Role of Primary Care in the Prevention of Melasma

Melasma is often referred to as the mask of pregnancy. Affecting 15% to 50% of pregnant individuals, melasma (or chloasma) presents as irregular, light to dark brown macules in a symmetrical pattern on sun-exposed areas of the body — most commonly the face.^1,2  Melasma can occur in both men and women but is considerably more prevalent in women, affecting approximately 5 to 6 million women in the United States. This statistic is likely an underestimate, failing to account for those who are misdiagnosed or do not present to clinic for treatment.^1-4

Melasma is an acquired hypermelanosis that is distributed in various facial patterns, with malar and centrofacial (forehead, nose, cheeks, upper lip, and chin) being the most common and mandibular involvement seen less often.^2,5 The majority of patients exhibit only hyperpigmentation, but those who also experience increased inflammation may develop itching, tingling, dryness, and erythema.⁵ Clinical diagnosis is based on presentation and patient history, which most often includes pregnancy, the use of oral contraceptive pills (OCPs), or a family member who has had the disease.² Although the specific cause of melasma is unknown, a genetic predisposition has been suggested, as has a role for increased hormonal activity.²

Treatment generally involves ineffective topical therapies, expensive cosmetic procedures, minimal long-term improvement, and recurrence.^3,6 Although melasma is a dermatologic complaint, primary care physicians (PCPs) and those providing women’s health should be able to recognize and manage it. Interventions made in the primary care office can help prevent the occurrence and improve overall management of melasma. 

Why is Prevention Important?

Ineffective Treatment

Although several treatments are effective in reducing hyperpigmentation, melasma is a chronic illness and relapse is very common once therapy is withdrawn.^5,7,8 Similarly, maintenance regimens can help manage relapses, but they have limitations. First-line topical therapies, such as hydroquinone or the triple combination of hydroquinone, a retinol, and steroid, can only be used for a limited time for safety reasons.⁷ The use of serial chemical peels and laser treatments can become extremely costly.⁷ Thus, if melasma can be prevented or its severity controlled with protective measures, its course and management can be much improved.

Long-term use of high-quality broad-spectrum sunscreen that protects against both ultraviolet (UV) and visible light (VL) may help prevent the development of initial melasma lesions, decrease the likelihood of recurrences, and help maintain the positive results obtained with initial treatment. However, it usually cannot resolve existing lesions or prevent recurrences completely.⁹ Furthermore, no definitive treatment option is effective for every individual with melasma, so prevention is vital.

Effect on Mental Health

Although melasma primarily affects the face,  it has been associated with an increase in psychiatric illnesses and a possible decrease in quality of life (QoL) in a significant number of patients.⁸ The chronic and recurrent nature of this disease, along with the lack of a definitive gold standard treatment, increases the mental health burden. Although melasma is not currently classified as a psycho-cutaneous disorder, its association with psychiatric conditions is significant, emphasizing the need for effective prevention and management.¹⁰

Cross-sectional studies have used psychiatric scales — including the 4-item Perceived Stress Scale, World Health Organization Disability Assessment Scale 2.0, and Hospital Anxiety Depression Scale — as well as the Melasma Area and Severity Index (MASI) to assess the prevalence of psychiatric diseases in individuals with melasma vs those without the disease.^10,11 Anxiety, depression, and adjustment disorder were seen approximately 20% more often in patients with melasma.^10,11 Although causation cannot be established, the correlation between melasma and depressive and stress disorders suggests that this recurring dermatologic syndrome affects more than the face and has an important relationship with the patient’s QoL.

Pathogenesis

The full etiology and pathogenesis of melasma have yet to be elucidated; however, hormones and UV exposure are thought to play significant roles.

The increased prevalence of melasma in women during the child-bearing years, especially in those who are pregnant or taking OCPs, suggests a hormonal influence on the development of this disease.^1-3 Therefore, several possible theories have emerged regarding the impact of hormonal activity on the etiology of melasma. For example, an increased number of progesterone receptors has been observed in the epidermis of melasma lesions vs healthy skin.¹²

Evidence suggests, however, that the estrogen level reached during pregnancy or estrogen-containing contraceptive use has a greater effect on the hypermelanosis seen in patients with melasma. Estrogen is believed to augment the H19 downregulation already associated with the development of melasma.⁴ The H19 gene transcribes noncoding RNA, which influences gene expression. Researchers have noted downregulation of the H19 gene in the skin of melasma patients. In one study, increased melanogenesis was observed in H19-gene depleted tissue cultures.⁴ When estrogen was added to these cultures, an increase in the melanin biomarker tyrosinase and a further increase in melanogenesis were observed, further supporting the relationship between the H19 gene and melasma.

