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Chapter

Melasma: A Review about

Pathophysiology and Treatment
Marisa Gonzaga da Cunha and Ana Paula da Silva Urzedo

Abstract

Melasma is a very common disease that is manifested by increased skin pigmenta-

tion mostly in the face but also in the décolleté, neck, and arms. It is presented as
irregular, light to dark brown spots, placed on the forehead. Cheek bones, mandible,
and supralabial region. It usually affects women in higher phototypes (III−V), more
commonly at a rate of nine women: one man. Melasma is a multifactorial disease, and
we know that some conditions, such as pregnancy, contraceptives, thyroid diseases,
hormone replacement, and solar exposure, could be a trigger to develop this illness.
Despite not being a serious condition, melasma causes discomfort for those who have
it, and it could compromise the patient’s quality of life. The goal of this chapter is to
understand the pathogenic mechanism of melasma as well as revise the treatments of
this disorder.

Keywords: melasma, melasma treatments, melasma oral treatments, laser, pulsed light
intense, peelings and melasma, hormones and melasma

1. Introduction

Melasma is a condition that affects millions of individuals around the world,

most often women than men, in the proportion of 9:1. Although it is not a serious
disease, it has a very important psychological impact on people who suffer from this
condition.
It is known to affect people with higher phototypes; it is related to exposure to UV
radiation and visible light, as well as thyroid disorders, and the use of contraceptives,
hormone replacement, and drugs for epilepsy [1, 2].

2. Methodology

The authors made research on the platform PubMed with the terms: “melasma,”
“melasma and treatment,” melasma and pathophysiology,” “melasma and new treat-
ments,” “melasma and oral treatments,” and “melasma and laser.”
More than 10,660 papers were found. The papers included in this chapter have
been published in the last 5 years.

1
Pigmentation Disorders - Etiology and Recent Advances in Treatments

3. Objective

The objective of this chapter is to review the pathophysiology of Melasma and

discuss both current treatments and the ones about to come.

4. Etiopathogenesis

For a better understanding of pigmentation disorders, it is important to under-

stand the biology of melanocytes, which are neural crest-derived cells. During
embryogenesis, melanocytes’ precursor’s cells, called melanoblasts, migrate along the
dorsolateral pathway to reach the epidermis and hair follicles.
Causes for the increase in the production of melanin:

1. Expression of proopiomelanocortin (POMC) and its derivatives by cells within

the skin;

2. Number of melanocortin-1 receptors (MC1-R) on melanocytes;

3. Release of diacylglycerol (DAG) from the plasma membrane that activates pro-
tein kinase C;

4. Induction of SOS reaction for UVR-induced cell damage;

5. Production of nitric oxide (NO) that activates the cGMP pathway;

6. Production of cytokines and growth factors by keratinocytes [3].

Five main etiopathogenic mechanisms have been detected in melasma:

1. Inappropriate activation of melanocytes;

2. Aggregation of melanin and melanosomes in the dermis and epidermis;

3. Increased number of mast cells and solar elastosis;

4. Basement membrane changes;

5. Increased vascularization.

4.1 Inappropriate activation of melanocytes

The melanocytes are more active in the area of the melasma, and when exposed
to UV radiation or visible light, they increase the production of melanin through
organelles called melanosomes.
Melanin synthesis is closely related to the enzyme tyrosinase, which, in addition
to several other enzymatic processes, will convert tyrosine into eumelanin. After this
conversion, melanin will be distributed to the keratinocytes. Keratinocytes, fibro-
blasts, and other cells of the immune system will secrete paracrine factors related to
either inflammatory stimuli or sunlight.
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Melasma: A Review about Pathophysiology and Treatment
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Extracellular matrix (ECM) glycoproteins in peripheral cutaneous nerves can also

