Pharmacokinetic Evaluation of Oral Viscous Budesonide in Paediatric Patients with Eosinophilic Oesophagitis in Repaired Oesophageal Atresia.

Eosinophilic oesophagitis is a long-term complication of oesophageal atresia (EA), an uncommon condition that affects approximately 1 in 3500 infants. An exploratory, open-label phase 2 clinical trial was conducted in paediatric eosinophilic oesophagitis after oesophageal atresia (EoE-EA) to assess the safety, pharmacokinetics, and efficacy of oral viscous budesonide (OVB). In total, eight patients were enrolled in the study and assigned to a twice-daily dosing regimen of either 0.8 or 1 mg OVB, depending on age and height, administered for 12 weeks. OVB was safe and effective in the treatment of EoE-EA. The current investigation focuses on the pharmacokinetics of budesonide and the impact of an oral viscous formulation on its absorption and bioavailability. Using a non-linear mixed effects approach, two distinct absorption profiles were identified, despite marked interindividual variability in drug concentrations. Budesonide exposure was higher than previously reported in children following oral inhalation. Even though no significant effect has been observed on serum cortisol levels, future studies should consider exploring different doses, schedules, and/or treatment durations, as there may be an opportunity to reduce the risk of cortisol suppression.

Dose-dependent effects of enteral nutrition on the faecal microbiota and short chain fatty acids.

INTRODUCTION: Enteral nutrition (EN) involves replacing all or part of a person's habitual diet with a nutritional formula. The impact of varying doses of EN on the gut microbiome remains understudied. METHODS: Healthy adults replaced all (100% EN) or part (85% EN, 50% EN and 20% EN) of their energy requirements with EN for 7 days. Faecal samples were collected before and on day 7 of interventions. Faecal pH, short chain fatty acids (SCFAs), branched-chain fatty acids (BCFAs) and 16S rRNA sequencing were performed. Dietary assessment was performed with 7-day food diaries. RESULTS: Sixty-one participants (31 females; median (IQR) age: 24.7 (23.0-27.8) years) were recruited. A dose-dependent impact of EN on faecal microbiota, SCFAs, BCFAs) and pH was observed, with changes detectable at EN intakes of at least 50% of energy requirements. 100% and 85% EN reduced the abundance of fibre-fermenting taxa such as Agathobacter, Faecalibaterium, Succinivibrio and Acidaminococcus. In parallel, potentially harmful organisms like Eubacterium, Actinomyces, and Klebsiella increased. In the 50% EN group, adherence to a diet high in fish, vegetables, potatoes, non-alcoholic beverages, and fat spreads, and low in cereal products, milk, and meat negatively correlated with changes in microbiota structure (r = -0.75, P = 0.025). This signal was not observed when using compositional tools for microbiota analysis. CONCLUSIONS: EN detrimentally influences the faecal microbiota and diet-related bacterial metabolites in a dose-dependent manner, particularly at doses of at least 50%. The findings of this study have implications for the dietary management and counselling of patients receiving high volume EN.

Minimally Invasive Approaches to Diagnose and Monitor Eosinophilic GI Diseases.

PURPOSE OF REVIEW: This review seeks to understand novel avenues for eosinophilic GI disease management. Biomarkers offer a unique and non-invasive approach to tracking EoE disease progression. While no biomarkers have definitively met the diagnostic criteria for eosinophilic GI diseases, some biomarkers have been shown to be associated with disease activity. Here, we examine the potential of recently studied biomarkers. RECENT FINDINGS: Current research shows advancements in blood, luminal fluid, and breath testing. Particular areas of interest include mRNA analyses, protein fingerprinting, amplicon sequence variants (ASVs), T cells and IgE receptors, eosinophilic cationic proteins, cytokines, and nitric oxide exhalation. Preliminary results showed that mucosal biomarkers, directly captured from the esophagus, may reflect the best representation of biopsy-based results, in contrast to biomarkers obtained from indirect or peripheral (blood, breath) methods. However, this is based on limited clinical studies without sufficient numbers to evaluate true diagnostic accuracy. Large-scale randomized trials are needed to fully ascertain both the optimal sampling technique and the specific biomarkers that reflect diagnostic status of the disease.

