Study offers new insight into pediatric eczema
For the first time, researchers have identified the skin phenotype of pediatric atopic dermatitis (AD) — a finding that challenges the notion of filaggrin's central role in disease elicitation and instigation of the atopic march, according to a new study.
In a groundbreaking study on pediatric atopic dermatitis (AD), researchers found the skin phenotype in adults with AD is much different than that of new-onset AD in children.
This study, published online September 15 in the Journal of Allergy and Clinical Immunology and funded by the LEO Foundation, which owns LEO Pharma, offers new and important information about the common skin disease among children, according to study author Emma Guttman-Yassky, M.D., Ph.D., dermatology professor and vice chair at the Icahn School of Medicine at Mount Sinai.
"We now know a lot about eczema in adults. But the disease in adults is a chronic disease of many years of disease activity, because they usually have it from childhood. In fact, 85% of cases start in children," Dr. Guttman-Yassky says.
What researchers don't know is if AD of children and adults are similar.
The collaboration between dermatologist Dr. Guttman-Yassky and her lab at Icahn School of Medicine and pediatric dermatologist Dr. Amy Paller's lab at Northwestern University Feinberg School of Medicine, Chicago, accomplished something unique in the study of pediatric AD.
"[Dr. Paller] managed to get blood and skin biopsies from small children, less than five years old, and within six months of disease initiation, capturing real disease initiation. The children had moderate-to-severe disease," Dr. Guttman-Yassky says.
Researchers compared the findings in lesional and nonlesional skin of 19 pediatric AD patients, to lesional and nonlesional skin of 15 adults with AD and, for contrast and comparison, 10 adults with psoriasis and eight adult controls.
The early pediatric skin samples reveal distinct differences from adults with AD.
Like adults, in skin of children. there is activation of Th2 lymphocytes. But there also is marked activation of other cytokine axes that are usually not significantly up-regulated in adult AD, including Th17. The marked Th17, Th2 and Th22 activation at disease-onset was found not only in lesional but also nonlesional skin.
In fact, surprisingly, the phenotype of the infants and young children with early AD was found to share some molecular features with psoriasis, such as the Th17 up-regulation.
"The nonlesional skin of children is extremely abnormal — even more so than in adults. They have increased epidermal thickness and marked increases in immune cytokines, and that's probably representing a stage of ‘true’ disease initiation," Dr. Guttman-Yassky says. "And since atopic dermatitis is considered the window to the whole atopic march, children often start with atopic dermatitis/eczema in the first year of life, then progress to have food allergies, followed by nasal allergies and asthma. … the non-lesional [skin] of children with severe disease is so abnormal, perhaps, early systemic intervention may not only treat AD, but perhaps prevent development of the entire atopic march.”
The findings also challenge the widely held belief that filaggrin is the instigator of eczema and primary initiator of the atopic march.
"In this study that allowed us to look at disease initiation, we found that filaggrin expression in children was not abnormal as it is in adults. That's a really important point," Dr. Guttman-Yassky says. "In adults, filaggrin expression is really very abnormal, with very low levels of filaggrin."
Dr. Guttman-Yassky says the next step is to study systemic treatments, like dupilumab, in children with moderate-to-severe disease.
Disclosure: Dr. Guttman-Yassky is a board member for Sanofi Aventis, Regeneron and has received consultancy fees from Regeneron and Sanofi. She is also a board member of Stiefel/GlaxoSmithKline, MedImmune, Celgene, Anacor, AnaptysBio, Celsus, Dermira, Galderma, Glenmark, Novartis, Pfizer, Vitae and Leo Pharma; has received consultancy fees from MedImmune, Celgene, Stiefel/GlaxoSmithKline, Celsus, BMS, Amgen, Drais, AbbVie, Anacor, AnaptysBio, Dermira, Galderma, Glenmark, LEO Pharma, Novartis, Pfizer, Vitae, Mitsubishi Tanabe and Eli Lilly; and has received research support from Janssen, Regeneron, Celgene, BMS, Novartis, Merck, LEO Pharma and Dermira.