be affected by melanogenesis. These mechanisms increase the amount of melanin in
keratinocytes in the epidermis and macrophages in the dermis.
The receptor for tyrosine kinase (c-KIT) is able to place phosphate groups on
the tyrosine residues of other proteins, as well as activate autophosphorylation. The
KIT binding membrane (m-KIT) and its soluble form (s-KIT) have demonstrated
antagonistic mechanisms in vivo and in vitro. The binding of stem cell factors (SCF) to
m-KIT induces melanogenesis, while the s-KIT production suppresses melanogenesis
in human melanocyte culture.
UVB radiation increases SCF and m-KIT levels and decreases s-KIT expres-
sion levels, resulting in increased melanogenesis. The increase in SCF levels in
the dermis together with the increase in c-KIT in the epidermis of patients with
melasma is partially mediated through cell-cell interactions between melanocytes
and fibroblasts.
Fibroblasts secrete Wnt signaling modulators, which stimulate both melanogenesis
and melanosome transfer. The Wnt/β-catenin pathway includes a large family of
proteins with different cellular functions, such as melanoblast migration, prolifera-
tion, and pigmentation induction. Wnt1 is a beaded transmembrane receptor binding,
which promotes the accumulation and stabilization of β-catenin. When incubated in
cell culture, melasma fibroblasts also enhance melanogenesis, with overexpression of
nerve-derived growth factor.
Another implicated factor is the UV radiation that induces cyclooxygenase (COX-
2). COX-2 knock-down in melanocytes results in decreased expression of tyrosinase,
protein-1 (TRP-1), TRP-2, glycoprotein 100, and MITF. Besides, COX-2 siRNA-
transfected melanocytes show a reduction of alpha MSH.
Despite the whole face being exposed to the sun, it can be observed that only some
areas, mainly the ones rich in sebaceous glands, will be affected by melasma. This may
be due to the fact that these appendages have the ability to synthesize vitamin D and
secrete various cytokines and growth factors. Sebocytes are controlled by alpha-MSH,
which suggests a connection between these cells and melanocytes. Moreover, skin
surface lipids undergo oxidation by UVR, which can activate melanin synthesis in
melanocyte culture.
There is also a marked increase in superoxide dismutase activity, as well as a
significant reduction in glutathione levels in melasma patients, leading to the belief
that these people suffer from increased oxidative stress [4, 5].

4.2 Aggregation of melanin and melanosomes in the dermis and epidermis

Biopsies of areas affected by melasma demonstrate melanin increase in both

epidermis and dermis when compared to perilesional skin.
Rupture of the basement membrane causes melanocytes to descend into the
dermis as free melanocytes (melanocyte effusion). On electron microscopy, it can be
seen that melanocytes in the area with melasma have more dendrites than those in
normal skin. They also have more mitochondria, golgi complex, rough endoplasmic
reticulum, and ribosomes in their cytoplasm [4].

4.3 Increased number of mast cells and solar elastosis

Solar elastosis is the abnormal accumulation of elastic tissue in a dermis that is

chronically exposed to the sun, and this occurs in 83−93% of patients with melasma.
3
Pigmentation Disorders - Etiology and Recent Advances in Treatments

Mast cells are most prominent in the elastotic areas of the skin affected by
melasma. In the development of solar elastosis, mast cells have been shown to induce
fibroblasts to produce elastin, either directly or indirectly through other cells or cyto-
kines. Mast cells are capable of inducing vascular proliferation by various angiogenic
factors, such as VEGF, basic fibroblast growth factor (bFGF-2), and transforming
growth factor beta (TGF-β).
Mast cell tryptase and granzyme B are involved in basement membrane degrada-
tion after UV irradiation. Mast cells are involved with solar elastosis, vasodilation,
and basement membrane rupture, which can be seen in histology [4].

4.4 Basement membrane changes

The rupture of the basement membrane (BM) is described in several studies.

Vacuolar degeneration of basement cells and vacuolar degeneration of the basement
membrane and subbasement membrane region have been described.
Chronic exposure to UV radiation results in increased levels of matrix metal-
loproteinase 2 (MMP2), which degrades collagens IV and VI, leading to basement
membrane rupture. This allows melanocytes to descend through the dermis, which is
known as pendant melanocytes, and they can contribute to pigmentation both during
their migration into the dermis and after trauma or treatment.
BM damage, due to aging, environment, and iatrogenic factors, could facilitate the
migration of active melanocytes and melanin to the dermis, leading to the accumula-
tion of free melanin or melanophages, thus explaining the persistent hyperpigmenta-
tion in melasma.
BM degradation is also mediated by mast cells as seen above. The degradation
of these cells releases tryptase that can activate MMPs and cause direct damage to
extracellular matrix proteins.
Granzyme B, a serine protease expressed by a variety of immune and nonimmune
cells (including mast cells), accumulates in the extracellular space during chronic
inflammation and cleavage of various extracellular matrix proteins, possibly leading
to the ECM degradation after UV irradiation.
Melasma presents an accumulation of photodamaged fibroblasts, which leads us
to believe that the aging caused by UV radiation may be involved in the genesis of this
disease.
BM degradation may facilitate the transfer of multiple growth factors between
dermis and epidermis, which could lead to persistent hyperpigmentation [4].

