Objective Assessment of Erythema and Pigmentation of Melasma Lesions and Surrounding Areas in Long-Term Management Regimens With Triple Combination

April 2014 | Volume 13 | Issue 4 | Original Article | 444 | Copyright © April 2014

Doris Hexsel MD,a,b Mariana Soirefmann MD MsC,a,b Juliana Dumêt Fernandes MD PhD,c and Carolina Siega BSca

aBrazilian Center for Studies in Dermatology, Porto Alegre, RS, Brazil bDepartment of Dermatology, Pontificia Universidade Catolica do Rio Grande do Sul, Porto Alegre, RS, Brazil cUniversidade Federal da Bahia (UFBA), Salvador, BA, Brazil

BACKGROUND: Melasma has a negative impact on quality of life since it typically occurs on the face.
OBJECTIVES: To evaluate the erythema and pigmentation of melasma lesions and the surrounding areas in patients receiving triple combination (TC: hydroquinone, tretinoin, and fluocinolone acetonide) regimens.
METHODS: Patients first received an 8-week daily TC treatment and were then randomized to twice weekly or tapering regimen with TC. Melanin and erythema levels of lesions and surrounding areas were objectively measured using a narrowband reflectance spectrophotometer.
RESULTS: Progressive reduction in the mean melanin levels was observed in the treatment phase. Following both maintenance regimens, there was no difference between melanin levels in the melasma lesions. Adverse effects were rare in both phases of the study and there was borderline reduction in erythema with regimen II.
CONCLUSION: Both maintenance regimens were effective in maintaining results obtained during the initial treatment phase, and were safe and well-tolerated. Erythema was less intense with the tapering regimen.

J Drugs Dermatol. 2014;13(4):444-448.


Melasma is a cutaneous pigmentation condition affecting predominantly women. It is a highly prevalent condition observed by dermatologists,1 as it is a chronic disorder to which the therapeutic response is difficult to predict.2 Lesions are mainly located on the face and therefore the disease has a great negative impact on the quality of life of the patients. Traditional single-drug based treatments, including depigmenting agents (hydroquinone, azelaic acid, and others), chemical peels, and glycolic acid are commonly used. These therapies have partial and not curative effects, once relapses can happen, especially during summer.
Triple combination (TC) cream, which includes hydroquinone (HQ), tretinoin, and fluocinolone acetonide (FA) is considered as one of the most effective treatments for melasma, in association with photoprotection.2-5 Originally described by Kligman6 in 1975, the formula was composed of hydroquinone 5%, tretinoin 0.1% and dexamethasone 0.1%, and has been studied and modified several times. Currently, the TC cream with FA 0.01%, HQ 4%, and tretinoin 0.05% (TriLuma, Galderma, Switzerland) is the most widely used combination.2 The most effective depigmenting agent is considered to be HQ. Tretinoin not only has a depigmenting effect, but also is considered as the gold standard for photodamage therapy,7 and FA is a corticosteroid that exerts an anti-inflammatory action and suppresses melanin secretion while minimizing the adverse effects of the retinoids.
One study demonstrated better treatment outcomes of TC compared to double combinations, such as HQ + tretinoin, HQ + FA, and tretinoin + FA, with total or near total lesion clearance in the clinical evaluation.3 Mild to moderate adverse events were observed, the most common ones being erythema, flaking, and burning.3-5 Another study included 797 patients, only 2 of which who had used the medication for more than 6 months reported mild skin atrophy.5 The severity of melasma is traditionally evaluated using Melasma Area and Severity Index (MASI) scores. However, great inter-rater differences have been reported,8 highlighting the need for reliable objective assessments for melasma severity. Narrowband reflectance spectrophotometer is considered a sensitive, reproducible and specific method for objective measurements of skin color.9,10 It is a fast, inexpensive, and easy-to-use tool, capable of evaluating two particularly important components responsible for skin color in melasma: melanin and erythema.11