黄褐斑发病机制及治疗研究进展

doi:10.35541/cjd.20250078

中华皮肤科杂志 ›› 2025, Vol. 58 ›› Issue (9): 868-872.doi: 10.35541/cjd.20250078

黄褐斑发病机制及治疗研究进展

姜子琪¹ 钟菊丹¹ 陈廷巧² 陈瑾¹

¹重庆医科大学附属第一医院皮肤科，重庆 400016；²重庆医科大学附属妇女儿童医院皮肤和医学美容科，重庆 401120

收稿日期:2025-02-18 修回日期:2025-08-07 发布日期:2025-09-01
通讯作者: 陈瑾 E-mail:chenjin7791@163.com
基金资助:
国家自然科学基金（82404174）；重庆市自然科学基金（CSTB2023NSCQ-MSX0075）；重庆市级人才计划“包干制”项目（cstc2024ycjh-bgzxm0177）；重庆医科大学附属第一医院钱惪科技人才项目（2025QDTS-11）

Pathogenesis and treatment of melasma

Jiang Ziqi¹, Zhong Judan¹, Chen Tingqiao², Chen Jin¹

¹Department of Dermatology, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; ²Department of Dermatology and Medical Aesthetics, Women and Children's Hospital of Chongqing Medical University, Chongqing 401120, China

Received:2025-02-18 Revised:2025-08-07 Published:2025-09-01
Contact: Chen Jin E-mail:chenjin7791@163.com
Supported by:
National Natural Science Foundation of China （82404174）; Natural Science Foundation of Chongqing （CSTB2023NSCQ-MSX0075）; Chongqing Talent Plan Project （cstc2024ycjh-bgzxm0177）; Qian De Science and Technology Talent Project of the First Affiliated Hospital of Chongqing Medical University （2025QDTS-11）

摘要/Abstract

摘要： 【摘要】黄褐斑的发病机制复杂，除涉及黑素细胞功能异常外，其微环境中角质形成细胞、成纤维细胞、血管内皮细胞、肥大细胞、皮脂腺细胞等交互作用的失衡也与疾病进展密切相关。本文综述黄褐斑发病机制中涉及黑素细胞及其微环境的相关研究与治疗进展。

关键词: 黄褐斑, 黑素细胞, 发病机制, 治疗, 微环境

Abstract: 【Abstract】 Melasma is an acquired pigmentation disorder with complex pathogenesis. In addition to the dysfunction of melanocytes, the imbalance of the microenvironment, particularly the multicellular interactions among keratinocytes, fibroblasts, vascular endothelial cells, mast cells, and sebocytes, also contributes to the progression of melasma. This review summarizes relevant research progress on melanocytes and their microenvironment in the pathogenesis of melasma, as well as advances in the treatment of melasma.

Key words: Melasma, Melanocytes, Pathogenesis, Therapy, Microenvironment

姜子琪钟菊丹陈廷巧陈瑾. 黄褐斑发病机制及治疗研究进展[J]. 中华皮肤科杂志, 2025,58(9):868-872. doi:10.35541/cjd.20250078

Jiang Ziqi, Zhong Judan, Chen Tingqiao, Chen Jin. Pathogenesis and treatment of melasma[J]. Chinese Journal of Dermatology, 2025, 58(9): 868-872.doi:10.35541/cjd.20250078

