Journal of Clinical and Investigative Dermatology
Melasma and Common Pigmentary Dermatoses in Asian Individuals and an Overview of Their Treatment
Kyoung-Chan Park* and Soon-Hyo Kwon
- Seoul National University College of Medicine, Seoul National University Bundang Hospital, Korea
*Address for Correspondence: Kyoung Chan Park, Department of Dermatology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam-si, Gyeonggi-do 463-707, Korea, Tel: + 82-31-787-7311; Fax: + 82-31-787-4058; E-mail: firstname.lastname@example.org
Citation: Kwon SH, Park KC. Melasma and Common Pigmentary Dermatoses in Asian Individuals and an Overview of Their Treatment. J Clin Investigat Dermatol. 2014;2(1): 8.
Copyright © 2014 Park et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Journal of Clinical & Investigative Dermatology | ISSN 2373-1044 | Volume: 2, Issue: 1
Submission: 19 November 2013 | Accepted: 23 January 2014 | Published: 27 January 2014
Reviewed & Approved by: Dr. Shasa Hu, Assistant Professor in the Department of Dermatology and Cutaneous Surgery at University of Miami, USA.
AbstractAsian patients with Fitzpatrick skin types III-V have been highlighted in publications describing pigmentary dermatoses. Melasma is particularly common in Asia, while nevus of Ota, acquiredbilateral nevus of Ota-like macules (ABNOM), and Mongolian spots are also frequently seen. In Asian individuals, postinflammatory hyperpigmentation (PIH) frequently occurs after the treatment, especially laser and light therapies. Thus, prevention and management of PIH are extremely important concerns. This review discusses the pigmentary dermatoses commonly encountered in Asia, including melasma, ABNOM, nevi of Ota and Ito, and Mongolian spots, and the various treatment options that are either currently available or under investigation in vitro.
KeywordsAcquired bilateral nevus of Ota-like macules; Asian individuals; Melasma; Mongolian spot; Nevus of Ota; Pigmentary dermatosis
IntroductionPigmentary skin disorders are of great concerns among Asian patients. This could be attributed to an increased interest on their skin conditions observed in Asian women. The exponential growth in the market of cosmetic procedures in Asia has exacerbated this trend. As a rapid increase in the populations is expected in Asian countries, pigmentary skin disorders in Asian individuals and their treatment will receive more attention over the next several decades.
MelasmaMelasma is an acquired hypermelanosis characterized by symmetrical, irregular light-to-dark-brown macules and patches on sun-exposed area, especially on the face. It is common among Asian and Hispanic women during their third and fourth decades of life . A genetic predisposition, chronic exposure to ultraviolet (UV) radiation, and female sex hormones are typically considered to play main roles in its pathogenesis [2-5]. Histopathological findings include epidermal hyperpigmentation accompanied by an increased number of melanocytes, overexpression of melanogenic enzymes, and overlying dermal changes .
Niacinamide (vitamin B3) and melanosome transfer inhibitors: A reduction in melanosome transfer from melanocytes to keratinocytes results in hypopigmentation by blocking the dispersion of pigment to the keratinocytes. A serine protease inhibitor has been reported to modulate the activation of the protease-activated receptor 2, resulting in the accumulation of melanosomes within melanocytes in vitro [41,42]. Lectins and neoglycoproteins have also been shown to reduce melanosome transfer in vitro . Hakozaki et al. (2002) demonstrated that niacinamide suppresses melanosome transfer in vitro, and in a split-face trial, showed that 5% niacinamide cream significantly reduced hyperpigmentation and lightened basal skin color in eight weeks  (p<0.05).
Other compounds: Topical application of linolenic acid, linoleic acid, oleic acid, and phospholipase D2 resulted in hypopigmentation of the skin of guinea pigs after UV irradiation via the stimulation of tyrosinase ubiquitination and proteasomal degradation [45-48].
Several compounds that modify tyrosinase structures at glycosylation sites have been found to induce hypopigmentation in vitro, including glucosamine, tunicamycin, and calcium D-pantetheine-S-sulfonate [49,50].
Laser and light therapies
Intense-pulsed light therapy: Intense-pulsed light (IPL) therapy emits a broad spectrum of wavelengths with a cutoff shorter than the filter, and provides selective photothermolysis . Li et al. (2008) evaluated the efficacy and safety of IPL treatment in 89 Chinese patients with melasma. After four treatment sessions with threeweek intervals, significant reductions in the mean Melasma Area and Severity Index (MASI) score, from 15.2 to 5.2 (p<0.05), and in the melanin index, from 140.8 to 119 (p<0.05) were found . In this study, transient erythema and edema were the most common adverse events, and three patients experienced PIH.
