Publications by authors named "Mirna Chehade"

67 Publications

Treatment of Eosinophilic Esophagitis: Diet or Medication?

J Allergy Clin Immunol Pract 2021 Sep;9(9):3249-3256

Division of Allergy and Immunology, Department of Pediatrics, University of California, San Diego, Rady Children's Hospital, San Diego, Calif.

Eosinophilic esophagitis (EoE) is an antigen-triggered chronic disease of increasing prevalence in children and adults. Untreated or therapy-resistant EoE leads to complications of esophageal food impactions and luminal narrowing. The past decade has seen a number of new clinical trials for EoE therapies including elimination diets, proton pump inhibitors, swallowed topical corticosteroids, and biologics. In this review, we comment on the current state of the art for dietary and pharmacologic management of EoE and the need for future clinical trials to help tailor therapies to individual patients with this chronic disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaip.2021.07.029DOI Listing
September 2021

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, Tex; Department of Pathology, Baylor College of Medicine, Houston, Tex.

Background: End points 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: We sought 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 4 outcome domains for controlled and observational studies: histopathology, endoscopy, patient-reported symptoms, and EoE-specific quality of life. A total of 69 stakeholders (response rate 95.8%) prioritized 42 outcomes in a 2-round Delphi process, and the final ratification meeting generated consensus on 33 outcome measures. These included measurement of the peak eosinophil count, Eosinophilic Esophagitis Histology Scoring System, Eosinophilic Esophagitis Endoscopic Reference Score, and patient-reported measures of dysphagia and quality of life.

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 and will facilitate meaningful treatment comparisons and improve the quality of data synthesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaci.2021.07.001DOI Listing
July 2021

Do rural health disparities affect prevalence data in pediatric eosinophilic esophagitis?

J Allergy Clin Immunol Pract 2021 06;9(6):2549-2551

Department of Pediatrics, Division of Gastroenterology, Children's Hospital of Philadelphia, Perlman School of Medicine at the University of Pennsylvania, Philadelphia, Pa. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaip.2021.03.027DOI 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).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cgh.2021.05.053DOI Listing
June 2021

Noninvasive biomarkers identify eosinophilic esophagitis: A prospective longitudinal study in children.

Allergy 2021 Apr 27. Epub 2021 Apr 27.

Northwestern University Feinberg School of Medicine, Chicago, IL, USA.

Background: Esophageal histology is critical for diagnosis and surveillance of disease activity in eosinophilic esophagitis (EoE). A validated noninvasive biomarker has not been identified. We aimed to determine the utility of blood and urine eosinophil-associated proteins to diagnose EoE and predict esophageal eosinophilia.

Methods: Blood and urine were collected from children undergoing endoscopy with biopsy. Absolute eosinophil count (AEC), plasma eosinophil-derived neurotoxin (EDN), eosinophil cationic protein (ECP), major basic protein-1 (MBP-1), galectin-10 (CLC/GAL-10), Eotaxin-2 and Eotaxin-3, and urine osteopontin (OPN) and matrix metalloproteinase-9 (MMP-9) were determined. Differences were assessed between EoE and control, and with treatment response. The capacity to predict EoE diagnosis and esophageal eosinophil counts was assessed.

Results: Of 183 specimens were collected from 56 EoE patients and 15 non-EoE controls with symptoms of esophageal dysfunction; 33 EoE patients had paired pre- and post-treatment specimens. Plasma (CLC/GAL-10, ECP, EDN, Eotaxin-3, MBP-1) and urine (OPN) biomarkers were increased in EoE compared to control. A panel comprising CLC/GAL-10, Eotaxin-3, ECP, EDN, MBP-1, and AEC was superior to AEC alone in distinguishing EoE from control. AEC, CLC/GAL-10, ECP, and MBP-1 were significantly decreased in patients with esophageal eosinophil counts <15/hpf in response to treatment. AEC, CLC/GAL-10, ECP, EDN, OPN, and MBP-1 each predicted esophageal eosinophil counts utilizing mixed models controlled for age, gender, treatment, and atopy; AEC combined with MBP-1 best predicted the counts.

Conclusions: We identified novel panels of eosinophil-associated proteins that along with AEC are superior to AEC alone in distinguishing EoE from controls and predicting esophageal eosinophil counts.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/all.14874DOI Listing
April 2021

Diagnostic Delay in Patients with Eosinophilic Gastritis and/or Duodenitis: A Population-Based Study.