参考文献 60

［1］	Gu D, Pan R, Meng X, et al. What lies behind melasma: a review of the related skin microenvironment［J］. Int J Dermatol, 2025,64（2）:256⁃265. doi: 10.1111/ijd.17453.
［2］	Guida S, Longo C, Ronga R, et al. Melasma and reflectance confocal microscopy: from baseline to treatment monitoring［J］. Int J Dermatol, 2024,63（8）:1007⁃1012. doi: 10.1111/ijd.17117.
［3］	Hafeez F, Mata DA, Lian CG, et al. Prominent transepidermal melanin deposition is a distinguishing histopathological feature of melasma: a clinicopathologic study［J］. Dermatology, 2021,237（1）:145⁃147. doi: 10.1159/000504408.
［4］	Gautam M, Patil S, Nadkarni N, et al. Histopathological comparison of lesional and perilesional skin in melasma: a cross⁃sectional analysis［J］. Indian J Dermatol Venereol Leprol, 2019,85（4）:367⁃373. doi: 10.4103/ijdvl.IJDVL_866_17.
［5］	Chen IL, Wang YJ, Chang CC, et al. Computer⁃aided detection （CADe） system with optical coherent tomography for melanin morphology quantification in melasma patients［J］. Diagnostics （Basel）, 2021,11（8）doi: 10.3390/diagnostics11081498.
［6］	Wang YJ, Chang CC, Wu YH, et al. Adaptability of melanocytes post ultraviolet stimulation in patients with melasma［J］. Lasers Surg Med, 2023,55（7）:680⁃689. doi: 10.1002/lsm.23699.
［7］	Böhm M, Robert C, Malhotra S, et al. An overview of benefits and risks of chronic melanocortin⁃1 receptor activation［J］. J Eur Acad Dermatol Venereol, 2025,39（1）:39⁃51. doi: 10.1111/jdv. 20269.
［8］	Luo L, Zeng H, Hu Y, et al. The amino acid transporter SLC16A10 promotes melanogenesis by facilitating the transportation of phenylalanine［J］. Exp Dermatol, 2024,33（8）:e15165. doi: 10.1111/exd.15165.
［9］	Espósito A, de Souza NP, Miot L, et al. Deficit in autophagy: a possible mechanism involved in melanocyte hyperfunction in melasma［J］. Indian J Dermatol Venereol Leprol, 2021:1⁃3. doi: 10.25259/IJDVL_927_20.
［10］	Hakozaki T, Wang J, Laughlin T, et al. Role of interleukin⁃6 and endothelin⁃1 receptors in enhanced melanocyte dendricity of facial spots and suppression of their ligands by niacinamide and tranexamic acid［J］. J Eur Acad Dermatol Venereol, 2024,38 Suppl 2:3⁃10. doi: 10.1111/jdv.19719.
［11］	Bento⁃Lopes L, Cabaço LC, Charneca J, et al. Melanin's journey from melanocytes to keratinocytes: uncovering the molecular mechanisms of melanin transfer and processing［J］. Int J Mol Sci, 2023,24（14）. doi: 10.3390/ijms241411289.
［12］	Guo MS, Wu Q, Dong TT, et al. The UV⁃induced uptake of melanosome by skin keratinocyte is triggered by α7 nicotinic acetylcholine receptor⁃mediated phagocytosis［J］. FEBS J, 2023,290（3）:724⁃744. doi: 10.1111/febs.16613.
［13］	Murase D, Kusaka⁃Kikushima A, Hachiya A, et al. Autophagy declines with premature skin aging resulting in dynamic alterations in skin pigmentation and epidermal differentiation［J］. Int J Mol Sci, 2020,21（16）:5708. doi: 10.3390/ijms211 65708.
［14］	Kim JY, Kim J, Ahn Y, et al. Autophagy induction can regulate skin pigmentation by causing melanosome degradation in keratinocytes and melanocytes［J］. Pigment Cell Melanoma Res, 2020,33（3）:403⁃415. doi: 10.1111/pcmr.12838.
［15］	Lee KW, Ryu KJ, Kim M, et al. RCHY1 and OPTN are required for melanophagy, selective autophagy of melanosomes［J］. Proc Natl Acad Sci U S A, 2024,121（14）:e2318039121. doi: 10.1073/pnas.2318039121.
［16］	da Silva CN, Miot HA, Grassi TF, et al. Expression of endothelin⁃1, endothelin receptor⁃A, and endothelin receptor⁃B in facial melasma compared to adjacent skin［J］. Clin Cosmet Investig Dermatol, 2023,16:2847⁃2853. doi: 10.2147/CCID.S402168.
