Site Under Construction

Melasma in brown skin: part 2

Maria Juliet E. Macarayo, MD, FPDS and Evangeline B. Handog, MD, FPDS


Melasma, as elusive as it is, has yet to find an agent that will resolve its complexity. How to decrease the pigmentation may not be an enigma, but to get the result every dermatologist wishes to achieve and every melasma patient wishes to attain are the enigma. Hitting the principles of management (i.e. impeding activity of melanocytes, hindering synthesis of melanin, interrupting to eliminating melanin granules, and shielding from ultraviolet rays) known to us, may not be enough. Not only the patient’s condition has to be taken in its wholeness, but the patient’s personality, as well. Apart from taking into account the kind of melasma, the skin color and phototype the patient has, one must also consider prior treatments, expectations and adherence to therapy.


  1. Handog EB, Enriquez-Macarayo, MJ. Differential Diagnosis of Melasma in Brown Skin. In: Handog EB, En-riquez-Macarayo, MJ, eds. Melasma and Vitiligo in Brown Skin. Springer India 2017; 71-80.
  2. Handog EB, Macarayo MJE. How to Choose the Best Peeling for the Patient: Melasma. In: Tosti A, Grimes PE, De Padova MP, eds. Color Atlas of Chemical Peels 2nd ed. Springer-Verlag Berlin Heidelberg 2012: 123-40
  3. Moseley H, Cameron H, MacLeod T et al (2001) New sun- screens confer improved protection for photosen-sitive patients in the blue light region. Br J Dermatol 145:789–94
  4. Ni Z, Mu Y, Gulati O (2002) Treatment of melasma with Pycnogenol. Phytother Res 16:567–71
  5. Verallo-Rowell VM. Photoprotection in Brown Skin. In: Handog EB, Enriquez-Macarayo MJ, eds. Melasma and Vitiligo in Brown Skin. Springer India 2017: 337-50
  6. Briganti S, Camera E, Picardo M (2003) Chemical and instrumental approaches to treat hyperpigmentation. Pigment Cell Res 16(2):101–10
  7. Kim H, Choi HR, Kim DS, Park KC. Topical hypopigmenting agents for pigmentary disorders and their mech-anisms of action. Ann Dermatol 2012; 24(1): 1-6
  8. Espinal-Perez LE, Moncada B, Castanedo-Cazares JP. A double-blind randomized trial of 5% ascorbic acid vs. 4% hydroquinone in melasma. Int J Dermatol. 2004;43:604–7
  9. Monteiro RC, Kishore BN, Bhat RM, et al. A comparative study of the efficacy of 4% hydroquinone vs 0.75% kojic acid cream in the treatment of facial melasma. Indian J Dermatol. 2013;58:157
  10. Navarrete-Solís J, Castanedo-Cázares JP, Torres-Álvarez B, et al. A double-blind, randomized clinical trial of niacinamide 4% versus hydroquinone 4% in the treatment of melasma. Dermatol Res Pract 2011. 2011;379173
  11. Sarma N, Chakraborty S, Poojary SA et al. Evidence-based Review, Grade of Recommendation, and Suggest-ed Treatment Recommendations for Melasma. Indian Dermatol Online J 2017;8(6):406-42
  12. Chan R, Park KC, Lee MH, et al. A randomized controlled trial of the efficacy and safety of a fixed triple com-bination (fluocinolone acetonide 0.01%, hydroquinone 4%, tretinoin 0.05%) compared with hydroquinone 4% cream in Asian patients with moderate to severe melasma. Br J Dermatol. 2008;159:697–703
  13. Gold M, Rendon M, Dibernardo B, Bruce S, et al. Open label treatment of moderate or marked melasma with a 4% hydroquinone skin care system plus 0.05% tretinoin cream. J Clin Aesthet Dermatol. 2013;6:32–8
  14. Grimes P, Watson J, authors. Treating epidermal melasma with a 4% hydroquinone skin care system plus tretinoin cream 0.025%. Cutis. 2013;91:47–54
  15. Haddad AL, Matos LF, Brunstein F, et al. A clinical, prospective, randomized, double-blind trial comparing skin whitening complex with hydroquinone vs. placebo in the treatment of melasma. Int J Dermatol. 2003;42:153–6
  16. Ennes SBP, Paschoalick RC, Mota De Avelar Alchorne M. 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;11:173–79
  17. Ebanks JP, Wickett RR, Boissy RE. Mechanisms regulating skin pigmentation: the rise and fall 
of complex-ion and coloration. Int J Mol Sci. 2009;10(9):4066–87