J Allergy Clin Immunol Pract 2021 05 10;9(5):2050-2059.e20. Epub 2021 Jan 10.

Allakos Inc., Redwood City, Calif.

Background: Eosinophilic gastritis and/or eosinophilic duodenitis (EG/EoD) is characterized by persistent symptoms and elevated eosinophils in the gastrointestinal tract. Limited disease awareness and lack of diagnostic guidelines suggest that patients may remain undiagnosed or endure diagnostic delay.

Objective: To characterize the path to diagnosis for patients with EG/EoD in a representative population.

Methods: In this observational cohort study, 4108 eligible patients diagnosed with EG/EoD between 2008 and 2018 were identified in an administrative claims database in the United States. Patient medical claim history was analyzed to describe events related to diagnosis.

Results: Mean year from symptom presentation to diagnosis of EG/EoD was 3.6; factors contributing to diagnostic delay included delayed gastroenterologist referral, delayed esophagogastroduodenoscopy (EGD), and lack of biopsy collection and/or histopathologic evaluation. Missed diagnosis on index EGD occurred in 38.2% of patients, resulting in a mean increase of 1.6 years in time to diagnosis versus patients diagnosed on index EGD. Patients presented with nonspecific symptoms and 44.3% were diagnosed with another gastrointestinal condition before EG/EoD diagnosis. Independent predictors of >2-year diagnostic delay included adult age; prior diagnosis of irritable bowel syndrome, functional dyspepsia, or gastric/peptic ulcer; use of other procedures such as colonoscopy; presence of edema; and history of certain allergic diseases.

Conclusions: This study found that patients with EG/EoD experienced an average of 3.6 years between initial symptom presentation and diagnosis and revealed several factors contributing to diagnostic delay. We hope that these findings, together with heightened awareness and standardization of diagnostic guidelines, will improve the diagnostic journey of patients with EG/EoD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaip.2020.12.054DOI Listing
May 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.).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1056/NEJMoa2012047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600443PMC
October 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cgh.2020.08.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8108396PMC
August 2020

Elimination diets for eosinophilic esophagitis: making the best choice.

Expert Rev Clin Immunol 2020 07 4;16(7):679-687. Epub 2020 Aug 4.

Mount Sinai Center for Eosinophilic Disorders, Icahn School of Medicine at Mount Sinai , New York, NY, USA.

Introduction: Dietary elimination therapy has long been an option for patients with eosinophilic esophagitis (EoE). Multiple diets have been reported, with variable efforts involved, efficacy rates, costs, and long-term management plans. Although the pros and cons of dietary elimination therapy have been described, a clear method for deciding on who is the right candidate for a diet, and which diet is best for that candidate, has not been clearly delineated.

Areas Covered: This article covers the benefits and challenges of dietary elimination therapies for patients with EoE. It outlines factors to consider before opting for an elimination diet, and for choosing which specific elimination diet to follow. Efficacy rates and pros and cons of each specific elimination diet are also discussed. Peer-reviewed published studies testing various elimination diets in patients with EoE were used for that purpose.

Expert Opinion: Dietary elimination therapy is a long-term management option for patients with EoE. Shared decision making involving the patient and the medical provider is important. Multiple factors including demographics, diet, nutritional status, social and financial support, and acceptance of multiple endoscopies need to be considered. Ongoing multi-disciplinary support during the initiation and maintenance phases of the diet is crucial to ensure good outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/1744666X.2020.1801419DOI Listing
July 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MPG.0000000000002817DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574400PMC
October 2020

Identification of anoctamin 1 (ANO1) as a key driver of esophageal epithelial proliferation in eosinophilic esophagitis.

J Allergy Clin Immunol 2020 01 21;145(1):239-254.e2. Epub 2019 Oct 21.

Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Mary H Weiser Food Allergy Center and Department of Pathology, Ann Arbor, Mich. Electronic address:

Background: The pathology of eosinophilic esophagitis (EoE) is characterized by eosinophil-rich inflammation, basal zone hyperplasia (BZH), and dilated intercellular spaces, and the underlying processes that drive the pathologic manifestations of the disease remain largely unexplored.

Objective: We sought to investigate the involvement of the calcium-activated chloride channel anoctamin 1 (ANO1) in esophageal proliferation and the histopathologic features of EoE.

