Taking the red out of rosacea: Topical alpha-1-adrenergic receptor agonist shows promise

August 1, 2008

Topical treatment with a 0.05 percent solution of oxymetazoline in a small series of patients with erythematotelangiectatic rosacea has been associated with encouraging efficacy for reducing erythema and preventing erythematous flares. Aspect Pharmaceuticals is planning a clinical trial of a formula optimized for dermatologic use.

Key Points

National report - Limited experience in a small number of patients indicates that the erythema and flushing associated with rosacea may be safely and successfully treated with topical application of a selective alpha 1-adrenergic receptor agonist, such as oxymetazoline, researchers say.

Stuart D. Shanler, M.D., and Andrew Ondo, M.D., studied the topical use of oxymetazoline 0.05 percent to treat five patients with erythematotelangiectatic rosacea (ETR).

Four patients had primarily macular erythema and fine telangiectasias and were resistant to conventional topical treatments for rosacea; the fifth patient had primarily fixed telangiectasias, without significant erythema.

Outcome evaluations showed the benefits of treatment included improvements in erythema and a reduction in erythematous flares, as well as in the associated symptoms of burning and stinging.

The appearance of fine pink/red telangiectasias also improved, but no visible benefit was noted for the larger, fixed telangiectasias.

"Available treatments for rosacea have minimal to no effect on erythema and telangiectasias. While laser and light-based modalities may be beneficial, they are not always effective, and their use is accompanied by many limitations, including cost, availability, and the need for multiple treatments.

"The results achieved with topical oxymetazoline are exciting, but very early, and they need to be confirmed through more rigorous studies," Dr. Shanler tells Dermatology Times.

Patient responses to topical oxymetazoline were based on direct clinical assessment and review of high-resolution digital photographs taken pretreatment at one, two to three and 24 hours post application, and then again after longer-term treatment. The evaluations showed topical oxymetazoline had a rapid effect in reducing erythema.

With continued treatment, which extended up to two years in one patient, the responses remained durable, with no evidence of tachyphylaxis, rebound or adverse events.

"Loss of efficacy due to receptor desensitization and rebound vasodilation is a problem associated with use of intranasal oxymetazoline and other imidazoline- and amine-class nasal decongestants.

"There is some laboratory evidence that the potential for receptor desensitization varies depending on the agonist's selectivity for different alpha-adrenoreceptor subtypes and its duration of action. This may be a consideration in the development of a dermatologic medication that will provide optimal efficacy with minimal risks," Dr. Shanler says.

Oxymetazoline profile

Oxymetazoline is a synthetic, direct-acting sympathomimetic agonist that is highly selective for the alpha 1a adrenoceptor, but also partially selective for the alpha 2a receptor.

It was considered for the off-label treatment of the patients with ETR, based on recognition of its vasoconstrictive activity and the theory that the abnormal flushing and persistent erythema accompanying rosacea is mediated by dysregulation in the cutaneous vasomotor response, leading to vasodilation.

Dr. Shanler says that while the idea of using an alpha-adrenergic agonist as a topical vasoconstrictor to treat facial erythema is not new, previous attempts using clonidine, an alpha 2-adrenergic receptor agonist, have been unsuccessful.

More recent research, indicating that peripheral vascular smooth muscle contraction, may be predominantly mediated by alpha 1-adrenergic receptor subtypes, provides a biological basis for exploring the use of oxymetazoline.

"The positive responses achieved with the use of oxymetazoline support the hypothesis that the pathophysiology of the erythema and flushing of ETR may involve abnormalities in alpha adrenoceptors, likely of an alpha 1 subtype," Dr. Shanler says.

Dr. Shanler is a dermatologist in private practice in New York, and Dr. Ondo is in practice in Las Cruces, N.M.

Drs. Shanler and Ondo are corporate officers in Aspect Pharmaceuticals, a biotechnology company in Las Cruces, N.M.

Aspect Pharmaceuticals is now planning formal studies to evaluate the efficacy and safety of topical oxymetazoline and other selective alpha 1-adrenergic agonists in the treatment of ETR using preparations specifically formulated for the sensitive skin of rosacea patients.