Review Article

Latin American consensus on the treatment of melasma

Jorge Ocampo-Candiani,1 Roberto Alas-Carbajal,2 Jorge F. Bonifaz-Araujo,3
Hernando Mar
ın-Castro,4 Fernando Valenzuela-Ahumada,5
Jose
Luis Ve

liz-Barandiara

n,6 Agustina Vila Echague,7 David E. Zepeda-Reyes8 and
9
Helio A. Miot

1
Facultad de Medicina and Hospital Abstract

E. Gonzalez”,
Universitario “Dr. Jose Melasma is a chronic, relapsing hyperpigmentation disorder that primarily affects
Servicio de Dermatolog
ıa, Universidad
photoexposed areas, occurring most frequently in adult women with darker skin
Auto
noma de Nuevo Leo
n, Monterrey, N.L,
Mexico, 2IDCA Dermatolog
ıa and Hospital
phototypes. The primary factors contributing to its development include sun exposure, sex
Vivian Pellas, Managua, Nicaragua, hormones (e.g., pregnancy), and genetic predisposition. Melasma is highly prevalent in
3
Universidad Ute—Centro de Alta Latin America, where many countries lie in intertropical zones and exhibit significant ethnic
Especialidad Dermatolo
gica Skinpro, Quito, diversity because of centuries of intermixing among Native Americans, Europeans, and
Ecuador, 4Departamento de Dermatolog
ıa,
Sub-Saharan Africans. Nine Latin American experts formulated a DELPHI-based
Helpharma, CLIPSO (Cl
ınica para el
consensus to develop a valuable approach for treating melasma in this diverse population.
Manejo de Enfermedades
Inmunomediadas), Medellin, Colombia, After establishing an accurate diagnosis, assessing the impact on quality of life, and
5
Facultad de Medicina, Universidad de determining disease severity, the consensus recommends mitigating known triggers and
Chile, Santiago, Chile, 6Facultad de promoting rigorous photoprotection. Active therapy should be tailored based on individual
Medicina and CiruDerm, UNMSM, Lima,
characteristics (e.g., pregnancy status, previous treatments, skin sensitivity). Treatment
Peru, 7Private Practice, Buenos Aires,
Argentina, 8Zepeda Dermatolog
ıa, San
options include topical depigmenting agents, systemic therapies, and procedural
Salvador, El Salvador; and 9Departamento interventions such as laser therapy, microneedling, and chemical peels. Periodic
de Dermatolog
ıa, FMB-Unesp, Botucatu, reassessment of the treatment is essential, with strategies adjusted if targeted outcomes
SP, Brazil are not achieved. Once clinical remission is attained, patients should continue using topical
depigmenting agents and maintain strict photoprotection measures to prevent recurrence.
Keywords
melanosis; melasma; therapy; topical drugs;
consensus; Latin America.

Correspondence
Jorge Ocampo-Candiani
Facultad de Medicina and Hospital

E. Gonzalez”,
Universitario “Dr. Jose
Servicio de Dermatolog
ıa
Universidad Auto
noma de Nuevo Leo
n
Avenida Madero y Gonzalitos s/n
Colonia Mitras Centro
Monterrey N.L. 64460
Me
xico
E-mail: [email protected]

Conflict of interest: J. Ocampo-Candiani is

a speaker/advisor for Beiersdorf, Isd
ın,
Loreal, Pierre Fabre, Merz Aesthetics,
Novartis Pharmaceuticals Corp, and
receives institutional investigator’s
honoraria from Abbott Laboratories, Anacor
Pharmaceuticals, Inc., Bayer, Bristol. Myers
Squibb, Galderma Laboratories, L.P. (and
personal), GlaxoSmithKline, Janssen-Ortho
Inc., Merz Aesthetics (and personal),
Novartis Pharmaceuticals Corp. (and
personal), and Pfizer Inc. R. Alas Carbajal
1

ª 2024 the International Society of Dermatology. International Journal of Dermatology 2024

2 Review Article Latin American consensus

is on the advisory boards of Dermix and

Eucerin and is a speaker for Roche,
Eucerin, Dermix, and Medihealth. J.F.
Bonifaz Araujo receives funding from
Loreal, Eucerin, and Naos. H.E.
Marin-Castro HE is on the advisory boards
of Eucerin and Cantabria Labs and is a
speaker for Biopas, Novartis, ABBOTT,
Loreal, Naos, Eucerin, Sanofi, and Sensilis.
F. Valenzuela. Ahumada F is an advisor or
received speaking fees/participated in
clinical trials sponsored by AbbVie, Amgen,
Beiersdorf, Eli Lilly, LEO Pharma, Janssen-
Cilag, Novartis, Pfizer, UCB, and Sanofi.
J.L. Ve
liz Barandiara
n is a speaker for
Abbvie, Galderma, and Eucerin. A.
Vila-Echague is a speaker,
investigator/advisor for Candela, Deka, and
Nordlyss. D.E. Zepeda-Reyes is a speaker
and advisor for Beiersdorf, Loreal, and
Dermbiont Inc. and an investigator for Taro
Pharmaceutical and Novartis
Pharmaceutical Corp. H.A Miot is a speaker
and advisor for Beiersdorf, Isd
ın, Loreal
and Pierre Fabre.

