Epidemiology of Eosinophilic Esophagitis

The Index of Severity for Eosinophilic Esophagitis (I-SEE) was recently developed. We aimed to understand I-SEE scores in a longitudinal pediatric cohort and to determine the relationship between I-SEE and clinical features in children.

We performed a retrospective analysis on a prospectively enrolled cohort of children at a single center who were treated as part of routine clinical care. I-SEE was calculated at the diagnostic and follow-up endoscopies over a mean of 6.6 years. Scoring was 0 for inactive, 1–6 for mild, 7–14 for moderate, and ≥15 for severe eosinophilic esophagitis (EoE). We analyzed clinical, endoscopic, and histologic features at each instance. Symptoms were analyzed at the baseline, first follow-up, and last endoscopic instance.

Of 67 children who met study criteria of at least 3 endoscopies over at least 2 years of follow-up time, 43%, 36%, and 21% had mild, moderate, and severe I-SEE scores at baseline, respectively. Between the first and second endoscopic instances, there was a decrease in the group mean I-SEE from 9.7 ± 7.2 to 6.1 ± 5.9 (P < .001). By the last instance, the overall I-SEE score dropped to 3.9 (P < .001). Body mass index <5% and poor feeding were more common in the children with severe I-SEE scores at baseline, and both improved by the last instance. Fibrosis was improved by the last instance biopsy (P < .01).

I-SEE is a responsive severity metric in children treated long term during routine clinical care. Baseline low body mass index and poor feeding were more common in children with severe I-SEE scores.

Eosinophilic esophagitis (EoE) is diagnosed and monitored using esophageal eosinophil levels; however, EoE also exhibits a marked, understudied esophageal mastocytosis.

Using machine learning, we localized and characterized esophageal mast cells (MCs) to decipher their potential role in disease pathology.

Esophageal biopsy samples (EoE, control) were stained for MCs by anti-tryptase and imaged using immunofluorescence; high-resolution whole tissue images were digitally assembled. Machine learning software was trained to identify, enumerate, and characterize MCs, designated Mast Cell–Artificial Intelligence (MC-AI).

MC-AI enumerated cell counts with high accuracy. During active EoE, epithelial MCs increased and lamina propria (LP) MCs decreased. In controls and EoE remission patients, papillae had the highest MC density and negatively correlated with epithelial MC density. MC density in the epithelium and papillae correlated with the degree of epithelial eosinophilic inflammation, basal zone hyperplasia, and LP fibrosis. MC-AI detected greater MC degranulation in the epithelium, papillae, and LP in patients with EoE compared with control individuals. MCs were localized further from the basement membrane in active EoE than EoE remission and control individuals but were closer than eosinophils to the basement membrane in active EoE.

Using MC-AI, we identified a distinct population of homeostatic esophageal papillae MCs; during active EoE, this population decreases, undergoes degranulation, negatively correlates with epithelial MC levels, and significantly correlates with distinct histologic features. Overall, MC-AI provides a means to understand the potential involvement of MCs in EoE and other disorders.

La esofagitis eosinofílica es una enfermedad inflamatoria crónica inmunomediada del esófago. Su incidencia ha aumentado en los últimos años, representando una de las enfermedades esofágicas más prevalentes, con un impacto significativo en la salud física y la calidad de vida. La clínica es variable, siendo una causa cada vez más común de disfagia tanto en niños como en adultos. El patrón oro para el diagnóstico es la endoscopia digestiva alta con toma de biopsias parcheadas, demostrando un infiltrado inflamatorio mayor de 15 eosinófilos por campo de gran aumento. Actualmente se dispone de distintos tratamientos efectivos tanto para la inducción como para el mantenimiento de la remisión de la enfermedad, entre los que se incluyen los inhibidores de la bomba de protones, los corticoides tópicos deglutidos y las dietas de exclusión.

