Adult Eosinophilic Esophagitis Research Articles

Histological Outcomes of Pharmacological Interventions in Eosinophilic Esophagitis for Adults and Children: A Network Meta-analysis of Randomized Controlled Trials.

Multiple pharmacological interventions have been studied for managing eosinophilic esophagitis (EoE). We performed a comprehensive systematic review and network meta-analysis of all available randomized controlled trials (RCT) to assess the efficacy and safety of these interventions in EoE in adults and children. We performed a comprehensive review of Embase, PubMed, MEDLINE OVID, Cochrane CENTRAL, and Web of Science through May 10, 2023. We performed frequentist approach network meta-analysis using random effects model. We calculated the odds ratio (OR) with 95% CI for dichotomous outcomes. Our search yielded 25 RCTs with 25 discrete interventions and 2067 patients. Compared with placebo, the following interventions improved histology (using study definitions) in decreasing order on ranking: orodispersible budesonide (ODB) low dose, ODB high dose, oral viscous budesonide (OVB) high dose, fluticasone tablet 1.5mg twice daily, fluticasone 3mg twice daily, esomeprazole, dupilumab every 2 weeks, dupilumab weekly, OVB medium dose, fluticasone 3mg daily, cendakimab 180mg, prednisone, swallowed fluticasone, fluticasone tablet 1.5mg daily, OVB low dose, reslizumab 3mg/kg, reslizumab 1mg/kg, and reslizumab 2mg/kg. Network meta-analysis demonstrates histological efficacy of multiple medications for EoE. Because of the heterogeneity and large effect size, we recommend more trials comparing pharmacotherapeutic interventions with each other and placebo. An important limitation of this study is absence of clinical efficacy data due to insufficient data. Other limitations include heterogeneity of operator, population, and outcome analysis.

Baseline Peripheral Eosinophil Count Independently Predicts Proton Pump Inhibitor Response in Eosinophilic Esophagitis.

To assess the predictive value of baseline peripheral absolute eosinophil counts (AECs) for proton pump inhibitor (PPI) response in eosinophilic esophagitis (EoE). PPI leads to histologic remission in ~50% of EoE patients, although there are few distinguishing clinical features between PPI-responsive (PPI-r-EoE) and nonresponsive (PPI-nr-EoE) diseases. Peripheral eosinophilia is present in ~50% of EoE cases and is associated with eosinophil density on esophageal biopsy and worse clinical outcomes. The association between peripheral eosinophilia and PPI-responsiveness in EoE remains unclear. This is a retrospective cohort study of adult EoE patients at a tertiary center between 2012 and 2016. All patients underwent twice daily PPI trials for ≥8 weeks followed by repeat esophageal biopsies and were classified as PPI-r-EoE or PPI-nr-EoE based on histologic response (<15 eosinophils/high power field). Baseline peripheral AEC was obtained within 1 month before index endoscopy. Analyses were performed using Fisher exact/Student t test (univariate) and logistic regression (multivariable). One hundred eighty-three patients (91 PPI-nr-EoE and 92 PPI-r-EoE) were included. Mean peripheral AEC was higher among PPI-nr-EoE patients (0.41 vs 0.24 K/µL, P = 0.013). Baseline peripheral eosinophilia (>0.5 K/µL) was more prevalent among patients with PPI-nr-EoE (70.4% vs 45.5%, P = 0.023) and a history of food impaction (51.9% vs 23.7%, P = 0.0082). On multivariable analyses, peripheral eosinophilia remained an independent predictor for PPI response (adjacent odds ratio = 2.86, CI: 1.07-7.62, P = 0.036) and food impaction (adjacent odds ratio = 2.80, CI: 1.07-7.35, P = 0.037). Baseline peripheral eosinophilia independently predicts PPI nonresponse and food impaction in EoE patients. Peripheral AEC may help therapy selection in EoE and prevent delays in achieving histologic remission.

