BACKGROUND: Eosinophilic esophagitis (EoE) is an immune-mediated disease, manifested by dysphagia and characterized by intraepithelial infiltration: more than 15 eosinophils per field of view at x400 magnification, and requiring differential diagnosis with reflux esophagitis (RE).
OBJECTIVE: To access the implication of EoE histologic scoring system (EoEHSS) for differential diagnosis of EoE and RE and to characterize features of immune response in these diseases.
METHODS: 38 patients with EoE and 38 patients with RE were enrolled in the study. All the patients had esophagogastroduodenoscopy with biopsy. Biopsy specimens were stained with H&E and combined PAS/Alcian blue staining. Immunohistochemical evaluation was conducted with antibodies to CD3, CD4, CD8, CD20, CD56 and CD68.
RESULTS: Grade score of EoEHSS in EoE was 2.4 times more than in RE (p<0.05). Stage score in EoE was 2.75 more than in RE (p<0.05). Intraepithelial count of CD3+ T-lymphocytes comprised 87 (76-95.5) in high-power view in EoE and 45 (38.5-48.5) in high-power view in RE. Intraepithelial count of CD4+ T-lymphocytes was 35 (28-41.5) in high-power view in EoE and 19 (16.5- 22.5) in high-power view in RE. Intraepithelial count of CD8+ T-lymphocytes comprised 59 (50.5-67.5) in high-power field in EoE and 27 (24-28.5) in high-power field in RE.
CONCLUSIONS: The use of the EoEHSS histological rating scale for eosinophilic esophagitis is effective in the differential diagnosis of EoE and EC. Predominant cells in intraepithelial infiltrate are CD3+ T-lymphocytes both in EoE and RE, CD8+ cells prevail over CD4+ cells. In EoE intraepithelial count of CD3+ T-lymphocytes is 1.93 times more, count of intraepithelial CD4+ lymphocytes is 1.84 times more and count of CD8+ lymphocytes is 2.19 times more than in RE.
Эозинофильный эзофагит (ЭоЭ) — иммуноопосредованное заболевание пищевода, проявляющееся дисфагией и характеризующееся интраэпителиальной инфильтрацией: более 15 эозинофилов в поле зрения при увеличении в 400 раз, требующее дифференциальную диагностику с рефлюкс-эзофагитом (РЭ).
UNASSIGNED: Оценить значение шкалы патоморфологической оценки ЭоЭ (EoEHSS) в дифференциальной диагностике ЭоЭ и РЭ и охарактеризовать особенности иммунного ответа при этих заболеваниях.
UNASSIGNED: В исследование вошло 38 пациентов с ЭоЭ и 38 с РЭ, которым проведена эзофагогастродуоденоскопия с биопсией. Биоптаты окрашивали гематоксилином и эозином, а также реактивом Шиффа в сочетании с альциановым синим. Проводилось также иммуногистохимическое исследование с антителами к CD3, CD4, CD8, CD20, CD56 и CD68.
UNASSIGNED: Сумма баллов степени по шкале EoEHSS при ЭоЭ превышала данный показатель при РЭ в 2,4 раза (p<0,05), а сумма баллов стадии по шкале EoEHSS — в 2,75 раза (p<0,05). При увеличении в 400 раз в поле зрения число внутриэпителиальных CD3+ T-лимфоцитов составило при ЭоЭ 87 (76—95,5), при РЭ 45 (38,5—48,5); интраэпителиальных CD4+ T-лимфоцитов — при ЭоЭ 35 (28—41,5), при РЭ 19 (16,5—22,5); интраэпителиальных CD8+ T-лимфоцитов — при ЭЭ 59 (50,5—67,5), а при РЭ 27 (24—28,5).
UNASSIGNED: Применение шкалы гистологической оценки эозинофильного эзофагита EoEHSS эффективно в дифференциальной диагностике ЭоЭ и РЭ. Преобладающими клетками в интраэпителиальном инфильтрате как при ЭоЭ, так и при РЭ являются CD3+ T-лимфоциты, отмечается также преобладание CD8+ над CD4+ T-лимфоцитами. При ЭоЭ интраэпителиальное число CD3+ T-лимфоцитов превышает данный показатель при РЭ в 1,93 раза, число интраэпителиальных CD4+ лимфоцитов — в 1,84 раза, число интраэпителиальных CD8+ лимфоцитов — в 2,19 раза.

