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Background: The relationship between histologic disease activity in eosinophilic esophagitis (EoE) and generic measures of quality of life (QoL) is unclear. Aims: To determine differences in QoL in adults with EoE based on histologic activity and assess changes in QoL over time. Methods: We performed an analysis of prospectively collected data from patients in the University of North Carolina EoE Registry. Patients were categorized with histologically active (≥ 15 eosinophils per high-power field [eos/hpf]) or inactive (< 15 eos/hpf) disease. Dysphagia severity was measured with a Likert scale. QoL was measured with 36-Item Short Form (SF-36), compared between active and inactive groups, and assessed longitudinally. Results: Of 147 EoE cases, those with inactive disease (n = 56) reported less dysphagia severity (3.2 vs. 1.9; p = 0.003) and had lower endoscopic severity (3.8 vs. 1.0; p < 0.001) than those with active disease (n = 91). While SF-36 scores did not differ between active and inactive status, lower mental component scores (MCS) were seen in patients treated with empiric dietary elimination (44.9 vs. 50.8; p = 0.005). Dysphagia severity was negatively correlated with both physical component score (PCS) (r = −0.33; p < 0.001) and MCS (r = −0.18; p = 0.03). Despite more cases achieving histologic response over time, SF-36 scores did not improve on either raw or adjusted analyses. Conclusion: QoL measured by SF-36 in EoE was similar regardless of histologic disease activity and was in the range of population averages. General QoL metrics like the SF-36 do not appear to have substantial utility in EoE. [ABSTRACT FROM AUTHOR]

Background: Lymphocytic esophagitis (LyE) is a recently described clinicopathological condition, but little is known about its features and clinical associations.Aim: The aim of this study was to characterize patients with LyE, compare them to non-LyE controls, and identify risk factors.Methods: We conducted a retrospective study of all patients ≥18 years old who underwent upper endoscopy with esophageal biopsy between January 1, 2000, and June 1, 2012. Archived pathology slides were re-reviewed, and LyE was diagnosed if there was lymphocyte-predominant esophageal inflammation with no eosinophils or granulocytes. Three non-LyE controls groups were also defined: reflux, eosinophilic esophagitis (EoE), and normal. Clinical data were extracted from electronic medical records, and LyE cases were compared to non-LyE controls.Results: Twenty-seven adults were diagnosed with LyE, and the majority were female (63 %). The most common symptom was dysphagia (70 %). Fifty-two percentage had a prior or current diagnosis of reflux. Endoscopic findings included strictures (37 %), erosive esophagitis (33 %), rings (26 %), and hiatal hernia (26 %); 33 % of patients required dilation. After histology re-review, 78 % of LyE patients were found to have more than 20 lymphs/hpf. In comparison with the normal, reflux and EoE controls, patients with LyE tended to be nonwhite (p < 0.01), were more commonly tobacco users (p = 0.02) and less likely to have seasonal allergies (p = 0.02).Conclusion: LyE commonly presents with dysphagia due to esophageal strictures which require dilation. Smoking was associated with LyE, whereas atopy was not. LyE should be considered as a diagnostic possibility in patients with these characteristics undergoing upper endoscopy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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-β, 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. [ABSTRACT FROM AUTHOR]

OBJECTIVES:There is no 'gold standard' for assessing disease activity in patients with eosinophilic esophagitis (EoE). We aimed to compare physicians' judgment of EoE activity with patients' judgment of symptom severity. We also aimed to examine the relative contribution of symptoms as well as endoscopic and histologic findings in shaping physicians' judgment of EoE activity.METHODS:Six gastroenterologists (all EoE experts) assessed EoE-associated symptoms in adult patients. Patients completed a symptom instrument and provided global assessment of EoE symptom severity (PatGA) (Likert scale: 0 (inactive) to 10 (most active)). Following esophagogastroduodenoscopy with biopsy sampling, gastroenterologists provided a global assessment of EoE activity (PhysGA) (Likert scale from 0 to 10) based on patient history and endoscopic and histologic findings. Linear regression and analysis of variance was used to quantify the extent to which variations in severity of EoE symptoms and endoscopic and histologic findings explain variations in PhysGA.RESULTS:A total of 149 EoE patients were prospectively included (71.8% male, median age at inclusion 38 years, 71.8% with concomitant allergies). A moderate positive correlation between PhysGA and PatGA (rho=0.442, P<0.001) was observed and the mean difference in the Bland-Altman plot was 1.77. Variations in severity of endoscopic findings, symptoms, and histologic findings alone explained 53%, 49%, and 30%, of the variability in PhysGA, respectively. Together, these findings explained 75% of variability in PhysGA.CONCLUSIONS:Gastroenterologists rate EoE activity mainly on the basis of endoscopic findings and symptoms and, to a lesser extent, on histologic findings. [ABSTRACT FROM AUTHOR]

