Scientists Discover Clues To Rosacea Skin Ailment

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Main Category: Dermatology
Also Included In: Immune System / Vaccines;  Genetics
Article Date: 06 Aug 2007 - 3:00 PDT

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A new study by scientists from the US, France and Japan appears to have found what causes acne rosacea to develop, a common inflammatory skin ailment that affects the over 30s and is also known as adult acne.

The research is published in the advanced online edition of the journal Nature Medicine and was led by Dr Richard L. Gallo, professor of medicine and chief of the Division of Dermatology at the University of California, San Diego (UCSD) School of Medicine and the Dermatology section of the Veterans Affairs San Diego Healthcare System.

Acne rosacea is an inflammatory skin disease that affects about 14 million Americans between the age of 30 and 60 and is more common in women than in men. It is more likely to affect fair skinned people of European or Celtic descent. Rosacea is characterized by facial redness (erythema), bumps and pimples (papulopustules), and spider veins (telangiectasia). The condition is chronic and gets worse over time. It is cyclical and flares up for weeks and months and then subsides. There is no effective treatment although antibiotics are sometimes prescribed with mixed results.

Triggers for rosacea usually involve anything that causes the face to become flushed such as demanding exercise, sunburn, stress, anxiety, and sudden changes in temperature like moving from a cold to a hot environment. Other triggers arise from food and drink that cause flushing such as alcohol, hot caffeine drinks (tea, coffee), and certain spicy foods. Rosacea can even be triggered by blushing with embarrassment.

The scientists found that people with rosacea have high levels of the anti microbial peptide cathelicidin in their skin and the proteins this produces are different to those found in people who do not have the disease. Another important contributor is an enzyme called stratum corneum tryptic enzyme (SCTE).

Gallo said:

"It's like having lots of gasoline and a match."

He and his team found that over-production of two inflammatory proteins leads to high levels of a third protein that causes rosacea symptoms, "A trifecta of unfortunate factors in people with rosacea," said Gallo.

They first noticed in the laboratory that anti-microbial peptides, small proteins of the immune system, caused the same redness of skin, bumps, pimples and spider veins seen in rosacea patients. And these peptides were triggered by the same things as rosacea.

When they looked at patients with rosacea they found that every one of them had more of these peptides than normal.

The surprising thing about the discovery is that the precursor to the peptides they found is another peptide, cathelicidin, which is thought to protect the skin from infection. A range of other diseases with skin inflammation is linked to a shortage of cathelicidin. But in rosacea patients the scientists found the opposite: too much cathelicidin, altough it was a different type to that found in people who do not have the disease.

They also found that patients with rosacea had too much SCTE, which converts cathelicidin into the immune system peptides that lead to rosacea.

So they tested the effect of the two substances by injecting laboratory mice with the cathelicidin peptides found in rosacea, adding SCTE, and increasing their protease activity by switching off a gene (Spink5, the protease inhibitor). Each of these increased inflammation of the skin.

They also tested the role that cathelicidin plays in helping inflammation caused by SCTE by deleting the gene that codes for it in mice, the Camp gene.

Gallo explained that:

"Too much SCTE and too much cathelicidin leads to the abnormal peptides that cause the symptoms of this disease."

He also explained why antibiotics sometimes work in treating rosacea, even though the condition is not caused by bacteria:

"Antibiotics tend to alleviate the symptoms of rosacea in patients because some of them work to inhibit these enzymes. Our findings may modify the therapeutic approach to treating rosacea, since bacteria aren't the right target."

"Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea."
Kenshi Yamasaki, Anna Di Nardo, Antonella Bardan, Masamoto Murakami, Takaaki Ohtake, Alvin Coda, Robert A Dorschner, Chrystelle Bonnart, Pascal Descargues, Alain Hovnanian, Vera B Morhenn and Richard L Gallo.
Nature Medicine Published online: 05 August 2007.
doi:10.1038/nm1616

Abstract.

Written by: Catharine Paddock
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