Unmasking Melasma: Confronting the Treatment Challenges
Abstract
:1. Introduction
2. Topical Therapy
2.1. Photoprotection
2.2. Hydroquinone and Triple-Combination Therapy
2.3. Azelaic Acid
2.4. Retinoids
2.5. Corticosteroids
2.6. L-Ascorbic Acid
2.7. Kojic Acid
2.8. Tranexamic Acid
2.9. Niacinamide
2.10. Arbutin
3. Oral Therapy
3.1. Oral Tranexamic Acid
3.2. Glutathione
4. Procedural Therapy
4.1. Platelet-Rich Plasma
4.2. Intralesional Tranexamic Acid
4.3. Chemical Peels
4.4. Laser and Light-Based Therapy
5. Novel Strategies in Melasma Treatment
6. Maintenance Therapy
7. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Arrowitz, C.; Schoelermann, A.M.; Mann, T.; Jiang, L.I.; Weber, T.; Kolbe, L. Effective Tyrosinase Inhibition by Thiamidol Results in Significant Improvement of Mild to Moderate Melasma. J. Investig. Dermatol. 2019, 139, 1691–1698.e6. [Google Scholar] [CrossRef]
- Majid, I.; Aleem, S. Melasma: Update on Epidemiology, Clinical Presentation, Assessment, and Scoring. J. Skin. Stem Cell. 2022, 8, e120283. [Google Scholar] [CrossRef]
- Liu, W.; Chen, Q.; Xia, Y. New Mechanistic Insights of Melasma. Clin. Cosmet. Investig. Dermatol. 2023, 16, 429–442. [Google Scholar] [CrossRef]
- Espósito, A.C.C.; Cassiano, D.P.; da Silva, C.N.; Lima, P.B.; Dias, J.A.F.; Hassun, K.; Bagatin, E.; Miot, L.D.B.; Miot, H.A. Update on Melasma—Part I: Pathogenesis. Dermatol. Ther. 2022, 12, 1967–1988. [Google Scholar] [CrossRef] [PubMed]
- Rajanala, S.; Maymone, M.B.d.C.; Vashi, N.A. Melasma Pathogenesis: A Review of the Latest Research, Pathological Findings, and Investigational Therapies. Dermatol. Online J. 2019, 25, 10. [Google Scholar] [CrossRef]
- Artzi, O.; Horovitz, T.; Bar-Ilan, E.; Shehadeh, W.; Koren, A.; Zusmanovitch, L.; Mehrabi, J.N.; Salameh, F.; Isman Nelkenbaum, G.; Zur, E.; et al. The Pathogenesis of Melasma and Implications for Treatment. J. Cosmet. Dermatol. 2021, 20, 3432–3445. [Google Scholar] [CrossRef]
- Böhm, M. Disorders of Melanin Pigmentation. In Braun-Falco’s Dermatology, 4th ed.; Plewig, G., French, L., Ruzicka, T., Kaufmann, R., Hertl, M., Eds.; Springer: Berlin/Heidelberg, Germany, 2022; pp. 1245–1279. [Google Scholar] [CrossRef]
- Türkmen, H.; Yörük, S. Risk Factors of Striae Gravidarum and Chloasma Melasma and Their Effects on Quality of Life. J. Cosmet. Dermatol. 2023, 22, 603–612. [Google Scholar] [CrossRef]
- Filoni, A.; Mariano, M.; Cameli, N. Melasma: How Hormones Can Modulate Skin Pigmentation. J. Cosmet. Dermatol. 2019, 18, 458–463. [Google Scholar] [CrossRef] [PubMed]
- Ogbechie-Godec, O.A.; Elbuluk, N. Melasma: An Up-to-Date Comprehensive Review. Dermatol. Ther. 2017, 7, 305–318. [Google Scholar] [CrossRef]
- Piętowska, Z.; Nowicka, D.; Szepietowski, J.C. Understanding Melasma-How Can Pharmacology and Cosmetology Procedures and Prevention Help to Achieve Optimal Treatment Results? A Narrative Review. Int. J. Environ. Res. Pub. Health 2022, 19, 12084. [Google Scholar] [CrossRef]
- Zhu, Y.; Zeng, X.; Ying, J.; Cai, Y.; Qiu, Y.; Xiang, W. Evaluating the quality of life among melasma patients using the MELASQoL scale: A systematic review and meta-analysis. PLoS ONE 2022, 17, e0262833. [Google Scholar] [CrossRef]
- Sheth, V.M.; Pandya, A.G. Melasma: A comprehensive update: Part II. J. Am. Acad. Dermatol. 2011, 65, 699–714. [Google Scholar] [CrossRef] [PubMed]
- Heidemeyer, K.; Cazzaniga, S.; Feldmeyer, L.; Imstepf, V.; Adatto, M.; Lehmann, M.; Rammlmair, A.; Pelloni, L.; Seyed Jafari, S.M.; Bossart, S. Skin hyperpigmentation index in melasma: A complementary method to classic scoring systems. J. Cosmet. Dermatol. 2023, 22, 3405–3412. [Google Scholar] [CrossRef] [PubMed]
- Cassiano, D.P.; Espósito, A.C.C.; Da Silva, C.N.; Lima, P.B.; Dias, J.A.F.; Hassun, K.; Miot, L.D.B.; Miot, H.A.; Bagatin, E. Update on Melasma—Part II: Treatment. Dermatol. Ther. 2022, 12, 1989–2012. [Google Scholar] [CrossRef]
- Jiryis, B.; Toledano, O.; Avitan-Hersh, E.; Khamaysi, Z. Management of Melasma: Laser and Other Therapies—Review Study. J. Clin. Med. 2024, 13, 1468. [Google Scholar] [CrossRef]
- Morgado-Carrasco, D.; Piquero-Casals, J.; Granger, C.; Trullàs, C.; Passeron, T. Melasma: The need for tailored photoprotection to improve clinical outcomes. Photodermatol. Photoimmunol. Photomed. 2022, 38, 515–521. [Google Scholar] [CrossRef] [PubMed]
- Desai, S.R.; Alexis, A.F.; Elbuluk, N.; Grimes, P.E.; Weiss, J.; Hamzavi, I.H.; Taylor, S.C. Best practices in the treatment of melasma with a focus on patients with skin of color. J. Am. Acad. Dermatol. 2024, 90, 269–279. [Google Scholar] [CrossRef] [PubMed]
- Shetty, N.P.; Taylor, S.C.; Lim, H.W. Personalized photoprotection: Commentary on “Adjusting best practices in the treatment of melasma with a focus on patients with skin of color”. J. Am. Acad. Dermatol. 2023, 89, 635–636. [Google Scholar] [CrossRef]
- Schwartz, C.; Jan, A.; Zito, P.M. Hydroquinone. In StatPearls; StatPearls Publishing: Treasure Island, FL, USA, 2024. Available online: https://www.ncbi.nlm.nih.gov/books/NBK539693/ (accessed on 28 May 2024).
