https://doi.org/10.5812/jssc.120283

Melasma: Update on Epidemiology, Clinical Presentation, Assessment, and Scoring

authors:

avatar Imran Majid ORCID 1 , * , avatar Samia Aleem 2

Cutis Institute of Dermatology, Srinagar, Kashmir, India
JK Health Services, Kashmir, India
Journal of Skin and Stem Cell: Vol.8, issue 4; e120283
published online: January 25, 2022
article type: Review Article
received: October 12, 2021
revised: December 11, 2021
accepted: December 22, 2021

how to cite: Majid I, Aleem S. Melasma: Update on Epidemiology, Clinical Presentation, Assessment, and Scoring. J Skin Stem Cell. 2021;8(4):e120283. https://doi.org/10.5812/jssc.120283.

Abstract

Melasma is a common dermatosis, presenting as ill-defined light to dark brown pigmentation of photo-exposed areas, most commonly the face. Its exact prevalence is unknown, but it is commoner in intermediate skin phototypes and women of reproductive age. Its treatment and monitoring have significance due to its chronic recalcitrant history and psychosocial impact. Various indices and tools like the melasma area and severity Index (MASI), melasma severity index (MSI), and Melasma Quality of Life Scale (MELASQoL) have been formulated for measuring severity and treatment response. In this review, particular emphasis has been laid on melasma's epidemiological and clinical aspects and its assessment and scoring.

1. Context

Melasma is a common acquired pigmentary disorder, presenting as irregular light to dark brown macules on the face, mainly the cheeks, forehead, and nose (1). The term ‘melasma’ is derived from the Greek word "melas," meaning black, pointing to the color of clinical lesions. The actual prevalence of melasma is unknown, reportedly ranging from approximately 1 to 33%, depending on the location of the population (2). It is observed in people of all ethnic backgrounds and geographical areas, but populations with constitutionally darker skin, living in areas of the world with intense sun exposure, are more affected than those with lighter skin types. Among the darker skin types, it is more commonly observed in those with light brown skin types, especially Latinos and Asians (3).

Melasma is a multifactorial disorder with a variable interplay between genetic, hormonal, and environmental factors. Sun exposure, family history, and pregnancy are the most commonly observed factors associated with melasma development (2, 4, 5). On histopathology, there is an increase in epidermal melanin and melanosome number and transfer in epidermal melasma. However, melanophages are visible in the superficial and deep dermis in dermal melasma. Treatment of melasma includes topical demalanising agents with particular emphasis on photoprotection. Chemical peels and laser therapy are the other modalities used (6). Being a chronic recalcitrant dermatosis, with variable severity ranging from ‘barely visible’ to ‘severe disfigurement,' melasma has a significant effect on the quality of life of the affected individuals (7).

2. Epidemiology

Melasma has been observed to be one of the commonest dermatoses across all world countries. It was the most common pigmentary disorder and fourth among dermatoses in 546 dermatological patients in Nepal (8). Similarly, melanodermatosis, including melasma, was the third most frequent cause of skin-related consultations among 57,343 patients in a Brazilian study (9). In a study conducted in Saudi Arabia, pigmentary dermatosis represented the fourth largest dermatosis group (10). Pigmentary disorders were also the third most frequently observed dermatosis among 2,000 dermatological patients in Washington, with melasma patients comprising the second largest group (11). However, the true prevalence of melasma in the community is still underestimated due to milder disease going unreported or managed even by over-the-counter self-medication.

Globally, the prevalence of melasma is variable. As a multifactorial disorder, its prevalence has been observed from 1% in the general population to 9 - 50% in high-risk populations (12-15). This wide range of prevalence has been chiefly attributed to variations in ethnic composition and levels of photo exposure among populations residing in various geographic regions. Melasma has been reported across all ethnic groups and populations, although with variable prevalence. Pigmented phenotypes have had a higher prevalence in Southeast Asians, Middle East Asians, Mediterranean Africans, Hispanic-Americans, and Brazilians (1, 15, 16). Although it presents in 0.25 to 4% of dermatology clinic patients in Southeast Asia (17), a prevalence as high as 40% has been reported in the population (1). It is the most typical hyperpigmentary disorder among Indians (3). A prevalence of 2.9% was observed in the Arab population in Saudi Arabia compared to a 13.4 - 15.5% prevalence in Arabs residing in America (18, 19). Similarly, a prevalence of 1.5% was noted in Ethiopia (20). In another study from Brazil, 34% of women and 6% of men were noted with features of melasma (21). Among 1,000 Latino patients, a prevalence of 8.2% was noted (22, 23). Similarly, among a Latino population in Texas, the USA, 8.8% had melasma, and 4.0% gave a history of its presence (14). It was observed in 2.5% of Hispanic-American immigrants in Spain compared to only 0.5% of the Spanish population in Spain (Table 1).