Findings with respect to both progesterone and estrogen help support the hormonal-influence theory of melasma development in pregnant persons and those starting OCPs.³ Further research is needed to better understand these relationships. 

Unprotected UV radiation exposure is considered the most important environmental trigger of melasma.^1-3,13 UV radiation may cause keratinocytes to increase the production of cytokines that stimulate melanogenesis.¹ The pathogenesis of UV radiation and melasma is believed to also involve activated nitric oxide and melanogenesis caused by reactive oxygen species and oxidative stress.¹² Furthermore, prolonged sun exposure also damages the integrity of the stratum corneum and delays barrier recovery of the epidermis. This effect on recovery may play a role in the recurrence of melasma with subsequent UV radiation.¹³

Visible light is also a component of solar radiation. It can induce hyperpigmentation similar to that caused by UV radiation, especially in darker-skinned patients.^14,15Visible light can also produce reactive oxygen species that lead to the release of inflammatory cytokines and enzymes that damage the matrix of the skin.¹⁴

A patient history of frequent sun exposure or use of tanning beds confers high risk for the development of melasma. Lifestyle or environmental factors also increase the likelihood of recurrent melasma, underscoring the importance of implementing preventative measures.

Risk Factors

Pregnancy

As noted, pregnancy has long been associated with the development of melasma. In a European global questionnaire and multicenter studies performed in Brazil and India, more than 75% of patients with melasma had a history of at least 1 pregnancy.¹⁶ Multiple pregnancies increased the odds of onset during pregnancy, such that individuals with 2 pregnancies were twice as likely as those with only 1 pregnancy to develop melasma. This exponential relationship was consistent, with a history of 3 pregnancies correlating with a 3-fold increase in risk.¹⁷

A possible explanation for why female sex hormones trigger melasma is that during the third trimester of pregnancy, elevated levels of placental, ovarian, and other hormones stimulate melanogenesis.³ Specifically, an increase in pituitary hormones is linked to transcription of genes related to melanogenesis, (eg, tyrosinase) and a further increase in pigmentation.³ As noted, increases in estrogen and progesterone levels during and after pregnancy may also lead to melanogenesis. These hormone changes may explain why melasma is seen more commonly in women who have a history of pregnancy than those who do not.¹⁷

Oral Contraceptive Pills

Studies support a relationship between the use of estrogen-containing OCPs and the development of melasma; more than 80% of women with melasma have a history of OCP use.¹⁸

Researchers have also investigated various birth control options and whether combination OCPs (COCPs; estrogen plus progesterone) contribute more often to the development of melasma than monotherapy (progesterone alone). Further research is needed to understand this relationship, but limited study evidence indicates that higher systemic progesterone levels from COCPs could increase the likelihood of melasma development compared with a levonorgestrel-releasing intra-uterine device (LNG-IUD). Levonorgestrel is a progesterone derivative, and an LNG-IUD does not contain estrogen. The FDA found that only 0.06% of patients with an LNG-IUD had melasma.¹⁹ This implies that progesterone is not the main or only hormonal culprit in the development of melasma, at least not at the concentration in an LNG-IUD. Combination OCPs increase progesterone serum levels 10 times higher than LNG-IUDs¹⁹ and release estrogen. These higher levels of both estrogen and progesterone in patients taking COCPs (compared with progesterone-only IUDs) supports a need for further exploration of the role both hormones have in the development of melasma. Some evidence suggests patients who are taking OCPs and experience melasma may benefit from a change to an alternative contraception option, such as an LNG-IUD.¹⁹

Skin Types

Melasma occurs in all ethnic groups but has an increased prevalence in East Asian, Indian, and Middle Eastern populations.³ This predominance correlates with an increased prevalence of melasma in those with Fitzpatrick skin types III and IV.^1-3 Fitzpatrick skin type classification is based on tanning ability, color, and typical features (Table) .^1-3 Types III and IV feature increased epidermal melanin as well as larger and more widely distributed melanosomes.²⁰

Melanosomes are synthesized in melanocytes and transported to neighboring keratinocytes where they cause pigmentation of skin and hair.²¹ A decreased degradation of melanosomes in keratinocytes and therefore, increased number of mature melanosomes, has been associated with the epidermal hyperpigmentation seen in melasma.^1,4 Unlike non-lesion skin, in which melanin pigment is limited to the stratum basal layer of the epidermis, melasma lesions have melanin in all layers, including the top layer, or stratum corneum.^1,3 The epidermis in melasma also shows melanocytic hyperactivity and hypertrophy without melanocytic hyperplasia.^1,3 Although non-modifiable, this risk factor is important to consider when discussing melasma prevention with patients. In addition to increased hormonal activity, patients should be evaluated and counseled based on skin type, particularly those with types III or IV.  

