JAN-FEB 2016

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© GETTY IMAGES is unclear. "I think that people who believe rosacea is caused by Demodex mites are a little mono-focused," says Mary Lupo, MD, founder of the Lupo Center for Aesthetic & General Dermatology in New Orleans. "We all have Demodex mites—but there's a subset of people that mounts a more robust infl ammatory response to them." Cleveland-based scientist and dermatologist Daniel Popkin, MD, PhD, is similarly skeptical of the research— though antimicrobial/antiparasitic topicals such as ivermectin kill the mites and appear to work, a crucial step was skipped. "There are associations with this mite and rosacea, and indeed the ivermectin cream works, but the researchers never actually looked at mite counts. It would have been a good opportunity to address the relationship between mites and rosacea," he says. Rosacea typically affects patients with lighter skin types, particularly skin types I and II (though it does occasionally affect darker-skinned patients too). It's no surprise then that in his research on genetic and environmental contributions to rosacea, Dr. Popkin found that the main risk factor was sun exposure, followed by the patient's age. "The biggest driver by far was sun exposure, and then age was also an independent predictor. They are obviously co-linear in the sense that as you get older you have more cumulative sun exposure, but even independent of each other there was a signal there," he says. It's not uncommon for rosacea triggered by sun exposure to also result in photo damage—increases in infl ammatory mediators lead to increases in free radical production. "Patients with rosacea tend to have concomitant photo damage; erythema develops as a result of free radical production, subsequent infl ammation and chronic sun exposure, which leads to collagen degradation," says Dr. Berson. "These patients with sensitive skin have compromised barrier function, chronic oxidative damage and increased blood fl ow to the skin." Patients most commonly present with erythematotelangiectatic rosacea—fl ushing, redness and dilated capillaries—and some develop papules and pustules as well. "It's the redness and visible vessels that have traditionally been the more diffi cult aspect to treat," says New York City-based dermatologist Diane S. Berson, MD. "Patients with rosacea tend to have skin that's very sensitive and very easily infl amed." CAUSES AND TRIGGERS While physicians and researchers now have a more thorough understanding of how certain triggers cause fl are-ups in patients with rosacea, the specifi c cause of the disease has not been identifi ed. "There are many different infl ammatory mediators involved with the pathogenesis of rosacea, and every day we're learning more," Dr. Berson says. "Triggers may stimulate increased innate immunity, infl ammation and vascular hyperactivity." "Over the past several years, we have learned a lot about how and what the trigger factors of rosacea are causing," says Julie C. Harper, MD, president-elect of the American Acne and Rosacea Society and private practice physician at the Dermatology and Skin Care Center of Birmingham in Birmingham, Alabama. "An up-regulation of the innate immune response has garnered the most attention, with an increase in toll-like receptor 2 (TLR2) and cathelicidin activity in rosacea-prone skin 'turning on' infl ammation. A trigger—such as Demodex mites or the bacteria in Demodex—activates TLR2, which in turn triggers cathelicidin. And cathelicidins, such as LL-37, promote infl ammation in the skin." Dr. Harper notes that some transient receptor potential channels (TRPs) also may play a role in the development of rosacea. "Certain TRPs mediate a response to spicy or hot sensations in the skin, leading to a neurogenic vasodilation," she says. The theory that Demodex mites trigger infl ammation is a popular one, though how or why they may affect rosacea | JANUARY/FEBRUARY 2016 33 Addressing the infl ammation of rosacea systemically may reduce a patient's cardiovascular risk factors as well.

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