Treatment of refractory melasma with the MedLite C6 Q-switched Nd:YAG laser and alpha arbutin: A prospective study

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1 See discussions, stats, and author profiles for this publication at: Treatment of refractory melasma with the MedLite C6 Q-switched Nd:YAG laser and alpha arbutin: A prospective study Article in Journal of Cosmetic and Laser Therapy June 2010 Impact Factor: 1.11 DOI: / Source: PubMed CITATIONS 20 READS author: Niwat Polnikorn Chivasom International Health Resort 36 PUBLICATIONS 364 CITATIONS SEE PROFILE Available from: Niwat Polnikorn Retrieved on: 10 May 2016

2 A Prospective Study of Nd:YAG Laser and Alpha-Arbutin Therapy for Melasma Treatment of Refractory Melasma with the MedLite C 6 Q-Switched Nd:YAG Laser and Alpha Arbutin: A Prospective Study Niwat Polnikorn, MD Clinical Professor and Director, Kasemrad Aesthetics Center Kasemrad Prachacheun Hospital 950 Prachacheun Road, BangSue Bangkok 10800, Thailand niwatpol@gmail.com The author has no financial interest in HOYA ConBio, Inc. Objective: Evaluate the effectiveness of a Q-switched Nd:YAG laser (MedLite C6, HOYA ConBio, Fremont CA) and 7% alpha arbutin solution (Skin Advance Laboratory, Japan) in the treatment of melasma. Methods: Prospective study of 35 refractory melasma cases treated with 10 weekly laser sessions, 2 monthly follow-up treatments and topical 7% alpha arbutin solution. Clinical photographs and severity grading on a 5 point scale by two independent evaluators at each visit. Results: At 6 months, 30% of study subjects received results in the excellent clearance category (>81% reduction of melasma) and 36.7% received good (51-80% reduction) clearance. Mild and transient side effects included discomfort during treatment, erythema, whitening of fine hair and urticaria. Three cases of mottling hypopigmentation (8.57%) and 2 cases of recurrence of

3 melasma (5.71%) were recorded. Conclusion: Combination therapy with the MedLite C6 and 7% alpha arbutin solution is an effective and well-tolerated treatment for refractory melasma. Melasma is the most common hyperpigmentation disorder in Asians, and is one of the most difficult to treat. Therapy for this disfiguring condition accounts for more than 50% of aesthetic consultations in Asian countries. The pathogesis of melasma is complex and related to genetics and hormonal factors as well as to photodamage. The lesions occur mainly in middle-aged women on sun-exposed areas of the face, especially on the cheeks, forehead and upper lip. Lesions begin as a brownish asymptomatic irregular border of macules that slowly spreads out, forming brownish patches. Spontaneous remission after menopause is possible, but most of these patients will have the lesions for life. In a clinical sense, melasma usually begins as epidermal hyperpigmentation. Damaged skin basement membranes can lead to melanins dropping into the dermis. Epidermal melasma will be transformed to dermal or combined type melasma with persistent dermal melanophages. 1,2,3 A recent study confirmed the histologic presence of dermal melanophages in up to 2/3 of melasma cases in Asian skin types. 4,5 The presence of dermal melanophages is one important factor which contributes to the resistance of this condition to treatment. Even though total clearing in up to 50% of cases is possible with a topical agent such as Kligman s formula, recurrence is inevitable. Topical treatments with hydroquinone result in only temporary clearing, with the added possibility of long-term complications. 5,6,7,8 Alpha arbutin, a naturally occurring beta-d-glucopyranoside of

4 hydroquinone, has been shown to be a potent competitive inhibitor of tyrosinase without the side effects. 9,10,11 Only recently have lasers been evaluated for the treatment of this condition. Most of the early studies reported poor results and complications. Pigment-specific lasers operating on the principle of selective photothermolysis were effective in many cases of epidermal hyperpigmentation. However, the single pass high energy fluences used to treat melasma commonly resulted in post-treatment hyperpigmentation or permanent hypopigmentation. 12,13,14 In contrast to other lasers used for the treatment of melasma, the unique collimated, flat-top beam profile of the MedLite C6 Nd:YAG laser (HOYA ConBio, Fremont CA) enables the fragmentation and dispersion of melanins without damage to the pigmented cells. Intensive treatment with the MedLite C6 resulted in rapid clearance of refractory melasma, and common recurrence was controlled with topical alpha arbutin. This study reports the efficacy of repetitive sub-photothermolytic (<5 J/cm 2 ) laser sessions in combination with a 7% alpha arbutin solution for the successful long-term treatment of refractory melasma. Materials/Methods: Thirty-five female patients (aged years) with refractory melasma signed an informed consent and were enrolled in this study. All enrolled subjects had dermal or combined type melasma on the face which persisted for more than six months and had failed to respond to conventional treatment with hydroquinone cream or Kligman s formula. Exclusion criteria included photosensitive conditions or sensitivity to hydroquinone or arbutin, treatment with laser or Intense Pulsed Light (IPL) within 1 month, and/or inability to comply with the 6

