Melasma Treatments: a Review of Laser Therapies and the Integration of Reflectance Confocal Microscopy

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

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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

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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). The study pointed out the need for longer follow- apart. There was a significant improvement in MASI ups to assess the efficacy of FP.36 score at the two-month visit from baseline (p=.004) but The Fraxel laser, which is FDA approved for the treat- the improvement declined at the four-month follow-up ment of melasma, has not provided results as dramatic as (p=0.10) There was significant improvement in melanin

those with CO2 lasers. It is associated with a lesser downtime index at the two-month follow-up (p=.02) but not at the and decreased risk of complications. In darker skin tones, four-month follow-up (p=.39). A total of 15 percent of there is a higher risk of PIH when treating melasma patients. patients had a 50-100 percent clearing of their melasma Naito conducted a study on six Chinese females who had and 32.5 percent had a 26-50 percent clearing. Three resistant melasma. They were treated with FP at four-week patients developed mild PIH and two had acneiform erup- intervals with a total of three to four sessions. Three patients tions. The square-shaped VSP Er:YAG pulses provide more improved by 50 percent, two by 30 percent and one by 20 controlled heating in an effort to maximize efficacy. The percent. However, at the two-month follow-up, the mean downtime observed with this modality is much less, and improvement noted was only 35 percent.37-38 the secondary PIH that was observed healed within two Graber, et al. highlighted the low incidence of side effects weeks. However, the clinical efficacy of VSP Er:YAG is lower with FP in their study involving 961 patients who were than that of FP.44 treated with Fraxel SR. Only 7.6 percent developed compli- Q-Switched Lasers. Several pigment lasers have been cations, the most common being acneiform eruptions (1.9 used to target melasma, as melanin has a wide absorption percent) and herpes simplex virus outbreaks (1.8 percent). spectrum (500-1100nm).These lasers include the pigmented There were no long-term sequelae.39 lesion pulsed dye laser (510nm), the Q-switched ruby laser In spite of this promising data, a recent review concluded (694nm), the Q-switched alexandrite laser (755nm) and the that fluences and densities used for FP need to be conserva- Q-switched Nd:YAG laser (1064nm).45 40 tive, as the risks for PIH remain. Treatments need to be Nouri, et al. designed a study to compare pulsed CO2 laser conservative and placed at intervals of four to six weeks alone with the combination of pulsed CO2 laser followed each.41-42 FP has shown potential in the treatment of therapy by Q-switched alexandrite laser (QSAL) in the treatment resistant melasma, but more systematic studies with follow- of dermal-type melasma. The combination would mount a up analyses need to be done. two-pronged attack by eliminating the superficial abnormal Erbium:YAG laser. Erbium:YAG lasers emit light with a melanocytes and the hyperpigmented epidermis with the

wavelength of 2,940nm that makes water its chromophore. pulsed CO2 laser and then target the denuded dermis with It is highly absorbed by water-containing tissue, which helps the deeper melanin using the QSAL. Eight patients with the laser to ablate skin with minimal thermal damage. dermal-type melasma as diagnosed by Wood’s lamp exami- Manalato, et al. evaluated the role of Er:YAG laser nation were first given a two week course of tretinoin 0.05% resurfacing in refractory melasma. Ten female patients cream, hydroquinone 4% cream, and hydrocortisone 1% with melasma unresponsive to previous therapy were cream, to be applied twice daily. The patients were random- included in this study. Full face skin resurfacing using an ized into groups of four and then one group was treated

Er:YAG laser (2.94 microm) was performed using 5.1-7.6J/ with one pass of the Coherent® 950 μsec pulsed CO2 laser set cm2 energy. Adverse effects, such as prolonged erythema, at 300mJ/cm2 followed by another pass with the Q-switched infection, and hyperpigmentation, were recorded. The alexandrite pigmented dye laser at a fluence of 6J/cm2. The

mean melanin reflectance spectrometry decreased from other four patients were treated with the pulsed CO2 laser 48.8 to 43.6 at the six month follow-up. The mean MASI alone. Patients were evaluated every four weeks for up to scores decreased from 19.1 to 10.6. Results showed definite six months post-laser therapy. All four of the patients in improvement of melasma immediately after laser surgery; the combination arm showed complete resolution without however, between three and six weeks postoperatively, any peripheral hyperpigmentation. Those in the control there was universal development of post-inflammatory group also showed complete resolution of melasma at the hyperpigmentation treated with topical azelaic acid, GA six month follow-up. No patient in the combination group peels, and sunscreen.43 showed any signs of hyperpigmentation at the more than

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TABLE 1.