Patients with eosinophilic oesophagitis in Denmark have higher use of psychotropic drugs: A Danish nationwide study of psychotropic drug use in 3367 patients and 16,835 matched comparators.

BACKGROUND: Eosinophilic oesophagitis (EoE) is a chronic, immune-mediated disease of the oesophagus. Eosinophilic oesophagitis is associated with a substantial disease burden affecting the quality of life and affecting mental health. There are limited data describing the incidence of psychiatric disorders and the use of psychotropic drugs (PDs) in EoE patients. OBJECTIVES: The aim was to investigate whether EoE patients in Denmark have higher use of PDs, contacts with the department of psychiatry, and attempts of suicide or intentional self-harm compared with the general population after being diagnosed with EoE. METHODS: This study was a nationwide, population-based register study including 3367 EoE patients and 16,835 age- and sex-matched comparators. A register-based EoE definition was used to identify cases. Incident PD use was extracted from the prescription register and information regarding psychiatric contacts was retrieved from the Danish Psychiatric Central Research Register. RESULTS: The 5-year incidence of PD use in EoE patients was 13.8% compared to 7.1% of the matched comparators (Hazard ratio 1.83; confidence interval 1.6-2.0; p ≤ 0.001). Antidepressants were the most frequently prescribed PD, whereas antipsychotics were the least prescribed PD. Increasing age, lower educational level, and comorbidity (Charlson Comorbidity Index score ≥1) were associated with the prescription of PDs. The risk of PD use was lower in men than in women with EoE. CONCLUSION: Treatment with PDs were more common in EoE patients after they were diagnosed than in the general Danish population, indicating that EoE patients have an increased risk of psychiatric disorders.

Eosinophilic oesophagitis in a Nigerian adolescent: a case report.

Eosinophilic oesophagitis (EoE) is a chronic immune and antigen-mediated disease characterized by symptoms related to oesophageal dysfunction, and histologically, is marked by eosinophilic infiltrate in the oesophageal mucosa. It is prevalent in developed countries and considered rare in developing countries. There is an interplay of allergic and genetic factors in the aetiology of EoE. This is a report of EoE in a 15-year-old female adolescent in Nigeria who presented to the University of Calabar Teaching Hospital with recurrent vomiting, abdominal pain, weight loss, and dysphagia. She had received treatment for Gastro-oesophageal disease three years earlier and was lost to follow-up. Weight on admission was 39 kg and height 170 cm with a BMI below the 3rd centile. Peripheral blood showed an eosinophil count of four percent. The abdominal computed tomography (CT) scan and upper gastrointestinal (GI) series were normal. Faecal antigen for H. pylori and ova for stool parasites were negative. Histologic findings of proximal and distal oesophageal mucosal biopsies showed greater than 20 eosinophils per high power field. The histology of the stomach and duodenum were normal. She was initially treated with a protein pump inhibitor, with no improvement. Swallowed fluticasone propionate and eliminating peanuts, wheat, egg, and milk from her diet were introduced. Symptoms improved with the patient no longer vomiting and had an increase in weight gain. She was discharged to follow up. This case shows that EoE occurs in developing countries, but diagnosis may be missed. There is a need for a high index of suspicion among gastroenterologists in patients with symptoms suggestive of GERD not responding to therapy.

A complex case of dysphagia with dual aetiology.

A woman in her early 60s was referred with dysphagia and chest pain to a tertiary referral centre specialising in oesophageal disorders. Cardiac symptom origin and sinister oesophageal pathology had been excluded at her local hospital in NHS Scotland. Under multidisciplinary team oversight, reinvestigation of mucosal pathology and oesophageal motility ultimately uncovered both Type III achalasia and eosinophilic oesophagitis. This case demonstrates the benefit of including provocative testing during high-resolution manometry to reproduce relevant dysphagia and the importance of stopping proton-pump inhibitors long enough to uncover excessive eosinophils which could otherwise be masked. Ultimately, tailored management for both conditions separately was required to achieve symptoms resolution.