- Jimbow, K.; Obata, H.; Pathak, M.A.; Fitzpatrick, T.B. Mechanism of Depigmentation by Hydroquinone. J. Investig. Dermatol. 1974, 62, 436–449. [Google Scholar] [CrossRef] [PubMed]
- Chan, R.; Park, K.C.; Lee, M.H.; Lee, E.-S.; Chang, S.E.; Leow, Y.H.; Tay, Y.-K.; Legarda-Montinola, F.; Tsai, R.-Y.; Tsai, T.-H.; et al. A Randomized Controlled Trial of the Efficacy and Safety of a Fixed Triple Combination (Fluocinolone Acetonide 001, Hydroquinone 4, Tretinoin 005) Compared with Hydroquinone 4 Cream in Asian Patients with Moderate to Severe Melasma. Br. J. Dermatol. 2008, 159, 697–703. [Google Scholar] [CrossRef]
- Austin, E.; Nguyen, J.K.; Jagdeo, J. Topical Treatments for Melasma: A Systematic Review of Randomized Controlled Trials. J. Drugs Dermatol. 2019, 18, S1545961619P1156X. [Google Scholar]
- González-Molina, V.; Martí-Pineda, A.; González, N. Topical Treatments for Melasma and Their Mechanism of Action. J. Clin. Aesthet. Dermatol. 2022, 15, 19–28. [Google Scholar] [PubMed]
- Lazar, M.; De La Garza, H.; Vashi, N.A. Exogenous Ochronosis: Characterizing a Rare Disorder in Skin of Color. J. Clin. Med. 2023, 12, 4341. [Google Scholar] [CrossRef]
- Sauer, N.; Oślizło, M.; Brzostek, M.; Wolska, J.; Lubaszka, K.; Karłowicz-Bodalska, K. The Multiple Uses of Azelaic Acid in Dermatology: Mechanism of Action, Preparations, and Potential Therapeutic Applications. Postepy. Dermatol. Alergol. 2023, 40, 716–724. [Google Scholar] [CrossRef]
- Searle, T.; Ali, F.R.; Al-Niaimi, F. The Versatility of Azelaic Acid in Dermatology. J. Dermatol. Treat. 2022, 33, 722–732. [Google Scholar] [CrossRef]
- Akl, E.M. Liposomal Azelaic Acid 20% Cream vs Hydroquinone 4% Cream as Adjuvant to Oral Tranexamic Acid in Melasma: A Comparative Study. J. Dermatol. Treat. 2022, 33, 2008–2013. [Google Scholar] [CrossRef]
- Tehrani, S.; Tehrani, S.; Esmaili-Azad, M.; Vaezi, M.; Saljoughi, N. Efficacy and Safety of Azelaic Acid 20% plus Hydroquinone 5% in the Management of Melasma. Iran. J. Dermatol. 2012, 2012, 11–14. [Google Scholar]
- Albzea, W.; AlRashidi, R.; Alkandari, D.; Sadan, M.; Alkandari, A.; Alkanderi, J.J.; AlHajri, M.T.; Almutairi, S.N.; Alenzi, A.; Alanazi, S.; et al. Azelaic Acid Versus Hydroquinone for Managing Patients with Melasma: Systematic Review and Meta-Analysis of Randomized Controlled Trials. Cureus 2023, 15, e41796. [Google Scholar] [CrossRef] [PubMed]
- Ortonne, J.-P. Retinoid Therapy of Pigmentary Disorders. Dermatol. Ther. 2006, 19, 280–288. [Google Scholar] [CrossRef]
- Griffiths, C.E.M.; Finkel, L.J.; Ditre, C.M.; Hamilton, T.A.; Ellis, C.N.; Voorhees, J.J. Topical Tretinoin (Retinoic Acid) Improves Melasma. A Vehicle-Controlled, Clinical Trial. Br. J. Dermatol. 1993, 129, 415–421. [Google Scholar] [CrossRef] [PubMed]
- Kimbrough-Green, C.K.; Griffiths, C.E.; Finkel, L.J.; Hamilton, T.A.; Bulengo-Ransby, S.M.; Ellis, C.N.; Voorhees, J.J. Topical Retinoic Acid (Tretinoin) for Melasma in Black Patients. A Vehicle-Controlled Clinical Trial. Arch. Dermatol. 1994, 130, 727–733. [Google Scholar] [CrossRef] [PubMed]
- Truchuelo, M.T.; Jiménez, N.; Jaén, P. Assessment of the Efficacy and Tolerance of a New Combination of Retinoids and Depigmenting Agents in the Treatment of Melasma. J. Cosmet. Dermatol. 2014, 13, 261–268. [Google Scholar] [CrossRef] [PubMed]
- Pathak, M.A.; Fitzpatrick, T.B.; Kraus, E.W. Usefulness of Retinoic Acid in the Treatment of Melasma. J. Am. Acad. Dermatol. 1986, 15, 894–899. [Google Scholar] [CrossRef]
- Menter, A. Rationale for the Use of Topical Corticosteroids in Melasma. J. Drugs Dermatol. 2004, 3, 169–174. [Google Scholar]
- Gupta, A.K.; Gover, M.D.; Nouri, K.; Taylor, S. The Treatment of Melasma: A Review of Clinical Trials. J. Am. Acad. Dermatol. 2006, 55, 1048–1065. [Google Scholar] [CrossRef] [PubMed]
- Mahajan, V.K.; Patil, A.; Blicharz, L.; Kassir, M.; Konnikov, N.; Gold, M.H.; Goldman, M.P.; Galadari, H.; Goldust, M. Medical Therapies for Melasma. J. Cosmet. Dermatol. 2022, 21, 3707–3728. [Google Scholar] [CrossRef]
- Ravetti, S.; Clemente, C.; Brignone, S.; Hergert, L.; Allemandi, D.; Palma, S. Ascorbic Acid in Skin Health. Cosmetics 2019, 6, 58. [Google Scholar] [CrossRef]
- Ebanks, J.; Wickett, R.; Boissy, R. Mechanisms Regulating Skin Pigmentation: The Rise and Fall of Complexion Coloration. Int. J. Mol. Sci. 2009, 10, 4066–4087. [Google Scholar] [CrossRef]
- De Dormael, R.; Bastien, P.; Sextius, P.; Gueniche, A.; Ye, D.; Tran, C.; Chevalier, V.; Gomes, C.; Souverain, L.; Tricaud, C. Vitamin C Prevents Ultraviolet-Induced Pigmentation in Healthy Volunteers: Bayesian Meta-Analysis Results from 31 Randomized Controlled versus Vehicle Clinical Studies. J. Clin. Aesthet. Dermatol. 2019, 12, E53–E59. [Google Scholar]
- Boo, Y.C. Ascorbic Acid (Vitamin C) as a Cosmeceutical to Increase Dermal Collagen for Skin Antiaging Purposes: Emerging Combination Therapies. Antioxidants 2022, 11, 1663. [Google Scholar] [CrossRef] [PubMed]
- Darr, D.; Combs, S.; Dunston, S.; Manning, T.; Pinnell, S. Topical Vitamin C Protects Porcine Skin from Ultraviolet Radiation-Induced Damage. Br. J. Dermatol. 1992, 127, 247–253. [Google Scholar] [CrossRef]
- Espinal-Perez, L.E.; Moncada, B.; Castanedo-Cazares, J.P. A Double-blind Randomized Trial of 5% Ascorbic Acid vs. 4% Hydroquinone in Melasma. Int. J. Dermatol. 2004, 43, 604–607. [Google Scholar] [CrossRef]
- Correia, G.; Magina, S. Efficacy of Topical Vitamin C in Melasma and Photoaging: A Systematic Review. J. Cosmet. Dermatol. 2023, 22, 1938–1945. [Google Scholar] [CrossRef] [PubMed]
- Taylor, M.B.; Yanaki, J.S.; Draper, D.O.; Shurtz, J.C.; Coglianese, M. Successful Short-Term and Long-Term Treatment of Melasma and Postinflammatory Hyperpigmentation Using Vitamin C with a Full-Face Iontophoresis Mask and a Mandelic/Malic Acid Skin Care Regimen. J. Drugs Dermatol. 2013, 12, 45–50. [Google Scholar] [PubMed]
- Zhou, H.L.; Hu, B.; Zhang, C. Efficacy of 694-Nm Fractional Q-Switched Ruby Laser (QSRL) Combined with Sonophoresis on Levorotatory Vitamin C for Treatment of Melasma in Chinese Patients. Lasers Med. Sci. 2016, 31, 991–995. [Google Scholar] [CrossRef] [PubMed]
- Balevi, A.; Ustuner, P.; Özdemir, M. Salicylic Acid Peeling Combined with Vitamin C Mesotherapy versus Salicylic Acid Peeling Alone in the Treatment of Mixed Type Melasma: A Comparative Study. J. Cosmet. Laser Ther. 2017, 19, 294–299. [Google Scholar] [CrossRef]