Methods: We examined mRNA and protein expression of ANO1 in esophageal biopsy samples from patients with EoE and in mice with EoE. We performed molecular and cellular analyses and ion transport assays on an in vitro esophageal epithelial 3-dimensional model system (EPC2-ALI) and murine models of EoE to define the relationship between expression and function of ANO1 and esophageal epithelial proliferation in patients with EoE.

Results: We observed increased ANO1 expression in esophageal biopsy samples from patients with EoE and in mice with EoE. ANO1 was expressed within the esophageal basal zone, and expression correlated positively with disease severity (eosinophils/high-power field) and BZH. Using an in vitro esophageal epithelial 3-dimensional model system revealed that ANO1 undergoes chromatin modification and rapid upregulation of expression after IL-13 stimulation, that ANO1 is the primary apical IL-13-induced Cl transport mechanism within the esophageal epithelium, and that loss of ANO1-dependent Cl transport abrogated esophageal epithelial proliferation. Mechanistically, ANO1-dependent regulation of basal cell proliferation was associated with modulation of TP63 expression and phosphorylated cyclin-dependent kinase 2 levels.

Conclusions: These data identify a functional role for ANO1 in esophageal cell proliferation and BZH in patients with EoE and provide a rationale for pharmacologic intervention of ANO1 function in patients with EoE.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaci.2019.07.049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7366251PMC
January 2020

Efficacy of Dupilumab in a Phase 2 Randomized Trial of Adults With Active Eosinophilic Esophagitis.

Gastroenterology 2020 01 5;158(1):111-122.e10. Epub 2019 Oct 5.

Regeneron Pharmaceuticals, Inc, Tarrytown, New York.

Background & Aims: Eosinophilic esophagitis (EoE) is an allergen-mediated inflammatory disease with no approved treatment in the United States. Dupilumab, a VelocImmune-derived human monoclonal antibody against the interleukin (IL) 4 receptor, inhibits IL4 and IL13 signaling. Dupilumab is effective in the treatment of allergic, atopic, and type 2 diseases, so we assessed its efficacy and safety in patients with EoE.

Methods: We performed a phase 2 study of adults with active EoE (2 episodes of dysphagia/week with peak esophageal eosinophil density of 15 or more eosinophils per high-power field), from May 12, 2015, through November 9, 2016, at 14 sites. Participants were randomly assigned to groups that received weekly subcutaneous injections of dupilumab (300 mg, n = 23) or placebo (n = 24) for 12 weeks. The primary endpoint was change from baseline to week 10 in Straumann Dysphagia Instrument (SDI) patient-reported outcome (PRO) score. We also assessed histologic features of EoE (peak esophageal intraepithelial eosinophil count and EoE histologic scores), endoscopically visualized features (endoscopic reference score), esophageal distensibility, and safety.

Results: The mean SDI PRO score was 6.4 when the study began. In the dupilumab group, SDI PRO scores were reduced by a mean value of 3.0 at week 10 compared with a mean reduction of 1.3 in the placebo group (P = .0304). At week 12, dupilumab reduced the peak esophageal intraepithelial eosinophil count by a mean 86.8 eosinophils per high-power field (reduction of 107.1%; P < .0001 vs placebo), the EoE-histologic scoring system (HSS) severity score by 68.3% (P < .0001 vs placebo), and the endoscopic reference score by 1.6 (P = .0006 vs placebo). Dupilumab increased esophageal distensibility by 18% vs placebo (P < .0001). Higher proportions of patients in the dupilumab group developed injection-site erythema (35% vs 8% in the placebo group) and nasopharyngitis (17% vs 4% in the placebo group).

Conclusions: In a phase 2 trial of patients with active EoE, dupilumab reduced dysphagia, histologic features of disease (including eosinophilic infiltration and a marker of type 2 inflammation), and abnormal endoscopic features compared with placebo. Dupilumab increased esophageal distensibility and was generally well tolerated. ClinicalTrials.gov, Number: NCT02379052.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1053/j.gastro.2019.09.042DOI Listing
January 2020

Eosinophilic gastrointestinal disorders: The journey to diagnosis remains arduous.

Authors:
Mirna Chehade

Ann Allergy Asthma Immunol 2020 03 17;124(3):229-230. Epub 2019 Sep 17.

Mount Sinai Center for Eosinophilic Disorders, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.anai.2019.09.011DOI Listing
March 2020

The asymptomatic patient with eosinophilic esophagitis: To treat or not to treat?