Funding source: None.

doi: 10.1111/ijd.17522

Several factors contributing to a decreased quality of life, as

Introduction
measured by the MelaQoL, include a history of previous treat-
Melasma is a chronic acquired and relapsing hyperpigmentation ments for melasma (indicative of recurrence) and a history of
disorder characterized by significant dysfunction in melanogene- mental or mood disorders.11
sis because of complex interactions between the epidermis and
dermis involving multiple cell types. Ultraviolet light (UV) expo- Physiopathology
sure impacts the epidermis and upper dermis, triggering the Melanogenesis is regulated through various signaling networks.
production of various mediators of dermal inflammation, endo- Although melasma is clinically characterized by epidermal
thelial proliferation, fibrosis activation, and increased hyperpigmentation, the histopathological changes affect both
melanogenesis,1,2 among other factors.3,4 the epidermis and upper dermis. Figure 2 outlines the predomi-
Melasma diagnosis relies on its clinical manifestations nant mechanisms involved in the skin changes observed in indi-
(Table 1). It presents as brown patches, especially on the face. viduals with melasma.
The Melasma Area and Severity Index (MASI) is widely used.5
Supporting diagnostic tools are available.6–8 Epidemiology
The differential diagnosis of melasma includes several skin Melasma is one of the five most common dermatoses in Mexico
conditions involving hyperpigmentation (Table 2). and Brazil and a leading cause of dermatological
consultation.1,12–17 However, as Table 3 illustrates, epidemiolog-
Quality of life ical data on melasma in Latin America are limited and variable.
Despite being asymptomatic, pigmentary disorders can signifi- According to Cestari et al., the overall prevalence in the Latin
cantly impact the quality of life. Melasma affects appearance American population is 10%.18 The Brazilian Society of Dermatol-
and interpersonal relationships.9,10 Psychometric questionnaires ogy conducted a survey in 2024, where the prevalence of facial
are employed to evaluate this negative impact on the quality of melasma was 36.3%.19 Pregnant Latinas have a prevalence
life. Figure 1 summarizes the characteristics of two tools, the between 50% and 80%, a third of them with a chronic form, sug-
Dermatology Life Quality Index (DLQI) and the Melasma Quality gesting that Latino ancestry could be a predictive factor.16
of Life Scale (MelaQoL), for assessing patients’ quality of life The frequency of pigmentation disorders is likely higher in the
with melasma. Latino population.20

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 Latin American consensus Review Article 3

Table 1 The main characteristics involved in the diagnosis Table 2 Foremost differential diagnoses of melasma
of melasma
Condition Differential features
Domain Characteristics
Postinflammatory Brown, pink, or red spots with irregular
Clinical Acquired hyperpigmentation characterized by brown hyperpigmentation distribution coinciding with an area of previous
manifestations patches with irregular, symmetrical, and generally injury or inflammation
bilateral borders located in photoexposed areas of Friction melanosis Because of chronic irritation in areas of constant
the face friction such as the neck, armpits, or groin
Associated Mostly asymptomatic. There may be pruritus, tingling, Pigmented lichen Dark brown to black, flat, itchy lesions
symptoms xerosis, redness or telangiectasias planus
Affected Young, adult women, mainly of Asian or Hispanic Poikiloderma of It affects the neck and lower part of the face,
population origin and most frequently in Fitzpatrick skin Civatte causing irregularly distributed redness,
phototypes III and IV telangiectasias, atrophy, and pigmentation
Anatomical • Centrofacial pattern: forehead, cheeks, nose, upper Ephelides Small, numerous, and typically darker in the
regions where lip, and chin summer
it manifests • Malar pattern: lateral areas of the cheeks Solar lentigo Well-defined lesions associated with chronic sun
itself • Mandibular pattern: lower jaw exposure in older adults
• Extrafacial melasma: at older ages, associated with Riehl’s melanosis Result of contact dermatitis, often related to
menopause cosmetics and with a cross-linked pattern
Evaluation MASI and its modifications Ochronosis It can be endogenous (congenital) or exogenous
Severity Mild, moderate, or severe (associated with hydroquinone use); both have
Support for the • Wood lamp examination blue or black spots
diagnosis • Dermoscopy Hori’s nevus Hyperpigmented macules in the periocular area,
• Confocal microscopy bilateral and symmetrical, blue-gray in tone
Addison’s disease Endocrine condition, with generalized
Leading domains that support the diagnosis, classification, and eval- hyperpigmentation, affects the mucous
uation of melasma. membranes
MASI, Melasma Area and Severity Index. Fusca line Hyperpigmented band of light brown that extends
horizontally along the forehead, respecting the
hairline
In Peru, melasma comprises between 4% and 10% of new Pigment A homogeneous, bilateral, well-defined
dermatology referrals.21 In Puerto Rico, men accounted for 10% demarcation lines hyperpigmented patch that is located and
of melasma cases.22 on the face extends from the lateral orbital edges or corners
of the mouth
Results of three studies evaluating Latino male workers in
Maturational It affects temporal and periocular regions in dark-
North Carolina (USA) implied that genetic factors influence the pigmentation skinned people and is usually associated with
prevalence of the disease.20 insulin resistance

Associated factors Diverse features of other hyperpigmentation conditions than

Exposure to UV radiation is the most critical factor associated melasma.

