Lasers, lights, and compounds for melasma in aesthetics


      Melasma is a chronic and relapsing skin condition. Although melasma is usually asymptomatic, it can be associated with immense psychosocial stress and greatly impact a patient's quality of life. Over the years, many different treatments have been used, ranging from daily photoprotection, topical lightening creams, and oral agents to laser and light-based therapies; however, efficacy is often limited with such treatments, and there is currently no effective modality to prevent recurrence. Although treatment strategies had originally centered on the use of hydroquinone, newer modalities now include oral tranexamic acid and lasers. We examined previous and ongoing debates related to melasma treatments and have reviewed the current efficacy and safety of available treatments. Critical components essential to the successful management of melasma are the setting of patient expectations and assurance of treatment compliance.
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        • Rajaratnam R
        • Halpern J
        • Salim A
        • Emmett C.
        Interventions for melasma.
        Cochrane Database Syst Rev. 2010; 7CD003583
        • Grimes PE
        • Yamada N
        • Bhawan J.
        Light microscopic, immunohistochemical, and ultrastructural alterations in patients with melasma.
        Am J Dermatopathol. 2005; 27: 96-101
        • Shankar K
        • Godse K
        • Aurangabadkar S
        • et al.
        Evidence-based treatment for melasma: expert opinion and a review.
        Dermatol Ther. 2014; 4: 165-186
        • Balkrishnan R
        • McMichael AJ
        • Camacho FT
        • et al.
        Development and validation of a health-related quality of life instrument for women with melasma.
        Br J Dermatol. 2003; 149: 572-577
        • Tamega A de A
        • Miot LDB
        • Bonfietti C
        • Gige TC
        • Marques MEA
        • Miot HA
        Clinical patterns and epidemiological characteristics of facial melasma in Brazilian women.
        J Eur Acad Dermatol Venereol. 2013; 27: 151-156
        • Kwon S-H
        • Hwang Y-J
        • Lee S-K
        • Park K-C.
        Heterogeneous pathology of melasma and its clinical implications.
        Int J Mol Sci. 2016; : 17
        • Noh TK
        • Choi SJ
        • Chung BY
        • et al.
        Inflammatory features of melasma lesions in Asian skin.
        J Dermatol. 2014; 41: 788-794
        • Bak H
        • Lee HJ
        • Chang S-E
        • Choi J-H
        • Kim MN
        • Kim BJ.
        Increased expression of nerve growth factor receptor and neural endopeptidase in the lesional skin of melasma.
        Dermatol Surg. 2009; 35: 1244-1250
        • Kim EH
        • Kim YC
        • Lee E-S
        • Kang HY.
        The vascular characteristics of melasma.
        J Dermatol Sci. 2007; 46: 111-116
        • Trivedi MK
        • Yang FC
        • Cho BK.
        A review of laser and light therapy in melasma.
        Int J Womens Dermatol. 2017; 3: 11-20
        • McKesey J
        • Tovar-Garza A
        • Pandya AG.
        Melasma treatment: an evidence-based review.
        Am J Clin Dermatol. 2020; 21: 173-225
        • Lakhdar H
        • Zouhair K
        • Khadir K
        • et al.
        Evaluation of the effectiveness of a broad-spectrum sunscreen in the prevention of chloasma in pregnant women.
        J Eur Acad Dermatol Venereol. 2007; 21: 738-742
        • Sarkar R
        • Ghunawat S
        • Narang I
        • Verma S
        • Garg VK
        • Dua R.
        Role of broad-spectrum sunscreen alone in the improvement of melasma area severity index (MASI) and Melasma Quality of Life Index in melasma.
        J Cosmet Dermatol. 2019; 18: 1066-1073
        • Jutley GS
        • Rajaratnam R
        • Halpern J
        • Salim A
        • Emmett C.
        Systematic review of randomized controlled trials on interventions for melasma: an abridged Cochrane review.
        J Am Acad Dermatol. 2014; 70: 369-373
        • Duteil L
        • Esdaile J
        • Maubert Y
        • et al.
