Figure. Clinical photographs of the forehead taken under UV light before treatment (A), at the end of the treatment (B), and after 1 summer (C). Left side of the patient's face has been treated with the triple combination cream, right side with both the cream and pulsed-dye laser.
Passeron T, Fontas E, Kang HY, Bahadoran P, Lacour J, Ortonne J. Melasma Treatment With Pulsed-Dye Laser and Triple Combination Cream: A Prospective, Randomized, Single-Blind, Split-Face Study. Arch Dermatol. 2011;147(9):1106-1108. doi:10.1001/archdermatol.2011.255
Author Affiliations: Departments of Dermatology (Drs Passeron, Bahadoran, Lacour, and Ortonne) and Clinical Research (Dr Fontas), University Hospital of Nice, and INSERM U895, CM3 (Dr Passeron), Nice, France; and Department of Dermatology, Ajou University School of Medicine, Suwon, South Korea (Dr Kang).
Recent data show that melasma lesions have, in addition to increased pigmentation, more elastosis and vascularization than perilesional skin.1- 3 The stabilized formulation of Kligman preparation has shown significant improvements in the treatment of melasma.4 However, most of the treatments only target the pigmentation, and none of them has been demonstrated so far to prevent the frequent relapses.
Pulsed-dye laser treatment (PDL) is considered the gold standard therapy for vascular lesions. By targeting not only melanin but also vascularization and at least in part elastosis, PDL might provide, in combination with blanching cream, an effective and complete therapeutic approach for melasma. The objective of this pilot study was to evaluate the dual treatment of fixed triple combination cream (TCC) and PDL in the treatment of melasma.
We conducted a controlled, randomized, single-blind, split-face clinical trial. Patients seeking treatment for melasma were included. Exclusion criteria were skin phototype V, medical history of allergy to the compounds of the TCC, or current pregnancy or breastfeeding.
All patients applied to the entire face the TCC containing hydroquinone, 4%; tretinoin, 0.05%; and fluocinolone acetonide, 0.01% (Tri-Luma Cream; Galderma Laboratories LP, Fort Worth, Texas), once a day for 4 months. The PDL treatment (Vbeam; Candela Corporation, Wayland, Massachusetts) was started after 1 month of TCC applications. Three sessions of PDL were performed at 3-week intervals on the half face that was randomly assigned. For each session, a first passage was performed on melasma lesions aiming at removing the hyperpigmentation (compression handpiece of 10 mm; pulse duration, 1.5 milliseconds; fluency, 7 J/cm2). A second passage was performed immediately afterwards, using a regular handpiece of 7 mm in diameter on the entire hemiface with a 10% overlap of treatment spots to target the vessels (pulse duration, 20 milliseconds; fluency, 10 J/cm2; dynamic cooling device, 30/40). All the patients were told to apply the entire face a sunscreen of sun protection factor 50 or higher (combining Mexoryl SX and XL; L ’Oreal, Paris, France) during the entire study duration.
The main criterion of evaluation was the Melasma Area and Severity Index (MASI)5 calculated by an independent physician blinded to treatment on standardized digital photographs (VISIA; Canfield Imaging Systems, Fairfield, New Jersey). Tolerance and satisfaction were graded by the patients on a visual analog scale (VAS). To avoid confusion of results possibly caused by spontaneous improvement of melasma that is usually observed during autumn and winter months, all the patients were included at the end of winter season and a final visit was scheduled after the summer, at least 2 months after the last treatment.
Between- and within-group comparisons of hemifacial MASI scores as well as analyses of tolerance and patient satisfaction were performed using the Wilcoxon signed-rank test (SPSS software, version 11.0; SPSS Inc, Chicago, Illinois).
Eighteen patients, all white women, were included (4 skin phototype II; 8 phototype III; and 6 phototype IV). One patient dropped out after 1 month of treatment for professional reasons. The mean age was 41 years (range, 33-56 years). The results are summarized in the Table. The Figure shows the clinical appearance of 1 patient before treatment, after treatment, and after 1 summer. Tolerance of the cream alone was excellent (9.3 of 10) and good when the laser was added (7.3 of 10) (P < .001), while patient satisfaction was graded at 6 of 10 for the cream alone and 7.1 of 10 for the combined approach (P < .05). Patient satisfaction was significantly greater for the combination treatment in patients with skin phototypes II and III (P < .01), while no significant differences between the 2 treatment groups were reported for phototype IV. A transient and mild irritation due to the cream was reported by half of the patients. Postinflammatory hyperpigmentation (PIH) was observed in 3 patients, all phototype IV, treated with PDL.
The use of PDL in association with a bleaching cream appears beneficial in treating melasma in patients with skin phototypes II and III. Hyperpigmentation is not homogeneous in melasma, and the split-face trial design may have deficiencies in detecting improvement. However, not only did the between-group comparisons show statistical differences, but the within-group comparisons showed significant differences after the summer compared with the initial score for the PDL-treated side, while the difference was no longer significant in the group treated with only the cream. Those data strongly support the beneficial effect of the PDL treatment despite the heterogeneity of the hyperpigmentation. Half of the patients with dark skin developed a PIH. The use of a PDL passage to target the melanin and to try enhancing the depigmentation might be responsible for the high percentage of PIH in dark-skinned patients. This pass targeting melanin should not be used for further studies.
To our knowledge, this is the first time that a treatment has been shown to prevent, at least partially, relapse of melasma. Melanocytes express vascular endothelial growth factor (VEGF) receptors 1 and 2 and neuropilin. Thus, the VEGF and skin vascularization might play a role in the pigmentation processes and therefore in melasma.6 By targeting the vascular component in melasma lesions, the PDL may decrease the melanocyte stimulation and subsequently the relapses. These results emphasize the necessity for a broader approach for melasma treatment targeting all components of this complex disorder. Additional studies with several years of follow-up are now required to draw definitive conclusions about the prevention of relapses and to determine the optimal parameters and schedule of treatment.
Correspondence: Dr Passeron, Department of Dermatology, University Hospital of Nice, Rte de St-Antoine de Ginestiere, 06200 Nice, France (email@example.com).
Accepted for Publication: March 28, 2011.
Author Contributions: Drs Passeron and Ortonne had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Passeron, Fontas, Lacour, and Ortonne. Acquisition of data: Passeron and Kang. Analysis and interpretation of data: Passeron, Fontas, Bahadoran, Lacour, and Ortonne. Drafting of the manuscript: Passeron, Fontas, and Ortonne. Critical revision of the manuscript for important intellectual content: Passeron, Fontas, Kang, Bahadoran, Lacour, and Ortonne. Statistical analysis: Fontas. Obtained funding: Passeron and Ortonne. Administrative, technical, and material support: Lacour and Ortonne. Study supervision: Passeron.
Financial Disclosure: Galderma provided the TCC used in the study.
Funding/Support: This study was supported by the Nice University Hospital (CHU Nice) and the Association Ni çoise pour l ’Etude de la Dermatologie (ANED).
Role of the Sponsors: The sponsors had no role in the design and conduct of the study; in the collection, analysis, and interpretation of data; or in the preparation, review, or approval of the manuscript.
Trial Registration: clinicaltrials.gov Identifier: NCT00863178
Previous Presentation: This research was presented at the 18th Congress of the European Academy of Dermatology and Venereology; October 2009; Berlin, Germany.
Additional Contributions: Charlotte Sakarowitch, provided valuable help in the statistical analysis review.