The Redness Remover

Tanghetti et al (J Drugs Dermatol. 2015;14:33-40) discuss the use of topical brimonidine for the redness associated with rosacea. Brimonidine is the newest therapeutic to combat the erythema associated with rosacea of all subtypes. It is a topical α₂-adrenergic agonist that causes peripheral vasoconstriction via a direct effect on smooth muscle receptors. The authors describe 2 large studies that studied the safety and efficacy of topical brimonidine and also give consensus recommendations regarding optimal utilization while minimizing adverse effects, such as the “rebound” phenomena described. It is important to note that it is not a traditional rebound effect, as it does not occur once the medication has stopped; however, it is a worsening of the erythema during active treatment with brimonidine. The authors discuss the various cases reported to the manufacturer after the medication was released. The most frequently associated side effects reported were erythema in almost all cases, flushing, feeling of heat or burning sensation, and rarely pain. Other issues such as dermatitis, pruritus, facial swelling, and pallor were seen in less than 10% of reports each.

These rebound effects were most likely to occur in the first 15 days after initiation of therapy, mainly in the first week. They also were noticed at 2 other time points—3 to 6 hours and 10 to 12 hours after application—which allowed the identification of 2 types of reactions based on the time to onset postapplication: appearing within 3 to 6 hours and observed after 10 to 12 hours. These events have been given new names. “Paradoxical erythema” is the redness appearing within 3 to 6 hours after application, which can be worse than baseline. “Exaggerated recurrence of erythema” is the redness that is greater than baseline and occurs as therapy wears off, approximately 10 to 12 hours after application. Allergic contact dermatitis also has been associated with the medication and can therefore be a source of redness 3 to 4 months after initiation.

What’s the issue?

The erythema associated with rosacea can be a distressing symptom for both the patient and the dermatologist. It can be difficult to treat and quite often recalcitrant to multiple treatments. Although pulsed dye laser is an effective therapy for treating telangiectases and dilated blood vessels, it can be expensive for many patients. Topical brimonidine represents a novel therapeutic to combat one of the most remarkable symptoms of rosacea. However, because of the possibility of this increased redness after use, Tanghetti et al suggest the following treatment algorithm:

• “Assess” the patient and rule out other causes of redness or associated conditions, such as seborrheic dermatitis or lupus.
• “Educate” the patient regarding the known triggers of rosacea flair and how they can be best avoided. Also educate that brimonidine only treats redness and not the papules, pustules, or other symptoms of rosacea.
• “Inhibit” inflammation that is currently present using gentle skin care practices, mild cleansers, and barrier-restoring emollients.
• “Optimize” the application of brimonidine. Instruct how to apply a pea-sized amount in the morning or how patients can best time the application to coincide with daily events or social events.
• “Understand” that worsening redness may occur, which can be key to patient satisfaction. Patients should be made aware that there is a risk for worsening redness in 10% to 20% of patients. It usually occurs within the first 2 weeks of starting the medication and it may be seen soon after application (3–6 hours) or after treatment has subsided (10–12 hours). Generally this worsening will subside within 12 to 24 hours after discontinuation. Also symptoms can be treated throughout with the use of nonsteroidal anti-inflammatory medications, antihistamines, topical calcineurin inhibitors, and topical steroids, if necessary.

What has been your experience with brimonidine gel and how do you manage these patients?

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