5 month follow-up visit schedule. On the first day of treatment, the subject s face was thoroughly cleansed. Five standardized clinical photographs were taken. The treatment areas were then pre-cooled with cooled air (- 20 C) from the Criojet (Crio Medizintechnik Gmbh,Germany) for a few minutes. Laser safety precautions were followed according to the manufacturer s instructions. MedLite C6 laser parameters were set at 1064 nm, 6 mm spot size, Joules/cm 2, 10 Hertz. Laser pulses were delivered perpendicular to the surface with 10% linear overlapping in a small treatment plot (approximately 3x3cm 2 ) for 10 passes. The direction of the laser beam was then changed and delivered perpendicularly to the previous line of treatment for another 10 passes. After each small treatment plot was completed, the treatment was extended to adjacent areas to cover the entire face. Immediately after the treatment of each area the following clinical endpoints were observed: 1. Lightening of epidermal hyperpigmentation 2. Whitening of fine hair 3. Grayish darkening of dermal hyperpigmented lesions 4. Perilesional erythema Prior to each successive treatment, five standard studio-type photographs were taken. MedLite C6 laser treatment was performed at weekly intervals for 10 weeks. Subjects were instructed to apply a topical 7% alpha arbutin solution (Skin Advance Laboratory, Japan) twice daily with a broad-spectrum sunscreen of SPF 50 and PFA +++ (Antihelios XL, La Roche Posay, France)

6 after treatment. Subjects were also advised to avoid sunlight. After completion of the first ten laser treatments, subjects underwent two further MedLite C6 laser sessions at one month intervals, comprising a total of six months of treatment. Clinical findings and side effects were recorded at each visit. Results: All enrolled subjects were followed to the end of the study. At each visit, severity scores on a 5 point scale were assigned by an independent evaluator (4= no change, 3= 0-25% fading of lesions, 2= 26-50% fading of lesions, 1= 51-80% fading of lesions, 0= 100% clearance). Table 1: Mean severity scores after combination therapy at 2 weeks, 4 weeks, 6 weeks, 8 weeks, 3 months and 6 months after commencement of treatment

7 Table 2: Percentage of good (51-80% fading of lesions) and excellent (>80% clearance) results at 24 weeks, after 10 MedLite C6 laser sessions F/U wks 0-25% 26-50% 51-80% >81% All subjects showed a gradual reduction of hyperpigmentation beginning with the first treatment (Table 1). After the completion of ten MedLite C6 laser sessions, 48.39% of subjects showed a 26-50% fading of melasma lesions and 29.03% showed a 51-80% reduction of melasma lesions (Table 2). Clinical improvement continued even after the conclusion of the intensive weekly treatment phase. After ten weekly treatments and two subsequent monthly treatments, 30% of study subjects received an excellent result of a greater than 81% reduction of melasma. Furthermore, 36.67% of study subjects received good results of a 51-80% reduction in melasma lesions, resulting in an overall good to excellent response in 66.67% of participants (Table 2). Clinical improvements in two subjects are demonstrated in Figures 1-8. Both subjects represent cases of refractory dermal melasma which failed to respond to standard topical drug preparations (Kligman s formula), Q-switched ruby laser and Er:YAG laser treatment. Both had excellent responses to combination therapy as evidenced at the six month visit.

8 Figures 1, 2: Pre-treatment refractory melasma

9 Figures 3, 4: Post 10 weekly treatments and 2 monthly treatments with the MedLite C6 laser

10 Figures 5, 6: Pre-treatment of a second case of refractory melasma

11 Figures 7, 8: Post 10 weekly treatments and 2 monthly treatments with MedLite C6 laser Side effects of laser treatment were noted as follows: discomfort (100%), erythema (100%), whitening of fine hair (100%) and physical urticaria (5.7%). Side effects were mild and transient, with the exception of whitening of fine hair, which persisted until the hair was naturally shed. Adverse events included mottling hypopigmentation in 3 cases (8.57%) and recurrence of melasma in 2 cases (5.71%). Mottling hypopigmentation resolved spontaneously within a few months (Figures 9,10).

