Publications by authors named "Ikuo Hirano"

155 Publications

Development of a Core Outcome Set for Therapeutic Studies in Eosinophilic Esophagitis (COREOS).

J Allergy Clin Immunol 2021 Jul 6. Epub 2021 Jul 6.

Inform Diagnostics, Irving, TX, USA; Department of Pathology, Baylor College of Medicine, Houston, TX, USA.

Background: Endpoints used to determine treatment efficacy in eosinophilic esophagitis (EoE) have evolved over time. With multiple novel therapies in development for EoE, harmonization of outcomes measures will facilitate evidence synthesis and appraisal when comparing different treatments.

Objective: To develop a core outcome set (COS) for controlled and observational studies of pharmacologic and diet interventions in adult and pediatric patients with EoE.

Methods: Candidate outcomes were generated from systematic literature reviews and patient engagement interviews and surveys. Consensus was established using an iterative Delphi process, with items voted on using a 9-point Likert scale and with feedback from other participants to allow score refinement. Consensus meetings were held to ratify the outcome domains of importance and the core outcome measures. Stakeholders were recruited internationally and included adult and pediatric gastroenterologists, allergists, dieticians, pathologists, psychologists, researchers, and methodologists.

Results: The COS consists of four outcome domains for controlled and observational studies: histopathology, endoscopy, patient-reported symptoms, and EoE-specific quality of life (QoL). A total of 69 stakeholders (response rate 95.8%) prioritized 42 outcomes in a two-round Delphi process and the final ratification meeting generated consensus on 33 outcome measures. These included measurement of the peak eosinophil count, EoE Histology Scoring System, EoE Endoscopic Reference Score, and patient-reported measures of dysphagia and QoL.

Conclusions: This interdisciplinary collaboration involving global stakeholders has produced a COS that can be applied to adult and pediatric studies of pharmacologic and diet therapies for EoE, which will facilitate meaningful treatment comparisons and improve the quality of data synthesis.
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http://dx.doi.org/10.1016/j.jaci.2021.07.001DOI Listing
July 2021

Reply.

Clin Gastroenterol Hepatol 2021 Jun 29. Epub 2021 Jun 29.

Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

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http://dx.doi.org/10.1016/j.cgh.2021.06.033DOI Listing
June 2021

Low Prevalence of Extraesophageal Gastrointestinal Pathology in Patients with Eosinophilic Esophagitis.

Dig Dis Sci 2021 Jun 30. Epub 2021 Jun 30.

Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, 676 North Saint Clair, Suite 1400, Chicago, IL, 60611, USA.

Background: Limited data are available to support current guidelines recommendations on obtaining gastric and duodenal biopsies of patients with clinical and histologic manifestations consistent with eosinophilic esophagitis (EoE) to rule out eosinophilic gastritis (EG) or duodenitis (EoD). Our study examined the prevalence of concomitant extraesophageal, gastrointestinal pathology to better characterize the diagnostic yield of additional biopsies.

Methods: This was a single-center, retrospective study which utilized ICD 9 codes (530.13) and search queries of pathology reports ("Eosinophilic esophagitis," "EoE") to identify EoE patients. Patient endoscopy reports, pathology reports, and office notes were manually reviewed to characterize cases.

Results: The electronic health record search yielded 1,688 EoE adults. In those who had extra-esophageal biopsies obtained, EG was identified in 34 (3.4%), H. pylori in 45 (4.6%), EoD in 27 (3.3%), and histology consistent with celiac disease in 20 (2.5%). Endoscopic abnormalities were found in the stomach of 92% of patients with EoE and EG and in the duodenum of 50% of patients with EoE and EoD. Symptoms of dyspepsia and/or abdominal pain occurred in a significantly greater proportion of patients with extraesophageal disease (64% vs. 19% in EoE group, p < 0.001). Overall, extraesophageal pathology would have been missed in 1.4% of patients lacking either symptoms or endoscopic signs suggestive of extraesophageal disease.

Conclusions: The yield of gastric and duodenal biopsies in adults with EoE is low, with 6.5% of patients demonstrating histologic features of celiac disease, Helicobacter pylori, EG, and/or EoD. Biopsies of extraesophageal, gastrointestinal sites in patients with suspected or previously diagnosed EoE should consider symptom and endoscopy manifestations as well as the potential impact of histopathologic findings on clinical management.
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http://dx.doi.org/10.1007/s10620-021-07087-yDOI Listing
June 2021

Long-Term Treatment of Eosinophilic Esophagitis with Budesonide Oral Suspension.

Clin Gastroenterol Hepatol 2021 Jun 25. Epub 2021 Jun 25.

Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.

Background And Aims: We evaluated treatment withdrawal, long-term outcomes and safety of budesonide oral suspension (BOS) 2.0 mg b.i.d. in patients with eosinophilic esophagitis who completed a 12-week induction study.

Methods: Induction full responders (≤6 eosinophils per high-power field [eos/hpf] and ≥30% reduction in Dysphagia Symptom Questionnaire [DSQ] score) to BOS 2.0 mg b.i.d. (ORBIT1/SHP621-301/NCT02605837) were randomized to continue BOS (BOS-BOS) or withdraw to placebo (BOS-PBO) for 36 weeks (ORBIT2/SHP621-302/NCT02736409). Induction partial- and non-responders, and patients who received induction placebo, received BOS for 36 weeks. The primary endpoint was the proportion of BOS-BOS and BOS-PBO patients who relapsed (≥15 eos/hpf and ≥4 days of dysphagia [DSQ] over 2 weeks) by week 36. The key secondary endpoint was the proportion of induction partial- and non-responders who fully responded after 52 weeks' total BOS therapy. Secondary endpoints included: proportion of induction full responders with histologic responses (≤1, ≤6, <15 eos/hpf) at week 12 of the extension study, and safety outcomes.