with the development of melasma,3,14 followed in order by

others, as illustrated in Figure 3. questions to settle these controversies were formulated to be
solved following the DELPHI methodology through an anony-
Methodology mous survey round.23 In February 2024, the DELPHI survey
From September 2023 to May 2024, nine Latin American der- results were presented, the second draft of the manuscript
matologists from Argentina, Brazil, Chile, Colombia, Ecuador, El was reviewed, and the topics that did not reach at least 75%
Salvador, Mexico, Nicaragua, and Peru, all with recognized aca- of participants’ agreement were formulated as questions for a
demic careers, clinical practices, and scientific expertise, collab- second round DELPHI survey. In April, the second DELPHI
orated to collect and analyze international and Latin American survey results were presented, the final draft of the manu-
publications on melasma. script was reviewed, and a plan for the final submission docu-
The collaboration began with an initial meeting in Septem- ment was accepted. In May 2024, the final submission
ber 2023. Relevant topics were defined and assigned to document was reviewed, and the submission process was
experts to identify and review current literature to generate planned.
baseline updated information on melasma. In October, experts The results reflect the viewpoints unanimously agreed upon
analyzed the baseline information to specify the final topics for by the participating experts. Unsettled issues were considered
the consensus and agreed upon developing the first draft. In consensual when at least 75% of participants agreed. Poll distri-
December, the first draft was reviewed. Topics where no bution for controversial issues not reaching consensus was
unanimous consensus was reached were identified, and included in the results where relevant.

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4 Review Article Latin American consensus

Figure 1 The influence of melasma on patients’ quality of life is primarily reflected in emotional distress, expressed by dissatisfaction,
frustration, shame, depression related to their skin condition, and feeling “unattractive,” affecting their social life10

Since VL also induces pigmentation,31 a broad-spectrum sun-

Results and discussion
screen with iron oxide as a VL-absorbing pigment is
The baseline reviewed information was summarized in the intro- recommended.32 Oral antioxidants are considered a comple-
duction of this paper. mentary treatment to photoprotection.33
Melasma is the leading cause of dermatological consultation
in Latin America, and its management remains unstandardized Topical agents
because of circumstances such as ethnic diversity across geo- Topical agents are prevailing elements of melasma treatment.
graphical regions.24–26 As is common in other medical areas,27 The decision on which agents to use is influenced not only by
existing treatment guidelines for melasma are based on scien- scientific evidence but also by regional availability, ethnicity,
tific evidence and incorporate expert opinions to fill evidence drugs’ safety profile, suitability during pregnancy, skin sensitiv-
gaps. In Latin America, published treatment guidelines include a ity, and the intensity of sun exposure. Topical treatments’ ancil-
regional one in 200919 and a national one in Mexico (2018),1 lary antioxidant, anti-inflammatory, and broad-spectrum
Chile (2021),28 Peru (2021),29 and Brazil (2022).30 photoprotection actions should be considered.
Table 4 lists the unanimous consensus statements and those Table 6 presents selected clinically efficacious topical agents,
with a ≥ 75% agreement in the Delphi surveys, and Table 5 lists including new substances such as isobutylamido thiazolyl resor-
the differences identified between existing continental guide- cinol (ITR) (ThiamidolTM), niacinamide, and tranexamic acid
lines. Topics that did not reach a consensus are indicated in the (TA), promising alternatives with satisfactory results. However,
corresponding section of the discussion. A melasma manage- more randomized, placebo-controlled trials involving large
ment algorithm for Latin American countries was developed as patient groups are needed to confirm their efficiency.34
part of the consensus. Arbutin is a hydroquinone variant with a
concentration-dependent melanogenesis inhibition and a com-
Treatments ponent of various depigmenting products.35
Managing melasma is a challenge demanding a comprehensive Azelaic acid inhibits tyrosinase and has antiproliferative and
understanding of its etiology, triggering factors, and variability in cytotoxic properties against tumor cells. Its clinical efficacy is
patient response to therapeutic interventions. Factors such as equal to 4% hydroquinone and superior to 2% hydroquinone.36
pregnancy, the use of phototoxic drugs, sun exposure patterns, Glycolic acid inhibits tyrosinase, facilitates skin turnover, and
and previous treatment outcomes must be considered. Thera- reduces melanin formation. It enhances the efficacy of other
peutic approaches are often combined for optimal results. topical treatments, especially on darker skin, where it works
more quickly. Glycolic acid can be more irritating than hydroqui-
Photoprotection none alone, and there is a small risk of postinflammatory hyper-
Photoprotection is essential to reducing the incidence and pigmentation, particularly on dark skin. Moisturizers can help
severity of melasma. Appropriate behavior during sun exposure, mitigate these effects.
wearing suitable clothing, and using recommended sunscreens Hydroquinone is considered as a reference for treating hyper-
are the mainstays of modern photoprotection (Figure 4). pigmentation. It is available at 4% for the active treatment

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 Latin American consensus Review Article 5

