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The Treatment of Rosacea Anetta E Review The Treatment of Rosacea Anetta E. Reszko MD, PhD; Diane Berson MD Rosacea is a chronic condition affecting the facial and frequently ocular tissues. It is historically underdi- agnosed and affects people of all ethnicities, with higher overall prevalence in people of Celtic descent. The exact pathophysiology of rosacea is poorly understood. A variety of medical therapies, depending on the subtype, are available to treat the various signs and symptoms of rosacea. osacea is a common, chronic skin disorder differentiated from chronic sun damage and photoder- that frequently affects light-skinned white matitis. Papulopustular rosacea must be distinguished population. Overall prevalence of rosacea from acne vulgaris, seborrheic dermatitis, lupus miliaris ranges from less than 1% up to 10%. The disseminates faciei, collagen vascular diseases, perioral nose, cheeks, chin, forehead, and glabella dermatitis, and Demodex folliculitis. Differential diag- areR the most frequently affected sites. The disease has a nosis of ocular rosacea includes allergic conjunctivitis variety of clinical manifestations ranging from flushing, and blepharitis. persistent COSerythema, telangiectasias, papules, pustules, DERM Therapy of rosacea is centered on symptomatic and sebaceous gland hyperplasia. Significant psycho- improvement, including reduction of facial erythema logical stress and perceived diminished quality of life and number of inflammatory lesions; decrease in the often accompany this condition.1 The pathogenesis is number, duration and intensity of flares; and reduc- likely multifactorial and includes genetic and vascular tion of concomitant symptoms of itching, burning, and elements, climatic exposures, pilosebaceous unit abnor- facial tenderness. malities, and possibly microbial organisms and antimi- In addition to medical therapy, sun protection and crobialDo antibodies.2 Notappropriate Copy skin care regimen need to be chosen because Diagnosis of rosacea is based primarily on clinically rosacea patients often exhibit marked skin sensitivity and recognizable morphologic characteristics. An expert suffer from intolerance to skin products and cosmetics.3 committee assembled by the National Rosacea Society In a National Rosacea Society survey of 1066 patients, on the classification and staging of rosacea defined and 41% reported that certain skin care products aggravated classified rosacea in April 2002 into 4 clinical subtypes their condition and 27% said certain cosmetics also based primarily on morphologic characteristics. The caused rosacea flare-ups. Ingredients frequently quoted subtypes include erythematotelangiectatic rosacea (ETR), as triggers for irritation include alcohol (66%), witch papulopustular rosacea (PR), phymatous rosacea, and hazel (30%), fragrance (30%), menthol (21%), pepper- ocular rosacea. mint (14%), and eucalyptus oil (13%). Most respondents In order to design appropriate treatment regimen it is said they avoided astringents, exfoliating agents, and essential to correctly identify the subtype of rosacea. In other types of products that may be too harsh for sen- addition, rosacea has to be distinguished from its clini- sitive skin.4 Triggers for cutaneous flushing should be cal mimickers. Erythematotelangiectatic rosacea must be identified and eliminated. Commonly identifiable trig- gers include topical cosmetics and corticosteroids, alco- hol, tobacco, exercise, hormonal changes, sun exposure, Drs. Reszko and Berson are from the Department of Dermatology, Weill hot weather, exercise, ingestion of hot or spicy foods/ Cornell Medical College of Cornell University, New York, New York. drink, caffeine, emotional stress, and medications such The authors report no conflict of interest in relation to this article. as topical and systemic steroids, niacin, and nitroglyc- Correspondence: Anetta E. Reszko, MD, PhD, 1305 York Ave, erin. A flare of rosacea may be anticipated when steroids 9th Floor, New York, NY 10021 ([email protected]). are discontinued and may be dramatic. 186 Cosmetic Dermatology® • APRIL 2011 • VOL. 24 NO. 4 www.cosderm.com Copyright Cosmetic Dermatology 2011. No part of this publication may be reproduced, stored, or transmitted without the prior written permission of the Publisher. Figure 1. Facial redness associated with the erythemato- telangiectatic rosacea subtype. Flushing, persistent red- ness, and visible blood vessels also may appear. Currently, the following medications are the only patients with moderate facial ETR was evaluated in drugs that are approved by the US Food and Drug a case series on 29 patients.5 Evaluation measures Administration (FDA) for the treatment of rosacea: included spectrophotometric erythema scores, blinded • Topical medications: metronidazole gel, cream, investigator grading, and patient assessment of severity lotion 0.75% and 1%; azelaic acid cream 15% and 20%; and associated symptoms. Both PDL and IPL resulted sulfacetamide 10% with sulfur 5% gel, cream, topical in reduction in cutaneous erythema, telangiectasia, and suspension,COS wash) DERMpatient-reported associated symptoms. No significant • Systemic: Oracea 30 mg immediate release and difference was noted between PDL and IPL treatment. 