Results: The randomized withdrawal period enrolled 48 patients (BOS-BOS, n=25; BOS-PBO, n=23); 106 induction partial- and non-responders and 65 induction placebo patients received BOS. More BOS-PBO than BOS-BOS patients relapsed over 36 weeks (43.5% vs 24.0%; P=.131) and had histologic responses at week 12 of therapy (P<.001). Overall, 13.2% of induction partial- and non-responders fully responded at week 36. BOS was well-tolerated; therapy duration was not associated with new safety concerns.

Conclusion: For induction full responders, continuing BOS numerically improved maintenance of efficacy versus withdrawal. Longer therapy duration did not raise safety concerns. ClinicalTrials.gov:NCT02736409.
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http://dx.doi.org/10.1016/j.cgh.2021.06.020DOI Listing
June 2021

Esophageal Hypervigilance and Symptom-Specific Anxiety in Patients with Eosinophilic Esophagitis.

Gastroenterology 2021 Jun 19. Epub 2021 Jun 19.

Department of Medicine, Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.

Background & Aims: Patient symptom reporting often does not correlate with the pathophysiological markers of esophageal disease, including eosinophilic esophagitis (EoE). Esophageal hypervigilance and symptom-specific anxiety are emerging as important considerations in understanding symptom reporting. As such, we aimed to conduct the first study of these constructs in EoE.

Methods: A retrospective review of an EoE patient registry was conducted and included eosinophils per high power field (from esophagogastroduodenoscopy biopsy: proximal, distal), endoscopic reference score, distal distensibility plateau (functional luminal imaging probe), Brief Esophageal Dysphagia Questionnaire, Visual Dysphagia Question of EoE Activity Index, Northwestern Esophageal Quality of Life scale, and the Esophageal Hypervigilance and Anxiety Scale. Correlational and regression analyses evaluated relationships of hypervigilance and anxiety with Brief Esophageal Dysphagia Questionnaire, Visual Dysphagia Question of EoE Activity Index, and Northwestern Esophageal Quality of Life scale when controlling for histology and endoscopic severity.

Results: One hundred and three patients had complete data, 69.9% were male, and the mean (SD) age was 40.66 (13.85) years. Forty-one percent had elevated dysphagia and 46% had elevated hypervigilance and anxiety. Esophageal symptom-specific anxiety emerged as the most important predictor of Brief Esophageal Dysphagia Questionnaire severity (44.8% of the variance), Visual Dysphagia Question of EoE Activity Index severity (26%), and poor health-related quality of life (HRQoL) (55.3%). Hypervigilance was also important, but to a lesser extent. Pathophysiological variables did not significantly predict symptoms or HRQoL. Recent food impaction can predict symptom-specific anxiety and proton pump inhibitor use can reduce hypervigilance.

Conclusions: Hypervigilance and symptom-specific anxiety are important for our understanding of self-reported patient outcomes in EoE. These processes outweigh endoscopic and histologic markers of EoE disease activity across dysphagia, difficulty eating, and HRQoL. Clinicians should assess hypervigilance and anxiety, especially in patients with refractory symptoms and poor HRQoL.
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http://dx.doi.org/10.1053/j.gastro.2021.06.023DOI Listing
June 2021

Determination of Biopsy Yield That Optimally Detects Eosinophilic Gastritis and/or Duodenitis in a Randomized Trial of Lirentelimab.

Clin Gastroenterol Hepatol 2021 Jun 2. Epub 2021 Jun 2.

Baylor College of Medicine, Houston, Texas.

Background & Aims: Eosinophilic gastritis (EG) and eosinophilic duodenitis (EoD), characterized by chronic gastrointestinal (GI) symptoms and increased numbers or activation of eosinophils and mast cells in the GI tract, are likely underdiagnosed. We aimed to determine rates of EG and EoD and number of biopsies required to optimize detection using screening data from a randomized trial of lirentelimab (AK002), an antibody against siglec-8 that depletes eosinophils and inhibits mast cells. We also characterized endoscopic features and symptoms of EG and EoD.

Methods: Subjects with moderate-to-severe GI symptoms, assessed daily through a validated patient-reported outcome questionnaire, underwent endoscopy with a systematic gastric and duodenal biopsy protocol and histopathologic evaluation. EG diagnosis required presence of ≥30 eosinophils/high-power field (eos/hpf) in ≥5 hpfs and EoD required ≥30 eos/hpf in ≥3 hpfs. We analyzed diagnostic yields for EG and EoD and histologic, endoscopic, and clinical findings.

Results: Of 88 subjects meeting symptom criteria, 72 were found to have EG and/or EoD (EG/EoD), including patients with no prior diagnosis of EG/EoD. We found that GI eosinophilia was patchy and that examination of multiple biopsies was required for diagnosis-an average of only 2.6 per 8 gastric biopsies and 2.2 per 4 duodenal biopsies per subject met thresholds for EG/EoD. Evaluation of multiple nonoverlapping hpfs in each of 8 gastric and 4 duodenal biopsies was required to capture 100% of EG/EoD cases. Neither endoscopic findings nor symptom severity correlated with eosinophil counts.

Conclusions: In an analysis of patients with moderate-to-severe GI symptoms participating in a clinical trial of lirentelimab for EG/EoD, we found eosinophilia to be patchy in gastric and duodenal biopsies. Counting eosinophils in at least 8 gastric and 4 duodenal biopsies is required to identify patients with EG/EoD, so they can receive appropriate treatment. (ClinicalTrials.gov, Number: NCT03496571).
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http://dx.doi.org/10.1016/j.cgh.2021.05.053DOI Listing
June 2021

Long-Lasting Dissociation of Esophageal Eosinophilia and Symptoms Following Dilation in Adults with Eosinophilic Esophagitis.

Clin Gastroenterol Hepatol 2021 May 29. Epub 2021 May 29.

Digestive Health Institute, Children's Hospital Colorado, Gastrointestinal Eosinophilic Diseases Program, Section of Pediatric Gastroenterology, Hepatology and Nutrition, University of Colorado School of Medicine, Aurora, Colorado, USA.

Background And Aims: Esophageal dilation improves dysphagia but not inflammation in eosinophilic esophagitis (EoE) patients. We investigated if dilation modifies the association between symptoms and esophageal eosinophil count (eos/hpf).

