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Adrenal Insufficiency in Pediatric Eosinophilic Esophagitis Patients Treated with Swallowed Topical Steroids.

ABSTRACT: Swallowed topical steroids (STS) are the only effective pharmacological therapy for eosinophilic esophagitis (EoE). Thus far, studies of small populations of EoE patients have reported conflicting results in relation to adrenal insufficiency (AI). We sought to measure AI in a clinical setting in children taking STS for EoE. We performed a quality improvement study of pediatric EoE patients seen in a multidisciplinary clinic, who were treated with STS for at least 3 months. Two hundred twenty-five patients completed questionnaires to assess for signs of AI. All patients were requested to have fasting morning cortisol levels completed and if abnormal (<5??g/dL or 139?nmol/L) twice, endocrinology consultation, and low-dose adrenocorticotropic hormone stimulation test were performed. A peak stimulated cortisol level of <18??g/dL or 500?nmol/L was diagnostic of AI. Five of 106 STS-treated EoE patients who had morning cortisol levels drawn had AI. All 5 of these patients had asthma and were on additional topical steroid treatments. The number of steroid modalities and dose of steroid were not significant risk factors. Despite this low percentage, the life-threatening potential of AI warrants patient screening, as patients with iatrogenic AI are typically asymptomatic until an emergency triggers adrenal crisis. Further multicenter studies are needed to better define the risk attributable to STS alone, particularly in patients receiving combined steroid modalities.

SUBMITTER: Hsu S

PROVIDER: S-EPMC5649406 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Adrenal Insufficiency in Pediatric Eosinophilic Esophagitis Patients Treated with Swallowed Topical Steroids.

Hsu Stephanie S Wood Colleen C Pan Zhaoxing Z Rahat Haseeb H Zeitler Philip P Fleischer David D Menard-Katcher Calies C Furuta Glenn T GT Atkins Dan D

Pediatric allergy, immunology, and pulmonology 20170901 3

Swallowed topical steroids (STS) are the only effective pharmacological therapy for eosinophilic esophagitis (EoE). Thus far, studies of small populations of EoE patients have reported conflicting results in relation to adrenal insufficiency (AI). We sought to measure AI in a clinical setting in children taking STS for EoE. We performed a quality improvement study of pediatric EoE patients seen in a multidisciplinary clinic, who were treated with STS for at least 3 months. Two hundred twenty-fiv ...[more]

PMID: 29062584

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Project description:Eosinophilic esophagitis (EoE) is a chronic TH2 inflammatory disease characterized by tissue remodeling that leads to esophageal strictures and food impactions. Effects of therapy on long-term remodeling in patients with pediatric eosinophil-associated diseases have not been previously described.We sought to understand the long-term control of esophageal remodeling in patients with EoE.We assessed endoscopic and histologic remodeling and TGF-?1 expression in esophageal biopsy specimens from children (n = 32) with EoE treated with topical corticosteroids (TCSs) over 10 years (mean, 4.5 years). We used standardized EoE scoring tools to gauge endoscopic and symptom features.Seven hundred thirty-eight biopsy specimens from 246 endoscopic procedures were evaluated over 10 years. Four hundred eighty-six biopsy specimens had adequate lamina propria for evaluation of subepithelial remodeling. The severity of epithelial esophageal eosinophilia correlated with epithelial remodeling (basal zone hyperplasia, desquamation, and dilated intercellular spaces; P < .0001), lamina propria eosinophilia (P < .0001), and fibrosis (P < .0001). Sixteen subjects were initial responders (<15 eosinophils/high-power field) to TCSs. Responders and nonresponders spent 54% and 97% of their total disease duration with active EoE (P < .001) and 23% and 53% (P < .02) with maximal fibrosis scores, respectively. Responders had lower endoscopy scores during their disease duration (P = .013). Having less than 15 eosinophils/high-power field at any time correlated with lower fibrosis and endoscopic severity. TGF-?1(+) cell counts decreased in responders at the first biopsy, but this was not sustained. Symptoms did not correlate with other disease features.Children with EoE have substantial esophageal remodeling, which associates with inflammation and can improve in a sustainable manner with TCSs. Although endoscopic features correspond to histologic features, symptoms did not correlate with inflammation or fibrosis.

