COVER FOCUS Melasma Treatments: A Review of Laser Therapies and the Integration of Reflectance Confocal Microscopy Reflectance confocal microscopy may play a role in melasma stratification and treatment assessment. BY MAHIN ALAMGIR, MD, CINDY WASSEF, MD, MAJID HAMIDI, AND BABAR K. RAO, MD he currently available laser melasma treatments have classifying all melasma as the mixed type with either epider- varying utility values. Finding the appropriate treat- mal or dermal components predominating. ment should be based upon skin type, the type of With this understanding, the need to treat melasma melasma, previous response to other treatments, and becomes imperative. While a plethora of inexpensive yet scientificT evidence. Using reflectance confocal microscopy for marginally efficacious topical applications is available, an melasma class identification as well as for monitoring treat- analysis of laser treatments is necessary, given their signifi- ment can provide insight into the effectiveness of therapy. cant cost and possible adverse outcomes. Our goal is to Melasma is a dysfunction of the skin’s pigmentation factory. review current laser treatment modalities for melasma, Melanin, produced by melanocytes, and stored in melano- focusing on long-term benefits and effects of these treat- somes, is the skin’s natural pigment.1 These melanin-laden ments. The use of confocal microscopy for diagnosis and cells contribute to the color of skin.2 Melanin synthesis starts stratification into melasma types as well as assessment of with the conversion of L-tyrosine to L-dopa, which in turn is therapy will also be addressed for each modality reviewed. converted to L-dopa-quinone inside the melanosomes.3 The reaction is catalyzed by the enzyme tyrosinase, and a dysfunc- METHODS tion of these biochemical reactions leads to melasma. The A literature review was conducted through PubMed and result is a light to grey-brown hypermelanosis of sun-exposed Ovid search engines. Search terms included “melasma,” “recal- areas.4 It is most commonly observed among women,5, 6 with citrant melasma,” and “melasma laser treatments.” Each treat- highest prevalence seen in Fitzpatrick skin types IV to VI.4, 7-10 ment was also used as a search term along with “confocal Among women, those of child-bearing age are at the highest microscopy” to find specific articles in which both are discussed. risk; men, on the other hand, represent only 10 percent of those affected.11-13 RESULTS Histologically, melasma is divided into three types: epider- Laser Treatments. Laser treatments have shown promise mal, dermal, and mixed, demarcated by Wood’s lamp.10, 14,15 in the treatment of melasma, especially in darker-skinned There is increased melanin in the basal, suprabasal, and stra- patients. There are a number of laser modalities that can be tum corneum in epidermal melasma. In the dermal variety, used to treat melasma, including ablative and nonablative the superficial and deep dermis are laden with melanophag- fractional lasers, Q-switch lasers, and Erbium:YAG lasers. 3,4,12 es in the perivascular array. The mixed type has pigment Ablative CO2 Laser. The ablative carbon dioxide (CO2) deposition in the epidermis and dermis.15 laser has many uses including treatment of the sequelae of New data now supports the use of reflectance confo- photoaging. A short, high-energy burst of the 10,600nm CO2 cal microscopy in the classification of melasma. Confocal wavelength laser vaporizes intra- and extracellular water, microscopy quantifies the amount of pigment in each layer, causing tissue ablation. The short burst is targeted to limit 28 PRACTICAL DERMATOLOGY JUNE 2014 COVER FOCUS PRACTICAL POINTER Fractional photothermolysis (FP) combines the efficacy of ablative and the tolerability of non-ablative lasers to treat Selection of appropriate treatment for melasma should be conditions like melasma. The device emits pixilated light based upon skin type, the type of melasma, previous response to create three-dimensional zones of thermal damage or to other treatments, and scientific evidence. Using reflectance ‘microthermal zones’ (MTZs). The small zones of thermal confocal microscopy for melasma class identification as well damage allow for rapid epidermal repair, while resurfacing at as for monitoring treatment can provide insight into the the same time. It differs from ablative skin resurfacing in not effectiveness of therapy. producing a uniform patch of epidermal or dermal injur.32 Hantash and colleagues using a 1550nm single-mode fiber laser found that FP created MTZs with an intact stratum dermal injury to reduce the likelihood of scarring, while corneum. Within the epidermis there was vacuolar forma- stimulating neocollagenesis. Other lasers with wavelengths tion from extruded dermal material as the dermal-epidermal that are highly absorbed by water are also termed ablative junction is weakened above the zones of coagulation. The and include the erbium yttrium aluminium garnet (Er:YAG; epidermal debris