Current Methods of Melasma Treatment: History
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Subjects: Chemistry, Applied
Contributor:
Agata Wawrzyńczak

Melasma is a fairly common condition that is the result of hyperpigmentation caused by increased melanin secretion. In the course of melasma, certain areas of the skin become darker than the rest of the epidermis. Although the pathogenesis remains incompletely clarified, several contributing factors have been identified, namely exposure to ultraviolet and visible light, family predisposition, pregnancy, and the use of exogenous hormones. Since current beauty standards associate healthy skin with its flawless and uniform color, people strive to eliminate any unaesthetic discoloration.

  • hyperpigmentation
  • melasma
  • treatment
  • chemical peels
  • topical therapy
  • lasers

1. Introduction

Current beauty canons in some cultures particularly value light skin color since it is associated with health, beauty, and prosperity, while darker skin tones may be correlated with a lower social class [1]. Sometimes the lightening of skin pigmentation has a medical justification—this is especially the case with dermatological conditions and dysfunctions based on excessive melanin synthesis. Skin afflictions such as melasma, freckles, birthmarks, senile/solar lentigo, pigmented acne scars, post-inflammatory hyperpigmentation, and lentigines are among the most commonly diagnosed skin conditions based on the process of hyperpigmentation. They are caused by a disruption of the melanogenesis process that occurs in human skin. During this process, melanin is produced, the light-absorbing pigment that determines the coloration of human skin and hair. Melanin is produced in melanocytes, which are specialized cells located mostly in the epidermal-dermal junction. From melanocytes, melanin is distributed by melanosomes (specialized lysosome-lineage organelles) and through the elongated dendrites to neighboring keratinocytes [2].
The precursor in melanogenesis is L-tyrosine, the amino acid that, through a series of enzymatic reactions, including the hydroxylation of L-tyrosine to L-3,4,-dihydroxyphenylalanine (L-DOPA) and the oxidation of L-DOPA to dopachinone, is eventually converted to brown-black eumelanin or yellow-red pheomelanin. One of the enzymes involved in the conversion of L-tyrosine to melanin is tyrosinase. Inhibiting its activity is the main target of many topically applied whitening preparations. Important regulators of melanogenesis are also melanotropin, adrenocorticotropic hormone (ACTH), and some cytokines. The processes leading to the onset of pigmentary disorders are very complex and have still not been fully clarified. Three mechanisms are considered the main triggers for the lesions named hypermelanosis and include: (1) an increase in the number of melanocytes; (2) a disturbance in the melanin synthesis process; and (3) a disturbance in the growth, transport, and transfer of melanosomes to keratinocytes. Uncontrolled melanocyte proliferation is a feature of melanomas, pigmented nevi, and lentigines, among others. In the cases of melasma, post-inflammatory hyperpigmentation, and freckles, it is currently accepted that the predominant pathological process is excessive melanin production. Hypermelanosis can be caused by several genetic and environmental factors, the most important of which are inflammation, hormonal factors, drugs, exposure to UV radiation, visible light and heat, and mechanical trauma [3].