Project description:BACKGROUND AND AIMS:Eosinophilic esophagitis (EoE) is a chronic disorder in children that requires continued assessment of disease activity, involving repeated sedation, endoscopy, and biopsy analysis. We investigated whether mucosal impedance measurements can be used to monitor disease activity in pediatric patients with EoE. METHODS:We measured mucosal impedance at 3 locations in the esophagus in pediatric patients (1-18 years old; 32 with active EoE, 10 with inactive EoE, 32 with nonerosive reflux disease [NERD]) and 53 children with symptoms but normal findings from histologic analyses (controls) undergoing routine esophagogastroduodenoscopy at the Vanderbilt Pediatric Gastroenterology Clinic. Pathologists reviewed biopsies per routine protocol, determined eosinophilic density, and graded spongiosis on an ordinal visual scale. Mucosal impedance measurements were compared within patient groups. The primary outcome was correlation of mucosal impedance measurements with disease activity, based on severity of spongiosis and eosinophil counts. RESULTS:Mucosal impedance measurements were significantly lower in patients with active EoE at 2, 5, and 10?cm above the squamo-columnar junction (median values of 1069, 1368, and 1707, respectively) compared to patients with inactive EoE (median values of 3663, 3657, and 4494, respectively), NERD (median values of 2754, 3243, and 4387), and controls (median values of 3091, 3760, and 4509) (P?<?0.001 for all comparisons to patients with active EoE). We found inverse correlations between mucosal impedance measurements and eosinophil count (P?<?0.001), and spongiosis severity (P?<?0.001). CONCLUSIONS:Mucosal impedance measurements may provide immediate information about mucosal inflammation in children. Patients with active EoE have significantly lower mucosal impedance values than patients with inactive EoE, NERD, or controls; mucosal impedance measurements correlate inversely with eosinophil counts and spongiosis severity. Mucosal impedance is a promising rapid and less-invasive method to monitor EoE activity in pediatric patients with EoE; it could reduce costs and risks of disease monitoring.

Project description:OBJECTIVES:No formal comparative effectiveness studies have been conducted to evaluate the effect of eosinophilic esophagitis (EoE) treatment choice on long-term growth in pediatric patients. Long-term studies of inhaled corticoid steroids in asthma, however, suggest possible effects on linear growth. The aim of this study was to compare longitudinal, anthropometric growth in children with EoE according to treatment approach. METHODS:We conducted a retrospective, multicenter cohort study of anthropometric growth (height and body mass index [BMI] z scores) in pediatric (<18 years of age) patients newly diagnosed with EoE across 5 clinical sites between 2005 and 2014. We compared differences in growth according to treatment approach over a 12-month period. Modification by sex and age was examined and sensitivity analyses were conducted to assess robustness of results given study assumptions. RESULTS:In the 409 patients identified, the mean age and proportion male differed by treatment (P?=??<?0.01 and P?=?0.04, respectively). Baseline growth measures were associated with slight impairment of height at diagnosis (median baseline height z score of -0.1 [interquartile range -0.9, 0.8]). In general, treatment approach was not associated with any significant increase or decrease in expected growth over a 12-month period. Subtle decrease in linear growth was observed with treatment using a combined elemental and topical steroid (? height z score [adjusted]: -0.04; 95% confidence interval [CI]: -0.08, -0.01). Differences in linear growth differed by sex (P for interaction <0.01). For elemental formula in combination with topical steroids, only girls exhibited a significant decline in linear growth (? height z score [adjusted]: -0.24; 95% CI: -0.32, -0.17). A slight reduction in BMI was observed for patients treated with a combination of elemental diet and dietary elimination (? BMI z score [adjusted]: -0.07; 95% CI: -0.13, -0.01). CONCLUSIONS:Treatment of EoE, in general, is not associated with major anthropometric growth changes in most pediatric patients. Slight linear growth impairment was observed for topical steroid treatment, and sex differences in growth by treatment approach were observed. Future prospective studies should evaluate the effect of treatment on optimal growth and development and over a longer period of follow-up.

Dataset Information

Adrenal Insufficiency in Pediatric Eosinophilic Esophagitis Patients Treated with Swallowed Topical Steroids.

Publications

Adrenal Insufficiency in Pediatric Eosinophilic Esophagitis Patients Treated with Swallowed Topical Steroids.

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