A213 DUPILUMAB EFFICACY IN EOSINOPHILIC ESOPHAGITIS PERSISTS FOR HISTOLOGIC, SYMPTOMATIC, AND ENDOSCOPIC OUTCOMES REGARDLESS OF CONCOMITANT HIGH-DOSE PROTON PUMP INHIBITOR USE

Abstract Background Proton-pump inhibitor (PPI) therapy is the most commonly used first-line therapy for eosinophilic esophagitis (EoE) but data informing long-term outcomes are limited. Aims This pre-specified analysis of data from the phase 3 LIBERTY EoE TREET (NCT03633617) study assessed the efficacy of weekly dupilumab vs placebo in patients (pts) with and without concomitant PPI use. Methods Pts with peak intraepithelial eosinophil (eos) count ≥15 eos/high-power field (hpf) after ≥8 weeks’ high-dose PPI were randomized to dupilumab or placebo. Pts on high-dose PPIs at screening remained on a high-dose regimen during the treatment period; switching of PPI types was permitted but new initiation of PPIs was prohibited. Endpoints at Week 24 were: proportion of pts achieving ≤6 eos/hpf, absolute change from baseline in Dysphagia Symptom Questionnaire (DSQ) score, % change in peak eos count, absolute change in Endoscopic Reference Score (EREFS) and Histologic Scoring System (HSS) grade/stage scores. Results In Parts A and B, respectively, 61.9% and 71.3% of pts in the dupilumab group and 64.1% and 72.2% in the placebo group were using PPIs at randomization. For pts treated with dupilumab vs placebo in Parts A and B, respectively, ≤6 eos/hpf was achieved by 69.2% (95% confidence interval [CI] 48.2–85.7) vs 8.0% (95% CI 1.0–26.0) and 59.6% (95% CI 45.8–72.4) vs 7.0% (95% CI 2.0–17.0) of pts using PPIs, and by 43.8% (95% CI 19.8–70.1) vs 0% (95% CI 0–23.2) and 56.5% (95% CI 34.5–76.8) vs 4.5% (95% CI 0.1–22.8) of pts not using PPIs. Least squares mean change from baseline in DSQ score for dupilumab vs placebo was –18.5 vs –12.9 and –21.8 vs –14.0 for pts using PPIs in Parts A and B, respectively, and –27.8 vs –3.8 and –28.4 vs –13.3 for those not using PPIs (Figure 1). Dupilumab improved outcomes vs placebo for secondary endpoints, with comparable results in pts with and without concomitant PPI use. Absolute change from baseline in EREFS score is shown in Figure 1. Dupilumab was generally well tolerated. Conclusions Dupilumab improved histologic, symptomatic, and endoscopic aspects of EoE in adults and adolescents, up to 24 weeks, regardless of concomitant high-dose PPI use. Figure 1. Effect of dupilumab 300 mg qw versus placebo on primary endpoints (A) proportion of patients with peak esophageal intraepithelial eosinophil count of ≤6 eos/hpf (B) absolute change from baseline in DSQ total score at Week 24 (C) absolute change from baseline in EREFS total score at Week 24, by concomitant PPI use CI, confidence interval; DSQ, Dysphagia Symptom Questionnaire; EREFS, endoscopic reference score; eos, eosinophils; hpf, high-power field; LS, least squares; PPI, proton pump inhibitor; pt, patient; qw, once weekly; SE, standard error. Funding Agencies Research sponsored by Sanofi and Regeneron Pharmaceuticals Inc.

Clinical practices and adherence to guidelines for eosinophilic esophagitis: A European survey

