Corrigendum: Accuracy and Safety of the Cytosponge for Assessing Histologic Activity in Eosinophilic Esophagitis: A Two-Center Study.

This corrects the article DOI: 10.1038/ajg.2017.244.

Accuracy and Safety of the Cytosponge for Assessing Histologic Activity in Eosinophilic Esophagitis: A Two-Center Study.

OBJECTIVES: Management of eosinophilic esophagitis (EoE) requires repeated endoscopic mucosal sampling to assess disease activity. A less invasive and expensive means of monitoring of EoE is required. The objective of this study was to assess the accuracy, safety, and tolerability of the cytosponge compared to endoscopy and biopsy for histologic assessment of EoE. METHODS: In this prospective two-center cross-sectional study, patients with known EoE underwent cytosponge sampling followed by endoscopy and biopsy. Sample adequacy and eosinophil counts (eos/HPF) were determined for both cytosponge and endoscopic samples. The cytosponge was assessed for diagnostic accuracy, safety, and patient preference as compared to endoscopy. RESULTS: Six patients (7%) failed to swallow the sponge. One hundred and five procedures were successfully performed in 80 patients (66% male, 100% white, 19% stricture). The cytosponge sample was adequate in 102 and the biopsy in 104; 101 procedures had adequate samples by both techniques. Fifty-seven biopsies were graded as active EoE with ≥15 eos/HPF as the gold standard. Eosinophil counts highly correlated between the biopsy and cytosponge (r=0.78, P<0.0001). Using a cutoff of ≤15 eos/HPF for inactive disease, the sensitivity and specificity of the cytosponge was 75% and 86%, respectively. Six patients had active EoE on cytosponge not found on biopsy. For biopsies with inactive EoE, the cytosponge identified 38/44. No complications occurred, and cytosponge endoscopic abrasion scores were low (0.34/4). Patients preferred cytosponge to endoscopy with higher rating scores (7.27 vs. 6.11, P=0.002). CONCLUSIONS: Compared to endoscopy with biopsy, cytosponge provided a minimally invasive, safe, well tolerated, and accurate method to assess EoE histologic activity. (ClinicalTrial.gov number NCT01585103).

A Gene Expression Panel is Accurate for Diagnosis and Monitoring Treatment of Eosinophilic Esophagitis in Adults.

OBJECTIVE: Eosinophilic esophagitis (EoE) can be difficult to diagnose. We aimed to evaluate whether a gene expression score could differentiate adult EoE cases from non-EoE controls and to determine whether scores normalized after treatment for EoE. METHODS: We analyzed prospectively collected esophageal biopsies from EoE patients (diagnosed as per consensus guidelines and after a proton pump inhibitor trial) and non-EoE controls. Gene expression for a previously constructed 94 gene panel was quantified for a single RNA-later preserved biopsy. For diagnosis, a summary expression score and the area under the receiver operating characteristic curve (AUC) were calculated. For treatment response (defined as <15 eosinophils per high-power field), pretreatment and posttreatment EoE samples were compared. RESULTS: For 91 EoE cases and 174 controls, gene scores for EoE cases were lower than non-EoE controls (mean 198 vs. 420; P<0.001), with an AUC of 0.927. A score ≤263 yielded a positive predictive value=91%; a score ≥349 yielded a negative predictive value=90%; only 12% of subjects had an indeterminate score (264-348) by this classification scheme. For the 89 EoE cases with paired pretreatment and posttreatment samples, overall gene scores improved after treatment from 199 to 343 (P<0.001). This normalization was seen only in cases with histological response (202 vs. 425; P<0.001); scores were unchanged in non-responders (189 vs. 226; P=0.25). CONCLUSIONS: A gene expression score has high diagnostic utility for distinguishing EoE patients from non-EoE controls in adults and can be used in clinical algorithms. Because it is highly responsive to treatment, the test could be used to monitor disease status.

Association Between Body Mass Index and Clinical and Endoscopic Features of Eosinophilic Esophagitis.