Laser Treatment Use of Reflectance Confocal Microscopy (RCM)

Ablative CO2 Laser No studies with RCM reported Fractional No studies with RCM reported Photothermolysis Erbium:YAG Laser No studies with RCM reported Q-switched Laser Zhou, et al.69: Melasma areas imaged before treatment, after treatment, and at follow-up appointment. RCM showed decrease in bright melanin particle in basal layer and fewer melanin particles immediately after treatment. Repeat imaging in those patients with recurrence of melasma after treatment showed a return to baseline melanin levels. This lead to the conclusion that the results of this laser may be temporary. Intense Pulsed Light Yamashita, et al.70: RCM images taken before and after IPL. Before IPL, increased signals indicated pigmentation presence. Following IPL, collapse of melanin caps with melanosome dispersal to keratinocytes seen. Melanosomes in epidermal basal layer rapidly migrated to surface

six month follow-up; two patients in the CO2 laser only in an inactive stage, or does not contain a melanosome, the group had peripheral hyperpigmentation in the long-term Q-switch laser does not affect these cells.47 follow-up evaluation. A longer follow-up evaluation of these The 1,064nm QS-Nd:YAG has a longer wavelength patients is needed to assess the efficacy of these two laser (>600nm), which is well absorbed by melanin. It is consid- modalities. This study also lacked an objective parameter for ered a safer option in darker skin types as its lower energy measure of pigmentation.46 spares injury to the epidermis. However, PIH with the use of Angsuwarangsee, et al. conducted a split-face designed the QS-Nd:YAG laser is still common in Asian skin types.50 study on six Thai females who were treated with combined Wang, et al. reported results of their trial in which they

Ultrapulse CO2 laser (Lumenis) and QSAL on one side of combined low energy QS Nd: YAG and QSAL to treat the face and QSAL alone on the other side. These patients patients with melasma. A total of 32 patients each rated were suffering with refractory melasma. The rationale was their improvements according to the following scale: to use an ablative laser to remove the excess epidermal Pigment subsided by > or = 90 percent was regarded as melanin and abnormal melanocytes and then follow with “cured,” by 60-89 percent as “remarkably improved,” by a Q-switched laser to target the deeper melanocytes in 30-59 percent as “effective,” and by < 30 percent as “inef- the dermis without causing side effects. The patients were fective.” At the conclusion of this study, 21 patients (65.6 evaluated for up to six months. Their results indicated percent) rated themselves as cured after 10.2 +/- 3.5 times that the combined treatment had a statistically significant of treatments, 11 patients (34.4 percent) were remarkably reduction of both the indices, whereas the side treated with improved after 11.4 +/- 2.5 times of treatment. The rates of just QSAL did not show significant results. Two of the six “cured” and “remarkably improved” were 81.3 percent and females developed severe PIH, and this was treated with 4% 18.7 percent among patients with light brown melasma and HQ three months after the laser treatment. There were no 50.0 percent and 50.0 percent among patients with dark serious complications. Two patients had transient hypopig- brown melasma (P < 0.05). No patient suffered from hyper- mentation and contact dermatitis on the combination side, pigmentation or scarring; there was one episode of hypopig- which resolved spontaneously. The number of cases in this mentation. This study concluded that QS Nd: YAG and study is small, but the split-face design helps to overcome QSAL are safe modalities in those with skin of color, but the patient-to-patient variation. However, the study subjects did amount of pigment in lesions and disease course can change not have long-term follow-up.47 the treatment outcome.51 QSAL has a longer wavelength of 755nm, which helps Another study explored the effect of low-dose 1064nm it to penetrate the dermis and target the dermal melano- Q-switched Nd:YAG laser (QSNYL) alone on melasma in cytes.48-49 The Angsuwarangsee, et al. study supports previ- 20 patients at fluences of 2.0-3.5 J/cm2. The treatment was ous reports on the ineffectiveness of Q-switch lasers alone performed five times within a one-week interval. The L-value in treating with dermal melanosis. Q-switch lasers target the from the chromatometer, which reflects the lightness of melanosome as their chromophore, and if the melanocyte is skin, was increased (0.86 +/- 1.67, p < 0.05). The melanin