Methods: Adults enrolled in a multisite, prospective Consortium of Gastrointestinal Eosinophilic Disease Researchers OMEGA observational study (NCT02523118) completed the symptom-based EoE activity index (EEsAI) patient-reported outcome instrument and underwent endoscopy with biopsies. Patients were stratified based on dilation status as absent, performed ≤1 and >1 year before endoscopy. Assessments included Spearman's correlations of the relationship between symptoms and eos/hpf and linear regression with EEsAI as the outcome, eos/hpf as predictor, and interaction for dilation and eos/hpf.

Results: Amongst 100 patients (n=61 male, median age 37 years), 15 and 40 patients underwent dilation ≤1 year and >1 year before index endoscopy, respectively. In non-dilated patients, association between eos/hpf and symptoms was moderate (Rho=0.49, p-value<0.001); for 10 eos/hpf increase, the predicted EEsAI increased by 2.69 (p-value=0.002). In patients dilated ≤1 and >1 year before index endoscopy, this association was abolished (Rho=-0.38, p-value=0.157 for ≤1 year and Rho=0.02, p-value=0.883 >1 year); for 10 eos/hpf increase, the predicted EEsAI changed by -1.64 (p-value=0.183) and 0.78 (p-value=0.494), respectively). Dilation modifies association between symptoms and eos/hpf (p-value=0.005 and p-value=0.187 for interaction terms of eos/hpf and dilation ≤1 year and >1 year before index endoscopy, respectively).

Conclusion: In non-dilated EoE adults, eos/hpf correlates modestly with symptoms; this correlation was no longer appreciated in dilated patients, and the dilation effects lasted longer than one year. Dilation status should be considered in studies evaluating EoE treatment and for clinical follow-up.
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http://dx.doi.org/10.1016/j.cgh.2021.05.049DOI Listing
May 2021

Budesonide Oral Suspension Improves Outcomes in Patients With Eosinophilic Esophagitis: Results from a Phase 3 Trial.

Clin Gastroenterol Hepatol 2021 Apr 19. Epub 2021 Apr 19.

Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

Background & Aims: Eosinophilic esophagitis (EoE) is a chronic, immune-mediated disease for which there is currently no pharmacologic therapy approved by the US Food and Drug Administration.

Methods: In this double-blind, placebo-controlled, phase 3 trial, patients 11-55 years of age with EoE and dysphagia were randomized 2:1 to receive budesonide oral suspension (BOS) 2.0 mg twice daily or placebo for 12 weeks at academic or community care practices. Co-primary endpoints were the proportion of stringent histologic responders (≤6 eosinophils/high-power field) or dysphagia symptom responders (≥30% reduction in Dysphagia Symptom Questionnaire [DSQ] score) over 12 weeks. Changes in DSQ score (key secondary endpoint) and EoE Endoscopic Reference Score (EREFS) (secondary endpoint) from baseline to week 12, and safety parameters were examined.

Results: Overall, 318 patients (BOS, n = 213; placebo, n = 105) were randomized and received ≥1 dose of study treatment. More BOS-treated than placebo-treated patients achieved a stringent histologic response (53.1% vs 1.0%; Δ52% [95% confidence interval (CI), 43.3%-59.1%]; P < .001) or symptom response (52.6% vs 39.1%; Δ13% [95% CI, 1.6%-24.3%]; P = .024) over 12 weeks. BOS-treated patients also had greater improvements in least-squares mean DSQ scores and EREFS over 12 weeks than placebo-treated patients: DSQ, -13.0 (SEM 1.2) vs -9.1 (SEM 1.5) (Δ-3.9 [95% CI, -7.1 to -0.8]; P = .015); EREFS, -4.0 (SEM 0.3) vs -2.2 (SEM 0.4) (Δ-1.8 [95% CI, -2.6 to -1.1]; P < .001). BOS was well tolerated; most adverse events were mild or moderate in severity.

Conclusions: In patients with EoE, BOS 2.0 mg twice daily was superior to placebo in improving histologic, symptomatic, and endoscopic outcomes over 12 weeks. BOS 2.0 mg twice daily was well tolerated. ClinicalTrials.gov number: NCT02605837.
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http://dx.doi.org/10.1016/j.cgh.2021.04.022DOI Listing
April 2021

Defining the functionally sufficient regulatory region and liver-specific roles of the erythropoietin gene by transgene complementation.

Life Sci 2021 Mar 16;269:119075. Epub 2021 Jan 16.

Division of Oxygen Biology, United Centers for Advanced Research and Translational Medicine, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan. Electronic address:

Background: Erythropoietin (EPO) is an essential growth factor for erythroid cells and is mainly secreted from the kidneys and subsidiarily from the livers of adult mammals in an anemia/hypoxia-inducible manner.

Aim And Method: To elucidate the regulatory mechanisms of stress-inducible and cell type-specific Epo gene transcription, the rate-limiting step of EPO production, we investigated the sufficiency of a 180-kb genomic fragment flanking the mouse Epo gene locus for recapitulating endogenous Epo gene function by a transgene complementation strategy.

Key Findings: While Epo gene-deficient mice exhibited lethal anemia in utero with defects in erythroblast proliferation and maturation, Epo-knockout mice integrated with the 180-kb Epo transgene showed normal erythropoiesis throughout life. In the transgene-rescued mice, liver-specific deletion of the transgene by the Cre-loxP recombination system caused neonatal anemia with erythropoietic defects in the liver but not in the spleen, indicating the essential function of hepatic EPO on normal erythropoiesis in the liver, which is the major erythropoietic site in late embryonic and neonatal stages.

Significance: These results demonstrate that the 180 kb Epo gene flanking region contains the fully functional Epo gene unit and that EPO from the liver dominantly stimulates hepatic erythropoiesis but contributes less to erythropoiesis in other organs.
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http://dx.doi.org/10.1016/j.lfs.2021.119075DOI Listing
March 2021

Type 2 Immunity and Age Modify Gene Expression of Coronavirus-induced Disease 2019 Receptors in Eosinophilic Gastrointestinal Disorders.