        A method to assess the protective efficacy of sunscreens against visible light-induced pigmentation.
        Photodermatol Photoimmunol Photomed. 2017; 33: 260-266
        • Duteil L
        • Cardot-Leccia N
        • Queille-Roussel C
        • et al.
        Differences in visible light-induced pigmentation according to wavelengths: a clinical and histological study in comparison with UVB exposure.
        Pigment Cell Melanoma Res. 2014; 27: 822-826
        • Mahmoud BH
        • Ruvolo E
        • Hexsel CL
        • et al.
        Impact of long-wavelength UVA and visible light on melanocompetent skin.
        J Invest Dermatol. 2010; 130: 2092-2097
        • Regazzetti C
        • Sormani L
        • Debayle D
        • et al.
        Melanocytes sense blue light and regulate pigmentation through Opsin-3.
        J Invest Dermatol. 2018; 138: 171-178
        • Castanedo-Cazares JP
        • Hernandez-Blanco D
        • Carlos-Ortega B
        • Fuentes-Ahumada C
        • Torres-Álvarez B.
        Near-visible light and UV photoprotection in the treatment of melasma: a double-blind randomized trial.
        Photodermatol Photoimmunol Photomed. 2014; 30: 35-42
        • Boukari F
        • Jourdan E
        • Fontas E
        • et al.
        Prevention of melasma relapses with sunscreen combining protection against UV and short wavelengths of visible light: a prospective randomized comparative trial.
        J Am Acad Dermatol. 2015; 72 (e1): 189-190
        • Dumbuya H
        • Grimes PE
        • Lynch S
        • et al.
        Impact of iron-oxide containing formulations against visible light-induced skin pigmentation in skin of color individuals.
        J Drugs. Dermatol. 2020; 19: 712-717
        • Lyons AB
        • Trullas C
        • Kohli I
        • Hamzavi IH
        • Lim HW.
        Photoprotection beyond ultraviolet radiation: a review of tinted sunscreens.
        J Am Acad Dermatol. 2021; 84: 1393-1397
        • Ruvolo E
        • Fair M
        • Hutson A
        • Liebel F.
        Photoprotection against visible light-induced pigmentation.
        Int J Cosmet Sci. 2018; 40: 589-595
        • Bissonnette R
        • Nigen S
        • Bolduc C
        • Méry S
        • Nocera T.
        Protection afforded by sunscreens containing inorganic sunscreening agents against blue light sensitivity induced by aminolevulinic acid.
        Dermatol Surg. 2008; 34: 1469-1476
        • Grimes PE.
        Management of hyperpigmentation in darker racial ethnic groups.
        Semin Cutan Med Surg. 2009; 28: 77-85
        • Ennes SBP
        • Paschoalick RC
        • Alchorne MMDA.
        A double-blind, comparative, placebo-controlled study of the efficacy and tolerability of 4% hydroquinone as a depigmenting agent in melasma.
        J Dermatol Treat. 2000; 11: 173-179
        • Amer M
        • Metwalli M.
        Topical hydroquinone in the treatment of some hyperpigmentary disorders.
        Int J Dermatol. 1998; 37: 449-450
        • Nordlund JJ
        • Grimes PE
        • Ortonne JP.
        The safety of hydroquinone.
        J Eur Acad Dermatol Venereol. 2006; 20: 781-787
        • Cestari T
        • Arellano I
        • Hexsel D
        • Ortonne JP
        Latin American Pigmentary Disorders Academy. Melasma in Latin America: options for therapy and treatment algorithm.
        J Eur Acad Dermatol Venereol. 2009; 23: 760-772
        • Gheisari M
        • Dadkhahfar S
        • Olamaei E
        • Moghimi HR
        • Niknejad N
        Najar Nobari N. The efficacy and safety of topical 5% methimazole vs 4% hydroquinone in the treatment of melasma: a randomized controlled trial.
