John L Lyles1, Lisa J Martin2, Tetsuo Shoda3, Margaret H Collins4, Michael P Trimarchi3, Hua He5, Leah C Kottyan6, Vincent A Mukkada7, Marc E Rothenberg8. 1. Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. 2. Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio. 3. Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. 4. Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio; Division of Pathology and Laboratory Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio. 5. Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. 6. Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio; Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. 7. Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio. 8. Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio; Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. Electronic address: Marc.Rothenberg@cchmc.org.
Abstract
BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic, food antigen-mediated disease characterized by esophageal dysfunction and intraepithelial eosinophil accumulation. OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic, food antigen-mediated disease characterized by esophageal dysfunction and intraepithelial eosinophil accumulation. OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Authors: Jamie Tanzer; Di Meng; Asa Ohsaki; Julie M Caldwell; Melissa K Mingler; Marc E Rothenberg; Michiko K Oyoshi Journal: PLoS One Date: 2022-06-27 Impact factor: 3.752
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