  18. Dayal S, Sahu M, Dua R. Combination of glycolic acid peel and topical 20% azelaic cream in melasma pa-tients: efficacy and improvement in quality of life. J Cosmetic Dermatol 2017;16(1):35-42
  19. Rajaratnam R, Halpern J, Salim A, Emmett C. Interventions for melasma. Cochrane Database Syst Rev. 2010;CD003583
  20. Farshi S. Comparative study of therapeutic effects of 20% azelaic acid and hydroquinone 4% cream in the treatment of melasma. J Cosmet Dermatol. 2011;10(4):282–287
  21. Bansal C, Naik H, Kar HK, Chauhan A. A comparison of low-fluence 1064-nm Q-switched Nd:YAG laser with topical 20% azelaic acid cream and their combination in melasma in Indian patients. J Cutan Aesthet Surg. 2012;5:266–72
  22. Lim JT. Treatment of melasma using Kojic acid in a gel containing hydroquinone and glycolic acid. Derma-tol Surg. 1999;25:282–4.
  23. Deo KS, Dash KN, Sharma YK et al. Kojic acid vis-à-vis its combinations with hydroquinone and betame-thasone valerate in melasma: a randomized single blind comparative study of efficacy and safety. Indian J Dermatol 2013;58(4): 281-5.
  24. Sehgal V, Verma P, Srivstava G, et al. Melasma: treatment strategy. J Cosm 
Laser Ther. 2011;13:265–79
  25. Kimbrough-Green CK, Griffiths CE, Finkel LJ, et al. Topical retinoic acid for melasma in black patients. Arch Dermatol. 1994;130:727–33
  26. Leenutaphong V, Nettakul A, Rttanasuwon P. Topical isotretinoin for melasma in Thai patients: a vehicle-controlled clinical trial. J Med Assoc Thai. 1999;82:868– 74
  27. Dogra S, Kanwar AJ, Parasad D. Adapalene in the treatment of melasma: a preliminary report. J Dermatol. 2002;29:539–40
  28. Kameyama K, Sakai C, Kondoh C, et al. Inhibitory effect of magnesium L-ascorbyl-2-phosphate (VC-PMG) on melanogenesis in vitro and in vivo. 
J Am Acad Dermatol. 1996;34(1):29–33
  29. Huh CH, Seo KI, Park JY, et al. A randomized, double-blind, placebo-controlled trial of vitamin C iontophore-sis in melasma. Dermatology. 2003;206:316–20
  30. Huh CH, Seo KI, Park JY, et al. A double blind randomized trial of 5% 
ascorbic acid vs 4% hydroquinone in melasma. Int J Dermatol. 2004;43(8):604–7
  31. Soliman MM, Ramadan SA, Bassiouny DA, Abdelmalek M. Combined trichloroacetic acid peel and topical ascorbic acid versus trichloroacetic acid peel alone in the treatment of melasma: A comparative study. J Cosmet Dermatol. 2007;6:89–94
  32. Burke KE. Interaction of vitamins C and E as better cosmeceuticals. Dermatol Ther. 2007; 20: 314–21
  33. Lin J, Selim A, Shea C, et al. UV photoprotection by combination topical antioxidants vitamin C and E. J Am Acad Dermatol. 2003;48:866–74
  34. Ibrahim ZA, Gheida SF, El Maghraby GM, Farag ZE. Evaluation of the efficacy and safety of combinations of hydroquinone, glycolic acid, and hyaluronic acid in the treatment of melasma. J Cosmet Dermatol. 2015;14:113–23
  35. Piamphongsant T. Treatment of melasma: a review 1271 with personal experience. Int J Dermatol 1998;37:897–903
  36. Handog EB, Vitug RL, Masa EJ et al. A prospective, randomized, double-blind, placebo controlled trial on the efficacy of 8% indomethacin cream in the treatment of melasma in Filipino women. RITM, Philippines 2005 unpublished
  37. Tirado-Sanchez A, Santamaria Roman A, Ponce Olivera RM. Efficacy of dioic acid compared with hydroqui-none in treatment of melasma. Int J Dermatol. 2009;48:893–5
  38. Banihashemi MD, Zabolinejad N, Jaafari M, et al. Comparison of therapeutic effects of liposomal tranexamic acid and conventional hydroquinone on melasma. J Cosm Dermatol. 2015;14:1–4
  39. Ebrahimi B, Naeini F. Topical tranexamic acid as a promising treatment for melasma. J Res Med Sci. 2014;19(8):753–7
  40. Zhong SM, Sun N, Liu HX, et al. Reduction of facial pigmentation of melasma by topical lignin peroxidase: A novel fast-acting skin-lightening agent. Exp Ther Med. 2015;9:341–4
  41. Mauricio T, Karmon Y, Khaiat A. A randomized and placebo-controlled study to compare the skin-lightening efficacy and safety of lignin peroxidase cream vs. 2% hydroquinone cream. J Cosmet Dermatol. 2011;10:253–9.
