Letter to the Editor : Melasma Showing Response to Combination Therapy with Oral Tranexamic Acid and the Q-Switched Nd:YAG Laser

( Bum Joon Ko ),( Ga Hee Jung ),( Yung Lip Park ),( Jong Suk Lee ),( Kyu Uang Whang ),( Sung Yul Lee ) 대한피부과학회 2014 대한피부과학회지 Vol.52 No.10

Melasma is a relatively common skin disorder associated with dark, brown, symmetrical patches of hyperpigmentation involving the sun-exposed areas of the face. While various treatments are currently being used, there is no treatment regarded as entirely satisfactory1,2. Recently, the low-fluence 1064 nm Q-switched Nd:YAG (QSNY) laser has bee shown to be an effective and safe treatment option for patients with melasma1. Additionally, topical, intralesional tranexamic acid administration has been reported to improve clinical efficacy in melasma treatment2. Therefore, we attempted to treat patients with melasma using oral tranexamic acid and QSNY laser combination therapy. Two female patients, aged 38 and 43 years (Fitzpatrick skin type IV), were observed to have symmetric, multi-size, brown-colored patches on the malar area that had onset several weeks prior to examination (Fig. 1A, 2A). They both had normal menstruation with no significant past medical history. They were diagnosed with melasma based upon clinical appearance. The severity of the melasma was assessed using the modified Melasma Area and Severity Index (mMASI), with scores of 7.5 and 7.8. We began to treat for melasma with a combination of oral tranexamic acid (500 mg twice daily) and once-weekly use of the QSNY laser (Revlite®, HOYA ConBio, USA) set at 1,064 nm wavelength, 8 mm spot size, and 2.8 J/cm2. After 12 weeks, their melasma lesions greatly improved without complications, and mMASI scores decreased to 4.8 and 5.0 (Fig. 1B, 2B). Melasma may be treated using various therapeutic methods including topical or oral agents, chemical peeling, or laser treatment. These methods have been used alone or together as a form of combination therapy1. However, a satisfactory treatment regimen has yet to be found for patients with melasma and dark skin. QSNY treatment is based on photothermal and photomechanical interactions induced by selective photothermolysis. The 1064 nm QSNY laser can cause dermal and epidermal melanosome rupture in melanocytes and destructionof dermal melanophages1. Recently, the use of the 1064 nm QSNY laser has become increasingly referred to as “laser toning” for melasma in Asian countries. Although multiple passes of the low-fluence laser are delivered to obtain clinical improvement with less downtime in laser toning, it is possible to cause painful swelling and post- inflammatory hyper- or hypo-pigmentation1. Tranexamic acid is used as a hemostatic agent due to its selective antifibrolytic action. More recently, tranexamic acid has been used in the treatment of hyperpigmentation. Ultraviolet irradiation induces plasminogen activator synthesis and increases plasmin activity in keratinocytes and stimulates the release of arachidonic acid. Free arachidonic acid stimulates melanogenesis via its metabolite, prostaglandin. Tranexamic acid attaches to the lysine-binding site of plasminogen activator, which inhibits the plasminogen/ plasmin system. This results in interference with keratinocyte- melanocyte interactions and lower arachidonic acid and prostaglandin levels2,3. This mechanism down-regulates the tyrosine activity of melanocytes, resulting in improvement in patients with melasma hyperpigmentation lesions. Karn et al.4 reported that the addition of oral tranexamic acid provided rapid and sustained improvement in the treatment of melasma as compared to routine topical therapies only. Histologically, tranexamic acid decreases the epidermal pigmentation associated with melasma and also reverses melasma-related dermal changes, such as increased numbers of vessels and mast cells3. Side effects of tranexamic acid, such as gastrointestinal discomfort and hypomenorrhea, were observed in 5.4-8.1%of patients in 1 study; however, no severe complications were found until 6 months had passed, and the recurrence of melasma was observed in only a small portion of treated patients3. Currently, there are no long-term follow-up studies regarding this combination therapy. A 4-week follow-up study showed that in combination with low- fluence QSNY, oral tranexamic acid enhanced the efficacy of laser treatments, and reduced the risk of laser side effects by allowing for longer laser treatment intervals5. However, the treatment of melasma remains challenging due to its frequent recurrence, even after successful removal of lesions. Therefore, a long-term follow-up study of ongoing treatment is needed.We observed improvement in our patients with melasma after oral tranexamic acid and QSNY laser treatment. Therefore, we suggest that combination therapy using tranexamic acid and the QSNY laser should be considered as an effective modality for the treatment of melasma.

