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Rosacea Editorials
Treatment of Rosacea: Expert Insight on Trends and Best Practice
Rosacea is a chronic inflammatory disease that has been estimated to affect 16 million people in America alone. It is characterized by a range of clinical symptoms notably erythema, telangiectasia, papules, pustules, plaques, edema, skin discomfort, phymatous changes and ocular involvement. In addition to clinical symptoms, the condition is recognized to affect both social and professional lives and can lead to psychosocial issues.
In clinical practice, patients often present with a specific range of symptoms, with one or two primary symptoms observed as the leading ones. For didactical reasons, the typical classifications outline certain rosacea “subtypes” (erythematotelangiectatic -ETR, papulopustular -PPR, phymatous -PHY and ocular -OR) or subforms such as granulomatous rosacea and Morbus Morbihan.
When developing the treatment plan for an individual patient, we need to be careful not to try to fit a patient to a subtype, or fit treatment by subtype, but rather identify the leading symptom(s) and tailor the treatment plan to the individual’s set of symptoms. This, in my experience, yields better patient outcomes.
This is an exciting time in the advancement of our understanding and treatment of rosacea, with further elucidation of the pathophysiology coupled with the development of new therapies to treat the disease. Inflammation is the key underlying mechanism, giving rise to the varying symptoms. New scientific data continues to demonstrate the involvement of infiltrates, changes in pro-inflammatory cytokine profile and gene upregulation, therefore raising the need for most patients to receive basic anti-inflammatory therapy.
Articles
Treating Inflammation in Rosacea: Current Options and Unmet Needs
Rosacea is a disease resulting from dysregulation of innate, adaptive, and neurovascular immune systems. Inflammatory pathways activated in rosacea can explain many of its signs and symptoms. Current treatments address some of these inflammatory processes, alleviating erythema and decreasing papules and pustules. However, for the majority of patients, complete clearance of these features is not currently achievable even with combination therapy. There is a need to address the spectrum of inflammatory processes involved in rosacea and for more efficacious agents with the goal of providing complete clearance for patients.
J Drugs Dermatol. 2020;19(6): doi:10.36849/JDD.2020.5187
Efficacy and Safety of Ivermectin 1% Cream in Treatment of Papulopustular Rosacea: Results of Two Randomized, Double-Blind, Vehicle-Controlled Pivotal Studies
Papulopustular rosacea (PPR) is a chronic inflammatory disorder characterized by facial papules, pustules, and persistent erythema. It is highly prevalent and associated with adverse impact on quality of life and depression. The etiology of rosacea is multifactorial. In addition to neurovascular dysregulation, the facial skin of patients with rosacea is affected by augmented proinflammatory immune responses. The principal active cathelicidin peptide (LL-37) is highly concentrated in skin affected by rosacea and can contribute to acute inflammation. Moreover, PPR is characterized by the presence of inflammatory infiltrates that accompany flares, along with a heightened immune response involving neutrophilic infiltration and increased gene expression of IL-8.5 In addition to exogenous factors (including UV light, heat, and alcohol), it may be triggered by Demodex folliculorum mites. Some studies of PPR observed higher mite densities compared to controls. Therefore, a multitude of factors can activate neurovascular and/or immune responses, and consequential inflammation leading to flares of rosacea.
Update on the Management of Rosacea: A Status Report on the Current Role and New Horizons With Topical Azelaic Acid
Azelaic acid (AzA) 15% gel has been available in the United States for slightly over a decade, approved for treatment of the inflammatory lesions (papules and pustules) of rosacea. Efficacy and safety have been established in multiple studies both as monotherapy and in combination with oral doxycycline. Azelaic acid 15% gel has been shown not to induce epidermal permeability barrier impairment, and proper skin care reduces the likelihood of neurosensory adverse effects of stinging and burning that can affect a subset of patients with rosacea. Azelaic acid 15% gel appears to produce a quicker onset of clinical effect than metronidazole in some patients when either agent is used in combination with subantimicrobial dose doxycycline; however, both topical agents are effective when used in this combination approach for papulopustular rosacea (PPR). Although more information is needed on the modes of action of AzA in the treatment of rosacea, downregulation of the cathelicidin pathway appears to be one operative mode of action based on in vitro and in vivo studies, including data from patients treated with AzA 15% gel for PPR. Azelaic acid 15% foam is currently in the latter stages of development for PPR, with pivotal studies demonstrating efficacy and favorable tolerability, including a very low incidence of stinging, burning, and itching even without the use of designated skin care products.
J Drugs Dermatol. 2014;13(suppl 12):s101-s107.
Case Reports
A Sequential Approach to the Treatment of Severe Papulopustular Rosacea Not Responding to Traditional Treatment
We report the case of a German female patient presenting with papulopustular rosacea (PPR) with a high count of facial inflammatory lesions and severe erythema who had not responded well to treatment with traditional therapies for a decade. In this patient, a sequential therapy consisting of oral modified-release doxycycline 40 mg (initially as monotherapy, then in combination with topical metronidazole), followed by topical ivermectin 10 mg/g was both rapidly active and effective. Following reduction of the inflammation with modified-release doxycycline 40 mg upfront and the disease becoming moderate in severity, the dose of this agent could be reduced and combination therapy with metronidazole 7.5 mg/g lotion started to continue decreasing inflammatory lesions count and erythema severity, before treatment with the recently approved agent ivermectin 10 mg/g was implemented to provide almost complete clearance. This sequential treatment was effective in reducing both the number of papules and pustules and the severity of erythema, with a good safety profile. In addition, a large improvement was documented in the patient’s DLQI score, contributing to her overall wellbeing.
J Drugs Dermatol. 2016;15(6):769-771.
Paradoxical Erythema Reaction of Long-term Topical Brimonidine Gel for the Treatment of Facial Erythema of Rosacea
In 2013 brimonidine tartrate gel 0.33% (Mirvaso Gel, Galderma Laboratories, LP, Fort Worth, TX) was approved by the US Food and Drug Administration for the treatment of facial erythema of rosacea. It is the first and only drug on the market to address the hallmark redness of this chronic, inflammatory disease. Commonly reported adverse events include erythema/flushing worse than at baseline, most often occurring with the first application. We report a unique case of facial erythema of rosacea that responded to brimonidine gel with effective blanching for two years until the patient developed a paradoxical erythema reaction. This is an adverse reaction physicians should be aware of with continued prescription of brimonidine gel for their rosacea patients.
J Drugs Dermatol. 2016;15(6):763-765.
Topical Treatment With Liposomal Sodium Copper Chlorophyllin Complex in Subjects With Facial Redness and Erythematotelangiectatic Rosacea: Case Studies
Physicians are often presented with patients complaining of facial redness and difficult to control rosacea. The water soluble sodium copper chlorophyllin complex has been shown to have anti-oxidant, anti-inflammatory, and anti-bacterial activities in vitro and anti-redness, pore reduction, and anti-acne activities in pilot clinical studies. In these case studies, the safety and efficacy of a topical gel containing a liposomal suspension of sodium copper chlorophyllin complex was assessed in subjects with facial redness and erythematotelangiectatic rosacea.
J Drugs Dermatol. 2015;14(10):1157-1159.