- Speeckaert, R.; Bulat, V.; Speeckaert, M.M.; Van Geel, N. The Impact of Antioxidants on Vitiligo and Melasma: A Scoping Review and Meta-Analysis. Antioxidants 2023, 12, 2082. [Google Scholar] [CrossRef] [PubMed]
- Pazyar, N.; Molavi, S.N.; Hosseinpour, P.; Hadibarhaghtalab, M.; Parvar, S.Y.; Dezfuly, M.B. Efficacy of Intradermal Injection of Tranexamic Acid and Ascorbic Acid versus Tranexamic Acid and Placebo in the Treatment of Melasma: A Split-face Comparative Trial. Health Sci. Rep. 2022, 5, e537. [Google Scholar] [CrossRef]
- Chib, S.; Jamwal, V.L.; Kumar, V.; Gandhi, S.G.; Saran, S. Fungal Production of Kojic Acid and Its Industrial Applications. Appl. Microbiol. Biotechnol. 2023, 107, 2111–2130. [Google Scholar] [CrossRef] [PubMed]
- Saeedi, M.; Eslamifar, M.; Khezri, K. Kojic Acid Applications in Cosmetic and Pharmaceutical Preparations. Biomed. Pharmacother. 2019, 110, 582–593. [Google Scholar] [CrossRef]
- Lim, J.T.E. Treatment of Melasma Using Kojic Acid in a Gel Containing Hydroquinone and Glycolic Acid. Dermatol. Surg. 1999, 25, 282–284. [Google Scholar] [CrossRef]
- Monteiro, R.C.; Kishore, B.N.; Bhat, R.M.; Sukumar, D.; Martis, J.; Ganesh, H.K. 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. [Google Scholar] [CrossRef] [PubMed]
- Bhagwat, P.V.; Manangi, S.; Dani, A.; Kudligi, C. Efficacy and Safety of 2% Kojic Acid Containing Formulation versus Modified Kligman’s Formula in Melasma—A Comparative Study. J. Pak. Assoc. Dermatol. 2017, 26, 183–187. [Google Scholar]
- Maeda, K. Mechanism of Action of Topical Tranexamic Acid in the Treatment of Melasma and Sun-Induced Skin Hyperpigmentation. Cosmetics 2022, 9, 108. [Google Scholar] [CrossRef]
- Atefi, N.; Dalvand, B.; Ghassemi, M.; Mehran, G.; Heydarian, A. Therapeutic Effects of Topical Tranexamic Acid in Comparison with Hydroquinone in Treatment of Women with Melasma. Dermatol. Ther. 2017, 7, 417–424. [Google Scholar] [CrossRef]
- Janney, M.; Subramaniyan, R.; Dabas, R.; Lal, S.; Das, N.; Godara, S. A Randomized Controlled Study Comparing the Efficacy of Topical 5% Tranexamic Acid Solution versus 3% Hydroquinone Cream in Melasma. J. Cutan. Aesthet. Surg. 2019, 12, 63. [Google Scholar] [CrossRef]
- El-Husseiny, R.; Rakha, N.; Sallam, M. Efficacy and Safety of Tranexamic Acid 5% Cream vs Hydroquinone 4% Cream in Treating Melasma: A Split-face Comparative Clinical, Histopathological, and Antera 3D Camera Study. Dermatol. Ther. 2020, 33. [Google Scholar] [CrossRef]
- Thieman, T.; Swali, R.; Adams, J. 33031 Use of Topical Tranexamic Acid in Patients with Melasma: A Narrative Review. J. Am. Acad. Dermatol. 2022, 87, AB126. [Google Scholar] [CrossRef]
- Desai, S.; Ayres, E.; Bak, H.; Manco, M.; Lynch, S.; Raab, S.; Du, A.; Green, D.; Skobowiat, C.; Wangari-Talbot, J.; et al. Effect of a Tranexamic Acid, Kojic Acid, and Niacinamide Containing Serum on Facial Dyschromia: A Clinical Evaluation. J. Drugs Dermatol. 2019, 18, 454–459. [Google Scholar]
- Madaan, P.; Sikka, P.; Malik, D.S. Cosmeceutical Aptitudes of Niacinamide: A Review. Recent. Adv. Antiinfect. Drug Discov. 2021, 16, 196–208. [Google Scholar] [CrossRef]
- Boo, Y.C. Mechanistic Basis and Clinical Evidence for the Applications of Nicotinamide (Niacinamide) to Control Skin Aging and Pigmentation. Antioxidants 2021, 10, 1315. [Google Scholar] [CrossRef] [PubMed]
- Navarrete-Solís, J.; Castanedo-Cázares, J.P.; Torres-Álvarez, B.; Oros-Ovalle, C.; Fuentes-Ahumada, C.; González, F.J.; Martínez-Ramírez, J.D.; Moncada, B. A Double-Blind, Randomized Clinical Trial of Niacinamide 4% versus Hydroquinone 4% in the Treatment of Melasma. Dermatol. Res. Pract. 2011, 2011, 1–5. [Google Scholar] [CrossRef]
- Allouche, J.; Rachmin, I.; Adhikari, K.; Pardo, L.M.; Lee, J.H.; McConnell, A.M.; Kato, S.; Fan, S.; Kawakami, A.; Suita, Y.; et al. NNT Mediates Redox-Dependent Pigmentation via a UVB- and MITF-Independent Mechanism. Cell 2021, 184, 4268–4283. [Google Scholar] [CrossRef] [PubMed]
- Pedroso, A.G.; Furtado, G.R.D.; Barbosa, K.L. Niacinamide for the Treatment of Melasma: An Integrative Review of Randomized Clinical Trials. Res. Soc. Dev. 2022, 11, e198111133581. [Google Scholar] [CrossRef]
- Saeedi, M.; Khezri, K.; Seyed Zakaryaei, A.; Mohammadamini, H. A Comprehensive Review of the Therapeutic Potential of A-arbutin. Phytoth. Res. 2021, 35, 4136–4154. [Google Scholar] [CrossRef] [PubMed]
- Boo, Y.C. Arbutin as a Skin Depigmenting Agent with Antimelanogenic and Antioxidant Properties. Antioxidants 2021, 10, 1129. [Google Scholar] [CrossRef]
- Searle, T.; Al-Niaimi, F.; Ali, F.R. The Top 10 Cosmeceuticals for Facial Hyperpigmentation. Dermatol. Ther. 2020, 33, e14095. [Google Scholar] [CrossRef]
- Hamed, S.H.; Sriwiriyanont, P.; deLong, M.A.; Visscher, M.O.; Wickett, R.R.; Boissy, R.E. Comparative Efficacy and Safety of Deoxyarbutin, a New Tyrosinase-Inhibiting Agent. J. Cosmet. Sci. 2006, 57, 291–308. [Google Scholar]
- Anwar, A.I.; Asmarani, Y.; Madjid, A.; Patellongi, I.; Adriani, A.; As’ad, S.; Kurniadi, I. Comparison of 2% Deoxyarbutin and 4% Hydroquinone as a Depigmenting Agent in Healthy Individuals: A Double-blind Randomized Controlled Clinical Trial. J. Cosmet. Dermatol. 2021, 20, 3953–3959. [Google Scholar] [CrossRef]
- Nguyen, J.; Rajgopal Bala, H.; Ross, A.; Wong, C.C.; Paul, E.; Rodrigues, M. Effect of Oral Tranexamic Acid on Erythema Index in Patients with Melasma. Aust. J. Dermatol. 2021, 62, 206–209. [Google Scholar] [CrossRef]
- Feng, X.; Su, H.; Xie, J. Efficacy and Safety of Tranexamic Acid in the Treatment of Adult Melasma: An Updated Meta-analysis of Randomized Controlled Trials. J. Clin. Pharm. Ther. 2021, 46, 1263–1273. [Google Scholar] [CrossRef] [PubMed]
- Godse, K.; Sarkar, R.; Mysore, V.; Shenoy, M.M.; Chatterjee, M.; Damisetty, R.; Shah, S.; Vedamurthy, M.; Aurangabadkar, S.; Srinivas, C.; et al. Oral Tranexamic Acid for the Treatment of Melasma: Evidence and Experience-Based Consensus Statement from Indian Experts. Indian J. Dermatol. 2023, 68, 178–185. [Google Scholar] [CrossRef]
- Malik, F.; Hanif, M.; Mustafa, G. Combination of Oral Tranexamic Acid with Topical 3% Tranexamic Acid versus Oral Tranexamic Acid with Topical 20% Azelaic Acid in the Treatment of Melasma. J. Coll. Physicians Surg. Pak. 2019, 29, 502–504. [Google Scholar] [CrossRef]
- Agamia, N.; Apalla, Z.; Salem, W.; Abdallah, W. A Comparative Study between Oral Tranexamic Acid versus Oral Tranexamic Acid and Q-Switched Nd-YAG Laser in Melasma Treatment: A Clinical and Dermoscopic Evaluation. J. Dermatol. Treat. 2021, 32, 819–826. [Google Scholar] [CrossRef]