P268 : Characterization of dermal melanin in melasma

( Sang Jin Kim ),( Hee Young Kang ) 대한피부과학회 2014 대한피부과학회 학술발표대회집 Vol.66 No.2

Background: Melasma is a common acquired hyperpigmentary disorders occurring on the face. Traditionally, melasma has been classified into ‘epidermal’, ‘dermal’ and ‘mixed’ types according to the location of melanin pigment and dermal type of melasma was thought to be intractable. Objectives: We investigated clinical and histological characteristics of melasma with melanin in the dermis. Methods: Total 105 lesional skin samples and 21 perilesional normal skin samples were analyzed immunohistochemically. Results: 40 of 105 lesional skin samples and 8 of 21 perilesional normal skins had melanin in the dermis. All melasma with dermal melanin were mixed type and there was no true dermal type of melasma. The amount of dermal melanin in the lesion was compared with that of in the perlesional normal skin. Although the amount was slightly increased in the lesion, there was no statistically significant difference. Moreover, the amount was minimal compared with that of Riehl melanosis, well-known acquired dermal melanosis. The clinical and histological characteristics of melasma groups with dermal melanin were compared with melasma groups without dermal melanin. The melasma severity and histological changes including basement membrane, solar elastosis, and vascularity were assessed. There were no significant differences in all parameters between two groups. Conclusion: These findings suggest the amount of dermal melanin in melasma is minimal and is likely too low to be of clinical significance.

기미 환자의 삶의 질 평가

조태호 ( Tae Ho Cho ),홍석범 ( Seok Beom Hong ),류지호 ( Ji Ho Ryou ),이무형 ( Mu Hyoung Lee ) 대한피부과학회 2007 대한피부과학회지 Vol.45 No.3

Background: Melasma is a common pigmentary disorder of facial skin. It can have significant emotional, social, and psychological effects. But little is known about the impact of melasma on the quality of life (QOL) in Korean patients. Objective: The purpose of this study was to investigate the quality of life in patients with melasma. Methods: A total of 100 patients with melasma were enrolled and interviewed against the Melasma Quality of Life scale (MELASQOL), which was recently developed by Balkrishnan et al. The patients were also evaluated by the investigator using the Melasma Area and Severity Index (MASI). Results: The average score of MELASQOL was 41.2. A high score meant that melasma had a great effect on quality of life. It was high in patients with high MASI scores (p<0.01), young patients (p<0.01), and short duration of melasma (p<0.05). It was also high in those who had a high education level (p<0.05), or a previous treatment history (p<0.01). However, presence or absence of other skin diseases or preceding causes made no significant difference. Conclusion: This study shows that melasma has significant impact on the QOL of Korean melasma patients. Therefore, in addition to treating melasma, clinicians need to consider the psychosocial aspects of improving QOL in order to give patients optimal satisfaction. (Korean J Dermatol 2007;45(3):232~236)

Novel severity quantitative analysis method for melasma

( Jaeyoung Kim ),( Geo Han ),( Onseok Lee ),( Seunghan Ha ),( Jaewoo Ahn ),( Chilhwan Oh ) 대한피부과학회 2015 대한피부과학회 학술발표대회집 Vol.67 No.2

Background: Melasma is a common pigmentary skin disease with patchy facial skin discoloration and typically appears on upper cheeks, upper lip, forehead, and chin. The most common severity assessment method of melasma is Melasma Area Severity Index(MASI)score. However,ordinary MASI scoring system has some downsides due to the observer``s subjective visual judgment. Objectives: This study aimed to develop a new advanced severity assessment method of melasma based on computerized optical imaging analysis system. Methods: We proposed a new analysis method for the quantitative assessing of melasma. In order toquantitatvely analyze the involvement area, we divided frontal, cheek and chin region in patients. The divided images were processed to define the melasma lesions by the multi-threshold method and gradient mask were apply to correct the curvature error of facial contour.Degree of darkness and homogenesis were measured based on intensity of gray level and difference of gray level in melasma lesions. Results: The proposed new quantitative assessment method for melasma is more objective and accurate than ordinary MASI method. also, our method is able to quantify a minute difference of pigmented pattern among melasma patients. Conclusion: We developed the quantitative assessment method for melasma using computerized optical imaging analysis.Based on the results, our new computerized optical imaging system could be used as valuable tools to assess the severity of various pigmentary skin diseases

What Should Be Considered in Treatment of Melasma

( Hee Young Kang ),( Jean Paul Ortonne ) 대한피부과학회 2010 Annals of Dermatology Vol.22 No.4

