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Background and Aims: Ultrasonography has shown that eosinophils accumulate in each segment of the esophageal mucosa in human EoE, ultimately promoting esophageal motility dysfunction; however, no mechanistic evidence explains how or why this accumulation occurs., Methods: Quantitative PCR, ELISA, flow cytometry, immunostaining, and immunofluorescence analyses were performed using antibodies specific to the related antigens and receptors., Results: In deep esophageal biopsies of EoE patients, eosinophils and mast cells accumulate adjacent to nerve cell-derived VIP in each esophageal segment. qRT -PCR analysis revealed five- to sixfold increases in expression levels of VIP , CRTH2 , and VAPC2 receptors and proteins in human blood- and tissue-accumulated eosinophils and mast cells. We also observed a significant correlation between mRNA CRTH2 levels and eosinophil- and nerve cell-derived VIP s in human EoE ( p < 0.05). We provide evidence that eosinophil and mast cell deficiency following CRTH2 antagonist treatment improves motility dysfunction in a chronic DOX-inducible CC10-IL-13 murine model of experimental EoE., Conclusions: CRTH2 antagonist treatment is a novel therapeutic strategy for inflammatory cell-induced esophageal motility dysfunction in IL-13-induced chronic experimental EoE.

Eosinophilic esophagitis (EoE) is a rare atopic disorder associated with esophageal dysfunction, including difficulty swallowing, food impaction, and inflammation, that develops in a small subset of people with food allergies. Genome-wide association studies (GWASs) have identified 9 independent EoE risk loci reaching genome-wide significance (p < 5 × 10 -8 ) and 27 additional loci of suggestive significance (5 × 10 -8  < p < 1 × 10 -5 ). In the current study, we perform linkage disequilibrium (LD) expansion of these loci to nominate a set of 531 variants that are potentially causal. To systematically interrogate the gene regulatory activity of these variants, we designed a massively parallel reporter assay (MPRA) containing the alleles of each variant within their genomic sequence context cloned into a GFP reporter library. Analysis of reporter gene expression in TE-7, HaCaT, and Jurkat cells revealed cell-type-specific gene regulation. We identify 32 allelic enhancer variants, representing 6 genome-wide significant EoE loci and 7 suggestive EoE loci, that regulate reporter gene expression in a genotype-dependent manner in at least one cellular context. By annotating these variants with expression quantitative trait loci (eQTL) and chromatin looping data in related tissues and cell types, we identify putative target genes affected by genetic variation in individuals with EoE. Transcription factor enrichment analyses reveal possible roles for cell-type-specific regulators, including GATA3. Our approach reduces the large set of EoE-associated variants to a set of 32 with allelic regulatory activity, providing functional insights into the effects of genetic variation in this disease., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background/Aims: Asymptomatic esophageal eosinophilia (aEE) is considered to be a potential precursor of eosinophilic esophagitis (EoE). However, there are few clinical parameters that can be used to evaluate the disease. Therefore, we aimed to clarify the factors involved in the symptoms of EoE by examining the clinicopathological differences between aEE and EoE. Methods: We reviewed 41 patients with esophageal eosinophilia who underwent endoscopic ultrasonography and high-resolution manometry. They were divided into the aEE group (n=16) and the EoE group (n=25) using the Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease score. The patients’ clinicopathological findings were collected and examined. Results: The median Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease score was 3.0 in the aEE group and 10.0 in the EoE group. There was no significant difference in patient characteristics, endoscopic findings and pathological findings. The cutoff value for wall thickening was 3.13 mm for the total esophageal wall thickness and 2.30 mm for the thickness from the surface to the muscular layer (total esophageal wall thickness: 84.0% sensitivity, 75.0% specificity; thickness from the surface to the muscular layer: 84.0% sensitivity, 68.7% specificity). The high-resolution manometry study was abnormal in seven patients (43.8%) in the aEE group and in 12 (48.0%) in the EoE group. The contractile front velocity was slower in the EoE group (p=0.026). Conclusions: The esophageal wall thickening in the lower portion of the esophagus is an important clinical factors related to the symptoms in patients with EoE. [ABSTRACT FROM AUTHOR]

