Early-life levels of protein-bound ceramides are predictive of atopic dermatitis development

Dr. Ujwal M
MBBS, MD. DVL, Consultant Dermatologist
Raghavendra Skin Care
Bengaluru

Atopic dermatitis (AD), or eczema, is a common chronic inflammatory skin disorder in early life, primarily linked to skin barrier dysfunction. The stratum corneum—the outermost skin layer—relies on lipids, particularly ceramides, for its barrier function. While ceramide abnormalities are known in AD, it remains unclear whether such changes precede disease onset and could serve as predictive markers, especially for different AD phenotypes.

This study analyzed data from the PEBBLES trial, which evaluated the use of a ceramide-dominant emollient in preventing AD in infants with a family history of allergic disease. For this analysis, skin lipid samples from the forearms of 133 infants with family history of allergic disease were collected at 6 weeks using tape strips. Lipids were quantified via liquid chromatography-tandem mass spectrometry, and AD diagnosis was confirmed at age 1 using modified UK criteria. Allergic sensitization was assessed with skin prick tests.

Among 176 lipid species analyzed, 12 belonged to the protein-bound ceramide (POS) class. Increased levels of POS ceramides with 30- or 32-carbon fatty acid chains (e.g., PO30:0-C20S) were significantly associated with reduced risk of AD, particularly in unadjusted models. Conversely, certain free ceramides and ceramide ratios were linked with increased risk. Adjusted analyses confirmed only a few associations—particularly PO30:0-C20S, N26:0-C20S, and N24:0-C22S—as significantly associated with AD.

In predictive models, PO30:0-C20S demonstrated the strongest ability to discriminate AD risk, with an AUC of 0.7 when added to standard risk factors.

Lower levels of protein-bound ceramides are associated with the onset of nonatopic atopic dermatitis, suggesting they may contribute to disease development and serve as valuable predictors of AD risk.

Reference: Chang CL, Berdyshev E, Milanzi E, et al. Early-life protein-bound skin ceramides help predict the development of atopic dermatitis. J Allergy Clin Immunol. 2025;155(3):856–864.