10 mg delayed release doxycycline A topical selective a-agonist, oxymetazoline, repre- Other non–FDA-approved treatments used off-label sents a novel approach to management of ETR-associated also have been beneficial and will be discussed below. erythema and flushing. A small study showed notable benefit with the use of oxymetazoline in reducing the ETR flares and the inflammatory symptoms in patients with The DoETR subtype is clinically characterizedNot by diffuse traditional Copy medication-resistant ETR.8 erythema and telangiectasias on the cheeks, forehead, Facial edema may be a prominent clinical feature of dorsal nose, or sometimes entire face (Figure 1). Patients rosacea. Recurrent vasodilation results in a feeling of frequently complain of intolerance or sensitivity to topi- fullness of the cheeks and visible subtle induration of the cal products and cosmetics. cheeks, so-called solid facial edema. Solid facial edema of This type of rosacea is best treated with avoidance ETR can respond to isotretinoin. of triggers leading to flushing, strict photoprotection, electrosurgery, and phototherapy. In recent years photo- PR therapy and laser therapies have been gaining popularity The PR subtype is characterized by papules and pus- as treatments of rosacea-associated erythema and telangi- tules often on an erythematous base primarily affect- ectasias. Laser therapies include pulsed dye laser (PDL), ing the nose, cheeks, and forehead. Predilection of potassium-titanyl-phosphate (KTP) laser, Nd:YAG laser, the lesions on the central, convex aspect of the face, or intense pulsed light (IPL).5,6 In a study of 34 patients sometimes with corresponding central facial edema, is with ETR, IPL treatment resulted in overall patient and frequently noted. physician reported over 50% improvement in 73% and 83% of patients, respectively.6 The results were sustained TOPICAL THERAPIES at 6 months. In a different study 83% of patients had The major topical antibiotics used to treat PR are less facial redness, 75% noted less flushing and better metronidazole, clindamycin, and erythromy- skin texture, and 64% noted fewer acneform breakouts.7 cin. Other topical therapies include azelaic acid, The use of nonpurpuragenic PDL and IPL treatment pimecrolimus, antiparasitics, a-adrenergic ago- to reduce erythema, telangiectasia, and symptoms in nists, and topical sulfacetamide 10% with sulfur 5%. www.cosderm.com VOL. 24 NO. 4 • APRIL 2011 • Cosmetic Dermatology® 187 Copyright Cosmetic Dermatology 2011. No part of this publication may be reproduced, stored, or transmitted without the prior written permission of the Publisher. The TreaTmenT of rosacea Metronidazole was shown as a main modulator of the inflamma- Clinical efficacy of topical metronidazole in the treatment tory response modulated by azelaic acid in normal of rosacea has been shown in a number of clinical tri- human keratinocytes.16 als.9-12 The mechanism of action of metronidazole is not Clinical safety and efficacy of azelaic acid gel 15% yet well established, but appears to be anti-inflammatory. applied twice daily for 12 weeks has been demonstrated Topical metronidazole is commercially available in a gel, in 2 phase 3, vehicle-controlled, randomized trials of lotion, and cream 0.75% for twice-daily use and a gel 1% 664 patients with PR. On average, improvement of ery- for once-daily use. Twice-daily metronidazole 0.75% thema ranged from 44% to 46% in patients treated with was shown to be well tolerated and effective in the azelaic acid, compared with 28% to 29% in the vehicle treatment of 582 patients with mild to moderate PR.12 group. A mean reduction in inflammatory papules and Mean erythema severity score was reduced by 50% by pustules ranged from 51% to 58% in the azelaic acid week 12 of treatment.13 In a 12-week, randomized con- group, compared with 39% to 40% in the vehicle group. trol study, Jorizzo et al14 showed that once-daily dosing Data from 3 clinical trials analyzed by Cochrane review of metronidazole cream 1% is as effective as twice-daily showed rates of improvement in azelaic acid group of dosing. Metronidazole is generally well tolerated and has 70% to 80% compared with 50% to 55% in the placebo a low incidence of adverse side effects. Most commonly group.9 In a randomized trial comparing topical metroni-
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