Paradoxical Erythema Reaction of Long-term Topical Brimonidine Gel for the Treatment of Facial Erythema of Rosacea

June 2016 | Volume 15 | Issue 6 | Case Reports | 763 | Copyright © June 2016

Erin Lowe MSIVa and Scott Lim DOb

aLake Erie College of Osteopathic Medicine, Erie, PA
bLLC, Erie, PA

In 2013 brimonidine tartrate gel 0.33% (Mirvaso Gel, Galderma Laboratories, LP, Fort Worth, TX) was approved by the US Food and Drug Administration for the treatment of facial erythema of rosacea. It is the first and only drug on the market to address the hallmark redness of this chronic, inflammatory disease. Commonly reported adverse events include erythema/flushing worse than at baseline, most often occurring with the first application. We report a unique case of facial erythema of rosacea that responded to brimonidine gel with effective blanching for two years until the patient developed a paradoxical erythema reaction. This is an adverse reaction physicians should be aware of with continued prescription of brimonidine gel for their rosacea patients.

J Drugs Dermatol. 2016;15(6):763-765.


A 41-year-old Caucasian female of Fitzpatrick skin phototype II with a history of acne and long-standing erythematotelangiectatic rosacea involving the nose, cheeks, forehead, and chin presented with a facial rash. Onset was insidious over the prior two months. The rash started as symmetric clusters of pruritic papules (Figure 1) and progressed to burning erythematous patches of the bilateral zygoma, upper malar, and infraorbital areas (Figure 2). There was no scaling, vesicles, or crust; urticaria and facial edema were absent.
The patient's facial skin-care routine included brimonidine tartrate gel 0.33% twice daily for the facial redness of rosacea and metronidazole gel 1% nightly for inflammatory lesions of rosacea. She had been using these products with much success for two years. There was no recent change in soaps, moisturizers, sunscreen, or make-up. She presented to her PCP several times for treatment. Initially, she was advised to use hydrocortisone ointment and diphenhydramine, then prescribed a five day regimen of oral prednisone, and finally administered a cortisone injection. All of these medications decreased the intensity of pruritus but did nothing for the erythema.
When the patient first noticed the rash developing, she applied brimonidine gel more frequently. The medication, which previously had caused predicable effects of skin blanching for 12 hours, now only controlled her facial redness for 5 hours, at which point a worsening patchy erythema significantly more intense than baseline erythema would develop. The itching and burning remained constant with or without brimonidine application. She finally visited her Dermatologist, who suspected a paradoxical reaction to brimonidine. Within 48 hours of discontinuing brimonidine gel her rash completely cleared.


Rosacea is a chronic inflammatory facial dermatosis with an average prevalence rate of 10-22% worldwide.1 It is characterized by erythema with or without transient papules and pustules, and is divided into four subtypes: erythematotelangiectatic, papulopustular, phymatous, and ocular. Facial redness affects up to 87% of rosacea sufferers and can be present in all subtypes.2 Available medical therapies for the inflammatory lesions of rosacea include topicals metronidazole, azelaic acid, and ivermectin, as well as oral tetracyclines. However, these agents produce no decrease in the diffuse background erythema caused by transient and/or permanent dilation of superficial cutaneous vasculature. The first and only current pharmacological agent on the market to address the facial redness of rosacea is brimonidine tartrate gel, a highly selective alpha-2 adrenergic agonist. When applied topically it causes peripheral vasoconstriction via a direct effect on the smooth-muscle sheath of superficial cutaneous blood vessels. The blanching effects last 10-12 hours at which point the patient is expected to return to baseline erythema.2
Brimonidine gel was approved by the US Food and Drug Administration in 2013 for topical treatment of persistent facial erythema of rosacea in adults 18 years and older. Safety and efficacy were studied in two large scale phase III studies, one long-term 52 week safety study, and one reanalysis report sponsored by Galderma Laboratories.3,4,5 The most frequently