Pediatric Eosinophilic Esophagitis Symptom Scores (PEESS v2.0) identify histologic and molecular correlates of the key clinical features of disease

Abstract

Background The Pediatric Eosinophilic Esophagitis Symptom Score (PEESS® v2.0) measures patient-relevant outcomes. However, whether patient-identified domains (dysphagia, gastrointestinal reflux disease (GERD), nausea/vomiting, and pain) align with clinical symptomology and histopathologic and molecular features of eosinophilic esophagitis (EoE) is unclear. Objective The purpose of this study was to determine if clinical features of EoE, measured through the PEESS® v2.0, associate with histopathologic and molecular features of EoE. This represents a novel approach for analysis of allergic diseases, given the availability of allergic tissue biopsy specimens. Methods We systematically recruited treated and untreated, pediatric patients with EoE (aged 2–18 years) and examined parent proxy–reported symptoms using the PEESS® v2.0. Clinical symptomology was collected by questionnaire. Esophageal biopsy samples were quantified for levels of eosinophils, eosinophil peroxidase (EPX) immunohistochemical staining, and mast cells. Molecular features were assessed by the EoE Diagnostic Panel (94 EoE-related gene transcripts). Associations between domain scores and clinical symptoms and biologic features were analyzed using Wilcoxon Rank Sum and Spearman correlation. Results The PEESS® v2.0 domains correlated to specific parent-reported symptoms: dysphagia (p = 0.0012), GERD (p = 0.0001), and nausea/vomiting (p < 0.0001). Pain correlated with multiple symptoms (p < 0.0005). Dysphagia correlated most strongly with overall histopathology, particularly in the proximal esophagus (p ≤ 0.0049). Markers of esophageal activity (EPX) were significantly associated with dysphagia (strongest r = .37; p = 0.02). Eosinophil levels were more associated with pain (r = 0.27; p=0.06) than for dysphagia (r = 0.24; p = 0.13). The dysphagia domain correlated the most with esophageal gene transcript levels, predominantly with mast cell–specific genes. Conclusion We have 1) established a validated, parent proxy–report measure for pediatric EoE — the PEESS® v2.0; 2) verified that parent-proxy effectively captures symptoms; 3) determined that the dysphagia domain most closely aligns with symptoms and tissue-based molecular biomarkers; 4) established that symptoms correlate EPX staining; and 5) observed association between mast cells and dysphagia.

Eosinophil progenitor levels are increased in patients with active pediatric eosinophilic esophagitis

“…The current disease monitoring standard dictates that all patients undergo invasive endoscopy with tissue biopsies due to poor correlation between clinical symptoms and tissue inflammation [10]. Any reduction of invasive procedures through the use of less-invasive blood biomarkers would be valuable.…”

The antiprotease SPINK7 serves as an inhibitory checkpoint for esophageal epithelial inflammatory responses

“…Here, we focused on uncovering the mechanism of allergic inflammation in eosinophilic esophagitis (EoE), a chronic, food-driven, inflammatory allergic disease of the esophagus ( 3 ). EoE is diagnosed according to the number of infiltrating eosinophils in the esophageal squamous epithelium, but other associated inflammatory cells are likely involved including mast cells, basophils, and lymphocytes ( 4 – 6 ). Besides being a recently emerging allergic disease that is in need of deeper understanding, EoE provides a unique opportunity to probe human allergic inflammation at the tissue level, as the diseased tissue is readily available for experimental investigation by routine endoscopic biopsies.…”

Gender‐specific differences in the molecular signatures of adult Eosinophilic Oesophagitis

“…Eosinophilic Eosophagitis (EoE) is a chronic inflammatory disorder of the esophagus, seen in both children and adults, and is 3–4 times more common in males than females [2]. Diagnosis of EoE has relied on quantification of eosophageal eosinophils by biopsy and patient-reported symptoms but recent studies have supported the use of tissue-based molecular biomarker assessment, based on gene expression signatures [3], aiding patient diagnosis [4]. Strong correlations between gene expression profiles and symptoms were found, particularly dysphagia [4].…”

“…Diagnosis of EoE has relied on quantification of eosophageal eosinophils by biopsy and patient-reported symptoms but recent studies have supported the use of tissue-based molecular biomarker assessment, based on gene expression signatures [3], aiding patient diagnosis [4]. Strong correlations between gene expression profiles and symptoms were found, particularly dysphagia [4]. Early work looking at the EoE-associated transcriptional profile concluded that there were no differences between males and females [5] but this was performed in childhood EoE and recent studies have demonstrated that gender significantly influences the clinical presentation of adult EoE, particularly dysphagia [6–8].…”