Joint ESPGHAN/NASPGHAN Guidelines on Childhood Eosinophilic Gastrointestinal Disorders Beyond Eosinophilic Esophagitis.

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.

There is a long way from current clinical practice in Denmark compared to recent published English guideline on management of children with eosinophilic oesophagitis.

BACKGROUND: A low incidence of eosinophilic esophagitis (EoE) in children in the North Denmark Region (NDR) were measured in 2007-2017. Few of the children diagnosed before 2017 were treated to remission suggesting a lack of awareness. While there currently are no guidelines for treating EoE in Denmark, a new English guideline was published in 2022 renewing focus on the disease. OBJECTIVE: The aim of this study was to measure the difference of current Danish clinical practice for treatment and follow-up of EoE children in the NDR with the new English guideline from the British Society of Gastroenterology (BSG) and the British Society of Pediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN). METHODS: This retrospective, register-based DanEoE cohort study included 31 children diagnosed with EoE between 2007 and 2021 in NDR. Medical records were reviewed and information about treatment and follow-up were collected. RESULTS: In 32% of the children with EoE in the NDR, first-line treatment corresponded with the new English guideline. One in 6 children were never started on any treatment even though treatment always is recommended. Histologic evaluation within 12 weeks as recommended was performed in 13% of the children. CONCLUSIONS: In Denmark focus on improving EoE treatment and follow-up for children is needed, as there is a significant difference between current clinical practice and the recommendations in the new English guideline.

A retrospective cohort study on oesophageal food bolus obstruction in the North Denmark region in 2021-two thirds were never diagnosed with a cause.

BACKGROUND: Food bolus obstruction (FBO) leading to hospital treatment is often associated with eosinophilic oesophagitis (EoE), stenosis, or oesophageal cancer (1). Danish national guidelines recommend that patients with FBO undergo a diagnostic upper endoscopy within two weeks of presentation to exclude possible malignancy, and histological evaluation of eight biopsies (2, 3). AIMS: The aims of this study were to (1) report the incidence and describe the causes and treatment of FBO in the North Denmark Region (NDR), (2) determine the proportion of patients who underwent upper endoscopy and biopsy according to regional and national guidelines, and (3) identify International Classification of Diseases 10th Revision (ICD-10) diagnosis and procedure codes applied to the hospital visits due to FBO in the NDR. METHODS: Among all acute hospital visits in the NDR in 2021, all visits with ICD-10 codes possibly reflecting FBO, as well as a random sample of 14,400 visits with unspecific ICD-10 codes (R and Z codes), were screened manually for possible FBO. Diagnosis, follow-up, and treatment of all patients with FBO were recorded. RESULTS: The median patient age was 66.0 (Q1-Q3: 49.8-81.0) years, and half of the patients had experienced FBO before. Two thirds of patients (66.0%) were never diagnosed with a cause of FBO, followed by 17.3% with EoE. 30% of patients did not undergo upper endoscopy within two weeks of the hospital visit, and 50.7% were never biopsied in the oesophagus. Of 1886 hospital visits with registry ICD-10 codes that possibly reflected FBO, 8.4% were due to FBO, while FBO was present in 0.028% of the random sample of unspecific ICD-10 codes. CONCLUSIONS: Most hospitalized FBO patients in the NDR in 2021 were never diagnosed with a cause. In these patients there is a high risk of overlooked EoE or upper gastrointestinal cancers. The area needs immediate focus and changed routines to improve treatment and prevent new FBO.

Retrospective cohort study: Effect of age as a barrier to diagnosis of eosinophilic oesophagitis.

