A ceramide deficiency to predict children's eczema?

Infant eczema, in brief.

More common than one might think, eczema in infants is a chronic inflammatory skin disease that affects approximately 20% of children under five years old. It typically begins between the second and fourth month of life and is recognised by the red, dry, and rough patches it causes, often located on the scalp and skin folds. These lesions are accompanied by a pruritus that is very distressing for the baby who does not understand its origin and for the parents who often struggle to soothe it.

The causes of infant eczema are multifaceted, combining genetic predispositions - for example, mutations of the gene coding for filaggrin, a major protein of the horny layer whose role is to aggregate keratinocytes - and environmental factors (pollution, allergens, etc.). Naturally more fragile than that of adults, the skin of newborns is quite permeable to external irritants. Moreover, when they suffer from atopic dermatitis, their epidermis shows an alteration of its barrier function, largely due to an insufficient production of sebum and lipids. This is compounded by an immune component: children predisposed to eczema secrete large amounts of immunoglobulin E (IgE), antibodies, in response to environmental antigens, causing redness and skin dryness. This inflammatory environment further disrupts the skin barrier function and promotes the entry of allergens, laying the groundwork for a vicious cycle.

Despite this complexity, most researchers agree that the impairment of the skin barrier precedes inflammation, a hypothesis strengthened by the recent study conducted by LOWE A. J. and his team.

Do certain types of ceramides allow us to predict atopic dermatitis in babies?

Naturally present in the stratum corneum, ceramides are lipids that play a crucial role in the skin's barrier function. Indeed, they are responsible for the cohesion between keratinocytes, thus limiting transepidermal water loss. Composed of a sphingoid base and a fatty acid, ceramides account for approximately 50% of the lipids in the epidermis and actively contribute to the structuring of intercellular lipids, in the form of lamellar sheets. A deficiency in ceramides, whether genetic or acquired, impairs the barrier function and increases skin permeability, thereby promoting the penetration of allergens and irritants and skin inflammation. This imbalance is often observed in atopic dermatitis.

Some irregularities in the skin's lipid composition, detectable from the first few weeks of life, could predict the future risk of developing atopic dermatitis.

This is the conclusion of the study conducted by LOWE A. J. and his team with 133 infants who have a family history of allergies. At the age of six weeks, specific adhesive strips were used to collect surface cells from the babies' forearm skin. This technique is non-invasive and painless for the children. The samples were then analysed by mass spectrometry to establish a precise map of the lipids present, particularly ceramides. Over 700 lipid molecules were quantified. At the age of one, the prevalence of eczema was 32% (43 children out of 133).

In infants who later develop atopic dermatitis, statistical analysis of collected lipids revealed a significant decrease in a subgroup of ceramides known as "protein-bound ω-hydroxy ceramides" (POS). These POS, particularly the long-chain Cer-EOS (esterified ω-hydroxyacyl-sphingosine) (C30:0, C32:0, C34:0), are structural lipids that anchor to the stratum corneum via glutamic acid, proteins of the same layer. They play a fundamental role in the skin's seal and mechanical resilience. Overall, researchers observed that the skin of infants who later developed atopic dermatitis had 23.2% fewer POS than the skin of those without eczema at one year. Among the most discriminating POS, the PO30:0-C20S and the PO32:0-C20S had significantly lower concentrations, respectively by 30.7% and 36.4%.

These results are particularly noteworthy as at six weeks, none of the infants had yet shown visible signs of eczema, suggesting that these POS could serve as predictive biomarkers.

It's also worth noting that this study has several major methodological strengths that reinforce the credibility of its results. Firstly, its design allows for the temporal placement of events: lipid samples were taken before the onset of the first symptoms of atopic dermatitis, which helps distinguish cause and effect. Additionally, the lipid analysis was conducted blindly using a standardised method. However, several limitations, acknowledged by the authors themselves, must be highlighted. The spectrometry device used does not allow for the analysis of all skin lipids, leaving out some potentially relevant molecules. Moreover, samples were taken only from the inner side of the forearm, which may not reflect the lipid profiles of other body regions, such as the scalp, which can also present eczema patches. Lastly, 133 infants represent a small cohort, which reduces statistical power and increases the margin of error. Furthermore, all the included families had a history of allergies, which limits the generalisation of the results.

Further studies would therefore be beneficial to reinforce these observations. For instance, RNA sequencing of the samples could identify the genetic pathways and genes modulated prior to the clinical onset of eczema. This information could assist in better understanding the early mechanisms of the disease, or even open the way for predictive approaches during pregnancy, in connection with the genetic tests already sometimes carried out to search for certain mutations. Moreover, extended monitoring beyond the first year of life, for example at two or three years, would allow for the inclusion of cases of eczema with a later onset, which may not be detected at 12 months.

Ceramides as future biomarkers for eczema?

The identification of a lipid profile associated with an increased risk of atopic dermatitis could be a significant advancement in understanding the initiation of this disease. Today, predicting infant eczema is very challenging, particularly in children whose parents are not familiar with the dermatosis. If the results of LOWE's study were to be confirmed, it would be feasible to identify infants with a fragile skin barrier who are thus more likely to develop eczema lesions. This could be done with a simple, non-invasive and painless skin sample. It could thus be possible to act upstream, even before atopic dermatitis triggers. This could translate into the use of creams and balms rich in ceramides from the first weeks of life, to restore the lipid balance before the entry of allergens and the onset of eczema.

However, despite the significant interest in this study, these perspectives remain hypothetical. Further research, conducted on larger and more diverse cohorts, is necessary to validate the robustness of the proposed predictive model and confirm that lipid alterations precede the development of atopic dermatitis. Moreover, the integration of this type of analysis into dermatological and/or paediatric consultations implies overcoming several methodological, logistical, and economic challenges. In other words, while this avenue is promising, it cannot be concretely applied for at least several years.