BackgroundWe aimed to assess the clinical practices and adherence to guidelines for adult Eosinophilic Esophagitis (EoE) patients in Europe. MethodsA cross-sectional web survey containing 23 questions was distributed to members of the European Consortium for Eosinophilic Diseases of the Gastrointestinal Tract (EUREOS) and the Italian Association of Hospital Gastroenterologists and digestive endoscopists (AIGO). We conducted a subgroup analysis to assess the impact of EoE expertise and practice setting on clinical practices. Results228 physicians from 18 European countries participated. Adherence to guidelines varied from 72% to 98.6%. 83.4% of total respondents obtained ≥ 6 esophageal biopsies in suspected EoE. 42% of total respondents, 82.5% of EoE experts (vs. non-experts 33%; P < 0.0001), and 55% of academics (vs. 29.1 non-academics; P < 0.0001) routinely used the EREFS score. Regarding first-line therapy, 82.9% of total respondents prescribed proton pump inhibitors, 41.6% topical steroids, 20.6% elimination diets, and 9.2% combination therapies. Only 72% of respondents used symptoms and endoscopy with <15 Eosinophils/HPF to define treatment response. 21.5% of all respondents did not prescribe maintenance therapies and 12.7% discontinued therapy before response evaluation endoscopy. ConclusionOur findings revealed significant heterogeneity in practice patterns and suboptimal adherence to EoE guidelines across Europe. Expertise in EoE and working in an academic hospital positively influenced clinical practices and adherence to guidelines.

Clinical Utility of Dupilumab for the Treatment of Eosinophilic Esophagitis in Pediatric Patients

Background:Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus characterized by symptoms of esophageal dysfunction and 15 or more eosinophils per high-powered field (HPF) on esophageal biopsy. Treatment options for EoE include proton pump inhibitors (PPIs), topical corticosteroids (TCS), dietary elimination, and dupilumab. Dupilumab is monoclonal antibody against IL-4 and IL-13 administered subcutaneously and was granted FDA approval for EoE in adults and adolescents recently in 2022. Outcomes of real-world, clinical use of dupilumab for EoE remains unknown.&#x0D; Objectives:To observe outcomes in pediatric patients with EoE treated with dupilumab.&#x0D; Methods:A retrospective cohort study of pediatric patients prescribed dupilumab for EoE was conducted. Medical records were reviewed for demographic and clinical information as well as endoscopic and histologic findings before and after dupilumab treatment.&#x0D; Results:A total of 28 patients were included (mean age 15y, 71.4% male). Mean baseline maximum eosinophils/HPF was 48 ± 41. 75% of patients were treated with combination therapy of EoE with diet elimination, PPIs, or TCS prior to being prescribed dupilumab. Prior authorization for dupilumab was required in 85.7% of cases. Ten patients had follow-up endoscopy with biopsy after starting dupilumab, and among these patients the mean maximum eosinophils/HPF with dupilumab significantly improved from 44 ± 37 to 13 ± 15 (p=0.027). Among 12 patients who had follow up clinic visits, two patients reported pain or swelling at injection sites, but no otheradverse events were reported&#x0D; Conclusions:Dupilumab significantly improves histologic findings of EoE and is well tolerated among pediatric patients. We hope for continued monitoring of these patients to understand the clinical utility of dupilumab for EoE over time.

Eosinophilic esophagitis in adults and adolescents: epidemiology, diagnostic challenges, and management strategies for a type 2 inflammatory disease.

Eosinophilic esophagitis (EoE) is recognized as a chronic type 2 inflammatory disease characterized by the eosinophilic infiltration of the esophageal tissue, posing a significant disease burden and highlighting the necessity for novel management strategies to address unmet clinical needs. To critically evaluate the existing literature on the epidemiology and management of EoE, identify evidence gaps, and assess the efficacy of current and emerging treatment modalities. An extensive literature review was conducted, focusing on the epidemiological trends, diagnostic challenges, and therapeutic interventions for EoE. This was complemented by a survey among physicians and consultations with a scientific expert panel, including a patient's association (ESEO Italia), to enrich the study findings. The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, scrutinizing epidemiological studies and management research to compile comprehensive insights into the disease's landscape. The physician survey and expert panel discussions aimed to bridge identified evidence gaps. The review included 59 epidemiological and 51 management studies, uncovering variable incidence and prevalence rates of EoE globally, with an estimated diagnosed prevalence of 41 per 100,000 in Italy. Diagnostic challenges were identified, including nonspecific symptoms and the lack of definitive biomarkers, which complicate the use of endoscopy. Treatment options such as elimination diets, proton-pump inhibitors, and swallowed corticosteroids were found to have varying success rates, while Dupilumab, an emerging therapy targeting interleukin (IL)-4 and IL-13, shows promise. Despite advancements in understanding and managing EoE, significant unmet clinical needs remain, particularly in biomarker identification, therapy personalization, and cost-effectiveness evaluation. A comprehensive, multidimensional approach to patient management is required, emphasizing the importance of early symptom recognition, accurate diagnosis, and tailored treatment strategies. Dupilumab offers potential as a novel treatment, underscoring the need for future research to explore the economic and social dimensions of EoE care pathways.

