Psoriasis is a disease of the skin (your natural barrier between the inner body and the environment); it reacts to outside stimuli through irritation and inflammation. Due to this concept, researchers at the National Institutes of Health have a new insight after reviewing the findings of a genetic study.

Researchers from the National Human Genome Research Institute, the National Eye Institute, and the National Institute of Child Health and Human Development (all of which are part of the National Institutes of Health) report that overproduction of a specific protein disrupts the protective properties of the skin barrier.
Once the skin barrier is compromised, immune-system-stimulating chemicals can enter the body and cause an inflammatory reaction that, in turn, stimulates skin cells to grow too rapidly. The skin becomes more porous, allowing even more impurities to enter, creating a vicious cycle - leading to psoriasis.

By creating a temporary, artificial barrier that blocks allergens (impurities), it may be possible to halt this cycle, allowing the skin to recuperate. The solution could be as simple as developing a lotion that effectively blocks allergens from getting through damaged skin.

These defects in the skin may be as important to psoriasis as the immune system is. Doctors have also found that individuals with eczema or psoriasis are also likely to develop hay fever and asthma, suggesting a common culprit for both disorders.

The focus of the study was a gene called connexin 26 which makes a protein that forms the connection between skin cells. In unbroken skin, the protein is not made once there is enough to hold the cells together. Cuts or scrapes trigger the protein production again while the new skin cells heal the wound. This protein production is active in psoriatic skin tissues, but further study was needed to see what part it had in psoriasis.

A line of transgenic mice that overproduce connexin26 was created to determine the protein's connection with psoriasis. These are mice whose gene structure has been altered by adding genes from another species, in this case, human genes. The resulting mice developed psoriatic-type skin sores, just like humans with psoriasis.

"Hopefully, this will help us understand the complex genetics of psoriasis," said Julia A. Segre, Ph.D., an investigator in NHI's Genetics and Molecular Biology Branch and the senior author on the paper. "Previous genetic studies have focused on the genes that regulate immune response. We are now examining the effect of genes that are involved in both regulating the growth of skin cells and signaling to the immune cells."

The problem causing psoriasis may simply be the body over-reacting to impurities getting through the skin. "The skin goes into a stress response and overcompensates by trying to rebuild the barrier too fast, actually becoming less effective," Dr. Segre said. "The skin cells grow so fast that they fail to make a normal barrier, and the body is stimulating the immune response because of material (chemicals and allergens) coming through the barrier."

Understanding the genetics of skin disorders like psoriasis and eczema may well have important implications for more serious illnesses, such as asthma. It is not uncommon for a family doctor to face the dilemma of a child who has eczema or psoriasis and then have to decide how aggressively to treat the disease. Eczema is not particularly dangerous, but children presenting with eczema commonly go on to develop asthma, which severely compromises quality of life and in rare cases can be lethal.

Treating eczema with immune-suppressing drugs, which may also prevent asthma from developing, may cause undesirable side effects. If the barrier theory is correct, both disorders as well as psoriasis would be corrected simply though barrier application at the first signs of the skin disorder.

The genetic studies suggest that researchers now need to focus on both turning down the immune response and therefore the production of connexin26's protein, as well as restoring a normal skin barrier to keep the outside world out of the body. An artificial, temporary barrier (such as a specifically developed lotion) may be just the thing to accomplish this feat.