Rosacea treatment shifts focus

Rosacea has always been challenging to treat, but continued research of late has forged a better understanding of the potential pathogeneses of the disease, with the common denominator appearing to be inflammation. Although more work needs to be done, this relatively new insight into rosacea has already opened the door for novel effective therapeutic approaches, bringing much needed relief to rosacea patients.

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Much has been learned over the past decade about rosacea, but perhaps one of the most important pieces of the rosacea puzzle is that it is now understood to be a chronic inflammatory disorder; as such, the focus of treatment options has slowly shifted towards the anti-inflammatory and away from the antibiotic approach.

“We now know that rosacea is not an infectious disorder but a chronic inflammatory disorder, all of which leads to the concept that antibiotics are not the right way to go about treating it,” says Hilary E. Baldwin, M.D., Department of Dermatology, SUNY Downstate Medical Center, Brooklyn, New York.

Although antibiotics are effective in the treatment of rosacea, they work by being anti-inflammatory agents. When full dose antibiotic agents are used, Dr. Baldwin says that more harm is ultimately caused than good, including the potential development of antibiotic resistances. According to Dr. Baldwin, the tetracycline class of antibiotics frequently used in rosacea is, in fact, a very good anti-inflammatory drug and in order to maximize the anti-inflammatory effect, lower doses of the antibiotic should be used.

“Recognizing that doxycycline has both anti-inflammatory and antibiotic capacities, we started playing around with anti-inflammatory dose doxycycline for the treatment of rosacea, and found a dose that was low enough not to be an antibiotic but high enough to impart a full anti-inflammatory ability. This was in part a kind of verification that rosacea indeed was a chronic inflammatory disease where there was an up-regulation of cathelicidins and matrix metalloproteinases in the epidermis that were suppressed by doxycycline,” Dr. Baldwin says.

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There is an acute difference however between doxycycline (Oracea, Galderma), which is 40mg of doxycycline in a controlled dosing manner (and an anti-inflammatory dose), and low-dose antibiotics. At 40mg, doxycycline does not have antibiotic capabilities and therefore is not an antibiotic but instead an anti-inflammatory drug. According to Dr. Baldwin, 50mg/day doxycycline or minocycline, although effective in rosacea, are antibiotic doses, and low-dose at that. Antibiotic resistance is encouraged by inadequate dosing with antibiotics. Therefore, one could argue that 200mg/day is a less harmful dose than 50mg/day.

NEXT: Causes of inflammation

Causes of inflammation

It has been speculated that Demodex , a parasitic mite normally found in and around the hair follicles, could be partly responsible for rosacea flares; specifically, Bacillus oleronius-the bacteria that live inside Demodex. According to Dr. Baldwin, ivermectin, commonly used to treat Demodex infestation, is now also available in a new topical formulation (Soolantra, Galderma) that is proving to be effective in the treatment of rosacea as well, lending credence to Demodex and the inflammation that it causes being at least partly responsible for the disease.

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According to Dr. Baldwin, the current conventional wisdom for rosacea is that the innate immune system, which is supposed to tell the difference between foreign and self, is possibly not working as well as it should be in terms of appropriately recognizing the commensal organisms that live and breed naturally on the skin such as P. acnes, S. epidermidis, and perhaps Demodex. The result is an inflammatory response to these organisms by the innate immune system, translating clinically into rosacea.

In addition to killing Demodex, Dr. Baldwin says that ivermectin is a very good anti-inflammatory drug and the new topical formulation of ivermectin also has a very good moisturizing base, which acts as an excellent barrier repair cream. It still remains unclear however in which capacity these therapeutic effects of topical ivermectin are responsible for the improvement of rosacea symptoms, a question that would be a potential focus for future clinical studies.

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“I believe that there should be a definite shift away from using antibiotics at antibiotic doses for the treatment of rosacea. We are in a good position now where we have a lot of good medications that we can use that are not antibiotics and it is my opinion that we should not be using antibiotics for the treatment of rosacea until all other avenues have been exhausted,” Dr. Baldwin says.

NEXT: Beyond the skin

Beyond the skin

There is also increasing evidence that rosacea is not only a skin disease but a systemic one as well. Patients with rosacea are at an increased risk of coronary artery disease and other forms of vascular disease, perhaps even stroke, much like psoriasis patients.

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According to Dr. Baldwin, numerous studies^1-2 suggest that the tetracycline class of antibiotic specifically is associated with a reduction in coronary artery disease, with one study³ finding that first-time heart attacks are most likely to occur in patients receiving tetracycline.

“It is possible that if you take the tetracycline class of antibiotics for rosacea, maybe you are not only improving the symptoms of rosacea, but you are also doing yourself a service in terms of your cardiovascular health. There is evidence that doxycycline 20 mg BID is able to reduce C-reactive protein, a marker for coronary artery disease,” Dr. Baldwin says.

Disclosures: Dr. Baldwin is on the speakers bureaus for Galderma and Bayer

References:

1. Duman N et al. Rosacea and cardiovascular risk factors: a case control study. J Eur Acad Dermatol Venereol. 2014 Sep;28(9):1165-9.

2. Hua TC et al. Cardiovascular comorbidities in patients with rosacea: A nationwide case-control study from Taiwan. J Am Acad Dermatol. 2015 Aug;73(2):249-54.

3. Meier CR et al. Antibiotics and risk of subsequent first-time acute myocardial infarction. JAMA. 1999 Feb 3;281(5):427-31.