Skin Biomarkers Found to Predict Development of Pediatric Atopic Dermatitis

Significant alterations were observed in lipid levels and other skin biomarkers for infants who later developed atopic dermatitis (AD) vs those who did not, according to study findings published recently in Current Medical Research and Opinion.

In examining risk factors for the development of pediatric AD, parental history of atopic disease and occurrence of common filaggrin gene (FLG) mutations have been cited. Moreover, patients with AD have important alterations in extra-cellular lipid composition, noted researchers, such as shorter chain lengths of fatty acids (FAs) in ceramides and of free FAs, which further reduce the performance of the skin barrier.

“Several hundreds of ceramide species can be identified, which differ in the type of sphingoid base (SB) and FA chain. There are 4 main SBs, dihydrosphingosine (DS), sphingosine (S), 6-hydroxy-sphingosine (H), and phytosphingosine (P), which in combination with varying FA chains give rise to 12 main ceramide (CER) classes,” they explained.

“Identification of predictive biomarkers is important to guide future prevention efforts and ultimately halt the atopic march…The role of the chain length variability of the SB in AD has not been investigated.”

The study authors conducted a nested case-control study of the prospective Copenhagen Baby Skin birth cohort to determine whether selected skin biomarkers, derived via stratum corneum tape strips in infants with clinically normal skin at 2 months of age, were different in children who develop AD in the first year of life vs those who do not.

Natural moisturizing factor (NMF), corneocyte surface protrusions, cytokines, free SBs of different chain lengths, and their ceramides were analyzed from tape strips collected at 2 months of age before onset of AD using liquid chromatography, atomic force microscopy, multiplex immunoassay, and liquid chromatography mass spectrometry, respectively.

Of the 300 children followed prospectively from birth until 2 years of age, 44 random children with onset of AD in the first year of life were matched on sex and season of birth with 44 children who did not develop AD.

Among children who developed AD, 66% had parental history of atopy compared with 52% of children who did not develop AD (P = .4). The median age of AD onset was 4.0 months, and the median Eczema Area and Severity Index (EASI) score was 4.2.

Between the 2 cohorts, significant alterations were observed for 4 lipid markers, with P levels shown to be significantly lower in children who developed AD vs children who did not (median 240 vs 540 pmol/mg; P < .001).

The 2 groups of children also differed in the relative amounts of SB of different chain lengths (C17, C18, and C20), and thymus- and activation-regulated chemokine (TARC/CCL17) was slightly higher in those who developed the skin disease.

P was indicated to have the highest prediction accuracy among the biomarkers (75.6%), whereas the combination of 5 lipid ratios (DS, S, P, H, CER) gave an accuracy of 89.4%. NMF and corneocyte surface texture ratios were conversely similar for both cohorts.

The researchers acknowledged that since no predictive studies have been done for other skin diseases (eg, psoriasis), findings may not be specific to AD. The selection of biomarkers previously identified in clinical studies was also noted as a limitation, as some important biomarkers may have been overlooked.

Reference

Rinnov MR, Hailing AS, Gerner T, et al. Skin biomarkers predict development of atopic dermatitis in infancy. Allergy. Published online September 16, 2022. doi:10.1111/all.15518