A genetic finding by researchers at the National Institutes of Health provides new insight into the cause of a series of related, common and complex illnesses - including hay fever and asthma as well as the skin disorders eczema and psoriasis - and suggests a novel therapeutic approach. These illnesses are essentially inflammatory disorders of the tissues that separate the inside of the body from the outside world, such as the skin and the linings of the throat and lungs.

In the May issue of The Journal of Clinical Investigation, researchers from the National Human Genome Research Institute, the National Eye Institute, and the National Institute of Child Health and Human Development, all part of the National Institutes of Health, report that excessive production of a specific protein disrupts the protective properties of the skin barrier. Once the skin barrier is compromised, immune-system-stimulating chemicals — allergens — can enter the body and cause an inflammatory reaction that, in turn, stimulates skin cells to grow rapidly, further diminishing the protective function of the skin. The compromised barrier, in turn, becomes more porous to allergens that then stimulate more inflammation in a cycle that eventually produces common skin conditions such as psoriasis and eczema.

It may, however, be possible to break the cycle by creating a temporary, artificial barrier on the skin that blocks incoming allergens. The solution could be as simple as developing a lotion that effectively blocks allergens from getting through damaged skin. Keeping allergens out of the skin would keep the immune system from over-stimulating cell growth, giving the skin time to re-create a normal barrier. Current therapies for these skin conditions principally focus on suppressing the immune system, but the medicines used can produce undesired side-effects.

"The human body is an incredibly complex system," said Elias A. Zerhouni, M.D., director of the National Institutes of Health. "Only by conducting this kind of basic research can we hope to understand the causes of complex diseases. And only by understanding disease can we produce a future in which we can predict who is at risk, pre-empt the illness from ever occurring and personalize the treatment when it does."

Several recent studies have suggested that defects in the skin barrier may be as important to eczema and psoriasis as the hyperactive response of the immune system. In addition, doctors have observed that individuals with eczema are also likely to develop hay fever and asthma, suggesting a common mechanism for both disorders. The other risk factor for these conditions is having a relative with the disorder, suggesting a genetic connection.

To test whether a defective skin barrier can actually produce these diseases, a team of NIH researchers focused on a specific gene called connexin 26, which makes a protein that forms connections between skin cells that create the normal barrier. When the skin is intact, the production of connexin 26 is turned off once there is enough to hook all the skin cells together. When skin is damaged by a cut or a scrape, connexin 26 is produced while new skin cells reproduce and heal the wound. Researchers have shown that connexin 26 production is turned on in the sore skin of people with psoriasis, but it wasn't clear what role connexin 26 played in the disorder.