Ann Allergy Asthma Immunol 2019 06;122(6):550-551

Jaffe Food Allergy Institute, Division of Allergy and Immunology, Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.anai.2019.03.035DOI Listing
June 2019

Feeding difficulties in children with non-IgE-mediated food allergic gastrointestinal disorders.

Ann Allergy Asthma Immunol 2019 06 26;122(6):603-609. Epub 2019 Mar 26.

The Ellyn Satter Institute, Madison, Wisconsin.

Objective: To review the signs and symptoms of feeding difficulties in children with non-IgE-mediated food allergic gastrointestinal disorders and provide practical advice, with the goal of guiding the practitioner to timely referral for further evaluation and therapy. Various management approaches are also discussed.

Data Sources: Articles and chapters related to normal feeding patterns and the diagnosis and management of feeding difficulties in children were reviewed.

Study Selections: Selections were based on relevance to the topic and inclusion of diagnostic and management recommendations.

Results: Because most non-IgE-mediated food allergic gastrointestinal disorders occur in early childhood, feeding skills can be disrupted. Feeding difficulties can result in nutritional deficiencies, faltering growth, and a significant impact on quality of life. Specific symptoms related to each non-IgE-mediated food allergic gastrointestinal disorder can lead to distinctive presentations, which should be differentiated from simple picky eating. Successful management of feeding difficulties requires that the health care team views the problem as a relational disorder between the child and the caregiver and views its association with the symptoms experienced as a result of the non-IgE-mediated food allergic gastrointestinal disorder. Addressing the child's concern with eating needs to be done in the context of the family unit, with coaching provided to the caregiver as necessary while ensuring nutritional adequacy. Treatment approaches, including division of responsibility, food chaining, and sequential oral sensory, are commonly described in the context of feeding difficulties.

Conclusion: A multidisciplinary approach to management of feeding difficulties in non-IgE-mediated food allergic gastrointestinal disorders is of paramount importance to ensure success.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.anai.2019.03.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237234PMC
June 2019

Variation in Endoscopic Activity Assessment and Endoscopy Score Validation in Adults With Eosinophilic Esophagitis.

Clin Gastroenterol Hepatol 2019 07 23;17(8):1477-1488.e10. Epub 2018 Nov 23.

Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.

Background & Aims: Eosinophilic esophagitis (EoE) is assessed endoscopically (endoscopic activity), based on grades of edema, rings, exudates, furrows, and strictures (EREFS). We examined variations in endoscopic assessments of severity, developed and validated 3 EREFS-based scoring systems, and assessed responsiveness of these systems using data from a randomized placebo-controlled trial of patients with EoE.

Methods: For the development set, 5 gastroenterologists reviewed EREFS findings from 266 adults with EoE and provided endoscopist global assessment scores (EndoGA, scale of 0 to 10); variation (ΔEndoGA) was assessed using linear regression. We evaluated simple scores (features given arbitrary values from 0 to 3) and developed 2 scoring systems (adjusted score range, 0-100). We then fitted our linear regression model with mean EndoGA to data from 146 adults recruited in centers in Switzerland and the United States between April 2011 and December 2012. For the validation set, we collected data from 120 separate adults (recruited in centers in Switzerland and the United States between May 2013 and July 2014), assessing regression coefficient-based scores using Bland-Altman method. We assessed the responsiveness of our scoring systems using data from a randomized trial of patients with EoE given fluticasone (n=16) or placebo (n=8).

Results: The distribution of EndoGA values differed among endoscopists (mean ΔEndoGA, 2.6±1.8; range 0-6.6). We developed 2 regression-based scoring systems to assess overall and proximal and distal esophageal findings; variation in endoscopic features accounted for more than 90% of the mean EndoGA variation. In the validation group, differences between mean EndoGA and regression-based scores were small (ranging from -4.70 to 2.03), indicating good agreement. In analyses of data from the randomized trial, the baseline to end of study change in patients given fluticasone was a reduction of 24.3 in simple score (reduction of 4.6 in patients given placebo, P=.052); a reduction of 23.5 in regression-based overall score (reduction of 6.56 in patients given placebo, P=.12), and a reduction of 23.8 (reduction of 8.44 in patients given placebo, P=.11).

Conclusion: Assessments of endoscopic activity in patients with EoE vary among endoscopists. In an analysis of data from a randomized controlled trial, we found that newly developed scoring systems are no better than simple scoring system in detecting changes in endoscopic activity. These results support the use of a simple scoring system in evaluation of endoscopic activity in patients with EoE. clinicaltrials.gov no: NCT00939263 and NCT01386112.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cgh.2018.11.032DOI Listing
July 2019

Open-label, add-on trial of cetirizine for neuromyelitis optica.