Prevention

The strong association between modifiable risk factors and the formation of lesions provides PCPs the opportunity to educate patients and provide tools to reduce the severity of hyperpigmentation or prevent lesion development entirely.

When PCPs counsel patients who are pregnant or taking OCPs, they can provide education on melasma and how hormones affect the skin. Because female hormones are dynamic variables critical in several physiologic processes, they are not easily controlled or limited, especially during pregnancy.¹⁷ However, patients at higher risk for melasma due to non-modifiable hormone risk factors should be counseled on their increased risk, how the disease presents, and what factors they can modify, such as solar radiation. The use of a daily sunscreen as soon as a patient starts on OCPs or becomes pregnant may be an important and manageable step toward preventing melasma or reducing its severity. This is especially important in those with Fitzpatrick skin types III and IV.¹²

Research has identified which sunscreens are most effective in reducing occurrence and severity of melasma lesions.^1,2 Most commercial sunscreens only protect against UV radiation and usually only wavelengths of less than 380 nm. These sunscreens do not protect against radiation from VL or of longer wavelengths.¹⁴ Tinted (colored) sunscreens, conversely, contain titanium dioxide as well as iron oxides, which are capable of blocking both VL and UV radiation.^14,15

In a study of the effect that tinted sunscreen may have on melasma lesions, a group of patients using UV-VL (tinted) sunscreen showed 15%, 28%, and 4% greater improvement in MASI score, colorimetry, and melanin analysis, respectively, compared with a group that used UV-only sunscreen.¹⁴MASI is calculated through visual inspection of the face and assessment of the percentage of affected area, hyperpigmentation, and homogeneity of the pigmentation. These results help support the positive effect of VL protection on melasma.¹⁴ Patients using UV-only sunscreen may not realize that they are still receiving damaging VL radiation and are therefore at continued risk for developing hyperpigmented lesions.^14,15

The best practice with regard to melasma prevention in the primary care setting would include counseling on the daily use of a tinted broad-spectrum sunscreen with a sun protection factor of at least 30 that incorporates physical blocking agents (eg, zinc oxide and titanium dioxide) and iron oxide for every pregnant patient or patient started on OCPs. This is especially important for individuals with Fitzpatrick skin types III or IV.¹²

Conclusion

Melasma is an often-overlooked skin disease that can have significant effects on facial aesthetics, mental health, and overall QoL. Although a referral to dermatology is recommended once a patient is diagnosed with melasma, PCPs play a critical role in the prevention and early management of this skin disorder. Patient education should include counseling on risk factors, limiting exposure to UV and VL radiation, and the use of tinted sunscreens as appropriate. These preventative measures can greatly affect not only the incidence and prevalence of melasma, but also recurrence and long-term management outcomes for patients with this disease. 

Kendra Summers, PA-S, is a recent graduate of Augusta University’s class of 2023. Elizabeth Prince-Coleman, MPA, PA-C, has been in practice for almost 9 years with Augusta University Health. She also serves as the program director for the Augusta University PA Program.