OBJECTIVES:Proton-pump inhibitor-responsive esophageal eosinophilia (PPI-REE) is a newly recognized entity that must be differentiated from eosinophilic esophagitis (EoE). Little is known about this condition. We aimed to determine the prevalence of PPI-REE and EoE in patients undergoing upper endoscopy and determine features that distinguish the two groups.METHODS:This prospective study conducted at the University of North Carolina from 2009 to 2011 enrolled consecutive adult patients undergoing outpatient upper endoscopy. Subjects had esophageal biopsies to quantify the maximum eosinophil count per high-power field (eos/hpf; hpf=0.24 mm2). If biopsies revealed ≥15 eos/hpf, subjects were treated with twice daily PPI for 8 weeks and endoscopy was repeated. If ≥15 eos/hpf persisted despite PPI therapy, EoE was diagnosed. If there were <15 eos/hpf, PPI-REE was diagnosed. The proportion of patients in each group was calculated, and patients with EoE and PPI-REE were compared.RESULTS:Of the 223 subjects enrolled, 173 had dysphagia and 50 did not. Of those with dysphagia, 66 (38%) had ≥15 eos/hpf. After the PPI trial, 40 (23%) were confirmed to have EoE, and 24 (14%) had PPI-REE. Of those without dysphagia, 2 (4%) had ≥15 eos/hpf, and after the PPI trial, 1 (2%) had EoE. Compared with EoE, PPI-REE patients were more likely to be older and male and less likely to have typical endoscopic findings of EoE. However, none of the individual factors was independently predictive of PPI-REE status on multivariable analysis. Similarly, although some endoscopic findings were differentially distributed between PPI-REE and EoE, none were significantly associated with disease status on multivariable analysis.CONCLUSIONS:Esophageal eosinophilia is common among patients undergoing esophagogastroduodenoscopy for dysphagia. Although EoE was seen in nearly a quarter of patients with dysphagia, PPI-REE was almost as common, and accounted for over one-third of those with ≥15 eos/hpf. No clinical or endoscopic features independently distinguished PPI-REE from EoE before the PPI trial. [ABSTRACT FROM AUTHOR]

OBJECTIVES:Features of eosinophilic esophagitis (EoE) and gastroesophageal reflux disease (GERD) overlap. We aimed to determine whether staining for tissue biomarkers would differentiate EoE from GERD, suggesting utility for diagnosis of EoE.METHODS:In this case-control study, EoE patients defined by consensus guidelines were compared to GERD patients with eosinophils on esophageal biopsy. Immunohistochemistry was performed for major basic protein (MBP), eotaxin-3, leukotriene A4 hydrolase (LTA4H), and leukotriene C4 synthase (LTC4S). After masking, the maximum staining density (cells per mm2) was quantified for each marker and compared between groups. Receiver operator characteristic curves were constructed, and the area under the curve (AUC) calculated to assess the diagnostic utility of each of the biomarkers alone and in combination with eosinophil counts.RESULTS:There were 51 EoE cases (mean age 24; mean 143 eosinophils per high-power field (eos per h.p.f.)) and 54 GERD controls (mean age 34; mean 20 eos per h.p.f.). The MBP density was higher in EoE than in GERD (1479 vs. 59 cells per mm2; P<0.001), as was the eotaxin-3 density (2219 vs. 479; P<0.001). There were no differences for LTA4H and LTC4S. MBP density and eosinophil count correlated (R=0.81; P<0.001); correlation with eotaxin-3 was weaker (R=0.25; P=0.01). The AUC for diagnosis of EoE was 0.96 for MBP, 0.87 for eotaxin-3, 0.58 for LTA4H, 0.66 for LTC4S, and 0.99 for the combination of MBP, eotaxin-3, and eosinophil count.CONCLUSIONS:Patients with EoE had substantially higher levels of MBP and eotaxin-3 staining than GERD patients. These markers may have utility as a diagnostic assay for EoE. [ABSTRACT FROM AUTHOR]

OBJECTIVES:Eosinophilic esophagitis (EoE) is thought to be more common among males and Caucasians, but little is known about the disease presentation among patients with different genders or racial backgrounds. The objective of this study was to determine the clinical, endoscopic, and histologic characteristics of patients with EoE of different genders or racial backgrounds.METHODS:We conducted a retrospective study of the University of North Carolina EoE clinicopathologic database between January 2000 and December 2008. Cases of EoE were defined per 2007 consensus guidelines and stratified by race and gender for comparison.RESULTS:In all, 208 incident EoE cases were identified (76% males, mean age 26 years, 82% Caucasian, and 12% African American). Caucasians were older at diagnosis than African Americans (27.1 vs. 19.0 years, P=0.05), less likely to present with failure-to-thrive (9 vs. 30%, P=0.002), and more likely to have esophageal rings (41 vs. 12%, P=0.005). These findings persisted after stratification by age. A higher proportion of males were diagnosed under the age of 18 as compared with females (48 vs. 64%, P=0.05). Males were more likely to report dysphagia and food impaction as symptoms (71 vs. 53%, P=0.02 and 35 vs. 20%, P=0.05, respectively), and these findings also persisted after stratification by age. The remainder of clinical, endoscopic, and histologic features did not differ by either race or gender.CONCLUSIONS:While age and dysphagia differed by gender and race among EoE patients, the majority of symptoms and findings were not different across groups, even after stratification by age. Clinicians should maintain a high index of suspicion for EoE, regardless of race or gender, and obtain esophageal biopsies to confirm the diagnosis. [ABSTRACT FROM AUTHOR]