Neurol Neuroimmunol Neuroinflamm 2018 Mar 2;5(2):e441. Epub 2018 Feb 2.

Corinne Goldsmith Dickinson Center for Multiple Sclerosis (I.K.S., M.F., C.F., S.E., F.L.), Department of Neurology, Icahn School of Medicine at Mount Sinai, NY; Department of Pediatrics (R.T., L.C.), University of Utah, Salt Lake City; Drug Discovery Institute (T.A.K.), Mount Sinai Center for Eosinophilic Disorders (M.C.), Jaffe Food Allergy Institute (M.M.), Department of Pediatrics, and Department of Microbiology (T.M.), Icahn School of Medicine at Mount Sinai, NY; Department of Neurology (J.R.), University of Utah, Salt Lake City.

Objective: This pilot study preliminarily examined the efficacy and tolerability of cetirizine as an add-on to standard therapy for neuromyelitis optica (NMO).

Methods: Eligible participants met the Wingerchuk 2006 diagnostic criteria or had a single typical episode along with positive NMO immunoglobulin G. After baseline clinical and laboratory assessments, participants began treatment with cetirizine 10 mg orally daily, in addition to their usual disease-modifying therapy for NMO, and continued for 1 year. The primary end point was the annualized relapse rate (ARR) while on the same disease-modifying therapy before starting cetirizine compared with after taking cetirizine. Additional end points included disability (Expanded Disability Status Scale [EDSS]), relapse severity, tolerability, especially with respect to drowsiness measured by the Epworth Sleepiness Scale (ESS), and laboratory parameters.

Results: The ARR before cetirizine was 0.4 ± 0.80 and after cetirizine was 0.1 ± 0.24 ( = 0.047). There was no statistically significant difference in the EDSS (mean 3.9 ± 2.18 before the start of the study and 3.2 ± 2.31 at the conclusion of the study, = 0.500). The ESS remained fairly consistent throughout the study (mean 6.5 ± 5.33 at baseline and 6.9 ± 4.50 at month 12, = 0.740). Laboratory studies were unrevealing.

Conclusions: In this pilot study, cetirizine was well tolerated, and the prespecified primary efficacy end point was satisfied. However, the open-label design and the small sample size of this pilot study preclude definitive conclusions. Further research is needed.

Classification Of Evidence: This study provides Class IV evidence that in patients with NMO, the addition of cetirizine to standard therapy is safe, well tolerated, and reduces relapses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/NXI.0000000000000441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6201737PMC
March 2018

New diagnostic criteria for eosinophilic esophagitis: Will they influence our practice?

Authors:
Mirna Chehade

Ann Allergy Asthma Immunol 2018 09;121(3):266-267

Mount Sinai Center for Eosinophilic Disorders, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.anai.2018.07.031DOI Listing
September 2018

Eosinophilic esophagitis 25 years after its recognition: Where do we stand?

Authors:
Mirna Chehade

Ann Allergy Asthma Immunol 2018 08;121(2):141-142

Mount Sinai Center for Eosinophilic Disorders, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.anai.2018.06.019DOI Listing
August 2018

Phenotypic Characterization of Eosinophilic Esophagitis in a Large Multicenter Patient Population from the Consortium for Food Allergy Research.

J Allergy Clin Immunol Pract 2018 Sep - Oct;6(5):1534-1544.e5. Epub 2018 Aug 1.

Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.

Background: Eosinophilic esophagitis (EoE) is increasingly common, but data on phenotypic aspects are still incomplete.

Objectives: To describe the clinical, endoscopic, and histopathologic features of a large number of children and adults with EoE across the United States.

Methods: This was a multisite single visit registry enrolling subjects aged 6 months to 65 years with EoE. Participants provided responses regarding their medical history, with verification of the diagnosis and history by the study teams.

Results: A total of 705 subjects were analyzed (median [interquartile range] age at enrollment 11.2 [6.7-17.7] years, 68.2% male, 87.9% whites). Of these, 67 subjects had concurrent gastrointestinal eosinophilia, with gastric mucosa most common. An age- and race-dependent time gap was present between symptom onset and time of diagnosis (adults and whites with longer gap). Food allergy and atopic dermatitis were associated with a decrease in this gap. Symptoms varied with age (more dysphagia and food impaction in adults) and with race (more vomiting in non-whites). Esophageal rings and strictures at diagnosis were more common in adults, although esophageal eosinophilia was comparable among age groups. Concomitant allergic disease (91%), infectious/immunologic disorders (44%), neurodevelopmental disorders (30%), and failure to thrive (21%) were common. Depression/anxiety increased with age. EoE was reported in 3% of parents and 4.5% of siblings.