incorporates dermal melanin, which is 2,940 nm) or yttrium scandium gallium garnet (YSGG; 2,790 ‘shuttled’ out. This is then exfoliated along with the stratum nm).16,17 Upon histologic analysis, the effects produced by corneum. This mechanism of shuttling of dermal content these lasers are seen as ablated micro-columns. The cavitites underlies the removal of dermal melanin.33 are lined by eschar, and annular zones of coagulation are The dermal injury wrought by FP leads to the release of found in the adjacent areas. The stratum corneum is absent, inflammatory mediators that remodel the dermal matrix as these are ablative lasers.18,19 through increased collagen synthesis and fibroblastic activ- These lasers are not without their drawbacks. Increased ity. Goldberg, et al. undertook a study to link the histologic downtime, oozing, crusting, edema, burning discomfort, and ultrastructural changes brought about by treatment milia, exacerbation of acne, oozing or crusting, and intermit- with FP. They examined biopsy specimens from 10 subjects tent pruritus are some sequelae. Post-inflammatory hyper- who had epidermal melasma. They had been treated with pigmentation (PIH) in darker skin types is reported in up to 1550nm erbium:glass laser (Fraxel SR 750, Solta Medical) 40 to 50 percent of cases.20-26 every two weeks for four sessions. The specimens were taken Trelles, et al. designed a trial to compare the effect of topi- post-treatment and three months after the last session. A cal bleaching agents to pulsed CO2 laser used alone or in relative decrease in melanocytes on histology compared to combination. They enrolled 30 females with both epidermal baseline was observed. Electron microscopy examination and mixed melasma, and divided them into three groups. revealed fewer melanocytes and an absence of melanin in the Group A was given a maintenance topical regimen of bleach- surrounding keratinocytes compared to pre-treatment speci- ing creams, Group B was given laser treatment, and Group C mens. The results of the study correlated the clinical efficacy was given both. The overall efficacy was a 100 percent in all observed with the histological picture.34 three groups at the first month, but declined subsequently in Rokhsar, et al. conducted a study on 10 female patients groups A and B. Group C maintained their clinical efficacy at with melasma who had not responded to previous interven- the 12-month follow-up. The single laser treatment was used tions. They were treated at one- to two-week intervals with to minimize thermal damage that could induce a relapse of the Fraxel laser (Solta Medical). Between four and six treat- melasma. Once the abnormal melanocytes were removed, ment sessions were given. Physician evaluation determined the topical cream helped in the maintenance of the results. that 60 percent of patients achieved 75 to 100 percent clear- More controlled studies of this manner with a larger number ing and 30 percent had less than 25 percent improvement. of patients and longer follow-ups will help further elucidate The patients had similar assessments except for one patient, the efficacy of this combined regimen.27 who graded herself as 50 to 75 percent improved as opposed Fractional Photothermolysis. Nonablative fractional lasers to the physician grading of greater than 75 percent.35 were developed to overcome the side effects of traditional A clinical study was conducted by Lee, et al. on 25 ablative lasers while achieving the therapeutic goal. They do patients who received four monthly FP sessions and were not achieve the same therapeutic efficacy as their ablative followed up to 24 weeks after treatment completion. Six of counterparts but carry a more favorable adverse effect pro- the 25 patients were evaluated as improved by the investi- file. The most commonly used lasers in this modality are the gators at the end of four sessions, and at the 24-week post- 585- to 595nm pulsed-dye lasers, the 1,320nm Nd:YAG laser, treatment follow-up, four out of 25 were given a similar the 1,450nm diode laser, the 1,064nm Q-switched Nd:YAG rating. The investigators observed clinical improvements in laser, and the intense pulsed light source.19,28-31 60 percent, and patients in 44 percent, at four weeks after JUNE 2014 PRACTICAL DERMATOLOGY 29 COVER FOCUS treatment, but the figures decreased to 52 percent and 35 Er:YAG lasers have shown favorable results in skin resur- percent, respectively, at 24 weeks after treatment. Mean facing with less downtime and more favorable side effects MASI scores decreased significantly from 7.6 to 6.2(p=0.03). than other laser modalities. A variable square pulsed (VSP) Mean melanin index decreased significantly after the first Er:Yag laser was tested in the treatment of epidermal type two sessions but relapsed slightly in subsequent follow-ups. melasma in 20 Thai women who received two passes at a Hyperpigmentation was observed in three of 23 patients (13 fluence of 0.4 J/cm2.Two treatments were given one month percent).