  42. Draelos ZD. A split-face evaluation of a novel pigment-lightening agent compared with no treatment and hydroquinone. J Am Acad Dermatol. 2015;72:105– 7
  43. Adalatkhah H, Sadeghi-Bazargani H. The first clinical experience on efficacy of topical flutamide on melasma compared with topical hydroquinone: A randomized clinical trial. Drug Des Devel Ther. 2015;9:4219–25
  44. Hantash B, Jimenez F. A split-face, double-blind, randomized placebo-controlled pilot evaluation of a novel oligopeptide for the treatment of recalcitrant melasma. J Drugs Dermatol. 2009;8:732–5
  45. Macarayo MJE. Melasma. In: Abad-Casintahan MF, Macarayo MJE, Gabriel MTG, et al, eds. Clinician’s Hand-book in Dermatology. SRFPI 2016;71-75
  46. Gupta AK, Nouri K, Taylor S. The treatment of melasma: a review of clinical trials. J Am Acad Dermatol. 2006;55(6):1048–65
  47. Sheth V, Pandya A. Melasma: a comprehensive update Part II. J Am Acad Dermatol. 2011;65(4):699–714
  48. 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;37:224–33
  49. Taylor SC, Torok H, Jones T, et al. Efficacy and safety of a new triple-combination agent for the treatment of facial melasma. Cutis. 2003;72:67–72
  50. Grimes P, Kelly AP, Torok H, Willis I. Community-based trial of a triple-combination agent for the treatment of facial melisma. Cutis. 2006;77:177–84
  51. Cestari TF, Hexsel D, Viegas ML, et al. Validation of a melasma quality of life questionnaire for Brazilian Por-tuguese language: The MelasQoL-BP study and improvement of QoL of melasma patients after triple com-bination therapy. Br J Dermatol. 2007;1561:13–20
  52. Shankar K, Godse K, Aurangabadkar S, et al. Evidence-based treatment for melasma: expert opinion and a review. Dermatol Ther 2014;4:165-86
  53. Handog EB, Enriquez-Macarayo MJ, Hipolito R. Botanicals in Melasma. In Handog, EB, Enriquez-Macarayo MJ, eds. Melasma and Vitiligo in Brown Skin. Springer India 2017. 103-22
  54. Choi S, Park YI, Lee SK, et al. Aloesin inhibits hyperpigmentation induced by UV radiation. Clin Exp Dermatol. 2002;27:513–5
  55. Draelos ZD. Skin lightening preparations and the hydroquinone controversy. Dermatol Ther. 2007;20(5):308–13
  56. Boissy RE, Visscher M, DeLong MA. DeoxyArbutin: a novel reversible tyrosinase inhibitor with effective in vivo skin lightening potency. Exp Dermatol. 2005;14:601–8
  57. Polnikorn N. Treatment of refractory melasma with the MedLite C6 Q-switched Nd:YAG laser and alpha ar-butin: A prospective study. J Cosmet Laser Ther. 2010;12:126–3
  58. Ertam I, Mutlu B, Unal I, et al. Efficiency of ellagic acid and arbutin in melasma: a randomized, prospective, open-label study. J Dermatol. 2008;35(9):570-4
  59. Zubair S, Mujtaba G. Comparison of efficacy of topical 2% liquiritin, topical 4% liquiritin and topical 4% hy-droquinone in the management of melasma. JPAD. 2009;19:158–63
  60. Holloway VL. Ethnic cosmetic products. Dermatol Clin.2003;21:743–49
  61. Alvin G, Catambay N, Vergara A, Jamora MJ. A comparative study of the safety and efficacy of 75% mulberry (Morus alba) extract oil versus placebo as a topical treatment for melasma: a randomized, single-blind, placebo-controlled trial. J Drugs Dermatol. 2011;10(9):1025-31
