Dermal Pathology in Melasma: An Update Review

Figures & data

Table 1 Cell Differentiation in Dermal Pathology in Melasma

Cells	Definition	Role of Each Cell Involved in Dermal Pathologic Process
Pendulous melanocytes	- Melanocytes that protrude into the dermal layer and related to the hyperactivity of melanocytes	- Loss of basement membrane and cadherin expression by chronic UV exposure lead melanocytes to migrate deeper into the dermis
Melanophages	- Melanin-containing macrophages	- The phagocytized melanin in cytoplasmic granules within dermis layer leading to persistent of pigmentation
Fibroblasts	- Dermal resident cells, which can produce collagen and other fibers	- Upregulate the tropoelastin mRNA gene expression and elastin production by chronic UV radiation - Overexpress the cadherin 11 resulting in an increase of MMP-1 and MMP-2 expression and basement membrane disruption - Increased expression of stem cell factor
Mast cells	- Inflammatory cells that mediate inflammatory responses - The granules contain of several cytokines such as tryptase and histamine, which can be stimulated by the UV exposure	- Tryptase can activate the pro-collagenase enzymes leading to collagen degradation and elastotic materials - Produce VEGF leading to neovascularization - Produce inflammatory mediators such as TNF-α, TGF-β, IL-8

Abbreviations: IL-8, interleukin-8; MMP, matrix metalloproteinase; mRNA, messenger ribonucleic acid; TGF-β, transforming growth factor-β; TNF-α, tumor necrosis factor-α; UV, ultraviolet; VEGF, vascular endothelial growth factor.

Figure 1 Diagram demonstrated pathologic changes in the dermis of lesional melasma including basement membrane disruption, pendulous melanocytes, melanophages, mast cells, stem cell factor, solar elastosis, and neovascularization.

Figure 2 Histopathologic change in the dermis of lesional melasma. (A) Melanin deposition in the epidermis and solar elastosis in the dermis (arrow) (Hematoxylin and Eosin, HEx100) (B) pendulous melanocytes in the basal layer of epidermis (arrow) and increased dermal melanophages (arrowhead) (HE x400).

Table 2 The Dermal Pathology in Melasma Studies by the Non-Skin Biopsy Procedure

Authors/Country	N	Patients		Procedures			Result	P-value
		Sex	Skin Phototype	Methods	Location	Comparison
Kang et al (2010) France^Citation43	26	No data	Type II–V	RCM	Face	Perilesional areas	- Increased melanophages - Solar elastosis - Increased blood vessels	0.001 0.006 0.038
Costa et al (2012) Brazil^Citation44	1	Female	Type IV	RCM	Face	None	- Melanophages	N/A
Lentsch et al (2019) USA^Citation15	12	Female	Type III–V	MPM	Face	Perilesional areas	- Higher pigment amount in lesional skin epidermis - Increased solar elastosis	0.03 < 0.001
Zeng et al (2020) China^Citation45	196	163 Female	No data	RCM	Face	Normal skin	- Melanophages	N/A

Abbreviations: MPM, multiphoton microscopy; N/A, not available; RCM, reflectance confocal microscopy.

Table 3 Clinical Application from Dermal Changes in Melasma

Dermal Changes in Melasma	Specific Agents or Modalities	References
Pendulous or hyperactive melanocytes	- Whitening agents such as hydroquinone, azelaic acid, arbutin, licorice extract, linoleic acid, lignin peroxidase etc.	[^Citation46]
Solar elastosis	- Topical retinoids - Energy based devices such as fractional 2940-nm erbium:YAG, Low-fluence 1064-nm Q-switch ND:YAG, 1550-nm erbium glass laser	[^Citation47]
Mast cells	- Zinc - Tranexamic acid - Topical anti-histamine	[^Citation48,Citation49]
Neovascularization	- Tranexamic acid - Pulse dyed laser	[^Citation49^–^Citation51]

Abbreviations: ND:YAG, neodymium-doped yttrium aluminium garnet; nm, nanometer.

Kang HY, Bahadoran P, Suzuki I, et al. In vivo reflectance confocal microscopy detects pigmentary changes in melasma at a cellular level resolution. Exp Dermatol. 2010;19(8):e228–233. doi:10.1111/j.1600-0625.2009.01057.x

 PubMed Web of Science ®Google Scholar

Costa MC, Eljaiek HV, Abraham LS, Azulay-Abulafia L, Ardigo M. In vivo reflectance confocal microscopy in a typical case of melasma. An Bras Dermatol. 2012;87(5):782–784. doi:10.1590/S0365-05962012000500021

 PubMed Web of Science ®Google Scholar

Lentsch G, Balu M, Williams J, et al. In vivo multiphoton microscopy of melasma. Pigment Cell Melanoma Res. 2019;32(3):403–411. doi:10.1111/pcmr.12756

 PubMed Web of Science ®Google Scholar

Zeng X, Qiu Y, Xiang W. In vivo reflectance confocal microscopy for evaluating common facial hyperpigmentation. Skin Res Technol. 2020;26(2):215–219. doi:10.1111/srt.12782

 PubMed Web of Science ®Google Scholar

Draelos ZD. A split-face evaluation of a novel pigment-lightening agent compared with no treatment and hydroquinone. J Am Acad Dermatol. 2015;72(1):105–107. doi:10.1016/j.jaad.2014.09.011

 PubMed Web of Science ®Google Scholar

Griffiths CE, Finkel LJ, Ditre CM, Hamilton TA, Ellis CN, Voorhees JJ. Topical tretinoin (retinoic acid) improves melasma. A vehicle-controlled, clinical trial. Br J Dermatol. 1993;129(4):415–421. doi:10.1111/j.1365-2133.1993.tb03169.x

 PubMed Web of Science ®Google Scholar

Sharquie KE, Al-Mashhadani SA, Salman HA. Topical 10% zinc sulfate solution for treatment of melasma. Dermatol Surg. 2008;34(10):1346–1349. doi:10.1111/j.1524-4725.2008.34287.x

 PubMed Web of Science ®Google Scholar

Na JI, Choi SY, Yang SH, Choi HR, Kang HY, Park KC. Effect of tranexamic acid on melasma: a clinical trial with histological evaluation. J Eur Acad Dermatol Venereol. 2013;27(8):1035–1039. doi:10.1111/j.1468-3083.2012.04464.x

 PubMed Web of Science ®Google Scholar

Passeron T, Fontas E, Kang HY, Bahadoran P, Lacour JP, Ortonne JP. Melasma treatment with pulsed-dye laser and triple combination cream: a prospective, randomized, single-blind, split-face study. Arch Dermatol. 2011;147(9):1106–1108. doi:10.1001/archdermatol.2011.255

 PubMedGoogle Scholar