References

1. 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. Published online January 2, 2012. doi:10.1111/j.1468-3083.2011.04430.x
2. Hexsel D, Lacerda DA, Cavalcante AS, et al. Epidemiology of melasma in Brazilian patients: A multicenter study. Int J Dermatol. Published online August 22, 2013. doi:10.1111/j.1365-4632.2012.05748.x
3. Handel AC, Miot LD, Miot HA. Melasma: A clinical and epidemiological review. An Bras Dermatol. 2014;89(5):771-782. doi:10.1590/abd1806-4841.20143063
4. Kim NH, Lee CH, Lee AY. H19 RNA downregulation stimulated melanogenesis in melasma. Pigment Cell Melanoma Res. Published online December 4, 2009. doi:10.1111/j.1755-148X.2009.00659.x
5. Noh TK, Choi SJ, Chung BY, et al. Inflammatory features of melasma lesions in Asian skin. J Dermatol. Published online August 11, 2014. doi:10.1111/1346-8138.12573
6. Basit H, Godse KV, Al Aboud AM. Melasma. In: StatPearls [internet]. Treasure Island, FL: StatPearls Publishing; January 2023.
7. Sarkar R, Gokhale N, Godse K, et al. Medical management of melasma: A review with consensus recommendations by Indian pigmentary expert group. Indian J Dermatol. 2017;62(6):558-577. doi:10.4103/ijd.IJD_489_17
8. Pollo CF, Meneguin S, Miot HA. Evaluation instruments for quality of life related to melasma: An integrative review. Clinics (Sao Paulo). Published online May 21, 2018. doi:10.6061/clinics/2018/e65
9. Fatima S, Braunberger T, Mohammad TF, Kohli I, Hamzavi IH. The role of sunscreen in melasma and postinflammatory hyperpigmentation. Indian J Dermatol. 2020;65(1):5-10. doi:10.4103/ijd.IJD_295_18
10. Deshpande SS, Khatu SS, Pardeshi GS, Gokhale NR. Cross-sectional study of psychiatric morbidity in patients with melasma. Indian J Psychiatry. 2018;60(3):324-328. doi:10.4103/psychiatry.IndianJPsychiatry_115_16
11. Espósito MCC, Espósito ACC, Jorge MFS, D’Elia MPB, Miot HA. Depression, anxiety, and self-esteem in women with facial melasma: An internet-based survey in Brazil. Int J Dermatol. Published online March 17, 2021. doi:10.1111/ijd.15490
12. Ogbechie-Godec OA, Elbuluk N. Melasma: An up-to-date comprehensive review. Dermatol Ther (Heidelb). Published online July 19, 2017. doi:10.1007/s13555-017-0194-1
13. Lee DJ, Lee J, Ha J, Park KC, Ortonne JP, Kang HY. Defective barrier function in melasma skin. J Eur Acad Dermatol Venereol. Published online November 12, 2012. doi:10.1111/j.1468-3083.2011.04337.x
14. Castanedo-Cazares JP, Hernandez-Blanco D, Carlos-Ortega B, Fuentes-Ahumada C, Torres-Álvarez B. Near-visible light and UV photoprotection in the treatment of melasma: A double-blind randomized trial. Photodermatol Photoimmunol Photomed. Published online December 13, 2013. doi:10.1111/phpp.12086
15. Geisler AN, Austin E, Nguyen J, Hamzavi I, Jagdeo J, Lim HW. Visible light part II: Photoprotection against visible and ultraviolet light. J Am Acad Dermatol. Published online February 25, 2021. doi:10.1016/j.jaad.2020.11.074
16. KrupaShankar DS, Somani VK, Kohli M, et al. A cross-sectional, multicentric clinico-epidemiological study of melasma in India. Dermatol Ther (Heidelb). Published online March 19, 2014. doi:10.1007/s13555-014-0046-1
17. Ortonne JP, Arellano I, Berneburg M, et al. A global survey of the role of ultraviolet radiation and hormonal influences in the development of melasma. J Eur Acad Dermatol Venereol. Published online May 19, 2009. doi:10.1111/j.1468-3083.2009.03295.x
18. Rostami Mogaddam M, Safavi Ardabili N, Iranparvar Alamdari M, Maleki N, Aghabalaei Danesh M. Evaluation of the serum zinc level in adult patients with melasma: Is there a relationship with serum zinc deficiency and melasma? J Cosmet Dermatol. Published online November 12, 2017. doi:10.1111/jocd.12392
19. Locci-Molina N, Wang A, Kroumpouzos G. Melasma improving spontaneously upon switching from a combined oral contraceptive to a hormone-releasing intrauterine device: A report of four cases. Acta Derm Venereol. 2015;95(5):624-625. doi:10.2340/00015555-2013
20. Sharma AN, Patel BC. Laser Fitzpatrick skin type recommendations. In: StatPearls [internet]. Treasure Island, FL: StatPearls Publishing; March 9, 2022.
21. Wasmeier C, Hume AN, Bolasco G, Seabra MC. Melanosomes at a glance. J Cell Sci. 2008;121(pt 24):3995-3999. doi:10.1242/jcs.040667