BACKGROUND: Prior work suggests eosinophilic oesophagitis (EoE) is rare in those aged over 65 years. However, elderly patients with EoE experience a substantial diagnostic delay from symptom onset to diagnosis. AIMS: To assess if age predicted whether oesophageal biopsies were obtained in patients with EoE symptoms, what clinical features predict EoE in the elderly, and if EoE phenotype differs between elderly and non-elderly patients. METHODS: We conducted a retrospective cohort study utilising the University of North Carolina (UNC) electronic medical record, EoE clinicopathologic database and UNC endoscopy software from July 2008 to April 2021. A sample of 193 elderly and non-elderly patients with dysphagia, chest pain and/or heartburn were assembled. Patients with EoE were newly diagnosed per contemporaneous guidelines. Patient demographics, clinical characteristics and procedural data were extracted. Summary statistics, bivariate and multivariate analyses were performed. RESULTS: Of 193 patients, we included 91 elderly (47%) and 102 non-elderly (53%). Age independently predicted the odds of biopsies (adjusted odds ratio (aOR): 0.44 elderly vs. non-elderly; 95% CI: 0.21-0.92). Endoscopic features of EoE, but not symptoms, were more common in elderly than non-EoE elderly patients. Elderly patients with EoE differed from non-elderly only by time to diagnosis (aOR per year of symptoms preceding diagnosis: 1.08, 95% CI: 1.04-1.11). CONCLUSIONS: Elderly patients with EoE have <50% the odds of oesophageal biopsies. There were no significant differences between elderly and non-elderly EoE patients, although endoscopic features helped discriminate the two groups. Our findings suggest that older age represents a barrier to EoE diagnosis.

Incidence and prevalence of eosinophilic oesophagitis across Europe: A systematic review and meta-analysis.

BACKGROUND: Several studies have reported large increases in the incidence of eosinophilic oesophagitis (EoE) in the last 20 years. We aimed to systematically review the incidence and prevalence of EoE, focused on all European countries. METHODS: Systematic review and meta-analysis up to 31 December 2022, based on PubMed, CINAHL and extensive hand searching of reference lists. Twenty-five eligible studies were identified and included. RESULTS: For both adults and children, the highest EoE incidence and prevalence have been reported from regional studies in Spain. EoE incidence for both adults and children was significantly lower (p < 0.001) in nationwide studies (meta-analysis = 3.64 per 100,000 person-years overall) compared with regional or centre-based studies (7.16). EoE incidence and prevalence were significantly higher (p < 0.001) in adults than children. All studies that reported on longitudinal trends in EoE incidence showed increases over time, more markedly during more recent years. Larger increases in incidence tend to refer to regional rather than nationwide studies; from Spain, Switzerland and Denmark, both for paediatric and adult age groups. Increases in EoE incidence 100,000 person-years were larger than for incidence per number of diagnostic endoscopies. The most frequently reported co-morbidities in adults were rhinitis, followed by asthma, food allergy and gastroesophageal reflux disease, and in children, erosive oesophagitis, asthma, food allergy and rhinitis. CONCLUSIONS: The incidence of EoE has increased in Europe over the last 30 years, exceeding increases in the volume of oesophago-gastro-duodenoscopies performed. The patchy and low incidence and prevalence of EoE generally in Europe and compared with North America, may reflect a lack of clinical awareness and research focus rather than a genuinely low incidence of EoE. A co-ordinated Europe-wide study that uses standardised methodology is urgently needed to provide a comprehensive picture of EoE incidence and prevalence across Europe.

Review article: Emerging insights into the epidemiology, pathophysiology, diagnostic and therapeutic aspects of eosinophilic oesophagitis and other eosinophilic gastrointestinal diseases.