- McKesey, J.; Tovar-Garza, A.; Pandya, A.G. Melasma Treatment: An Evidence-Based Review. Am. J. Clin. Dermatol. 2020, 21, 173–225. [Google Scholar] [CrossRef]
- Yao, H.; Shen, S.; Gao, X.; Feng, J.; Song, X.; Xiang, W. Definition of Refractory Melasma and Its Treatment: A Review. Lasers Med. Sci. 2024, 39, 118. [Google Scholar] [CrossRef] [PubMed]
- Konisky, H.; Balazic, E.; Jaller, J.A.; Khanna, U.; Kobets, K. Tranexamic Acid in Melasma: A Focused Review on Drug Administration Routes. J. Cosmet. Dermatol. 2023, 22, 1197–1206. [Google Scholar] [CrossRef] [PubMed]
- Zhu, C.-Y.; Li, Y.; Sun, Q.-N.; Takada, A.; Kawada, A. Analysis of the Effect of Different Doses of Oral Tranexamic Acid on Melasma: A Multicentre Prospective Study. Eur. J. Dermatol. 2019, 29, 55–58. [Google Scholar] [CrossRef] [PubMed]
- Sonthalia, S.; Daulatabad, D.; Sarkar, R. Glutathione as a Skin Whitening Agent: Facts, Myths, Evidence and Controversies. Indian J. Dermatol. Venereol. Leprol. 2016, 82, 262. [Google Scholar] [CrossRef]
- Grimes, P.E.; Ijaz, S.; Nashawati, R.; Kwak, D. New Oral and Topical Approaches for the Treatment of Melasma. Int. J. Womens Dermatol. 2019, 5, 30–36. [Google Scholar] [CrossRef]
- Arjinpathana, N.; Asawanonda, P. Glutathione as an Oral Whitening Agent: A Randomized, Double-Blind, Placebo-Controlled Study. J. Dermatol. Treat. 2012, 23, 97–102. [Google Scholar] [CrossRef]
- Wahab, S.; Anwar, A.I.; Zainuddin, A.N.; Hutabarat, E.N.; Anwar, A.A.; Kurniadi, I. Combination of Topical and Oral Glutathione as a Skin-whitening Agent: A Double-blind Randomized Controlled Clinical Trial. Int. J. Dermatol. 2021, 60, 1013–1018. [Google Scholar] [CrossRef] [PubMed]
- Vladulescu, D.; Scurtu, L.G.; Simionescu, A.A.; Scurtu, F.; Popescu, M.I.; Simionescu, O. Platelet-Rich Plasma (PRP) in Dermatology: Cellular and Molecular Mechanisms of Action. Biomedicines 2023, 12, 7. [Google Scholar] [CrossRef]
- Acar, A.; Ozturk, A.; Sokmen, N.; Unal, I.; Ertam Sagduyu, I. Evaluation of Platelet-Rich Plasma Efficacy in Melasma. J. Cosmet. Laser Ther. 2022, 24, 36–39. [Google Scholar] [CrossRef] [PubMed]
- Hofny, E.R.M.; Abdel-Motaleb, A.A.; Ghazally, A.; Ahmed, A.M.; Hussein, M.R.A. Platelet-Rich Plasma Is a Useful Therapeutic Option in Melasma. J. Dermatol. Treat. 2019, 30, 396–401. [Google Scholar] [CrossRef] [PubMed]
- Zhao, L.; Hu, M.; Xiao, Q.; Zhou, R.; Li, Y.; Xiong, L.; Li, L. Efficacy and Safety of Platelet-Rich Plasma in Melasma: A Systematic Review and Meta-Analysis. Dermatol. Ther. 2021, 11, 1587–1597. [Google Scholar] [CrossRef] [PubMed]
- Abd Elraouf, I.G.; Obaid, Z.M.; Fouda, I. Intradermal Injection of Tranexamic Acid versus Platelet-Rich Plasma in the Treatment of Melasma: A Split-Face Comparative Study. Arch. Dermatol. Res. 2023, 315, 1763–1770. [Google Scholar] [CrossRef]
- Gamea, M.M.; Kamal, D.A.; Donia, A.A.; Hegab, D.S. Comparative Study between Topical Tranexamic Acid Alone versus Its Combination with Autologous Platelet Rich Plasma for Treatment of Melasma. J. Dermatol. Treat. 2022, 33, 798–804. [Google Scholar] [CrossRef]
- Sarkar, R.; Gupta, M. Platelet-Rich Plasma in Melasma—A Systematic Review. Dermatol. Surg. 2022, 48, 131–134. [Google Scholar] [CrossRef]
- Pixley, J.N.; Cook, M.K.; Singh, R.; Larrondo, J.; McMichael, A.J. A Comprehensive Review of Platelet-Rich Plasma for the Treatment of Dermatologic Disorders. J. Dermatol. Treat. 2023, 34, 2142035. [Google Scholar] [CrossRef]
- Batra, J.; Brar, B.; Kumar, S.; Arora, H. Tranexamic Acid in Melasma: Comparative Evaluation of Therapeutic Efficacy of Oral Tranexamic Acid versus Its Transepidermal Administration. J. Cutan. Aesthet. Surg. 2022, 15, 394. [Google Scholar] [CrossRef]
- Saleh, F.; Abdel-Azim, E.; Ragaie, M.; Guendy, M. Topical Tranexamic Acid with Microneedling versus Microneedling Alone in Treatment of Melasma: Clinical, Histopathologic, and Immunohistochemical Study. J. Egypt. Womens Dermatol. Soc. 2019, 16, 89. [Google Scholar] [CrossRef]
- Kaur, A.; Bhalla, M.; Pal Thami, G.; Sandhu, J. Clinical Efficacy of Topical Tranexamic Acid With Microneedling in Melasma. Dermatol. Surg. 2020, 46, e96–e101. [Google Scholar] [CrossRef]
- Zaky, M.S.; Obaid, Z.M.; Khalil, E.A.; Elsaie, M.L. Microneedling-assisted Topical Tranexamic Acid Solution versus 4% Hydroquinone for Treating Melasma: A Split-face Randomized Study. J. Cosmet. Dermatol. 2021, 20, 4011–4016. [Google Scholar] [CrossRef]
- Shamsi Meymandi, S.; Mozayyeni, A.; Shamsi Meymandi, M.; Aflatoonian, M. Efficacy of Microneedling plus Topical 4% Tranexamic Acid Solution vs 4% Hydroquinone in the Treatment of Melasma: A Single-blind Randomized Clinical Trial. J. Cosmet. Dermatol. 2020, 19, 2906–2911. [Google Scholar] [CrossRef]
- Kaleem, S.; Ghafoor, R.; Khan, S. Comparison of Efficacy of Tranexamic Acid Mesotherapy versus 0.9% Normal Saline for Melasma; A Split Face Study in a Tertiary Care Hospital of Karachi. Pak. J. Med. Sci. 2020, 36, 930–934. [Google Scholar] [CrossRef] [PubMed]
- Tehranchinia, Z.; Saghi, B.; Rahimi, H. Evaluation of Therapeutic Efficacy and Safety of Tranexamic Acid Local Infiltration in Combination with Topical 4% Hydroquinone Cream Compared to Topical 4% Hydroquinone Cream Alone in Patients with Melasma: A Split-Face Study. Dermatol. Res. Pract. 2018, 2018, 1–5. [Google Scholar] [CrossRef] [PubMed]
- Pazyar, N.; Yaghoobi, R.; Zeynalie, M.; Vala, S. Comparison of the Efficacy of Intradermal Injected Tranexamic Acid vs Hydroquinone Cream in the Treatment of Melasma. Clin. Cosmet. Investig. Dermatol. 2019, 12, 115–122. [Google Scholar] [CrossRef]
- Lueangarun, S.; Sirithanabadeekul, P.; Wongwicharn, P.; Namboonlue, C.; Pacharapakornpong, S.; Juntongjin, P.; Tempark, T. Intradermal Tranexamic Acid Injection for the Treatment of Melasma: A Pilot Study with 48-Week Follow-Up. J. Clin. Aesthet. Dermatol. 2020, 13, 36–39. [Google Scholar]
- Conforti, C.; Zalaudek, I.; Vezzoni, R.; Retrosi, C.; Fai, A.; Fadda, S.; Di Michele, E.; Dianzani, C. Chemical Peeling for Acne and Melasma: Current Knowledge and Innovations. G. Ital. Dermatol. Venereol. 2020, 155, 280–285. [Google Scholar] [CrossRef]
- Samargandy, S.; Raggio, B.S. Chemical Peels for Skin Resurfacing. In StatPearls; StatPearls Publishing: Treasure Island, FL, USA, 2024. Available online: https://www.ncbi.nlm.nih.gov/books/NBK547752/ (accessed on 3 June 2024).
