Implicating Differences Found Between Early Onset, Longstanding Atopic Dermatitis

Emma Guttman-Yassky, MD, PhD

For the first time, researchers have found substantial differences in the initiation of early onset atopic dermatitis (AD) in pediatric and that of the longstanding form of the disease in adults.

A wide genomic analyses conducted by a team from Mount Sinai Health System reported disparities in both lesional and non-lesional tissue in the skin of both patient groups with AD. The discovery could have a significant impact on the methodology of care for children with AD — a population that comprises 15-20% of US children.

The study observed the skin biopsies of 19 children, aged 3 months to 5 years old, with early onset AD that had been diagnosed in the previous 6 months and were suffering from a moderate to severe form of the disease. Researchers assessed AD severity through the Scoring Atopic Dermatitis (SCORAD) calculator. Pediatric patients reported a mean SCORAD score of 57.8, and a range from 33-84.

A group of 18 healthy subjects undergoing routine surgical procedures served as a control population, with tissue samples collecting during their surgeries for comparison.

Lesional and non-lesional tissues of 20 adults with AD — aged from 18-73 years — were pulled from previously reported cohort studies involving patients with similar disease severity. Subjects’ mean SCORAD score was 62.4, ranging from 44-97.

Microarray, RT-PCR, and fluorescence microscopy studies reported that pediatric patients had strong T helper cell (Th) 2 and Thr17/Th22-centered inflammation in their tissue. However, they lacked the Th1 activation and epidermal barrier abnormalities characteristically found in adult patients with AD. The discovery bucks even the basic understanding of disease pathology.

“A strong immune infiltrate and impaired skin are thought to characterize the disease, but their initial sequence and exact interplay are still not fully understood,” researchers wrote. “AD usually begins before age 5 years, with approximately 60% of patients experiencing disease onset within the first year of life.

The data suggests to researchers that abnormal barrier function in the skin of pediatric patients with AD indicates defects in tight junction proteins and lipid deposition, not reduced differentiation.

The inflammatory-based differentiation came as a big surprise to researchers, corresponding author Emma Guttman-Yassky, MD, PhD, Vice Chair, Department of Dermatology at the Icahn School of Medicine, said.

“We were quite impressed with the findings,” Guttman-Yassky said. “Children had no Th1 activation and no barrier abnormalities.”

Due to the severe rate of AD in pediatric patients, Guttman-Yassky emphasized the need to understand if breakthrough therapies currently developed, marketed for, and proven to benefit adult patients can apply to the younger population.

“However, according to this study, it is becoming clearer that the pediatric population may need different treatment approaches than adults as the AD phenotype shows major differences than the adult phenotype,” Guttman-Yassky said.

The findings also bring to question the role of phenotype in the development of the atopic march in patients, Guttman-Yassky said. The common theory suggests that patients with an allergic disease are more likely to develop another, or multiple allergic diseases in their lifetime. The progression commonly begins in infants with AD, who are likely to develop food allergies, asthma, or hay fever in their later childhood.

Regardless of its implications, the results have forced researchers to reconsider practice of pediatric AD care.

“I think we are in a very interesting time now,” Guttman-Yassky said.

The study, "Early-onset pediatric atopic dermatitis is characterized by Th2/Th17/Th22-centered inflammation and lipid alterations," was published online in the Journal of Allergy and Clinical Immunology Thursday morning.