Psoriasis is one of the most common human skin diseases. People with severe cases sometimes resort to immunosuppressive treatment to quell the skin scaling, itching and joint arthritis that are hallmarks of the disorder. But long-term administration of the medication can leave them vulnerable to infection and other unwanted side effects.

Now, researchers at the Stanford University School of Medicine have identified a new molecular target for potential therapies. A small protein in the skin called Rac1, which is involved in wound repair, appears to link well-known environmental triggers of the disease with a genetic predisposition to the condition. It also sheds light on the interplay between the skin and the immune system that is responsible for disease flare-ups.

“Normally there’s a quiet, ongoing conversation between the epidermis and our immune system as they work together to fight disease such as infections,” said Peter Marinkovich, MD, associate professor of dermatology. “In psoriasis, this has escalated into an uncontrollable shouting match that results in abnormal cellular proliferation, scaling and inflammation with no real effective therapies other than long-term immunosuppression. Targeting a protein in the skin, rather than quieting the immune system, could be a potential game changer for many patients and clinicians.”

A paper describing the research was published online June 13 in the Journal of Clinical Investigation. Marinkovich is the senior author, and postdoctoral scholar Marten Winge, MD, PhD, is the lead author.

Itchy, scaly patches of skin

About one of every 50 people in the world has psoriasis, which is a genetic disease characterized by itchy, scaly patches of thickened skin across the body. Many also experience pain and associated arthritis in nearby joints. It can occur at any age, and the severity of the condition can wax and wane throughout a person’s life.

Psoriasis flare-ups can be triggered when skin is damaged and the epidermal cells become hypersensitive to growth signals. That’s why many people struggle with the condition on their elbows, knees and other areas of the body that tend to get roughed up. But, strangely, the disease can also be activated in susceptible people by the bacteria that cause strep throat.

The exact mechanisms by which these events trigger the disease are unknown, and most therapies focus on quieting the immune system’s side of the noisy conversation.