Conclusions: Gastrointestinal eosinophilia is present in approximately 10% of patients with EoE; the symptom-diagnosis time gap is influenced by age, race, food allergy, and atopic dermatitis; symptoms vary with race; concurrent infectious/immunologic disorders and mental health disorders are common; and the level of esophageal eosinophils is comparable in patients with and without fibrostenotic features.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaip.2018.05.038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6132253PMC
November 2019

Eosinophilic esophagitis-Where are we today?

J Pediatr (Rio J) 2019 May - Jun;95(3):275-281. Epub 2018 Aug 1.

Icahn School of Medicine at Mount Sinai, Mount Sinai Center for Eosinophilic Disorders, New York, United States.

Objective: The objective of this review is to provide an overview of the practical diagnostic and therapeutic approaches to eosinophilic esophagitis and to increase the visibility of the disease among pediatricians.

Sources: A search of the MEDLINE, Embase, and CINAHL databases and recent consensus statements and guidelines were performed.

Summary Of The Findings: The definition of eosinophilic esophagitis is based on symptoms and histology. It is important to rule out other diseases associated with esophageal eosinophil-predominant inflammation. It is not yet clear whether the increased prevalence is due to a real increase in incidence or a result of increased awareness of the disease. Various options for management have been used in pediatric patients, including proton pump inhibitors, dietary restriction therapies, swallowed topical steroids, and endoscopic dilations. More recently, proton pump inhibitor-responsive esophageal eosinophilia and eosinophilic esophagitis have been contemplated on the same spectrum, and proton pump inhibitors should be considered the initial step in the treatment of these patients.

Conclusions: Eosinophilic esophagitis is a relatively new disease with a remarkable progression of its incidence and prevalence in the past two to three decades, and diagnostic criteria that are constantly evolving. It is important to better understand the pathogenesis of the disease, the predisposing factors, the natural history, and the categorization of varying phenotypes to develop diagnostic and therapeutic strategies that meet the clinical needs of patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jped.2018.06.012DOI Listing
October 2019

Updated International Consensus Diagnostic Criteria for Eosinophilic Esophagitis: Proceedings of the AGREE Conference.

Gastroenterology 2018 10 6;155(4):1022-1033.e10. Epub 2018 Sep 6.

Division of Pediatric Gastroenterology, Hepatology and Nutrition, Children's Hospital of Illinois, University of Illinois, Peoria, Illinois.

Background & Aims: Over the last decade, clinical experiences and research studies raised concerns regarding use of proton pump inhibitors (PPIs) as part of the diagnostic strategy for eosinophilic esophagitis (EoE). We aimed to clarify the use of PPIs in the evaluation and treatment of children and adults with suspected EoE to develop updated international consensus criteria for EoE diagnosis.

Methods: A consensus conference was convened to address the issue of PPI use for esophageal eosinophilia using a process consistent with standards described in the Appraisal of Guidelines for Research and Evaluation II. Pediatric and adult physicians and researchers from gastroenterology, allergy, and pathology subspecialties representing 14 countries used online communications, teleconferences, and a face-to-face meeting to review the literature and clinical experiences.

Results: Substantial evidence documented that PPIs reduce esophageal eosinophilia in children, adolescents, and adults, with several mechanisms potentially explaining the treatment effect. Based on these findings, an updated diagnostic algorithm for EoE was developed, with removal of the PPI trial requirement.

Conclusions: EoE should be diagnosed when there are symptoms of esophageal dysfunction and at least 15 eosinophils per high-power field (or approximately 60 eosinophils per mm) on esophageal biopsy and after a comprehensive assessment of non-EoE disorders that could cause or potentially contribute to esophageal eosinophilia. The evidence suggests that PPIs are better classified as a treatment for esophageal eosinophilia that may be due to EoE than as a diagnostic criterion, and we have developed updated consensus criteria for EoE that reflect this change.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1053/j.gastro.2018.07.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6174113PMC
October 2018

Genetic variants at the 16p13 locus confer risk for eosinophilic esophagitis.

