TherapeuTics for The clinician Treating Epidermal Melasma With a 4% Hydroquinone Skin Care System Plus Tretinoin Cream 0.025% Pearl Grimes, MD; JoAnne Watson, DPM We sought to evaluate the efficacy and tolerability erythema, peeling, and stinging sensation). The of treating melasma using a 4% hydroquinone skin 4% hydroquinone skin care system plus tretinoin care system, including a proprietary cleanser, cream 0.025% is effective and well-tolerated in toner, 4% hydroquinone, exfoliation enhancer, and the treatment of melasma. sunscreen, plus tretinoin cream 0.025%. Together Cutis. 2013;91:47-54. these products offer not only treatment of melasma but also a complete skin care regimen. Twenty participants with mild or moderate epidermal elasma is symmetric facial hypermelanosis melasma with Fitzpatrick skin types III to VI were characterized by patches of light brown or instructed to use the hydroquinone skin care M gray-brown macules on sun-exposed skin. system and tretinoin cream CUTISfor 12 weeks. It occurs most commonly in women, especially those Melasma severity, melasma pigmentation living in areas of intense sunlight.1 The misconcep- intensity, and melasma area and severity tion that melasma is merely a cosmetic nuisance index (MASI) score were significantly reduced from has resulted in underdiagnosis and undertreatment.2 week 4 onward relative to baseline (P≤.01). The However, the condition can cause great distress proportion of participants who felt embarrassed or and can have substantial negative effects on the self-conscious about their skin very much or a lot emotional well-being, social life, and quality of life declinedDo from 80% (16/20) toNot 20% (4/20) between (QOL) Copyof patients.3 baseline and week 12. Similarly, the proportion of Several factors may be involved in triggering those who made very much or a lot of effort to hide melasma, including genetic influences, pregnancy, their skin discoloration declined from 90% (18/20) UV light, oral contraceptives, phototoxic drugs, and to 37% (7/19). In total, 85% (17/20) of participants antiseizure drugs.4 Because exposure to UV light were satisfied with the overall effectiveness of the appears to be one of the most important triggers,5 a study treatment. Three participants had adverse broad-spectrum sunscreen should always be part of events probably related to treatment (dryness, any depigmenting treatment regimen; its inclusion has been proven to enhance the effectiveness of treat- ment.6 Hydroquinone is the most effective topical Dr. Grimes is from the Vitiligo and Pigmentation Institute of bleaching agent approved by the US Food and Drug Southern California, Los Angeles. Dr. Watson is from the Clinical Administration for the treatment of melasma.4 It Affairs Department, OMP, Inc, Long Beach, California. reduces the synthesis of melanin by inhibiting tyrosi- This study was supported by OMP, Inc. Dr. Grimes has been an nase activity and also may be involved in the degra- investigator or consultant for Aclaris Therapeutics, Inc; Clinuvel 4 Pharmaceuticals; Combe Inc; Merz Pharmaceuticals; SkinMedica; dation of melanosomes and melanocytes. Tretinoin 5,7,8 and Suneva Medical, Inc. She also has been an investigator and also is effective in the treatment of melasma. consultant for OMP, Inc, and Procter & Gamble; an investigator and Tretinoin may enhance the penetration of hydroqui- speaker for Galderma Laboratories, LP; and an investigator, consul- none through the stratum corneum, protect hydroqui- tant, and speaker for Allergan, Inc. Dr. Watson is an employee of and none from oxidation, and facilitate pigment removal holds stock and stock options in OMP, Inc. 9 Correspondence: Pearl Grimes, MD, Vitiligo and Pigmentation by accelerating keratinocyte turnover. Institute of Southern California, 5670 Wilshire Blvd, Ste 650, Although both hydroquinone and tretinoin are Los Angeles, CA 90036 ([email protected]). effective in treating melasma,10-12 a disadvantage WWW.CUTIS.COM VOLUME 91, JANUARY 2013 47 Copyright Cutis 2013. No part of this publication may be reproduced, stored, or transmitted without the prior written permission of the Publisher. Therapeutics for the Clinician of monotherapy with either agent is the prolonged skin (eg, from UV light) or facial sunburn; anticipated treatment time required before meaningful results need to use other medicated products on the face are achieved. For example, it has been reported that during the study; excessive or prolonged exposure to it may take 24 weeks to achieve notable improve- sunlight without protective clothing; and pregnancy, ment with tretinoin treatment.8 With combination breastfeeding, or planning to become pregnant during therapy, meaningful improvements can be achieved the study. more rapidly. The