Eosinophilic esophagitis as a side-effect of allergen immunotherapy: protocol for a systematic review and meta-analysis.

Background. Sensitization to food and airborne allergens is common in the majority of patients with eosinophilic esophagitis (EoE). Although there is not a direct cause-effect relationship of IgE-mediated allergy with the pathogenesis of EoE, there is a growing evidence that oral desensitization to food and sublingual immunotherapy (SLIT) may induce the development of EoE as an adverse effect. As part of the 'EoE and Allergen Immunotherapy (AIT)' Task Force funded by the European Academy of Allergy and Clinical Immunology (EAACI), a systematic approach will be followed to review the evidence from the published scientific literature on the development of EoE in children and adults under any type of AIT. Methods. This systematic review will be carried out following the PRISMA statement guidelines. Studies will be assessed for inclusion in the review according to the Population-Interventions-Comparators-Outcomes (PICO) criteria. Results. Expected outcomes will provide evidence on the AIT-EoE development connection. Conclusions. The findings from this review will be used as a reference to provide useful guidelines for physicians treating patients with EoE and/or are practicing AIT.

Artificial Intelligence Tools for the Diagnosis of Eosinophilic Esophagitis in Adults Reporting Dysphagia: Development, External Validation, and Software Creation for Point-of-Care Use

Despite increased awareness of eosinophilic esophagitis (EoE), the diagnostic delay has remained stable over the past 3 decades. There is a need to improve the diagnostic performance and optimize resources allocation in the setting of EoE. We developed and validated 2 point-of-care machine learning (ML) tools to predict a diagnosis of EoE before histology results during office visits. We conducted a multicenter study in 3 European tertiary referral centers for EoE. We built predictive ML models using retrospectively extracted clinical and esophagogastroduodenoscopy (EGDS) data collected from 273 EoE and 55 non-EoE dysphagia patients. We validated the models on an independent cohort of 93 consecutive patients with dysphagia undergoing EGDS with biopsies at 2 different centers. Models' performance was assessed by area under the curve (AUC), sensitivity, specificity, and positive and negative predictive values (PPV and NPV). The models were integrated into a point-of-care software package. The model trained on clinical data alone showed an AUC of 0.90 and a sensitivity, specificity, PPV, and NPV of 0.90, 0.75, 0.80, and 0.87, respectively, for the diagnosis of EoE in the external validation cohort. The model trained on a combination of clinical and endoscopic data showed an AUC of 0.94, and a sensitivity, specificity, PPV, and NPV of 0.94, 0.68, 0.77, and 0.91, respectively, in the external validation cohort. Our software-integrated models (https://webapplicationing.shinyapps.io/PointOfCare-EoE/) can be used at point-of-care to improve the diagnostic workup of EoE and optimize resources allocation.

Endoscopic Ultrasound Can Measure Esophageal Remodeling in Eosinophilic Esophagitis