Table 1.

Prevalence of Melasma in Various Geographical Regions and Populations

Geographical RegionsPrevalence of Melasma, %Reference
Southeast Asia0.025 - 4Pasricha et al. (17)
Saudi Arabia2.9Parthasaradhi and Al Gufai (18)
Arab-Americans13.4 - 15.5El-Essawi et al. (19)
Ethiopia1.5Hiletework (20)
Latinos8.2; 8.8Sanchez (22); Werlinger et al. (14)
Hispanics2.5Albares Tendero et al. (23)

3. Skin Types Involved

While melasma is observed throughout the spectrum of skin phototypes, it is more common in the middles and rare in extreme ends (24, 25). Melasma, a dermatosis due to a change in skin color, preferably affects the skin color. Therefore, it is more common in skin types III, IV, and V. Among melasma patients, as high as 90% have been observed with skin types III and IV only (26). Similar results were observed in various Brazilian studies, with most patients having skin types IV (40%) and skin type III (36%) followed by skin type V (10%) (27, 28). However, in another study, most of 188 patients had skin types IV and V (45% and 40%, respectively), with only 14% having skin type III (4).

A more common occurrence of melasma in middle skin types has been explained by the variable ability of different skin types to produce melanin on exposure to triggering factors. Due to their stable pigmentation, extreme skin types are uncommonly associated with melasma. Skin type I cannot tan and produce pigmentation on exposure to sunlight. Skin type VI cannot produce additional pigmentation since it has already produced it to its full potential (Table 2).

Table 2.

Prevalence of Melasma in Various Skin Types

CountrySkin Types, %Reference
BrazilIII - 34.4; IV - 38.4; V - 15.6Tamega et al. (27)
BrazilIII - 36; IV - 40; V - 10Hexsel et al. (28)
TunisiaIII - 14; IV - 45; V - 40Guinot et al. (4)
SingaporeIII & IV - 90Goh and Dlova (26)

4. Age Distribution

Melasma has a variable age of onset. The average age range of onset varies from 20 - 30 years in some studies to 36 - 40 years in some others (27, 29). Melasma has been shown to develop earlier in the life of patients with lower phototypes. The delay in the appearance of melasma has been attributed to the photoprotective role of melanin (27, 28). Mandibular melasma specifically has been associated with later onset as compared with other types (30).

5. Sex Distribution

Melasma is more commonly observed in females than males of the same age. Generally, a female predominance of 9 - 10:1 is observed. However, the prevalence ratio of females to males is highly variable, ranging from 4:1 to 39:1 (25). A multicentric study from Brazil with 953 melasma patients had a female to male ratio of 39:1. Similarly, in a study from Singapore, a ratio of 21:1 was observed (26, 28). However, in an Indian study of 312 patients, this ratio was reported to be 4:1 (29). Several studies involving melasma patients of different skin phototypes and geographical areas have noted the involvement of women in their reproductive years, suggesting the role of hormones in the etiopathogenesis of melasma (27-33). In a study, females aged 20 to 35 years constituted more than half of the patients. In another study, 87 (87%) women were 20 - 40 years old. Similarly, in studies from India and Singapore, the mean ages of melasma development were 30 and 34 years, respectively (4, 26-29)

6. Prevalence in Pregnancy

Melasma was observed in 39.5% of female patients, among whom pregnancy was detected in 9.5% in a population-based survey in an Iranian city (34). In a cross-sectional study in Tehran, another city from Iran, a prevalence of 15.8% was observed amongst pregnant women (12). Among 224 pregnant women, melasma was identified in 10.7% in a study from Brazil (35). Similarly, in an Indian study, a prevalence of 50.8% was reported in 2,000 randomly selected pregnant women (13). A prevalence of 63.5% was noted in another Southeast Asian country (36). However, a low prevalence of 5% was observed in a group of 60 pregnant women from France (37). Increased prevalence of melasma in pregnancy and altered hormonal state with high placental, ovarian, and pituitary levels point to the crucial roles of hormones in the pathogenesis of melasma (Table 3) (38).

Table 3.

Prevalence of Melasma in Pregnancy in Various Countries

CountryPrevalence of Melasma, %Reference
India50.8Rathore et al. (13)
Pakistan63.5Shanza et al. (35)
Iran 15.8Moin et al. (12)
Brazil10.7Hexsel et al. (34)
France5Esteve et al. (36)

Women with melasma were shown to have higher estradiol hormones, Luteinizing Hormone (LH), and Follicle-stimulating Hormone (FSH), in an Indian study (39). Its prevalence also increases among women using oral contraceptive pills and hormone replacement therapy and prostatic cancer women on estrogen therapy (40). Different countries report a different prevalence of melasma during pregnancy. This could be due to genetic factors and skin type differences, further confirming the increased prevalence of melasma in more melanized skin types (37).

