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The Argument For Orals The potential systemic implications of inflammation make a strong argument for the use of oral medications that decrease the inflammatory response throughout the body. Low-dose tetracycline derivatives—particularly doxycycline prescribed at 40mg—are effective in reducing the inflammatory response. "More than ever we are aware that oral medications can make responses much more rapid and complete," says Dr. Fried. "That and our additional understanding of inflammatory mediators really pushes us to say why don't we get this under control more quickly and quell the inflammation more quickly, because we don't want to leave inflammatory mediators floating around the body where they potentially could be damaging other organ systems." In some cases, antidepressants that help restore normal levels of neurotransmitters in the brain can also provide relief to patients, says Dr. Fried, who adds "Perhaps things like fish oil, vitamin D3 and evening primrose oil can play a role in decreasing inflammation in some people." Though inflammation is closely associated with rosacea, it also plays a key role in acne. "When we think of the pathogenesis of acne, there has been mouth. Because of that—and the fact that our society has developed a zero tolerance for side effects—many clinicians are fearful to move to some of the oral agents," says Dr. Fried. "I think what most of us do is, if we see someone who has really angry rosacea and we know the topicals will be ineffective or will take forever to become effective than many of us move toward the orals, particularly the low-dose doxycycline." He notes that when prescribed at doses under 50mg, doxycycline will not change the natural balance of bacteria and fungus in the body: "They cannot promote resistant bacteria, so we do tend to jump on board sooner. But on borderline calls, I think clinicians go either way." "Some of the inflammatory mediators actually cross over into the brain and directly affect what happens in the brain." a change—a whole shift," says Diane Berson, MD, associate clinical professor of dermatology at Cornell Medical College and attending dermatologist at New York Presbyterian Hospital. "We are now thinking that acne is more of an inflammatory condition. Rather than thinking of bacteria, we're thinking more of inflammation as being the root cause of acne." The Preference for Topicals Though oral medications can provide faster relief than topicals, the public's distrust of systemic medications may lead patients to opt first for topical interventions. "The public has become increasingly suspicious and fearful of anything taken by For mild to moderate cases of rosacea, there are several topical ingredients that can help reduce inflammation in the skin. "Some of the prescription medications that are out there—azelaic acid and metrodinazole—are antiinflammatory and proven to decrease redness and reactivity of the skin," says Dr. Fried. "We know that topical antioxidants, like green tea polyphenols, hyaluronic acid and caffeine, bind the free radicals and decrease local inflammation in the skin" Oral tretinoin and topical retinoids are front line treatments for acne that may also provide relief to rosacea patients. "One thing I want to get across to physicians is that retinoids are antiinflammatory," says Dr. Berson. "They decrease the inflammatory mediators Continued on page 20 medestheticsmagazine.com | July/August 2013 17 © istockphoto.com According to Richard Fried, MD, PhD, clinical director of Yardley Dermatology Associates and Yardley Clinical Research Associates in Yardley, Pennsylvania, the damaging effects of an over-aggressive inflammatory response may be more than skin deep. "Very recently, we've learned that some of the inflammatory mediators actually cross over into the brain and directly affect what happens in the brain," he says. "What seems to happen with certain inflammatory mediators, specifically neuropeptides, is once they enter the brain, they actually increase reuptake of neurotransmitters." The depletion of neurotransmitters, particularly the big three—serotonin, dopamine and norepinephrine—may create what Dr. Fried refers to as a "double hit theory." "Living with the entity of rosacea is, in its own right, depressing and, concomitantly, we may well be getting chemically depleted and depressed centrally," he says. "What do we do about this? The answer is that controlling inflammation in the skin is more important than ever."