Cutaneous ceramide synthesis is dysregulated in pediatric eosinophilic esophagitis.

Abstract

Eosinophilic esophagitis (EoE), like atopic dermatitis (AD), is a disease of epithelial barrier dysfunction. The predisposing factors remain under investigation and few commonalities between the skin and the esophagus are known. There are no surrogate markers for EoE risk. We sought to assess for concurrent skin and esophageal dysfunction by evaluating ceramide (CER) levels in the skin of children with EoE. We collected up to 21 skin tape strips (STSs) from the volar forearm of non-AD subjects with EoE (n = 21) and non-AD, non-EoE controls (n = 17) and evaluated skin lipid composition by liquid chromatography tandem mass spectrometry. Of the subjects with EoE, 38% were female, 57% had IgE-mediated food allergy, and 57% were in histologic remission at STS collection. The time between endoscopy and STS was 75.7 days (range, 0-467). Compared with controls, the skin of subjects with EoE had significant decreases in CERs with 22-carbon long-chain sphingosine or 22-carbon long-chain phytosphingosine and nonhydroxy fatty acids (P < .05) and in all α-hydroxy fatty acid-containing sphingosine CERs (with 18-, 20-, and 22-carbon long-chain sphingosines) (P < .01). Ultralong-chain fatty acid-containing CERs were particularly reduced in the skin of subjects with EoE. There are demonstrable differences in long-chain CERs in the skin of children with EoE but without AD as compared with non-AD, non-EoE subjects. These data suggest that skin barrier could be a biomarker for EoE and conceptually suggests that the skin and esophagus may represent a "unified epithelial barrier."