A significant reduction in the prevalence of melasma has been noted after 50 years of age, possibly due to the reverse alteration in the hormonal milieu compared with pregnancy. Further, aging reduces the number and activity of melanocytes (41, 42).

7. Melasma in Men

Although melasma is less frequent in men, they exhibit similar epidemiological, clinical, and histological features (31). Men constituted 25.8% of melasma patients in an Indian study, in contrast to 10% in a study from Puerto Rico, and demonstrated similar average age and disease duration to women (33.5 vs. 31.5 years and 3.5 vs. 3.1 years, respectively) (31, 43). Men have almost similar etiological factors, proving that, although female sex hormones are the predominant causal factor, they are not the only ones. Among men, like women, genetic factors, sun exposure, and outdoor work can affect the development and prevalence of the disease (43, 44). High prevalence of melasma (41%) among Indian paddy field workers further signifies the role of sun exposure in disease development (45). Sun exposure can be both a triggering and aggravating factor, with family history also having significance (4). Further, they were the most common risk factors (sun exposure 48.8%, family history 39.0%) in men, in contrast to pregnancy (45.3%) in women (43).

8. Clinical Features

Clinical melasma patients have symmetrical ill-defined hyperpigmented macules on the photo-exposed areas, especially the face, and rarely the upper chest and extremities (27, 31). According to the distribution of these macules, melasma has been classified into three clinical patterns. The centrofacial pattern affects the central face. Forehead, nose, cheeks, upper lip, and chin are involved. The malar pattern is characterized by the involvement of the cheeks and nose. The mandibular pattern involves the mandibular dermatome predominantly.

The most common clinical pattern is the centrofacial type, followed by maxillary melasma and then mandibular melasma (Figure 1), as observed in various Indian, Brazilian, and Indonesian studies (27, 46, 47). Similar observations were reported from Tunisia, where the most common type was centrofacial melasma, accounting for 76.1% of all cases, followed by malar (22.9%) and mandibular (1%) melasma (4). However, in a study from Singapore, malar melasma was the type noted in most patients (89%). Centrofacial (8%) and mandibular (3%) melasma were seen in a minority only (26). As the malar pattern has a high co-occurrence with glabellar lesions in centrofacial melasma, it has been proposed to be considered as part of the centrofacial classification (27).

Mandibular melasma is the least common morphologic type of melasma.
Mandibular melasma is the least common morphologic type of melasma.
Figure 1.

Mandibular melasma is the least common morphologic type of melasma.

True mandibular melasma, ie, restricted to the ramus of mandible only, is rare (27, 48). In an Indian study, 1.6% of exclusive mandibular melasma cases were noted. Similarly, two (3.7%) cases were reported in a Brazilian study (27, 29). Mandibular melasma is mainly associated with older individuals and is often related to more severe exposure to sunlight. Histopathological analysis of biopsies has confirmed significant actinic damage. Therefore, it has been proposed to represent a type of poikiloderma of Civatte (4, 30). Extra-facial melasma is a new, less typical pattern. It occurs on non-facial body parts, including the neck, sternum, and forearms. Melasma affecting the upper limbs has been observed mainly among postmenopausal women, especially women on hormone replacement therapy. This type of melasma resembles facial melasma both clinically and histopathologically (49, 50).

The color of melasma is commonly tan to brown. This color is associated with excessive epidermal pigmentation. Patients with dermal melasma have blue or black macules (31). It is associated with melanophages in the superficial and deep dermis. Wood's lamp examination also helps differentiate between epidermal and dermal types. The pigmentation is accentuated in the epidermal type and not increased in the dermal type (29). Dermoscopy has also proven to be beneficial in such melasma categorization. Regular brownish appearance, irregular bluish-gray, and a combination of both are observed in epidermal, dermal, and mixed types on dermoscopy, respectively (51).

9. Melasma Assessment and Scoring

The melasma severity assessment is essential to evaluate the clinical appearance and psychosocial impact due to disfigurement caused by melasma. It is also essential to assess the therapeutic efficacy of various treatment modalities. It can be challenging, and various objective or semi-objective methods are used.