- Sarkar, R.; Lakhani, R. Chemical Peels for Melasma: A Systematic Review. Dermatol. Surg. 2024, 50, 656–661. [Google Scholar] [CrossRef]
- Prasad, N.; Singh, M.; Malhotra, S.; Singh, N.; Tyagi, A.; Tyagi, S. Comparative Efficacy of Chemical Peeling Agents in the Treatment of Melasma. Cureus 2023, 15, e47312. [Google Scholar] [CrossRef] [PubMed]
- Basit, H.; Godse, K.V.; Al Aboud, A.M. Melasma. In StatPearls; StatPearls Publishing: Treasure Island, FL, USA, 2024. Available online: https://www.ncbi.nlm.nih.gov/books/NBK459271/ (accessed on 5 June 2024).
- Ho, S.G.Y.; Chan, H.H.L. The Asian Dermatologic Patient: Review of Common Pigmentary Disorders and Cutaneous Diseases. Am. J. Clin. Dermatol. 2009, 10, 153–168. [Google Scholar] [CrossRef] [PubMed]
- Fanous, N.; Zari, S. Universal Trichloroacetic Acid Peel Technique for Light and Dark Skin. JAMA Facial Plast. Surg. 2017, 19, 212–219. [Google Scholar] [CrossRef] [PubMed]
- Sarkar, R.; Bansal, S.; Garg, V.K. Chemical peels for melasma in dark-skinned patients. J. Cutan. Aesthet. Surg. 2012, 5, 247–253. [Google Scholar] [CrossRef] [PubMed]
- Sarkar, R.; Aurangabadkar, S.; Salim, T.; Das, A.; Shah, S.; Majid, I.; Singh, M.; Ravichandran, G.; Godse, K.; Arsiwala; et al. Lasers in Melasma: A Review with Consensus Recommendations by Indian Pigmentary Expert Group. Indian J. Dermatol. 2017, 62, 585–590. [Google Scholar] [CrossRef] [PubMed]
- Neagu, N.; Conforti, C.; Agozzino, M.; Marangi, G.F.; Morariu, S.H.; Pellacani, G.; Persichetti, P.; Piccolo, D.; Segreto, F.; Zalaudek, I.; et al. Melasma Treatment: A Systematic Review. J. Dermatol. Treat. 2022, 33, 1816–1837. [Google Scholar] [CrossRef] [PubMed]
- Lai, D.; Zhou, S.; Cheng, S.; Liu, H.; Cui, Y. Laser Therapy in the Treatment of Melasma: A Systematic Review and Meta-Analysis. Lasers Med. Sci. 2022, 37, 2099–2110. [Google Scholar] [CrossRef] [PubMed]
- Yi, J.; Hong, T.; Zeng, H.; Li, P.; Li, P.; Wang, S.; Chen, J.; Li, P.; Zhou, J. A Meta-Analysis-Based Assessment of Intense Pulsed Light for Treatment of Melasma. Aesth. Plast. Surg. 2020, 44, 947–952. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- Ertam Sagduyu, I.; Dirican, F.; Acar, A.; Unal, I. Efficacy of intense pulsed light therapy for melasma. J. Cosmet. Laser Ther. 2019, 21, 378–381. [Google Scholar] [CrossRef] [PubMed]
- Trivedi, M.K.; Yang, F.C.; Cho, B.K. A Review of Laser and Light Therapy in Melasma. Int. J. Womens Dermatol. 2017, 3, 11–20. [Google Scholar] [CrossRef] [PubMed]
- Aurangabadkar, S. Optimizing Q-Switched Lasers for Melasma and Acquired Dermal Melanoses. Indian. J. Dermatol. Venereol. Leprol. 2019, 85, 10. [Google Scholar] [CrossRef] [PubMed]
- Micek, I.; Pawlaczyk, M.; Kroma, A.; Seraszek-Jaros, A.; Urbańska, M.; Gornowicz-Porowska, J. Treatment of Melasma with a Low-fluence 1064 Nm Q-switched Nd:YAG Laser: Laser Toning in Caucasian Women. Lasers Surg. Med. 2022, 54, 366–373. [Google Scholar] [CrossRef]
- Shah, S.; Aurangabadkar, S. Laser Toning in Melasma. J. Cutan. Aesthet. Surg. 2019, 12, 76. [Google Scholar] [CrossRef] [PubMed]
- Ma, W.; Gao, Q.; Liu, J.; Zhong, X.; Xu, T.; Wu, Q.; Cheng, Z.; Luo, N.; Hao, P. Efficacy and Safety of Laser-related Therapy for Melasma: A Systematic Review and Network Meta-analysis. J. Cosmet. Dermatol. 2023, 22, 2910–2924. [Google Scholar] [CrossRef]
- Lee, Y.S.; Lee, Y.J.; Lee, J.M.; Han, T.Y.; Lee, J.H.; Choi, J.E. The Low-Fluence Q-Switched Nd:YAG Laser Treatment for Melasma: A Systematic Review. Medicina 2022, 58, 936. [Google Scholar] [CrossRef]
- Wanitphakdeedecha, R.; Sy-Alvarado, F.; Patthamalai, P.; Techapichetvanich, T.; Eimpunth, S.; Manuskiatti, W. The Efficacy in Treatment of Facial Melasma with Thulium 1927-Nm Fractional Laser-Assisted Topical Tranexamic Acid Delivery: A Split-Face, Double-Blind, Randomized Controlled Pilot Study. Lasers Med. Sci. 2020, 35, 2015–2021. [Google Scholar] [CrossRef]
- Aggarwal, I.; Rossi, M.; Puyana, C.; Tsoukas, M. Review of Fractional Nonablative Lasers for the Treatment of Dermatologic Conditions in Darker Skin Phototypes. Dermatol. Surg. 2024, 50, 459–466. [Google Scholar] [CrossRef]
- Zhao, S.; Wang, M.; Lai, X.; Yan, Y. Efficacy and Safety of Ablative Fractional Laser in Melasma: A Meta-Analysis and Systematic Review. Lasers Med. Sci. 2024, 39, 71. [Google Scholar] [CrossRef]
- Zhang, C.; Wu, T.; Shen, N. Effect of platelet-rich plasma combined with tranexamic acid in the treatment of melasma and its effect on the serum levels of vascular endothelial growth factor, endothelin-1 and melatonin. Pak. J. Med. Sci. 2022, 38, 2163–2168. [Google Scholar] [CrossRef]
- Tuknayat, A.; Thami, G.P.; Bhalla, M.; Sandhu, J.K. Autologous intralesional platelet rich plasma improves melasma. Dermatol. Ther. 2021, 34, e14881. [Google Scholar] [CrossRef]
- Adel, S.; Serri, A.; Abd El-Raheem, T. Study of autologous platelet-rich-plasma versus its combination with intense pulsed light in treatment of melasma. Dermatol. Ther. 2021, 34, e15008. [Google Scholar] [CrossRef]
- Sirithanabadeekul, P.; Dannarongchai, A.; Suwanchinda, A. Platelet-rich plasma treatment for melasma: A pilot study. J. Cosmet. Dermatol. 2020, 19, 1321–1327. [Google Scholar] [CrossRef]
- Ertam Sagduyu, I.; Marakli, O.; Oraloglu, G.; Bulut Okut, E.; Unal, I. Comparison of 1064 nm Q-switched Nd:YAG laser and Jessner peeling in melasma treatment. Dermatol Ther. 2022, 35, e15970. [Google Scholar] [CrossRef]
- Salvioni, L.; Morelli, L.; Ochoa, E.; Labra, M.; Fiandra, L.; Palugan, L.; Prosperi, D.; Colombo, M. The Emerging Role of Nanotechnology in Skincare. Adv. Colloid. Interface Sci. 2021, 293, 102437. [Google Scholar] [CrossRef] [PubMed]
- Singh, S.; Sharma, N.; Zahoor, I.; Behl, T.; Antil, A.; Gupta, S.; Anwer, M.K.; Mohan, S.; Bungau, S.G. Decrypting the Potential of Nanotechnology-Based Approaches as Cutting-Edge for Management of Hyperpigmentation Disorder. Molecules 2022, 28, 220. [Google Scholar] [CrossRef] [PubMed]
- Ghanbarzadeh, S.; Hariri, R.; Kouhsoltani, M.; Shokri, J.; Javadzadeh, Y.; Hamishehkar, H. Enhanced Stability and Dermal Delivery of Hydroquinone Using Solid Lipid Nanoparticles. Colloids Surf. B. Biointerfaces 2015, 136, 1004–1010. [Google Scholar] [CrossRef]
- Wu, P.-S.; Lin, C.-H.; Kuo, Y.-C.; Lin, C.-C. Formulation and Characterization of Hydroquinone Nanostructured Lipid Carriers by Homogenization Emulsification Method. J. Nanomater. 2017, 2017, 1–7. [Google Scholar] [CrossRef]
- Tangau, M.J.; Chong, Y.K.; Yeong, K.Y. Advances in Cosmeceutical Nanotechnology for Hyperpigmentation Treatment. J. Nanopart. Res. 2022, 24, 155. [Google Scholar] [CrossRef]
- Nikolaev, B.; Yakovleva, L.; Fedorov, V.; Li, H.; Gao, H.; Shevtsov, M. Nano- and Microemulsions in Biomedicine: From Theory to Practice. Pharmaceutics 2023, 15, 1989. [Google Scholar] [CrossRef]
