Dataset Information

Longitudinal Perspective on Managing Refractory Eosinophilic Esophagitis.

ABSTRACT: One half to one third of the patients with eosinophilic esophagitis (EoE) do not achieve histological remission on initial treatment. We wondered whether these treatment failure patients are a distinct clinical subset.To analyze EoE treatment outcomes in a predominantly pediatric population.We reviewed 100 serial EoE cases at Massachusetts General Hospital starting from 2007. We defined histological remission as peak esophageal eosinophil count of less than 10/hpf.Ninety-seven patients with EoE underwent initial treatments: 54 of 81 (67%) responded to dietary therapy, and 9 of 16 (56%) responded to topical glucocorticoids. Of the 34 who failed initial treatment, 24 underwent various second treatment regimens and 54% (13 of 24) responded. Eight of the remaining 11 who failed second treatment underwent additional treatments and 2 ultimately responded. The overall response rate by intent-to-treat analysis increased from 65% (63 of 97) with initial treatment to 78% (76 of 97) with rescue treatment, and further to 80% (78 of 97) with multiple treatments. On a per-protocol basis, the overall response rate was 93% (78 of 84); however, patients who failed the first 2 rounds of therapy had only a 20% response rate. Patients who responded to initial treatment were found to have more symptoms and endoscopic abnormalities. Comparison of patients who failed both initial and rescue therapy with those who responded to rescue therapy did not identify any differentiating clinical features.More than half of the patients who failed initial EoE treatment could still achieve histological remission with individualized rescue treatments. No clinical features could predict response to rescue treatment.

SUBMITTER: Leung J

PROVIDER: S-EPMC5045894 | biostudies-literature | 2015 Nov-Dec

REPOSITORIES: biostudies-literature

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Longitudinal Perspective on Managing Refractory Eosinophilic Esophagitis.

Leung John J Mehrzad Raman R Hundal Navneet Virk NV Alejos Alexandra A Hesterberg Paul E PE Katz Aubrey J AJ Yuan Qian Q Shreffler Wayne G WG

The journal of allergy and clinical immunology. In practice 20150903 6

<h4>Background</h4>One half to one third of the patients with eosinophilic esophagitis (EoE) do not achieve histological remission on initial treatment. We wondered whether these treatment failure patients are a distinct clinical subset.<h4>Objective</h4>To analyze EoE treatment outcomes in a predominantly pediatric population.<h4>Methods</h4>We reviewed 100 serial EoE cases at Massachusetts General Hospital starting from 2007. We defined histological remission as peak esophageal eosinophil coun ...[more]

PMID: 26342740

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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.

Project description:Eosinophilic esophagitis (EoE) is a chronic, allergen-driven inflammatory disease of the esophagus characterized predominantly by eosinophilic inflammation, leading to esophageal dysfunction. Converging data have placed the esophageal epithelium at the center of disease pathogenesis. In particular, the main EoE disease susceptibility loci at 2p23 and 5p22 encode for gene products that are produced by the esophageal epithelium: the intracellular protease calpain 14 and thymic stromal lymphopoietin, respectively. Furthermore, genetic and functional data establish a primary role for impaired epithelial barrier function in disease susceptibility and pathoetiology. Additionally, the EoE transcriptome, a set of genes dysregulated in the esophagi of patients with EoE, is enriched in genes that encode for proteins involved in esophageal epithelial cell differentiation. This transcriptome has a high proportion of esophagus-specific epithelial genes that are notable for the unexpected enrichment in genes encoding for proteases and protease inhibitors, as well as in IL-1 family genes, demonstrating a previously unappreciated role for innate immunity responses in the esophagus under homeostatic conditions. Among these pathways, basal production of the serine protease inhibitor, Kazal-type 7 (SPINK7) has been demonstrated to be part of the normal differentiation program of esophageal epithelium. Profound lost expression of SPINK7 occurs in patients with EoE and is sufficient for unleashing increased proteolytic activity (including urokinase plasminogen activator), impaired barrier function, and production of large quantities of proinflammatory and proallergic cytokines, including thymic stromal lymphopoietin. Collectively, we put forth a model in which the esophagus is normally equipped as an anti-inflammatory sensing organ and that defects in this pathway, mediated by epithelial protease/protease inhibitor imbalances, unleash inflammatory responses resulting in disorders, such as EoE.

Dataset Information

Longitudinal Perspective on Managing Refractory Eosinophilic Esophagitis.

Publications

Longitudinal Perspective on Managing Refractory Eosinophilic Esophagitis.

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