Although IPL is a good therapeutic option for melasma with promising results reported, melasma-like pigmentation following IPL treatment usually occurs, which is even more intensely pigmented than the melasma it treats. Laser energy induces hyperactive melanocytes through inflammation, increases prostaglandin and cytokine production in keratinocytes and fibroblasts, and disrupts the basement membrane. As a result, a mixture of PIH and aggravated melasma lesions forms [53,54]. Since subtle melasma is clinically invisible to the naked eye but is detected by UV photography in 28.3% of Asian patients, IPL treatment must be performed with caution .
Fractional 1,550-nm non-ablative laser therapy: Fractional photothermolysis creates numerous microthermal zones (MTZ) of thermal injury in the skin, while leaving the areas between them unaffected. Transepidermal elimination of the MTZ could effectively remove dermal melanophages . The unaffected areas may cause a more rapid recovery and theoretically, lower the risk of subsequent inflammation and PIH.
In a small clinical trial involving four-to-six sessions of fractional non-ablative laser treatment with one-to-two-week intervals, six out of 10 patients with Fitzpatrick skin types III-V achieved 75-100% clearance of the lesion, with PIH occurring in one patient . In contrast, a split-face study comparing fractional non-ablative laser treatment with TCC, found a significant worsening of pigmentation measured by a Mexameter® (p<0.05) and a higher incidence of PIH (31%) in the laser-treated group . However, in a similar eightweek trial performed by the same investigators, the study groups treated with either fractional non-ablative laser or TCC showed significant improvements in the investigator’s global assessment scores, and there was no statistical difference existed between the two groups .
Although fractional non-ablative laser is the only laser device approved by the FDA for melasma, the results vary and the high risk of PIH should be considered, especially in Asian patients. To lower the risk of the occurrence of PIH, treatment with lower fluences, variable pulses, and pretreatment with HQ for up to six weeks are recommended, particularly in patients who have a history of PIH .
Q-switched neodymium-doped yttrium aluminum garnet laser treatment : Exposure of skin to nanosecond-domain laser pulses affects the melanosomes through selective photothermolysis. However, laser treatment for melasma has been unsatisfactory because of the resulting inflammation and PIH. Since high-fluence laser irradiation increased the risk of adverse events, the concept of using collimated, low-fluence, 1,064-nm QSNYL treatment for melasma has been suggested. This “laser-toning” technique is popular in East Asian countries, and has become one of the first-line therapies for melasma. While its mechanism of action is unclear, several studies have found that ‘laser toning’ removes the melanosomes, but not the melanocytes. Furthermore, it damages the dendrites of the melanocytes without killing the cells, thereby functionally down-regulating the melanocytes in a process called “subcellular selective photothermolysis” [61,62]. Recently, reductions in the expression of proteins associated with melanogenesis, including TRP-1, tyrosinase-related protein-2, nerve growth factor, α-melanocyte-stimulating hormone, and tyrosinase, were also demonstrated after ‘laser toning’ .
In an eight-week trial, 58.8% of the patients who received ‘laser toning’ weekly, administered at 1.6-2.5 J/cm2, demonstrated an improvement of 50-75% in investigator’s global assessment scores . In this study, transient pain, erythema, and edema were commonly reported, while partially hypopigmented macules and diffuse hyperpigmentation rarely occurred. Wattanakrai et al. (2010) undertook a split-face trial to compare ‘laser toning’ with 2% HQ treatment . They found that the side that received ‘laser toning’ weekly, administered at 3.0-3.8 J/cm2 for five sessions, achieved marked improvements in the lightness index (L*) score (92.5%) assessed by a colorimeter, and in the modified MASI score (75.9%), compared with 19.7% and 24%, respectively, for the side administered 2% HQ. The investigators also reported that mottled hypopigmentation developed in three patients and melasma lesions recurred in all patients during follow-up.
Pulsed-dye laser treatment: Pulsed-dye laser (PDL) treatment is the gold standard therapy for vascular lesions. Evidence is accumulating that shows increased vascularization in melasma lesions, which may play a role in the recurrence of the disease [66-68]. An increase in the expression of vascular endothelial growth factor (VEGF) in keratinocytes has led to the suggestion that they may act in vessles, because functioning VEGF receptors were demonstrated in melanocytes in vitro [66,69]. Elevations in the levels of expression of c-kit, stem cell factor (SCF), and inducible nitric oxide synthase have also been observed, which could affect vascularization [70, 71].
