Cutaneous Ceramide Synthesis is Dysregulated in Pediatric Eosinophilic Esophagitis.

BACKGROUND: Eosinophilic esophagitis (EoE), like atopic dermatitis (AD), is a disease of epithelial barrier dysfunction. The predisposing factors remain under investigation and few links between the skin and esophagus are known. There are no surrogate markers for EoE risk. We evaluated ceramide levels in the skin of children with EoE to assess for concurrent skin and esophageal dysfunction. METHODS: We collected up to 21 skin tape strips (STS) from the volar forearm of non-AD EoE subjects (n=21) and non-AD non-EoE controls (n=17) and evaluated skin lipid composition by liquid chromatography tandem mass spectrometry. RESULTS: EoE subjects were 38% female, 57% had IgE mediated food allergy (FA), 57% were in histologic remission at STS collection. The time between endoscopy and STS was 75.7 days (range 0-467). Compared to controls, EoE subject's skin had significant decreases in ceramides with 22-carbon long chain sphingosine or 22-carbon chain phytosphingosine and non-hydroxy fatty acids (p<0.05), and in all alpha-hydroxy fatty acid-containing sphingosine ceramides (with18-, 20- and 22-carbon chain sphingosine) (p<0.01). Ultra-long chain fatty acid-containing ceramides were particularly reduced in the skin of EoE subjects. CONCLUSIONS: There are demonstrable differences in long chain ceramides in the skin of children with EoE but without AD as compared to 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".