Genes Immun 2019 04 8;20(4):281-292. Epub 2018 Jun 8.

Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Division of Allergy and Immunology, University of Cincinnati, Cincinnati, OH, USA.

Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus triggered by immune hypersensitivity to food. Herein, we tested whether genetic risk factors for known, non-allergic, immune-mediated diseases, particularly those involving autoimmunity, were associated with EoE risk. We used the high-density Immunochip platform, encoding 200,000 genetic variants for major auto-immune disease. Accordingly, 1214 subjects with EoE of European ancestry and 3734 population controls were genotyped and assessed using data directly generated or imputed from the previously published GWAS. We found lack of association of EoE with the genetic variants in the major histocompatibility complex (MHC) class I, II, and III genes and nearly all other loci using a highly powered study design with dense genotyping throughout the locus. Importantly, we identified an EoE risk locus at 16p13 with genome-wide significance (P=2.05 × 10, odds ratio = 0.76-0.81). This region is known to encode for the genes CLEC16A, DEXI, and CIITI, which are expressed in immune cells and esophageal epithelial cells. Suggestive EoE risk were also seen 5q23 (intergenic) and 7p15 (JAZF1). Overall, we have identified an additional EoE risk locus at 16p13 and highlight a shared and unique genetic etiology of EoE with a spectrum of immune-associated diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41435-018-0034-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6286696PMC
April 2019

New developments in patients with eosinophilic gastrointestinal diseases presented at the CEGIR/TIGERS Symposium at the 2018 American Academy of Allergy, Asthma & Immunology Meeting.

J Allergy Clin Immunol 2018 07 24;142(1):48-53. Epub 2018 May 24.

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

The Consortium of Eosinophilic Gastrointestinal Diseases and the International Gastrointestinal Eosinophil Researchers organized a day-long symposium at the recent 2018 Annual Meeting of the American Academy of Allergy, Asthma & Immunology, which was coupled for the first time with the World Allergy Organization meeting to create an international platform. The symposium featured experts in many facets of eosinophilic gastrointestinal diseases, including allergy, immunology, gastroenterology, pathology, and nutrition, and was a well-attended event. The basic science, genetics, cellular immunology, and clinical features of the diseases, with a focus on epithelial, eosinophil, and mast cell responses, as well as current and emerging treatment options, were reviewed. Here we briefly review some of the highlights of the material presented at the meeting.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaci.2018.05.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6129859PMC
July 2018

Solute carrier family 9, subfamily A, member 3 (SLC9A3)/sodium-hydrogen exchanger member 3 (NHE3) dysregulation and dilated intercellular spaces in patients with eosinophilic esophagitis.

J Allergy Clin Immunol 2018 12 4;142(6):1843-1855. Epub 2018 May 4.

Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Department of Pathology, Mary H Weiser Food Allergy Center, Michigan Medicine, University of Michigan, Ann Arbor, Mich. Electronic address:

Background: Eosinophilic esophagitis (EoE) is characterized by histopathologic modifications of esophageal tissue, including eosinophil-rich inflammation, basal zone hyperplasia, and dilated intercellular spaces (DIS). The underlying molecular processes that drive the histopathologic features of EoE remain largely unexplored.

Objective: We sought to investigate the involvement of solute carrier family 9, subfamily A, member 3 (SLC9A3) in esophageal epithelial intracellular pH (pH) and DIS formation and the histopathologic features of EoE.

Methods: We examined expression of esophageal epithelial gene networks associated with regulation of pH in the EoE transcriptome of primary esophageal epithelial cells and an in vitro esophageal epithelial 3-dimensional model system (EPC2-ALI). Molecular and cellular analyses and ion transport assays were used to evaluate the expression and function of SLC9A3.

Results: We identified altered expression of gene networks associated with regulation of pH and acid-protective mechanisms in esophageal biopsy specimens from pediatric patients with EoE (healthy subjects, n = 6; patients with EoE, n = 10). The most dysregulated gene central to regulating pH was SLC9A3. SLC9A3 expression was increased within the basal layer of esophageal biopsy specimens from patients with EoE, and expression positively correlated with disease severity (eosinophils/high-power field) and DIS (healthy subjects, n = 10; patients with EoE, n = 10). Analyses of esophageal epithelial cells revealed IL-13-induced, signal transducer and activator of transcription 6-dependent SLC9A3 expression and Na-dependent proton secretion and that SLC9A3 activity correlated positively with DIS formation. Finally, we showed that IL-13-mediated, Na-dependent proton secretion was the primary intracellular acid-protective mechanism within the esophageal epithelium and that blockade of SLC9A3 transport abrogated IL-13-induced DIS formation.