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index from the mexameter was significantly decreased tinocytes. Because of the high recurrence rate and presence (-28.23 +/- 28.21, p < 0.001). The study concluded that low- of increased melanin levels in these patients on RCM, the dose 1064nm QSNYL appeared to be an effective treatment effects of Nd:YAG may just be temporary.54 modality for melasma.52 Intense Pulsed Light. Intense Pulsed Light (IPL) is a The usefulness of Nd:YAG laser has been challenged due broadband light source that emits a continuous spectrum to side effects and comparable results to topical treatments. in the range of 515-1200nm. Yamashita, et al. studied the Wattankrai, et al. conducted a split-face randomized study photothermal effect of IPL using reflectance-mode confo- comparing the combination of QS-Nd:YAG laser and 2% cal microscopy (RCM) and optical coherence tomography hydroquinone with topical treatment in dermal or mixed- (OCT). RCM was used before and after IPL therapy. Images type melasma. The study consisted of 22 patients who were done prior to IPL showed higher reflectance signals in com- treated with 1,064nm QS-Nd:YAG laser, 6mm spot size, 3.0- parison to surrounding skin, representing the increase in to 3.8-J/cm2 fluence for five sessions at one-week intervals. pigment concentration. After IPL, RCM images showed a After five laser treatments, the colorimeter readings showed collapse of the melanin caps with dispersal of melanosomes that the laser side improved by an average of 94.5 percent in among the basal keratinocytes. The study showed that relative lightness index compared to 19.7 percent of those melanosomes in the epidermal basal layer rapidly migrated using HQ. The mMASI score for the laser side improved by to the skin surface. The IPL therapy had caused the dena- 72.5 percent, compared to 24 percent in the control group. turation of melanin caps-containing cells that had trig- Both these results represented a statistically significant gered the differentiation of basal keratinocytes that would improvement (p<0.001) at the three month follow-up. All replace those extruded. The IPL irradiated melanocytes in patients had a recurrence, and four out of 22 patients had the lesions were left intact and resumed their activity after rebound hyperpigmentation. After the five laser treatments, treatment. The authors concluded that IPL therapy needs to 13.6 percent (three of 22 patients) had developed mottled be combined with bleaching agents or Q-switched laser for hypopigmentation that gradually improved. The laser treat- suppression of melanocytes.55 ment was associated with significant side effects. More than Li, et al. enrolled 89 Chinese women with melasma to five treatments weekly were advised, with clinician evalua- study the efficacy and safety of IPL. Eighty-one percent of tion for the development of any hypopigmentation or leu- the patients had a mixed type melasma, and 19 percent had coderma, which contraindicate further treatments.53 epidermal type according to Wood’s lamp examination. The The effects of the Nd:YAG laser have also been assessed patients received a total of four treatments at three week by reflectance confocal microscopy imaging before and after intervals at an energy density of 13 to 17J/cm2, which was treatment. In a study conducted by Zhou, et al., 50 patients adjusted according to the skin type. were given nine weekly Nd:YAG laser treatments. Follow- Sixty-seven of 89 patients (75.3 percent) obtained 51 to up was conducted at three months after the completion of 100 percent improvement after four IPL sessions, according the treatments. Effectiveness of treatment was measured by to the overall evaluation by dermatologists, and this num- MASI scores and confocal microscopy. At the end of the nine ber rose to 69 at the three month follow-up (77.5 percent). treatments, there was a mean decrease in MASI score of 61.3 According to patient self-assessments, 65 of 89 patients percent. A more than 50 percent improvement was achieved noted improvement by 50 percent or more at the end of the by 70 percent of patients with 10 percent of patients report- trial, and 63 (70.8 percent) maintained this result at following a 100 percent improvement. At three month follow-up up. The mean MASI scores decreased significantly from melasma had recurred in 64 percent of patients. Before 15.2 to 5.2 after four sessions. All of the parameters were Nd:YAG laser, RCM imaging of affected areas yielded mul- reassessed at the three-month follow-up. The mean MASI tiple melanin particles in keratinocytes in the lower stra- score was 4.5 at the follow-up visit (p<0.01). Melanin Index tum spinosum and basal layers, creating “melanin caps.” (MI) decreased from 140.8 at baseline to 121.1 after four ses- Interspersed in the basal layer were large bright melanocytes. sions and was 119.7 at the 3-month follow-up visit (p<.001). After the treatments, RCM imaging of treated areas showed Patients with epidermal-type melasma responded better fewer melanin particles and the large melanin particle pre- to treatment than mixed type. The study concluded that viously in the basal layer were rarely found. Melanin level the therapeutic efficacy of IPL increases in epidermal-type appeared to return to baseline in those patients who had melasma and if the underlying hormonal etiology is absent. a recurrence at the three month follow-up. These findings It also showed that results achieved with IPL are maintained were indicative of the mechanism of action of Nd:YAG lasers, consistently up to three months after cessation of therapy.56 which is an inhibition of melanin formation in melanocytes In another study conducted by Zhou, et al., 38 patients and decreased transfer of melanin from melanocytes to kera- were treated with IPL for three to five sessions at 40-45