2. Treatment Methods

In general, hyperpigmentation can noticeably affect the quality of life, although it cannot be considered a detrimental or lethal disorder. There are several options for hyperpigmentation treatment available nowadays. They include mainly topical routes in the form of creams, gels, or ointments. However, quite often they are accompanied by various side effects such as drying, irritation, peeling, or hypopigmentation of the skin. Additionally, even prolonged treatment, which can last up to several years, may produce poor results and low patient satisfaction [3].
To avoid this situation, there is a drive to develop methods based on so-called combination therapies, which use peels and light- and laser-based treatments in addition to topical therapy. This is particularly advisable for dermal melasma, which is less likely to respond to topical therapy. Triple combination cream (TCC) is one of the primary topical treatments for melasma. In general, it consists of hydroquinone, a retinoid, and a fluorinated corticosteroid and is widely regarded as a safe and effective treatment for melasma. There are several options for the composition of TCC, such as 4% hydroquinone, 0.05% tretinoin, and 0.01% fluocinolone acetonide, with the so-called Kligman–Willis formula (5% hydroquinone, 0.1% tretinoin, and 0.1% dexamethasone) that has been used for hyperpigmentation treatment for more than 30 years [4][5].
Chemical peels are commonly used for several skin disorders, even though they may cause skin irritation and post-inflammatory hyperpigmentation. Glycolic acid seems to be the most broadly used for chemical peeling, whereas salicylic acid represents a safer choice for patients with sensitive skin and dark phenotypes [6]. Additionally, Jessner’s solution (an alcohol solution containing 14% resorcinol, salicylic acid, and lactic acid) could also be effective [7]. Looking for other options in the treatment of melasma, a study was conducted comparing the effectiveness of chemical peels based on 70% glycolic acid and 1% tretinoin, which showed that the efficiency of peels based on tretinoin was similar to those based on glycolic acid. Furthermore, the side effects in both groups of patients were rather negligible [8]. Quite frequently, attempts are also made to combine chemical peels with topical therapy. Chaudhary et al. described a study showing that the combination of topical application of 2% hydroquinone, 1% hydrocortisone, and 0.05% tretinoin with sequential use of glycolic acid-based peeling significantly improves the therapeutic efficiency in the treatment of melasma in Indian patients [9]. Hagag et al. conducted a similar study in which the efficiency of topically delivered nano-vitamin C enhanced with iontophoresis was compared with that of a chemical peel containing 20% trichloroacetic acid. The authors concluded that nanosomal vitamin C supported by iontophoresis may be an easy, safe, effective, painless, and non-invasive alternative in the treatment of melasma since its effectiveness was found to be as effective as trichloroacetic acid peelings [10].
In recent years, it has been well recognized that intense pulsed light, fractional and pigment lasers, or radiofrequency may be successfully used in melasma treatment [11][12][13][14]. However, it has also been documented that therapies based on laser and light sources can lead to adverse effects, namely paradoxical hyperpigmentation resulting from direct damage to the skin, especially for patients with high skin phototypes. Hence, it has also been suggested to limit this therapeutic approach to patients with disorders resistant to topical treatment [15]. It should also be taken into consideration that non-ablative fractional lasers are the only laser-based systems approved by the FDA (since 2003), producing well-documented results in the treatment of melasma [16].
Intense pulsed light uses a flash lamp light source to emit noncoherent light with wavelengths between 515 nm and 1200 nm. The application of filters allows the targeting of a particular chromophore, namely melanin, in the case of melasma [17]. Q-switched lasers generate high-intensity laser beams with very short pulse intervals. These types of lasers target melanin and are available in multiple wavelengths, with the most commonly used being 532 nm or 1064 nm from a neodymium-doped yttrium aluminum garnet (QS-Nd:YAG) laser [18]. Recently, comparative studies were also performed on 1064 nm QS-Nd:YAG laser and Jessner’s peeling, proving that these therapies are equally effective in the treatment of melasma [19]. Moreover, the skin-lightening effect achieved by laser therapy can be further sustained by using an appropriate combination therapy based on classical whitening substances, namely serums containing vitamin C, ferulic acid, and phloretin [20]. Pulsed-dye lasers target hemoglobin, which may be considered the vascular component of melasma [21]. In contrast, fractional lasers act by creating thousands of microthermal treatment zones with each pulse. These microthermal damages are able to penetrate into the deeper layers of the skin, influencing dermal melanin. The most important advantage of fractional laser therapy is that it does not create open wounds, allowing for faster recovery and reducing the risk of scarring or pigmentary alterations [22]. Elmorsy et al. showed that low-power fractional laser can serve as a safe and effective melasma treatment in patients with different skin types, especially Fitzpatrick skin type III. Additionally, its combination with Jessner’s peel gives faster improvement and higher patient satisfaction compared to separate treatments with laser or Jessner’s solution [23].
In addition to the laser-based equipment, devices using radiofrequency may also be used in the treatment of melasma. For example, a monopolar radiofrequency was successfully applied to facilitate the drug delivery of a phytocomplex of 1% kojic acid [24].
In the context of treating hyperpigmentation-based conditions, one of the most important aspects is preventive action, which in this case is mainly based on photoprotective measures. A natural factor that protects against the harmful effects of sunlight is eumelanin, one of the natural pigments of the skin, which is associated with dark skin pigmentation. The light phototype skin preferentially contains pheomelanin; the amount of eumelanin is not sufficient to provide full photoprotection, and therefore the application of complementary sunscreens is essential [2]. Today, many cosmetic UV filters with a wide range of photoprotection are available. In addition, much research is currently being conducted on new sunscreens and novel methods to incorporate them into cosmetic formulations and extend their durability after application to the skin [25]. It was found that the best solution for patients with hyperpigmentation-based skin conditions such as melasma is the use of broad spectrum sunscreens along with protection against visible light [26].