J Pediatr Gastroenterol Nutr 2021 05;72(5):718-722

Department of Bioengineering.

Abstract: Infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can lead to coronavirus-induced disease 2019 (COVID-19). The gastrointestinal (GI) tract is now an appreciated portal of infection. SARS-CoV-2 enters host cells via angiotensin-converting enzyme-2 (ACE2) and the serine protease TMPRSS2. Eosinophilic gastrointestinal disorders (EGIDs) are inflammatory conditions caused by chronic type 2 (T2) inflammation. the effects of the T2 atopic inflammatory milieu on SARS-COV-2 viral entry gene expression in the GI tract is poorly understood. We analyzed tissue ACE2 and TMPRSS2 gene expression in pediatric eosinophilic esophagitis (EoE), eosinophilic gastritis (EG), and in normal adult esophagi using publicly available RNA-sequencing datasets. Similar to findings evaluating the airway, there was no difference in tissue ACE2/TMPRSS2 expression in EoE or EG when compared with control non-EoE/EG esophagus/stomach. ACE2 gene expression was significantly lower in esophagi from children with or without EoE and from adults with EoE as compared with normal adult esophagi. Type 2 immunity and pediatric age could be protective for infection by SARS-CoV-2 in the gastrointestinal tract because of decreased expression of ACE2.
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http://dx.doi.org/10.1097/MPG.0000000000003032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048378PMC
May 2021

Eosinophilic Esophagitis: Etiology and Therapy.

Annu Rev Med 2021 01 23;72:183-197. Epub 2020 Nov 23.

Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA; email:

Eosinophilic esophagitis (EoE) is a relatively recently identified but now frequently encountered antigen/immune-mediated disease which places significant burden on patients and the healthcare system. With its growing prevalence and recognition by healthcare providers in multiple disciplines, substantial progress has been made regarding the diagnostic criteria, clinical evaluation, tools for disease assessment, and immune pathways related to pathogenesis. Current treatment goals focus on the amelioration of inflammation and prevention of remodeling consequences using proton pump inhibitors, swallowed topical steroids, elimination diets, and esophageal dilation. Ongoing research holds promise for more efficacious and targeted therapies as well as a personalized approach to the care of patients with EoE.
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http://dx.doi.org/10.1146/annurev-med-052819-023848DOI Listing
January 2021

Anti-Siglec-8 Antibody for Eosinophilic Gastritis and Duodenitis.

N Engl J Med 2020 10;383(17):1624-1634

From the University of North Carolina, Chapel Hill (E.S.D.); the University of Utah, Salt Lake City (K.A.P.); Mayo Clinic Rochester, Rochester, MN (J.A.M., A.C.B.); the University of Pennsylvania Perelman School of Medicine, Philadelphia (G.W.F.); Northwestern University, Chicago (N.G., I.H.); the Icahn School of Medicine at Mount Sinai, New York (M.C.); Baylor College of Medicine, Houston (R.M.G.); Tufts University, Boston (J.L.); the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (P.K., A.D.K.); Ventura Clinical Trials, Ventura (S.H.), and Allakos, Redwood City (C.S., A.T.C., B.S., A.P.K., H.S.R.) - both in California; Vanderbilt University, Nashville (M.V.); the Division of Allergy and Immunology, Cincinnati Children's Hospital, University of Cincinnati College of Medicine, Cincinnati (S.R.D., M.E.R.); and Pharma Data Associates, Piscataway, NJ (C.W.).

Background: Eosinophilic gastritis and duodenitis are characterized by gastrointestinal mucosal eosinophilia, chronic symptoms, impaired quality of life, and a lack of adequate treatments. Mast-cell activity may contribute to the pathogenesis of the conditions. AK002 (lirentelimab) is an anti-Siglec-8 antibody that depletes eosinophils and inhibits mast cells and that has shown potential in animal models as a treatment for eosinophilic gastritis and duodenitis.

Methods: In this phase 2 trial, we randomly assigned adults who had symptomatic eosinophilic gastritis, eosinophilic duodenitis, or both conditions in a 1:1:1 ratio to receive four monthly infusions of low-dose AK002, high-dose AK002, or placebo. The primary end point was the change in gastrointestinal eosinophil count from baseline to 2 weeks after the final dose; to maximize statistical power, we evaluated this end point in the placebo group as compared with the combined AK002 group. Secondary end points were treatment response (>30% reduction in total symptom score and >75% reduction in gastrointestinal eosinophil count) and the change in total symptom score.

Results: Of the 65 patients who underwent randomization, 43 were assigned to receive AK002 and 22 were assigned to receive placebo. The mean percentage change in gastrointestinal eosinophil count was -86% in the combined AK002 group, as compared with 9% in the placebo group (least-squares mean difference, -98 percentage points; 95% confidence interval [CI], -121 to -76; P<0.001). Treatment response occurred in 63% of the patients who received AK002 and in 5% of the patients who received placebo (difference, 58 percentage points; 95% CI, 36 to 74; P<0.001). The mean change in total symptom score was -48% with AK002 and -22% with placebo (least-squares mean difference, -26 percentage points; 95% CI, -44 to -9; P = 0.004). Adverse events associated with AK002 were similar to those with placebo, with the exception of higher percentages of patients having mild-to-moderate infusion-related reactions with AK002 (60% in the combined AK002 group and 23% in the placebo group).

Conclusions: In patients with eosinophilic gastritis or duodenitis, AK002 reduced gastrointestinal eosinophils and symptoms. Infusion-related reactions were more common with AK002 than with placebo. (Funded by Allakos; ENIGMA ClinicalTrials.gov number, NCT03496571.).
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http://dx.doi.org/10.1056/NEJMoa2012047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600443PMC
October 2020

Author Correction: Nrf2 contributes to the weight gain of mice during space travel.

Commun Biol 2020 Oct 7;3(1):566. Epub 2020 Oct 7.

Laboratory Animal Resource Center in Transborder Medical Research Center, and Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s42003-020-01292-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7542451PMC
October 2020

Maintenance Topical Steroid Therapy in Eosinophilic Esophagitis: Not So Hard to Swallow Any More?