Eosinophilic esophagitis (EoE) is an immune-mediated disease that manifests with dysphagia and is characterized by the predominantly eosinophilic infiltration of the esophageal mucosa. Several instruments have been developed to assess the symptoms of EoE: the Daily Symptom Questionnaire (DSQ), EoE Activity Index (EEsAI), Pediatric EoE Symptom Severity (PEESSv2), etc. The use of the EREFS is a gold standard for endoscopic diagnosis. The EoE histologic scoring system (EoEHSS) was elaborated for the assessment of histological features in EoE. However, the remission criteria are not clearly defined and vary greatly in different studies. Gastroenterologists establish the severity of EoE mainly based on endoscopic findings. At the same time, EoE requires a multidisciplinary approach. The recently developed Index of Severity of Eosinophilic Esophagitis (I-SEE) that is built on symptoms, endoscopic findings, and histological features is promising.

BACKGROUND: Eosinophilic esophagitis (EoE) is an immune-mediated esophageal disease with rising incidence. While proton pump inhibitors (PPIs) are the first-line treatment, a significant proportion of patients do not respond. This study aimed to determine if the EoE Histology Scoring System (EoEHSS) can predict PPI responsiveness.
METHODS: A cross-sectional study was conducted on 89 pediatric patients diagnosed with EoE between 2016 and 2022. Patients were categorized into PPI responders (PPIREoE) and non-responders (PPINREoE) based on post-treatment biopsies. EoEHSS values from biopsies of the esophagus (distal, middle, and proximal segments) were compared between the two groups.
RESULTS: No significant differences in EoEHSS scores were observed for the distal and proximal esophagus between the groups. However, the middle esophagus showed a significantly higher EoEHSS grade score in the PPINREoE group, indicating a more pronounced disease severity. Specific histological features, particularly eosinophilic abscesses and surface layering of the middle segment of the esophagus, were significantly different between the groups.
CONCLUSIONS: Performing a biopsy of each esophageal segment, particularly the middle, is crucial for diagnostic precision and predicting PPI responsiveness. The EoEHSS can serve as a valuable tool in predicting therapy response, emphasizing the need for personalized therapeutic approaches in EoE management.

UNASSIGNED: Eosinophilic esophagitis (EoE) is defined as esophageal dysfunction in the presence of > 15 intraepithelial eosinophils per high-power field (eos/hpf) in either the mid or distal esophagus. The current focus of EoE pathologic evaluation is the peak eosinophil count (PEC), although histologic features other than eosinophilic inflammation are also commonly observed. In addition, histologic variance between the mid and distal esophagus in EoE has not been rigorously studied. The aim of our study was to utilize a recently developed EoE histologic scoring system (EoEHSS) to compare the mid and the distal esophageal histology in patients with active EoE (EoE-A), EoE in remission (EoE-R), and gastroesophageal reflux disease (GERD).
UNASSIGNED: EoEHSS was used to prospectively evaluate the severity and extent of changes in multiple histopathologic features (PEC; basal zone hyperplasia (BZH); eosinophilic abscesses (EA); eosinophil surface layering (ESL); dilated intercellular spaces (DIS); surface epithelial alteration (SEA); dyskeratotic epithelial cells (DEC); lamina propria fibrosis (LPF)) in the mid and distal esophageal biopsies in 85 pediatric patients at a tertiary medical center. These patients were divided into three cohorts: EoE-A (n = 36), EoE-R (n = 12) and GERD (n = 37).
UNASSIGNED: Total grade (severity) and stage (extent) scores were significantly higher in EoE-A compared to EoE-R and GERD patients in both the mid and the distal esophagus. The mean total grade scores in the mid esophagus, but not the distal esophagus remained higher in EoE-R as compared to GERD patients. Specific histopathologic features independent of PEC were different in distal and mid esophagus in EoE-A. About one-half of children with active EoE had different EoEHSS scores in their mid and distal esophageal biopsies.
UNASSIGNED: EoEHSS yields histologic insights beyond those derived from PEC and helps in more objective, reproducible and accurate diagnosis of EoE and GERD. It also provides a more comprehensive understanding into the pathophysiology of EoE.