This entry is adapted from the peer-reviewed paper 10.3390/cosmetics10030086

References

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  2. Solano, F. Photoprotection and Skin Pigmentation: Melanin-Related Molecules and Some Other New Agents Obtained from Natural Sources. Molecules 2020, 25, 1537.
  3. Nautiyal, A.; Wairkar, S. Management of hyperpigmentation: Current treatments and emerging therapies. Pigment. Cell Melanoma Res. 2021, 34, 1000–1014.
  4. Gong, Z.; Lai, W.; Zhao, G.; Wang, X.; Zheng, M.; Li, L.; Yang, Q.; Dang, Y.; Liu, L.; Zou, Y. 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.
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  7. Dorgham, N.A.; Dorgham, D.A.; Hegazy, R.A.; Sharobim, A.K. Efficacy and Tolerability of Chemical Peeling as A Single Agent for Melasma in Dark-Skinned Patients: A Systematic Review and Meta-analysis of Comparative Trials. J. Cosmet. Dermatol. 2020, 19, 2812–2819.
  8. Faghihi, G.; Shahingohar, A.; Siadat, A.H. Comparison between 1% tretinoin peeling versus 70% glycolic acid peeling in the treatment of female patients with melasma. J. Drugs Dermatol. 2011, 10, 1439–1442.
  9. Chaudhary, S.; Dayal, S. Efficacy of combination of glycolic acid peeling with topical regimen in treatment of melasma. J. Drugs Dermatol. 2013, 12, 1149–1153.
  10. Hagag Sara, M.M.; Abd Allah, S.H. The effect of topical nano vitamin-C iontophoresis versus the effect of trichloroacetic acid 20% peel in treatment of melasma. Menoufia Med. J. 2022, 35, 489–495.
  11. Trivedi, M.K.; Yang, F.C.; Cho, B.K. A review of laser and light therapy in melasma. Int. J. Women’s Dermatol. 2017, 3, 11–20.
  12. Shah, S.D.; Aurangabadkar, S.J. Laser Toning in Melasma. J. Cutan. Aesthetic Surg. 2019, 12, 76–84.
  13. Mehrabi, J.N.; Bar-Ilan, E.; Wasim, S.; Koren, A.; Zusmanovitch, L.; Salameh, F.; Nelkenbaum, G.I.; Horovitz, T.; Zur, E.; Lim, T.S.; et al. A review of combined treatments for melasma involving energy-based devices and proposed pathogenesis-oriented combinations. J. Cosmet. Dermatol. 2021, 21, 461–472.
  14. Feng, J.; Shen, S.; Song, X.; Xiang, W. Efficacy and safety of picosecond laser for the treatment of melasma: A systematic review and meta-analysis. Lasers Med. Sci. 2023, 38, 84.
  15. McKesey, J.; Tovar-Garza, A.; Pandya, A.G. Melasma Treatment: An Evidence-Based Review. Am. J. Clin. Dermatol. 2020, 21, 173–225.
  16. Küçük, Ö.S. Current treatment approaches for melasma. Bezmialem Sci. 2018, 6, 54–62.
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  18. Kaminaka, C.; Furukawa, F.; Yamamoto, Y. The clinical and histological effect of a low-fluence Q-Switched 1064-nm neodymium:Yttrium-aluminum-garnet laser for the treatment of melasma and solar lentigines in asians prospective, randomized, and split-face comparative study. Dermatol. Surg. 2017, 43, 1120–1133.
  19. Sagduyu, I.E.; Marakli, O.; Oraloglu, G.; Okut, E.B.; Unal, I. Comparison of 1064 nm Q-switched Nd:YAG laser and Jessner peeling in melasma treatment. Dermatol. Ther. 2022, 35, e15970.
  20. Campos, V. 28379 Case report of effect of a topical antioxidant serum containing vitamin C, ferulic acid, and phloretin after Q-switched laser for treatment of melasma. J. Am. Acad. Dermatol. 2021, 85, AB186.
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