Background and AimsAlthough esophageal widening is a normal consequence of growth in pediatric individuals, esophageal remodeling plays a major role in the morbidity of pediatric and adult eosinophilic esophagitis (EoE). However, the disease is defined by esophageal dysfunction and mucosal eosinophilia. One potential explanation is the difficulty in quantitating remodeling. MethodsThis prospective, IRB-approved longitudinal study evaluated endoscopic ultrasound (EUS) in 78 children, adolescents, and young adults referred to a single academic medical center for esophageal indications. Patients with proven EoE had serial EUS exams that measured total wall thickness (TWT) and esophageal wall sublayers during routine endoscopies to manage their disease. Student t tests and mixed linear models were employed to compare groups. ResultsTWTs from the distal (2.3 ± 0.5 vs 1.7 ± 0.3, P < 0.01) and mid esophagus (2.1 ± 0.5 vs 1.6 ± 0.3, P < 0.05) were increased in active EoE patients > 10 years of age compared with similarly aged controls. After achieving clinical and histologic remission, their TWTs were significantly decreased (distal: 1.9 ± 0.4 vs 2.3 ± 0.5, P < 0.05; mid: 1.7 ± 0.4 vs 2.1 ± 0.5, P < 0.05). Mixed linear models further demonstrated that during active EoE, TWTs, esophageal muscle layers, and the mucosa and submucosa were thickened in older adolescents at both sites (P < 0.05 for each). In remission, TWTs returned to control values. ConclusionThis pilot study demonstrates that EUS, a unique application of point-of-care ultrasound, can identify the esophageal remodeling that occurs in older adolescents with active EoE. Furthermore, EUS has defined this remodeling as a transmural phenomenon that occurs in the mid and distal esophagus and can completely reverse with adequate treatment.

Changes in mucosal IgG4+- and IL-10+-cell frequencies in adults with eosinophilic esophagitis on a two-food elimination diet

Eosinophilic esophagitis (EoE) is increasingly diagnosed in patients with dysphagia. Type-2 immunity can induce EoE histopathology via non-IgE-dependent mechanisms, possibly involving IgG4 and IL-10. To elucidate the contribution of this response to EoE pathogenesis, we examined its association with clinical and histologic endpoints in adult EoE patients given a two-food elimination diet. IgG4- and IL-10-expressing cells were counted in esophageal biopsies and serum food-specific IgG4 measured at baseline and follow-up. Variables were correlated with histologic measures of disease activity. Patients exhibited significant reduction in esophageal eosinophilia and overall histology. A significant decrease in IL-10+-cell frequencies correlated with histologic changes. In contrast, a decline in serum and esophageal IgG4, while substantial, did not correlate with IL-10+-cell frequencies or histologic parameters. These results suggest a critical role of IL-10 in EoE pathogenesis. Conversely, IgG4 expression, while reflecting exposure to food antigens, is not obviously related to EoE histopathology or IL-10 expression.

Transcriptomic profiling of the acute mucosal response to local food injections in adults with eosinophilic esophagitis

Exposure of the esophageal mucosa to food allergens can cause acute mucosal responses in patients with eosinophilic esophagitis (EoE), but the underlying local immune mechanisms driving these acute responses are not well understood. We sought to gain insight into the early transcriptomic changes that occur during an acute mucosal response to food allergens in EoE. Bulk RNA sequencing was performed on esophageal biopsy specimens from adult patients with EoE (n= 5) collected before and 20 minutes after intramucosal injection of various food extracts in the esophagus. Baseline biopsy specimens from control subjects without EoE (n= 5) were also included. At baseline, the transcriptome of the patients with EoE showed increased expression of genes related to an EoE signature. After local food injection, we identified 40 genes with a potential role in the early immune response to food allergens (most notably CEBPB, IL1B, TNFSF18, PHLDA2, and SLC15A3). These 40 genes were enriched in processes related to immune activation, such as the acute-phase response, cellular responses to external stimuli, and cell population proliferation. TNFSF18 (also called GITRL), a member of the TNF superfamily that is best studied for its costimulatory effect on Tcells, was the most dysregulated early EoE gene, showing a 12-fold increase compared with baseline and an 18-fold increase compared with a negative visual response. Further experiments showed that the esophageal epithelium may be an important source of TNFSF18 in EoE, which was rapidly induced by costimulating esophageal epithelial cells with the EoE-relevant cytokines IL-13 and TNF-α. Our data provide unprecedented insight into the transcriptomic changes that mediate the acute mucosal immune response to food allergens in EoE and suggest that TNFSF18 may be an important effector molecule in this response.