Melasma is a common acquired hyperpigmentary skin disorder characterized by light to dark brown macules and patches occurring in the sun-exposed areas of the face. Melasma lesional skin is characterized by epidermal hyperpigmentation through increased melanogenesis in epidermal melanocytes. Some patients have dermal melanin but its amount is not significant and its distribution is very heterogeneous in the whole melasma lesional skin. Melasma is not homogeneous disease and there are personal characteristics of patients with melasma. The pathogenesis of melasma is not fully understood, but several hypotheses have been suggested. Increased vascularity in melasma lesions has suggested the role of increased number of enlarged vessels in the development of melasma. Endogeneous and exogeneous stimuli such as sex hormones and ultraviolet irradiation respectively may stimulate the microenvironment leading to the release of various mediators that cause activation of melanocytes and/or these stimuli may directly activate the melanocytes. Melasma patients may have specialized melanocytes with an intrinsic sensitivity to these stimuli. (Ann Dermatol 22(4) 373~378, 2010)

Epidemiology and clinical patterns of melasma in Korean patients

( Hyun Ji Kang ),( Tai Kyung Noh ),( Bo Young Chung ),( Mi Hye Lee ),( Chong Hyun Won ),( Mi Woo Lee ),( Jee Ho Choi ),( Sung Eun Chang ) 대한피부과학회 2015 대한피부과학회 학술발표대회집 Vol.67 No.2

Background: Melasma is a common acquired hyperpigmentary disorder that predominantly affects face. It frequently occurs among women with darker skin types and impacts quality of life. Objectives: To characterize the clinicoepidemiological features and the precipitating or aggravating factors of melasma in Korean patients. Methods: Present cross-sectional, multicenter study conducted in dermatological clinics of five tertiary hospitals in Korea. Four hundred and eleven patients with melasma completed a questionnaire concerning the clinical features and factors associated to their melasma, from January 2011 to August 2012. Results: Mean disease onset is 33.7【8.67. Most common triggering factor is sun exposure (68.4%) followed by pregnancy (27.0%) and emotional stress. Inflammatory status of face triggered and/or aggravated melasma in 61.1% of patients at least once. Dryness is the most common aggravating factor, followed by erythema/telangiectasia and itching/tingling. Concomitant pigmented disorders were post-inflammatory hyperpigmentation in 15.1%, followed by pigmented contact dermatitis including Riehl’s melanosis, and ABNOM. Conclusion: As it is well known that sun exposure and hormonal changes are most common cause of triggering the melasma, however, the inflammatory features may aggravate melasma in Asian patients. Therefore, these individual differences should be considered in the prevention as well as treatment of melasma.

P230 : Effects of fibroblast-derived factors from melasma skin on the melanogenesis of human melanocytes in culture and of pigmented epidermal equivalents

( Ji Won Byun ),( Hyo Jin Kim ),( In Seo Park ),( Gwang Seong Choi ),( Jeong Hyun Shin ) 대한피부과학회 2013 대한피부과학회 학술발표대회집 Vol.65 No.2

Background: Melasma is a common acquired hyperpigmentary disorder. Though its pathogenesis is known to be related with sun-exposure, sex hormone, and stress, it is poorly understood why it recurs easily and is frequently aggravated with treatments. We have demonstrated that repeated ultraviolet light exposure induced fibroblast senescence and increased SCF secretion from the fibroblasts. And we suggested a role of fibroblasts in the pathogenesis of hyperpigmentation disorders induced by chronic sun exposure such as melasma. Objectives: In this study, we wanted to know whether the primarily cultured fibroblasts from melasma tissue have a melanogenic function. Methods: We also investigated its cytokine profile and the effect on the cultured human epidermal melanocytes and the pigmented epidermal equivalents. Results: Fibroblasts from the melasma secreted more IL-1a, IL-6, IL-10, TNF-a, HGF, SCF, NGF-b, and NT-3. The perilesional skin fibroblasts had more NGF, NT-3 than buttock skin. The conditioned medium of fibroblasts from the melasma and perilesional skin increased melanogenesis of cultured human epidermal melanocytes by increasing tyrosinase, TRP1, TRP2 and SCF. In the study with pigmented epidermal equivalents, melanin, NGF, NGFR, and SCF were increased in the equivalents co-cultured with melasma and perilesional fibroblasts than buttock skin. Conclusion: We suggest melasma lesional as well as perilesional fibroblasts play an important role in the pathogenesis of melasma.