BACKGROUND: Eosinophilic gastrointestinal diseases (EGIDs) are chronic, immune-mediated disorders characterised clinically by gastrointestinal symptoms and histologically by a pathologic increase in eosinophil-predominant inflammation in the gastrointestinal tract, in the absence of secondary causes of eosinophilia. AIMS: To highlight emerging insights and research efforts into the epidemiology, pathophysiology, diagnostic and therapeutic aspects of eosinophilic oesophagitis (EoE) and non-EoE EGIDs, and discuss key remaining knowledge gaps. METHODS: We selected and reviewed original research, retrospective studies, case series, randomised controlled trials, and meta-analyses. RESULTS: Standardised nomenclature classifies EGIDs as EoE, eosinophilic gastritis (EoG), eosinophilic enteritis (EoN), and eosinophilic colitis (EoC). Incidence and prevalence of EoE are rising, emphasising the need to better understand how environmental risk factors and genetic features interact. Advances in understanding EoE pathophysiology have led to clinical trials of targeted therapy and the approval (in the United States) of dupilumab for EoE. Several therapies that are under investigation hope to satisfy both histologic and clinical targets. For non-EoE EGIDs, efforts are focused on better defining clinical and histopathologic disease determinants and natural history, as well as establishing new therapies. CONCLUSIONS: Unmet needs for research are dramatically different for EoE and non-EoE EGIDs. In EoE, non-invasive diagnostic tests, clinicopathologic models that determine the risk of disease progression and therapeutic failure, and novel biologic therapies are emerging. In contrast, in non-EoE EGIDs, epidemiologic trends, diagnostic histopathologic thresholds, and natural history models are still developing for these more rare disorders.

Eosinophilic oesophagitis: a common cause of food bolus obstruction.

BACKGROUND: Eosinophilic oesophagitis (EOE) is a known cause of food bolus obstruction (FBO) with rising incidence and prevalence. AIMS: To assess the rates of EOE in adult cases presenting with an FBO via prospective biopsy collection during index endoscopy. METHODS: Oesophageal FBO cases requiring gastroscopy between February 2014 and January 2021 at a single institution with a unified policy to perform biopsies on FBO cases were analysed using medical records, endoscopy and histology. Statistical analysis was undertaken to compare those with and without EOE as their final diagnosis, including the timing of oesophageal biopsy and the season that cases presented. RESULTS: One hundred ninety FBO presentations were analysed, 15 patients presented twice and one patient presented four times within the 7-year study period. Men represented 72% of cases. A total of 78% of cases had biopsies collected at an index or scheduled follow-up endoscopy. EOE was the cause of the FBO in 28% (53/190) of presentations. FBO secondary to EOE was more likely to occur in the spring and summer months (Australian September to March), with 39% (19 of 49) of cases presenting in spring attributable to EOE. CONCLUSION: EOE affects a significant proportion of patients presenting with FBO (28%); a high biopsy rate of 78% in FBO cases provides an opportunity for prompt diagnosis and treatment.

Addressing educational gaps through multidisciplinary team education in eosinophilic oesophagitis management.

Once considered a rare disease, eosinophilic oesophagitis (EoE) is becoming increasingly prevalent, yet many healthcare professionals (HCPs) remain unfamiliar with the underlying pathophysiology and optimal management approaches. For this study, we developed a faculty-led, online, continuing medical education activity on EoE. The effectiveness of this activity was evaluated according to Moore's framework, with changes in knowledge and competence (Moore's Levels 3 and 4) assessed for a cohort of gastroenterologists, dietitians, allergists and immunologists (N = 300), using questionnaires completed before and after participation. Changes in HCP confidence in treating EoE were also reported and remaining educational gaps were identified. The activity was viewed by a global audience of 5,330 participants within 6 months, and significant improvements in knowledge and competence were reported following participation in the activity across all specialities, regions and experience (mean [standard deviation] score pre- versus post-activity: 4.32 [1.38] versus 5.46 [0.82]; p < 0.001). Confidence in treating EoE also increased from pre- to post-activity, with the proportion of participants reporting that they felt moderately or extremely confident increasing from 53% to 82%. Several educational unmet needs were identified, which can be used to inform the design of future educational activities in EoE.

Elimination Diet or Swallowed Topical Steroid Treatment of Pediatric Eosinophilic Esophagitis: Five-Year Outcomes.

BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic, antigen-mediated disease of the esophagus commonly treated with swallowed topical steroids (STS) or elimination diets (EDs). Evidence of a long-term response to EDs in pediatric patients is sparse. OBJECTIVE: Our study sought to understand the natural history of pediatric EoE treated exclusively with EDs and to examine a similar population of STS-treated EoE subjects. We hypothesized that long-term adherence to an effective ED would result in ongoing EoE disease remission. METHODS: We conducted a retrospective study of pediatric EoE subjects who had at least 2 visits to a multidisciplinary clinic. Subjects were identified who had (1) a new referral with a suspected diagnosis of EoE; (2) received either EDs or STS alone, and (3) completed both a diagnostic and a posttreatment endoscopy. Concomitant proton-pump inhibitor use was allowed. We collected demographics, clinical features, treatment plans, and associated side effects on each subject. Remission was defined as fewer than 15 eosinophils/high-powered field. RESULTS: We screened the electronic medical record from 2015 to 2016 for subjects cared for in the Gastrointestinal Eosinophilic Diseases Program who fit criteria for inclusion in this analysis. One hundred ninety-nine subjects were identified, 16 who received exclusive EDs and 15 who were treated with STS. Treatment of these subjects was documented for 4.8 and 5.2 years, respectively (P = .51). Significant differences between the groups were observed in average age at EoE diagnosis (3.5 y ED vs 7.8 y STS; P = .002) and in number of endoscopies (6.6 in ED vs 4.5 in STS; P = .03). Fifteen of 16 subjects treated with ED attained histological remission. The initial effective ED removed a mean of 7.7 foods and the final ED removed a mean of 4 foods. No food impactions or esophageal dilations occurred in the ED group. The STS group required an average of 3.7 dose/formulation changes, 4 subjects required 1 or more dilations, 1 subject had 2 food impactions, and 2 were diagnosed with adrenal insufficiency. CONCLUSIONS: Treatment with either ED or STS can lead to long-term remission of EoE. In this study, fewer side effects developed in the ED group than the STS group, but the validity of this conclusion is limited by the small sample size and reinforces the need for prospective study to explore these initial findings.

Assessment of local and systemic signature of eosinophilic esophagitis (EoE) in children through multi-omics approaches.

Background: Eosinophilic oesophagitis (EoE) is a chronic food allergic disorder limited to oesophageal mucosa whose pathogenesis is still only partially understood. Moreover, its diagnosis and follow-up need repeated endoscopies due to absence of non-invasive validated biomarkers. In the present study, we aimed to deeply describe local immunological and molecular components of EoE in well-phenotyped children, and to identify potential circulating EoE-biomarkers. Methods: Blood and oesophageal biopsies were collected simultaneously from French children with EoE (n=17) and from control subjects (n=15). Untargeted transcriptomics analysis was performed on mRNA extracted from biopsies using microarrays. In parallel, we performed a comprehensive analysis of immune components on both cellular and soluble extracts obtained from both biopsies and blood, using flow cytometry. Finally, we performed non-targeted plasma metabolomics using liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS). Uni/multivariate supervised and non-supervised statistical analyses were then conducted to identify significant and discriminant components associated with EoE within local and/or systemic transcriptomics, immunologic and metabolomics datasets. As a proof of concept, we conducted multi-omics data integration to identify a plasmatic signature of EoE. Results: French children with EoE shared the same transcriptomic signature as US patients. Network visualization of differentially expressed (DE) genes highlighted the major dysregulation of innate and adaptive immune processes, but also of pathways involved in epithelial cells and barrier functions, and in perception of chemical stimuli. Immune analysis of biopsies highlighted EoE is associated with dysregulation of both type (T) 1, T2 and T3 innate and adaptive immunity, in a highly inflammatory milieu. Although an immune signature of EoE was found in blood, untargeted metabolomics more efficiently discriminated children with EoE from control subjects, with dysregulation of vitamin B6 and various amino acids metabolisms. Multi-blocks integration suggested that an EoE plasma signature may be identified by combining metabolomics and cytokines datasets. Conclusions: Our study strengthens the evidence that EoE results from alterations of the oesophageal epithelium associated with altered immune responses far beyond a simplistic T2 dysregulation. As a proof of concept, combining metabolomics and cytokines data may provide a set of potential plasma biomarkers for EoE diagnosis, which needs to be confirmed on a larger and independent cohort.