In a split-face trial, Passeron et al. (2011) compared TCC plus PDL with TCC alone in patients with Fitzpatrick skin types II-IV . At the end of treatment, the MASI scores were significantly lowered in both groups (p<0.05). However, while the improvement was sustained at the two-month follow-up assessment in the group that received combination treatment, it was not sustained in the group that received TCC alone.
Copper bromide laser treatment : Copper bromide lasers emit two wavelengths of light either separately or simultaneously: the 511-nm green beam for the treatment of pigmented lesions, and the 578-nm yellow beam for the treatment of vascular lesions. In a recent pilot study, 10 Korean patients were treated with copper bromide laser at two-week intervals for eight weeks to evaluate its efficacy and safety . At the onemonth post-treatment follow-up, the mean MASI score decreased modestly from 12.3 to 9.5. L* and the erythema index (a*), measured using a Chromameter®, showed significant improvements (p<0.05). Histopathologically, reductions in the expression of melan-A, CD34, ET-1, and VEGF were observed.
Systemic tranexamic acid
Though the exact pathogenesis remains poorly understood, melasma involves alterations in different dermal components as well as increases in epidermal pigmentation. It includes disruptions and thinning of the basement membrane, prominent solar elastosis, increases in vascularization, elevations in the expression of VEGF, c-kit, and SCF, and increases in the number of mast cells [54,66,70,74]. TXA inhibits plasmin, a key molecule in angiogenesis that converts extracellular matrix-bound VEGF into its free forms . TXA has also been reported to suppress neovascularization induced by basic fibroblast growth factor . Therefore, TXA could reverse melasmarelated dermal changes.
In a recent clinical trial that evaluated the efficacy of systemic TXA in the treatment of melasma, we demonstrated a decrease in the lesional melanin index and a* (erythema index) after 250 mg TXA was administered orally to 25 female study participants three-times daily for eight weeks (Figure 3) . Histological analysis showed significant reductions in epidermal pigmentation, vessel numbers, and mast cell counts. In another trial conducted by Wu et al. (2012), 64.8% of the patients who were administered 250 mg TXA orally twice daily for six months showed “excellent” or “good” outcomes six months after the treatment had ceased . In this study, gastrointestinal discomfort (5.4%) and hypomenorrhea (8.1%) were commonly reported, but no severe adverse events occurred.
Acquired Bilateral Nevus of Ota-Like MaculesABNOM, or Hori nevus, first described by Hori et al. (1984), is characterized by multiple bilateral speckled blue-brown or slate gray macules on the malar area or, less commonly, on the forehead, upper eyelids, and nose, with no ocular or mucosal involvement (Figure 4) . It is usually found in middle-aged Asian women, with a reported incidence of 0.8% in a population-based study . Histological findings include irregularly shaped, dendritic melanocytes dispersed in the papillary and mid-dermis, and particularly in the subpapillary dermis. The pathogenesis of ABNOM remains poorly understood, but it is known that ectopic dermal melanocytes resulting from incorrect migration during embryological development are activated in response to UV exposure, excessive levels of sex hormones, chronic inflammation, or other undiscovered factors [79, 81-84].
Nevi of Ota and ItoNevi of Ota and Ito, and Mongolian spots are three variants of dermal melanocytosis, which can be distinguished by their clinical manifestations . Nevus of Ota, first described by Ota in 1939, presents as a blue-black, brown, or gray patch on the face within the unilateral trigeminal nerve distribution at birth or during adolescence. Histologic findings are similar to those for ABNOM, except that the melanocytes in nevus of Ota are distributed diffusely throughout the papillary and reticular dermis .
Mongolian SpotsMongolian spots present as congenital blue-grayish macules, which are usually located in the sacral area of infants. Sometimes, they appear on the extremities or trunk and are called ectopic Mongolian spots. They can be seen in most Mongolian individuals during the neonatal period, then spontaneously regress. However, some Mongolian spots persist into adulthood, which is estimated to occur in 2.8-4.1% of Japanese patients aged 18-26 years [96,97]. Ectopic Mongolian spots are more likely to persist than typical Mongolian spots , and it is unlikely to spontaneously regress when a patient is older than 11 years [96,98]. Several studies have demonstrated good responses of persistent Mongolian spots to QS laser devices [99-102].
AcknowledgementsThis study was supported by a grant of the Korea Healthcare technology R&D Project, Ministry of Health & Welfare, Republic of Korea (Grant No: A100179).
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