The melasma area and severity index (MASI) is a scale used to measure the melasma severity. It was introduced in 1994 by Kimbrough-Green et al (51). The MASI is the most widely used outcome measure in melasma clinical studies. This is calculated using three variables, area (A), the severity of pigmentation (P), and homogeneity (H), on the four areas of the face, forehead (f), chin (c), right and left malar cheek (rm and lm, respectively) (Table 4). The MASI allows a quantitative assessment of melasma severity. Although its inter-rater reliability, temporal stability, and consistency have been confirmed, one of the homogeneity components is problematic, and its assessment is complex. Therefore, MASI was modified after the removal of this individual component. Thus, the modified MASI (mMASI) is easy to assess and calculate, with a total score ranging from 0 to 24 (52, 53).

Table 4.

Melasma Area Severity Index (MASI)

Melasma Area Severity Index
Areas and Their Scores in MASI
Face is divided into four areas for evaluation of melasma severity, %
Forehead (f) 30
Right malar region (rm) 30
Left malar region (lm)30
Chin (c) 10
Area of involvement (A): Gives a numeric value from 0 to 6, as follows, %
no involvement0
≤ 101
10 - 292
30 - 493
50 - 694
70 - 895
90 - 1006
Assessment of Darkness And Homogeneity
Darkness (D): Gives a value of 0 to 4 as follows
Normal skin color without evidence of hyperpigmentation0
Barely visible hyperpigmentation 1
Mild hyperpigmentation2
Moderate hyperpigmentation 3
Severe hyperpigmentation4
Homogeneity (H) of hyperpigmentation gives a value from 0 to 4, as follows
Normal skin color without evidence of hyperpigmentation0
Specks of involvement1
Small patchy areas of involvement < 1.5 cm diameter2
Patches of involvement > 2 cm diameter 3
Uniform skin involvement without clear areas4

The MASI score is then calculated by the following formula:

MASI = 0.3A(f)[D(f)+H(f)] + 0.3A(rm)[D(rm)+H(rm)] + 0.3A(lm)[D(lm)+H(rm)] + 0.1A(c) [D(c)+H(c)]

The Melasma Severity Score (MSS) is another widely applied score in large trials. The MSS is divided into four grades: clear, mild, moderate, and severe. In clinical trials of therapeutic modalities, clear or mild grades are taken as ideal outcomes. It is composed of objective data and patients’ subjective assessments (54). Therefore, it has significance for both clinicians and patients, as it is easily interpreted and understood by both (55).

Another recently reported score for melasma is the melasma severity index (MSI), which is supposed to overcome the limitations of MASI. In the MASI score, more weightage is given to the area of involvement than the intensity of pigmentation, which ideally should be the other way round. Thus, in the MSI scoring, to give the intensity of pigmentation its due importance in assessing disease severity and psychosocial impact, the 'area of involvement score' is multiplied by the square of the 'pigmentation score.' Secondly, the nose and upper lip are assessed separately because of the non-uniformity of pigmentation in some melasma cases (Figures 2 and 3). The MSI is calculated as follows:

MSI = 0.4(a × p2)l + 0.4(a × p2)r + 0.4(a × p2)n

Melasma with more severe pigmentation on the nose than on other affected areas.
Melasma with more severe pigmentation on the nose than on other affected areas.
Figure 2.

Melasma with more severe pigmentation on the nose than on other affected areas.

Severe melasma where the intensity of pigmentation is again more on the nose than on the malar area.
Severe melasma where the intensity of pigmentation is again more on the nose than on the malar area.
Figure 3.

Severe melasma where the intensity of pigmentation is again more on the nose than on the malar area.

In this formula, “a” denotes the area of involvement, “p” the severity of pigmentation, “l” the left face, “r” the right face, and “n” the nose and upper lip. Both the variables, ie, involvement area and pigmentation severity, are scored from 0 to 4 (56) (Table 5).

Table 5.

Melasma Severity Index (MSI Score)

Melasma Severity Index (MSI Score)
MSI scoreMSI = 0.4(a×p2)l + (a×p2)r + 0.2(a×p2)n a
Scoring of pigmentation
No visible pigmentation0
Barely visible pigmentation1
Mild pigmentation2
Moderate pigmentation3
Severe pigmentation4
Scoring for the area of involvement, %
≤ 101
11 - 302
31 - 603
> 604

a p: severity of pigmentation; a: area of involvement of face; l: left face; r: right face; n: nose; In case of uniform pigmentation over all the involved areas; MSI: max possible score = a×p2 = 4 × 42= 64