Background/Aims: Asymptomatic esophageal eosinophilia (aEE), characterized by eosinophil infiltration in the esophagus without clinical symptoms, has been reported as a precursor of eosinophilic esophagitis (EoE). Nevertheless, no report exists on the long-term clinical course of the disease. Therefore, this study aimed to investigate the long-term clinical course of aEE over 5 years, including the symptomatic conversion rate and the effect of treatments. Methods: We reviewed 28 patients with aEE who had been followed up for over 5 years with endoscopic monitoring. The basal characteristics of patients were compared with those of 58 patients diagnosed with EoE during the same period. Patients’ clinicopathological findings were collected and examined. Results: No significant differences in basal characteristics and histopathological findings were observed between the patients with aEE and those with EoE. The median follow-up duration was 64 months. Among the 28 patients with aEE, seven were treated with proton pump inhibitor or potassium-competitive acid blocker and the remaining 21 opted for follow-up with no medication. Among the treated patients, six (85.7%) exhibited endoscopic and pathologic improvements. Among the cases followed up without medication, the findings worsened in two (9.5%), improved spontaneously in seven (33.3%), and were unchanged in 12 (57.1%), and three (14.3%) developed symptoms at a mean time of 40 months. Symptoms developed in cases where endoscopic and pathologic findings remained unchanged or worsened during follow-up. Conclusions: Some patients with aEE had improved findings without treatment, whereas others developed symptoms, emphasizing the importance of long-term monitoring and individualized treatment decisions. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background and Aims: The Index of Severity for Eosinophilic Esophagitis (I-SEE) was recently developed. We aimed to understand I-SEE scores in a longitudinal pediatric cohort and to determine the relationship between I-SEE and clinical features in children., Methods: We performed a retrospective analysis on a prospectively enrolled cohort of children at a single center who were treated as part of routine clinical care. I-SEE was calculated at the diagnostic and follow-up endoscopies over a mean of 6.6 years. Scoring was 0 for inactive, 1-6 for mild, 7-14 for moderate, and ≥15 for severe eosinophilic esophagitis (EoE). We analyzed clinical, endoscopic, and histologic features at each instance. Symptoms were analyzed at the baseline, first follow-up, and last endoscopic instance., Results: Of 67 children who met study criteria of at least 3 endoscopies over at least 2 years of follow-up time, 43%, 36%, and 21% had mild, moderate, and severe I-SEE scores at baseline, respectively. Between the first and second endoscopic instances, there was a decrease in the group mean I-SEE from 9.7 ± 7.2 to 6.1 ± 5.9 (P < .001). By the last instance, the overall I-SEE score dropped to 3.9 (P < .001). Body mass index <5% and poor feeding were more common in the children with severe I-SEE scores at baseline, and both improved by the last instance. Fibrosis was improved by the last instance biopsy (P < .01)., Conclusions: I-SEE is a responsive severity metric in children treated long term during routine clinical care. Baseline low body mass index and poor feeding were more common in children with severe I-SEE scores., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Proton pump inhibitors (PPIs) are the first-line drug for eosinophilic esophagitis (EoE), although it is estimated that there is a lack of histological remission in 50% of patients. This research aimed to identify pharmacogenetic biomarkers predictive of PPI effectiveness and to study their association with disease features. Peak eosinophil count (PEC) and the endoscopic reference score (EREFS) were determined before and after an eight-week PPI course in 28 EoE patients. The impact of the signal transducer and activator of transcription 6 ( STAT6 ), CYP2C19 , CYP3A4 , CYP3A5, and ABCB1 genetic variations on baseline PEC and EREFS, their reduction and histological response, and on EoE symptoms and comorbidities was analyzed. PEC reduction was higher in omeprazole-treated patients (92.5%) compared to other PPIs (57.9%, p = 0.003). STAT6 rs12368672 (g.18453G>C) G/G genotype showed higher baseline PEC values compared to G/C and C/C genotypes (83.2 vs. 52.9, p = 0.027). EREFS reduction in STAT6 rs12368672 G/G and G/C genotypes was higher than in the C/C genotype (36.7% vs. -75.0% p = 0.011). However, significance was lost after Bonferroni correction. Heartburn incidence was higher in STAT6 rs167769 (g.27148G>A) G/G patients compared to G/A (54.55% vs. 11.77%, p = 0.030). STAT6 rs12368672G>C and rs167769G>A variants might have a relevant impact on EoE status and PPI response. Further research is warranted to clarify the clinical relevance of these variants.