4.5 Increased vascularization

A pronounced increase in vascularity is seen in melasma, and this can also be

observed in various inflammatory conditions, including the response to UV radiation.
Vascular endothelial growth factor (VEGF) is increased in the vessels in areas
affected by melasma. Normal human melanocytes express VEGF receptors in vitro.
Some of these receptors are functional, suggesting that VEGF plays a role in melano-
cyte behavior in the skin.
VEGF binds to specific receptors, which are also found on endothelial cells that
have been shown to stimulate pigmentation through the production of endothelin 1.
Endothelin 1 is released by the endothelium of microvessels inducing melanogenesis,
characterized by MIFT phosphorylation and increased tyrosinase levels. VEGF
also influences melanocytes by stimulating the release of arachidonic acid and the
4
Melasma: A Review about Pathophysiology and Treatment
DOI: [Link]

subsequent activation of phospholipase A. The increased production of melanin may

result from metabolites that are secreted in the arachidonic acid pathway. VEGF may
also partially affect pigmentation through positive regulation of the expression of
protease-activated receptors (PAR-2), especially in melasma patients with prominent
telangiectatic erythema.
Sex hormones alone, mainly estrogen, are not capable of inducing melasma
pigmentation, but they act synergistically with UVB radiation. However, estrogen can
perpetuate hyperpigmentation by increasing vascularity, which, in turn, stimulates
endothelin 1 secretion. As the sensitivity of cells to sex hormones is an individual
factor, this could probably explain the variability in susceptibility to developing the
disease [2, 4].

4.6 The role of visible light in melasma

A follow-up study by Regazzetti et al. was performed on normal human melano-

cytes (NHMs) in order to understand the mechanisms of blue-light-induced hyper-
pigmentation. Blue light has been shown to stimulate melanogenesis by acting on the
microphthalmia-associated transcription factor (MITF), the master pigmentation
gene.
Photons are absorbed and converted into a cellular response through a class of
G-protein-coupled receptors called opsins, which are light-activated. Traditionally,
opsins are well known for their role in the photoreception of the eye. However, recent
studies have shown that rhodopsin (OPN2), cone opsins (OPN1-SW), encephalopsin/
opsin-3 (OPN3), and neuropsin (OPN5) are expressed both in melanocytes and
keratinocytes. Notably, OPN2 and OPN3 were significantly more abundant than other
opsins. In Regazzetti’s study, after irradiating normal human melanocytes with blue
light, OPN3 was the only significantly expressed opsin. To investigate whether OPN3
could mediate the effects of blue light melanogenesis, OPN3 was knocked down using
small interfering RNA (siRNA). In NHMs with siRNA directed against OPN3, blue
light irradiation no longer had an effect on MITF phosphorylation [6].

5. Treatment

As melasma has a lot of pathways to induce melanogenesis, the treatment must

include many topical and systemic drugs. Antioxidants and photo protectors, as well
as lightning, laser, peeling, and other procedures are usually indicated.
In the paragraph below, we will discuss the indicated treatments and their mecha-
nisms of action (Tables 1 and 2).
Treating melasma is a challenge, and it is known that the treatment must address
the various mechanisms of hyperpigmentation of this condition.
The most frequently cited depigmenting topical agent in literature is still hydro-
quinone. It works by inhibiting the conversion of 1–3,4-dihydroxyphenylalanine into
melanin by competitive inhibition of tyrosinase. Although the risk seems to be only
theoretical, there might be side effects, such as exogenous ochronosis, permanent
depigmentation, and potential carcinogenic risk.
Up to now, other depigmenting agents considered safer to date are 4-n-butylresor-
cinol, niacinamide, ascorbic acid, resveratrol, azelaic acid, and kojic acid. However,
depigmenting agents alone are not able to improve the photoaging issue closely
related to melasma. Therefore, antiaging agents should be associated in order to try
5
Pigmentation Disorders - Etiology and Recent Advances in Treatments

