MIAMI BEACH – Rather than working to identify a particular rosacea subtype in your patient, adopt a simpler strategy and treat based on presenting signs, Dr. James Q. Del Rosso said at the South Beach Symposium.
"Why not evaluate and treat a patient with rosacea based on the clinical features they present with?" Dr. Del Rosso asked. For example, the common feature in the vast majority of patients is central facial diffuse erythema. "We are talking about 80% or 90% of the patients we see."
Rosacea is an umbrella term. "We talk a lot about subtypes, but that doesn’t necessarily answer all the questions," Dr. Del Rosso said. "I want to suggest we narrow the definition a bit so we focus on the more common clinical situations in practice."
Dr. James Del Rosso
In other words, rather than distinguishing papulopustular rosacea from erythematotelangiectatic or phymatous subtypes, consider whether a patient has intermittent or persistent rosacea. Intermittent rosacea features inflammatory lesions, perilesional erythema, and background erythema. In contrast, persistent rosacea will present as background erythema (more prominently), as well as telangiectasias and phymatous changes to the skin.
This classification reflects more "real world" presentations of rosacea, said Dr. Del Rosso, a dermatologist in group practice in Las Vegas.
Treatment
The clinical features of rosacea go beyond diagnosis classification and can guide selection of therapy as well. In terms of topical therapies, metronidazole 1% and 0.75% and azelaic acid 15% gel are approved by the Food and Drug Administration to treat papulopustular rosacea, which is characterized by inflammatory lesions, erythema, and telangiectasias.
"There is a mechanism supporting why topical or oral metronidazole is effective," Dr. Del Rosso said. Metronidazole modifies the augmented, innate immune response implicated early in the development of rosacea. In terms of azelaic acid, data about mechanism of action are only available in mice.
This immune response occurs very early in the pathogenesis of rosacea and during flares, Dr. Del Rosso said. Researchers have identified another important pathway, a neurogenic vascular dysregulation that could explain the vasodilation and diffuse erythema commonly seen in many patients. Although it is unclear which mechanism arises first, Dr. Del Rosso said, "I’m going to roll the dice and I will [guess that] innate immunity happens first."
Conventional oral agents can treat rosacea effectively as well. Tetracyclines, for example, work through a variety of anti-inflammatory effects. "Current evidence does not support the need to eradicate or suppress a bacterium," Dr. Del Rosso said. For this reason, multiple studies support the efficacy of subantimicrobial doxycycline for its anti-inflammatory actions (Am. J. Clin. Dermatol. 2010;11:217-22; Cutis 2010;86:16-25).
Recent evidence suggests lower-dose doxycycline (40-mg extended-release doxycycline, for example) is sufficient to inhibit matrix metalloproteinase (MMP) enzymes that break down connective tissue proteins (Pharmacol. Res. 2011;63:130-45). MMPs are upregulated in rosacea and other conditions that feature dermal destruction.
"All of the tetracyclines seem to work on blocking MMP activity, but doxycycline works the best," Dr. David E. Cohen said in a separate presentation at the meeting. Doxycycline can inhibit multiple pathways involved in rosacea, he said. Recent findings "suggest a previously unknown mechanism of action of subantimicrobial doxycycline."
Cathelicidin Pathways
Another new finding is that the MMP pathway and the cathelicidin pathways are no longer thought to be distinct, said Dr. Cohen of the department of dermatology at New York University Langone Medical Center in New York City.
"Last year I said these two things were independently elevated [in rosacea]," Dr. Cohen said. "Now we know they can trigger each other. It’s a vicious cycle, a vortex."
Cathelicidins are protective peptides in the skin. These endogenous players cleave and kill virus and fungi and recruit a host immune response, Dr. Cohen said. "They are inactive normally. So the cathelicidins are there for a good reason, but they are always ‘on’ in rosacea." When these peptides are overexpressed, as they are in rosacea, they can trigger inflammation and angiogenesis.
A specific cathelicidin garnering a lot of attention is LL-37, a vasoactive and inflammatory host-defense peptide also overexpressed in rosacea. "This is very important," Dr. Del Rosso said. "LL-37 just keeps popping up in the pathogenesis of skin disorders." Various levels of LL-37 are implicated in atopic dermatitis and cutaneous lupus, for example. In healthy skin, LL-37 helps to maintain homeostatic immunity and fights bacteria and viruses in the skin.
Dr. Del Rosso disclosed that he is a consultant, researcher, and member of the speakers bureaus for Allergan and Galderma. Dr. Cohen disclosed that he is a consultant for, receives honoraria from, and is on the advisory board for Galderma.