Important new studies, funded by the National Rosacea Society (NRS) research grants program, continue to increase understanding of how specific substances in the body can produce the signs and symptoms of rosacea, leading the way toward significant advances in the treatment of this widespread and often life-disruptive disorder.
"Thanks to the many thousands of rosacea sufferers who have donated to this program, we are making substantial headway in the search for more effective control of this disease that can affect the skin and eyes," said Dr. Jonathan Wilkin, chairman of the NRS medical advisory board, which selects grant proposals for funding.
In NRS-funded studies, a team led by Dr. Richard Gallo at the University of California-San Diego has found that rosacea's bumps and pimples may be the result of an immune-like reaction to environmental and emotional triggers. This reaction involves the abnormal production of cathelicidins in the body, and the scientists are now identifying further elements and reactions that may be part of this process.
Dr. Gallo explained that when the normal immune system is faced with any of a broad range of potential dangers -- such as emotional stress, heat or spicy foods -- receptors recognize the potential harm and protect the body by prompting the production of substances such as cathelicidins to neutralize any harmful effects. With rosacea, however, these protective substances take on abnormal forms and turn on the body itself, resulting in inflammation.
Last year the researchers published their discovery of abnormal cathelicidins in rosacea in the prestigious journal Nature Medicine.1 They also found that the forms of cathelicidins in rosacea may be due to an overabundance of yet another substance called kallikrein, which can spur dormant cathelicidins into action.
Further studies have now shown that the immune system of rosacea patients has a higher sensitivity to bacteria, stimulating the overabundance of kallikreins and other substances. In addition, vitamin D may play a critical role in the process as it was found to induce cathelicidins after being activated by injury or infection.
Dr. Martin Steinhoff and Dr. Thomas Luger, Department of Dermatology, University of Muenster, have been studying biological receptors, structures in human cells that bind with particular substances in the body to cause certain reactions or responses. Receptor dysfunctions may lead to disease, including rosacea, and thus identification of the mechanisms of these processes often leads to important therapeutic advances.
For example, proteinase-activated receptor 2 (PAR 2) can serve as a receptor for several molecules, including dust mite antigens and bacterial proteases, which have a high impact on inflammatory response in the skin.
In an NRS-funded study, the researchers are now defining which of the type of proteases known as kallikreins may be involved in the inflammatory responses as well as the stinging, burning and itching of rosacea. As part of their multi-pronged investigation, they recently discovered that endothelin-converting enzyme (ECE) acts on the neuropeptides known as substance P and calcitonin gene-related peptide (CGRP), and noted that any substance that inhibits ECE may be effective in the treatment of rosacea.
Yamasaki K, Di Nardo A, Bardan A, Murakami M, Ohtake T, Coda A, Dorschner RA, Bonnart C, Descarques P, Hovnanian A, Morhenn VB, Gallo RL. Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea. Nature Medicine 2007;13:975-980.