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Item A Rare Case of Esophageal Granular Cell Tumor in Eosinophilic Esophagitis(Elsevier, 2023-09-21) Abughofah, Yousaf; Kim, Grace E.; Chen, Dennis; Medicine, School of MedicineA 25-year-old man with recently diagnosed eosinophilic esophagitis presented for a surveillance esophagogastroduodenoscopy (EGD). He was incidentally found to have a 2-mm submucosal-appearing nodule with a yellow hue in the distal esophagus (Figure A, arrow). The patient denied unintentional weight loss; gastrointestinal symptoms; family history of gastrointestinal malignancy; or tobacco, alcohol, or drug history. Initial biopsies of the lesion showed normal pathology; repeat EGD with stacked biopsies showed granular cell tumor (GCT; Figure B, star) and endoscopic ultrasound showed no deep tumor invasion. The patient was referred for resection and underwent en bloc band-assisted endoscopic mucosal resection (Figures C and D) with pathology confirming GCT without additional abnormalities. Patient is currently asymptomatic and pending surveillance EGD.Item Budesonide Oral Suspension Improves Symptomatic, Endoscopic, and Histologic Parameters Compared With Placebo in Patients With Eosinophilic Esophagitis(Elsevier, 2017-03) Dellon, Evan S.; Katzka, David A.; Collins, Margaret H.; Hamdani, Mohamed; Gupta, Sandeep K.; Hirano, Ikuo; Pediatrics, School of MedicineBackground & Aims Pharmacologic treatment of eosinophilic esophagitis (EoE) is limited to off-label use of corticosteroids not optimized for esophageal delivery. We performed a randomized, controlled phase 2 trial to assess the ability of budesonide oral suspension (BOS), a novel muco-adherent topical steroid formulation, to reduce symptoms and esophageal eosinophilia in adolescents and adults with EoE. Methods In this multicenter, randomized, double-blind, placebo-controlled, parallel-group trial, 93 EoE patients between the ages of 11 and 40 years with dysphagia and active esophageal eosinophilia were randomized to receive either BOS 2 mg or placebo twice daily for 12 weeks. Co-primary outcomes were change in Dysphagia Symptom Questionnaire (DSQ) score from baseline, and proportion of patients with a histologic response (≤6 eosinophils/high-power field) after treatment. Endoscopic severity scores and safety parameters were assessed. Results At baseline, mean DSQ scores were 29.3 and 29.0, and mean peak eosinophil counts were 156 and 130 per hpf in the BOS and placebo groups, respectively. After treatment, DSQ scores were 15.0 and 21.5, and mean peak eosinophil counts were 39 and 113 per high-power field, respectively (P < .05 for all). For BOS vs placebo, change in DSQ score was −14.3 vs −7.5 (P = .0096), histologic response rates were 39% vs 3% (P < .0001), and change in endoscopic severity score was −3.8 vs 0.4 (P < .0001). Adverse events were similar between groups. Conclusions Treatment with BOS was well tolerated in adolescent and young adult patients with EoE and resulted in improvement in symptomatic, endoscopic, and histologic parameters using validated outcome instruments.Item Food‐induced immediate response of the esophagus—A newly identified syndrome in patients with eosinophilic esophagitis(Wiley, 2021-01) Biedermann, Luc; Holbreich, Mark; Atkins, Dan; Chehade, Mirna; Dellon, Evan S.; Furuta, Glenn T.; Hirano, Ikuo; Gonsalves, Nirmala; Greuter, Thomas; Gupta, Sandeep; Katzka, David A.; De Rooij, Willemijn; Safroneeva, Ekaterina; Schoepfer, Alain; Schreiner, Philipp; Simon, Dagmar; Simon, Hans Uwe; Warners, Marijn; Bredenoord, Albert-Jan; Straumann, Alex; Pediatrics, School of MedicineBackground Dysphagia is the main symptom of adult eosinophilic esophagitis (EoE). We describe a novel syndrome, referred to as “food-induced immediate response of the esophagus” (FIRE), observed in EoE patients. Methods Food-induced immediate response of the esophagus is an unpleasant/painful sensation, unrelated to dysphagia, occurring immediately after esophageal contact with specific foods. Eosinophilic esophagitis experts were surveyed to estimate the prevalence of FIRE, characterize symptoms, and identify food triggers. We also surveyed a large group of EoE patients enrolled in the Swiss EoE Cohort Study for FIRE. Results Response rates were 82% (47/57) for the expert and 65% (239/368) for the patient survey, respectively. Almost, 90% of EoE experts had observed the FIRE symptom complex in their patients. Forty percent of EoE patients reported experiencing FIRE, more commonly in patients who developed EoE symptoms at a younger age (mean age of 46.4 years vs 54.1 years without FIRE; P < .01) and in those with high allergic comorbidity. Food-induced immediate response of the esophagus symptoms included narrowing, burning, choking, and pressure in the esophagus appearing within 5 minutes of ingesting a provoking food that lasted less than 2 hours. Symptom severity rated a median 7 points on a visual