Active Mechanism of action Drug concentration

Hydroquinone Tyrosinase inhibitor 2−4%

4-N-butyl resorcinol Tyrosinase inhibitor 2−4%

Niacinamide Reduction of melanosome transfer anti- 5−10%

inflammatory antiaging

Ascorbic acid Antioxidant Tyrosinase inhibitor 5−25%

photoprotective effects

Azelaic acid Antiaging effect antiaging 10−20%

Kojic acid Tyrosinase inhibitor trapping free radicals 1−4%

Triple combination Depigment effect Tyrosinase inhibitor 4%, 0,05%

Hydroquinone tretinoin, Anti-inflammatory effect 0,01%
fluocinolone acetonide

Arbutin Tyrosinase inhibitor 1−3%

N-acetyl-4 s cysteamine phenol Antioxidant effects 5%

(NCAP4%)

Resveratrol Melanogenesis inhibitor Tyrosinase inhibitor 1%

Table 1.
Mainly topical treatments for melasma.

Korean red ginseng powder Korean red ginseng powder shows good tolerability and beneficial
effects for melasma

Polypodium leucotomos Oral PLE is not significantly better than placebo as an adjunct to topical
sunscreen for melasma oral polypodium leucotomos extract appears to
be a safe and effective adjunctive treatment in combination with topical
hydroquinone and sunscreen for melasma

Pycnogenol/grape seed extract Pycnogenol 75 mg is therapeutically effective and safe in patients

suffering from melasma
Grape seed extract is safe and useful for improving chloasma

Vitamin E Vitamin C + E combination treatment has significantly better results

than vitamin C alone for chloasma
Oral procyanidin + vitamins A, C, and E are safe and effective for
epidermal melasma.
Refs. [7–10].

Table 2.
Oral treatments for melasma.

and correct the photodamage, as this may be related to the frequent recurrences of
this condition.
The triple combination containing hydroquinone (HQ ) 4%, 0.05% tretinoin,
and 0.01% fluocinolone acetonide is the only FDA-approved drug that contains HQ
for the treatment of melasma. Tretinoin has depigmenting and antiaging effects.
Steroids inhibit the secretion of both ET-1 and granulocyte-macrophage colony-
stimulating factor (GM-CSF), acting against the inflammation present in melasma,
which is related to photodamage and melanogenesis. Azelaic acid is an anti-inflam-
matory agent with depigmenting properties that have been reported to reverse the
aging of human fibroblasts after PUVA induction. It also inhibits the secretion of
MMP-1 and growth factors, such as the hepatocyte growth factor (HGF) and the
6
Melasma: A Review about Pathophysiology and Treatment
DOI: [Link]

SCF, through the activation of the peroxisome proliferator-activated gamma recep-

tor (PPARy).
Wnt antagonists, including cardamonin and FTY720 (fingolimod), have been
shown to suppress melanogenesis in vitro. A recent study has demonstrated that
andropholide inhibits tyrosinase activity and melanin production via the Beta-catenin
degradation into B16F10 in the UVB-induced melanoma cells in guinea pigs [6].

5.1 New topical agents that target hyperactive melanocytes

Linoleic acid: has selectivity for tyrosinase in hyperactive melanocytes and

decreases UVB-induced hyperpigmentation.
Ascorbic acid: decreases dopaquinone oxidation into DHICA dihydrxyindole-
2-carboxylic acid), lowers tyrosinase activity, reduces dermal damage, promotes col-
lagen synthesis, and has both antioxidant and photoprotective effects, thus reducing
pigmentation.
N-acetyl-4S cysteamine phenol (NCAP4%): less irritating and more stable than
hydroquinone, is a tyrosinase inhibitor in hyperactive melanocytes, interfering with
the thiol system, decreasing intracellular glutathione, and favoring pheomelanin
synthesis [11].

5.2 New agents targeting melanogenesis

Aloesin: aloe vera extract that inhibits the conversion of tyrosinase into DOPA and
of DOPA to dopachrome.
Rucinol (4-n-butylresorcinol): a phenolic derivative that inhibits tyrosinase and
TYRP-1.
Flavonoids: benzopyrene derivatives, which are competitive inhibitors of
tyrosinase with anti-inflammatory effects and antioxidant properties. Hesperidin: a
flavonoid that protects against free radical-induced damage caused by UVR.
Epigallocatechin gallate: a phenolic compound, extracted from green tea, which
inhibits melanogenesis and has a significant anti-inflammatory, antioxidant and
anti-cancer effect.
Ellagic acid: a polyphenol derived from green tea, strawberries, and pomegranate
that can inhibit tyrosinase and melanocytic proliferation.
Gentisic acid: a compound extracted from the gentile roots that inhibit melanin
synthesis.
Hydroxycoumarin: occurs naturally in lactones that inhibit tyrosinase due to their
antioxidant action. Umbelliferone (7-hydroxycoumarin) has anti-inflammatory action.
Cinnamic acid: derived from ginseng, inhibits tyrosinase and is more potent than
hydroquinone.
Antisense oligonucleotides: act as a bleaching agent by downregulating the
production of enzymes that involve melanogenesis and decrease the activity of DOPA
oxidase [11].

