Rosacea is a chronic inflammatory skin condition that can be frustrating for patients and dermatologists, who may struggle to find the best treatment option to alleviate the burden of the disease. Its cause is multifactorial; researchers and dermatologists have hypothesized a number of factors, including aspects of the innate immune system, such as cathelicidins and mast cells; the neurovascular system; vascular changes caused by UV radiation; an increased presence of Demodex mites, and subsequently their associated bacteria; and a possible genetic connection.1
In 2017, an international expert group determined that rosacea classifications should be based on common phenotypes.2 This is an improvement on the classifications written 15 years’ prior, which determined four subtypes: erythematotelangiectatic, papulopustular, phymatous, and ocular.3 As a reminder, the Table lists a breakdown of the most common phenotypes of rosacea. Note that while the diagnostic features alone may indicate rosacea, the presence of two or more major phenotypes can also be considered as a reason for diagnosis.
Even with research focused on the pathogenesis of rosacea, there is still quite a bit that dermatologists and their counterparts do not know about the disorder.
At the ODAC Dermatology, Aesthetic, and Surgical Conference in Orlando, FL, Linda Stein Gold, MD, reviewed the known pathogenesis of rosacea and best treatment options for improving this skin condition. She is the director of dermatology, clinical research, and division head of dermatology at Henry Ford Health System in Detroit and West Bloomfield, MI.
Dr Stein Gold discussed treatment options, best practices, and new therapies with The Dermatologist.
Q. What is known about the pathogenesis of rosacea?
A. In terms of the pathogenesis of rosacea, we understand that this is an inflammatory disease at its core. We know that the innate immune system is revved up and hyperactive, and that there are certain triggers that can set off this process, such as stress, heat, and exercise. In addition, patients have an abnormality of the vascular system, and this vasodilation causes redness of the face.
Q. What are the current best practices for treating rosacea?
A. The best approach for treating rosacea is to tailor treatment based on the patient’s individual needs, which involves targeting the signs and symptoms that are present. For example, if a patient has papulopustules, it is best to use a topical or oral anti-inflammatory drug. A topical alpha-adrenergic receptor agonist is a good option for those with background erythema. If a patient has telangiectasias or phyma, then the best option is either using a device or a surgical approach.
Also, combination therapy is an effective strategy for treating rosacea. Using combination ivermectin with brimonidine, an alpha-adrenergic agonist, was associated with faster and more complete clearance of inflammatory lesions.5 This is a nice approach to start the two drugs at the same time. Similarly, more patients treated with combination ivermectin and sub-antimicrobial dose doxycycline achieved complete clearance compared with ivermectin alone in another study.6
Q. Which therapies are currently under investigation for rosacea?
A. Fortunately, we have a number of treatments that are currently under investigation. The first is a topical 1.5% minocycline foam. In a trial, about 50% of patients with moderate to severe papulopustular rosacea who were treated with minocycline foam were found to have clear or almost clear skin at the end of 12 weeks.7 This is a nice new treatment that is FDA approved in the 4% concentration for acne, with completed clinical trials for rosacea.
There is also a microencapsulated benzoyl peroxide formulation for rosacea. Benzoyl peroxide is not generally thought of as a treatment for rosacea because it is so irritating. However, this new formulation offers a delivery system that slowly releases the benzoyl peroxide. In a study, approximately 50% of patients achieved clear to almost clear skin at about 12 weeks of treatment, and the tolerability profile for this formulation is very favorable.8
Q. What aspects of rosacea still require further research into treatment options?
A. We do not have anything approved by the FDA for ocular rosacea. Patients with rosacea can have redness in their eyes or experience discomfort associated with the skin condition. Case reports have shown some success with the use of topical ivermectin on the eyelids of patients with ocular rosacea, but it is not FDA approved for this indication. n
References
1. Causes of rosacea: introduction. National Rosacea Society. https://www.rosacea.org/patients/causes-of-rosacea/introduction. Accessed January 29, 2020.
2. Gallo RL, Granstein RD, Kang S, et al. Standard classification and pathophysiology of rosacea: the 2017 update by the National Rosacea Society Expert Committee.
J Am Acad Dermatol. 2018;78(1):148-155. doi:10.1016/j.jaad.2017.08.037
3. Wilkin J, Dahl M, Detmar M, et al. Standard classification of rosacea: report of the National Rosacea Society Expert Committee on the classification and staging of rosacea. J Am Acad Dermatol. 2002;46(4):584-587. doi:10.1067/mjd.2002.120625
4. Stein Gold L. How do I treat rosacea in 2020. Presented at: ODAC Dermatology, Aesthetics, and Surgical Conference; January 17, 2020; Orlando, FL.
5. Stein Gold L, 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.
6. 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
7. Stein Gold L, Del Rosso JQ, Kircik L, et al. Minocycline 1.5% foam for the topical treatment of moderate-to-severe papulopustular rosacea: results of two phase 3, randomized, clinical trials [published online January 28, 2020]. J Am Acad Dermatol. doi:10.1016/j.jaad.2020.01.0443
8. Sol-Gel announces positive top-line results from Epsolay® phase 3 program in papulopustular rosacea [press release]. Ness Ziona, Israel: Sol-Gel; July 8, 2019. https://ir.sol-gel.com/news-releases/news-release-details/sol-gel-announces-positive-top-line-results-epsolayr-phase-3. Accessed February 4, 2020.