12 Figure 9: Hypopigmentation after two MedLite C6 Laser treatments in a case of rebound melasma

13 Figure 10: Mottling hypopigmentation after twelve MedLite C6 laser sessions Discussion: To treat melasma effectively (and for long-lasting results), practitioners should strive to control epidermal melanin synthesis, reduce melanin aggregation in both melanocytes and keratinocytes, increase melanin transportation into keratinocytes and also mobilize melanophages from the dermis. This is not possible with a single treatment method. From a theoretical point of view, combination treatments will ensure better, faster and longer-lasting results than a single treatment modality. 2,3 Tyrosinase enzyme is the most important enzyme in melanization. It changes dopa to dopaquinone and eumelanin. Topical application of tyrosinase inhibitors is the most widely

14 used method in the treatment of melasma. 15 Even though there are many new chemical products claiming to be effective bleaching agents, 1,9,17,18 hydroquinone (2-4%) is still the most widely prescribed topical bleaching treatment. 6 Hydroquinone usually results in short-term improvement. Between 30-40% of patients have total clearing within three months, followed by recurrence. However, long-term maintenance with even 2% hydroquinone is often related to many side effects (e.g. skin irritation, hypopigmentation, rebound hyperpigmentation and ochronosis). 16 Newer bleaching agents include kojic acid, arbutin (hydroquinone bound to glucose), licorice and ascorbic acid; however, these have all been found to be less effective than hydroquinone. 18 In order to enhance the effectiveness of hydroquinone, it has been combined with 0.05% retinoic acid and a steroid (0.1% dexamethasone) in a recipe known as Kligman s formula. 7 With the addition of this formula to hydroquinone, the percentage of cases with total clearing is increased to 50-60%. However, the side effects are increased as well, especially skin irritation, dryness, acneiform eruptions, rosacea-like dermatitis, skin atrophy and telangiectasia. Many patients develop steroid dependent rosacea-like facial dermatitis after prolonged application. 6,7,8 Arbutin-alpha glycosides and alpha arbutin have been shown to be more effective tyrosinase inhibitors than arbutin. 11 This topical whitening agent was selected as a maintenance treatment in this study. Despite the reported results of good treatment of melasma with dermabrasion 19, this modality has not gained wide acceptance. The prolonged post-operative downtime and the risk of complications seems to discourage both patients and physicians. Carbon dioxide laser resurfacing has been studied in melasma, but with poor results and unacceptable side effects.

15 Intra-epidermal laser resurfacing often results in severe post-treatment hyperpigmentation, while deep resurfacing (down to the mid-dermis) can result in persistent hypopigmentation. 21,22 Erbium:YAG laser resurfacing has been studied with a similar result. Intense pulsed light works by the production of epidermal necrosis from absorbed light that had been converted into heat. The effects are similar to intra-epidermal laser resurfacing. Postinflammatory hyperpigmentation (PIH) and persistent hypopigmentation are common, especially in dark skin types. 21 High energy pigment-selective lasers (e.g., 694nm Q-Switched ruby laser, 755nm Q-Switched alexandrite laser, 532nm frequency-doubled Q-Switched Nd:YAG laser and 1064nm Q-Switched Nd:YAG laser) have been studied for the treatment of melasma, also with poor results. Balanced normal skin color was rarely achieved. 13,14 The author reported better results after a combination of pulsed CO2 laser and Q-Switched alexandrite laser treatments in a split-face study. 22 The efficacy of this combination technique was believed to be due to the elimination of melanophages and a reduction of hyperactive epidermal and follicular melanocytes. Nevertheless, due to the complexity of these procedures, this combination laser treatment is still not widely accepted. Pigment lightening was a coincidental finding after the application of a new type of laser delivery system. A fractional laser delivers a pattern of tiny laser beams, producing microthermal necrotic zones or wounds that are a stimulus for skin rejuvenation. The original technology involved a diode laser but other lasers have since been modified to produce a similar result (e.g., pulsed carbon dioxide, pulsed Er:Glass). Preliminary data from non-control studies have shown fair to moderate results in the treatment of melasma 23,24,26. The