  62. Tadokoro T, Bonté F, Archambault JC, et al. Whitening efficacy of plant extracts including orchid extracts on Japanese female skin with melasma and lentigo senilis. J Dermatol. 2010;37(6):522–30
  63. Mendoza CG, Singzon IA, Handog EB. A randomized, double-blind, placebo-controlled clinical trial on the ef-ficacy and safety of 3% Rumex occidentalis cream versus 4% hydroquinone cream in the treatment of me-lasma among Filipinos. Int J Dermatol. 2014;53:1412–6
  64. Altaei T. The treatment of melasma by silymarin cream. BMC Dermatol. 2012;12:18
  65. Pineda RT, Chan G, Gabriel T. A randomized double 1275 blind placebo controlled comparative study on the safety and efficacy of 0.25% tetrahydrocurcumin (Turmeric) cream as depigmenting agent against 4% hy-droquinone cream. RITM, Philippines, 2006 unpublished
  66. Na JI, Choi SY, Yang SH, et al. Effect of tranexamic acid on melasma: A clinical trial with histological evalua-tion. J Eur Acad Dermatol Venereol. 2013;27:1035–9
  67. Podder I, Sarkar R. Systemic therapy for melasma: exploring newer options- a comprehensive review. Pig-ment Int 2017;4:78-84
  68. Lee HC, Thng TG, Goh CL. Oral tranexamic acid in the treatment of melasma: A retrospective analysis. J Am Acad Dermatol. 2016;75:385–92
  69. Shin JU, Park J, Oh SH, et al. 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 random-ized, prospective trial. Dermatol Surg 2013; 39: 435–42
  70. Padhi T, Pradhan S. Oral tranexamic acid with fluocinolone- based triple combination cream versus fluocino-lone-based triple combination cream alone in melasma: an open labeled randomized comparative trial. In-dian J Dermatol 2015; 60(5): 520.
  71. Karn D, Kc S, Amatya A, et al. Oral tranexamic acid for the treatment of melasma. Kathmandu Univ Med J 2012; 10: 40–3
  72. Tse TW, Hui E. Tranexamic acid: An important adjuvant in the treatment of melasma. J Cosmetic Dermatol. 2013;12:57–66
  73. Li Y, Sun Q, He Z, et al. Treatment of melasma with oral administration of compound tranexamic acid: A pre-liminary clinical trial. J Eur Acad Dermatol Venereol. 2014;28:393–4
  74. Wu S, Shi H, Wu H, et al. Treatment of melasma with oral administration of tranexamic acid. Aesthetic Plas-tic Surg. 2012;36:964–70
  75. Cho HH, Choi M, Cho S, Lee JH. Role of oral tranexamic acid in melasma patients treated with IPL and low fluence QS Nd:YAG laser. J Dermatol Treat. 2013;24:292–6
  76. Aamir S, Naseem R. Oral tranexamic acid in treatment of melasma in Pakistani population: A pilot study. J Pak Assoc Dermatol 2016;24: 198-203
  77. Tan AWM, Sen P, Chua SH, Goh BK. Oral tranexamic acid lightens refractory melasma. Australas J Dermatol. 2017;58(3):e105-8.
  78. Middelkamp-Hup MA, Pathak MA, Parrado C, et al. Orally administered Polypodium leucotomos extract decreases psoralen-UVA-induced phototoxicity, pigmentation, and damage of human skin. J Am Acad Der-matol. 2004;50(1):41–9
  79. Martin LK, Caperton C, Woolery-Lloyd H, et al. A randomized double-blind placebo controlled study evalu-ating the effectiveness and tolerability of oral Polypodium leucotomos in patients with melasma. American Academy of Dermatology Annual Meeting. San Diego: CA; Mar 16-20, 2012.
