Identification of subphenotypes of atopic dermatitis (AD) in children, with differing risk factors, prognoses, and comorbidities, could lead to a stratified approach to managing pediatric AD, said Lavinia Paternoster, PhD, of the University of Bristol, England, and her associates.

Mothers completed questionnaires about an itchy rash and other factors associated with atopic dermatitis (AD) both in an English birth cohort study of 14,701 children aged 6 months-16.5 years and in a Dutch multicenter birth cohort of 3,963 children aged 3 months-11 years. DNA tests determined whether the children had filaggrin (FLG) gene mutations and other genotypes associated with AD risk. To determine heterogeneity in patterns of AD, longitudinal latent class analysis was used.

The study identified six classes of AD in these children. Early-onset/early-resolving AD, occurring in 13%-15% of the children, was most prevalent and was associated with male gender. Children in this class had a favorable prognosis, and there was only a very weak association with asthma in later life.

Two classes of persistent disease were identified: early-onset persistent AD (rash occurring in most of this class by 30 months and resolving in half by 16.5 years) and early-onset/late-resolving AD (rash occurring in most by 30 months and resolving in most by 16.5 years). These classes, occurring in about 7% of the children, had the strongest association with an AD genetic risk score; a strong link with personal and parental history of atopic disease; and a strong tie to asthma.

An unrecognized class of mid-onset-resolving AD, occurring in 7% of children, was not significantly linked to FLG mutations but was tied to asthma. In those children, AD prevalence rose sharply from 2.5 years of age and peaked at about 6 years, Dr. Paternoster and her associates said.

The investigators also found an unaffected/transient AD class in which children either had never reported rash; had one or two isolated occasions of rash; or reported a rash consistent with AD at 6-18 months that declined with age. In the two cohorts, 58%-63% children fell into this class. Late-onset-resolving AD occurred in 7%-8% of children, with most developing rash by 12 years and declining by 16.5 years.

There was a preponderance of females in the early-onset persistent AD and the late onset classes, and more males in the early-onset resolving class. “The associations with asthma at ages 7 and 11-13 years were strongest with the persistent class, but all AD classes showed evidence of some increased risk of asthma at these ages,” Dr. Paternoster and her associates wrote.

“There was evidence that FLG null mutations were associated with all classes, however … the association was strongest in the group with early-onset-persistent disease,” the researchers said. The “heterogeneity of effect of genetic variants on different disease profiles, emphasizes the need for patient stratification in future genetic studies. Stratification may be used to increase the power to detect variants associated with specific classes; stratification could also allow the identification of phenotype-specific mechanistic pathways as future therapeutic targets.”

Read more at (J Allerg Clin Immunol. 2017 Nov 10. doi: 10.1016/j.jaci.2017.09.044 ).


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