        J Cosmet Dermatol. 2020; 19: 167-172
        • Ahmad Nasrollahi S
        • Sabet Nematzadeh M
        • Samadi A
        • et al.
        Evaluation of the safety and efficacy of a triple combination cream (hydroquinone, tretinoin, and fluocinolone) for treatment of melasma in Middle Eastern skin.
        Clin Cosmet Investig Dermatol. 2019; 12: 437-444
        • Arellano I
        • Cestari T
        • Ocampo-Candiani J
        • et al.
        Preventing melasma recurrence: Prescribing a maintenance regimen with an effective triple combination cream based on long-standing clinical severity.
        J Eur Acad Dermatol Venereol. 2012; 26: 611-618
        • Tse TW.
        Hydroquinone for skin lightening: safety profile, duration of use and when should we stop?.
        J Dermatolog Treat. 2010; 21: 272-275
        • Gandhi V
        • Verma P
        • Naik G.
        Exogenous ochronosis after prolonged use of topical hydroquinone (2%) in a 50-year-old Indian female.
        Indian J Dermatol. 2012; 57: 394-395
        • Rodrigues M
        • Pandya AG.
        Melasma: clinical diagnosis and management options.
        Australas J Dermatol. 2015; 56: 151-163
        • Ferreira Cestari T
        • Hassun K
        • Sittart A
        • de Lourdes
        • Viegas M.
        A comparison of triple combination cream and hydroquinone 4% cream for the treatment of moderate to severe facial melasma.
        J Cosmet Dermatol. 2007; 6: 36-39
        • Gong Z
        • Lai W
        • Zhao G
        • et al.
        Efficacy and safety of fluocinolone acetonide, hydroquinone, and tretinoin cream in chinese patients with melasma: a randomized, double-blind, placebo-controlled, multicenter, parallel-group study.
        Clin Drug Investig. 2015; 35: 385-395
        • Wang JV
        • Jhawar N
        • Saedi N.
        Tranexamic acid for melasma: evaluating the various formulations.
        J Clin Aesthet Dermatol. 2019; 12: E73-E74
        • Grimes PE
        • Bhawan J
        • Guevara IL
        • et al.
        Continuous therapy followed by a maintenance therapy regimen with a triple combination cream for melasma.
        J Am Acad Dermatol. 2010; 62: 962-967
        • Farshi S
        • Mansouri P
        • Kasraee B.
        Efficacy of cysteamine cream in the treatment of epidermal melasma, evaluating by Dermacatch as a new measurement method: a randomized double blind placebo controlled study.
        J Dermatolog Treat. 2018; 29: 182-189
        • Ahmed AM
        • Lopez I
        • Perese F
        • et al.
        A randomized, double-blinded, placebo-controlled trial of oral Polypodium leucotomos extract as an adjunct to sunscreen in the treatment of melasma.
        JAMA Dermatol. 2013; 149: 981-983
        • Goh C-L
        • Chuah SY
        • Tien S
        • Thng G
        • Vitale MA
        • Delgado-Rubin A.
        Double-blind, placebo-controlled trial to evaluate the effectiveness of polypodium leucotomos extract in the treatment of melasma in Asian skin: a pilot study.
        J Clin Aesthet Dermatol. 2018; 11: 14-19
        • Ogbechie-Godec OA
        • Elbuluk N.
        Melasma: an up-to-date comprehensive review.
        Dermatol Ther. 2017; 7: 305-318
        • Sonthalia S
        • Jha AK
        • Lallas A
        • Jain G
        • Jakhar D.
        Glutathione for skin lightening: a regnant myth or evidence-based verity?.
        Dermatol Pract Concept. 2018; 8: 15-21
        • Handog EB
        • Datuin MSL
        • Singzon IA.
        An open-label, single-arm trial of the safety and efficacy of a novel preparation of glutathione as a skin-lightening agent in Filipino women.
        Int J Dermatol. 2016; 55: 153-157
      1. Colferai MMT, Miquelin GM, Steiner D. Evaluation of oral tranexamic acid in the treatment of melasma [e-pub ahead of print]. J Cosmet Dermatol. doi: 10.1111/jocd.12830, accessed 1/25/2020.

