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Intradermal neuromodulator injections show promise for treating rosacea - particularly in the form of erythematotelangiectatic rosacea, flushing and rhinophyma, experts say.
Orlando, Fla. - Botulinum toxin type A (BoNTA) may provide a reasonable therapeutic option for some patients with rosacea, according to experts who spoke at the Orlando Dermatology meeting recently.
“It’s very important for us to be aware that we have a limited understanding of all that botulinum toxin A is doing within the skin,” says Erin Gilbert, M.D., Ph.D. “We have been using it for more than 15 years clinically for its cosmetic benefits, and we have not begun to address the potential therapeutic power of this drug.” Dr. Gilbert is assistant professor of dermatology at SUNY Downstate Medical Center, New York.
Among skin diseases, she says, “We know that the etiology of rosacea is multifactorial. For most people, there’s a strong inflammatory component.” As a clinician and researcher, she adds, “I approach rosacea from the perspective of neuroinflammation. We know that neuropeptide genes are dysregulated in rosacea. One of the relevant peptides may be vasoactive intestinal protein (VIP) peptide, while calcitonin gene-related peptide (CGRP) appears to play a larger role. These are common themes that are seen across the board in neuroinflammatory disorders.”
More on rosacea and BoNTA therapy
Other neurotransmitters, such as serotonin and acetylcholine, also play a role in rosacea pathology, Dr. Gilbert says. BoNTA is best known to directly affect the latter, she adds.
“The research that we have to date has shown us that by examining specific mechanisms within rosacea, we can potentially identify targets or mechanisms of action than can be further explored. We know, for example, that specific ion channels have been implicated in the inflammatory process; namely, transient receptor potential vanilloid (TRPV) 1 through 4 (Sulk M, Seeliger S, Aubert J, et al. J Invest Dermatol. 2012;132(4):1253-1262). These receptors are upregulated or downregulated in either erythematotelangiectatic or papulopustular rosacea,” she says.
Research also has shown that vascular dysregulation plays a role in the development of rosacea (Schwab VD, Sulk M, Seeliger S, et al. J Investig Dermatol Symp Proc. 2011;15(1):53-62), and that BoNTA may stabilize vascular hyperactivity (Dayan SH, Pritzker RN, Arkins JP. J Drugs Dermatol. 2012;11(12):e76-e79). Authors of the latter study surmise that the neuromodulator likely affects a neurogenic component that plays a role in vascular dysfunction, inflammation and hypersebaceous activity.
The latter study also provides anecdotal evidence of patients with rosacea experiencing improvement in erythema and flushing after treatment with intradermal microdroplets of onabotulinumtoxinA (Botox, Allergan). The treatment produced no adverse events, says study co-author Steven H. Dayan, M.D., a Chicago-based facial plastic surgeon. In another study, BoNTA reduced sebaceous gland hyperactivity and pore size (Shah AR. J Drugs Dermatol. 2008;7(9):847-850).
Overall, Dr. Gilbert says, “This is an area we’re beginning to investigate and publish on for the very first time. If you look on PubMed, you won’t find more than one or two papers that describe the use of botulinum toxin for rosacea.”
To address the dearth of data, “We must continue to explore clinical use further,” Dr. Gilbert says.
To that end, Dr. Gilbert says the first clinical trials are under way. For example, in early April, Dr. Dayan was compiling results of a 10-patient, investigator-initiated trial of incobotulinumtoxinA (Xeomin, Merz) for rosacea.
“Clinically,” he says, “I routinely offer this treatment to help reduce erythema, flushing and sebaceous activity. Therefore, I find it’s very popular for rhinophyma as well as rosacea.”
Over the past five or six years, Dr. Dayan estimates, he has treated more than 100 patients with rosacea using neuromodulators. Complications are rare, he adds: just one case of weakness in the facial mimetic muscles. Patients tolerate the low-dose treatment well, he says.
Furthermore, he says, the high dilution Dr. Dayan uses allows small volumes of product to produce maximal diffusion. In this regard, he typically uses 10 units per cheek, at a dilution of 7 cc saline per 100 units of incobotulinumtoxinA or onabotulinumtoxinA (label dosing for both products calls for 2.5 cc of saline per 100 units).
In Dr. Dayan’s recently completed double-blinded, placebo-controlled crossover study, patients received one treatment with incobotulinumtoxinA, then one treatment with saline, or vice versa, spaced three to five months apart.
“I don’t know if the study will prove the treatment to be safe and effective. I like to believe it will,” although the small patient population may prevent his drawing any significant conclusions, he says. Either way, Dr. Dayan says, “It’s a treatment that deserves more investigation.”
When treating patients, Dr. Gilbert subdivides the face to isolate the treatment area, and then injects four intradermal blebs around 1 cm apart.
“That is the diffusion area that we tend to see when we inject neurotoxins intramuscularly, and for hyperhidrosis,” she says.
It’s important to inject superficially, Dr. Gilbert notes, to avoid unwanted muscle paralysis. Besides the cheeks, she says, one can consider injecting the nose and chin.
A typical patient requires 10 to 15 units of onabotulinumtoxinA or incobotulinumtoxinA, or 20 to 30 units of abobotulinumtoxinA (Dysport, Medicis), depending on gender and size of the treatment area, Dr. Gilbert says. Patients tend to see consistent results about one month postinjection, she adds, and results last four to six months.
“My goal is to cover all the desired areas at a financially reasonable price,” Dr. Gilbert says. In this area, she says the average cost of treating rosacea with BoNTA, including the cheeks and nose, depending on the practitioner, ranges from $200 to $600.
“When you think about the price of prescription medications used over a long period, this is not an unreasonable alternative for some patients, provided the therapy is successful,” she says.
Physicians must inform patients that not everyone with rosacea will achieve success with BoNTA. The treatment works well overall, Dr. Dayan says. Nevertheless, he adds, “I don’t believe it works on everyone. There’s a select group of people on whom it works better. And I am not yet sure what makes someone an ideal candidate. Perhaps after we break the blind from the study, I’ll have more insight.”
Because patients will be paying out-of-pocket, Dr. Gilbert adds, “It’s very important for us to offer therapies that will provide them with the results they deserve and expect.”
In this regard, she says it’s critical to evaluate the subtype of rosacea upfront.
“In my experience, there’s been more success in treating flushing and erythematotelangiectatic rosacea,” Dr. Gilbert says.
Moreover, she says, “Combination therapy can often yield the best results. Our strength here is to treat what we know about a skin disease using the standard of care - and explore new areas of treatment that are safe and scientifically sound and provide us with new therapeutic options. Doing this will allow us to improve quality of life our patients.”
Disclosures: Dr. Gilbert is a consultant to Allergan and Merz Aesthetics. Dr. Dayan’s investigator-initiated trial was funded by Merz.