Background: To assess the efficacy of applying the endoscopic reference score for EoE (EREFS) in children with symptoms of esophageal dysfunction naïve to proton pump inhibitor (PPI) therapy., Methods: An observational cross-sectional study was conducted by reviewing reports and photographs of upper gastrointestinal endoscopies (UGE) and esophageal biopsies of patients with symptoms of esophageal dysfunction. Patients who were treated with PPI or had other conditions that may cause esophageal eosinophilia were excluded., Results: Of the 2,036 patients evaluated, endoscopic findings of EoE were identified in 248 (12.2%) and more than one abnormality was observed in 167 (8.2%). Among all patients, 154 (7.6%) presented esophageal eosinophilia (≥15 eosinophils per high power field) (P<0.01). In this group, 30 patients (19.5%) had normal endoscopy. In patients with EoE, edema (74% vs 6.5%, P<0.01) and furrows (66.2% vs 2.4%, P<0.01) were more prevalent than in the control group. Association of edema and furrows was more frequent in patients with EoE than in the control group (29.2% vs 1.6%, P<0.01, OR=24.7, CI=15.0-40.5). The presence of more than one endoscopic finding had sensitivity of 80.5%, specificity of 93.4%, positive predictive value (PPV) of 50%, negative predictive value (NPV) of 98.3%, and accuracy of 92.4%., Conclusion: In conclusion, this study showed that endoscopic features suggestive of EoE had high specificity and NPV for diagnosing EoE in children naïve to PPI therapy. These findings highlight the importance of the EREFS in contributing to early identification of inflammatory and fibrostenosing characteristics of EoE, making it possible to identify and to avoid progression of the disease., Background: • The EoE endoscopic reference score (EREFS) was developed and validated in adults and has been demonstrated to be an adequate tool for diagnosing and assessing treatment response in children., Background: • The presence of more than one endoscopic finding stronglysuggests EoE., Background: • The EoE endoscopic reference score presents high specificity and negative predictive value for diagnosing EoE in children naïve to proton pump inhibitor (PPI) therapy., Background: • Endoscopic findings suggestive of EoE in patients naïve to treatment may be useful to characterize disease phenotype and individualize treatment according to the initial clinical presentation.