        • Mekontso-Dessap A
        • Collet JP
        • Lebrun-Vignes B
        • Soubrié C
        • Thomas D
        • Montalescot G.
        Acute myocardial infarction after oral tranexamic acid treatment initiation.
        Int J Cardiol. 2002; 83: 267-268
        • Leminen H
        • Hurskainen R.
        Tranexamic acid for the treatment of heavy menstrual bleeding: efficacy and safety.
        Int J Womens Health. 2012; 4: 413-421
        • Tan AWM
        • Sen P
        • Chua SH
        • Goh BK.
        Oral tranexamic acid lightens refractory melasma.
        Australas J Dermatol. 2017; 58: e105-e108
        • Wu S
        • Shi H
        • Wu H
        • et al.
        Treatment of melasma with oral administration of tranexamic acid.
        Aesthetic Plast Surg. 2012; 36: 964-970
        • Lee HC
        • Thng TGS
        • Goh CL.
        Oral tranexamic acid (TA) in the treatment of melasma: a retrospective analysis.
        J Am Acad Dermatol. 2016; 75: 385-392
        • Endo Y
        • Nishimura S
        • Miura A.
        Deep-vein thrombosis induced by tranexamic acid in idiopathic thrombocytopenic purpura.
        JAMA. 1988; 259: 3561-3562
        • Woo KS
        • Tse LK
        • Woo JL
        • Vallance-Owen J.
        Massive pulmonary thromboembolism after tranexamic acid antifibrinolytic therapy.
        Br J Clin Pract. 1989; 43: 465-466
        • Kang H
        • Kim J
        • Goo B.
        The dual toning technique for melasma treatment with the 1064 nm Nd: YAG laser: a preliminary study.
        Laser Ther. 2011; 20: 189-194
        • Wattanakrai P
        • Mornchan R
        • Eimpunth S.
        Low-fluence Q-switched neodymium-doped yttrium aluminum garnet (1,064 nm) laser for the treatment of facial melasma in Asians.
        Dermatol Surg. 2010; 36: 76-87
        • Passeron T
        • Fontas E
        • Kang HY
        • Bahadoran P
        • Lacour J-P
        • Ortonne J-P.
        Melasma treatment with pulsed-dye laser and triple combination cream: a prospective, randomized, single-blind, split-face study.
        Arch Dermatol. 2011; 147: 1106-1108
        • Tse Y
        • Levine VJ
        • McClain SA
        • Ashinoff R.
        The removal of cutaneous pigmented lesions with the Q-switched ruby laser and the Q-switched neodymium: yttrium-aluminum-garnet laser: a comparative study.
        J Dermatol Surg Oncol. 1994; 20: 795-800
        • Taylor CR
        • Anderson RR.
        Ineffective treatment of refractory melasma and postinflammatory hyperpigmentation by Q-switched ruby laser.
        J Dermatol Surg Oncol. 1994; 20: 592-597
        • Wang C-C
        • Hui C-Y
        • Sue Y-M
        • Wong W-R
        • Hong H-S.
        Intense pulsed light for the treatment of refractory melasma in Asian persons.
        Dermatol Surg. 2004; 30: 1196-1200
        • Angsuwarangsee S
        • Polnikorn N.
        Combined ultrapulse CO2 laser and Q-switched alexandrite laser compared with Q-switched alexandrite laser alone for refractory melasma: split-face design.
        Dermatol Surg. 2003; 29: 59-64
        • Choi Y-J
        • Nam J-H
        • Kim JY
        • et al.
        Efficacy and safety of a novel picosecond laser using combination of 1 064 and 595 nm on patients with melasma: a prospective, randomized, multicenter, split-face, 2% hydroquinone cream-controlled clinical trial.
        Lasers Surg Med. 2017; 49: 899-907
        • Shin JU
        • Park J
        • Oh SH
        • Lee JH.