BACKGROUND: Because eosinophilic esophagitis (EoE) causes dysphagia, esophageal narrowing, and strictures, it could result in low body mass index (BMI), but there are few data assessing this. AIM: To determine whether EoE is associated with decreased BMI. METHODS: We conducted a prospective study at the University of North Carolina from 2009 to 2013 enrolling consecutive adults undergoing outpatient EGD. BMI and endoscopic findings were recorded. Incident cases of EoE were diagnosed per consensus guidelines. Controls had either reflux or dysphagia, but not EoE. BMI was compared between cases and controls and by endoscopic features. RESULTS: Of 120 EoE cases and 297 controls analyzed, the median BMI was lower in EoE cases (25 vs. 28 kg/m2, p = 0.002). BMI did not differ by stricture presence (26 vs. 26 kg/m2, p = 0.05) or by performance of dilation (26 vs. 27 kg/m2 for undilated; p = 0.16). However, BMI was lower in patients with narrow caliber esophagus (24 vs. 27 kg/m2, p < 0.001). EoE patients with narrow caliber esophagus also had decreased BMI compared to controls with narrow caliber esophagi (24 vs. 27 kg/m2, p = 0.001). On linear regression after adjustment for age, race, and gender, narrowing decreased BMI by 2.3 kg/m2 [95% CI -4.1, -0.6]. CONCLUSIONS: BMI is lower in EoE cases compared to controls, and esophageal narrowing, but not focal stricture, is associated with a lower BMI in patients with EoE. Weight loss or low BMI in a patient suspected of having EoE should raise concern for esophageal remodeling causing narrow caliber esophagus.

Accuracy of the Eosinophilic Esophagitis Endoscopic Reference Score in Diagnosis and Determining Response to Treatment.

BACKGROUND & AIMS: Little is known about the diagnostic utility of the Eosinophilic Esophagitis (EoE) Endoscopic Reference Score (EREFS), and how scores change in response to treatment. We investigated the operating characteristics of the EREFS in diagnosis of EoE, how the score changes with treatment, and ways to optimize scoring system. METHODS: We performed a prospective study of adults undergoing outpatient upper endoscopy from August 2011 through December 2013 at the North Carolina School of Medicine. Incident cases of EoE were diagnosed per consensus guidelines and were treated with topical steroids or dietary elimination (n = 67); 144 subjects without EoE were included as control subjects. EREFS scores were compared between cases and control subjects. For EoE cases, scores were compared before and after treatment. Area under the receiver operator characteristic curve analysis was used to determine diagnostic utility of the EREFS system. An iterative analysis was performed to determine optimal EREFS scoring weights. RESULTS: The mean total EREFS score was 3.88 for EoE cases and 0.42 for control subjects (P > .001); the score identified subjects with EoE with an area under the receiver operator characteristic curve of 0.934. After treatment of EoE cases, the mean score decreased from 3.88 to 2.01 (P > .001). This change was more prominent for patients with a histologic response (reduction to <15 eosinophils per high-power field) compared with nonresponders; posttreatment scores were 0.45 for responders versus 3.24 for nonresponders (P < .001). A weighted scoring system that doubled exudates, rings, and edema scores maximized the responsiveness of the total EREFS score. CONCLUSIONS: The EREFS classification system identifies patients with EoE an area under the receiver operator characteristic curve of 0.934; the score decreases with treatment, and histologic responders have significantly lower scores than nonresponders. This system can therefore be used to identify individuals with EoE and used as an endoscopic outcome measure to follow their response to treatment.

A Clinical Prediction Tool Identifies Cases of Eosinophilic Esophagitis Without Endoscopic Biopsy: A Prospective Study.

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 the University of North Carolina from July 2011 through December 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 histological, data was assessed. Receiver operator characteristic 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 eosinophils per high-power field (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.

Utility of a Noninvasive Serum Biomarker Panel for Diagnosis and Monitoring of Eosinophilic Esophagitis: A Prospective Study.

OBJECTIVES: Noninvasive 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 esophagogastroduodenoscopy. Incident cases of EoE were diagnosed per consensus guidelines; controls had gastroesophageal reflux disease (GERD) or dysphagia and did not meet the EoE criteria. EoE cases were treated with topical steroids and had repeat endoscopy. Pre- and post-treatment serum samples were analyzed in a blinded manner for interleukin (IL)-4, IL-5, IL-6, IL-9, IL-13, transforming growth factor (TGF)-α, TGF-ß, tumor necrosis factor-α, eotaxin-1, -2, and -3, thymic stromal lymphopoietin (TSLP), major basic protein, and eosinophil-derived neurotoxin. 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.