Using reflectance confocal microscopy to observe in vivo melanolysis after treatment with the picosecond alexandrite laser and Q-switched Nd:YAG laser in melasma

( Da Jung Jo ),( In-hye Kang ),( Ji Hwoon Baek ),( Min Jae Gwak ),( Sang Jun Lee ),( Min Kyung Shin ) 대한피부과학회 2018 대한피부과학회 학술발표대회집 Vol.70 No.2

Background: Melasma is an acquired type of hyperpigmentation that is characterized by the appearance of scattered light- to dark-brown macules and patches on the face. Recently, several lasers have been proposed as treatment options for melasma. In particular, the picosecond alexandrite laser is an ideal laser for selective photothermal melanolysis. Objectives: The aim of our study was to compare the effectiveness in melanolysis of a single treatment of the picosecond alexandrite laser with that of the Q-switched Nd:YAG laser using reflectance confocal microscopy imaging of the melasma lesions. Methods: We performed a spilt-face study using the picosecond alexandrite laser and Q-switched Nd:YAG laser in eight patients with melasma. Both melasma lesions and surrounding normal skin were examined under reflectance confocal microscopy 1 and 24 hours after treatment. The melanin intensity of each skin layer was investigated. Results: At baseline, melasma has irregular melanin distribution and a higher melanin density than surrounding normal skin under reflectance confocal microscopy. After a single treatment with either the picosecond alexandrite laser or the Q-switched Nd:YAG laser, both melanin-induced reflectance and melanin index decreased. Conclusion: Our findings suggest that it is feasible to assess the distribution of melanin by reflectance confocal microscopy and observe the melanolysis in melasma lesion after laser treatment.

Efficacy and safety of tranexamic acid in melasma: a systematic review and meta-analysis

( Seok Hoon Moon ),( Sang Hyun Cho ),( Jeong Deuk Lee ),( Hei Sung Kim ) 대한피부과학회 2016 대한피부과학회 학술발표대회집 Vol.68 No.2

Background: Tranexamic acid (TA) has been introduced as a novel treatment option for melasma, but there is still no consensus on its use. Objectives: We sought to assess the efficacy and safety of TA in the management of melasma. Methods: The authors performed an EMBASE, MEDLINE, Web of Science, Scopus, and Cochrane Central Register of Controlled Trials (CENTRAL) search for studies reporting outcome of TA treatment in patients with melasma. A meta-analysis was performed on TA-only observational studies with pre- and post-treatment Melasma Area and Severity Index (MASI), regardless of the mode of TA delivery. Also, studies comparing changes in MASI between a routine melasma treatment and that with TA as an adjuvant were analyzed. Results: Eleven studies with a total of 667 participants were included. Pooled data on TA-only observational studies with pre- and post-treatment MASI showed a 1.60 decrease in MASI (95% confidence interval [CI], 1.20-2.00; P<.001) after TA treatment. The addition of TA to routine treatment modalities resulted in a further decrease of MASI by 0.94 (95% CI, 0.10-1.79; P=.03). Side effects were minor with few reporting hypo-menorrhea, mild abdominal discomfort and transient skin irritation. Conclusion: The current limited evidence supports the efficacy and safety of TA, either alone or as an adjuvant to routine treatment modalities, in melasma. Randomized controlled trials on well-defined participants with long-term outcomes are needed.

기미 환자 치료 후 삶의 질 변화 평가

강홍규 ( Hong Kyu Kang ),백진옥 ( Jin Ok Baek ),노주영 ( Joo Young Roh ),이종록 ( Jong Rok Lee ) 대한피부과학회 2012 대한피부과학회지 Vol.50 No.7

Background: Melasma is an acquired, symmetrical hypermelanosis that occurs on sun-exposed areas of the skin. It has significant emotional and psychological effects on those affected with the condition. Melasma Quality of Life Scale (MELASQOL) is a specific questionnaire to identify the most impaired areas of melasma patient`s life. Objective: Our purpose of this study is to investigate the changing of MELASQOL after the treatment of melasma. Methods: A total of 27 volunteers with melasma were enrolled in this 8-week treatment study. The patients were instructed to apply an arbutin-containing cream, <at a frequency of> once a day for 8 weeks. The assessment of outcomes included the colorimetric value (L*) and MELASQOL score. Results: The arbutin-containing cream group increased more in the colorimetric values (L*) after the 8-week treatment (p<0.01). The MELASQOL score was decreased (p=0.02). No significant adverse reactions were observed. Conclusion: The treatment of melasma improves the QOL of melasma patients. (Korean J Dermatol 2012;50(7): 579∼583)