Skin biopsies from infants with atopic dermatitis feature important differences compared to adults with atopic dermatitis. These differences could change atopic dermatitis treatment for infants and toddlers with the disease, a study shows.
The study, which was published online May 3 in the Journal of Allergy and Clinical Immunology, characterizes immune and barrier properties in early-onset atopic dermatitis.
“This study shows that the pediatric atopic dermatitis phenotype is different than in adults,” said Emma Guttman-Yassky, M.D., Ph.D., Icahn School of Medicine at Mount Sinai, and the study’s corresponding author.
While treatments for early atopic dermatitis in children might be successfully targeted by Th2-directed strategies as in adults, it’s possible that children with the disease might also benefit from psoriasis targeting strategies with Th1/Interleukin (IL)-23 antagonists.
Dr. Guttman-Yassky and Amy Paller, M.D., from Northwestern University, where the children were recruited, and colleagues studied skin tissue samples from 19 children, ages three months to younger than 5 years old, with moderate-to-severe atopic dermatitis, comparing results to 18 age-matched controls, as well as 20 adults with moderate-to-severe atopic dermatitis and 11 healthy adult controls.
They found significant differences between pediatric patients with early-onset versus adult patients with longstanding atopic dermatitis in lesional and nonlesional tissues. Adult and pediatric atopic dermatitis patients shared notable Th2-centered inflammation. But pediatric atopic dermatitis skin had significantly skewed for Th17/Th22, while lacking the TH1 upregulation common in adult atopic dermatitis. Th17 skewing is a hallmark of adult psoriasis expression.
Filaggrin expression, which is common in adult atopic dermatitis, was absent in the pediatric patients’ skin samples in this study. And while epidermal differentiation and cornification products are generally downregulated in adult atopic dermatitis, children with the disease exhibited relatively normal expression in both.
“The lack of terminal differentiation abnormalities in children argues against the role of filaggrin as the instigator of AD and the atopic march,” Dr. Guttman-Yassky says.
Researchers noted lipid barrier defects in both pediatric and adult atopic dermatitis skin. But there were differences, including pediatric atopic dermatitis was associated with preferential downregulation of lipid-associated mediators, and children’s lipid barrier genes showed inverse correlations with trans-epidermal water loss—a measure of epidermal barrier function.
The epidermal differentiation complex present in adult atopic dermatitis only could result from chronic immune aberration, according to the authors.
Questions remain about whether the immune changes seen in this study cause atopic dermatitis pathology, which mechanism or mechanisms are responsible for the transition from pediatric to adult atopic dermatitis, and whether any of the mechanisms noted in the study are linked to whether a child will or will not outgrow the disease, according to the study.
Brunner, Patrick M. Zhang N, et al. “Early-onset pediatric atopic dermatitis is characterized by TH2/TH17/TH22-centered inflammation and lipid alteration.” Journal of Allergy and Clinical Immunology. Published online May 3, 2018. https://doi.org/10.1016/j.jaci.2018.02.040