Using Combination Therapies and Avoiding Subtypes for Rosacea

In this presentation on rosacea from Maui Derm NP+PA Fall 2021, Julie Harper, MD, explains why combination therapy is more effective and how classifying rosacea patients by subtype can lead to suboptimal treatments.

Subtypes for rosacea are outdated according to Julie Harper, MD, a board-certified dermatologist in private practice at the Dermatology and Skin Care Center of Birmingham in Birmingham, Alabama, who presented on the subject at the Maui Derm NP+PA Fall 2021 conference happening in person in Asheville, North Carolina, and virtually from September 30 to October 3, 2021.1

Harper continued, “Too often [patient’s rosacea] has multiple features. For example, let's say [the patient] would have had papulopustular rosacea, well, how often do you have papules and pustules, and you don't also have erythema? Then you end up just treating a part of the whole issue.”

Harper gave the example of a 28-year-old female patient who had flushing, persistent redness, sensitive skin, burning, and irritation that the patient felt was embarrassing and difficult to conceal. Harper said the first step is to use the STOP method to organize the first visit with a patient. STOP stands for:

S: Identify signs and symptoms of rosacea

T: Discuss triggers

O: Agree on outcome

P: Develop a plan.

She said this will make sure that both the patient and physician are on the same page with a treatment plan and outcomes.

There are 2 main targets in rosacea, according to Harper, the inflammation and the vessel. She emphasized that the vessel is often left untreated. Different triggers activate different pathways; some activate inflammation through innate immunity while others activate vasodilation directly.

She compared the multiple treatments to cutlery, the fork isn’t going to do the same job as a knife or a spoon, so when choosing treatments make sure to consider all the signs and symptoms.

For bumps, Harper continues, treatments include ivermectin, metronidazole, azelaic acid, sodium sulfacetamide sulfur, modified release doxycycline and minocycline. Then there are the erythema treatments like brimonidine and oxymetazoline. For the other signs, like telangiectasia or phyma, device-based treatments are very helpful.

The goals of combination therapy are to achieve clear skin quickly and to maximize periods of remission and minimizing the burden of disease.

Harper has used carvedilol, which is a blood pressure medication, to treat rosacea (Not FDA approved).She quoted a study in which 5 patients with either frequent flushing episodes or persistent erythema and burning sensations that were unsuccessful with previous treatments where carvedilol was added titrated up to a dose of 12.5mg for at least 6 months.2 It did improve patient redness.

She did touch on the subject of skin of color (SOC) rosacea because of a study that compare doxycycline and propranolol.3 There were 78 patients that were categorized into subtype, erythematotelangiectatic (ETR) or Papulopustular rosacea (PPR) and separated into either the doxycycline or propranolol groups or a combination of both. There was improvement for patients at every time point and though the propranolol worked faster than the doxycycline, both groups ended up the same according to Harper.

Botulinum Toxin (Botox) was another treatment for flushing and rosacea discussed by Harper and it does work, but it can be very expensive for the patient as insurance may not cover the treatment. Also be careful to avoid using too much and having an unwanted effect on facial muscle movement.

For persistent background erythema, Harper discussed oxymetazoline (Rhofade; EPI Health) and brimonidine (Mirvaso; Galderma). Each target 2 different alpha adrenergic receptors and both are effective. There is a combination study that combines brimonidine and ivermectin that found the combination treatment to be effective for the redness and bumps that rosacea can cause.4

Harper also talked about ocular rosacea in which a patient she had complained of dry/gritty eyes with occasional acne like lesions on the nose. She said that she focuses not only on good skincare, but also eye care for the patient. She said artificial tears can be a very important part of the skin care process and she uses topical azithromycin for one week per month with good success.

She did quote a study that combined ivermectin with modified release doxycycline versus topical ivermectin 1% cream and placebo.5 Patients did achieve clear or almost clear treatment faster with the combination treatment than with ivermectin and placebo, but had similar results in erythema reduction, reduction of stinging and burning.

“So, I guess my take home messages would be don't just use a fork when you can use more tools than that, use combination treatment,” Harper said. “Also really take the time to observe and document all of the signs and symptoms of rosacea that your patient exhibits and describes. And lastly, don’t forget to target the vessel in those rosacea patients who have erythema as part of their disease presentation.”


Julie Harper, MD, has a conflict of interest with Almirall, BioPharmX, Cutera, Cassiopea, EPI, Galderma, Journey, LaRoche-Posay, Ortho, Sun, and Vyne.


1. Harper J. Rosacea Update. Session presented at: Maui Derm NP+PA Fall 2021 conference Program; October 1, 2021; Accessed October 1, 2021. Asheville, North Carolina

2. Pietschke K, Schaller M. Long-term management of distinct facial flushing and persistent erythema of rosacea by treatment with carvedilol. J Dermatolog Treat. 2018;29(3):310-313. doi:10.1080/09546634.2017.1360991

3. Park J-M, Mun J-H, Song M, et al. Propranolol, doxycycline and combination therapy for the treatment of rosacea. J Dermatol. 2015;42(1):64-69. doi:10.1111/1346-8138.12687

4. Gold LS, Papp K, Lynde C, et al. Treatment of rosacea with concomitant use of topical ivermectin 1% cream and brimonidine 0. 33% gel: a randomized, vehicle-controlled study. J Drugs Dermatol. 2017;16(9):909-916.

5. Schaller M, Kemény L, Havlickova B, et al. A randomized phase 3b/4 study to evaluate concomitant use of topical ivermectin 1% cream and doxycycline 40-mg modified-release capsules, versus topical ivermectin 1% cream and placebo in the treatment of severe rosacea. J Am Acad Dermatol. 2020;82(2):336-343. doi:10.1016/j.jaad.2019.05.063