Figure 2 Different wavelengths of sun radiation, such as visible light (VL), ultraviolet A (UVA), and ultraviolet B (UVB), produce various
effects on the skin’s components. These radiations directly stimulate melanocytes’ melanogenesis (hyperfunctional melanocyte) and indirectly
through paracrine regulation. Fibroblasts’ and keratinocytes’ ultraviolet-mediated overexpression of cadherin 11 contributes to basement
membrane damage and melanocyte migration into the dermis (pendulous melanocyte). Keratinocytes increase melanocyte proliferation and
melanogenesis by secreting cytokines and hormones such as alpha-melanocyte-stimulating hormone (a-MSH), stem cell factor SCF, basic
fibroblast growth factor bFGF, inducible nitric oxide synthase iNOS, and prostaglandin E2 PG2. Fibroblasts’ increased expression of matrix
metalloproteinases (MMP) 1 and 2 leads to collagen degradation and elastotic material accumulation in the skin. Senescent fibroblasts
release several melanogenic growth factors, including Wingless-related integration site family member 1 inhibitory factor (WIF 1), Dickkopf
protein 1 (DKK1), neuregulin 1 gene (NRG1), SCF, and human secreted frizzled-related protein 2 (sFRP2). Mast cells release histamine,
which activates melanogenesis and tryptase production. Tryptase damages the basement membrane by degrading type IV collagen. Mast
cells also induce hypervascularization by secreting vascular endothelial growth factor (VEGF), transforming growth factor (TGF), and beta
fibroblast growth factor (bFGF). The inflamed endothelial cells produce endothelin 1 (ET1), which upregulates key genes for melanogenesis.
Sebocytes have been suggested to influence melanogenesis by secreting cytokines such as interleukins IL1a and IL6, synthesizing vitamin D
(VIT D), and producing growth factors such as angiopoietin and adipokine, which directly or indirectly modulate melanocyte function

phase and 2% for maintenance. It may cause temporary pig- to hydroquinone. In concentrations of 2%, it is a safe alternative
mentation changes, irritation, or, rarely, exogenous ochronosis. for patients who do not tolerate hydroquinone.40
It is not recommended for pregnant or breastfeeding women or Niacinamide is the active form of vitamin B3 and is essential
people with drug allergies.19,37 in melasma treatment. It stimulates the production of ceramides
Isobutylamido thiazolyl resorcinol is a potent inhibitor of recom- and other crucial stratum corneum lipids, strengthening the skin
binant human tyrosinase, outperforming arbutin, kojic acid, and barrier. Niacinamide decreases pigmentation, inflammation,
hydroquinone in depigmenting effectiveness. Studies have shown solar elastosis, and mast cell infiltration.41 It improves pigmenta-
that ITR improves mMASI Index scores significantly better than tion and decreases MASI score with no significant difference
2% hydroquinone and is no different from 4% hydroquinone.38,39 compared to hydroquinone.36
Kojic acid blocks tyrosinase activity by forming chelates with Tranexamic acid, traditionally used to control bleeding, is
copper at the enzyme’s active site. It is less irritating compared an emerging treatment for melasma. It inhibits plasminogen

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6 Review Article Latin American consensus

Table 3 Data from studies and surveys on the epidemiology of melasma in Latin America

Country Age group n Design Results

Brazil12 18+ 953 Cross-sectional, • 97.5% women

multicenter • Phototypes II (12.8%), III (36.3%), and IV (39.7%)
• Higher frequency in postmenopausal women (14.2% vs. 3.5%,
P < 0.0001)
Brazil13 Adults 1500 Population study 23.6% of men and 29.9% of women reported pigmentation disorders as
the main cause of dermatological consultation
Brazil14 — 302 Semi-structured • Intermediate skin phototypes III (34.4%) and IV (38.4%) prevailed
questionnaire for • Mean age of onset 27.5  7.8 years
melasma patients in • Family occurrence in 56.3%
a dermatology clinic • Triggered by pregnancy (36.4%), contraceptives (16.2%), and intense
sun exposure (27.2%)
• Zygomatic topography (83.8%), upper labial (51.3%), and frontal
(49.7%)
Brazil15 — 686 subjects from Complex segregation • 260 (38%) with facial melasma
67 families model • Demonstrating an autosomal dominant inheritance genetic component
Brazil16 42.1 years 515 employees Population survey • Melasma in 34% of women and 6% of men
average (SD • Most cases are females between 20 and 35 years old
11.2)
United Latino male 25 poultry farmers Direct exploration Prevalence of melasma 36.0%
States20 adults 54 peasants Direct exploration Prevalence of melasma 7.4%
300 peasants Teledermatology Prevalence of melasma 14.0%
image review
Peru22 — 1277 inhabitants of Direct exploration Melasma between 4% and 10% (in a population attending a particular
Cuzco, Peru practice)
Brazil16 20–60 BC 303 Random sampling of • Prevalence 36.3%
women from the • With mMASI <4 in 72.7%
general population • Pregnancy as a triggering factor in 49.1%
with facial melasma

