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Rosacea treatment is a marathon — not a sprint — and there’s a need for increased emphasis on a patient-centric approach to management that emphasizes patient education and individualized treatment plans, according to dermatologist Neal Bhatia, MD.

“Controlling erythema is what patients want, and even more so, they want something that’s tolerable,” said Bhatia, director of Clinical Dermatology at Therapeutics Clinical Research in San Diego, said at the most recent annual Integrative Dermatology Symposium. “Taking the DLQI [Dermatology Life Quality Index] and the patient’s experience into account is critical to making sure treatments work and are tolerated.”

During a presentation that highlighted newer therapies for rosacea and addressed both gaps in practice guidance and new directions in research, Bhatia said that the shift to an individualized phenotype-based approach for rosacea diagnosis from a criteria-heavy subtype approach — a paradigm shift endorsed by the National Rosacea Society in 2017 — supports a patient-centric approach.

“It’s about making the diagnosis more about morphology and pattern, and a little less about fitting into criteria,” he said, noting that clinicians can then target the features that are most bothersome to patients.

In the updated diagnosis and classification system, originally proposed by the global Rosacea Consensus panel, two features are independently diagnostic: Persistent, centrofacial erythema associated with periodic intensification and phymatous changes. Diagnosis can also be made with the presence of two or more “major features”: Flushing, telangiectasia, inflammatory lesions, and ocular manifestations.

Among the more recently approved treatments for rosacea — and among products and drug indications under study — “notice there’s a paucity of antibiotics, which is what we’re trying to get away from,” said Bhatia, referencing a 2021 review of new concepts in classification and treatment of rosacea. “And the antibiotics we do use are [recommended] at doses that are subantimicrobial, if you will…we want to get as much anti-inflammatory [dosing] as possible for rosacea patients.”

With doxycycline, for instance, less is more. He said, “100-mg and 40-mg doses both show the same 16-week efficacy” in decreasing the number of inflammatory lesions, noting that “we don’t need [the higher dose] to accomplish the same goal.” At the lower dose, it is not necessary to take doxycycline with food, he noted.

Bhatia emphasized that patient weight and rosacea severity based on inflammatory lesion count do not affect treatment efficacy of sub-antibiotic dosing. “It’s really important not to have that bias going in — to think that a patient who is heavier or more severe needs a higher dose,” he said, referencing a 2022 analysis he co-authored. “There’s really no difference — the absorption and mechanisms are the same.”

Other potential treatments under investigation include hydroxychloroquine, which may inhibit pro-inflammatory factors, and the interleukin (IL)-17 inhibitor secukinumab, Bhatia noted.

Topical Minocycline, Encapsulated Benzoyl Peroxide (BPO), Heparan Sulfate Analogs

“There’s been a resurgence of interest [in using minocycline] topically,” Bhatia said, which is significant given concerns about side effects and potential adverse events with long-term oral use. Minocycline foam, 1.5%, was approved by the US Food and Drug Administration (FDA) in 2020 for rosacea, and minocycline gel is under investigation as a potential treatment.

For patients who can tolerate minocycline foam, “we’re treating the scene of the crime, where the inflammation is,” he said. “There will be more activity where you need it, in the dermal stroma and epidermis,” and plasma concentration of minocycline will be low.

Minocycline foam, like other tetracyclines, has numerous impacts on the control of inflammation in rosacea, including stopping the activity and production of matrix metalloproteinases and reducing production of the LL-37 peptide. It is among the recently approved treatment options for rosacea that were not available when current published guidelines were last revised, according to a 2024 consensus opinion paper on diagnostic and therapeutic gaps co-authored by Bhatia.

Another is microencapsulated BPO cream 5%, which the FDA approved for treating rosacea in 2022. BPO is delivered gradually from tiny vesicles encapsulated with silica, which “makes it very easy to tolerate once it reaches the skin,” Bhatia said. A 2023 open-label extension study of two phase 3, vehicle-controlled trials demonstrated progressive clinical improvement in patients with rosacea, including reductions in erythema, and good tolerability for up to 52 weeks.