［17］	Cui YZ, Xu F, Zhou Y, et al. SPRY1 deficiency in keratinocytes induces follicular melanocyte stem cell migration to the epidermis through p53/stem cell factor/C⁃KIT signaling［J］. J Invest Dermatol, 2024,144（10）:2255⁃2266.e4. doi: 10.1016/j.jid.2024.02.018.
［18］	Shi HX, Zhang RZ, Xiao L, et al. Effects of keratinocyte⁃derived and fibroblast⁃derived exosomes on human epidermal melanocytes［J］. Indian J Dermatol Venereol Leprol, 2022,88（3）:322⁃331. doi: 10.25259/IJDVL_1087_19.
［19］	Fu C, Chen J, Lu J, et al. Roles of inflammation factors in melanogenesis （Review）［J］. Mol Med Rep, 2020,21（3）:1421⁃1430. doi: 10.3892/mmr.2020.10950.
［20］	Kim NH, Lee AY. Oxidative stress induces skin pigmentation in melasma by inhibiting hedgehog signaling［J］. Antioxidants （Basel）, 2023,12（11）. doi: 10.3390/antiox12111969.
［21］	Fang J, Ouyang M, Qu Y, et al. Advanced glycation end products promote melanogenesis by activating NLRP3 inflammasome in human dermal fibroblasts［J］. J Invest Dermatol, 2022,142（10）:2591⁃2602.e8. doi: 10.1016/j.jid.2022.03.025.
［22］	Espósito A, Brianezi G, Miot L, et al. Fibroblast morphology, growth rate and gene expression in facial melasma［J］. An Bras Dermatol, 2022,97（5）:575⁃582. doi: 10.1016/j.abd.2021.09.012.
［23］	Kim Y, Kang B, Kim JC, et al. Senescent fibroblast⁃derived GDF15 induces skin pigmentation［J］. J Invest Dermatol, 2020,140（12）:2478⁃2486.e4. doi: 10.1016/j.jid.2020.04.016.
［24］	Kapoor R, Dhatwalia SK, Kumar R, et al. Emerging role of dermal compartment in skin pigmentation: comprehensive review［J］. J Eur Acad Dermatol Venereol, 2020,34（12）:2757⁃2765. doi: 10.1111/jdv.16404.
［25］	Bellei B, Picardo M. Premature cell senescence in human skin: dual face in chronic acquired pigmentary disorders［J］. Ageing Res Rev, 2020,57:100981. doi: 10.1016/j.arr.2019.100981.
［26］	Wang Z, Chen Y, Pan S, et al. Quantitative classification of melasma with photoacoustic microscopy: a pilot study［J］. J Biomed Opt, 2024,29（Suppl 1）:S11504. doi: 10.1117/1.JBO.29.S1.S11504.
［27］	Pomerantz H, Christman MP, Bloom BS, et al. Dynamic optical coherence tomography of cutaneous blood vessels in melasma and vessel response to oral tranexamic acid［J］. Lasers Surg Med, 2021,53（6）:861⁃864. doi: 10.1002/lsm.23345.
［28］	Hara Y, Shibata T. Characteristics of dermal vascularity in melasma and solar lentigo［J］. Photodermatol Photoimmunol Photomed, 2024,40（2）:e12953. doi: 10.1111/phpp.12953.
［29］	Chang CC, Wang YJ, Huang L, et al. Photoaging features of melasma: an in vivo layered and quantitative analysis using computer⁃aided detection of cellular resolution full⁃field optical coherence tomography［J］. J Eur Acad Dermatol Venereol, 2024,38（10）:e870⁃e873. doi: 10.1111/jdv.19971.
［30］	Phansuk K, Vachiramon V, Jurairattanaporn N, et al. Dermal pathology in melasma: an update review［J］. Clin Cosmet Investig Dermatol, 2022,15:11⁃19. doi: 10.2147/CCID.S343332.
［31］	Espósito A, Brianezi G, de Souza NP, et al. Exploratory study of epidermis, basement membrane zone, upper dermis alterations and wnt pathway activation in melasma compared to adjacent and retroauricular skin［J］. Ann Dermatol, 2020,32（2）:101⁃108. doi: 10.5021/ad.2020.32.2.101.
［32］	Clayton RW, Langan EA, Ansell DM, et al. Neuroendocrinology and neurobiology of sebaceous glands［J］. Biol Rev Camb Philos Soc, 2020,95（3）:592⁃624. doi: 10.1111/brv.12579.