clinical improvement are seen, and its safety profile is

favorable.42
Triple combination cream is an FDA-approved formula con-
taining hydroquinone, tretinoin, and fluocinolone. The combina-
tion enhances tyrosinase inhibition, promotes cell renewal, and
reduces inflammation and skin irritation. However, it is not
recommended for use during pregnancy or breastfeeding and
may cause irritation, flaking, and burning.38
In addition to the topical agents reviewed above, others did
not reach 75% agreement among the consensus experts for
inclusion in the treatment algorithm in the first survey round and
went to a second round. In the second round, 4-n-butyl resor-
cinol (Rucinol) and cysteamine were recommended by 67% of
the participants; ascorbic acid by 44%; and pycnogenol, sily-
marin, and trichloroacetic acid by 33%. The reasons for this
were inconclusive scientific evidence and lack of availability or
limited use in the Latin American region. Retinoids and steroids
alone were recommended by 56% of the participants owing to
their consented use in fixed combinations.
Figure 3 Most recognized factors associated with melasma
Systemic medications
activation and limits melanocyte activity and melanin produc- Of the systemic drugs used in melasma, oral TA has more
tion. Compared to hydroquinone, no differences in MASI robust evidence.31 Its dosage varies across studies (250–
scores decrease, onset of action, and rapidity of 1000 mg/day). Higher doses are often associated with quicker

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 Latin American consensus Review Article 7

Table 4 Statements with unanimous consensus and Table 5 Identified differences between the present
a ≥ 75% agreement in the Delphi surveys consensus and existing continental treatment proposals

• Melasma management includes the correct use of photoprotection, Contributions included in the present Latin American consensus
topical agents, systemic medications, and melasma-aimed applica- compared to similar publications for the region,18 Mexico,1 Chile,28
ble procedures. Peru,29 and Brazil30
• Adequate photoprotection is essential to prevent, treat, and avoid
relapse of melasma. QoL Although QoL was addressed, no reference was made
• Topical agents are the prevailing component of melasma manage- to the convenience of professional psychological
ment; the decision of which agents to use is influenced not only by support for some patients.
scientific evidence but also by regional availability, ethnicity, the Systemic Hormonal, metabolic, and immune alterations
drugs’ safety profile, suitability during pregnancy, skin sensitivity, factors associated with melasma were identified. However,
and the intensity of sun exposure. none suggested referral to other specialists when
• Recommended topical agents for Latin American patients are (in these factors may play some role in disease
alphabetical order): arbutin, azelaic acid, glycolic acid, hydroqui- management.
none, isobutylamido thiazolyl resorcinol (ThiamidolTM), kojic acid, nia- Prevention All agree on the importance of photoprotection as a
cinamide, tranexamic acid, and triple combination cream. treatment pillar.
• Recently added topical agents, such as isobutylamido thiazolyl res- Topical agents Classical topical agents were discussed. However,
orcinol, niacinamide, and tranexamic acid, are promising alterna- only the most recent ones mentioned new agents like
tives with satisfactory results. Isobutylamido thiazolyl resorcinol.
• Among systemic agents, oral tranexamic acid has more robust effi- Systemic Emphasis was also put on the oral use of TA, but not
cacy supporting evidence, alone or combined with other treatment treatment all mentioned other potential systemic agents.
modalities. Other systemic agents for melasma treatment require Procedures Laser use was the most discussed procedure. Other
further investigation. procedures included in the present consensus are not
• Available procedures for melasma management complement topical approached in all of them, and combination with other
and oral treatments, enhancing depigmentation’s speed and effec- treatment modes is only mentioned in one.
tiveness when properly trained professionals use state-of-the-art Targeting No prior consensus has established a specific timeline
techniques. outcomes for achieving improvement to guide stepwise
• Recommended procedures include chemical peelings, microneed- decision-making in management.
ling, intradermal injections, laser therapy, platelet-rich plasma
(PRP), and microdermabrasion.
• Conventional and new combinations of topical agents and recom- Chemical peelings commonly used for melasma treatment
mended procedures merit further exploration. include Jessner’s solution, glycolic acid (50%), tretinoin (1%–
• Adding moisturizers to selected treatments helps restore the com- 5%), salicylic acid (20%–30%), lactic acid (82%), and trichloroa-
promised barrier function in melasma-affected skin.
cetic acid (20%).46–50 There is no clear evidence of superiority
• Proactive relapse prevention should be incorporated early as an
integral component of the treatment strategy. among these formulations or their sequential combination.
• The multifactorial nature of melasma necessitates an interdisciplin- Medium-depth peels should be avoided. Strict photoprotection
ary approach. is essential.
• Endocrinologists, gynecologists, and mental health professionals Microneedling involves creating microinjuries in the skin, pro-
aware of the effects concomitant conditions in their fields have on
moting melanin clearance.51 Its progressive depigmenting effect
dermal pigmentation should be consulted according to the patient’s
conditions. occurs over multiple sessions. It poses a lower risk of relapse
compared to deeper peels.52,53 Microneedling can be performed
on individuals with darker skin tones, although the efficacy of
results.43 However, lower doses are preferred to minimize different devices and protocols in melasma treatment is still
dose-dependent prothrombotic side effects. Most side effects of under investigation. It also serves as a potential strategy for
oral TA are transient, and it is crucial to observe formal contra- drug delivery by facilitating transepidermal penetration. One of
indications and precautions during its use.35 Its discontinuation the most studied applications involves using TA solution after
may lead to relapses. Oral TA can be used either as monother- microneedling, yielding comparable results to intradermal TA
apy or combined with other treatments.44 injections.54–56
Polypodium leucotomos is another systemic agent sometimes Superficial dermabrasion has shown a low risk of melasma
used for melasma management.29,45 These agents may offer addi- relapse in some studies involving hundreds of participants, but
tional therapeutic options, although their efficacy and safety profiles further validation is needed.57
require further investigation and validation in clinical settings. Recent studies have explored the intraepidermal application
of TA, which has shown promising results.58 Intradermal injec-
Procedures tions of TA every 14–21 days have been compared with topical
Several procedures complement topical and oral treatments to hydroquinone 4% and oral TA, with variable outcomes. How-
enhance the speed and effectiveness of depigmentation in mel- ever, intradermal TA injections do not demonstrate superiority
asma (Table 7). over oral administration in treating melasma.59