Eosinophilic esophagitis is a chronic immune-mediated inflammatory disease of the esophagus. Its incidence has increased in recent years and it is one of the most prevalent esophageal diseases, with a significant impact on physical health and quality of life. Symptoms are variable and it is an increasingly common cause of dysphagia in both children and adults. The gold standard for diagnosis is upper gastrointestinal endoscopy with biopsies of patches demonstrating inflammatory infiltrate with more than 15 eosinophils per high-power field. Various effective treatments are currently available for both induction and maintenance of disease remission, including proton pump inhibitors, swallowed topical corticosteroids, and exclusion diets.

Eosinophilic esophagitis (EoE) can coexist in individuals with food allergy.

To evaluate the characteristics of food-allergic patients with and without coexisting EoE using a large food allergy patient registry.

Data were derived from 2 Food Allergy Research & Education, Inc, Patient Registry surveys. A series of multivariable regression models were used to evaluate associations between demographic, comorbidity, and food allergy characteristics and the likelihood of reporting EoE.

Five percent (n = 309) of registry participants (n = 6074; ages <1 year->80 years, mean, 20.20 ± 15.37 years) reported having EoE. The odds of having EoE were significantly greater in male participants (adjusted odds ratio [aOR], 1.3; 95% CI, 1.04-1.72) and those with comorbid asthma (aOR, 2.0; 95% CI, 1.55-2.49), allergic rhinitis (aOR, 1.8; 95% CI, 1.37-2.22), oral allergy syndrome (aOR, 2.8; 95% CI, 2.09-3.70), food protein–induced enterocolitis syndrome (aOR, 2.5; 95% CI, 1.34-4.84), and hyper-IgE syndrome (aOR, 7.6; 95% CI, 2.93-19.92), though not atopic dermatitis (aOR, 1.3; 95% CI, 0.99-1.59), when adjusting for demographics (sex, age, race, ethnicity, and geographic location). Those with a greater number of food allergies (aOR, 1.3; 95% CI, 1.23-1.32), more frequent food-related allergic reactions (aOR, 1.2; 95% CI, 1.11-1.24), previous anaphylaxis (aOR, 1.5; 95% CI, 1.15-1.83), and health care utilization for food-related allergic reactions (aOR, 1.3; 95% CI, 1.01-1.67)—specifically intensive care unit admission (aOR, 1.2; 95% CI, 1.07-1.33)—were more likely to have EoE after controlling for demographics. However, no significant difference in ever using epinephrine for food-related allergic reactions was detected.

These self-reported data showed that coexisting EoE is associated with an increased number of food allergies, food-related allergic reactions per year, and measures of reaction severity, calling attention to the likely increased health care needs of food-allergic patients with EoE.

Pediatric patients with eosinophilic esophagitis (EoE) experience heterogeneous symptoms and the patient’s age may preclude reliable self-report of symptoms.

The goal of this study was to develop a patient-reported outcome and an observer-reported outcome questionnaire to evaluate the signs and symptoms of EoE in pediatric patients (≥1 to <12 y of age) in a clinical trial setting.

A concept-focused literature review, expert advice meetings, and concept elicitation interviews with pediatric EoE patients and their caregivers were conducted to identify disease-related signs and symptoms. Instructions, items, and response options were drafted. Cognitive debriefing interviews were conducted to evaluate children’s and caregivers’ ability to understand and respond to the questionnaires and to evaluate the comprehensiveness of the concepts measured.

Results from the literature review, expert advice meetings (n = 6), and concept elicitation interviews (n = 24) informed the development of the Pediatric Eosinophilic Esophagitis Sign/Symptom Questionnaire intended for use by patients (PESQ-P) with EoE 8 years or older to younger than 12 years and an observer-reported outcome questionnaire planned for use by caregivers of patients (PESQ-C) 1 year old or older to younger than 12 years. Both questionnaires measure the same concepts; the PESQ-P assesses the frequency, duration, and/or severity of symptoms and the PESQ-C assesses the presence/absence of the signs/symptoms. The cognitive debriefing interviews (n = 17) demonstrated that participants were able to comprehend and complete the questionnaires as intended.

This study provides evidence of the content validity of 2 novel questionnaires, PESQ-P and PESQ-C, designed to evaluate the symptom experience of pediatric EoE patients in a clinical trial setting.