Background & Aims: Chronic inflammation of eosinophilic esophagitis (EoE) results in progressive, fibrostenotic remodeling of the esophageal wall. This study aimed to demonstrate objective changes in esophageal distensibility relative to duration of EoE disease using a functional lumen imaging probe (FLIP)., Methods: Adult patients with EoE who completed a 16-cm FLIP protocol during endoscopy were evaluated in a cross-sectional study. FLIP analysis focused on distensibility plateau (DP) of the esophageal body. The time from onset of symptoms to time of endoscopy with FLIP was assessed, as was time from symptom onset to EoE diagnosis (ie, diagnostic delay)., Results: A total of 171 patients (mean age 38 ± 12 years; 31% female) were included; the median symptom duration was 8 (interquartile range, 3-15) years and diagnostic delay was 4 (interquartile range, 1-12) years. At the time of endoscopy with FLIP, there were 54 patients (39%) in histologic remission (<15 eosinophils per high-power field [eos/hpf]). Symptom duration and diagnostic delay were negatively correlated with DP (rho = -0.326 and -0.309; P values < .001). Abnormal esophageal distensibility (DP ≤17 mm) was more prevalent with increased duration of symptoms (P < .004): 23% at <5 years to 64% at ≥25 years. When stratifying the cohort based on mucosal eosinophil density, patients with ≥15 eos/hpf had significantly lower DP with greater symptom duration (P = .004), while there was not a significant difference among patients with <15 eos/hpf (P = .060)., Conclusions: Esophageal distensibility objectively measured with FLIP was reduced in EoE patients with greater symptom duration and diagnostic delay. This supports that EoE is a progressive, fibrostenotic disease and that FLIP may be a useful tool to monitor disease progression in EoE., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Introduction: Biochemical alterations in the esophagus of patients with eosinophilic esophagitis (EoE) are poorly understood. We used Raman spectroscopy through a pediatric endoscope to identify key Raman features reflective of the esophageal biochemical composition to differentiate between children with EoE from non-EoE controls and between children with active (aEoE) and inactive EoE (iEoE)., Methods: Spectral measurements were obtained using a customized pediatric endoscope-compatible fiber-optic Raman probe in real time during an esophagogastroduodenoscopy. Chemometric analysis was performed to identify key Raman features associated with EoE. Pearson correlation analysis was used to assess relationship between the key Raman features and EoE activity indices. Their diagnostic utility was ascertained using the receiver operator characteristic curve analysis., Results: Forty-three children were included in the study (EoE = 32 [74%] and non-EoE control = 11 [26%]; aEoE = 20 [63%] and iEoE = 12 [37%]). Raman intensities assigned to lipids, proteins, and glycogen:protein ratio accurately distinguished children with EoE from those without EoE and aEoE from iEoE. They significantly correlated with EoE activity indices. The Raman peak ratio for lipids had 90.6% sensitivity, 100% specificity, and an area under the curve of 0.95 to differentiate children with EoE from non-EoE controls. The glycogen:protein ratio had 70% sensitivity, 91.7% specificity, and an area under the curve of 0.75 to distinguish children with aEoE from iEoE., Discussion: Real-time intraendoscopy Raman spectroscopy is an effective method for identifying spectral markers reflective of the esophageal biochemical composition in children with EoE. This technique may aid in the diagnosis and monitoring of EoE and help to elucidate EoE pathogenesis., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Eosinophilic esophagitis (EoE) is a multifaceted disease characterized by a wide heterogeneity of clinical manifestations, endoscopic and histopathologic patterns, and responsiveness to therapy. From the perspective of an effective approach to the patient, the different inflammatory mechanisms involved in the pathogenesis of EoE and biologics, in particular monoclonal antibodies (mAbs), targeting these pathways are needed. Currently, the most relevant is dupilumab, which interferes with both interleukin (IL)-4 and IL-13 pathways by binding IL-4 receptor α, and is the only mAb approved by the European Medicine Agency and US Food and Drug Administration for the treatment of EoE. Other mAbs investigated include mepolizumab, reslizumab, and benralizumab (interfering with IL-5 axis), cendakimab and dectrekumab (anti-IL-13s), tezepelumab (anti-TSLP), lirentelimab (anti-SIGLEG-8), and many others. Despite the undeniable economic impact of biologic therapies, in the near future, there will be room for further reflection about the opportunity to prescribe biologic agents, not only as a last-line therapy in selected cases such as patients with comorbidities involving common pathways. Although recent findings are very encouraging, the road to permanent success in the treatment of EoE is still long, and further studies are needed to determine the long-term effects of mAbs and to discover new potential targets.

Introduction: Eosinophilic esophagitis (EoE) is a chronic, inflammatory, antigen-driven disease of the esophagus. Tissue EoE pathology has previously been extensively characterized by novel transcriptomics and proteomic platforms, however the majority of surface marker determination and screening has been performed in blood due to mucosal tissue size limitations. While eosinophils, CD4 + T cells, mast cells and natural killer (NK) T cells were previously investigated in the context of EoE, an accurate picture of the composition of peripheral blood mononuclear cells (PBMC) and their activation is missing., Methods: In this study, we aimed to comprehensively analyze the composition of peripheral blood mononuclear cells and their activation using surface marker measurements with multicolor flow cytometry simultaneously in both blood and mucosal tissue of patients with active EoE, inactive EoE, patients with gastroesophageal reflux disease (GERD) and controls. Moreover, we set out to validate our data in co-cultures of PBMC with human primary esophageal epithelial cells and in a novel inducible mouse model of eosinophilic esophagitis, characterized by extensive IL-33 secretion in the esophagus., Results: Our results indicate that specific PBMC populations are enriched, and that they alter their surface expression of activation markers in mucosal tissue of active EoE. In particular, we observed upregulation of the immunomodulatory molecule CD38 on CD4 + T cells and on myeloid cells in biopsies of active EoE. Moreover, we observed significant upregulation of PD-1 on CD4 + and myeloid cells, which was even more prominent after corticosteroid treatment. With co-culture experiments we could demonstrate that direct cell contact is needed for PD-1 upregulation on CD4 + T cells. Finally, we validated our findings of PD-1 and CD38 upregulation in an inducible mouse model of EoE., Discussion: Herein we show significant alterations in the PBMC activation profile of patients with active EoE in comparison to inactive EoE, GERD and controls, which could have potential implications for treatment. To our knowledge, this study is the first of its kind expanding the multi-color flow cytometry approach in different patient groups using in vitro and in vivo translational models., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Gruden, Kienzl, Ristic, Kindler, Kaspret, Schmid, Kargl, Sturm, Doyle, Wright, Baumann-Durchschein, Konrad, Blesl, Schlager and Schicho.)