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8 Review Article Latin American consensus

Figure 4 Consideration of all three components is crucial in primary prevention, during treatment periods, and in avoiding relapses

Injectable platelet-rich plasma (PRP) is used globally for vari- with moisturizers. Combining hyaluronic acid with ITR has been
ous medical purposes. It has been studied in several controlled shown to enhance clinical outcomes.39,70
trials for its additional depigmentation effects in melasma, with Combining oral TA with microneedling has optimized mel-
reductions ranging from 1.1 to 4.8 mMASI points. Despite its asma improvement, achieving a clinical reduction of 50% in
potential, PRP remains an experimental procedure in most Latin 60 days compared to 30% with the triple combination alone.54
American countries and is currently prohibited in clinical Laser or light therapies are typically combined with strict
settings.60 photoprotection and topical melanogenesis inhibitors, contribut-
ing to accelerated results in melasma treatment.71,72
Combinations
Clinical practice often combines multiple interventions to Algorithm for the treatment of melasma in Latin America
achieve faster and more effective results. Melasma treatment The expert group of the Latin American consensus on the Treat-
includes rigorous photoprotection,61–63 topical melanogenesis ment of Melasma proposed a management algorithm (Figure 5)
inhibitors, and various adjuvant therapies such as laser/light to personalize the management of melasma according to the indi-
treatments, intralesional therapy, antioxidants, and oral TA.31 vidual circumstances of each patient and the treatment setting.
The triple combination of hydroquinone, tretinoin, and a fluori- The specific details and usage of the therapeutic options men-
nated corticosteroid has demonstrated superior efficacy in treat- tioned in the algorithm can be found in the preceding sections.
ing melasma compared to individual agents alone.64–66 Following the initial evaluation of melasma, and based on its
Several combinations of active ingredients, such as ITR, reti- severity, patients are categorized into two groups: mild (mMASI
noic acid, and dexamethasone, have shown efficacy in improv- ≤5) or moderate to severe (mMASI >5). For both groups, it is
ing melasma.67 Further exploration of nonphenolic actives in recommended to start with sun photoprotection measures and
combination therapies is warranted to mitigate melanocyte concomitant administration of a topical depigmenting agent such
toxicity. as (in alphabetical order) arbutin, azelaic acid, glycolic acid,
New clinical interventions undergo rigorous testing against hydroquinone, ITR, kojic acid, niacinamide, TA, triple combina-
established treatments (e.g., triple combination or 4% hydroqui- tion cream. These agents can be used alone or in combination
none) to develop robust evidence of efficacy in the melasma according to their properties and safety profiles. In the moderate
treatment.68,69 to severe group, oral TA or other systemic medication is added,
Owing to the compromised barrier function observed in combined with available technological procedures as needed.
melasma-affected skin, it is advisable to combine treatments Evaluation of efficacy in melasma clinical trials ranges from 8 to

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 Latin American consensus Review Article 9

Table 6 Presiding characteristics of topical agents used for the treatment of melasma in Latin America

Active ingredient Mechanism of action Application methoda Side effects

Arbutin Tyrosinase reduction and melanocytes’ maturation inhibition. Low Twice daily Allergic contact
toxicity dermatitis
Azelaic acid Tyrosinase inhibition Once in the evening Irritation
Glycolic acid Tyrosinase inhibition Depends on concentration Irritant contact
(two to three times per dermatitis
week)
Hydroquinone Tyrosinase, peroxidase, and melanocyte inhibition. Melanocyte cells’ Once in the evening for Irritation
membrane destruction up to 6 weeks Hyperpigmentation
(Ochronosis)
Allergic contact
dermatitis
Isobutylamido Human tyrosinase inhibition Two to four times a day Irritation
thiazolyl resorcinol
(ThiamidolTM)
Kojic acid Tyrosinase inhibition It depends on the Irritant contact
concentration dermatitis
Niacinamide Melanosome transfer and melanocyte inhibition. Solar elastosis Once daily, combination Irritation
reduction. Anti-inflammatory and antiaging effect (via ceramide recommended
production stimulation). PAR-2 inhibition
Tranexamic acid Tyrosinase and melanocyte inhibition. Mast cells’ negative regulation. Twice daily Irritation
Plasmin inhibition (via arachidonic acid and a-MSH reduction). Solar
elastosis, VEGF, and Endothelin 1 reduction
Triple combination Tyrosinase, peroxidase, and melanocyte inhibition. Melanocytes’ Once in the evening for Not recommended in
cream membrane destruction. UVB-stimulated keratinocytes and tyrosinase up to 6 weeks pregnancy and
transcription inhibition. Melanosome transfer reduction. Keratinocyte breastfeeding
turnover increase. Mast cell recruitment and maturation Inhibition. Irritation
Anti-inflammatory effect

Listed agents were selected for their clinical efficacy and widespread availability in Latin America. They appear in alphabetical order.
a-MSH, alpha-melanocyte-stimulating hormone; PAR-2, protease-activated receptor 2; VEGF, vascular endothelial growth factor.
a
The suggested application method is for topical use and may vary according to patients’ characteristics, tolerability, other topical agents’ con-
comitant use, systemic medications, or accompanying procedures.