        Oral tranexamic acid enhances the efficacy of low-fluence 1064-nm quality-switched neodymium-doped yttrium aluminum garnet laser treatment for melasma in Koreans: a randomized, prospective trial.
        Dermatol Surg. 2013; 39: 435-442
        • Park KY
        • Kim DH
        • Kim HK
        • Li K
        • Seo SJ
        • Hong CK.
        A randomized, observer-blinded, comparison of combined 1064-nm Q-switched neodymium-doped yttrium-aluminium-garnet laser plus 30% glycolic acid peel vs. laser monotherapy to treat melasma.
        Clin Exp Dermatol. 2011; 36: 864-870
        • Lee DB
        • Suh HS
        • Choi YS.
        A comparative study of low-fluence 1064-nm Q-switched Nd:YAG laser with or without chemical peeling using Jessner's solution in melasma patients.
        J Dermatolog Treat. 2014; 25: 523-528
        • Jeong S-Y
        • Shin J-B
        • Yeo U-C
        • Kim W-S
        • Kim I-H.
        Low-fluence Q-switched neodymium-doped yttrium aluminum garnet laser for melasma with pre- or post-treatment triple combination cream.
        Dermatol Surg. 2010; 36: 909-918
        • Hofbauer Parra CA
        • Careta MF
        • Valente NYS
        • de Sanches Osório NEG
        • Torezan LAR
        Clinical and histopathologic assessment of facial melasma after low-fluence Q-switched neodymium-doped yttrium aluminium garnet laser.
        Dermatol Surg. 2016; 42: 507-512
        • Vachiramon V
        • Sirithanabadeekul P
        • Sahawatwong S.
        Low-fluence Q-switched Nd: YAG 1064-nm laser and intense pulsed light for the treatment of melasma.
        J Eur Acad Dermatol Venereol. 2015; 29: 1339-1346
        • Spierings NMK.
        Melasma: a critical analysis of clinical trials investigating treatment modalities published in the past 10 years.
        J Cosmet Dermatol. 2020; 19: 1284-1289
        • Manstein D
        • Herron GS
        • Sink RK
        • Tanner H
        • Anderson RR.
        Fractional photothermolysis: a new concept for cutaneous remodeling using microscopic patterns of thermal injury.
        Lasers Surg Med. 2004; 34: 426-438
        • Hantash BM
        • Bedi VP
        • Sudireddy V
        • Struck SK
        • Herron GS
        • Chan KF.
        Laser-induced transepidermal elimination of dermal content by fractional photothermolysis.
        J Biomed Opt. 2006; 11041115
        • Rokhsar CK
        • Fitzpatrick RE.
        The treatment of melasma with fractional photothermolysis: a pilot study.
        Dermatol Surg. 2005; 31: 1645-1650
        • Lee HS
        • Won CH
        • Lee DH
        • et al.
        Treatment of melasma in Asian skin using a fractional 1,550-nm laser: an open clinical study.
        Dermatol Surg. 2009; 35: 1499-1504
        • Kroon MW
        • Wind BS
        • Beek JF
        • et al.
        Nonablative 1550-nm fractional laser therapy versus triple topical therapy for the treatment of melasma: a randomized controlled pilot study.
        J Am Acad Dermatol. 2011; 64: 516-523
        • Wind BS
        • Kroon MW
        • Meesters AA
        • et al.
        Non-ablative 1,550 nm fractional laser therapy versus triple topical therapy for the treatment of melasma: a randomized controlled split-face study.
        Lasers Surg Med. 2010; 42: 607-612
        • Tourlaki A
        • Galimberti MG
        • Pellacani G
        • Bencini PL.
        Combination of fractional erbium-glass laser and topical therapy in melasma resistant to triple-combination cream.
        J Dermatolog Treat. 2014; 25: 218-222
        • Polder KD
        • Bruce S.
        Treatment of melasma using a novel 1,927-nm fractional thulium fiber laser: a pilot study.
        Dermatol Surg. 2012; 38: 199-206
        • Lee HM
        • Haw S
        • Kim JK
        • Chang SE
        • Lee MW.