Gastroenterology 2020 11 9;159(5):1653-1655. Epub 2020 Sep 9.

Center for Esophageal Diseases, Baylor University Medical Center; Center for Esophageal Research, Baylor Scott & White Research Institute, Dallas, Texas.

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http://dx.doi.org/10.1053/j.gastro.2020.09.005DOI Listing
November 2020

Nrf2 contributes to the weight gain of mice during space travel.

Commun Biol 2020 09 8;3(1):496. Epub 2020 Sep 8.

Laboratory Animal Resource Center in Transborder Medical Research Center, and Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.

Space flight produces an extreme environment with unique stressors, but little is known about how our body responds to these stresses. While there are many intractable limitations for in-flight space research, some can be overcome by utilizing gene knockout-disease model mice. Here, we report how deletion of Nrf2, a master regulator of stress defense pathways, affects the health of mice transported for a stay in the International Space Station (ISS). After 31 days in the ISS, all flight mice returned safely to Earth. Transcriptome and metabolome analyses revealed that the stresses of space travel evoked ageing-like changes of plasma metabolites and activated the Nrf2 signaling pathway. Especially, Nrf2 was found to be important for maintaining homeostasis of white adipose tissues. This study opens approaches for future space research utilizing murine gene knockout-disease models, and provides insights into mitigating space-induced stresses that limit the further exploration of space by humans.
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http://dx.doi.org/10.1038/s42003-020-01227-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7479603PMC
September 2020

Effectiveness and Safety of High- vs Low-Dose Swallowed Topical Steroids for Maintenance Treatment of Eosinophilic Esophagitis: A Multicenter Observational Study.

Clin Gastroenterol Hepatol 2020 Aug 13. Epub 2020 Aug 13.

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.

Background & Aims: Data evaluating efficacy of different doses of swallowed topical corticosteroids (STC) in the long-term management of eosinophilic esophagitis (EoE) are lacking. We assessed long-term effectiveness and safety of different STC doses for adults with EoE after achievement of histological remission.

Methods: We performed a retrospective multicenter study at five EoE referral centers (US and Switzerland). We analyzed data on 82 patients with EoE in histological remission and ongoing STC treatment with therapeutic adherence of ≥75% (58 males; mean age at diagnosis, 37.2±14.4 years). Patients were followed for a median of 2.2 years (interquartile range [IQR], 1.0-3.8 years). We collected data from 217 follow-up endoscopy visits. The primary endpoint was time to histological relapse.

Results: Histological relapse occurred in 67% of patients. Relapse rates were comparable in patients taking low dose (≤0.5 mg per day, n = 58) and high dose STC (>0.5 mg per day, n = 24) with 72 vs 54% (ns). However, histological relapse occurred significantly earlier with low dose STC (1.0 vs 1.8 years, P = .030). There was no difference regarding rates of and time to stricture formation for low vs high dose STC. Esophageal candidiasis was observed in 6% of patients (5% for low dose, 8% for high dose, ns). No dysplasia or mucosal atrophy was detected.

Conclusion: Histological relapse frequently occurs in EoE despite ongoing STC treatment regardless of STC doses. However, relapse develops later in patients on high dose STC without an increase in side-effects. Doses higher than 0.5 mg/day may be considered for EoE maintenance treatment, but advantage over lower doses appears to be small.
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http://dx.doi.org/10.1016/j.cgh.2020.08.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8108396PMC
August 2020

Food-induced immediate response of the esophagus-A newly identified syndrome in patients with eosinophilic esophagitis.

Allergy 2021 01 19;76(1):339-347. Epub 2020 Aug 19.

Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.

Background: 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.
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http://dx.doi.org/10.1111/all.14495DOI Listing
January 2021

High Patient Disease Burden in a Cross-sectional, Multicenter Contact Registry Study of Eosinophilic Gastrointestinal Diseases.

J Pediatr Gastroenterol Nutr 2020 10;71(4):524-529

Department of Pediatrics, Cincinnati Children's Hospital Medical Center.

Objectives: Clinical features of eosinophilic esophagitis (EoE) have been well-described in the literature, however, characterization of features experienced by patients with other eosinophilic gastrointestinal diseases (EGIDs) is lacking. Using data collected from a patient contact registry, we sought to characterize and contrast patient-reported gastrointestinal and extragastrointestinal symptoms and comorbidities in non-EoE EGIDs, including eosinophilic gastritis, gastroenteritis and colitis, relative to EoE.

Methods: We conducted a cross-sectional study of contact registry data collected from 2015 to 2018. Statistical comparisons were made using chi-square (categorical measures) and the Mann-Whitney U test (continuous measures). Multivariable analyses were used to evaluate associations between treatment and feelings of isolation.

Results: Of the 715 reporting an EGID diagnosis (n = 525 EoE; n = 190 non-EoE EGID), a higher proportion of those with a non-EoE EGID reported more frequent specific and nonspecific gastrointestinal symptoms, including nausea, abdominal pain, diarrhea, constipation, and bloating (P < 0.01 for all). Participants with a non-EoE EGID were more likely to report higher frequency of fatigue, isolation, and deep muscle or joint pain (P < 0.01 for all). Specific food elimination and elemental formula treatments were associated with increased odds of more frequent (at least weekly) feelings of isolation for participants with EoE (adjusted odds rtaio [aOR]: 2.4; 95% confidence interval [CI]: 1.5--4.1 for specific food elimination and adjusted OR: 1.9; 95% CI: 1.2--3.3 for elemental formula).

Conclusions: Significant differences exist in the symptoms and comorbidities experienced between those with EoE versus non-EoE EGIDs. Additional investigation is needed to elucidate the factors that may contribute to the high disease burden of these poorly understood conditions.
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http://dx.doi.org/10.1097/MPG.0000000000002817DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574400PMC
October 2020

An anti-IL-13 antibody reverses epithelial-mesenchymal transition biomarkers in eosinophilic esophagitis: Phase 2 trial results.

J Allergy Clin Immunol 2020 08 11;146(2):367-376.e3. Epub 2020 May 11.