12 weeks.40,73–75 In clinical practice, an efficacy review should If melasma relapses at any time or resistance to treatment
be performed after 6–8 weeks of treatment initiation in both appears, reevaluate the case as a new scenario and restart with
groups, as agreed by 78% of the participating experts (the other the algorithm’s initial flow.
22% noted it might be extended up to 12 weeks at the treating Keep in mind consultations with other specialists to rule out
physician’s discretion). If an improvement of 30% or more in the associated pathologies.
mMASI is detected, it is recommended to maintain the estab-
lished treatment until the maximum effect is reached. Subse- Prevention and relapse management
quently, move to the maintenance phase where photoprotection No treatment is entirely curative for melasma as yet, and relapses
is preserved, systemic drugs and procedures (if applicable) are are common, even after a positive response to treatment. There-
discontinued, and a topical depigmenting agent is continued fore, proactive relapse prevention should be incorporated early as
(reducing the frequency of application of phenolic derivatives an integral component of the treatment strategy.
such as hydroquinone or triple cream). Preference should be Certain factors have been identified as contributing to an
given to permanently applied cosmeceuticals with no long-term increased likelihood of relapse, such as the discontinuation of
adverse effects. oral TA and triple combination therapy. Ablative and proinflam-
If the mMASI improvement in patients with mild melasma matory treatments, including medium peels and rejuvenation
after 6–8 weeks of treatment was less than 30%, consider add- procedures, as well as sun exposure, noncompliance with main-
ing oral medication and proper procedures. tenance treatment, lack of protection against broad-spectrum
If improvement after 6–8 weeks of treatment was less than solar radiation, hormonal therapy, and pregnancy, are associ-
30% in patients with moderate to severe melasma, adjust ated with an increased risk of relapse. In contrast, interventions
depigmenting agents, systemic medication, and interdisciplinary such as microneedling and gentle microdermabrasion have
procedures; reassess at 6–8 weeks. been reported to result in lower relapse rates.33,52,54,76–79

ª 2024 the International Society of Dermatology. International Journal of Dermatology 2024

10 Review Article Latin American consensus

Table 7 Relevant procedures for the treatment of melasma Melasma most often occurs in women of childbearing age
and those who use oral contraceptives.80,84,85 In this group,
Chemical peelings changes such as increased transcription of tyrosinase and
• Classical adjuncts in the treatment of melasma
dopachrome tautomerase, which enhance physiological pigmen-
• Enhance epidermal turnover, resulting in the clearance of
melanosomes tation, are intensified by ovarian and placental hormones that
• Cost-effective, with minimal downtime, and can improve treatment promote pituitary hormones.
results The relationship between melasma and hormonal alterations
Microneedling in men remains controversial. Some studies report hormonal
• Leads melanin clearance through multiple superficial perforations
alterations in only 9.7% of male patients with melasma, while
from the epidermis to the upper dermis, promoting neocollagenesis,
fibroblast replication, and a high rate of epidermal turnover others have detected decreased testosterone levels.23,86,87
• Tranexamic acid can be used by this route Additionally, some reports link the increase in melasma to the
• Can be conducted using robotic devices or needled rollers widespread use of finasteride88 and the administration of exoge-
• Sessions can be performed every 14 to 28 days, and there is mini- nous estrogens to men.89
mal downtime
Several skin conditions, including melasma, significantly
Laser therapy
• Short-pulse (nanoseconds) lasers destroy melanin by photoacoustic impact patients’ mental health and psychological well-being.
effects, such as Q-switched and ultrashort-pulse (pico-seconds) When detected, emotional and psychological support, including
lasers professional psychological intervention, is essential.90,91
• Picosecond lasers have the least inflammatory and photothermal It is advisable to consider a thyroid profile, a female or male hor-
effects
monal profile as appropriate, and psychological assessments of
Microdermabrasion
• Reported as an effective adjuvant treatment, resulting in a low risk mental, mood, or psychiatric status. Additional evaluations, such as
of relapse tests for metabolic syndrome or liver function, may be required
• Subsequent trials are needed to validate this procedure based on availability and the specific needs of each case.
Intradermal injections
• Several solutions, such as tranexamic acid, vitamin C, glutathione,
Perspectives on the treatment of melasma
triamcinolone, and hyaluronic acid, have been studied
• Systematic investigations are still pending Over the years, understanding melasma’s pathophysiology and
Platelet-rich plasma injection treatment has evolved into a sophisticated multimodal
• Relies on the release of growth factors from intradermally injected, approach. With growing knowledge of melasma’s pathogenesis,
highly concentrated platelets new and effective treatments are being incorporated into the
• Exhibits significant variability in terms of activation, centrifugation
therapeutic arsenal, such as VL protectants containing iron
regimens, final platelet concentration, and treatment protocols
• Variations pose challenges to the consistency and reliability of oxide, novel topical agents like pigment-correcting serums and
results across different studies flutamide, and oral administration of P. leucotomos.92
Current melasma treatments incorporate new agents that tar-
Procedures that may complement topical and oral treatments to get various aspects of the condition, from classic approaches
intensify depigmentation’s speed and effectiveness. attacking the melanogenesis pathway to novel strategies
addressing overactive melanocytes, reducing inflammation and
It is crucial to differentiate relapse from resistance or treat- free radical production, and inhibiting melanosomal transfer to
ment failure, where the condition does not show improvement keratinocytes, among other pathways.93
despite treatment efforts. Advanced imaging techniques such as reflectance spectros-
copy and reflectance confocal microscopy are gaining traction
Multidisciplinary approach for diagnosis. These techniques provide detailed analyses of
The multifactorial nature of melasma necessitates an interdisci- melasma characteristics at the cellular and molecular levels.
plinary approach. Although current evidence is insufficient for These advancements open new possibilities for personalized
specific recommendations, there is consensus on the impor- treatment, marking a more sophisticated melasma evaluation
tance of involving endocrinologists, gynecologists, and mental and management era.
health professionals when the patient’s condition warrants it. Procedures complement underlying treatments. Microneed-
These specialists should be aware of the effects of common ling, for example, can enhance their effectiveness and delay
conditions in their fields on dermal pigmentation. relapses. Phenol-croton peels show promising results in
Thyroid hormones, among other endocrine factors, have long-term remission. Other technologies, such as TA intrader-
been linked to the development of melasma.80 A meta-analysis mal therapy, PRP, and various laser techniques (e.g., picosec-
observed that serum levels of thyroid-stimulating hormone and ond pulse laser and pulsed dye laser), are also being
thyroid peroxidase antibodies were higher in patients with mel- explored.31
asma, particularly in women.81 Other authors have corroborated The accumulation of advanced glycation end products
these findings.82,83 (AGEs) contributes to the yellowing of photoaged skin and may