        Split-face study using a 1,927-nm thulium fiber fractional laser to treat photoaging and melasma in Asian skin.
        Dermatol Surg. 2013; 39: 879-888
        • Niwa Massaki ABM
        • Eimpunth S
        • Fabi SG
        • Guiha I
        • Groff W
        • Fitzpatrick R
        Treatment of melasma with the 1,927-nm fractional thulium fiber laser: a retrospective analysis of 20 cases with long-term follow-up.
        Lasers Surg Med. 2013; 45: 95-101
        • Lyons AB
        • Moy RL
        • Herrmann JL.
        A randomized, controlled, split-face study of the efficacy of a picosecond laser in the treatment of melasma.
        J Drugs Dermatol. 2019; 18: 1104-1107
        • Chalermchai T
        • Rummaneethorn P.
        Effects of a fractional picosecond 1,064 nm laser for the treatment of dermal and mixed type melasma.
        J Cosmet Laser Ther. 2018; 20: 134-139
        • Wang YJ
        • Lin ET
        • Chen YT
        • et al.
        Prospective randomized controlled trial comparing treatment efficacy and tolerance of picosecond alexandrite laser with a diffractive lens array and triple combination cream in female asian patients with melasma.
        J Eur Acad Dermatol Venereol. 2020; 34: 624-632
        • Lee M-C
        • Lin Y-F
        • Hu S
        • et al.
        A split-face study: comparison of picosecond alexandrite laser and Q-switched Nd:YAG laser in the treatment of melasma in Asians.
        Lasers Med Sci. 2018; 33: 1733-1738
        • Trelles MA
        • Velez M
        • Gold MH.
        The treatment of melasma with topical creams alone, CO2 fractional ablative resurfacing alone, or a combination of the two: a comparative study.
        J Drugs Dermatol. 2010; 9: 315-322
        • Nouri K
        • Bowes L
        • Chartier T
        • Romagosa R
        • Spencer J.
        Combination treatment of melasma with pulsed CO2 laser followed by Q-switched alexandrite laser: a pilot study.
        Dermatol Surg. 1999; 25: 494-497
        • Manaloto RM
        • Alster T.
        Erbium:YAG laser resurfacing for refractory melasma.
        Dermatol Surg. 1999; 25: 121-123
        • Wanitphakdeedecha R
        • Manuskiatti W
        • Siriphukpong S
        • Chen TM.
        Treatment of melasma using variable square pulse Er:YAG laser resurfacing.
        Dermatol Surg. 2009; 35: 475-481
        • Sheth VM
        • Pandya AG.
        Melasma: a comprehensive update: part II.
        J Am Acad Dermatol. 2011; 65: 699-714
        • Rahman Z
        • Alam M
        • Dover JS.
        Fractional laser treatment for pigmentation and texture improvement.
        Skin Therapy Lett. 2006; 11: 7-11
        • Figueiredo Souza L
        • Trancoso Souza S
        Single-session intense pulsed light combined with stable fixed-dose triple combination topical therapy for the treatment of refractory melasma.
        Dermatol Ther. 2012; 25: 477-480
        • Goldman MP
        • Gold MH
        • Palm MD
        • et al.
        Sequential treatment with triple combination cream and intense pulsed light is more efficacious than sequential treatment with an inactive (control) cream and intense pulsed light in patients with moderate to severe melasma.
        Dermatol Surg. 2011; 37: 224-233
        • Shakeeb N
        • Noor SM
        • Ullah G
        • Paracha MM.
        Efficacy of intense pulse light therapy and tripple combination cream versus intense pulse light therapy and tripple combination cream alone in epidermal melasma treatment.
        J Coll Physicians Surg Pak. 2018; 28: 13-16
        • Chung JY
        • Lee JH
        • Lee JH.
        Topical tranexamic acid as an adjuvant treatment in melasma: side-by-side comparison clinical study.
        J Dermatolog Treat. 2016; 27: 373-377