Miller School Dermatologists Identify Genetic Triggers for Chronic Itch

A groundbreaking study by a team of University of Miami Miller School of Medicine dermatologists has identified the genetic triggers for chronic itch in patients with atopic dermatitis (eczema) and psoriasis.

“This is the first study examining all the molecular targets of chronic itch in humans with these widespread skin diseases,” said Gil Yosipovitch, M.D., professor of dermatology and director of the Miami Itch Center, one of the nation’s only comprehensive, multidisciplinary clinics dedicated to the diagnosis and management of itch disorders. “Our laboratory findings point the way to potential new clinical strategies, while expanding our understanding of the human genome.”

Yosipovitch was co-author of a new study, “The Genetics of Chronic Itch: Gene Expression in the Skin of Atopic Dermatitis and Psoriasis Patients with Severe Itch,” published January 6 in the Journal of Investigative Dermatology. Leigh A. Nattkemper, Ph.D., an instructor in the Department of Dermatology and Cutaneous Surgery, was the lead author, and Kristen M. Sanders, M.S., a graduate student, was a co-author.

Every year, more than 3 million Americans are diagnosed with eczema, a rash that often develops in childhood and frequently runs in families. Another 3 million people are treated for psoriasis, a disorder that leads to dry, scaly patches on the skin.

“We used RNA sequencing to analyze the complete transcriptome [genetic expression] in skin from 25 eczema patients who complained of chronic itch and 25 without itch,” Yosipovitch said. “We also compared skin samples from 25 psoriasis patients with itch and 25 without itch, as well as site-matched biopsies from 30 healthy controls.”

After identifying 18,000 differentially expressed genes common to itchy eczema and psoriatic skin compared with healthy skin, the Miller School researchers determined that almost 2,000 genes were differentially expressed between itchy and non-itchy skin in atopic and psoriatic subjects.

“By considering the itch-associated proteins analyzed in our molecular studies and immunohistochemistry studies, we were able to identify a fingerprint of itch-associated mediators and receptors in eczema and psoriasis,” Yosipovitch said.

Although there were differences in the proteins associated with each group of skin samples, the researchers identified a common set of components for both itchy and non-itchy eczema and psoriasis.

“These proteins are connected to all aspects of itch transmission at the peripheral level and are expressed by skin cells, immune cells, and nerves,” Yosipovitch said. “This ‘itchscriptome’ analysis will lead to an increased understanding of the molecular mechanisms of the chronic skin diseases and provide new targets for itch treatment.”

The study was partially financed by Denmark’s Leo Foundation, which supports international dermatological research projects and activities that address issues in disease understanding, disease treatment, disease awareness and patient wellbeing.

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