International Journal of Dermatology 2024 ª 2024 the International Society of Dermatology.

 Latin American consensus Review Article 11

Figure 5 Best expected response—after an initial evaluation, photoprotection, and topical depigmenting agents should be started for mild
and moderate to severe melasma patients. In the moderate to severe group, start oral tranexamic acid and add treatment procedures as
needed. Review efficacy after 6–8 weeks of treatment. With a > 30% mMASI improvement, continue the established treatment until the
maximum response, followed by maintenance therapy. <30% mMASI improvement (at the 6–8 weeks efficacy review)—For the mild group,
start oral tranexamic acid and add treatment procedures as needed. For the moderate to severe group, reevaluate the case and adjust the
depigmenting agent, oral therapy, or procedures as required before the following 6–8 weeks efficacy review. Relapse or resistance—This can
occur at any time during treatment. Restart with the algorithm’s initial flow

play a role in hyperpigmentation disorders. Increased levels of Collinsella spp., may influence the appearance and develop-
AGEs have been observed in the dermis of sun-exposed skin, ment of melasma.99 Promising probiotics that inhibit melanin
melasma, and lentigo solar lesions, suggesting a potential direct production and tyrosinase activity, leading to skin lightening,
promotion of epidermal melanin levels.94,95 Various natural com- include Bifidobacterium adolescentis, Lactobacillus helveticus
pounds are being investigated for their potential to inhibit AGE NS8, and Rhodobacter sphaeroides.100
formation, with ongoing studies to define their mechanisms of Today, melasma is considered a dynamic process, with new
action, safety, and efficacy.96 treatment strategies emerging from a better understanding of its
Photobiomodulation is emerging as a promising, noninvasive pathogenesis. Ongoing clinical trials are helping identify triggers
procedure for melasma treatment. This technique uses lasers and refine therapeutic approaches.
or other low-intensity light sources to achieve therapeutic effects In conclusion, managing melasma as a chronic, relapsing
without causing destruction. The most used spectral regions are condition presents challenges, particularly given the diverse
red (600–700 nm) and near-infrared (780–1100 nm). Photobio- populations across Latin America. Successful interventions must
modulation can potentially reduce erythema and vascularization, consider individual characteristics such as skin tone, triggering
improve dermal conditions,97 and possibly help develop future factors, disease severity, prior treatment experiences, preg-
resistance to UV rays.98 nancy status, and sun exposure habits.
The skin microbiome plays an important role in various skin
disorders and is a significant immune system regulator. Probio-
Acknowledgments
tics have been shown to have distinct advantages in skin disor-
ders, including melasma, because of their anti-inflammatory We thank Beiersdorf-Eucerin for the financial support, SPRIM
activities, antioxidant properties, UV protection, and tyrosinase PRO for its support in logistics and the DELPHI process, and
inhibition activity. Certain strains of gut microbiota, such as Dr. Thor Nissen for the medical writing.

ª 2024 the International Society of Dermatology. International Journal of Dermatology 2024

12 Review Article Latin American consensus

19 Dias MO, Minagawa FH, Teixeira De Abreu AF, Barbosa MMC,

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