Analysis of eosinophilic esophagitis in children with repaired congenital esophageal atresia

Abstract

Background: A high prevalence of eosinophilic esophagitis (EoE) has been preliminarily reported in patients after repair of esophageal atresia (EA), but the basis of this association is unknown Objectives: We aimed to (1) characterize the EoE transcriptome in patients with EA, (2) compare the EoE transcriptome in patients with EoE and EA with that in patients with EoE alone, and (3) identify transcripts that could predispose patients with EA to EoE. Methods: This single-center, population-based, retrospective study identified 4 EoE study cohorts: healthy control subjects, patients with EA and EoE (EA+EoE+), patients with EA without EoE (EA+EoE-), and patients with EoE without EA (EA-EoE+). Molecular signatures were assessed by using the EoE diagnostic panel, a 94-gene expression quantitative PCR array. Results: In a cohort of 110 pediatric patients with surgically repaired EA, 20 (18%) patients were given a diagnosis of EoE, representing a 364-fold enrichment of EoE in patients with EA compared with the general pediatric population. EoE diagnostic panel analyses revealed a major overlap between the EA+EoE+ and EA-EoE+ cohorts. A proportion (approximately 25%) of EoE signature genes were dysregulated in patients with EA+EoE-compared with healthy control subjects, including those involved in epithelial barrier function and type 2-associated inflammatory responses. Patients with EA+EoE+ exhibit a more severe EoE clinical phenotype than those with EA-EoE+ in terms of dysphagia and dilation need. Conclusions: Patients with EA have increased risk of EoE. Patients with EoE with EA have a similar molecular profile compared with that of patients with EoE without EA.

Eosinophilic Esophagitis in Esophageal Atresia

“…It is now accepted that EoE is the result of a T-helper cell 2–type immune response in which eotaxin 3 and interleukins (IL) 4, 5, and 12 and 13 are upregulated (27–29). The gene for eotaxin-3, which is a chemoattractant and activating factor for eosinophils, has been shown to be increased 53-fold above normal levels in patients with EoE (28, 30, 31). Both EA and EoE are polygenic conditions, and recently, Gorter et al postulated a possible genetic association between EA and EoE through mutations in the FOX gene cluster (6).…”

“…This underscores the importance of being aware of the risk of EoE and performing endoscopies with sufficient numbers of biopsies at multiple levels, irrespective of the age in symptomatic EA patients. Also EA patients with EoE had a more-severe clinical phenotype, with higher incidence of dysphagia, episodes of food bolus impaction and strictures requiring dilation than in those with EoE alone without EA and EA patients without EoE, highlighting the importance of timely diagnosis and treatment of EoE in EA patients (31). This study found that 2 genes (ANO1 and CTNNAL1) were expressed more in EA patients with EoE than in EoE patients without EA.…”

Advances in eosinophilic diseases in 2018

“…Krishnan et al 23 examined the relationship between EoE and congenital esophageal atresia. After finding a large increased risk for EoE in patients with surgically repaired esophageal atresia (364-fold enrichment), the investigators probed the related disease pathogenesis by subjecting the esophageal tissue to molecular profiling with the EoE Diagnostic Panel, a set of 94 transcripts associated with EoE.…”

AGA Commentary on Eosinophilic Esophagitis Guidelines

“…Since the discovery of this disease, a vexing problem is the inability, either symptomatically or by objective testing, to definitively distinguish GERD from EoE. 7 Furthermore, other esophageal diseases such as achalasia 8 or esophageal astresia 9 have been described with mucosal eosinophilia with an unclear relationship to EoE. As a result, good clinical judgment is a mainstay in sorting out potentially complex interactions of these diseases in the face of possible EoE.…”