［33］	Flori E, Mastrofrancesco A, Mosca S, et al. Sebocytes contribute to melasma onset［J］. iScience, 2022,25（3）:103871. doi: 10. 1016/j.isci.2022.103871.
［34］	Liu LX, Liao ZK, Dong BQ, et al. Tranexamic acid ameliorates skin hyperpigmentation by downregulating endothelin⁃1 expression in dermal microvascular endothelial cells［J］. Ann Dermatol, 2024,36（3）:151⁃162. doi: 10.5021/ad.23.108.
［35］	Zhu JW, Ni YJ, Tong XY, et al. Tranexamic acid inhibits angiogenesis and melanogenesis in vitro by targeting VEGF receptors［J］. Int J Med Sci, 2020,17（7）:903⁃911. doi: 10.7150/ijms.44188.
［36］	Konisky H, Balazic E, Jaller JA, et al. Tranexamic acid in melasma: a focused review on drug administration routes［J］. J Cosmet Dermatol, 2023,22（4）:1197⁃1206. doi: 10.1111/jocd. 15589.
［37］	Poostiyan N, Alizadeh M, Shahmoradi Z, et al. Tranexamic acid microinjections versus tranexamic acid mesoneedling in the treatment of facial melasma: a randomized assessor⁃blind split⁃face controlled trial［J］. J Cosmet Dermatol, 2023,22（4）:1238⁃1244. doi: 10.1111/jocd.15580.
［38］	Jia Z, Tian K, Zhong Y, et al. Effectiveness of combination therapy of broadband light and intradermal injection of tranexamic acid in the treatment of chloasma［J］. J Cosmet Dermatol, 2023,22（5）:1536⁃1544. doi: 10.1111/jocd.15632.
［39］	Bertold C, Fontas E, Singh T, et al. Efficacy and safety of a novel triple combination cream compared to Kligman's trio for melasma: a 24⁃week double⁃blind prospective randomized controlled trial［J］. J Eur Acad Dermatol Venereol, 2023,37（12）:2601⁃2607. doi: 10.1111/jdv.19455.
［40］	Vladulescu D, Scurtu LG, Simionescu AA, et al. Platelet⁃rich plasma （PRP） in dermatology: cellular and molecular mechanisms of action［J］. Biomedicines, 2023,12（1）:7. doi: 10.3390/biomedicines12010007.
［41］	Manole CG, Soare C, Ceafalan LC, et al. Platelet⁃rich plasma in dermatology: new insights on the cellular mechanism of skin repair and regeneration［J］. Life （Basel）, 2023,14（1）. doi: 10.3390/life14010040.
［42］	Abd Elraouf IG, Obaid ZM, Fouda I. Intradermal injection of tranexamic acid versus platelet⁃rich plasma in the treatment of melasma: a split⁃face comparative study［J］. Arch Dermatol Res, 2023,315（6）:1763⁃1770. doi: 10.1007/s00403⁃023⁃02580⁃y.
［43］	Simin H, Siliang X, Wei C, et al. Efficacy of microneedle as an assisted therapy for melasma: a meta⁃analysis and systematic review of randomized controlled trials［J］. Aesthetic Plast Surg, 2025,49（6）:1755⁃1769. doi: 10.1007/s00266⁃024⁃04395⁃2.
［44］	Hofny ER, Abdel⁃Motaleb AA, Hamed SA, et al. Trichloroacetic acid with microneedling versus trichloroacetic acid alone for treating melasma［J］. Dermatol Surg, 2023,49（1）:66⁃71. doi: 10.1097/DSS.0000000000003641.
［45］	Ramírez⁃Oliveros JF, de Abreu L, Tamler C, et al. Microneedling with drug delivery （hydroquinone 4% serum） as an adjuvant therapy for recalcitrant melasma［J］. Skinmed, 2020,18（1）:38⁃40.
［46］	Bhattacharjee R, Hanumanthu V, Thakur V, et al. A randomized, open⁃label study to compare two different dosing regimens of oral tranexamic acid in treatment of moderate to severe facial melasma［J］. Arch Dermatol Res, 2023,315（6）:1831⁃1836. doi: 10.1007/s00403⁃023⁃02549⁃x.
［47］	Polat Y, Saraç G. Comparison of clinical results of oral tranexamic acid and platelet rich plasma therapies in melasma treatment［J］. Dermatol Ther, 2022,35（7）:e15499. doi: 10.1111/dth.15499.
