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Effects of allergen sensitization on response to therapy in children with eosinophilic esophagitis.

ABSTRACT: BACKGROUND:In children with eosinophilic esophagitis (EoE) foods are the most common disease triggers, but environmental allergens are also suspected culprits. OBJECTIVE:To determine the effects of environmental allergen sensitization on response to treatment in children with EoE in the southeastern United States. METHODS:Patients 2 to 18 years old who were referred to the Arkansas Children's Hospital Eosinophilic Gastrointestinal Disorders Clinic from January 2012 to January 2016 were enrolled in a prospective, longitudinal cohort study with collection of demographics, clinical symptoms, medical history, allergy sensitization profiles, and response to treatment over time. Comparisons were made between complete responders (peak esophageal eosinophil count <15 per high-power field [HPF]) and nonresponders (>25 eosinophils per HPF) after treatment with diet elimination alone, swallowed corticosteroids alone, or diet elimination and swallowed corticosteroids. Sensitization patterns to environmental allergens found in the southeastern United States were analyzed for the effect on treatment response. RESULTS:A total of 223 individuals were enrolled. Of these, 182 had environmental allergy profiling and at least one endoscopy while receiving proton pump inhibitor (PPI) therapy. Twenty-nine individuals had PPI-responsive EoE and were excluded from further analysis, leaving 123 individuals with non-PPI-responsive EoE who were further analyzed; 72 (58.5%) were complete responders and 33 (26.8%) were nonresponders. Seventeen individuals (13.8%) were partial responders (?1 but ?25 eosinophils per HPF) and excluded from further analysis. Nonresponders were more likely to be sensitized to perennial allergens (P = .02). There was no significant difference in response based on seasonal allergen sensitization. Individuals with mold or cockroach sensitization were more likely to fail combination diet and swallowed corticosteroid treatment (P = .02 and P = .002). CONCLUSION:Perennial allergen and mold sensitization may lead to nonresponse to EoE treatment in some patients. Additional studies are needed to further understand the effect of environmental allergens on EoE. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT01779154.

SUBMITTER: Pesek RD

PROVIDER: S-EPMC6166246 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Effects of allergen sensitization on response to therapy in children with eosinophilic esophagitis.

Pesek Robert D RD Rettiganti Mallikarjuna M O'Brien Erin E Beckwith Sarah S Daniel Caroline C Luo Chunqiao C Scurlock Amy M AM Chandler Peggy P Levy Rebecca A RA Perry Tamara T TT Kennedy Joshua L JL Chervinskiy Sheva S Vonlanthen Maryelle M Casteel Helen H Fiedorek Stephen C SC Gibbons Troy T Jones Stacie M SM

Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology 20170701 2

<h4>Background</h4>In children with eosinophilic esophagitis (EoE) foods are the most common disease triggers, but environmental allergens are also suspected culprits.<h4>Objective</h4>To determine the effects of environmental allergen sensitization on response to treatment in children with EoE in the southeastern United States.<h4>Methods</h4>Patients 2 to 18 years old who were referred to the Arkansas Children's Hospital Eosinophilic Gastrointestinal Disorders Clinic from January 2012 to Janua ...[more]

PMID: 28676207

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Project description:BACKGROUND & AIMS:The endoscopic reference score (EREFS) is used to determine severity of 5 endoscopic findings: edema, rings, exudates, furrows, and strictures. Little is known about the relationship between EREFSs and histologic markers of disease activity in children with eosinophilic esophagitis (EoE). We aimed to determine whether the EREFS can be used to identify children with EoE and how it changes with treatment. METHODS:We performed a prospective study of consecutive children (ages 2-17 years) undergoing diagnostic or post-treatment endoscopy scored real-time with EREFS from December 2012 through 2016. Findings from 192 diagnostic endoscopies and 229 post-treatment endoscopies were evaluated, from 371 children. Incident EoE cases were diagnosed based on 2011 consensus guidelines. Patients were treated with either elimination diet or topical steroids. Subjects who underwent endoscopy for symptoms of esophageal dysfunction but had normal esophageal findings from histology analysis were used as controls. EREFS and receiver operating characteristic curves were determined for incident EoE cases (n = 77) vs controls (n = 115), patients with active EoE (n = 101) vs inactive EoE after treatment (n = 128), and paired pre- and post-treatment cases of EoE (n = 85). Component and composite scores were correlated with eosinophilia. RESULTS:Visual detection of more than 1 esophageal abnormality during the diagnostic endoscopy identified children with EoE with 89.6% sensitivity and 87.9% specificity. EREFS correlated with peak level of eosinophilia (P < .001) at all esophageal levels. Children who responded to therapy had mean EREFSs of 0.5 compared to 2.4 in non-responders. In comparing pre-treatment vs post-treatment data from 85 patients, we found a significant reduction in the composite EREFS (from 2.4 to 0.7) (P < .001) among patients who responded to treatment; 92% of responders had a reduced EREFSs after treatment. EREFSs identified children with EoE with an area under the curve value (AUC) of 0.93. EREFSs identified children with active EoE following treatment with an AUC of 0.81 before treatment and an AUC of 0.79 after treatment. CONCLUSIONS:In a prospective study of children undergoing diagnostic or post-treatment endoscopy, we found the EREFS to accurately identify those with EoE. Children who responded to therapy had lower EREFS scores than non-responders. EREFSs can be used to measure outcomes of pediatric patients, in conjunction with histology findings, and assess treatments for children with EoE.

Project description:BackgroundEosinophilic esophagitis (EoE) is a chronic immune-mediated inflammatory disorder and represents the leading cause of food impaction. The pathogenesis of EoE is the result of an interplay between genetic, environmental and host immune system factors. New therapeutic approaches for EoE have been proposed. In this manuscript we review the current evidence regarding EoE management in pediatric age, with a particular focus on new findings related to the efficacy and safety of monoclonal antibodies.Main bodyConventional therapies have failed in treating some patients with EoE, which then requires aggressive procedures such as esophageal dilatation. The most effective available medical therapy for EoE is swallowed topic corticosteroids (fluticasone propionate and budesonide), which have two main drawbacks: they are related to well-known adverse effects (especially in the paediatric population), and there are not enough long-term data to confirm that they are able to reverse the remodelling process of the esophageal mucosa, which is the major cause of EoE symptoms (including dysphagia, abdominal pain, nausea, obstruction, perforation and vomiting). The monoclonal antibodies appear to be an interesting therapeutic approach. However, the studies conducted until now have shown substantial histological improvement not coupled with significant clinical improvements and no significant relationship between a decreasing number of eosinophils and clinical symptoms, highlighting the importance in the pathogenesis of EoE of cells such as T-helper cells, mast cells, B cells, epithelial cells and natural killer cells.ConclusionsMonoclonal antibodies targeting a signal involved in the pathogenesis of EoE may not break the complex self-propagating inflammatory activation responsible for perpetuation of the inflammatory response and the development of symptoms and complications. We speculate that combined biological therapies targeting more than one molecule or cell may provide better results, with conventional therapies potentially enhancing the effects of antibodies. However, further studies should aim to find the best therapeutic approach to target the cells involved in the remodelling process and to reverse the histological changes in this complex clinical condition.

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Effects of allergen sensitization on response to therapy in children with eosinophilic esophagitis.

Publications

Effects of allergen sensitization on response to therapy in children with eosinophilic esophagitis.

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