5.3 Agents against reactive oxygen species (ROS) and inflammation

Liquorice extract: derived from the root of Glycyrrhiza glabra, inhibits melanin
synthesis and disperses melanin, in addition to decreasing ROS production. It has
anti-inflammatory effects and decreases UVB-induced hyperpigmentation in guinea
pigs after 3 weeks of use.
7
Pigmentation Disorders - Etiology and Recent Advances in Treatments

Acidified amino acid peels: peels with a pH close to the skin’s pH have antioxidant
and tyrosinase inhibitory effects.
Orchid extract: strong antioxidant activity. It has proven to be as effective as
vitamin C in a study with 48 melasma patients.
Coffeeberry extract: has antioxidant properties and reduces hyperpigmentation as
well as photodamage.
Mulberry extract: derived from the Morus alba, its extract is a free radical chelator
and a tyrosinase inhibitor.
Pycnogenol (oral): derived from the bark of Pinus pinaster, it presents antioxidant
and anti-inflammatory activity.
Polypodium leucotomos (oral): this extract works by inhibiting UVR-induced
ROS, including superoxide anions.
Alpha tocopherol: strong anti-inflammatory and marked antioxidant activity.
Proanthocyanidin (oral): grape seed extract with antioxidant action. A study
conducted on women submitted to a 6-month treatment has shown whitening in 10
out of 12 women [11].

5.4 Melanosomal transfer: Protease-activated receptor2

Niacinamide or vitamin B3: active amide of niacin, interferes with melanosome

transfer to the surrounding keratinocytes by inhibiting PAR-2.
Liquiritin: leads to a skin-lightening effect through dispersion of melanin.
Soymilk, soybean (topical): the serine protease inhibitors, such as soy trypsin
inhibitor (STI) and Bowman-Birk inhibitor (BBI), found in soybeans have been
shown to inhibit melanosome phagocytosis by keratinocytes via the inhibition of
PAR-2. Newer agents that target the defective barrier, such as soy topically applied
and active soy moisturizers containing nondenatured serine protease inhibitors
(STI and BBI), can decrease UVB-induced pigmentation by restoring the skin
barrier [11].

5.5 Agents targeting the vascular component

The systemic tranexamic acid (TXA) is an anti-fibrinolytic agent, which has

been shown to be an inhibitor of both UV-radiation-induced melanogenesis and
neovascularization, by blocking the plasminogen activator and plasmin activ-
ity. Oral administration is at a dose of 250 mg from 2 to 3 times a day for 2 to
3 months, with a significant decrease in both melanin and erythema indexes in
the skin with melanin lesions. Histology demonstrates a decrease in pigment,
number of vessels, and mast cells. There is a decrease in ET-1 expression. Despite
being well tolerated, we must be aware that this drug has, in theory, thrombogenic
potential. TXA can also be injected in intradermotherapy associated with lasers
and microneedling, but there are not enough studies and the results are still
limited [11].

5.6 Agents that target mast cells

5.6.1 Tranexamic acid

Zinc: reduces mast cell secretion and has an antioxidant effect [11].

8
Melasma: A Review about Pathophysiology and Treatment
DOI: [Link]

5.7 Agents with hormonal targets

Flutamide is an antiandrogenic agent that can influence alpha-melanocyte-

stimulating hormone and cyclic adenosine monophosphate, which are key regulators
of melanogenesis [11].