Celgene Corporation, Summit, NJ.

Background: Fibrostenosis, the most serious eosinophilic esophagitis (EoE) complication, is mediated by epithelial-mesenchymal transition (EMT). Transitioned cells contribute to pathogenesis by overproducing extracellular matrix.

Objective: Our aim was to determine whether RPC4046 (anti‒IL-13 mAb) modulates EMT biomarkers in biopsy samples from adults with active EoE in a substudy of a double-blind, placebo-controlled phase 2 trial.

Methods: Baseline and week 16 esophageal biopsy samples were taken from 69 patients who were randomized to weekly treatment with subcutaneous RPC4046, 180 mg (n = 19), 360 mg (n = 26), or placebo (n = 24). Duplex immunofluorescence slides stained for E-cadherin and vimentin were digitally analyzed by mapping each epithelial cell and recording fluorescence intensities. End points included change from baseline to week 16 in percentage of vimentin-positive epithelial cells (primary), total E-cadherin expression, and vimentin-to-E-cadherin ratio per cell (an average of 47,000 cells per biopsy sample analyzed).

Results: The mean percentage of vimentin-positive cells decreased by 0.94%, 2.75%, and 4.24% in the placebo, low-dose, and high-dose groups, respectively (P =.032 for the high-dose vs placebo group). Mean E-cadherin expression per cell increased 5.6-fold in both dose groups versus in the placebo group (high-dose group P = .047). The increases in E-cadherin expression per cell from baseline to week 16 were correlated with improvements in histology, eosinophil counts, endoscopic findings, and symptoms.

Conclusion: RPC4046 significantly reduced EMT markers in adults with active EoE, with greater effects at 360 mg. Together with results for eosinophil density and clinical end points from the main trial, these data support the hypothesis that pharmacologic IL-13 inhibition ameliorates both inflammatory and remodeling pathways and could potentially reduce the risk of fibrostenotic complications.
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http://dx.doi.org/10.1016/j.jaci.2020.03.045DOI Listing
August 2020

AGA Institute and the Joint Task Force on Allergy-Immunology Practice Parameters Clinical Guidelines for the Management of Eosinophilic Esophagitis.

Gastroenterology 2020 05;158(6):1776-1786

Division of Gastroenterology and Hepatology, Veterans Affairs Northeast Ohio Healthcare System, Case Western Reserve University School of Medicine, Cleveland, Ohio.

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http://dx.doi.org/10.1053/j.gastro.2020.02.038DOI Listing
May 2020

Editorial: fluticasone propionate orally disintegrating tablets-interesting concept but is it going anywhere? Authors' reply.

Aliment Pharmacol Ther 2020 05;51(10):990-991

Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

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http://dx.doi.org/10.1111/apt.15713DOI Listing
May 2020

AGA institute and the joint task force on allergy-immunology practice parameters clinical guidelines for the management of eosinophilic esophagitis.

Ann Allergy Asthma Immunol 2020 05;124(5):416-423

Division of Gastroenterology and Hepatology, Veterans Affairs Northeast Ohio Healthcare System, Case Western Reserve University School of Medicine, Cleveland, Ohio.

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http://dx.doi.org/10.1016/j.anai.2020.03.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8135034PMC
May 2020

Improvements in Dysphagia and Pain With Swallowing in Patients With Eosinophilic Esophagitis Receiving Budesonide Oral Suspension.

Clin Gastroenterol Hepatol 2021 04 6;19(4):699-706.e4. Epub 2020 Apr 6.

Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.

Background & Aims: Quantification of eosinophilic esophagitis (EoE) symptoms is crucial for assessing treatment outcomes. We aimed to explore the effect of budesonide oral suspension (BOS) on dysphagia and pain with swallowing.

Methods: We performed a secondary analysis of data from a phase 2 multicenter, double-blind, trial (conducted from July 2012 through October 2014) of patients with EoE, 11-40 y old, who were randomly assigned to groups given placebo or BOS (2.0 mg twice daily) for 12 weeks. Symptoms were quantified using the Dysphagia Symptom Questionnaire (DSQ) from baseline to week 12 of therapy.

Results: Overall, 93 patients were randomly assigned to groups; the prespecified modified intention-to-treat analysis set comprised 87 patients (38 from the placebo group and 49 from the BOS group). Improvements from baseline in least-squares mean (standard error) DSQ (Q2+Q3) scores were observed. The difference between groups was statistically significant only at week 12 (placebo vs BOS: week 4, -4.9 [1.7] vs -7.4 [1.5]; P = .265; week 8, -7.4 [2.1] vs -10.3 [1.8]; P = .288; week 12, -7.5 [1.9] vs -14.3 [1.7]; P = .01). Similar findings were observed for pain (Q4) scores (placebo vs BOS: week 4, -2.5 [0.8] vs -3.3 [0.7]; P = .484; week 8, -3.0 [0.8] vs -4.9 [0.7]; P = .066; week 12, -3.1 [0.8] vs -4.9 [0.7]; P = .109). More severe DSQ and DSQ+pain scores were associated with presence of other symptoms (such as regurgitation) and physician-rated severity. Improvements in DSQ and DSQ+pain scores were greater in patients with either a histologic or endoscopic response than in patients without a response.

Conclusions: In a secondary analysis of data from a phase 2 trial of patients with EoE, we found evidence for improvements in dysphagia and pain scores in patients who received BOS (2.0 mg twice daily) vs placebo. Pain with swallowing should be considered in the clinical assessment of patients with EoE. ClinicalTrials.gov no: NCT01642212.
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http://dx.doi.org/10.1016/j.cgh.2020.03.060DOI Listing
April 2021

Spotlight: Treatment of Eosinophilic Esophagitis (EoE).

Gastroenterology 2020 05 6;158(6):1788. Epub 2020 Apr 6.

Section of Allergy/Immunology, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, CO.

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http://dx.doi.org/10.1053/j.gastro.2020.03.069DOI Listing
May 2020

Long-term Efficacy and Tolerability of RPC4046 in an Open-Label Extension Trial of Patients With Eosinophilic Esophagitis.