analogue scale from 1 to 10. Fresh fruits/vegetables and wine were the most frequent triggers. Endoscopic food removal was significantly more commonly reported in male patients with vs without FIRE (44.3% vs 27.6%; P = .03). Conclusions Food-induced immediate response of the esophagus is a novel syndrome frequently reported in EoE patients, characterized by an intense, unpleasant/painful sensation occurring rapidly and reproducibly in 40% of surveyed EoE patients after esophageal contact with specific foods.Item Loss of Endothelial TSPAN12 Promotes Fibrostenotic Eosinophilic Esophagitis via Endothelial Cell–Fibroblast Crosstalk(AGA, 2022-02) Shoda, Tetsuo; Wen, Ting; Caldwell, Julie M.; Morgenstern, Netali Ben-Baruch; Osswald, Garrett A.; Rochman, Mark; Mack, Lydia E.; Felton, Jennifer M.; Abonia, J. Pablo; Arva, Nicoleta C.; Atkina, Dan; Bonis, Peter A.; Capocelli, Kelley E.; Collins, Margaret H.; Dellon, Evan S.; Falk, Gary W.; Gonsalves, Nirmala; Gupta, Sandeep K.; Hirano, Ikuo; Leung, John; Menard-Katcher, Paul A.; Mukkada, Vincent A.; Putnam, Philip E.; Rudman Spergel, Amanda K.; Spergel, Jonathan M.; Wechsler, Joshua B.; Yang, Guang-Yu; Aceves, Seema S.; Furuta, Glenn T.; Rothenberg, Marc E.; Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR) Investigators Group; Medicine, School of MedicineBackground & Aims Eosinophilic esophagitis (EoE) can progress to fibrostenosis by unclear mechanisms. Herein, we investigated gene dysregulation in fibrostenotic EoE, its association with clinical parameters and specific pathways, and the functional consequences. Methods Esophageal biopsies from subjects with EoE were collected across 11 Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR) sites (n = 311) and two independent replication cohorts (n = 83). Inclusion criteria for fibrostenotic EoE were endoscopic rings, stricture, and/or a history of dilation. Endoscopic, histologic, and molecular features were assessed by the EoE endoscopic reference score (EREFS), EoE Histology Scoring System (HSS), EoE Diagnostic Panel (EDP), and RNA sequencing. Esophageal endothelial TSPAN12 expression and functional effects on barrier integrity and gene expression were analyzed in vitro. Results TSPAN12 was the gene most correlated with fibrostenosis (r = -0.40, P < .001). TSPAN12 was lower in fibrostenotic EoE and correlated with EREFS, EDP, and HSS (r = 0.34–0.47, P < .001). Lower TSPAN12 associated with smaller esophageal diameter (r = 0.44, P = .03), increased lamina propria fibrosis (r = -0.41, P < .001), and genes enriched in cell cycle–related pathways. IL-13 reduced TSPAN12 expression in endothelial cells. Conversely, anti-IL-13 therapy increased TSPAN12 expression. TSPAN12 gene silencing increased endothelial cell permeability and dysregulated genes associated with extracellular matrix (ECM) pathways. Endothelial cell–fibroblast crosstalk induced ECM changes relevant to esophageal remodeling. Conclusions Patients with fibrostenotic EoE express decreased levels of endothelial TSPAN12. We propose that IL-13 decreases TSPAN12, likely contributing to the chronicity of EoE by promoting tissue remodeling through fibroblast-endothelial cell crosstalk.Item Serum MicroRNA-21 as a Biomarker for Allergic Inflammatory Disease in Children(Bentham, 2016) Sawant, Deepali V.; Yao, Weiguo; Wright, Zachary; Sawyers, Cindy; Tepper, Robert S.; Gupta, Sandeep K.; Kaplan, Mark H.; Dent, Alexander L.; Department of Microbiology & Immunology, IU School of MedicineMicroRNAs (miRs) have emerged as useful biomarkers for different disease states, including allergic inflammatory diseases such as asthma and eosinophilic esophagitis (EoE). Serum miRs are a possible non-invasive method for diagnosis of such diseases. We focused on microRNA-21 (miR-21) levels in serum, in order to assess the feasibility of using this gene as a non-invasive biomarker for these diseases in the clinic, as well as to better understand the expression pattern of miR-21 in allergic inflammation. We used quantitative PCR (QPCR) to assay miR-21 and other control miRs in esophageal biopsies from EoE patients and serum samples from EoE and asthma patients. Serum levels of miR-21 were significantly elevated in patients with asthma, whereas serum miR-21 levels were not associated with the presence of allergen-specific IgE (i.e. atopy). Esophageal biopsies showed a large elevation of miR-21 in EoE and an increase in miR-21 in EoE serum. Control U6 miR did not vary between asthma and control patients, however EoE serum had significantly decreased U6 microRNA compared to controls. The decreased U6 in EoE sera did not completely account for the relative increase in miR-21 in the sera of EoE patients. We report for the first time that miR-21 is elevated in the sera of both asthma and EoE patients. We find no relation between serum miR-21 levels and atopy. Our results thus suggest miR-21 is a novel biomarker for human allergic inflammatory diseases.