following washout periods were required: We sought to evaluate the efficacy and tolerability 1 week for medicated facial cleansers and facial hair of treating melasma using a 4% hydroquinone skin removal procedures; 30 days for topical prescription care system plus tretinoin cream 0.025%, which not treatments, sunbathing and UV-light therapy, topical only treats melasma but also provides a complete skin medications, bleaching products, and photosensitiz- care regimen including protection from UV light. ing procedures or medications on the face includ- ing corticosteroids, hydroquinone, -hydroxy acids, Methods b-hydroxy acids, kojic acid, retinoic acid, retinol, Participants—Female patients were eligible to enroll salicylic acid, and vitamin C and vitamin D products in the study if they met the following inclusion or derivatives; 6 weeks for facial microdermabrasion; criteria: mild or moderate epidermal melasma, con- 12 weeks for systemic steroids; and 6 months for firmed with Wood lamp examination; minimal to photoallergic, phototoxic, and photosensitizing drugs marked intensity of melasma pigmentation; cutaneous or systemic retinoids, methotrexate, laser resurfacing melanosis that had been stable over the preceding procedures, deep skin peels, and injection of dermal 3 months; Fitzpatrick skin types III to VI; and aged fillers or botulinum toxin type A. 25 to 65 years. The study was conducted in accordance with the Participants were required to be willing to refrain 2004 version of the Declaration of Helsinki and all from the following throughout the study: facial use participants signed informed consent. The study was of nonstudy topical products including medications, performed between May 2010 and September 2010. moisturizers, sunscreens, fragrances, and medicated Treatment Regimen—Participants were instructed makeup, though oil-free noncomedogenicCUTIS makeup, to use the 4% hydroquinone skin care system plus mascara, eyeliner, eye shadow, and lipstick were tretinoin cream 0.025% on their entire face for allowed; facial procedures including chemical peels, 12 weeks. The 4% hydroquinone skin care system facial microdermabrasion, laser resurfacing, nonab- involved applying the following proprietary products: lative laser, light or radiofrequency treatment, and foaming gel cleanser (Nu-Derm® Foaming Gel), toner injection of dermal fillers or botulinum toxin type A; (Nu-Derm Toner), 4% hydroquinone (1 g)(Nu-Derm facial hair removal, except plucking of eyebrows with Clear), exfoliation enhancer containing -hydroxy tweezers,Do which was allowed; andNot use of systemic reti- acids (0.5Copy g)(Nu-Derm Exfoderm Forte), and sun- noids, methotrexate, photoallergic drugs, phototoxic screen (Nu-Derm Healthy Skin Sun Protection drugs, and photosensitizing drugs. Sunbathing, the use SPF 35)(all Nu-Derm products from OMP, Inc). The of tanning booths, and the facial use of tanning prod- cleanser, toner, and hydroquinone were applied twice ucts also were prohibited; participants were required daily, and the exfoliation enhancer and sunscreen to wear appropriate protective clothing when exposed were applied each morning. Tretinoin cream 0.025% to the sun. Participants taking oral contraceptives or (0.5 g) was mixed with 4% hydroquinone (0.5 g) hormonal replacement therapy were required not to (Nu-Derm Blender) and applied each evening. alter their treatment during the study. On the instruction of the investigator, participants Exclusion criteria included the following: his- could use a study moisturizer (Nu-Derm Action) for tory or presence of any facial skin condition that dryness or 0.5% hydrocortisone (Nu-Derm Tolereen) might interfere with diagnosis or evaluation during for other tolerability issues such as itching, erythema, the study; known hypersensitivity or allergy to sul- and irritation, as needed. This study was unblinded fites or ingredients in the study treatment products, and the investigator and participants were aware of including parabens and aloe; history of increased the treatment being given. pigmentation and/or contact dermatitis with prior Outcome Measures—The investigator evaluated use of hydroquinone or tretinoin; dermal melasma melasma severity, melasma pigmentation intensity, or a combination of dermal or epidermal melasma; melasma area and severity index (MASI) score, postinflammatory hyperpigmentation; vitiligo; history melasma improvement, erythema, dryness, peeling, or presence of Ota nevus; depressed or atrophic macu- and burning/stinging at baseline and/or weeks 4, 8, lar lesions; requirement for hormonal treatment that and 12 (Tables 1 and 2). Participants completed a might enhance pigmentation; irritation of exposed questionnaire13 at each time point asking them to 48 CUTIS® WWW.CUTIS.COM Copyright