5.8 Newer agents with unique mechanisms: Potential targets of the future

Curcumin (topical) is a bioactive compound extracted from the rhizome of

Curcuma longa and its use is well-established in traditional Chinese medicine for the
treatment of various skin diseases. It inhibits UVB-induced production of ROS and
the expression of matrix metalloproteinase in vitro by blocking the activation of
the UVB-induced mitogen-activated protein kinase, the nuclear factor-κB, and the
AP-1 transcription factor signal pathway. Curcumin gel has been useful in the repair
of photodamaged skin as well as for the associated pigmentary changes and solar
elastosis. In view of its anti-inflammatory, free radical scavenging, and UV-protective
activities, curcumin may serve as a new skin-lightening agent in the future, both in
topical and oral preparations.
Lignin peroxidase (LP, topical use) is an enzyme derived from the fungus
Phanerochaete chrysosporium. Since lignin is structurally similar to melanin,
lignin-degrading enzymes can be utilized to decolorize melanin. Lignin peroxidase is
marketed as a formulation containing the active enzymatic component and its activa-
tor (hydrogen peroxide), causing the destruction of eumelanin.
Treatments with technologies, such as intense pulsed light (IPL), fractional
laser, 1550 nm nonablative laser, Q-Switched neodynium-doped yttrium aluminum
garnet laser (QSNYL), pulsed dye laser (PDL), and copper-bromide laser, have
shown positive results. Laser toning using collimated, low fluence, 1064 nm QSNYL
removes melanosomes and damages the dendrites of melanocytes without destroying
the entire melanocyte (“subcellular selective photothermolysis”). Nevertheless, the
accumulation of energy from several sessions can cause depigmented mottling lesions
similar to scars, which makes melanogenesis difficult [11, 12].
Newer sunscreens: visible light (VL) and infrared light (IR) have been shown
to play an important role in hyperpigmentation, especially in the darker skin types
(III, IV, or V). VL may induce the production of ROS, leading to DNA damage. IR
light provokes the activation of the endothelin receptor B and the mitogen-activated
protein kinase, which facilitates melanogenesis. Sunscreens containing iron-oxide are
effective against hyperpigmentation induced by VL.
Other new UV-VL sunscreens that allow absorption of the radiation in the VL
spectrum and systemic antioxidants, such as vitamin A, C, and E, carotenoids, and
beta-carotene, may provide additive protection. Nonorganic and organic filters that
absorb or reflect IR are currently available. Also, topical antioxidants may be able
to offer some protection against IR-related damage. However, their clinical efficacy
remains to be determined.

6. Discussion

Melasma is a multifactorial disease and until now there is not a universal treatment
to solve it. At the moment, the first choice to treat melasma is the triple association

9
Pigmentation Disorders - Etiology and Recent Advances in Treatments

of tretinoin, hydroquinone, and fluocinolone acetonide associated with a broad-

spectrum pigmented sunscreen, but this treatment presents some side effects, such
as exogenous ochronosis and depigmentation, in confetti when used for a long time.
Despite all the knowledge about the pathophysiology of melasma, we do not have the
cure for the disease. There are many new drugs with different targets to control the
pigmentation, but, unfortunately, there is often resurgence of melasma. The discov-
ery of the influence of the vessels in the pathogenesis of melasma was very important,
and there are some papers about the use of oral tranexamic acid with encouraging
results, but these treatment regimens must be reserved for refractory cases.
Concerning peeling, laser, and other technologies, some publications show good
results, but there is not a big study with a long follow-up period to confirm efficacy. It
is very important to bear in mind that melasma is a chronic disease and these treat-
ments, which are very expensive for the patients, could sometimes generate false
expectations.

7. Conclusion

Melasma is a very common disease that is a challenge to manage. More research

about de pathogenesis of the disease is necessary, leading to the development of new
drugs and therapies to control it.
To sum up, the most interesting approach to treat the disease involves a rotation of
treatments and removing the causes that worsen the condition, as well as teaching the
patient to make up and camouflage the lesions.

8. Key points in this chapter

1. Melasma is a multifactorial disease.

2. Sunscreen with pigment has a very important role in the treatment.

3. Topical treatment with different targets in the pathophysiology of melasma

could control the disease.

4. Laser, peelings, and micro-needling could be an interesting adjuvant treatment.

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Melasma: A Review about Pathophysiology and Treatment
DOI: [Link]

Author details

Marisa Gonzaga da Cunha1 and Ana Paula da Silva Urzedo2*

1 Cosmiatry Department, Faculdade de Medicina do ABC Department of

Dermatology, SP, Brazil

2 Cosmiatry Clinic, Faculdade de Medicina do ABC Department of Dermatology,

Brazil

*Address all correspondence to: apurzedo.71@[Link]

© 2022 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of
the Creative Commons Attribution License ([Link]
which permits unrestricted use, distribution, and reproduction in any medium, provided
the original work is properly cited.
11
Pigmentation Disorders - Etiology and Recent Advances in Treatments

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