The health-related quality of life (HRQoL) tool is one of the scales used to measure the psychosocial impact of various diseases, including dermatological ones. The Melasma Quality of Life Scale (MELASQoL), a modified version of HRQoL, is used in melasma. Besides, it also helps guide treatment methods by tracking changes in patients' HRQoL. The tool includes ten questions about disease impact on the life quality rated on the Likert Scale. It emphasizes the aspects of life most adversely affected by melasma, ie, social life, recreation/leisure, and emotional wellbeing (57). The Visual Analog Scale (VAS) is another tool used for evaluating a patient’s state of mind due to a disease. A score is obtained on a “0 - 10” enumerated vertical line based on a person's emotional state. Emotions felt by melasma patients can range from “no disturbance” to “feeling of hostility.” Accordingly, the VAS value of “0” indicates no feeling of disturbance, “1 - 4” dysphoria, “5 - 6” anxiety, and “7 - 10” a feeling of hostility towards melasma (58). Other similar scales used in melasma studies are the Dermatology Life Quality Index (DLQI) and SKINDEX-16 (59-61).

10. Conclusions

Melasma is a widespread facial pigmentation disorder with a very high prevalence in people with skin color. The condition is more common in the female sex and pregnancy and is associated with a significant impact on the quality of life. The MASI and MSI scoring systems can be used to assess the melasma severity or its response to treatment.

References

  • 1.

    Sheth VM, Pandya AG. Melasma: a comprehensive update: part I. J Am Acad Dermatol. 2011;65(4):689-97. [PubMed ID: 21920241]. https://doi.org/10.1016/j.jaad.2010.12.046.

  • 2.

    Sarkar R, Arora P, Garg VK, Sonthalia S, Gokhale N. Melasma update. Indian Dermatol Online J. 2014;5(4):426-35. [PubMed ID: 25396123]. [PubMed Central ID: PMC4228635]. https://doi.org/10.4103/2229-5178.142484.

  • 3.

    Sivayathorn A. Melasma in Orientals. Clin Drug Invest. 1995;10(Supplement 2):34. https://doi.org/10.2165/00044011-199500102-00006.

  • 4.

    Guinot C, Cheffai S, Latreille J, Dhaoui MA, Youssef S, Jaber K, et al. Aggravating factors for melasma: a prospective study in 197 Tunisian patients. J Eur Acad Dermatol Venereol. 2010;24(9):1060-9. [PubMed ID: 20202051]. https://doi.org/10.1111/j.1468-3083.2010.03592.x.

  • 5.

    Trivedi MK, Yang FC, Cho BK. A review of laser and light therapy in melasma. Int J Womens Dermatol. 2017;3(1):11-20. [PubMed ID: 28492049]. [PubMed Central ID: PMC5418955]. https://doi.org/10.1016/j.ijwd.2017.01.004.

  • 6.

    Ball Arefiev KL, Hantash BM. Advances in the treatment of melasma: a review of the recent literature. Dermatol Surg. 2012;38(7 Pt 1):971-84. [PubMed ID: 22583339]. https://doi.org/10.1111/j.1524-4725.2012.02435.x.

  • 7.

    Freitag FM, Cestari TF, Leopoldo LR, Paludo P, Boza JC. Effect of melasma on quality of life in a sample of women living in southern Brazil. J Eur Acad Dermatol Venereol. 2008;22(6):655-62. [PubMed ID: 18410339]. https://doi.org/10.1111/j.1468-3083.2007.02472.x.

  • 8.

    Walker SL, Shah M, Hubbard VG, Pradhan HM, Ghimire M. Skin disease is common in rural Nepal: results of a point prevalence study. Br J Dermatol. 2008;158(2):334-8.

  • 9.

    Sociedade Brasileira de Dermatologia, Sociedade Brasileira de Dermatologia. Nosologic profile of dermatologic visits in Brazil. An Bras Dermatol. 2006;81:549-58.

  • 10.

    Alakloby OM. Pattern of skin diseases in Eastern Saudi Arabia. Saudi Med J. 2005;26(10):1607-10.

  • 11.

    Halder RM, Grimes PE, McLaurin CI, Kress MA, Kenney Jr JA. Incidence of common dermatoses in a predominantly black dermatologic practice. Cutis. 1983;32(4):388-90.

  • 12.

    Moin A, Jabery Z, Fallah N. Prevalence and awareness of melasma during pregnancy. Int J Dermatol. 2006;45(3):285-8. [PubMed ID: 16533230]. https://doi.org/10.1111/j.1365-4632.2004.02470.x.

  • 13.

    Rathore SP, Gupta S, Gupta V. Pattern and prevalence of physiological cutaneous changes in pregnancy: a study of 2000 antenatal women. Indian J Dermatol Venereol Leprol. 2011;77(3):402. [PubMed ID: 21508591]. https://doi.org/10.4103/0378-6323.79741.

  • 14.

