- Top of page
- Material and Methods
BACKGROUND Pigment lasers have been used in melasma with unsatisfactory results.
OBJECTIVE To determine the effectiveness and safety of 1,064-nm Q-switched neodymium-doped yttrium aluminum garnet (QS-Nd:YAG) laser treatment of melasma in Asians.
MATERIALS AND METHODS Split-face randomized study comparing combination QS-Nd:YAG laser and 2% hydroquinone with topical treatment in dermal or mixed-type melasma. Twenty-two patients were treated with 1,064-nm QS-Nd:YAG laser, 6-mm spot size, 3.0- to 3.8-J/cm2 fluence for five sessions at 1-week intervals. Pigmentation was objectively recorded using a colorimeter (lightness index score), and subjective assessments were evaluated using the modified Melasma Area and Severity Index (mMASI) score.
RESULTS After five laser treatments, statistically significant improvement of melasma from baseline was observed in colorimeter (p<.001) and mMASI score (p<.001) on the laser side. The laser side achieved an average 92.5% improvement in relative lightness index and 75.9% improvement in mMASI, compared with 19.7% and 24%, respectively, on the control side (p<.001). Mottled hypopigmentation developed in three patients. During follow-up, four of 22 patients developed rebound hyperpigmentation, and all patients had recurrence of melasma.
CONCLUSION QS-Nd:YAG laser treatment for melasma in Asians produced only temporary improvement and had side effects. Common complications were hypopigmentation, melasma recurrence, and rebound hyperpigmentation.
The authors have indicated no significant interest with commercial supporters.
Melasma is a common cosmetic problem in Asians. Because of its refractory and recurrent nature, especially the mixed or dermal component, melasma is often difficult to treat.1 Broad-spectrum (ultraviolet A plus ultraviolet B) sunscreens and topical hydroquinone (HQ) are the most commonly used treatments for melasma. Other topical lightening agents include retinoic acid, azelaic acid, and kojic acid. Physical therapies such as chemical peels, dermabrasion, lasers, and intense pulsed light (IPL) have also been used with varying degrees of success and side effects.2,3
There have been some reports of more successful treatment of melasma using resurfacing lasers (erbium:YAG, combination pulsed carbon dioxide (CO2) laser followed by Q-switched (QS) alexandrite laser (QSAL), and combined ultrapulse CO2 laser and QSAL) but with significant downtime and frequent postinflammatory hyperpigmentation.4–6 Recent reports of using fractional resurfacing lasers to treat therapy-resistant melasma have indicated improvement in melasma with less risk and downtime.7 Melasma has also been treated with various pigment-specific lasers, but the results were disappointing,8–12 often resulting in severe postinflammatory hyperpigmentation.13
In QS-Nd:YAG laser treatment for benign pigmented lesion removal, the laser targets melanin particles found within melanocytes, keratinocytes, or dermal melanophages, and multiple treatments are required. Recently Polnikorn described a new technique of repetitive subthreshold pulsed 1,064-nm QS-Nd:YAG laser treatments that was effective for the treatment of refractory dermal melasma.14
The objective of the current study was to explore the effectiveness and safety of multiple treatments with a low sub-photothermolytic fluence, 1,064-nm QS-Nd:YAG laser to treat melasma in Asians.
- Top of page
- Material and Methods
The effectiveness of lasers in pigmented lesions is based on the theory of selective photothermolysis introduced by Anderson and Parrish, which states that, when a specific wavelength of energy is delivered in a period of time shorter than the thermal relaxation time of the target chromophore, heat and injury are restricted to the target, with less damage to the surrounding tissue.20 The thermal relaxation time of melanosomes ranges from 50 to 500 nsec, and the absorption spectrum of melanin is broad. IPL and short-pulsed pigment-specific lasers using standard fluences, some combined with ablative lasers, have been used in melasma, with varying results, often with side effects, especially postinflammatory hyperpigmentation.8–13,17,21,22
The pathophysiology of melasma is unknown. An abnormal epidermis, abnormal dermis, or overactive melanocytes may cause melasma. There is a greater number and more activity of melanocytes, resulting in a large amount of melanosome transfer to the epidermis and dermis. The clinical and histologic characteristics of melasma vary according to the location of melanin. Three patterns of melasma pigmentation are recognized: an epidermal type with hyperactive epidermal melanocytes and pigment deposit in the basal or suprabasal layer; a dermal type with melanin-laden macrophages in the superficial and mid-dermis, especially around the perivascular melanophages; and the mixed type, featuring the epidermal and dermal type with hyperactive epidermal melanocytes and dermal melanophages.23,24 The histopathology of the melanin pigment in dermal and mixed melasma is similar to tattoo pigment. It has been shown that a single laser session for tattoo removal with pigment laser is slow and that multiple treatments are required.
In the past, the use of pigmented lesion dye laser (510 nm), frequency-doubled QS-Nd:YAG (532 nm), QS-ruby laser (694 nm), and QSAL (755 nm) have been used to treat melasma, with disappointing results, some with worse postinflammatory hyperpigmentation. The near-infrared 1,064-nm QS-Nd:YAG has a longer wavelength (>600 nm), which is well absorbed by melanin and to a lesser extent by hemoglobin, making it generally safer in darker skin types because it spares injury to the epidermis to a greater degree than shorter wavelengths. It has the added benefit of deeper skin penetration. However, in Asian skin, postinflammatory hyperpigmentation is common after 1,064-nm QS-Nd:YAG laser treatments.25
Polnikorn reported two case treatments of refractory dermal melasma using 10 weekly treatments with the 1,064-nm QS-Nd:YAG laser at sub-threshold photothermolytic fluences (<5 J/cm2), resulting in reduction of epidermal and dermal pigmentation with no recurrences at 1-year and 6-month follow-up respectively.14 Our data show that five weekly treatments of low-fluence 1,064-nm QS-Nd:YAG laser is an effective treatment for dermal and mixed melasma. In this study, we used a colorimeter to allow more accurate and objective quantification of pigmentation and the split-face study design to eliminate the problem of individual variability. We also showed that colorimeter measurements correlated with subjective clinical evaluation using the mMASI score. We demonstrated that this treatment without downtime produced significant and rapid results, although after five laser sessions, the results were not curative, and recurrence of melasma was the rule. Adding other therapeutic options2,3 to the topical 2% hydroquinone used in our study may have more successfully maintained the treatment results.