Background/aims: Asymptomatic esophageal eosinophilia (aEE) is considered to be a potential precursor of eosinophilic esophagitis (EoE). However, there are few clinical parameters that can be used to evaluate the disease. Therefore, we aimed to clarify the factors involved in the symptoms of EoE by examining the clinicopathological differences between aEE and EoE., Methods: We reviewed 41 patients with esophageal eosinophilia who underwent endoscopic ultrasonography and high-resolution manometry. They were divided into the aEE group (n=16) and the EoE group (n=25) using the Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease score. The patients' clinicopathological findings were collected and examined., Results: The median Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease score was 3.0 in the aEE group and 10.0 in the EoE group. There was no significant difference in patient characteristics, endoscopic findings and pathological findings. The cutoff value for wall thickening was 3.13 mm for the total esophageal wall thickness and 2.30 mm for the thickness from the surface to the muscular layer (total esophageal wall thickness: 84.0% sensitivity, 75.0% specificity; thickness from the surface to the muscular layer: 84.0% sensitivity, 68.7% specificity). The high-resolution manometry study was abnormal in seven patients (43.8%) in the aEE group and in 12 (48.0%) in the EoE group. The contractile front velocity was slower in the EoE group (p=0.026)., Conclusions: The esophageal wall thickening in the lower portion of the esophagus is an important clinical factors related to the symptoms in patients with EoE.

Background: Celiac disease (CD) is an immune-mediated enteropathy that has been associated with other immune-related gastrointestinal disorders, such as eosinophilic esophagitis (EoE) and lymphocytic gastritis (LG). To our knowledge, this is the first study in Saudi Arabia that has described such an association., Aim: To evaluate the prevalence of EoE and LG in children and adolescents with CD., Methods: This was a retrospective cross-sectional study of all pediatric patients (aged 0-18 years) with CD following up at King Abdulaziz University Hospital, between January, 2014, and December, 2021. The study examined clinical, demographic, endoscopic, and histopathological data., Results: Seventy-five patients with CD were included in the analysis. The median age was 12 years (range, 2-18 years). Male constituted 54.7% of the overall cohort ( n  = 41). The most common clinical symptoms were short stature (54.7%), weight loss (34.7%), abdominal pain (33.3%), abdominal distension (29.3%), anorexia (29.3%), diarrhea (24%), and vomiting (21.3%). The esophageal biopsy results reported were basal cell hyperplasia in 24 patients (32.9%), esophageal eosinophilia in 23 patients (31.5%), and EoE in 3 patients (4.1%). The gastric biopsy results were normal in 40 patients (53.3%). The most common abnormality was chronic inactive gastritis with no Helicobacter pylori (HP) infection (16%). LG was found in 3 patients (4%)., Conclusions: The prevalence of EoE in this cohort of patients with CD was lower than the prevalence recorded in a number of other studies. Further studies are needed to determine the effects of a gluten-free diet (GFD) on EOE and LG., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Meshari A. Alaifan et al.)

