Update on the Management of Rosacea: A Status Report on the Current Role and New Horizons With Topical Azelaic Acid
December 2014 | Volume 13 | Issue 12 | Supplement | s101 | Copyright © 2014
James Q. Del Rosso DO FAOCDa and Leon H. Kircik MDb
aLas Vegas Skin and Cancer Clinics/West Dermatology Group, Henderson, NV; Touro University College of Osteopathic Medicine, Henderson, NV
bIcahn School of Medicine at Mount Sinai, New York, NY; Indiana University School of Medicine, Indianapolis, IN;
Physicians Skin Care, PLLC, Louisville, KY
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.
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Since the publication of the landmark article by the National Rosacea Society in 2002, which introduced a standard classification system for rosacea, there has been a plethora of basic science and clinical research publications addressing the clinical presentations of rosacea and the underlying pathophysiologic mechanisms that appear to correlate with specific visible manifestations.1-6 The magnitude of the individual contribution of each of these mechanisms can vary among different patients, thus accounting for the range of differences in the clinical presentations of rosacea.3,4,7-9
The 2 main pathophysiologic mechanisms fundamental to rosacea that have been reported based on several studies are neurovascular dysregulation and abnormal immune detection and response, with both signaled by a variety of exogenous triggers.3-13 A greater understanding of these underlying pathophysiologic pathways has led to improved correlations between the clinical features of rosacea and the integration of specific therapies, although much more research needs to be completed to achieve further understanding because the pathophysiology of rosacea and the natural history of its progression are complex. 3-5,14,15 The current belief is that rosacea, especially in its most common clinical presentations, is an inflammatory facial skin disorder most commonly affecting adults who are affected by rosacea-prone skin.3-6,10,11,16,17 Essentially, rosacea-prone skin is “wired differently,” with the facial skin of those with rosacea exhibiting physiochemical, neurovascular, and microanatomic and ultrastructural differences compared with normal skin.3-13,15-17 Various triggers that have been noted to incite flares of rosacea (such as ambient heat, ultraviolet light exposure, spicy foods, and Demodex mite proliferation) induce the onset of central facial vasodilation and cutaneous inflammation due to the heightened responsiveness of both neurovascular and innate immunologic pathways associated with rosacea-prone skin.3-12,16,17
Most of the development of medical therapies for rosacea occurred while the pathophysiology was not well understood.1,5,13 As a result, researchers were limited by the absence of specific targets against which to direct therapies, which hampered the development of therapeutic agents for rosacea.5 Prior to 2013, only 3 medical therapies have been submitted to the United States (US) Food and Drug Administration (FDA) for approval for rosacea, with all 3 receiving an approved indication for the inflammatory lesions (papules and pustules) of rosacea, commonly referred to as papulopustular rosacea (PPR). These 3 agents are topical metronidazole (first formulation 0.75% gel, approved in 1988; 0.75% and 1% available subsequently in multiple formulations); azelaic acid (AzA) 15% gel (approved in 2002); and doxycycline 40 mg modified-release capsule once daily (doxy-MR 40 mg QD, approved in 2006).15,18 Most recently, alpha-adrenergic agonists (brimonidine 0.33% gel, approved in August 2013; oxymetazoline in Phase 3 studies) have been