- Tomić, I.; Juretić, M.; Jug, M.; Pepić, I.; Cetina Čižmek, B.; Filipović-Grčić, J. Preparation of in Situ Hydrogels Loaded with Azelaic Acid Nanocrystals and Their Dermal Application Performance Study. Int. J. Pharm. 2019, 563, 249–258. [Google Scholar] [CrossRef]
- Çağlar, E.Ş.; Pekcan, A.N.; Okur, M.E.; Ayla, Ş.; Üstündağ Okur, N. Preparation, Optimization and in Vivo Anti-Inflammatory Evaluation of Hydroquinone Loaded Microemulsion Formulations for Melasma Treatment. J. Res. Pharm. 2019, 23, 662–670. [Google Scholar] [CrossRef]
- Kusumawardani, A.; Paramitasari, A.R.; Dewi, S.R.; Betaubun, A.I. The Application of Liposomal Azelaic Acid, 4-n Butyl Resorcinol and Retinol Serum Enhanced by Microneedling for Treatment of Malar Pattern Melasma: A Case Series. Dermatol. Rep. 2019. [Google Scholar] [CrossRef]
- Taghavi, F.; Banihashemi, M.; Zabolinejad, N.; Salehi, M.; Jaafari, M.R.; Marhamati, H.; Golnouri, F.; Dorri, M. Comparison of Therapeutic Effects of Conventional and Liposomal Form of 4% Topical Hydroquinone in Patients with Melasma. J. Cosmet. Dematol. 2019, 18, 870–873. [Google Scholar] [CrossRef] [PubMed]
- Liga, S.; Paul, C.; Moacă, E.-A.; Péter, F. Niosomes: Composition, Formulation Techniques, and Recent Progress as Delivery Systems in Cancer Therapy. Pharmaceutics 2024, 16, 223. [Google Scholar] [CrossRef] [PubMed]
- Divanbeygikermani, M.; Pardakhty, A.; Amanatfard, A. Kojic Acid and Hydroquinone Non-Ionic Surfactant Vesicles for Topical Application. Int. Pharm. Acta 2018, 1, 110. [Google Scholar] [CrossRef]
- Fernández-García, R.; Lalatsa, A.; Statts, L.; Bolás-Fernández, F.; Ballesteros, M.P.; Serrano, D.R. Transferosomes as Nanocarriers for Drugs across the Skin: Quality by Design from Lab to Industrial Scale. Int. J. Pharm. 2020, 573, 118817. [Google Scholar] [CrossRef]
- Li, J.; Duan, N.; Song, S.; Nie, D.; Yu, M.; Wang, J.; Xi, Z.; Li, J.; Sheng, Y.; Xu, C.; et al. Transfersomes Improved Delivery of Ascorbic Palmitate into the Viable Epidermis for Enhanced Treatment of Melasma. Int. J. Pharm. 2021, 608, 121059. [Google Scholar] [CrossRef]
- Karamanidou, T.; Bourganis, V.; Gatzogianni, G.; Tsouknidas, A. A Review of the EU’s Regulatory Framework for the Production of Nano-Enhanced Cosmetics. Metals 2021, 11, 455. [Google Scholar] [CrossRef]
- Raj, S.; Jose, S.; Sumod, U.S.; Sabitha, M. Nanotechnology in cosmetics: Opportunities and challenges. J. Pharm. Bioallied Sci. 2012, 4, 186–193. [Google Scholar] [CrossRef]
- EUR-Lex. Access to European Union Law. Regulation (EC) No 1223/2009 of the European Parliament and of the Council of 30 November 2009 on Cosmetic Products. OJ L 342/59, 2009. Available online: https://eur-lex.europa.eu/legal-content/EN/ALL/?uri=celex%3A32009R1223 (accessed on 27 July 2024).
- Doolan, B.J.; Gupta, M. Melasma. Aust. J. Gen. Pract. 2021, 50, 880–885. [Google Scholar] [CrossRef]
- Shankar, K.; Godse, K.; Aurangabadkar, S.; Lahiri, K.; Mysore, V.; Ganjoo, A.; Vedamurty, M.; Kohli, M.; Sharad, J.; Kadhe, G.; et al. Evidence-based treatment for melasma: Expert opinion and a review. Dermatol. Ther. 2014, 4, 165–186. [Google Scholar] [CrossRef] [PubMed]
- Arellano, I.; Cestari, T.; Ocampo-Candiani, J.; Azulay-Abulafia, L.; Bezerra Trindade Neto, P.; Hexsel, D.; Machado-Pinto, J.; Muñoz, H.; Rivitti-Machado, M.C.; Sittart, J.A.; 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. [Google Scholar] [CrossRef] [PubMed]
Scoring System | Parameters | Formula | Total Score |
---|---|---|---|
MASI | A: area of involvement (0: absent; 1: <10%; 2: 10–29%; 3: 30–49%; 4: 50–69%; 5: 70–89%; 6: 90–100%); | 0.3A (D + H) forehead + 0.3A (D + H) right malar + 0.3A (D + H) left malar + 0.1A (D + H) chin | 0–48 |
D: darkness (0: absent; 1: slight; 2: mild; 3: marked; 4: severe) | |||
H: homogeneity (0 = no pigment; 1 = specks; 2 ≤ 2 cm patches; 3 ≥ 2 cm patches; 4 = homogeneous) | |||
mMASI | A: area of involvement (0: absent; 1: <10%; 2: 10–29%; 3: 30–49%; 4: 50–69%; 5: 70–89%; 6: 90–100%); | 0.3A × D forehead + 0.3A × D right malar + 0.3A × D left malar + 3A × D chin | 0–24 |
D: darkness (0: absent; 1: slight; 2: mild; 3: marked; 4: severe) | |||
MSS | Intensity of pigmentation | NA | 1: mild; 2: moderate; 3: severe |
MSI | p: pigmentation (0: no visible pigmentation; 1: barely visible pigmentation; 3: moderate pigmentation; 4: severe pigmentation) | 0.4 (a × p2) left face + 0.4 (a × p2) right face + 0.2 (a × p2) nose | Scoring of pigmentation: 0–4 Scoring of area of involvement: 0–4 |
a: area of involvement (1: ≤10%; 2: 11–30%; 3: 31–60%; 4: >60%) |
Author, Year [Reference Number] | Study Design | Examinees/Patients | Treatment Method | Wks/ Mo | Method of Assessment | Results |
---|---|---|---|---|---|---|
Chan, R. et al., 2008 [22] | Multicentre, randomized, controlled, investigator-blinded, parallel comparison study | 251 | TC (fluocinolone acetonide 0.01%, HQ 4%, tretinoin 0.05%) vs. HQ 4% | 8 wks | GSS, patient satisfaction | GSS: mild or no melasma in 64.2% of the TC patient group vs. 39.4% in HQ group (p < 0.001). Patient satisfaction: 70.8% in the TC group vs. 49.6% in the HQ group. |
Akl, E. et al., 2022 [28] | Randomized controlled study | 50 | Liposomal AZA 20% cream + oral TXA (250 mg daily) vs. HQ 4% cream + oral TXA (250 mg daily) | 3 mo | mMASI, DLQI | mMASI: better improvement in liposomal AZA group vs. HQ group (p < 0.001). QoL: better improvement in liposomal AZA group vs. HQ group (p < 0.001) Liposomal AZA 20% was more tolerable (p < 0.0001). |
Tehrani, S. et al., 2012 [29] | Double-blind randomized clinical trial | 64 | AZA 20% cream + HQ 5% vs. HQ 5% alone | 4 mo | MASI | AZA 20% + HQ 5%: quicker and more effective therapeutic response. MASI score reduction: from 9.35 to 2.9 in the AZA + HQ group and from 9.58 to 4.02 in the HQ group. |
Griffiths, C.E.M. et al., 1993 [32] | Double-blind, randomized, vehicle-controlled clinical trial | 38 | Topical tretinoin 0.1% vs. vehicle | 40 wks | Clinical evaluation, colorimetry, patient self- assessment | Clinical improvement: 68% in the tretinoin group vs. 5% in vehicle group (p = 0.0006). Colorimetry: lightening by 0.9 units (tretinoin group) vs. by 0.3 units (vehicle) (p = 0.01). AE: erythema and desquamation in 88% (tretinoin group) vs. 29% (vehicle). |
Espinal-Perez, L.E. et al., 2004 [44] | Randomized, double-blind, split-face study | 16 | 5% L-ascorbic acid cream vs. 4% HQ cream | 16 wks | Calorimetry, subjective evaluation, digital photography | Colorimetry: no statistically significant difference. Subjective evaluation: “good” or “excellent” in 93% in the HQ-treated skin vs. 62.5% in the ascorbic acid-treated skin (p < 0.05). Skin irritation: 8.75% of HQ-treated skin vs. 6.25% of ascorbic acid-treated skin. |