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day intervals. Patients received follow-up at 30 days, three Melasma is a difficult skin condition to treat. Future stud- months, six months, and some at even more than one ies must focus on assessing the long-term results of the cur- year. Improvement was graded based upon reductions of rently available and widely used treatments. hyperpigmented areas and decrease of dark tones, with 80-100 percent reduction graded as excellent, 60-79 percent CONCLUSION reduction graded as good, 40-59 percent reduction graded Lasers are another treatment optios for patients with as moderate, and <39 percent reduction graded as poor. At melasma refractory to topical treatment. While many topical the end of the study, 18 patients were graded as excellent, treatments exist that are inexpensive and have minimal side 11 as good, five as moderate, and four as poor. In the cases effects, laser therapy is both expensive and ridden with poten- graded poor, hyperpigmented areas returned within two tial adverse effects. Careful measures must be taken prior to to four months. No side effects were reported at the end of choosing the appropriate laser as well as during therapy. The four to five treatments.54 use of RCM to better classify melasma type as well as choose the most appropriate laser is underutilized and would greatly DISCUSSION help in minimizing adverse effects. Its use will help in provid- Based upon studies available that addressed long-term ing the most precise and customizable level of care. n results, IPL provided long-lasting laser treatment for melasma. Few physicians use these methods in clinical practice All of the authors have no financial ties to disclose. due to side effects. IPL is known to cause scarring and ery- All of the above authors contributed to construction of this thema in darker skinned people. Although the IPL studies manuscript. No funding or financial support was received conducted were limited by the number of participants and from sponsors or any other sources. by the limited time frame for follow-up, the use of these Dr. Rao is a consultant for Caliber ID. All other authors treatment modalities should be further explored. have no conflict of interest. In addition, this literature review yielded very few studies using confocal microscopy to assess treatment efficacy. Mahin Alamgir, MD is a research assistant at Rao In the above listed categories, RCM evaluation of melasma Dermatology, New York City. site before and after treatment were only seen in the use Cindy Wassef, MD is a PGY-1 Internal Medicine resident of IPL and Nd:Yag lasers. In addition, the ability of RCM to at Morristown Medical Center, Morristown, NJ. She will be better stratify melasma patients into groups based upon starting her dermatology residency at Stony Brook University, depth of deposition of pigment will aid in choosing the laser Stony Brook, NY in July 2015. best suited for the patient. RCM can also offer insight of the Majid Hamidi is a graduate of University of Hartford, effects of laser treatments through serial imaging and assess- Hartford, CT. ment, which would be difficult to achieve with biopsies Babar K. Rao, MD is an Associate Clinical Professor of because of location of melasma lesions preodminantly on Dermatology at Rutgers Robert Wood Johnson Medical School, the face. This offers the ability to analyze the mechanism by Somerset, NJ. which these lasers work at a cellular level and whether their 1. Miot LD, Miot HA, Silva MG, Marques ME. Physiopathology of Melasma. An Bras Dermatol. 