Conclusions: SLC9A3 plays a functional role in DIS formation, and pharmacologic interventions targeting SLC9A3 function may suppress the histopathologic manifestations in patients with EoE.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaci.2018.03.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6448407PMC
December 2018

Biological Therapies for Eosinophilic Esophagitis: Where Do We Stand?

Clin Rev Allergy Immunol 2018 Oct;55(2):205-216

Mount Sinai Center for Eosinophilic Disorders, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1198, New York, NY, 10029, USA.

Eosinophilic esophagitis (EoE) is an immune-mediated, chronic esophageal disease characterized by esophageal symptoms and esophageal eosinophilia. It is triggered by foods and possibly by environmental allergens. Currently, there are no FDA-approved therapies for EoE. Commonly used treatments include dietary restrictions and topical corticosteroids. Many of these therapies are suboptimal in their efficacy, have side effects, or diminish patients' quality of life. Biologic therapies for EoE have therefore been sought as an alternative. The mechanism by which food allergens trigger EoE is thought to be a T helper type 2 (Th2) reaction, resulting in secretion of the cytokines IL-4, IL-5, and IL-13. IL-5 induces eosinophil production and trafficking to the esophagus, and IL-13 induces esophageal epithelial cells to secrete eotaxin-3, which drives eosinophil chemotaxis and activation. Mepolizumab and reslizumab, two anti-IL-5 antibodies, were studied in children and adults with EoE and resulted in reduction of esophageal tissue and blood eosinophils, but no significant reduction in symptoms. QAX576, an anti-IL-13 antibody, was studied in adults with EoE and showed a decrease in the esophageal eosinophil load and a trend towards clinical improvement. Since in situ IgE production was demonstrated in the EoE esophagus, omalizumab, an anti-IgE antibody, was studied in patients with EoE and not found to be overall beneficial. Furthermore, given the increased esophageal epithelial cell TNF-α expression in EoE, infliximab, an anti-TNF-α antibody, was studied in patients with EoE, with lack of success both clinically and histologically. In summary, although none of the biologicals studied so far in EoE have been highly effective, many demonstrated some histological benefit, especially those that targeted the Th2 axis. Therefore, the future for biologicals is promising as the pathophysiology of EoE is better understood, clinical assessment tools are validated, identification of patient subsets that respond best to biologicals is made, and dosages of biologicals are optimized.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12016-018-8674-3DOI Listing
October 2018

Creating a multi-center rare disease consortium - the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR).

Transl Sci Rare Dis 2017 Dec 18;2(3-4):141-155. Epub 2017 Dec 18.

Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.

 Eosinophilic gastrointestinal disorders (EGIDs) affect various segments of the gastrointestinal tract. Since these disorders are rare, collaboration is essential to enroll subjects in clinical studies and study the broader population. The Rare Diseases Clinical Research Network (RDCRN), a program of the National Center for Advancing Translational Sciences (NCATS), funded the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR) in 2014 to advance the field of EGIDs. CEGIR facilitates collaboration among various centers, subspecialties, patients, professional organizations and patient-advocacy groups and includes 14 clinical sites. It has successfully initiated two large multi-center clinical studies looking to refine EGID diagnoses and management. Several pilot studies are underway that focus on various aspects of EGIDs including novel therapeutic interventions, diagnostic and monitoring methods, and the role of the microbiome in pathogenesis. CEGIR currently nurtures five physician-scholars through a career training development program and has published more than 40 manuscripts since its inception. This review focuses on CEGIR's operating model and progress and how it facilitates a framework for exchange of ideas and stimulates research and innovation. This consortium provides a model for progress on other potential clinical areas.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3233/TRD-170016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5757645PMC
December 2017

Development of IgE-mediated immediate hypersensitivity to a previously tolerated food following its avoidance for eosinophilic gastrointestinal diseases.

J Allergy Clin Immunol Pract 2018 Mar - Apr;6(2):649-650. Epub 2017 Sep 22.

Pediatric Allergy and Immunology, Icahn School of Medicine at Mount Sinai, New York, NY; Mount Sinai Center for Eosinophilic Disorders, Icahn School of Medicine at Mount Sinai, New York, NY. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaip.2017.08.014DOI Listing
November 2019
-->