What Is Up and Coming in Rosacea?

In her session, “Rosacea: What’s New and What’s Coming,” presented at Fall Dermatology Week 2022, Linda Stein Gold, MD, discussed the pathogenesis, novel topical treatment options, and systemic approaches to rosacea.

Dr Stein Gold started with the pathogenesis of rosacea, which involves an abnormality of the innate immune system and upregulation of the antimicrobial peptides and cathelicidin pathway. “We know that there are a number of triggers that set this process off. And overall, we end up with an inflammatory condition that can manifest in a number of ways.”

Next, she moved on to the treatment options. Patients manifest different signs and symptoms of rosacea. Treatments are mix and matched for a comprehensive approach to treatment.

Dr Stein Gold further mentioned mast cells, which play a central role in the pathogenesis of rosacea. “Mast cells are involved in recruiting certain immune cells, which helps to amplify the overall inflammatory response. They are also involved in angiogenesis and vasodilation,” She stated. “Mast cells have a lot of different properties and potentially could be a target of treatment that would help in the underlying pathogenesis of the disease.”

She also elaborated on rosacea characterized by a profoundly diminished skin barrier: “The barrier of rosacea patients is actually very similar to the abnormal barrier of atopic dermatitis patients. So, we have to pay attention to repairing the skin barrier in any treatment regimen that we put in place for our rosacea patients.”

Dr Stein Gold moved to demodex categorized by two different types: demodex brevis and demodex folliculorum. Referring to a study, “The presence of demodex folliculorum was found to be higher in the [patients] who have metabolic syndrome compared to the healthy group; high blood sugar levels may make them more susceptible to infestation of demodex folliculorum.”

Dr Stein Gold addressed the questions about whether rosacea is associated with other inflammatory conditions. “Some studies did show that there was an increase in certain dyslipidemias in hypertension, possibly an increase in blood pressure, but they didn't find a significant increase in ischemic heart disease, stroke, diabetes, or high-density lipoprotein.”

What is up and coming in rosacea? Dr Stein Gold started with minocycline, which:

• reduces LL-37
• reduces matrix metalloproteinase production (MMP 2 and 9) associated with:
  • stratum corneum permeability barrier dysfunction
  • dysregulation of neuroimmune and neurovascular activities
  • changes in density of mast cells and sensory nerves
• inhibits neutrophil chemotaxis and oxidative bursts.

“Tetracycline antibiotics are associated with numerous nonantibiotic properties that are important for rosacea pathophysiology, including decreasing inflammation,” she stated. “Minocycline is a large molecule that is very challenging to deliver topically, challenging to keep it stable in a topical formulation, and challenging to create a cosmetically acceptable vehicle.”

There is a minocycline foam 1.5% (FMX103) available. “The proportion of patients achieving IGA [Investigator’s Global Assessment scale] treatment success in both FMX103 1.5% treatment groups was statistically significant as compared with [the] vehicle at week 12,” Dr Stein Gold reported. “After using this drug, once a day for 12 weeks, we had about 50% of patients getting to clear, almost clear, using this drug as monotherapy.” The drug was well tolerated, and there was no evidence of minocycline-induced hyperpigmentation.

There is also a low dose oral minocycline, which is subantimicrobial: doxycycline (DFD-29). “[DFD-29 would] hopefully have all of the benefits of the anti-inflammatory properties without the antimicrobial properties,” she stated.

“What about the use of benzoyl peroxide (BPO) for the treatment of rosacea?” asked Dr Stein Gold. As a standard of treatment, it is irritating. However, “microencapsulation stabilizes the BPO and reduces direct exposure to the skin, theoretically reducing irritation.”

Dr Stein Gold gave insights into another treatment option, sarecycline, which is US Food and Drug Administration approved for the treatment of acne. Sarecycline is a good treatment option in terms of it being more anti-inflammatory than its tetracycline colleagues, and it also has a narrow spectrum of activity.

In conclusion, Dr Stein Gold said, “We have some wonderful treatments available for us and we have some very exciting agents in the pipeline. So, aim for clear skin.”

Reference

Stein Gold L. Rosacea: what’s new and what’s coming. Presented at: Dermatology Week 2022; September 14-17, 2022; Virtual.