Clin Gastroenterol Hepatol 2021 03 21;19(3):473-483.e17. Epub 2020 Mar 21.

Division of Medicine, Gastroenterology, Feinberg School of Medicine, Chicago, Illinois.

Background & Aims: The short-term efficacy of RPC4046, a monoclonal antibody against interleukin-13, has been shown in patients with eosinophilic esophagitis (EoE). We investigated the long-term efficacy and safety of RPC4046 in an open-label, long-term extension (LTE) study in adults with EoE.

Methods: We analyzed data from 66 patients who completed the 16-week, double-blind, induction portion of a phase 2 study of RPC4046 (180 mg or 360 mg/wk) vs placebo and then completed a 52-week LTE, receiving open-label RPC4046 360 mg/wk. The study was conducted at 28 centers in 3 countries; patients were enrolled between September 2014 and January 2017. Outcomes were stratified by double-blind dose group and included esophageal eosinophil counts, EoE endoscopic reference score, EoE histologic scoring system score, symptom-based EoE activity index score, and safety.

Results: By week 12 of the LTE, esophageal eosinophil mean and peak counts, total EoE endoscopic reference scores, and EoE histologic scoring system grade and stage scores did not differ considerably between patients who originally received placebo vs RPC4046. Most patients maintained responses through week 52. Symptom remission (symptom-based EoE activity index score, ≤20) increased from 14% at LTE entry to 67% at LTE week 52 in placebo‒RPC4046 patients and from 30% to 54% in RPC4046‒RPC4046 (either dose) patients. Of the 28 patients who did not have a histologic response to RPC4046 during the double-blind induction phase, 10 patients (36%) achieved response during the LTE. The most common adverse events were upper respiratory tract infection (21%) and nasopharyngitis (14%).

Conclusions: One year of treatment with RPC4046 is generally well tolerated and results in continued improvement and/or maintenance of endoscopic, histologic, and clinical measures of EoE disease activity relative to baseline.

Trial Registration: NCT02098473.
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http://dx.doi.org/10.1016/j.cgh.2020.03.036DOI Listing
March 2021

Randomised clinical trial: the safety and tolerability of fluticasone propionate orally disintegrating tablets versus placebo for eosinophilic oesophagitis.

Aliment Pharmacol Ther 2020 04 9;51(8):750-759. Epub 2020 Mar 9.

Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Background: APT-1011, a fluticasone propionate orally disintegrating tablet formulation, is under investigation for the treatment of eosinophilic oesophagitis (EoE).

Aims: To evaluate the safety and tolerability of APT-1011 administered to patients with EoE and to assess the effect on clinical symptoms of EoE, endoscopic appearance and oesophageal eosinophilia.

Methods: A randomised, double-blind, placebo-controlled, multicentre, phase 1b/2a study was conducted at seven medical centres in the US to evaluate the safety and tolerability of APT-1011 over 8 weeks in adults and adolescents with EoE. Participants were randomised to placebo (n = 8), 1.5 mg APT-1011 BID (n = 8) or 3.0 mg APT-1011 QD (n = 8). Safety and tolerability were assessed as the primary outcome; histologic and endoscopic measures were assessed as exploratory outcomes.

Results: There were no deaths, serious treatment-emergent adverse events (TEAEs), severe TEAEs or discontinuations from the study related to a TEAE. In one participant randomised to 1.5 mg APT-1011 BID, a reduction in cortisol was observed, but without evidence of adrenal insufficiency. Compared with placebo, treatment with APT-1011 resulted in greater reductions in oesophageal eosinophil counts, EoE Endoscopic Reference Score, patient global assessment and symptom-based EoE activity index from baseline to end of treatment (Week 8).

Conclusions: APT-1011 was safe and well tolerated in adolescents and adults with EoE. Exploratory efficacy outcomes demonstrated improvement in histologic and endoscopic findings as well evidence of symptom improvement. The results of this study support the continued development of APT-1011 for the treatment of EoE (NCT-01386112).
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http://dx.doi.org/10.1111/apt.15670DOI Listing
April 2020

Clinical outcomes of adults with eosinophilic esophagitis with severe stricture.

Gastrointest Endosc 2020 07 16;92(1):44-53. Epub 2020 Jan 16.

Division of Gastroenterology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

Background And Aims: Eosinophilic esophagitis (EoE) is an inflammatory disease of the esophagus. Its prevalence has been increasing steadily over the past 3 decades. The prognosis of patients with EoE presenting with severe esophageal strictures is poorly understood. The aim of this study was to describe the clinical outcomes of patients with EoE with severe strictures and identify factors associated with a greater likelihood of improvement in esophageal diameter.

Methods: This study is a retrospective chart review of patients with EoE with severe stricture, defined as an esophageal diameter of 10 mm or less at one point in their disease course. Each patient's clinical course was followed during standard-of-care follow-up with medical or dietary therapy in conjunction with repeated esophageal dilation. Multivariate regression analysis was performed to determine which variables are associated with endoscopic response, defined by an improvement in esophageal diameter to 13 mm and to 15 mm.

Results: From a cohort of 1091 adults with EoE, severe strictures were identified in 66 patients (7%). Of the 66 patients, 59 (89%) achieved an esophageal diameter of ≥13 mm and 43 (65%) achieved ≥15 mm. Initial diameter (odds ratio, 1.58; 95% confidence interval, 1.06-2.35; P = .025) and histologic remission (odds ratio, 34.97; 95% confidence interval, 6.45-189.49; P < .0001) were significantly associated with achieving a diameter ≥15 mm. Age at diagnosis, gender, and number of months to maximum esophageal diameter were not associated with achieving either diameter.

Conclusions: Most patients with EoE with severe stricture experienced improvement in esophageal diameter to ≥15 mm with treatment, suggesting that the currently available treatment options are effective for patients with severe strictures. The most significant factors associated with disease reversibility are initial esophageal diameter and histologic remission.
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http://dx.doi.org/10.1016/j.gie.2020.01.015DOI Listing
July 2020

Approaches and Challenges to Management of Pediatric and Adult Patients With Eosinophilic Esophagitis.

