Skin lipid problems predict eczema in infancy

Melbourne research suggests a damaged skin barrier precedes atopic dermatitis some children, and hints at new treatment targets.

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Infants who develop atopic dermatitis are more likely to have disrupted skin lipid profiles, according to new Australian research.

The findings suggest skin abnormalities precede the development of eczema, which may translate into new early detection and intervention strategies in young children.

“This study describes for the first time that reduced levels of POS ceramides with 30 and 32 carbon fatty acid chain at age six weeks are associated with an increased risk of ‘AD without sensitisation’ by age one year, while there was limited evidence of association between AD and other skin lipids,” the authors said. 

Lipids, such as protein-bound ω-hydroxyl sphingosine ceramides (POS ceramides), are a vital part of the skin barrier, said the researchers, which were led by the University of Melbourne’s Allergy and Lung Health Unit.

“These findings are supported by the role that POS ceramides play as a scaffold for lamellae formation in the intercellular lipid matrix to form and maintain the skin barrier function,” they wrote in the Journal of Allergy and Clinical Immunology.

Using data from a separate phase 3 randomised controlled trial on eczema, the researchers studied 133 infants with a family history of allergies, assessing their skin lipid profiles at six weeks of age and tracking how many had atopic dermatitis at one year.

The samples, taken with tape strips from the infants’ forearms, were analysed with liquid chromatography-tandem mass spectrometry. Sensitisation was assessed with a skin prick test.

One in three participants had atopic dermatitis by the age of one – 13% had atopic dermatitis without sensitisation, 18% had atopic dermatitis with sensitisation and 13% had sensitisation without atopic dermatitis.

Researchers found that infants with higher levels of POS ceramides, particularly those with a 30- or 32- chain fatty acid, were less likely to develop eczema.

After adjusting for confounders, only PO30:0-C20S was tied to later eczema development (odds ratio, 0.62), and there was a nonsignificant trend for atopic dermatitis without sensitisation – but none for atopic dermatitis with sensitisation. PO30:0-C20S is a major POS ceramide in the skin, the authors said.

These findings could mean skin barrier problems caused by POS levels in the very young led to eczema, but not through the sensitisation pathway, they wrote.

“There is ongoing debate on whether AD leads to sensitisation or vice versa, and our findings may support that an impaired eczematous skin barrier precedes sensitisation development, at least in a subset of children.

“Children with ‘AD without sensitisation’ by age one year are at increased risk of developing sensitization at older ages. It is possible that early-life lipid restoration interventions for AD prevention may also prevent sensitisation and other forms of allergies from developing.

In addition, they found that seven free ceramide species and two [lipid] ratios were associated with eczema at age one.

“We also observed that inclusion of skin lipids into existing risk prediction models slightly improved predictive accuracy in identifying children who would develop AD,” the authors wrote.

Sydney dermatologist Dr Jacqueline Matulich, who has a special interest in paediatric dermatology, said the findings “support our understanding about specific lipid deficiencies in people with atopic dermatitis”.

“It is common practice to recommend ceramide containing moisturisers for children with atopic dermatitis to address these presumed deficiencies.

“However, much more research is required to build and extend on these findings before we can translate such findings into a test to identify those at risk,” said the Chatswood Dermatology Centre clinician.

It was possible other confounding factors played a role in the links found in this small study, and it was possible different lipids interacted in synergistic or antagonistic ways that weren’t captured by the study, the authors noted. 

Journal of Allergy and Clinical Immunology, 11 February 2025