16 mechanism of pigment lightening may be explained by the partial destruction of epidermal melanocytes and the trans-epidermal elimination of dermal melanophages. 25 In dark skin types, postinflammatory hyperpigmentation (PIH) is not an uncommon result of this process. The results reported here of a study of combination therapy with the Q-switched Nd:YAG MedLite C6 laser and a 7% alpha arbutin solution provide evidence of a safe and effective option in the treatment of refractory dermal melasma. The repetitive sub-photothermolytic fluence (3-3.4 J/cm 2 ) was able to produce immediate lightening of epidermal melasma. Dermal melasma responded after a few further treatments. Even in refractory dermal melasma, fading of greater than 50% of lesions was achieved in 66.67% of subjects in a six month time period. The mechanism of depigmentation with this new technique is still not fully understood. The author postulates that immediate lightening should be the result of fragmentation and dispersion of melanins. Long-term results should be explained by the reduction of active epidermal melanocytes and dermal melanophages. Repetitive subthreshold Q-switched Nd:YAG laser treatments also produce superficial ablation and neocollagenesis in the upper dermis, resulting in the additional benefits of the reduction of wrinkles and in the appearance of smaller pores. Long-term maintenance with a safe topical whitening agent (e.g., 7% alpha arbutin) and a broad-spectrum sunscreen is essential for the prevention of recurrence. This is an important alternative to the use of hydroquinone, with its long-term complications. In the author s experience, combination therapy with the MedLite C6 and topical 7% alpha arbutin is the most effective method of treatment for dermal and combined melasma. Serious complications are uncommon. Mottling hypopigmentation in this

17 study was believed to be the result of a too aggressive destruction of melanocytes. If such an effect is detected early, the practitioner can avoid re-treating those areas. In these cases, repigmentation should follow within a few months. In this study, the percentage of recurrence of melasma was 5.71%, which is considerably lower than the rate of recurrence with topical treatment. The author has had success in re-treating these cases with another course of MedLite C6 laser sessions. References: 1. Gupta AK, Gover MD, Nouri K, Taylor S. The treatment of melasma: a review of clinical trials. J Am Acad Dermatol 2006; 55, Prignano F, Ortanne JP, Buggiani G, Lotti T. Therapeutic approaches in melasma. Dermatol Clin 2007; 25: Grimes PE. Melasma: Etiologic and therapeutic consideration. Arch Dermatol 1995; 131: Kang WH, Yoon KH, Lee ES et al. Melasma: histopathological characteristics in 56 Korean patients. Brit J Dermatol 2002; 146: Cestari TF, Hassun K, Sittart A, Viegas MdL. A comparison of triple combination cream and hydroquinone 4% cream for the treatment of moderate to severe facial melasma. J Cosmet Dermatol 2007; 6: Haddad AL, Matos LF, Bruenstein F, Ferreira LM, Silva A, Costa D Jr. A clinical, prospective, randomized, double-blind trial comparing skin whitening complex with hydroquinone vs. placebo in treatment of melasma. Int J Dermatol 2003; 42:

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19 glycolic acid. Dermatol Surg 1999; 25: Huerta Brogeras M, Sanchez Vira M. Exogenous ochronosis. J Drugs Dermatol 2006; 5: Kunachak S, Leedaudomlipi P, Wongwaisayawan S. Dermabrasion : a curative treatment for melasma. Aesthetic Plastic Surgery 2001; 25: Nouri K,Bowes L, Chartier T, Romangosa R, Spencer J. Combination treatment of melasma with pulsed CO2 laser followed by Q-switched alexandrite laser : a pilot study. Dermatol Surg 1999; 25: Angsuwarangsee S, Polnikorn N. Combination ultrapulse CO2 laser and Q-switched alexandrite laser compared with Q-switched alexandrite laser alone for refractory melasma. Dermatol Surg 2003; 29: Malaloto RM, Alster T. Erbium-YAG laser resurfacing for refractory melasma. Dermatol Surg 1999; 25: Rokhsar CK, Fitzpatrick RE. The treatment of melasma with fractional photothermolysis: a pilot-study. Dermatol Surg 2005; 31: Naito SK. Fractional photothermolysis treatment for resistant melasma in Chinese female. J Cosmet Laser Ther 2007; 9: Tannous ZS, Astner S. Utilizing fractional resurfacing in therapy resistant melasma. J Cosmet Laser Ther 2005; 7: Hantash BM, Bali VP, Surireddy V et al. Laser-induced transepidermal elimination of dermal content by fractional thermolysis. J Biomed Opt 2006 Jul-Aug; 11(4):