Rosacea Update: Facial Erythema’s Importance

Authors of a newly published paper called on clinicians who treat rosacea patients to put greater emphasis on persistent facial erythema which, they wrote, is 1 of the most common and challenging features of this chronic skin disease.¹

Achieving optimal patient outcomes often means treating more than the papules and pustules, according to Richard Gallo, MD, PhD, chairman of the Department of Dermatology at the University of California San Diego and an editorial advisory board member for Dermatology Times®.

“The facial erythema also needs to be addressed,” Gallo said.

What Was Missing in Assessing and Treating Rosacea

New insights into rosacea’s pathogenesis and pathophysiology have resulted in significant changes in recent years, including a new classification system. Classifying rosacea is no longer based on the 4 subtypes of erythematotelangiectatic, papulopustular, phymatous, and ocular rosacea described 20 years ago.² An update by the Global Rosacea Consensus (GRC) panel first published in 2016 transitioned to a phenotype-based approach to rosacea diagnosis and classification.³

The GRC’s update recognized rosacea as a single disease with several potential phenotypes that can occur at various times and in different combinations. That signaled a paradigm shift in how dermatologists assess and ultimately treat rosacea.

But the impact of facial erythema remains underappreciated, according to Gallo. To highlight its importance, a panel of US dermatologists recently convened for a National Rosacea Society (NRS) roundtable discussion and addressed what dermatologists need to know about facial erythema in rosacea. A summary of that roundtable was published August 2021 in the Journal of Drugs in Dermatology (JDD).⁴

One of the most important factors is how prevalent and disruptive the phenotype of facial erythema is for all patients who have rosacea, according to Gallo, who led the roundtable and was lead author of the paper.

Persistent facial erythema has gone largely under the radar in rosacea research and might be somewhat ignored in clinical practice, he told Dermatology Times®.

“There has not been an organized and concerted effort to collect the data and understand that aspect of the disease,” Gallo said. “Previously, we recognized a classification of symptoms that had a subtype of facial erythema, but that subtype got lost when we started thinking about people with rhinophyma; people with papules and pustules; and people with ocular rosacea. The reality is the prevalence of facial erythema is very high across all patients with rosacea.”

Patients generally do not fit squarely into the old subtype classifications, according to roundtable participant and author Julie Harper, MD, president and owner of the Dermatology and Skin Care Center of Birmingham in Alabama.

“You might look at a patient with papules and pustules. How many of them don’t also have erythema? It’s almost zero,” Harper said.

Patients Want Solutions for Facial Redness

Patients describe persistent facial redness as one of the most disruptive rosacea manifestations, according to recent studies and surveys, according to Harper. But, she added, physicians often dismiss facial erythema as a less serious phenotype.

“There have been surveys done in the past that show that patients are as bothered by the erythema as they are by the bumps—in some cases, even more so,” she said.

For example, research shows persistent facial erythema significantly impacts patients’ quality of life (QOL).

Findings from a survey⁵ of more than 700 rosacea patient respondents who self-evaluated their erythema as mild to severe suggest that the QOL impact from severe erythema was comparable to that of patients with atopic dermatitis and psoriasis, according to the JDD paper.

An NRS survey of 1675 rosacea patients found 82% of those with erythema indicated the condition had a negative impact on their general outlook on life, with the figure rising to 90% for those with moderate to severe redness.⁶

Shift Diagnostics from Subtypes to Phenotypes

Today’s dermatologists should be sure to accurately characterize and describe the rosacea phenotype, according to Gallo.

Persistent facial erythema and less common phymatous changes are diagnostic phenotypes. Major signs are flushing, papules and pustules, telangiectasia, and some ocular manifestations. The presence of any 2 major phenotypes can be considered diagnostic.

Burning, stinging, edema, dryness and ocular changes, including “honey crust” and collarette accumulation at the lash base, lid margin irregularity, and evaporative tear dysfunction are secondary phenotypes, according to the authors.

In essence, dermatologists are moving away from subtyping a person rather than subtyping the lesions, according to Harper.

“If you look at a patient and document every phenotypic expression of rosacea that they have, the patient in front of you might have papules and pustules but also erythema, telangiectasia, and maybe phymatous changes. They might even have ocular disease,” Harper said. “And from there, you come up with your treatment plan.”

Effectively Treating Rosacea

Treating rosacea is not simply treating inflammation, according to Harper.

“Inflammation is an important part of what we see clinically, and it is an important part of the pathogenesis, but it is just 1 thing that we treat,” she said. “Another part of rosacea that is so important is the blood vessels. For our patients who have erythema, so much of that comes from chronically dilated blood vessels.”