Introduction: Noneosinophilic esophagitis eosinophilic gastrointestinal disorders (non-EoE-EGIDs) have limited treatment options to induce histologic and clinical remission. Dupilumab is a human monoclonal antibody against the interleukin-4 receptor ɑ subunit, which has been reported to induce improvement in pediatric patients with non-EoE-EGIDs., Methods: We conducted a retrospective chart review to identify if patients with eosinophilic gastritis (EoG) and/or eosinophilic duodenitis (EoD) experience clinical and histologic remission with dupilumab., Results: Twelve patients were included (2 patients with EoG and EoD, 3 patients with EoG only, and 7 patients with EoD only). All patients experienced improvement of at least 1 symptom on dupilumab, 3 patients (25%) had no change in severity of 1 or more of their symptoms, and no patients had worsening symptoms. On dupilumab, 2 patients with EoG (40%) and 3 patients with EoD (33.3%) were completely asymptomatic. Histologic changes were investigated in a subanalysis including 8 patients (2 patients with EoG and EoD, 2 patients with EoG only, and 4 patients with EoD only). Median peak gastric eosinophil counts in patients with EoG reduced from 80.5 eos/hpf (min-max 32-150, Q1-Q3 45.5-111) to 7.5 eos/hpf (min-max 0-28, Q1-Q3 1.5-16.8). Median peak duodenal eosinophil counts in patients with EoD reduced from 39 eos/hpf (min-max 30-50, Q1-Q3 37.3-46.3) to 16.5 eos/hpf (min-max 0-50, Q1-Q3 8-38.5). All 4 patients (100%) with EoG and 4 patients (66.6%) with EoD had histologic remission on dupilumab., Discussion: In this retrospective case series, we showed preliminary evidence that dupilumab may be effective in inducing histologic and symptomatic remission in patients with non-EoE-EGIDs., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Summary: 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. [ABSTRACT FROM AUTHOR]

Abstract 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.

The prevalence of diseases characterised by eosinophilia is on the rise, emphasising the importance of understanding the role of eosinophils in these conditions. Eosinophils are a subset of granulocytes that contribute to the body's defence against bacterial, viral, and parasitic infections, but they are also implicated in haemostatic processes, including immunoregulation and allergic reactions. They contain cytoplasmic granules which can be selectively mobilised and secrete specific proteins, including chemokines, cytokines, enzymes, extracellular matrix, and growth factors. There are multiple biological and emerging functions of these specialised immune cells, including cancer surveillance, tissue remodelling and development. Several oral diseases, including oral cancer, are associated with either tissue or blood eosinophilia; however, their exact mechanism of action in the pathogenesis of these diseases remains unclear. This review presents a comprehensive synopsis of the most recent literature for both clinicians and scientists in relation to eosinophils and oral diseases and reveals a significant knowledge gap in this area of research. [ABSTRACT FROM AUTHOR]

(1) Background: Eosinophilia has traditionally been linked to eosinophilic asthma, for which it is the gold-standard prognostic biomarker. However, the association between eosinophilia and the presence of other diseases and comorbidities is yet unclear. (2) Methods: For this retrospective study, we reviewed the electronic medical records of 49,909 subjects with blood eosinophilia to gather data on the presence of asthma, COPD, sleep apnea, tuberculosis, dyslipidemia, hypertension, and other cardiovascular diseases and severe CRSwNP among these subjects. Demographic features including age, sex, and smoking habits were collected, as well as the number of hospitalizations and emergency department visits. T-tests, ANOVA, Fisher test, and logistic regression models were used. (3) Results: For all age groups studied, eosinophilia was significantly more prevalent among asthmatic subjects than nonasthmatics, especially in patients also presenting CRSwNP, hypertension, and dyslipidemia. The likelihood of developing asthma, COPD, and CRSwNP, and hospitalization, was increased when BEC was above 600 eosinophils/μL. The association between asthma, CRSwNP, and BEC was corroborated by multiple logistic regressions models. (4) Conclusions: We demonstrated the association of having over 600 blood eosinophils/μL with a higher number of hospitalizations and comorbidities (CRSwNP and COPD), which proves that BEC is a highly useful parameter to consider in subjects who present blood eosinophilia. [ABSTRACT FROM AUTHOR]