Gastroenterology 2020 03 10;158(4):840-851. Epub 2019 Dec 10.

Digestive Health Institute, Children's Hospital Colorado, Gastrointestinal Eosinophilic Diseases Program, University of Colorado School of Medicine, Aurora, Colorado.

Treatment of eosinophilic esophagitis has progressed from elemental formula for children and esophageal dilation for adults to selective exclusion of food triggers and swallowed topical corticosteroids. Management guidelines are available from the American Gastroenterological Association and the Joint Task Force on Allergy Immunology Practice Parameters. We cannot, however, evaluate the efficacy of treatments without a definition of response. We propose a treat-to-target approach, based on symptoms and findings from endoscopy and histology. This approach addresses dissociations between outcomes, such as symptom persistence despite normalization of histologic features and symptom resolution after esophageal dilation despite histologic features of active disease. Eosinophilic esophagitis can now be treated with biologic agents that target specific immune pathways, and findings from prospective trials have indicated that less-restrictive, empiric, elimination diets can be effective and reduce the need for repeated endoscopic assessment of disease activity during food reintroduction. We also discuss eosinophilic esophagitis subtypes, factors associated with disease, and advances in management.
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http://dx.doi.org/10.1053/j.gastro.2019.09.052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063595PMC
March 2020

Association Between Endoscopic and Histologic Findings in a Multicenter Retrospective Cohort of Patients with Non-esophageal Eosinophilic Gastrointestinal Disorders.

Dig Dis Sci 2020 07 26;65(7):2024-2035. Epub 2019 Nov 26.

Center for Esophageal Diseases and Swallowing and Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, CB #7080, Chapel Hill, NC, 27599, USA.

Background: Little is known about the endoscopic and histologic findings of non-esophageal eosinophilic gastrointestinal diseases (EGID).

Aim: To characterize the presenting endoscopic and histologic findings in patients with eosinophilic gastritis (EG), eosinophilic gastroenteritis (EGE), and eosinophilic colitis (EC) at diagnosis and 6 months after initiating the treatment.

Methods: We conducted a retrospective cohort study at 6 US centers associated with the Consortium of Eosinophilic Gastrointestinal Researchers. Data abstracted included demographics, endoscopic findings, tissue eosinophil counts, and associated histologic findings at diagnosis and, when available, after initial treatment.

Results: Of 373 subjects (317 children and 56 adults), 142 had EG, 123 EGE, and 108 EC. Normal endoscopic appearance was the most common finding across all EGIDs (62% of subjects). Baseline tissue eosinophil counts were quantified in 105 (74%) EG, 36 (29%) EGE, and 80 (74%) EC subjects. The mean peak gastric eosinophil count across all sites was 87 eos/hpf for EG and 78 eos/hpf for EGE. The mean peak colonic eosinophil count for EC subjects was 76 eos/hpf (range 10-500). Of the 29% of subjects with post-treatment follow-up, most had an improvement in clinical, endoscopic, and histologic findings regardless of treatment utilized. Reductions in tissue eosinophilia correlated with improvements in clinical symptoms as well as endoscopic and histologic findings.

Conclusions: In this large cohort, normal appearance was the most common endoscopic finding, emphasizing the importance of biopsy, regardless of endoscopic appearance. Decreased tissue eosinophilia was associated with improvement in symptoms, endoscopic, and histologic findings, showing that disease activity is reversible.
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http://dx.doi.org/10.1007/s10620-019-05961-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7315780PMC
July 2020

Molecular, endoscopic, histologic, and circulating biomarker-based diagnosis of eosinophilic gastritis: Multi-site study.

J Allergy Clin Immunol 2020 01 16;145(1):255-269. Epub 2019 Nov 16.

Division of Allergy and Immunology, University of Cincinnati College of Medicine and Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. Electronic address:

Background: Eosinophilic gastritis (EG) is a clinicopathologic disorder with marked gastric eosinophilia and clinical symptoms. There is an unmet need among patients with EG for more precise diagnostic tools.

Objective: We aimed to develop tissue- and blood-based diagnostic platforms for EG.

Methods: Patients with EG and control subjects without EG were enrolled across 9 Consortium of Eosinophilic Gastrointestinal Disease Researchers-associated sites. An EG Diagnostic Panel (EGDP; gastric transcript subset) and EG blood biomarker panel (protein multiplex array) were analyzed. EGDP scores were derived from the expression of 18 highly dysregulated genes, and blood EG scores were derived from dysregulated cytokine/chemokine levels.

Results: Gastric biopsy specimens and blood samples from 185 subjects (patients with EG, n = 74; control subjects without EG, n = 111) were analyzed. The EGDP (1) identified patients with active EG (P < .0001, area under the curve ≥ 0.95), (2) effectively monitored disease activity in longitudinal samples (P = .0078), (3) highly correlated in same-patient samples (antrum vs body, r = 0.85, P < .0001), and (4) inversely correlated with gastric peak eosinophil levels (r = -0.83, P < .0001), periglandular circumferential collars (r = -0.73, P < .0001), and endoscopic nodularity (r = -0.45, P < .0001). For blood-based platforms, eotaxin-3, thymus and activation-regulated chemokine, IL-5, and thymic stromal lymphopoietin levels were significantly increased. Blood EG scores (1) distinguished patients with EG from control subjects without EG (P < .0001, area under the curve ≥ 0.91), (2) correlated with gastric eosinophil levels (plasma: r = 0.72, P = .0002; serum: r = 0.54, P = .0015), and (3) inversely correlated with EGDP scores (plasma: r = -0.64, P = .0015; serum: r = -0.46, P = .0084). Plasma eotaxin-3 levels strongly associated with gastric CCL26 expression (r = 0.81, P < .0001).

Conclusion: We developed tissue- and blood-based platforms for assessment of EG and uncovered robust associations between specific gastric molecular profiles and histologic and endoscopic features, providing insight and clinical readiness tools for this emerging rare disease.
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http://dx.doi.org/10.1016/j.jaci.2019.11.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6949389PMC
January 2020
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