There are 2 FDA approved prescription medications for treating erythema from neurovascular dysregulation: brimonidine and oxymetazoline, both of which are alpha agonists.

“The first thing that is important to know is brimonidine and oxymetazoline are not the same,” Harper said. “While both are alpha agonists, they have different receptor selectivity.”

Brimonidine, which begins acting in 30 minutes with an often dramatic reduction in erythema, is predominantly an alpha 2 agonist, while oxymetazoline, which has a gradual onset with peak erythema reduction in about 3 hours and lasts throughout the day, is predominately an alpha 1a agonist, according to Harper.

“Because they have different receptor selectivity, they are going to have different activity in the skin,” Harper said. “For example, we know that brimonidine has been associated with more erythema as an adverse effect either at the end of the day or even paradoxically in the middle of the day,” Harper said.

The erythema exacerbation seen with brimonidine does not tend to occur with oxymetazoline. However, she said both drugs have transient effects.

A tip to optimize outcomes with the alpha agonists to treat rosacea is to not use the medicines on an as-needed basis, according to Harper.

“When using alpha agonists to help with erythema it’s important that we don’t just focus on using the medication intermittently or using it as a cosmetic agent,” she said. “The vasodilation that leads to redness in rosacea happens over time. To combat this chronic vasodilation, we should vasoconstrict daily, not intermittently. Daily use of the product may have a bigger impact on progression of rosacea than we thought previously.”

Devices Expand Treatment Options

Anti-inflammatory therapies can help reduce perilesional erythema from papules and pustules, and light devices such as pulsed dye and potassium titanyl phosphate (KTP) lasers and intense pulsed light (IPL) are well-established ways to effectively remove telangiectasia and reduce erythema.

“If you are not using a laser to treat erythema, you should find somebody who does. It can be very helpful for people with persistent erythema and telangiectasia in rosacea,” Harper said. “Telangiectasia, in particular, is probably not going to budge with an alpha agonist because they are fixed and don’t have smooth muscle in their walls. So often with telangiectasia, you have to rely on a laser or light device to treat them.”

More Answers Mean More Questions

Even with this new recommendation, Gallo told Dermatology Times®, discussions on the roundtable and writing the paper reminded him how much more there is to do and learn about rosacea.

“Much of what we understand about the pathophysiology of the disease has focused on understanding the telangiectasia and development of papules, but we need to learn a lot more about why there is the overall field of fixed central facial erythema in this disease,” Gallo said. “We need to learn what central facial erythema really is. Is it vasodilatation? Is it an abnormality in the blood vessels? And how much of it is active inflammation vs a vasoactive response?”

There is also room for improvement in today’s rosacea treatment therapies, according to Gallo.

“There is not a clear understanding of the adrenergic agonist approach that can transiently decrease the facial erythema. Does that have benefit in inflammation? Are there alternative mixed approaches where combination therapies may be more effective on facial erythema than we know?” he asked. “All those questions remain unanswered I think, in part, because there wasn’t a focus on understanding that aspect of the phenotype. But that is changing.” And, he added, there are even more changes ahead.

Disclosures:

Gallo is a cofounder, scientific adviser, consultant, and has equity in MatriSys Bioscience; and is a consultant for, receives income from, and has equity in Sente Inc.

Harper has consulting and/or speaking ties with Almirall, Cutera, BioPharmX, EPI Health, Vyne Therapeutics, Galderma, Ortho Dermatologics, Sol-Gel, and Sun Pharma.

References:
1. Gallo RL, Baldwin HE, Stein Gold L. Update on facial erythema in rosacea. J Drugs Dermatol. 2021;20(8):861-864. doi:10.36849/JDD.6062

2. 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

3. Tan J, Almeida LM, Bewley A, et al. Updating the diagnosis, classification, and assessment of rosacea: recommendations from the global ROSacea COnsensus (ROSCO) panel. Br J Dermatol. 2017;176(2):431-438. doi: 10.1111/bjd.15122

4. Gallo RL, Baldwin H, Gold LS, Harper J. Update on facial erythema in rosacea. J Drugs Dermatol. 2021;20(8):861-864. doi:10.36849/JDD.6062

5. 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

6. New rosacea survey shows emotional toll of facial redness equals impact of bumps, pimples. National Rosacea Society. January 15, 2014. Accessed September 14, 2021. https://www.rosacea.org/press/2014/january/new-rosacea-survey-shows-emotional-toll-of-facial-redness-equals-impact-of-bumps-pimples