Oesophageal wall thickness assessment at endoscopic ultrasound in children and adolescents with eosinophilic oesophagitis: a case-control study.

PURPOSE: Eosinophilic oesophagitis (EoE) is a chronic immune-mediated disease, and an endosonographic evaluation may help the diagnosis. The main objectives of this study were to measure the thickness of the oesophageal wall using a radial endoscopic ultrasound (EUS), mucosa/submucosa (MSM), muscularis propria (MP) and mucosa to muscularis propria (MMP); to compare these measurements between patients with and without EoE; to correlate them with the Endoscopic Reference Score (EREFS); and to evaluate the diagnostic accuracy of these measurements. METHODS: Children and adolescents (aging from 4 to 17 years) were evaluated in this prospective cross-sectional study. A radial EUS at 12 MHz frequency was used, and EREFS was employed to grade macroscopic findings. Accuracy of the measurements for the diagnosis of EoE was assessed by receiver operating characteristics (ROC) curve. RESULTS: Twenty-six (19 M/7 F) patients (median age 10.83 years, range 5.65-17.46) were evaluated. EoE was diagnosed in 6 patients. The mean (and SD) oesophageal wall thicknesses in the distal oesophagus in millimetres in groups with and without EoE, respectively, were: MSM 1.07 (0.44) and 1.11 (0.33); MP 0.67 (0.25) and 0.60 (0.19); and MMP 1.73 (0.46) and 1.72 (0.32). Mid-oesophagus: MSM 1.16 (0.34) and 1.15 (0.34); MP 0.63 (0.16) and 0.60 (0.2); and MMP 1.79 (0.41) and 1.74 (0.34). In the ROC curve, the distal MP layer thickness presented better discriminative performance, with an area under the curve of 0.61 (95% CI 0.28-0.93) at 0.73 mm cut-off (66.67% sensitivity, 80% specificity, likelihood ratios of 3.33 for positive and 0.42 for negative test). CONCLUSION: The evaluation of oesophageal thickness measurements by EUS is not useful for diagnosing EoE.

Predictors of histologic response to dietary therapy in eosinophilic oesophagitis.

BACKGROUND: Dietary therapy successfully treats eosinophilic oesophagitis (EoE), but limited data exist on predictors of patient response. AIMS: To determine response rates and to identify predictors of histologic response to elimination diets in adults with EoE METHODS: This was a retrospective, single-centre study of adults with PPI-refractory EoE undergoing dietary therapy with six food elimination diet (SFED) or extended six food elimination diet (ExSFED) in an outpatient setting from January 2012 to January 2019. Patient demographics, radiologic and endoscopic findings, endoscopic reference (EREF) scores, histology and symptoms were evaluated before and after food elimination. Histologic response was assessed via tissue obtained from endoscopically-guided biopsy or Cytosponge. Dietary therapy adherence was assessed via structured phone interview. Multivariable logistic regression analysis was performed to identify predictors of dietary response. RESULTS: We included 68 patients, of whom 62% had a histologic response to dietary therapy (81% to SFED, 19% to ExSFED). Median duration of follow-up was 45 months (IQR, 34-53 months). On multivariable analysis, higher pre-SFED EREF score was the only variable associated with dietary non-response (OR 0.07, 95% CI 0.49, 0.98; p = 0.04). CONCLUSIONS: In adults with EoE, histologic dietary non-response to SFED was associated with a higher pre-SFED EREF score, suggesting that fixed structural disease may predict dietary non-response. Our additional observations of poor correlation between symptomatic and histologic flares, and identification of ExSFED responders, suggest that histologic confirmation should be sought before committing patients to lifelong dietary changes. We also recommend the consideration of restricting legumes and corn in SFED non-responders as ExSFED detected additional dietary responders.