［48］	Minni K, Poojary S. Efficacy and safety of oral tranexamic acid as an adjuvant in Indian patients with melasma: a prospective, interventional, single⁃centre, triple⁃blind, randomized, placebo⁃control, parallel group study［J］. J Eur Acad Dermatol Venereol, 2020,34（11）:2636⁃2644. doi: 10.1111/jdv.16598.
［49］	Martinez⁃Rico JC, Chavez⁃Alvarez S, Herz⁃Ruelas ME, et al. Oral tranexamic acid with a triple combination cream versus oral tranexamic acid monotherapy in the treatment of severe melasma［J］. J Cosmet Dermatol, 2022,21（8）:3451⁃3457. doi: 10.1111/jocd.14942.
［50］	Dias J, Lima PB, Cassiano DP, et al. Oral ketotifen associated with famotidine for the treatment of facial melasma: a randomized, double⁃blind, placebo⁃controlled trial［J］. J Eur Acad Dermatol Venereol, 2022,36（2）:e123⁃e125. doi: 10.1111/jdv.17692.
［51］	Han R, Sun Y, Su M. Efficacy and safety of low⁃fluence 730⁃nm picosecond laser in the treatment of melasma in Chinese patients［J］. Dermatol Surg, 2025,51（2）:166⁃170. doi: 10.1097/DSS. 0000000000004393.
［52］	Liang S, Shang S, Tan A, et al. Comparative efficacy and safety of the novel picosecond alexandrite laser and the traditional combined Q⁃switched and long⁃pulse Nd: YAG lasers in melasma treatment: a randomized evaluator⁃blinded trial［J］. Lasers Med Sci, 2025,40（1）:29. doi: 10.1007/s10103⁃025⁃04286⁃1.
［53］	Zhou Y, Li Y, Hamblin MR, et al. Comparison of 755⁃nm picosecond alexandrite laser versus 1064⁃nm Q⁃switched Nd:YAG laser for melasma: a randomized, split⁃face controlled, 2⁃year follow⁃up study［J］. Lasers Surg Med, 2024,56（3）:263⁃269. doi: 10.1002/lsm.23763.
［54］	Galache TR, Sena MM, Tassinary J, et al. Photobiomodulation for melasma treatment: Integrative review and state of the art［J］. Photodermatol Photoimmunol Photomed, 2024,40（1）:e12935. doi: 10.1111/phpp.12935.
［55］	Chen L, Xu Z, Jiang M, et al. Light⁃emitting diode 585 nm photomodulation inhibiting melanin synthesis and inducing autophagy in human melanocytes［J］. J Dermatol Sci, 2018,89（1）:11⁃18. doi: 10.1016/j.jdermsci.2017.10.001.
［56］	Jin S, Chen L, Xu Z, et al. 585 nm light⁃emitting diodes inhibit melanogenesis through upregulating H19/miR⁃675 axis in LEDs⁃irradiated keratinocytes by paracrine effect［J］. J Dermatol Sci, 2020,98（2）:102⁃108. doi: 10.1016/j.jdermsci.2020.03.002.
［57］	Dai X, Jin S, Xuan Y, et al. 590 nm LED irradiation improved erythema through inhibiting angiogenesis of human microvascular endothelial cells and ameliorated pigmentation in melasma［J］. Cells, 2022,11（24）:3949. doi: 10.3390/cells11243949.
［58］	Han HJ, Kim JC, Park YJ, et al. Targeting the dermis for melasma maintenance treatment［J］. Sci Rep, 2024,14（1）:949. doi: 10.1038/s41598⁃023⁃51133⁃w.
［59］	Gulfan M, Wanitphakdeedecha R, Wongdama S, et al. Efficacy and safety of using noninsulated microneedle radiofrequency alone versus in combination with polynucleotides for the treatment of melasma: a pilot study［J］. Dermatol Ther （Heidelb）, 2022,12（6）:1325⁃1336. doi: 10.1007/s13555⁃022⁃00728⁃8.
［60］	Mokhtari F, Bahrami B, Faghihi G, et al. Fractional erbium:YAG laser （2940 nm） plus topical hydroquinone compared to intradermal tranexamic acid plus topical hydroquinone for the treatment of refractory melasma: a randomized controlled trial［J］. J Dermatolog Treat, 2022,33（5）:2475⁃2481. doi: 10.1080/09546634.2021.1968996.

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黄褐斑发病机制及治疗研究进展

Pathogenesis and treatment of melasma

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