Monteiro, R.C. et al., 2013 [54] | Randomized, controlled trial | 60 | 4% HQ cream vs. 0.75% KA + 2.5% vitamin C | 12 wks | MASI | MASI: significantly decreased in both groups (p ≤ 0.001, respectively). AE: erythema in 6.7% of patients receiving 4% HQ cream and 3.3% of patients receiving 0.75% KA cream. |
Bhagwat, P.V. et al., 2017 [55] | Comparative clinical study | 60 | Modified Kligman’s formula (2% HQ, 0.025% tretinoin, 0.01% fluocinolone acetonide cream) vs. 2% KA + octinoxate + allantoin containing gel | 3 mo | MASI, colour photography | MASI mean reduction: MKF (2.08, 26.22%, p < 0.0001) vs. 2% KA group (6.67, 66.5%, p < 0.0001). Better efficacy in MKF vs. 2% KA group (p < 0.0001). |
Atefi, N. et al., 2017 [57] | Randomized, double-blinded clinical trial | 60 | Topical TXA 5% vs. topical HQ 2% | 12 wks | MASI | MASI: significantly lower in both groups AE: none in TXA group, erythema and skin irritation in the HQ group (p = 0.131). Patient satisfaction: 33.3% in TXA group vs. 6.7% in HQ group (p = 0.015). |
Janney, M. et al., 2019 [58] | Prospective, randomized, single-blind study | 100 | Topical 5% TXA vs. 3% HQ cream | 12 wks | Serial digital photographs, MASI, patient satisfaction score | Reduction of MASI: 27% (TXA group) vs. 26.7% (HQ group); no significant difference between the groups (p > 0.05) Patient satisfaction: higher in TXA group (p = 0.03) AE: mild irritation (3/50, TXA group), mild erythema and irritation (19/50, HQ group). |
El-Husseiny, R. et al., 2020 [59] | A split-face comparative clinical trial | 100 | TXA 5% cream vs. HQ 4% cream | 12 wks | Photography, Wood’s light, Hemi-MASI, MELASQoL histopathology | Significant improvement on both TXA 5% and HQ 4% sides of the face. Hemi-MASI, MELASQOL scores, and Antera Average Level of Melanin: no significant difference between the two treatments (p > 0.05). Area % of melanin: significant reduction with TXA 5% compared to HQ 4% (p = 0.000). |
Navarrete-Solís, J. et al., 2011 [64] | Double-blind, left–right randomized clinical trial | 27 | 4% niacinamide cream vs. 4% HQ cream | 8 wks | Chromametry, calorimetry, MASI, histopathology | Chromametry: pigment improvement in both groups. Calorimetry: no statistical differences between sides (p = 0.78). MASI reduction: 70% with H vs. 62% with niacinamide. Histopathology of niacinamide-treated side: significantly decreased epidermal melanin (p < 0.0007), decreased inflammatory infiltrate (p = 0.01), reduced solar elastosis. AE (erythema, pruritus, burning): mild in 18% (niacinamide) vs. moderate in 29% (HQ). |
Anwar, A.I. et al., 2021 [71] | Double-blind randomized controlled study | 59 | 2% dA serum vs. 4% HQ, | 12 wks | Skin brightness (L* value; chromameter) MI, EI (Mexameter®) | Both 2% dA and 4% HQ showed significant skin depigmentation (increase in L* value and decrease in melanin index) at the end of the study (p < 0.05). |
Nguyen, J. et al., 2021 [72] | Randomized, double-blind, placebo-controlled trial | 17 | Oral TXA (250 mg) vs. placebo | 12 wks, follow-up at 24 wks | Clinical photographs, EI (Mexameter®) | EI: greater median decrease in TXA group vs. placebo; no statistically significant difference (p = 0.53 and 0.37, respectively). Clinical improvement only in TXA group. |
Malik, F. et al., 2019 [75] | Interventional comparative study | 100 | Oral TXA (250 mg twice daily) + topical 3% TXA vs. oral TXA (250 mg twice daily) + topical 20% AZA | 6 mo | MASI | 2 and 4 mo: no significant difference (p = 0.20, p = 0.89) 6 mo: mean MASI significantly lower in oral + topical TXA group (6.06 ± 5.06 vs. 10.62 ± 7.43, p = 0.001). |
Zhu, C.-Y. et al., 2019 [80] | Multicentre prospective clinical trial | 72 | Oral TXA at doses of 500 mg, 750 mg, 1000 mg, or 1500 mg daily | 8 wks | Clinical and VISIA® photographs, MASI, MI, blood and coagulation tests | Efficacy: all doses effective for improvement; correlated with dosage and treatment time MASI, MI: no significant differences between doses. Blood tests: D-dimers and FDP within normal range. AE: irregular menstruation, upset stomach; no significant differences between different dose groups. |
Arjinpathana, N. and Asawanonda, P. 2012 [83] | Randomized, double-blind, placebo-controlled trial | 60 | Oral GSH (500 mg/day, in two divided doses) vs. placebo | 4 wks | MI (Mexameter®) UV spots, skin evenness, and pore size (VISIA® system), self-reported satisfaction | MI: significant reductions in the GSH group, no changes in the placebo group/increase on the face (p = 0.021 and 0.036, respectively). UV spots: a smaller increase with GSH vs. placebo. Skin evenness and pore size: improved in GSH group, not statistically significant. Satisfaction: higher in the GSH group (average 3.06/4) vs. placebo group (average 2.13). AE: minimal; flatulence (GSH), constipation (placebo). |
Wahab, S. et al., 2021 [84] | Double-blind, randomized, controlled clinical trial. | 46 | Group 1: topical and oral placebo Group 2: topical GSH and oral placebo Group 3: topical placebo and oral GSH Group 4: topical and oral GSH Topical preparation: serum containing 2% GSH and vitamin C Oral preparation: 600 mg GSH, 50 mg alpha lipoic acid, 4 mg zinc picolinate | 8 wks | MI (Mexameter®) Skin brightness (L* score; chromameter) | Combination therapy showed significantly lower MI and higher L* scores compared to monotherapies and placebo (p < 0.05). L* score: statistically significant in the combination group (p < 0.05). |
Author, Year [Reference Number] | Study Design | Examinees/Patients | Treatment Method | Wks/ Mo | Method of Assessment | Results |
---|---|---|---|---|---|---|
Balevi, A. et al., 2017 [48] | Randomized, mono-blinded study | 50 | 30% SA peel + vitamin C mesotherapy vs. 30% SA peel alone, every 2 wks | 2 mo; follow-up for 6 mo | MelasQoL, MASI | MelasQoL: greater reduction in SA + vitamin C group (p < 0.046, respectively) MASI: greater decrease in SA + vitamin C group, without significant difference AE: burning sensation |
Pazyar, N. et al., 2022 [50] | Prospective, double-blind, split-face, randomized controlled clinical trial. | 24 | TXA (50 mg/mL) + ascorbic acid (50 mg/mL) vs. TXA (50 mg/mL) + placebo, every 2 wks | 12 wks, follow up-for 12 wks | MASI, pain levels | MASI: significantly lower in the intervention group at weeks 8 and 12 (p < 0.001, respectively) Pain levels: notably higher in the intervention group |
Zhang, C. et al., 2022 [125] | Retrospective analysis | 80 | Oral TXA (250 mg) vs. PRP + oral TXA (250 mg) | 3 mo, follow-up at 3 and 6 mo | MASI, serum levels of VEGF, ET-1, and MSH, AE, recurrence rates | Total efficacy: 73.68% (TXA group) vs. 90.48% (PRP +TXA group), (p < 0.05, respectively) AE: in 5.26% (TXA group) vs. 7.14% (PRP + TXA group) Disease recurrence: similar at 3 months; lower in PRP + TXA at 6 months (4.76% vs. 21.05%), (p < 0.05) VEGF, ET-1, and MSH: greater changes in oral TXA group compared to PRP + oral TXA |