We emphasize that this treatment, although it produced initial beneficial results to patients, was not without side effects. After the five laser treatments, 13.6% (3/22 patients) developed faint, spotty hypopigmentation that improved during follow-up. All cases had recurrence of melasma within the 12-week follow-up; with 18.2% (4/22 patients) experiencing rebound hyperpigmentation. Therefore, after completing the study period, many patients sought additional once-weekly laser treatments to treat their recurrent melasma, and many patients came back with side effects of disfiguring hypopigmented macules intermingled with mottling hyperpigmented macules in areas of melasma. Tan and colleagues reported two cases of biopsy-proven hydroquinone-induced exogenous ochronosis. One of these two cases had also undergone 1,064-nm QS-Nd:YAG laser therapy for worsening melasma, and the clinical examination described mottled, reticulate, lace-like hyperpigmented macules of ochronosis with confetti-like hypopigmented macules similar to our patients.26 Mottled hypopigmentation has also been reported after QS-Nd:YAG laser for skin rejuvenation.27
After treatment of benign acquired melanocytic nevi with QS lasers, reduction of epidermal melanocytes and numbers of functional and dermal melanocytic nests was noted, with increased dermal melanophages and mild dermal fibrosis.28 The QS-Nd:YAG (1,064 nm) laser has been shown to cause dermal and epidermal melanosome rupture, melanosome rupture in melanocytes, and destruction of dermal melanophages.29,30 Anderson and colleagues30 conducted a study examining selective photothermolysis of cutaneous pigmentation using QS-Nd:YAG laser after single-pulse exposures at 1,064, 532, and 355 nm in guinea pigs, demonstrating melanosome rupture within melanocytes and keratinocytes. Only 532 and 1,064 nm at threshold and suprathreshold exposures produced permanent leukotrichia due to follicular depigmentation. At sub-threshold exposures, none of the three wavelengths caused hypopigmentation, but they stimulated melanogenesis and prominence of dendritic melanocytes in guinea pig skin. From our results, we postulate that the initial lightening of melasma was due to melanin granule dispersion and fragmentation. The laser treatment may also produce nonspecific dermal wound and induce inflammation, which facilitates migration of melanophages. There was no epidermal disruption when low fluence was used, but the inflammation may cause increased epidermal turnover. Repeated laser treatments may reduce or exhaust hyperactive melanocytes, which may be the cause of confetti-like hypopigmented macules. We observed that the complication of mottled hypopigmentation after melasma treatment occurs gradually and often significantly affects the patient. Treatment of hypopigmentation is difficult and may lead to worsening of the melasma; at the same time, bleaching agents can cause worsening of hypopigmentation. Alternatively, multiple subthreshold exposures to the 1,064-nm wavelength may stimulate melanogenesis in some areas and produce rebound hyperpigmentation similar to the guinea pig model.30 Therefore, to avoid these serious complications, we caution the use of too many (more than 5 approaching up to 10 treatments) or too frequent (every week) QS-Nd:YAG laser sessions. We propose that the observation of even slight hypopigmentation should contraindicate further treatment with sub-threshold fluence, 1,064-nm QS-Nd:YAG lasers.
Most of the patients also observed the benefits of improvement in skin texture and lightened skin color on the laser-treated side. Textural changes such as this are thought to be the result of collagen remodeling and are the basis of improvement seen with treatment of photoaged skin or “photorejuvenation effect” using nonablative lasers. The nonablative, dermal remodeling effects of the 1,064-nm QS-Nd:YAG laser in the treatment of wrinkles and atrophic acne scars have been clinically and histologically confirmed.31–37
The repeated use of nonablative lasers and light sources for skin rejuvenation and melasma can be addictive to patients because there is no downtime. Therefore, the effect of repeated exposure to longer wavelength radiation in human skin is an important issue to be considered. An in vitro study by Chan and colleagues38 on the effect of sublethal QS 755-nm lasers on the expression of p16INK4a in melanoma cell lines found that sublethal laser damage could increase DNA damage, which leads to greater p16 expression. More recently, Chan and colleagues further demonstrated in an animal study that repeated treatment with high-energy laser and IPL exposure, although it did not cause any toxicity or tumor in mice, produced elevations of p16 and proliferating cell nuclear antigen expression, indicating DNA damage.27 The long-term safety of large-spot-size, low-fluence QS-Nd:YAG laser in the treatment of melasma and skin rejuvenation is not known and should be further studied.
Multiple treatments with a 1,064-nm QS-Nd:YAG laser at lower sub-photothermolytic fluence for treatment of dermal and mixed melasma produced only temporary improvement of melasma (MASI, chromometer pigmentation measurements). However, complications of recurrent melasma, rebound hyperpigmentation, and mottled hypopigmentation were common, making this a discouraging treatment for melasma. We caution the use of this laser treatment to more than five once-weekly treatments with the careful surveillance of development of hypopigmentation or leucoderma, which should contraindicate further QS-Nd:YAG laser treatments. The long-term safety of this treatment protocol needs to be studied because the total cumulative energy after multiple subthreshold laser treatments may be higher than used in standard energy treatment.