  80. Nestor MS, Berman B, Swenson N. Safety and efficacy of oral Polypodium leucotomos extract in healthy adult subjects. J Clin Aesthet Dermatol. 2015;8(2):19–23
  81. Zhou LL, Baibergenova A. Melasma: Systematic review of the systemic treatments. Int J Dermatol 2017;58:902-8
  82. Choudhry SZ, Bhatia N, Ceilley R, et al. Role of oral Polypodium leucotomos extract in dermatologic diseas-es: a review of the literature. J Drugs Dermatol. 2014;13(2):148–53
  83. Schalka S, Vitale-Villarejo MA, Monteiro-Agelune C, Pinto-Bombarda PC. The benefits of using a compound containing Polypodium leucotomos extract for reducing erythema and pigmentation resulting from ultravi-olet radiation. Surg Cosmet Dermatol. 2014;6(4):344–8
  84. Winkelmann RR, Del Rosso J, Rigel DS. Polypodium leucotomos extract: a status report
  85. on clinical efficacy and safety. J Drugs Dermatol. 2015;14(3):254–61
  86. Ahmed AM, Lopez I, Perese F, et al. A randomized, double- blinded, placebocontrolled trial of oral Polypo-dium leucotomos extract as an adjunct to sunscreen in the treatment of melasma. JAMA Dermatol 2013; 149: 981–3
  87. Goh CL, Chuah SY, Tien S, Delgado-Rubin A. Double-blind, placebo-controlled trial to evaluate the effective-ness of Polypodium leucotomos extract in the treatment of melasma in Asian skin: a pilot study. J Clin Aesth Dermatol 2018;11(3):14-19
  88. Sarkar R, Chugh S, Garg VK. Newer and upcoming therapies for melasma. Indian J Dermatol Venereol Leprol 2012;78:417–28 Ni Z,
  89. Mu Y, Gulati O. Treatment of melasma with Pycnogenol®. Phytother Res 2002;16:567-71.
  90. Handog EB, Galang DA, de Leon-Godinez MA, Chan GP. A randomized, doubleblind, placebo-controlled trial of oral procyanidin with vitamins A, C, E for melasma among Filipino women. Int J Derma-tol. 2009;48(8):896–901.
  91. Sonthalia S, Daulatabad D, Sarkar R. Glutathione as a skin whitening agent: Facts, myths, evidence and con-troversies. Indian J Dermatol Venereol Leprol 2016;82(3)262-72
  92. Seçkin HY, Kalkan G, Baş Y, et al. Oxidative stress status in patients with melasma. Cutan Ocul Toxicol 2014;33:212-7
  93. Villarama CD, Maibach HI. Glutathione as a depigmenting agent: An overview. Int J Cosmet Sci 2005;27:147-53
  94. Arjinpathana N, Asawanonda P. Glutathione as an oral whitening agent: A randomized, double-blind, place-bo-controlled study. J Dermatol Treat 2012;23:97102
  95. Handog EB, Datuin MS, Singzon IA. An open-label, single-arm trial of the safety and efficacy of a novel prep-aration of glutathione as a skin- lightening agent in Filipino women. Int J Dermatol 2016;55:153-7
  96. Stahl W, Sies H. Photoprotection by dietary carotenoids: concept, mechanisms, evidence and future devel-opment. Mol Nutr Food Res 2012; 56: 287–95
  97. Teo WL, Gan E, Jinghan A, et al. Double blind placebo controlled trial to evaluate of the effectiveness of a di-etary supplement rich in carotenoids as adjunct to topical lightening cream for the treatment of melasma: a pilot study. J Pigment Disord 2015; 2: 164
  98. Hamadi SA, Mohammed MM, Aljaf AN, et al. The role of topical and oral melatonin in management of me-lasma patients. J Assn Arab Univ Basic Appl Sci 2010; 1: 30–42
  99. 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;26:611–8

REquesting Permission

Melasma in brown skin: part 2