Eosinophilic gastrointestinal diseases with esophageal involvement: Analysis of 212 patients

BackgroundPrimary eosinophilic gastrointestinal diseases (EGID) are chronic inflammatory disorders of the gastrointestinal tract with unknown etiology.Features, utility, and evolution are still unknown in screening for EGID in adult patients with eosinophilic esophagitis (EoE). ObjectivesTo evaluate the prevalence, characteristics, comorbidities, and evolution of EGID in adults diagnosed with EoE and investigate differences between both groups. MethodsProspective unicenter observational and analytical study. Gastric and duodenal biopsies were obtained during upper baseline endoscopy in all consecutive EoE adult patients evaluated. A colonoscopy with colon biopsies was performed upon persistent diarrhea and normal duodenal biopsies. Results212 EoE patients were included. Nine patients (4.3%) also showed significant eosinophilic infiltration in at least one organ within the digestive tract. The most common site affected was the small bowel (78%). Gastrointestinal symptoms (43% vs. 100%, p<0.002) and, more specifically, either abdominal pain or diarrhea (17% vs. 78%, p<0.001), some food sensitizations, and digestive comorbidities (p<0.05) were significantly more common in patients with EGID. Gastrointestinal symptoms were present in 94/212 (44%) patients, of whom 9 (10%) had EGID. Considering only abdominal pain or diarrhea, 20% suffered from it. ConclusionsEGID rarely coexist with EoE, even when gastrointestinal symptoms are present. These findings advise against routine gastric, duodenal, or colon biopsies in adult EoE patients with gastrointestinal symptoms. Most of the characteristics of EoE do not change due to having EGID except gastrointestinal symptoms, digestive comorbidities, and sensitizations to some foods. The evolution was generally favorable despite intermittent adherence to treatment, especially maintenance.

Novel corticosteroid formulations in the treatment of eosinophilic esophagitis: what is the evidence?

Eosinophilic esophagitis (EoE) is a food allergen-induced disease of the esophagus. Chronic, eosinophil-predominant inflammation eventually leads to fibrosis, esophageal dysfunction and severe morbidity. Swallowed topical corticosteroids (STCs) are a mainstay of anti-inflammatory therapy in the treatment of active EoE. Data on the efficacy of novel corticosteroid formulations, developed specifically for esophageal delivery, have recently become available. A comprehensive review was performed aiming to summarize evidence on the role of STCs in the treatment of EoE. Two biomedical bibliographic databases (PubMED, EMBASE) were searched for articles providing original information on the efficacy and safety of STCs in adult EoE patients. Budesonide orodispersible tablet (BOT) and budesonide oral suspension (BOS) both surpassed placebo formulations regarding the efficacy of inducing and maintaining histologic, symptomatic and endoscopic remission. Overall, BOT displayed the highest grade of efficacy with clinico-histologic remission rates up to 75% after 1 year. Fluticasone propionate (APT-1011) achieved and maintained histologic and endoscopic responses in the majority of patients, whereas only a positive trend was demonstrated for symptomatic improvement. Mometasone and ciclesonide were studied in a limited number of smaller-scale trials and placebo-controlled data are required to substantiate the promising findings. All STCs displayed a similar side effects profile and were generally considered safe and well-tolerated. Current evidence supports long-term treatment with novel corticosteroid formulations, challenging the established treatment paradigm of EoE. BOT appears to be the most effective steroid therapy, although head-to-head comparative trials between STCs are needed.

Expression profiling identifies key genes and biological functions associated with eosinophilic esophagitis in human patients.

Eosinophilic Esophagitis (EoE) is a chronic allergic disease characterized by progressive inflammation of the esophageal mucosa. This chronic inflammatory disorder affects up to 50 per 100,000 individuals in the United States and Europe yet is limited in treatment options. While the transcriptome of EoE has been reported, few studies have examined the genetics among a cohort including both adult and pediatric EoE populations. To identify potentially overlooked biomarkers in EoE esophageal biopsies that may be promising targets for diagnostic and therapeutic development. We used microarray analysis to interrogate gene expression using esophageal biopsies from EoE and Control subjects with a wide age distribution. Analysis of differential gene expression (DEGs) and prediction of impaired pathways was compared using conventional transcriptome analysis (TAC) and artificial intelligence-based (ADVAITA) programs. Principal Components Analysis revealed samples cluster by disease status (EoE and Control) irrespective of clinical features like sex, age, and disease severity. Global transcriptomic analysis revealed differential expression of several genes previously reported in EoE (CCL26, CPA3, POSTN, CTSC, ANO1, CRISP3, SPINK7). In addition, we identified differential expression of several genes from the MUC and SPRR families, which have been limited in previous reports. Our findings suggest that there is epithelial dysregulation demonstrated by DEGs that may contribute to impaired barrier integrity and loss of epidermal cell differentiation in EoE patients. These findings present two new gene families, SPRR and MUC, that are differentially expressed in both adult and pediatric EoE patients, which presents an opportunity for a future therapeutic target that would be useful in a large demographic of patients.