    Werlinger KD, Guevara IL, Gonzalez CM, Rincon ET, Caetano R, Haley RW, et al. Prevalence of self-diagnosed melasma among premenopausal Latino women in Dallas and Fort Worth, Tex. Arch Dermatol. 2007;143(3):424-5. [PubMed ID: 17372115]. https://doi.org/10.1001/archderm.143.3.424.

  • 15.

    Taylor SC. Epidemiology of skin diseases in ethnic populations. Dermatol Clin. 2003;21(4):601-7. https://doi.org/10.1016/s0733-8635(03)00075-5.

  • 16.

    Perez M, Luke J, Rossi A. Melasma in Latin Americans. J Drugs Dermatol. 2011;10(5):517-23.

  • 17.

    Pasricha JS, Khaitan BK, Dash S. Pigmentary disorders in India. Dermatol Clin. 2007;25(3):343-52. [PubMed ID: 17662900]. https://doi.org/10.1016/j.det.2007.05.004.

  • 18.

    Parthasaradhi A, Al Gufai AF. The pattern of skin diseases in Hail Region, Saudi Arabia. Ann Saudi Med. 1998;18(6):558-61. [PubMed ID: 17344753]. https://doi.org/10.5144/0256-4947.1998.558.

  • 19.

    El-Essawi D, Musial JL, Hammad A, Lim HW. A survey of skin disease and skin-related issues in Arab Americans. J Am Acad Dermatol. 2007;56(6):933-8. [PubMed ID: 17321004]. https://doi.org/10.1016/j.jaad.2007.01.031.

  • 20.

    Hiletework M. Skin diseases seen in Kazanchis health center. Ethiop Med J. 1998;36(4):245-54.

  • 21.

    Ishiy PS, Silva LR, Penha MA, Handel AC, Miot HA. Skin diseases reported by workers from UNESP campus at Rubiao Jr, Botucatu-SP (Brazil). An Bras Dermatol. 2014;89(3):529-31. [PubMed ID: 24937840]. [PubMed Central ID: PMC4056724]. https://doi.org/10.1590/abd1806-4841.20142875.

  • 22.

    Sanchez MR. Cutaneous diseases in Latinos. Dermatol Clin. 2003;21(4):689-97. https://doi.org/10.1016/s0733-8635(03)00087-1.

  • 23.

    Albares Tendero MP, Belinchon Romero I, Ramos Rincon JM, Sanchez Paya J, Costa AL, Perez Crespo M, et al. Dermatoses in Latin American immigrants seen in a tertiary hospital. Eur J Dermatol. 2009;19(2):157-62. [PubMed ID: 19106052]. https://doi.org/10.1684/ejd.2008.0600.

  • 24.

    Handel AC, Miot LD, Miot HA. Melasma: a clinical and epidemiological review. An Bras Dermatol. 2014;89(5):771-82. [PubMed ID: 25184917]. [PubMed Central ID: PMC4155956]. https://doi.org/10.1590/abd1806-4841.20143063.

  • 25.

    Handel AC, Lima PB, Tonolli VM, Miot LD, Miot HA. Risk factors for facial melasma in women: a case-control study. Br J Dermatol. 2014;171(3):588-94. [PubMed ID: 24749693]. https://doi.org/10.1111/bjd.13059.

  • 26.

    Goh CL, Dlova CN. A retrospective study on the clinical presentation and treatment outcome of melasma in a tertiary dermatological referral centre in Singapore. Singapore Med J. 1999;40(7):455-8.

  • 27.

    Tamega Ade A, Miot LD, Bonfietti C, Gige TC, Marques ME, Miot HA. Clinical patterns and epidemiological characteristics of facial melasma in Brazilian women. J Eur Acad Dermatol Venereol. 2013;27(2):151-6. [PubMed ID: 22212073]. https://doi.org/10.1111/j.1468-3083.2011.04430.x.

  • 28.

    Hexsel D, Lacerda DA, Cavalcante AS, Machado Filho CA, Kalil CL, Ayres EL, et al. Epidemiology of melasma in Brazilian patients: a multicenter study. Int J Dermatol. 2014;53(4):440-4. [PubMed ID: 23967822]. https://doi.org/10.1111/j.1365-4632.2012.05748.x.

  • 29.

    Achar A, Rathi SK. Melasma: a clinico-epidemiological study of 312 cases. Indian J Dermatol. 2011;56(4):380-2. [PubMed ID: 21965843]. [PubMed Central ID: PMC3178998]. https://doi.org/10.4103/0019-5154.84722.

  • 30.

    Mandry Pagan R, Sanchez JL. Mandibular Melasma. P R Health Sci J. 2000;19:231-431.