Eosinophilic esophagitis (EoE) is a chronic, food antigen-mediated disease characterized by esophageal dysfunction and intraepithelial eosinophil accumulation.
We hypothesized that very early onset EoE (V-EoE) would be enriched for early-life and genetic factors and have worse presentation and prognosis than later-onset pediatric EoE (L-EoE).
We conducted a single-site, retrospective review comparing patients diagnosed at age 12 months or less (V-EoE, n = 57) and age 14 to 18 years (L-EoE, n = 70). These patients underwent medical record, EoE Histology Scoring System, Endoscopic Reference Score, and EoE Diagnostic Panel assessment when sample availability permitted. Genetic association used 2 EoE genotype repositories. Data were analyzed using chi-square tests, t tests, Wilcoxon rank-sum tests, Spearman correlations, cluster analysis, and logistic regression.
Among pediatric patients with EoE, diagnosis most commonly occurred within early life (0-24 months, 17%). V-EoE was more likely to attain histologic remission via dietary restriction (P < .0001). Basal zone hyperplasia and eosinophil inflammation were greater in V-EoE (P < .05). Esophageal strictures more commonly occurred in L-EoE (P = .03). V-EoE had lower endoscopic scores (P < .05). Molecular expression was very similar between groups. Cesarean delivery was more common in patients with V-EoE (P = .03). Patients with V-EoE demonstrated enrichment of CAPN14 common genetic variants.
Early-life diagnosis of EoE is a common occurrence. V-EoE responds to standard therapy without early evidence for complications, suggesting a less severe prognosis than hypothesized. Molecular pathogenesis is preserved between V-EoE and L-EoE. Cesarean delivery and CAPN14 genetic variation likely promote earlier disease development.

Gastrointestinal side effects are common during oral immunotherapy (OIT) and eosinophilic esophagitis (EoE) is a potential complication. We aimed to characterize eosinophilic gastrointestinal responses to peanut OIT, in which peanut protein is given orally, with incremental increases in dose over time.
Twenty adults with IgE-mediated peanut allergy were randomly assigned to groups given peanut OIT (n = 15) or placebo (n = 5); 1 additional subject withdrew before randomization. Serial gastrointestinal biopsies were collected at baseline (n = 21, 0 weeks), following dose escalation (n = 10, 52 weeks), and during the maintenance phase (n = 11, 104 weeks). Endoscopic findings were characterized using the EoE endoscopic reference score. Biopsies were assessed for eosinophils per high-power field (eos/hpf) and other pathology features using EoE histologic scoring system scores. We performed immunohistochemical analyses of eosinophil peroxidase deposition, quantified using automated image analysis.
At baseline, no subjects reported current gastrointestinal symptoms. However, 3 of the 21 subjects (14%) had esophageal peak eosinophil counts ≥15 eos/hpf and all subjects had dilated intercellular spaces (DIS). OIT induced or exacerbated esophageal eosinophilia (EE) at 52 weeks in most subjects (peak eosinophil counts >5 eos/hpf in 6 of 7 patients [86%]; peak eosinophil counts ≥15 eos/hpf in 4 of 7 patients [57%]). One subject met clinicopathologic criteria for EoE and withdrew; no significant changes in esophageal peak eosinophil counts were observed in the placebo group. EE in the OIT group corresponded with significant increases in EoE histologic scoring system scores and deposition of eosinophil peroxidase. In 4 of 6 participants (67%), OIT-induced EE and gastrointestinal eosinophilia resolved by the end of the maintenance phase. Gastrointestinal symptoms were not clearly associated with EE or gastrointestinal eosinophilia.
In this pilot study, we found that peanut OIT-induced EE and gastrointestinal eosinophilia are usually transient and are not always associated with gastrointestinal symptoms. Clinicaltrials.gov no: NCT02103270.

The short-term efficacy of RPC4046, a monoclonal antibody against interleukin-13, has been shown in patients with eosinophilic esophagitis (EoE). We investigated the long-term efficacy and safety of RPC4046 in an open-label, long-term extension (LTE) study in adults with EoE.
We analyzed data from 66 patients who completed the 16-week, double-blind, induction portion of a phase 2 study of RPC4046 (180 mg or 360 mg/wk) vs placebo and then completed a 52-week LTE, receiving open-label RPC4046 360 mg/wk. The study was conducted at 28 centers in 3 countries; patients were enrolled between September 2014 and January 2017. Outcomes were stratified by double-blind dose group and included esophageal eosinophil counts, EoE endoscopic reference score, EoE histologic scoring system score, symptom-based EoE activity index score, and safety.
By week 12 of the LTE, esophageal eosinophil mean and peak counts, total EoE endoscopic reference scores, and EoE histologic scoring system grade and stage scores did not differ considerably between patients who originally received placebo vs RPC4046. Most patients maintained responses through week 52. Symptom remission (symptom-based EoE activity index score, ≤20) increased from 14% at LTE entry to 67% at LTE week 52 in placebo‒RPC4046 patients and from 30% to 54% in RPC4046‒RPC4046 (either dose) patients. Of the 28 patients who did not have a histologic response to RPC4046 during the double-blind induction phase, 10 patients (36%) achieved response during the LTE. The most common adverse events were upper respiratory tract infection (21%) and nasopharyngitis (14%).
One year of treatment with RPC4046 is generally well tolerated and results in continued improvement and/or maintenance of endoscopic, histologic, and clinical measures of EoE disease activity relative to baseline.
NCT02098473.