OBJECTIVES:Mast cells may contribute to the pathogenesis of eosinophilic esophagitis (EoE), but their role in diagnosis is unknown. Our aim was to determine whether tryptase staining of esophageal mast cells differentiates EoE from gastroesophageal reflux disease (GERD) and has utility for diagnosis of EoE.METHODS:We performed a case-control study comparing patients with EoE, defined by consensus guidelines, to GERD patients with eosinophils on esophageal biopsy. Immunohistochemistry was performed with mast cell tryptase. The density (mast cells/mm2) and intensity (0-4 scale) of mast cell staining was compared between groups after masking the diagnosis. Receiver operating characteristic (ROC) curves were constructed, and the area under the curve (AUC) was calculated to assess mast cell staining as both a stand-alone diagnostic test and an adjunctive assay with eosinophil counts.RESULTS:Fifty-four EoE (mean age 24 years; 69% male; mean 146 eosinophils per high-power field (eos/hpf)) and 55 GERD (mean age 34 years; 60% male; mean 20 eos/hpf) patients were analyzed. The maximum epithelial tryptase density was higher in EoE than in GERD (162±87 mast cells/mm2 vs. 67±54; P<0.001). Mast cells were diffusely distributed throughout the biopsy in more EoE than GERD patients (41 vs. 7%; P<0.001). Tryptase density and eosinophil count were only weakly correlated (R2=0.09; P=0.002). The AUC was 0.84 for tryptase staining alone, and 0.96 for the combination of mast cells and eosinophils.CONCLUSIONS:Patients with EoE have higher levels of tryptase-positive mast cells compared with GERD patients, improving the diagnostic value of biopsies beyond eosinophil counts alone. Mast cell tryptase may have utility as a diagnostic assay for EoE. [ABSTRACT FROM AUTHOR]

Background: Diagnosis of eosinophilic esophagitis (EoE) requires quantification of esophageal eosinophilia.Aims: The aims of this study were to assess inter- and intraobserver reliability for measuring esophageal eosinophil counts and to validate a novel method of determining tissue eosinophil density using digitized histopathology slides.Methods: Patients were selected from the University of North Carolina EoE clinicopathologic database. Glass slides were de-identified and scanned to create digitized slides. Using a set protocol, 40 slides were read by each of three pathologists for interobserver measures, and were also reread by one pathologist as traditional glass slides. Different sets of 20 unique slides were read twice by each pathologist for intraobserver measures. Correlation and agreement were calculated with Pearson's rho and the kappa statistic.Results: There was excellent correction between digitized images and glass slides (r = 0.91-0.95, P < 0.001). For maximum eosinophil densities, interobserver correlations were 0.91, 0.76, and 0.79. For mean densities, interobserver correlations were 0.90, 0.89, and 0.85. Intraobserver correlations for maximum densities were 0.99, 0.94, and 0.96, and for mean densities were 0.97, 0.87, and 0.89 (P < 0.001 for all correlations). Agreement was in the "substantial" to "near-perfect" range for pathologists using several diagnostic cut-points for EoE.Conclusions: Both inter- and intraobserver correlations were excellent for determining eosinophil densities and counts. A method of using digitized slides was valid when compared with traditional glass slides. This protocol could be adopted for research and clinical purposes to further standardize the diagnostic process for EoE. [ABSTRACT FROM AUTHOR]

BACKGROUND: Eosinophilic esophagitis (EoE) is an emerging clinicopathologic entity defined by abnormal esophageal eosinophilic infiltration. Our understanding of this disease is hampered by the lack of a uniform diagnostic standard. The aim of this systematic review was to determine the range of diagnostic strategies and histologic criteria in the EoE literature. METHODS: The MEDLINE-indexed literature from 1950 through December 31, 2006 was independently searched by two investigators. To identify additional relevant studies, bibliographies were hand searched, as were the published proceedings of the 2000–2006 American College of Gastroenterology and American Gastroenterological Association national meetings. Data were extracted from all human EoE case reports, case series, cross-sectional and cohort studies, and clinical trials. RESULTS: Of 318 publications initially identified, 116 original articles, 39 abstracts, and 69 reviews were included. We found 10 different histologic definitions of EoE, ranging from 5 to 30 eosinophils per high-powered field (hpf), though 41 (35%) of the original articles did not state their diagnostic criteria. In the 13 original articles (11%) reporting an hpf area, the eosinophil density per mm2 varied 23-fold. There was also variation in esophageal biopsy protocols, but specific protocols were reported in just 45 (39%) original articles. CONCLUSIONS: Significant variability in diagnostic criteria for eosinophilic esophagitis exists, and in a large proportion of studies, criteria are not reported. Because of this lack of a common disease definition, conclusions drawn from the cumulative EoE literature should be viewed with caution. A consensus research-quality standard for diagnosis of eosinophilic esophagitis is needed. [ABSTRACT FROM AUTHOR]