Baseline Gastrointestinal Eosinophilia Is Common in Oral Immunotherapy Subjects With IgE-Mediated Peanut Allergy

Abstract

Rationale: Oral immunotherapy (OIT) is an emerging treatment for food allergy. While desensitization is achieved in most subjects, many experience gastrointestinal symptoms and few develop eosinophilic gastrointestinal disease. It is unclear whether these subjects have subclinical gastrointestinal eosinophilia (GE) at baseline. We aimed to evaluate the presence of GE in subjects with food allergy before peanut OIT. Methods: We performed baseline esophagogastroduodenoscopies on 21 adults before undergoing peanut OIT. Subjects completed a detailed gastrointestinal symptom questionnaire. Endoscopic findings were assessed using the Eosinophilic Esophagitis (EoE) Endoscopic Reference Score (EREFS) and biopsies were obtained from the esophagus, gastric antrum, and duodenum. Esophageal biopsies were evaluated using the EoE Histologic Scoring System. Immunohistochemical staining for eosinophil peroxidase (EPX) was also performed. Hematoxylin and eosin and EPX stains of each biopsy were assessed for eosinophil density and EPX/mm² was quantified using automated image analysis. Results: All subjects were asymptomatic. Pre-existing esophageal eosinophilia (>5 eosinophils per high-power field [eos/hpf]) was present in five participants (24%), three (14%) of whom had >15 eos/hpf associated with mild endoscopic findings (edema, linear furrowing, or rings; median EREFS = 0, IQR 0-0.25). Some subjects also demonstrated basal cell hyperplasia, dilated intercellular spaces, and lamina propria fibrosis. Increased eosinophils were noted in the gastric antrum (>12 eos/hpf) or duodenum (>26 eos/hpf) in 9 subjects (43%). EPX/mm² correlated strongly with eosinophil counts (r = 0.71, p < 0.0001). Conclusions: Pre-existing GE is common in adults with IgE-mediated peanut allergy. Eosinophilic inflammation (EI) in these subjects may be accompanied by mild endoscopic and histologic findings. Longitudinal data collection during OIT is ongoing.

Keywords: Eosinophilic Esophagitis; adverse event; biopsy; endoscopy; eosinophil; gastrointestinal; oral immunotherapy; peanut food allergy.

Figure 1

(A) Endoscopic picture of the esophagus showing mild longitudinal furrows (e.g., yellow arrow) and mild edema. (B) Endoscopic picture of the distal esophagus with mild edema. (C) Esophagitis Endoscopic Reference Score (EREFS) distributed over the proximal esophagus (PE), middle esophagus (ME), and distal esophagus (DE). E, edema; R, rings; Ex, exudate; F, furrows; S, strictures.

Figure 2

EPX immunohistochemistry highlights gastrointestinal eosinophilic inflammation. Low and high magnification view of serial sections (H&E, columns 1 and 2, and EPX, columns 3 and 4) demonstrating eosinophilia in the esophagus (top row), gastric antrum (middle row) and proximal duodenum (bottom row). Yellow arrows denote eosinophils on H&E stains. Scale bars at high power (columns 1 and 3) and low power (columns 2 and 4) are 25 and 100 microns, respectively.

Figure 3

Gastrointestinal eosinophilia is common in adults with IgE-mediated peanut allergy. Eosinophil distribution and EPX deposition (A) in the proximal esophagus (PE), middle esophagus (ME), distal esophagus (DE), gastric antrum (GA), and duodenum (Du). Blue circles correspond to the left axis (eos/hpf) and red circles correspond to the right axis (EPX/mm²). Eosinophil counts were obtained from H + E stains. When plotted against one another, EPX/mm² correlates strongly with eos/hpf (B).

Figure 4

Additional pathologic findings (A) Proximal esophagus with increased intraepithelial lymphocytes and congested papillae. Two intraepithelial eos/hpf were seen elsewhere. (B) Middle esophagus with normal epithelium and a single intraepithelial eosinophil (inset). (C) Distal esophagus with mild basal cell hyperplasia and up to 35 intraepithelial eos/hpf (D) Middle esophagus with reactive epithelial nuclei and increased intraepithelial eosinophils (inset) up to 7/hpf. (E) Antral stomach mucosa with focal mild non-specific inflammation with lymphocytes and eosinophils (inset). (F) Duodenal mucosa with focal lamina propria neutrophils (inset) in one villus. (H&E images × 400). Arrows indicate eosinophils.

Figure 5

Eosinophilic Esophagitis Histologic Scoring System (EoEHSS). Frequency of histological findings in the proximal esophagus (PE), middle esophagus (ME), or distal esophagus (DE) based on Collins' grading to include eosinophilic inflammation (EI), basal cell hyperplasia (BZH), dilated intercellular spaces (DIS), lamina propria fibrosis (LPF), eosinophilic abscess (EA), eosinophil surface layering (SL), surface epithelial alteration (SEA), and dyskeratotic epithelial cells (DEC). Top panel represents Stage (extent of disease); bottom panel represents Grade (severity of disease).

Figure 6

Overall Eosinophil Histologic Scoring System (EoEHSS) at baseline endoscopy. Final score for Grade (left panel) and Stage (right panel) at each site in the esophagus. PE, proximal esophagus; ME, middle esophagus; DE, distal esophagus.