Background & Aims Distinguishing between eosinophilic esophagitis (EoE), gastroesophageal reflux disease (GERD), and proton pump inhibitor-responsive esophageal eosinophilia (PPI-REE) is challenging. We assessed whether immunohistochemical analysis of esophageal tissues for major basic protein (MBP), eotaxin3, and tryptase can be used in diagnosis of EoE and to differentiate EoE from PPI-REE. Methods We conducted a prospective study of 196 consecutive adults who underwent outpatient endoscopy at the University of North Carolina from 2009 through 2012. Incident cases of EoE were diagnosed per consensus guidelines. Patients with gastroesophageal reflux disease or dysphagia served as controls. PPI-REE was defined as a symptomatic and histologic response to a PPI. Immunohistochemistry was performed to quantify MBP, eotaxin3, and tryptase. The maximum density of epithelial staining was determined for each assay; levels were compared between EoE and control, and then EoE and PPI-REE groups, and receiver operator characteristic (ROC) curves were constructed. Results Esophageal tissues from patients with EoE (n=50) had a median 951 MBP-positive cells/mm2 whereas those from controls (n=123) had a median 2 MBP-positive cells/mm2 (P<.001). Samples from patients with EoE had a median 155 eotaxin3-positive cells/mm2 and those from controls (n=123) had 18 MBP-positive cells/mm2 (P<.001). Samples from patients with EoE had a median 249 tryptase-positive cells/mm2 and those from controls (n=123) had 11 tryptase-positive cells/mm2 (P<.001). Levels of MBP, eotaxin3, tryptase, and the combination of all 3 identified patients with EoE with area under the ROC curve values of 0.99, 0.94, 0.99, and 1.00. Analyses of only samples with eosinophil counts of 10–100 eos/hpf produced similar results. No marker distinguished EoE from PPI-REE. Esophageal tissues from patients with PPI-REE (n=23) had 987 MBP-positive cells/mm2 (P=.18, compared with controls), 160 eotaxin3-positive cells/mm2 (P=.33), and 243 tryptase-positive cells/mm2 (P=.28). Conclusions Esophageal tissues from patients with EoE have substantially higher levels of MBP, eotaxin3, and tryptase than controls, based in immunohistochemical analysis. Assays for the 3 markers identify patients with EoE 100% accuracy, but cannot distinguish EoE from PPI-REE.

The variability of eosinophilic infiltrates in eosinophilic esophagitis is not well described. This study aimed to determine the distribution of esophageal eosinophilia and the utility of histologic cut-points for eosinophilic esophagitis diagnosis in subjects undergoing endoscopy. We performed a prospective study of adults undergoing outpatient endoscopy. Research protocol esophageal biopsies were obtained from all subjects. Incident cases of eosinophilic esophagitis were diagnosed per consensus guidelines. Biopsies were interpreted following a validated protocol, and maximum eosinophil counts (eosinophils per high-power field; eos/hpf) were determined. Histologic analyses were performed on a per-patient, per-biopsy, and per-hpf basis. There were 213 patients, yielding 923 esophageal biopsies with 4588 hpfs. Overall, 48 patients (23%), 165 biopsy fragments (18%), and 449 hpfs (10%) had ≥ 15 eos/hpf; most subjects had no or low levels of eosinophils. In the eosinophilic esophagitis cases, 119 biopsy fragments (63%) and 332 hpfs (36%) had ≥ 15 eos/hpf. There was a mean 104-fold difference between the lowest and highest hpf eosinophil count for the eosinophilic esophagitis patients; 85% of the biopsies from eosinophilic esophagitis cases also had at least one hpf with < 15 eos/hpf. The cut-point of 15 eos/hpf had a sensitivity of 100% and specificity of 96% for diagnosis of eosinophilic esophagitis. In conclusion, most patients have little to no esophageal eosinophilia. In patients with eosinophilic esophagitis, there was marked variability in the eosinophil counts by biopsy and by hpf within a given biopsy. Additionally, the 15 eos/hpf cut-point was highly sensitive and specific for eosinophilic esophagitis. Multiple esophageal biopsies from different locations should be obtained to optimize eosinophilic esophagitis diagnosis.

Objectives Non-invasive biomarkers would be valuable for diagnosis and monitoring of eosinophilic esophagitis (EoE). The aim of this study was to determine the utility of a panel of serum biomarkers for the diagnosis and management of EoE. Methods We conducted a prospective cohort study of consecutive adults undergoing outpatient EGD. Incident cases of EoE were diagnosed per consensus guidelines; controls had GERD or dysphagia and did not meet EoE criteria. EoE cases were treated with topical steroids and had repeat endoscopy. Pre- and post-treatment serum samples were analyzed in a blinded fashion for: IL-4, IL-5, IL-6, IL-9, IL-13, TGF-α, TGF-β, TNF-α, eotaxin-1, -2, and -3, TSLP, major basic protein (MBP), and eosinophil-derived neurotoxin (EDN). Cases and controls were compared at baseline, and pre- and post-treatment assays were compared in cases. Results A total of 61 incident EoE cases and 87 controls were enrolled; 51 EoE cases had post-treatment serum analyzed. There were no significant differences in any of the biomarkers between EoE cases and controls at baseline. IL-13 and eotaxin-3 for cases and controls were 85 ±160 vs 43 ±161 pg/mL (p=0.12), and 41 ±159 vs 21 ±73 (p=0.30). There were no significant differences in assay values among cases before and after treatment. There were also no differences after stratification by atopic status or treatment response. Conclusions A panel of inflammatory factors known to be associated with EoE pathogenesis were not increased in the serum, nor were they responsive to therapy. None of these biomarkers are likely candidates for a serum test for EoE. Histologic analysis for diagnosis and management of EoE continues to be necessary, and novel, less invasive, biomarkers are needed.

In a prospective study of patients with EoE, we found that a cutpoint of <15 eos/hpf identifies most patients with symptom and endoscopic improvements, providing support for the current diagnostic threshold. A lower threshold (<5 eos/hpf) identifies most patients with a combination of symptom and endoscopic responses; this cutpoint might be used in situations that require a stringent histologic threshold.

Objectives Eosinophilic esophagitis (EoE) is difficult to distinguish from gastroesophageal reflux (GERD) and other causes of dysphagia. We assessed the utility of a set of clinical and endoscopic features for predicting EoE without obtaining esophageal biopsies. Methods We prospectively enrolled consecutive adults undergoing outpatient upper endoscopy at University of North Carolina from 7/2011–12/2013. Incident cases of EoE were diagnosed per consensus guidelines. Non-EoE controls had either GERD- or dysphagia-predominant symptoms. A predictive model containing clinical and endoscopic, but no histologic data was assessed. Receiver operator characteristic (ROC) curves were constructed and the area under the curve (AUC) was calculated. Results A total of 81 EoE cases (mean age 38 years; 60% male; 93% white; 141 eos/hpf) and 144 controls (mean age 52, 38% male; 82% white; 3 eos/hpf) were enrolled. A combination of clinical (age, sex, dysphagia, food allergy) and endoscopic (rings, furrows, plaques, hiatal hernia) features was highly predictive of EoE. The AUC was 0.944, with sensitivity, specificity, and accuracy of 84%, 97%, and 92%. Similar values were seen after limiting controls to those with only reflux or dysphagia, or to those with esophageal eosinophilia not due to EoE. Conclusions We validated a set of clinical and endoscopic features to predict EoE with a high degree of accuracy, and allow identification of those at very low risk of disease. Use of these predictors at the point-of-care will avoid the effort and expense of low-yield histological examinations for EoE.