Emma Guttman-Yassky, MD, PhD
An estimated 31 million adults, and between 10 and 20 percent of children in the United States, have atopic dermatitis (AD), a common skin disorder commonly known as eczema. Another 8 million U.S. adults have psoriasis. Both are chronic and complex inflammatory skin conditions that involve systemic inflammation, skin-barrier disruption, and genetic and environmental factors.
AD results in widespread rashes and patches of dry, itchy skin when an individual’s immune system goes into overdrive. It highly interferes with a patient’s everyday life, causing a terrible itch that often disrupts sleep and other daily activities. Psoriasis is a disorder that causes skin cells to multiply up to 10 times faster than normal, making the skin build up into bumpy red patches covered with silvery white scales. Over the years, researchers, including Emma Guttman-Yassky, MD, PhD, at the Icahn School of Medicine at Mount Sinai, have made vast advances in understanding and treating AD and psoriasis.
Most recently, Dr. Guttman-Yassky, working with researchers from Mount Sinai and collaborating institutions, revealed progress on another front—finding a gene biomarker that could accurately differentiate between AD and psoriasis using less-invasive adhesive skin tape strips and avoiding skin biopsy.
“In the past, skin tissue biopsies have always been considered the gold standard for distinguishing between inflammatory skin diseases, but they can cause pain, scarring, and increased risk of infection,” says Dr. Guttman-Yassky, an expert in the molecular and cellular pathomechanisms of inflammatory skin disease. Her past revolutionary research on AD promoted development of targeted therapeutics for it. “Using small adhesive tape strips may provide, for the first time, a minimally invasive alternative to skin biopsies for monitoring biomarkers of patients with these particular skin diseases and beyond.” The team’s findings were published online in The Journal of Allergy and Clinical Immunology on Tuesday, July 21.
While tape strips are currently being used to help define unique genes and pathways, what the researchers were lacking was a comprehensive tape-strip molecular profile that would accurately capture the global gene signatures of lesional and nonlesional skin in AD and psoriasis—and differentiate one from the other.
Adhesive tapes are able to characterize atopic dermatitis and psoriasis skin profiles and identify a single biomarker that is able to accurately discriminate between these conditions with 100 percent accuracy.
In the study, the researchers evaluated tape strips obtained from 20 adults with moderate to severe AD, 20 with moderate to severe psoriasis, and 20 healthy individuals. The tape strips were placed on the skin and pressure was applied with fingers for approximately five seconds to capture the stratum corneum—the outer layer of the skin—and the upper part of the granular layer, a thin layer of cells.
From each subject, 20 tape strips were collected, some from lesions and the rest from clinically unaffected skin. The skin cells collected from the tape strips were subjected to global molecular profiling for identification of disease-related biomarkers.
After analysis, the researchers identified a single gene biomarker, nitride oxide synthase 2 (NOS2) that—with 100 percent accuracy— was able to distinguish between AD and psoriasis.
The researchers also captured other genes related to immune and epidermal barrier function that were dysregulated in AD and/or psoriasis, and that also distinguished each disease from the other. For example, tape strips from AD patients strongly expressed cell markers related to T-helper 2 (Th2) immune response, which is characteristic of AD, while psoriasis patients displayed much higher levels of Th1 and Th17 cytokines, which are characteristic of psoriasis.
Dr. Guttman-Yassky is the Sol and Clara Kest Professor and Vice Chair of the Kimberly and Eric J. Waldman Department of Dermatology at the Icahn School of Medicine at Mount Sinai. In January 2021, she will become its Chair—the first woman to serve as Chair of a Department of Dermatology in New York State. She will succeed Mark Lebwohl, MD, a legendary physician who has served with distinction as Chair of the Department for 24 years. Dr. Lebwohl has been promoted to Dean for Clinical Therapeutics.
Earlier in July, Dr. Guttman-Yassky received a National Institutes of Health (NIH) / National Institute of Allergy and Infectious Disease (NIAID) grant to study immune responses of patients with inflammatory skin diseases in the setting of COVID-19 infection.
Specifically, she will investigate whether systemic medications and biologics, such as dupilumab—a monoclonal antibody that binds to an inflammatory molecule, IL-4 receptor alfa, and inhibits the inflammatory response that leads to rashes and itching from atopic dermatitis/eczema—may have a positive or negative impact on COVID-19 responses in patients who have the disease. This two-year award is an addition to a seven-year grant by the NIH/NIAID to study mechanisms leading to variations in atopic dermatitis phenotypes.
Preliminary anecdotal reporting has shown that patients who have moderate to severe atopic dermatitis who take a biologic treatment such as dupilumab seem to be protected from developing serious complications of COVID-19 and are also less likely to be hospitalized due to complications.
According to Dr. Guttman-Yassky, Mount Sinai’s dermatology practices have more than 1,200 moderate-to-severe atopic dermatitis patients who are taking dupilumab, and no patients in her practice, to her knowledge, have reported being hospitalized with COVID-19, although many, she says, have been exposed to the disease.
The ultimate goal of the study is to help determine whether systemic treatments, including specific monoclonal antibodies, impact responses to COVID-19 infection, and whether some of these treatments can protect from deleterious COVID-19 effects.
“Understanding these immune responses in the presence of patients with atopic dermatitis is extremely important, as it will help to guide how we treat patients with COVID-19 during this very critical period and help provide a possible new treatment directed towards this virus,” she says. “This research project has the potential to directly impact the medical care of tens of thousands of patients in the United States with atopic dermatitis on systemic medications in the setting of the COVID-19 pandemic, reducing morbidity and mortality, particularly in populations disproportionately affected, such as African Americans.”