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Persistent Erythema: An Unmet Need in Rosacea Care

June 2020

The National Rosacea Society (NRS) recently brought together a number of experts in the pathophysiology, management, and research of rosacea for a roundtable discussion on persistent facial erythema.1 This group of key opinion leaders emphasized the critical need for a shift in how dermatology addresses persistent erythema, citing current literature, advances in management options, and clinical experiences. Among the leading voices at the roundtable was Richard L. Gallo, MD, PhD, a distinguished professor and the founding chairman of the department of dermatology at the University of California San Diego. He is also a member of the Medical Advisory Board of the NRS.

“Persistent erythema is the most frequent phenotype associated with rosacea,” said Dr Gallo, “and unfortunately it has many of the most severe impacts on quality of life. Combined with that, our treatment approaches for persistent erythema are perhaps most limited. So, we have a great need in that particular phenotype presentation in rosacea patients to advance therapy.”

The updated classification system for rosacea based on phenotypes of the condition categorizes persistent erythema as a primary diagnostic feature.2 Thiboutot et al3 outlined the standard management options for rosacea, using the classification system as an avenue to determine a patient care plan. “The revised classification system allowed for a multiphenotype approach to treatment, where therapies can be individualized to the patient,” explained Dr Gallo. “Further, as described in the 2019 update, by recognizing that a single individual can have multiple phenotypes, it allows the practitioner to select treatment designed specifically for each individual phenotype.”

Yet as Dr Gallo noted, the available rosacea treatments do little to address persistent erythema, thus leaving patients susceptible to a decreased quality of life with social and emotional effects.4 Current options approved to treat erythema include brimonidine and oxymetazoline, both alpha agonists, and light devices (intense pulse light, pulsed dye, and potassium titanyl phosphate).1

Dr Gallo also described how rosacea’s phenotypes may be connected by an underlying chronic inflammation.1 

“Inflammation is a hallmark of rosacea. Unlike other skin diseases, rosacea is a disorder of innate immunity, where an excessive sensitivity to the environment around the individual with rosacea leads to various manifestations of inflammation. That can be sensations of burning and itching, it can be vasoactive changes such as vasodilation, it can be vasoproliferative changes such as telangiectasia, or it can be frank recruitment of inflammatory cells such as papules or pustules and then later infiltration, which is the phymatous changes of rosacea,” said Dr Gallo. Future research should zero in on the role of inflammation in rosacea, such as preventing MRGX2 from triggering a mast cell-induced inflammatory immune response,5 with the ultimate goal of creating a therapeutic option that addresses multiple phenotypes, including its most common in persistent facial erythema, in a “one-punch-knockout” treatment.

Notably, Dr Gallo highlighted similarities between coronavirus disease (COVID-19) and rosacea using inflammation as a bridge between the two seemingly unrelated conditions. “There are several parallels actually between some of the disease manifestations of COVID-19 and rosacea. It’s interesting that things that we’re learning about how the virus triggers excess inflammatory response in the epithelium of the lung and then some of the dermatologic manifestations we’re seeing from the COVID-19 virus, such as the vascular responses, may give us clues into better understanding rosacea.”

Other research on persistent erythema in rosacea, said Dr Gallo, should focus on elucidating how the environment affects the vascular response.

In addition, the roundtable underscored the need to streamline the quantification of phenotype severity as well as evaluation of quality of life. According to Dr Gallo, a simplified scoring system that could be easily adaptable by large populations of practitioners would contribute immediately to dermatology’s understanding of patients and their rosacea. “That [scoring system] will help subcategorize individuals and help quantify how different phenotypes affect different individuals differently. With that understanding, we will then be able to gauge appropriateness of effective therapies, the appropriateness of combination therapies, and the utility of newly discovered therapies for rosacea.”


References
1. Terhaar E. Leading dermatologists urge greater focus on facial redness at NRS roundtable. National Rosacea Society. May 12, 2020. Accessed June 1, 2020. https://www.rosacea.org/blog/2020/may/dermatologists-urge-greater-focus-on-facial-redness-roundtable

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. Thiboutot D, Anderson R, Cook-Bolden F, et al. Standard management options for rosacea: the 2019 update by the National Rosacea Society Expert Committee. J Am Acad Dermatol. 2020;82(6):1501-1510. doi:10.1016/j.jaad.2020.01.077

4. Baldwin HE, Harper J, Baradaran S, Patel V. Erythema of rosacea affects health-related quality of life: results of a survey conducted in collaboration with the National Rosacea Society. Dermatol Ther (Heidelb). 2019;9(4):725-734. doi:10.1007/s13555-019-00322-5

5. Mascarenhas NL, Wang Z, Chang YL, Di Nardo A. TRPV4 mediates mast cell activation in cathelicidin-induced rosacea inflammation. J Invest Dermatol. 2014;137(4):972-975. doi:10.1016/j.jid.2016.10.046