Advances in Managing Rosacea

04/10/2012

The 2012 Annual American Academy of Dermatology (AAD) Meeting, held last month in San Diego, CA, featured many interesting presentations about ongoing research and new treatment options for a variety of conditions. One of the many conditions discussed during the conference was rosacea, which causes erythema, pimples, pustules and a flushing and blushing phenomenon.1 The condition is classified into four subtypes: erythematotelangiectatic rosacea (facial redness), papulopustular rosacea (bumps and pimples), phymatous rosacea (skin thickening) and ocular rosacea (eye irritation).1 The primary FDA-approved therapies currently used to treat rosacea include 40 mg doxycycline in a rapid-release form, topical metronidazole and topical azelaic acid.

The scientific sessions and presentations at the Annual AAD Meeting highlighted existing and emerging areas of interest in rosacea. Data published in late 2011 also reflect some emerging concepts in the area of rosacea, which is thought to affect at least 16 million Americans.2 While no new medications have, at present, been approved for rosacea, there are a number of new treatments nearing FDA approval that have the potential to improve the lives of numerous patients with the disease. Compliance, an issue that every physician deals with, continues to be a concern for dermatologists treating rosacea patients, although there are strategies to help increase medication adherence. In addition, new research is leading the way to a better understanding of the development and progression of rosacea.

This review will highlight the ongoing issue of compliance, drugs in development for rosacea and emerging areas of research.

Compliance

As with almost any condition, a frequent problem dermatologists face when treating rosacea patients is compliance. Julie Harper, MD, FAAD, clinical associate professor at the University of Alabama at Birmingham, calls it “a huge issue.”

Dr. Harper“I think some of the time, people are just lying, but I think another part of the time, people really do think that they’re doing better than they are,” Dr. Harper explains. “I think compliance is an issue even if the patients don’t realize it. They might come in and say, ‘I do this every single day,’ but that’s probably not true — it may be, but it probably isn’t, so [compliance] is definitely a big issue.”

According to Joseph Fowler, Jr., MD, of Dermatology Specialists, PSC, in Louisville, KY, the University of Louisville Department of Medicine and the University of Kentucky, there are two ways to look at compliance.

“Compliance with topicals can be an issue for a couple of reasons,” Dr. Fowler explains. “The main one is that, in people with rosacea, their skin is more sensitive, so a lot of things burn when they rub creams and gels and such on their skin. They’ll sting and burn more than the rest of us, so, obviously, if they have a medication that stings and burns a lot, they’re not going to use it as well. From a systemic standpoint, you’ve always got the issue of is the patient going to take a pill every day or if are there going to be side effects.”

Dr. Fowler believes doxycycline 40 mg USP (Oracea) is a significant advance toward increased topical compliance.

Dr. Fowler“I think [compliance] is a big area where the new medication that’s been out for a few years, Oracea, has a great benefit, because, compared to high-dose doxycycline, it has virtually no adverse effects — it can still have some, but it’s much less likely — and, also, there’s much less likelihood of the development of bacterial resistance,” he explains. “Compliance is critical, and I think these advances can help with it.”

Dr. Harper believes there are a number of strategies that can improve compliance.

“There are a couple of things that are really important,” Dr. Harper explains. “Probably the most important part is making sure that patients are part of the decision-making process of how we’re going to treat it. Usually, in rosacea, we’re talking about adult patients. They can have a say — does this patient prefer to swallow a pill or do they prefer to put something on? Or are they so motivated that they want to do both? Letting them have a part of the decision-making process will help them buy into the treatment plan a little bit more and then hopefully be more adherent with it.”

In addition, dermatologists may be able to increase compliance by taking more time with patients during office visits, to make sure patients fully understand the disease.

“We often think of acne and rosacea being very quick visits in the office, but it shouldn’t be very quick — there should be a lot of discussion that goes on,” Dr. Harper explains. This includes talking about the relapsing-and-remitting nature of rosacea, the chronicity and the connection between adherence and improvement.

“Helping people to understand the natural history of the condition will, I think, help them to treat it better, because, otherwise, the first flare-up they have, they give up.”

Treatments in Development and Emerging Research

Medications on Track for FDA Approval

RosaceaTwo drugs are in the process of being approved by the FDA that may also lead to increased compliance and improved patient outcomes, both in terms of clearance and satisfaction.

Patients with rosacea experience redness that is exacerbated by a flushing-and-blushing phenomenon. Photo courtesy of the National Rosacea Society.