The phenotype of adults with complicated eosinophilic esophagitis is dominated by a 5-year longer diagnostic delay: A population-based study of the DanEoE cohort.

The DanEoE is a previously described population- and register-based cohort of 236 adult patients with eosinophilic esophagitis (EoE) in a well-defined Danish region with a population of 580 000 and free medical treatment. The aim of the study was to compare the phenotype and treatment response between EoE patients with complications to patients without complications at diagnosis. A retrospective cross-sectional study of the DanEoE cohort's 236 adult EoE patients diagnosed between 2007 and 2017 in the North Denmark Region. Patients were divided into a group who had had complications (dilated or food bolus obstruction [FBO]) before or at the diagnosis, and a group without. At the diagnostic endoscopy, 61% had never had a complication, and 39% had either had FBO (n = 77) or been dilated (n = 15). The complicated group had the same mean age at symptom debut (37 [SD = 16] vs 37 [SD = 17] years, P = 1.0), but were diagnosed significantly later with a resulting longer diagnostic delay (13 [SD = 13] vs 7.9 [SD = 11] years, P = 0.01). Almost half of all patients were never treated to symptomatic remission (uncomplicated 40%, complicated 49%). The histological remission was not secured in the majority (uncomplicated 68%, complicated 70%). Despite this, <15% of patients with previous FBO experienced this after the diagnosis. In the population-based DanEoE cohort, results indicated that the complicated EoE phenotype was a patient with a 5-year longer diagnostic delay. In the current study, the complication status did not predict the treatment response.

Are patients with eosinophilic esophagitis treated at an academic hospital comparable to a patient from a population-based cohort? Not in Denmark.

Little are known about differences in eosinophilic esophagitis (EoE) patients in the general population compared with patients treated at academic hospitals. This might affect the generalizability of study results. The aims of the study were to compare clinical features, and complications of EoE between patients from a population-based cohort (DanEoE) and patients from an academic hospital cohort in Copenhagen (EoE-Cph). The DanEoE cohort is a population- and register-based cohort including all 236 adult EoE patients diagnosed in the North Denmark Region in 2007-2017 previously described in detail. The new EoE-Cph cohort consists of 245 consecutively referred adult patients to a dedicated EoE center in an Academic Hospital in the Danish capital in 2013-2020. Data were collected from medical registries and medical files. Patients in the academic cohort were at symptom debut 12 (SD 16) years younger (P = 0.001). At the time of diagnosis they were 5.4 (SD 15) years younger (P < 0.001). Where Gastro-esophageal reflux disease (GORD) was present in one-third of the population-based cohort, this was only observed in 14% of the EoE-Cph group (P < 0.05). Food bolus obstruction before diagnosis was 24% less common in the EoE-Cph patients (P < 0.001). Results indicated that EoE patients referred to a Danish EoE center is a selected subgroup with disease debut at a younger age, less comorbid GORD, and rarely food bolus obstruction before diagnosis. This suggests that study results from academic hospitals might not have generalizability to the average EoE patient in a population.