2009 ; 84 (6): 623-635. mechanism offers a long-term or short-term treatment of 2. Gupta AK, Gover MD, Nouri K, Taylor S. The Treatment of Melasma: A Review of Clinical Trials. J Am Acad Dermatol. melasma. When patients are refractory to many treatments, 2006 Dec; 55(6) 1048-1065. 3. Nordlund JJ. The Pigmentary System Physiology and Pathophysiology. New York: Oxford University Press, 1998. it becomes beneficial to advise a patient to have a noninva- 4. Grimes, PE. Melasma: Etiologic and Therapeutic Considerations. Arch Dermatol. 1995 Dec; 131 (12): 1453-1457. sive imaging assessment in order to understand the patho- 5. Goh CL, Dlova CN. A Retrospecitve Study on the Clinical Presentation and Treatment Outcome of Melasma in a Tertiary Dermatological Referral Centre in Singapore. Singapore Med J. 1999 Jul; 40(7): 455-458. physiology of their lesions. 6. Kauh YC, Zachian TF. Melasma. Adv Exp Med Biol. 1999; 455: 491-499. 7. Sanchez NP, Pathak MA, Sato S et al. Melasma: A Clinical, Light Microscopic, Ultrastructural, and Immunofluoresence An important point in the treatment of melasma is the Study. J Am Acad Dermatol. 1981 Jun; 4(6): 698-710. customization of treatments for each patient. The plethora 8. Taylor SC. Epidemiology of Skin Diseases in People of Color. Cutis. 2003 Apr; 71(4): 271-275. 9. Pandya AG, Guevara IL. Disorders of Hyperpigmentation. Dermatol Clin. 2000 Jan; 18(1): 91-98. of treatments available is a result of their variable usefulness 10. Pathak MA, Fitzpatrick TB, Kraus EW. Usefulness of Retinoic Acid in the Treatment of Melasma. J Am Acad Dermatol. for melasma. Finding treatment for each patient while tak- 1986; 15:894-899. 11. Karen JK, Pomeranz MK. “Skin Changes and Diseases in Pregnancy.” Dermatology in General Medicine. Eds. Klaus ing into account their melasma type and how each type has Wolff, Lowell A. Goldsmith, Stephen I Katz, Barbara A. Gilchrest, Amy S. Paller, David J. Lefell. New York: McGraw-Hill, 2008. 955-962. responded to treatments in the patient’s past is important 12. Vazquez M, Maldonado H, Benaman C, Sanchez JL. Melasma in Men: a Clinical and Histologic Study. Int J Dermatol. when making a treatment plan. Because of the exacerbat- 1988; 27:25-27. 13. Menter A. Rationale for the Use of Topical Corticosteroids in Melasma. J Drugs Dermatol. 2004; 3(2): 169-174. ing effects of the sun on melasma, it is necessary to counsel 14. Kang WH, Yoon KH, Lee ES et al. Melasma: Histopatholoigcal Characteristics in 56 Korean Patients. Br J Dermatol. 2002 patients on the need for adequate sun protection and sun Feb; 146(2): 228-237. 15. Gilchrest BA, Fitzpatrick TB, Anderson RR et al. Localization of Malanin Pigmentation in the Skin with Wood’s avoidance in order to maintain results from various treatments for as long as possible. (Continued on page 37)

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