“Can one take a little holiday? You can take a month off here and there, or you can wind down to every other day,” said Bhatia, a co-investigator of the extension study. “You can find a routine that patients can handle.”

For topicals, patience is key. “We need to remind patients to give it a few days because rosacea skin is very sensitive and very inflamed, and the tolerability needs to be worked through,” he said.

In the research space, there is growing interest in heparan sulfate, an essential glycosaminoglycan that contributes to skin development and homeostasis and preserves the structural integrity of collagen and elastin fibers. The LL-37 peptide believed to play a role in rosacea pathogenesis has been shown to be inhibited by binding to heparan sulfate, but in inflammatory disorders, heparan sulfate is degraded by heparanase.

An exogenous heparan sulfate analog cannot be degraded by heparanase, however. In a 2023 small, single-center, randomized double-blind study of a low–molecular weight analog of heparan sulfate formulated into a cream, patients undergoing pulsed dye laser (PDL) treatments who also were treated with the cream had significantly more improvement in erythema over 8 weeks than those who received PDL treatments with a vehicle cream, likely resulting from inhibition of LL-37–induced IL-8 cytokine release, Bhatia pointed out.

“We’re seeing more movement in this direction,” he said, toward heparan sulfate analogs as potential treatment options.

In addition to better addressing patient-centric approaches, future guidance on rosacea management should better address the treatment of nonresponders, Bhatia noted at the meeting. This and other gaps in current guidance — including combination therapies, maintenance therapy beyond 12-16 weeks, and the diagnosis and treatment of rosacea in patients with skin of color — are discussed in the 2024 consensus paper.

Botanical Ingredients, Natural Options

Of relevance for rosacea, Bhatia added, are reported successes with botanical serums as an adjunct to aesthetic/cosmetic rejuvenation procedures such as lasers and radiofrequency microneedling procedures. Such serums contain antioxidant and anti-inflammatory ingredients derived from plant and fruit extracts — cucumber, thyme, olive leaf, mulberry root, and grapefruit, for example — that can calm post-procedure erythema and swelling, he said, referring to a 2024 paper on the complementary use of botanical-containing topical treatments as an adjunct to aesthetic laser or microneedling radiofrequency treatments.

There are lessons for rosacea. “These are things patients are looking for, that we should use with procedures for treating rosacea…that we should include in [treatment] combinations,” he said.

Additionally, some patients want a natural treatment plan, and there are natural options that have been shown, for instance, to impact histamine release and helper T-cell activation, have significant antioxidant activities, and inhibit arachidonic acid pathways, Bhatia said, referring to a 2024 review on the management of rosacea with natural compounds.

Licorice, colloidal oat powder, and feverfew are among natural compounds making their way onto the menu for rosacea management, Bhatia said. The Glycyrrhiza glabra and G inflata species of licorice plants are known to be rich in flavonoids and saponins, he said, and to inhibit the generation of superoxide anion and cyclooxygenase activity. Licorice has long been used in alternative and complementary medicine to treat various inflammatory conditions.

Creams containing licochalcone A derived from G inflata licorice have been shown in studies to reduce erythema in various cohorts, including a group with erythema caused by shaving and ultraviolet exposure, Bhatia pointed out.

These studies are among those discussed in the 2024 review of management of rosacea with natural compounds. Not all the natural products included have been studied in rosacea, according to the authors, but they have been shown to address symptoms/features that are common in rosacea and may be most beneficial in combination with other medical treatments.

Bhatia disclosed affiliations with AbbVie, Advanced Derm Solutions, Almirall, Arcutis, Beiersdorf, Biofrontera, BMS, BI, Ferndale, Galderma, Incyte, ISDIN, J&J, LaRoche-Posay, Leo, Eli Lilly, Novartis, Ortho, Pfizer, Regeneron, Sanofi, Sun Pharma, and Verrica.