  • 31.

    Kang WH, Yoon KH, Lee ES, Kim J, Lee KB, Yim H, et al. Melasma: histopathological characteristics in 56 Korean patients. Br J Dermatol. 2002;146(2):228-37. https://doi.org/10.1046/j.0007-0963.2001.04556.x.

  • 32.

    Ortonne JP, Arellano I, Berneburg M, Cestari T, Chan H, Grimes P, et al. A global survey of the role of ultraviolet radiation and hormonal influences in the development of melasma. J Eur Acad Dermatol Venereol. 2009;23(11):1254-62. [PubMed ID: 19486232]. https://doi.org/10.1111/j.1468-3083.2009.03295.x.

  • 33.

    Edalat Khah H, Amani F, Rezaifar G. Prevalence of melasma in women in Ardebil city in 2002. Iran J Dermatol. 2004;7(2):72-7.

  • 34.

    Hexsel D, Rodrigues TC, Dal'Forno T, Zechmeister-Prado D, Lima MM. Melasma and pregnancy in southern Brazil. J Eur Acad Dermatol Venereol. 2009;23(3):367-8. [PubMed ID: 18631207]. https://doi.org/10.1111/j.1468-3083.2008.02885.x.

  • 35.

    Shanza I, Aisha M, Majid S. Physiological skin changes during pregnancy. J Pakistan Assoc Dermatologists. 2018;28:219-23.

  • 36.

    Esteve E, Saudeau L, Pierre F, Barruet K, Vaillant L, Lorette G. Physiological cutaneous signs in normal pregnancy: a study of 60 pregnant women. Ann Dermatol Venereol. 1994;121(3):227-31.

  • 37.

    Martin AG, Leal-Khouri S. Physiologic skin changes associated with pregnancy. Int J Dermatol. 1992;31(6):375-8. [PubMed ID: 1512085]. https://doi.org/10.1111/j.1365-4362.1992.tb02662.x.

  • 38.

    Hassan I, Kaur I, Sialy R, Dash RJ. Hormonal milieu in the maintenance of melasma in fertile women. J Dermatol. 1998;25(8):510-2. [PubMed ID: 9769595]. https://doi.org/10.1111/j.1346-8138.1998.tb02445.x.

  • 39.

    Perez-Bernal A, Munoz-Perez MA, Camacho F. Management of facial hyperpigmentation. Am J Clin Dermatol. 2000;1(5):261-8. [PubMed ID: 11702317]. https://doi.org/10.2165/00128071-200001050-00001.

  • 40.

    Miot LD, Miot HA, Silva MG, Marques ME. [Physiopathology of melasma]. An Bras Dermatol. 2009;84(6):623-35. Portuguese. [PubMed ID: 20191174]. https://doi.org/10.1590/s0365-05962009000600008.

  • 41.

    Videira IF, Moura DF, Magina S. Mechanisms regulating melanogenesis. An Bras Dermatol. 2013;88(1):76-83. [PubMed ID: 23539007]. [PubMed Central ID: PMC3699939]. https://doi.org/10.1590/s0365-05962013000100009.

  • 42.

    Sarkar R, Puri P, Jain RK, Singh A, Desai A. Melasma in men: a clinical, aetiological and histological study. J Eur Acad Dermatol Venereol. 2010;24(7):768-72. [PubMed ID: 20015053]. https://doi.org/10.1111/j.1468-3083.2009.03524.x.

  • 43.

    Pichardo R, Vallejos Q, Feldman SR, Schulz MR, Verma A, Quandt SA, et al. The prevalence of melasma and its association with quality of life in adult male Latino migrant workers. Int J Dermatol. 2009;48(1):22-6. [PubMed ID: 19126046]. [PubMed Central ID: PMC2621062]. https://doi.org/10.1111/j.1365-4632.2009.03778.x.

  • 44.

    Shenoi SD, Davis SV, Rao S, Rao G, Nair S. Dermatoses among paddy field workers--a descriptive, cross-sectional pilot study. Indian J Dermatol Venereol Leprol. 2005;71(4):254-8. [PubMed ID: 16394434]. https://doi.org/10.4103/0378-6323.16617.

  • 45.

    Damevska K. New Aspects of Melasma/Novi aspekti melazme. Serbian J Dermatology Venereol. 2014;6(1):5-18. https://doi.org/10.2478/sjdv-2014-0001.

  • 46.

    Suryanigsih BE. Characteristics of facial melasma on Javanese women in Yogyakarta, Indonesia. J Pakistan Assoc Dermatologists. 2018;28(3):306-10.

  • 47.