Guy F. Webster, MD, PhD, a clinical professor of dermatology at Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA, says that the data on the first drug, brimonidine tartate gel, was the newest item about rosacea that was presented at the 2012 Annual AAD Meeting. The drug is currently approved for the treatment of glaucoma (Alphagan P/brimonidine tartrate ophthalmic solution), which means, according to Dr. Webster, that there won’t be significant safety concerns about the drug.

Dr. Harper concurs. She also believes brimonidine will be a significant, positive addition to the array of treatment options currently available for rosacea.

“Brimonidine is strictly geared at redness, so hopefully, when it does get FDA-approved, it will be looking at the transient redness, the flushing and blushing in individuals who have that component of rosacea, because, really, everything that we have until this point for rosacea is FDA-approved for the pimples, the papules, the bumps, and, they might say, the redness associated with the bumps, but we don’t have any product that is specifically FDA-approved for redness,” Dr. Harper explains.

The other medication that should be approved in the near future by the FDA for rosacea is a topical form of oxymetazalone, which is currently approved as a nasal spray (Afrin). The drug is a vasoconstrictor that will be indicated, like brimonidine, for redness; the emergence of two new drugs for the erythema of rosacea is “huge,” according to Dr. Fowler.

Dr. Harper believes that both of these drugs have the potential to significantly improve the symptoms of rosacea, an outcome that has the potential to increase compliance as well.

“The new products that are coming out are going to have a pretty immediately gratifying effect,” she explains. “They’re going to work pretty fast — you can see improvement in a day or two [with these new products], or within a week — that’s a very short period of time to see improvement. Putting it on causes vasoconstriction, so, if you get immediate gratification from a product like that, you’re going to be more likely to use it. I think we’ll see better adherence with the products like that, that have an immediate effect.”
 
Emerging Research

The Neurological Component of Rosacea. In February, two articles in the Journal of Investigative Dermatology (JID) highlighted the possible role of the neurological system in the development and progression of rosacea.

The first study found that mast cells and fibroblasts were increased in rosacea patients’ skin. According to the study abstract, “sensory nerves were closely associated with blood vessels and mast cells and were increased in erythematous rosacea.”3 In addition, this study confirmed the “upregulation of genes involved in vasoregulation and neurogenic inflammation, which indicates that dysregulation of mediators and receptors implicated in neurovascular and neuroimmune communication may be crucial at early stages of rosacea.”3

The second study in JID demonstrated that “transient receptor potential (TRP) ion channels of vanilloid type (TRPV) may play a role in the development and progression of rosacea.”3 The team of researchers, many of whom were the same on both JID studies, analyzed the expression and distribution of TRPV receptors in various subtypes of rosacea on non-neuronal cells with immunohistochemistry, morphometry, double immunofluorescence and quantitative real-time PCR (qRt-PCR). This revealed that “dermal immunolabeling of TRPV2 and TRPV3 and gene expression of TRPV1 is significantly increased in erythematotelangiectatic rosacea (ETR). Papulopustular rosacea (PPR) displayed an enhanced immunoreactivity for TRPV2, TRPV4 and also of TRPV2 gene expression. In phymatous rosacea (PhR)-affected skin, dermal immunostaining of TRPV3 and TRPV4 and gene expression of TRPV1 and TRPV3 was enhanced, whereas epidermal TRPV2 staining was decreased.”3

Dr. WebsterDespite the recent research, Dr. Webster does not yet view the neurological component of rosacea as an emerging area of study, but believes it should be.

“The control of blushing and flushing is neurologic, and there may be a role for nerves in controlling the inflammatory response,” he explains, adding that he sees further study about the neurological aspect of the development and the expression/control of rosacea — the flushing and blushing — as an upcoming area of research.

The Role of Demodex Mites. Demodex mites are “little mites that live on our skin,” Dr. Fowler explains. “There seem to be some people who have either rosacea or a rosacea-like dermatitis on their face that, if you kill the Demodex, they get better. All of us have some Demodex on our skin and on our face, but not all of us have rosacea, so maybe some people with rosacea have more Demodex, or maybe they have some inflammatory response to the Demodex.”

Topical crotamiton (Eurax) is a scabicide that is used to treat scabies and that has been shown also to reduce itching.4 According to Dr. Fowler, several small studies have looked at topical crotamiton for the treatment of Demodex in rosacea patients, and some efficacy has been demonstrated.

“Eurax has been out for many, many years, and, in addition to being a miticide, it also has an indication as an anti-pruritic, so, for people with sensitive skin, it might help their skin feel better a little bit,” explains Dr. Fowler. “Certainly, not everyone will respond to this treatment. It’s a case-by-case thing – but maybe the occasional patient will have a response to this who hasn’t responded well to the other options.”