Tuknayat, A. et al., 2021 [126] | Open-labelled prospective trial | 40 | PRP administered intralesionally 1/month | 3 mo, 3-mo follow-up | mMASI, patient satisfaction, AE | mMASI: 54.5% average reduction at 6 months Patient satisfaction: >90% were pleased or very pleased No relapse during follow-up AE: xerosis (35%) and pruritus (25%); no serious adverse effects |
Adel, S. et al., 2021 [127] | Randomized prospective split-face study | 20 | PRP + IPL vs. PRP alone, every 2 wks | 6 wks | MASI, mMASI, patient and physician satisfaction on a 4-point scale | MASI: decrease from 16.3 ± 7.7 to 10.9 ± 6.3 (33%) (p < 0.05) mMASI: decrease on both PRP (22.86%) and PRP + IPL (23.85%) side; not statistically significant (p-value > 0.05) Patient and physician satisfaction: no statistically significant difference (p-value > 0.05) |
Sirithanabadeekul, P. et al., 2019 [128] | Randomized, split-face, single-blinded prospective trial | 10 | PRP injected intradermally vs. normal saline; every 2 wks | 6 wks, follow-up at 10 wks | mMASI, EI, MI (Mexameter®), melanin levels (Antera® 3D), patient satisfaction | MI, EI: no statistically significant changes Melanin levels: significant reduction on the PRP-treated side (from 0.61 ± 0.02 to 0.57 ± 0.03) at week 6 (p = 0.038) mMASI: significantly greater mean improvement on the PRP side (1.03 ± 0.44) (p = 0.042) Patient satisfaction: improvement at every visit in PRP-side, no change on the saline-treated side |
Abd Elraouf, I.G. et al., 2023 [89] | Prospective, split-face, randomized, controlled clinical trial | 40 | Intradermal TXA (4 mg/mL), vs. PRP; every 4 wks | 8 wks | Digital photography, mMASI, | Mean mMASI: decreased from 4.59 to 2.49 (45.67%) on the TXA side vs. from 4.72 to 2.17 (53.66%) on the PRP side; significant improvement on both sides (p < 0.001) AE: pain and erythema more common in TXA, but not statistically significant |
Gamea, M.M. et al., 2022 [90] | Randomized controlled trial | 40 | Topical TXA 5% in liposome base (twice daily) vs. topical TXA 5% in liposome base + intradermal PRP every 3 wks | 12 wks | mMASI, patient satisfaction surveys | mMASI: mean improvement from 11.7 to 4.8 in TXA group vs. from 12.1 to 3.6 in TXA + PRP group Patient satisfaction: greater in TXA + PRP (p = 0.024, p = 0.029) |
Batra, J. et al., 2022 [93] | Randomized controlled trial | 40 | Oral TXA (250 mg, twice daily) vs. transepidermal TXA solution (4 mg/mL) (using a dermaroller) at 2-week intervals | 12 wks + 12 wks follow-up | MASI, patient satisfaction | MASI: similar decrease in both groups (oral TXA: 3.10 ± 3.38, Group B: 3.09 ± 1.32) (p < 0.0001, respectively) Patient satisfaction: slightly higher percentages of “very good” responses in oral TXA group Relapse uncommon in both groups |
Saleh, F. et al., 2019 [94] | Randomized controlled trial | 42 | 4% topical TXA + microneedling vs. microneedling alone; every 2 wks | 12 wks | MASI, photographic evaluation, histopathological evaluation, immunohistochemistry | MASI: decreased in both groups, mean reduction percentage higher in TXA + microneedling group (62.1% vs. 22.5%) (p = 0.001) Clinical improvement: better in TXA + microneedling (p = 0.001) Histopathology: greater reduction in epidermal melanin and dermal melanophages in TXA + microneedling group A substantially higher % reduction in MART-1-positive cell number in TXA + microneedling (60.8%) vs. microneedling alone (37.5%) (p = 0.001) |
Kaur, A. et al., 2020 [95] | Prospective, randomized, open-label, split-face study | 40 | Microneedling + 10% TXA vs. microneedling + distilled water; every 2 wks | 6 wks, follow-up at 8 wks | Clinical images, mMASI, patient satisfaction scores, AE | Mean mMASI: mean improvement of 65.92% (microneedling + TXA) vs. of 20.75% (microneedling+ distilled water) AE: minor (erythema, dryness, burning, pruritus); patients could not differentiate between sides Patient satisfaction: higher on microneedling + TXA side |
Zaky, M.S. et al., 2021 [96] | Prospective, randomized, open-label trial | 50 | Topical 4% HQ nightly vs. microneedling + topical 4% TXA, every other week | 8 wks | mMASI | mMASI: decreased by 54.8% in HQ group (p < 0.001) vs. by 57.4% in TXA + microneedling group (p < 0.001) |
Shamsi Meymandi, S. et al., 2020 [97] | Single-blind, randomized clinical trial | 60 | microneedling + topical 4% TXA (monthly) vs. topical 4% HQ (nightly) | 12 wks | MASI, patient and physician assessments | MASI: no significant difference between groups (decrease from 12.89 ± 5.16 to 6.84 ± 4.31 in microneedling + TXA group vs. decrease from 13.56 ± 4.88 to 7.16 ± 4.38 in HQ group) (p < 0.01) Patient satisfaction > physician satisfaction in both groups (p < 0.01) |
Kaleem, S. et al., 2020 [98] | Non-randomized clinical trial | 60 | TXA (4 mg/mL) vs. normal saline injections, 2-week intervals | 12 wks | H-mMASI, patient satisfaction | H-mMASI: decrease from 3.19 ± 2.57 to 1.52 ± 1.20 (TXA side) (p < 0.05) vs. from 3.19 ± 2.57 to 1.52 ± 1.20 (saline side) (p < 0.05); on TXA side remained at 1.62 ± 1.27 at follow-up (maintenance effect) Patient satisfaction: 90% good to excellent satisfaction with TXA, poor response on the saline side |
Agamia, N. et al., 2021 [76] | Comparative study | 60 | Oral TXA (250 mg/day) vs. oral TXA + Qs-Nd laser (1064 nm, 2 J/cm², every 2 weeks) | 3 mo | mMASI score, dermoscopy | mMASI: substantially greater decrease in oral TXA + Qs-Nd laser group (p = 0.036) dermoscopy: significant improvement in telangiectasia (both groups) AE: transient in both groups Clearance of melasma in 60% of TXA + Qs-Nd laser group before end of scheduled sessions |
Micek, I. et al., 2022 [118] | Clinical trial | 40 | 1064 nm Qs-Nd:YAG Laser pulse length 5 ns, 6–8 mm in diameter, energy density 1.7–3.5 J/cm2, 5 Hz. | 9 treatments (7 to 14-day intervals), 1-year follow-up | MI, EI (Mexameter MX18®), mMASI, participant self-assessment | MI, mMASI: significant reduction (p < 0.0001) EI: significant reduction (p < 0.001) Participant satisfaction: 70% met expectations Maintained improvement in melasma at one-year follow-up No serious AE reported |
Ertam Sagduyu, I. et al., 2022 [129] | Randomized controlled trial | 39 | Jessner peeling vs. 1064 nm Qs-Nd:YAG | 4 weeks | MASI | MASI change: Jessner peeling group (3.35 ± 3.92), vs. Qs-Nd:YAG group (4 ± 4.46), no significant difference between the groups |
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Parać, E.; Bukvić Mokos, Z. Unmasking Melasma: Confronting the Treatment Challenges. Cosmetics 2024, 11, 143. https://doi.org/10.3390/cosmetics11040143
Parać E, Bukvić Mokos Z. Unmasking Melasma: Confronting the Treatment Challenges. Cosmetics. 2024; 11(4):143. https://doi.org/10.3390/cosmetics11040143
Chicago/Turabian StyleParać, Ena, and Zrinka Bukvić Mokos. 2024. "Unmasking Melasma: Confronting the Treatment Challenges" Cosmetics 11, no. 4: 143. https://doi.org/10.3390/cosmetics11040143