    Katsambas A, Antoniou C. Melasma. Classification and treatment. J Eur Acad Dermatol Venereol. 1995;4(3):217-23. https://doi.org/10.1111/j.1468-3083.1995.tb00341.x.

  • 48.

    Ritter CG, Fiss DVC, Borges da Costa JAT, De Carvalho RR, Bauermann G, Cestari TF. Extra‐facial melasma: clinical, histopathological, and immunohistochemical case‐control study. J Eur Acad Dermatol Venereol. 2013;27(9).

  • 49.

    O'Brien TJ, Dyall-Smith D, Hall AP. Melasma of the arms associated with hormone replacement therapy. Br J Dermatol. 1999;141(3):592-3. [PubMed ID: 10583090]. https://doi.org/10.1046/j.1365-2133.1999.03079.x.

  • 50.

    Errichetti E, Lallas A. Hyperpigmented dermatoses. In: Lallas A, Errichetti E, Ioannides D, editors. Dermoscopy in General Dermatology. CRC Press; 2018. https://doi.org/10.1201/9781315201733-7.

  • 51.

    Kimbrough-Green CK, Griffiths CE, Finkel LJ, Hamilton TA, Bulengo-Ransby SM, Ellis CN, et al. Topical retinoic acid (tretinoin) for melasma in black patients. A vehicle-controlled clinical trial. Arch Dermatol. 1994;130(6):727-33. [PubMed ID: 8002642].

  • 52.

    Pandya AG, Hynan LS, Bhore R, Riley FC, Guevara IL, Grimes P, et al. Reliability assessment and validation of the Melasma Area and Severity Index (MASI) and a new modified MASI scoring method. J Am Acad Dermatol. 2011;64(1):78-83. [PubMed ID: 20398960]. https://doi.org/10.1016/j.jaad.2009.10.051.

  • 53.

    Rodrigues M, Ayala-Cortes AS, Rodriguez-Arambula A, Hynan LS, Pandya AG. Interpretability of the Modified Melasma Area and Severity Index (mMASI). JAMA Dermatol. 2016;152(9):1051-2. [PubMed ID: 27144383]. https://doi.org/10.1001/jamadermatol.2016.1006.

  • 54.

    Taylor SC, Torok H, Jones T, Lowe N, Rich P, Tschen E, et al. Efficacy and safety of a new triple-combination agent for the treatment of facial melasma. Cutis. 2003;72(1):67-73.

  • 55.

    Majid I, Haq I, Imran S, Keen A, Aziz K, Arif T. Proposing Melasma Severity Index: A New, More Practical, Office-based Scoring System for Assessing the Severity of Melasma. Indian J Dermatol. 2016;61(1):39-44. [PubMed ID: 26955093]. [PubMed Central ID: PMC4763693]. https://doi.org/10.4103/0019-5154.174024.

  • 56.

    Balkrishnan R, McMichael AJ, Camacho FT, Saltzberg F, Housman TS, Grummer S, et al. Development and validation of a health-related quality of life instrument for women with melasma. Br J Dermatol. 2003;149(3):572-7. [PubMed ID: 14510991]. https://doi.org/10.1046/j.1365-2133.2003.05419.x.

  • 57.

    Aitken RCB. Measurement of Feelings using visual analogue scales. Proc R Soc Med. 1969;62(10):989-93. https://doi.org/10.1177/003591576906201005.

  • 58.

    Sarkar R, Garg V, Bansal S, Sethi S, Gupta C. Comparative Evaluation of Efficacy and Tolerability of Glycolic Acid, Salicylic Mandelic Acid, and Phytic Acid Combination Peels in Melasma. Dermatol Surg. 2016;42(3):384-91. [PubMed ID: 26859648]. https://doi.org/10.1097/DSS.0000000000000642.

  • 59.

    Mazurek K, Pierzchala E. Comparison of efficacy of products containing azelaic acid in melasma treatment. J Cosmet Dermatol. 2016;15(3):269-82. [PubMed ID: 27028014]. https://doi.org/10.1111/jocd.12217.

  • 60.

    Kim SJ, Park JY, Shibata T, Fujiwara R, Kang HY. Efficacy and possible mechanisms of topical tranexamic acid in melasma. Clin Exp Dermatol. 2016;41(5):480-5. [PubMed ID: 27135282]. https://doi.org/10.1111/ced.12835.

  • 61.

    Dayal S, Sahu P, Dua R. Combination of glycolic acid peel and topical 20% azelaic acid cream in melasma patients: efficacy and improvement in quality of life. J Cosmet Dermatol. 2017;16(1):35-42. [PubMed ID: 27500896]. https://doi.org/10.1111/jocd.12260.