Rosacea: We Still Haven’t Found What We’re Looking For

In May 1987, U2 released “I Still Haven’t Found What I’m Looking For” as a single from their legendary fifth album, The Joshua Tree. The song became their second consecutive #1 hit in the United States to chart on the Billboard Hot 100.1 Here I am, almost 4 decades later, composing an editorial focused on where we are now in dermatology with rosacea. The first thought that came to mind is that U2 was right—and still is—because with rosacea, we still haven’t found what we’re looking for.

In this editorial, I am discussing cutaneous rosacea, not including ocular disease and phymatous changes. The first challenge with cutaneous rosacea is to get the dermatology community on the same page with what the clinical disease state includes, as the individual “dots” that comprise the pathophysiology of rosacea are not similarly connected in each affected patient. This confounds our ability to effectively treat the disease state in many cases, as the clinical manifestations of rosacea are highly variable, reflecting relative contributions from different components of the pathophysiology.^2-5

On top of this challenge, the vast majority of US Food and Drug Administration (FDA)–approved therapies for rosacea have been directed at reducing papules and pustules, which are not present in all patients, and their associated perilesional erythema.^6,7 We have only had topical alpha agonists as FDA-approved therapies for persistent facial erythema, the superficial vascular component of rosacea that is distinct from the papulopustular component and can intensify during flares with flushing episodes. A major limitation of the alpha-agonist topical approach is the short duration of their effects, which last only hours, and the need for consistent application over time, which can be frustrating for patients. Physical modalities such as lights and lasers offer marked assistance, especially for the superficial vascular component, but may be limited by availability, cost, and differences in expertise. Is the above challenging enough? Keep in mind that I still have not addressed the skin barrier aspects of the disease, symptomatology, and patient education challenges.

I don’t want to sound as if dermatology has been defeated, as we have actually been able to provide marked improvement for many patients with rosacea.^6-9 This is especially true in those who present with papules and pustules and also are compliant and patient enough to allow for the integration of the topical and/or physical therapies needed to treat the vascular components including telangiectasias. What has lagged has been the ability to develop a more comprehensive selection of pharmaceutical options, as most have targeted the papulopustular manifestation of the disease. There are many highly effective options in this “papules and pustules of rosacea” space, including topical ivermectin, azelaic acid, and metronidazole, along with the addition of a foam formulation of minocycline, a microencapsulated formulation of benzoyl peroxide, and low-dose oral minocycline. What mostly limits experience with newer FDA-approved therapies is access for patients due to insurance coverage issues and generic substitutions. Overall, the development of newer FDA-approved pharmacologic therapies has become relatively stagnant and remains so at the present time.^6-9

So where are we now? Much of the emphasis on rosacea management has transitioned to alternative areas of consideration, including skin care and barrier dysfunction, the role of vitamins and other nutrients, and use of natural compounds.

An algorithm created by a consensus panel of dermatologists has provided foundational measures recommended for use in all patients with rosacea and rosacea-prone skin, including education, behavioral modifications, recognition and avoidance of triggers, avoidance of skin irritants, preventive skin care, and sun photoprotection measures.¹⁰ The algorithm emphasizes that assessment of an individual’s facial skin condition and grading of cutaneous rosacea are very important at the first visit and continually thereafter during treatment while the preventive measures continue. Individual dermatology panels have published on skin care nuances suggested for specific patient subgroups such as skin of color and Asian and Latino populations.^11-13 While the importance of skin care and skin barrier function in rosacea are well known to the dermatology community, it is essential for clinicians to consistently emphasize this importance to their patients and their staff.

A relatively recent publication has thoroughly addressed the potential roles of vitamins and nutrients in rosacea, discussing both systemic supplementation and topical approaches. A variety of ingredients were evaluated—including vitamin B3, a vitamin A derivative, vitamin C, vitamin D, zinc formulations, and omega-3 fatty acids—demonstrating a range of outcomes.¹⁴ There are data that support the potential of vitamins and nutrients as an adjunctive approach; however, at present, this area holds potential for future advancement without any definitive products or well-established recommendations available. More well-designed studies that are targeted for specific rosacea populations are needed.

A large array of natural compounds, primarily botanicals and phytochemicals, have been discussed in the literature for both short- and long-term management of rosacea.¹⁵ Many cosmeceutical products are gaining public notoriety, as the concept of “natural” is appealing to the lay population due to the assumption that natural implies greater safety, which is not necessarily true. Semenescu et al¹⁵ provided a very comprehensive review of the applicable characteristics of several plant-based agents and potential mechanisms that may be beneficial as adjunctive agents in rosacea. Similar to vitamins and nutrients, there is some scientific basis for the routine integration of natural phytochemicals, but research is needed with well-designed studies used in targeted specific rosacea populations.

Unfortunately, I cannot finish this editorial with ground-breaking news about a new gamechanger approach or product; however, I can tell you that dermatology never gives up. Advances in developing adjunctive therapies and future disease targets such as mast cell activation, microvesicle particles, NLRP3 inflammasome pathway, and Janus kinase inhibition are always in motion, and we continue to try to find what we’re looking for.¹⁶