Eosinophilic gastrointestinal diseases with esophageal involvement: Analysis of 212 patients

BackgroundPrimary eosinophilic gastrointestinal diseases (EGID) are chronic inflammatory disorders of the gastrointestinal tract with unknown etiology.Features, utility, and evolution are still unknown in screening for EGID in adult patients with eosinophilic esophagitis (EoE). ObjectivesTo evaluate the prevalence, characteristics, comorbidities, and evolution of EGID in adults diagnosed with EoE and investigate differences between both groups. MethodsProspective unicenter observational and analytical study. Gastric and duodenal biopsies were obtained during upper baseline endoscopy in all consecutive EoE adult patients evaluated. A colonoscopy with colon biopsies was performed upon persistent diarrhea and normal duodenal biopsies. Results212 EoE patients were included. Nine patients (4.3%) also showed significant eosinophilic infiltration in at least one organ within the digestive tract. The most common site affected was the small bowel (78%). Gastrointestinal symptoms (43% vs. 100%, p<0.002) and, more specifically, either abdominal pain or diarrhea (17% vs. 78%, p<0.001), some food sensitizations, and digestive comorbidities (p<0.05) were significantly more common in patients with EGID. Gastrointestinal symptoms were present in 94/212 (44%) patients, of whom 9 (10%) had EGID. Considering only abdominal pain or diarrhea, 20% suffered from it. ConclusionsEGID rarely coexist with EoE, even when gastrointestinal symptoms are present. These findings advise against routine gastric, duodenal, or colon biopsies in adult EoE patients with gastrointestinal symptoms. Most of the characteristics of EoE do not change due to having EGID except gastrointestinal symptoms, digestive comorbidities, and sensitizations to some foods. The evolution was generally favorable despite intermittent adherence to treatment, especially maintenance.

Adult eosinophilic esophagitis and advances in its treatment

Adult eosinophilic esophagitis and advances in its treatment

Proteomic analysis of the esophageal epithelium reveals key features of eosinophilic esophagitis pathophysiology.

Eosinophilic esophagitis (EoE) is a chronic non-IgE-mediated allergic disease of the esophagus. An unbiased proteomics approach was performed to investigate pathophysiological changes in esophageal epithelium. Additionally, an RNAseq-based transcriptomic analysis in paired samples was also carried out. Total proteins were purified from esophageal endoscopic biopsies in a cohort of adult EoE patients (n = 25) and healthy esophagus controls (n = 10). Differentially accumulated (DA) proteins in EoE patients compared to control tissues were characterized to identify altered biological processes and signaling pathways. Results were also compared with a quantitative proteome dataset of the human esophageal mucosa. Next, results were contrasted with those obtained after RNAseq analysis in paired samples. Finally, we matched up protein expression with two EoE-specific mRNA panels (EDP and Eso-EoE panel). A total of 1667 proteins were identified, of which 363 were DA in EoE. RNA sequencing in paired samples identified 1993 differentially expressed (DE) genes. Total RNA and protein levels positively correlated, especially in DE mRNA-proteins pairs. Pathway analysis of these proteins in EoE showed alterations in immune and inflammatory responses for the upregulated proteins, and in epithelial differentiation, cornification and keratinization in those downregulated. Interestingly, a set of DA proteins, including eosinophil-related and secreted proteins, were not detected at the mRNA level. Protein expression positively correlated with EDP and Eso-EoE, and corresponded with the most abundant proteins of the human esophageal proteome. We unraveled for the first time key proteomic features involved in EoE pathogenesis. An integrative analysis of transcriptomic and proteomic datasets provides a deeper insight than transcriptomic alone into understanding complex disease mechanisms.

Treatment of eosinophilic esophagitis - advancements and perspectives

In recent years significant progress has been made in the treatment of eosinophilic esophagitis (EoE), especially in the area of topical corticosteroids. Novel EoE-specific formulations have been developed and first approvals have been obtained for induction and maintenance of remission in adult EoE patients with the orodispersible budesonide tablet in Germany and other European and non-EU countries. A novel budesonide oral suspension is currently under priority review by the FDA for first approval in the U.S. In contrast, the scientific evidence on the efficacy of proton pump inhibitors remains limited. Moreover, new biologicals have been identified which showed promising results in phase 2 trials and are now being studied in phase 3. This article aims to summarize and discuss recent advances and perspectives in the treatment of EoE.