Very early onset eosinophilic esophagitis is common, responds to standard therapy, and demonstrates enrichment for CAPN14 genetic variants - 09/01/21
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.
Il testo completo di questo articolo è disponibile in PDF.Graphical abstract |
Key words : Infancy, environment, cesarean delivery, genetics, molecular pathogenesis, EoEHSS, EREFS, EDP, CAPN14, ACTG2
Abbreviations used : ACTG2, BZH, CAPN14, CCHMC, EDP, EGD, EI, EoE, EoEHSS, EREFS, EWT, IQR, L-EoE, MM, PCA, SNP, TSLP, V-EoE
Mappa
| This work was supported in part by the National Institutes of Health (grant no. K24 DK100303 to J.L.L. and grant nos. U19 AI070235, R01 AI124355, R01 DK107502, R37 A1045898, and P30 DK078392 [Gene and Protein Expression Core]); the Campaign Urging Research for Eosinophilic Disease (to M.E.R.); and the Sunshine Charitable Foundation and its supporters, Denise and David Bunning (to M.E.R.). |
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| Disclosure of potential conflict of interest: M. H. Collins has received research funding from Meritage Pharma, Inc, Receptos/Celgene, Regeneron, and Shire, a Takeda company, and is a consultant for Allakos, AstraZeneca, Esocap, GlaxoSmithKline, Receptos/Celgene, Regeneron, Robarts Clinical Trials, and Shire, a Takeda company. V. A. Mukkada has received research funding from Meritage Pharma, Inc, and Shire, a Takeda company, and is a consultant for Shire, a Takeda company. M. E. Rothenberg is a consultant for Pulm One, Spoon Guru, ClostraBio, Serpin Pharm, Allakos, Celgene, Astra Zeneca, and Arena Pharmaceuticals and has an equity interest in the first 5 listed and royalties from reslizumab (Teva Pharmaceuticals), PEESSv2 (Mapi Research Trust), and UpToDate and is an inventor of patents owned by Cincinnati Children’s Hospital Medical Center. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 147 - N° 1
P. 244 - Gennaio 2021 Ritorno al numero
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