenty-one IBD patients (33 CD, 81 UC and seven unclassified) underwent colectomy during prospective follow-up in the Swiss Inflammatory Bowel Disease Cohort Study. Within the 114 patients with UC or CD any EIM was reported in 40 (nine CD and 31 UC) patients. Activity of EIMs ceased entirely after colectomy in 21 patients (52.5%). Complete cessation of EIM after colectomy was higher in patients with UC versus CD with 58.1% versus 33.3%. After colectomy, 29 out of the 114 patients (25.4%) experienced any EIM. Two thirds of these (19 patients) represented persisting EIMs, while in one third (10 patients) EIM represented a de-novo event after colectomy. Overall, 13.5% of IBD patients developed a de-novo EIM after colectomy. CONCLUSIONS: In IBD patients undergoing colectomy, EIMs present prior to surgery will persist in about half of patients. Complete cessation of EIM after colectomy may be less common in CD than in UC. In patients who never experienced EIMs prior to colectomy de-novo manifestations thereafter should be expected in up to one in seven patients.

Emerging Therapies for Eosinophilic Gastrointestinal Diseases.

Besides eosinophilic esophagitis, other eosinophilic gastrointestinal diseases (EGIDs), such as eosinophilic gastritis, eosinophilic gastroenteritis, and eosinophilic colitis, are increasingly diagnosed over the last decade. Whereas diagnosis and therapy of eosinophilic esophagitis have been standardized, the diagnosis and therapy of other EGIDs are areas of active research. Motivated by the increasing prevalence of these conditions, concerted efforts of different stakeholders have led to the evaluation of targeted biologic therapies for EGID management over the last couple of years, and several promising molecules are currently in the pipeline. This review article provides an overview of targeted biologic therapies for use in EGIDs.