Melasma Treatment & Management

Melasma can be difficult to treat. The pigment of melasma develops gradually, and resolution is also gradual. Resistant cases or recurrences of melasma occur often and are certain if strict avoidance of sunlight is not rigidly heeded. All wavelengths of sunlight, including the visible spectrum, are capable of inducing melasma. The best treatment remains a topical hydroquinine cream, sun avoidance, and no estrogen exposure. Boosters are only of limited benefit. A chemical peel or laser treatment may help in about one third of the cases, one third of cases remain the same, and another one third of cases show hyperpigmentation.^[8]

Quick fixes with destructive modalities (eg, cryotherapy, medium-depth chemical peels, lasers) yield unpredictable results and are associated with a number of potential adverse effects, including epidermal necrosis, postinflammatory hyperpigmentation, and hypertrophic scars.^{[9, 10]} The precise manner in which these modalities can be used has not been fully delineated. However, in some experienced hands, they have been anecdotally reported to be safe and effective and to produce results much quicker than topical medications.^[11] Jeong et al report that combination treatment with Triple Combination cream followed by laser treatment (1064-nm Q-switched Nd:YAG) was effective, with no adverse effects.^[12] Although the study was small, it suggests that topical treatment should be started at least 8 weeks prior to laser treatment for melasma in order to achieve optimal results.^[13]

Another study compared topical treatment with triple topical therapy with nonablative fractional laser therapy.^[14] Both treatments were somewhat beneficial. However, the study did not clearly identify patients who experienced flare ups after the laser therapy. Typically, reactive hyperpigmentation develops in around one third of the cases, especially in patients with dark complexions. The current recommendations are to treat with triple cream for 8 weeks before a fractional laser treatment. Patients must still be warned of the potential flare-up. Absolute light avoidance is necessary; thus, a good sunscreen must be used during the day, even when inside.

More careful study is needed before they can be recommended as a standard treatment. Topical hydroquinone remains the criterion standard for treatment, and, at concentrations of 4% or less, few patients experience adverse effects from the topical treatment.^[15]

In an attempt to hasten resolution of melasma, many practitioners attempt mild exfoliation with superficial chemical peels. The rational is that if melanogenesis is inhibited with bleaching agents and keratinocyte turnover is increased, the time to resolution can be reduced. A number of studies have shown that treating melasma with superficial chemical peels and a bleaching agent is safe and effective. Whether superficial chemical peels versus bleaching agents alone actually hasten the resolution of pigment is debated. Studies comparing bleaching agents alone to the combination of bleaching agents and superficial chemical peels are ongoing and may help to resolve the debate.

The mainstay of treatment for melasma remains topical depigmenting agents. Hydroquinone (HQ) is most commonly used.^[16] It is a hydroxyphenolic chemical that inhibits tyrosinase, leading to the decreased production of melanin. Additionally, cytotoxic metabolites may cause interference with melanocyte function and viability. HQ can be applied in cream form or as an alcohol-based solution.

Concentrations vary from a 2% concentration available in the United States without a prescription to a standard 4% concentration and even higher when compounded. Efficacy is directly linked to concentration, but the incidence of adverse effects also increases with concentration. All concentrations can lead to skin irritation, phototoxic reactions with secondary postinflammatory hyperpigmentation, and irreversible exogenous ochronosis (reported even with long-term use of 2% HQ). Special care must be taken not to prescribe the monobenzyl ether of HQ (Benoquin), which causes an irreversible localized and generalized vitiligolike leukoderma.

The use of tretinoin (trans- retinoic-acid) can be effective as monotherapy.^{[17, 18]} However, the response to treatment is less than with HQ and can be slow, with improvement taking 6 months or longer.

As such, combinations of tretinoin with HQ, with or without a topical corticosteroid, have been promoted.^[19] In fact, the only topical ointment currently approved by the US Food and Drug Administration (FDA) for the treatment of melasma is the Triple Combination Cream, a composite of hydroquinone 4%, tretinoin 0.05%, and fluocinolone acetonide 0.01%. Comparative studies of the effectiveness of the Triple Combination cream vs topical HQ suggest that the combination cream is faster and more effective at reducing melasma pigmentation, but it does carry a slightly increased risk of an adverse reaction.^[20]

The major adverse effect is mild, generally skin irritation, especially when the more effective, higher concentrations are used. Temporary photosensitivity and paradoxical hyperpigmentation can also occur. Tretinoin is believed to work by increasing keratinocyte turnover and thus limiting the transfer of melanosomes to keratinocytes. A 2010 study found that Triple Combination cream is safe and effective when used intermittently or continuously for up to 24 weeks.^[21]

Azelaic acid, available as a 20% cream-based formulation, appears to be an effective alternative to 4% HQ and may be superior to 2% HQ in the treatment of melasma.^{[22, 23]} The mechanism of action is not fully understood. DNA synthesis is reduced, and mitochondrial cellular energy products are inhibited in melanocytes. Unlike HQ, azelaic acid seems to target only hyperactive melanocytes and thus will not lighten skin with normally functioning melanocytes. The primary adverse effect is skin irritation. No phototoxic or photoallergic reactions have been reported.

Other depigmenting agents that have been studied in the treatment of melasma are 4-N -butylresorcinol, phenolic-thioether, 4-isopropylcatechol, kojic acid, and ascorbic acid.^[24] It has been suggested that taking an oral proanthocyanidin (a class of flavonols) along with a vitamin regimen may significantly reduce pigmentation. At this time, the mechanism for this treatment method is not fully understood. Significantly more study is necessary before this method of treatment could be deemed effective. One major benefit to this mode, however, is that the use of proanthocyanidin is a natural treatment method, and it is a safe alternative in patients who exhibit a moderate or severe adverse reaction to a topical treatment.^[25]

Regardless of the treatments used, all will fail if sunlight is not strictly avoided. Prudent measures to avoid sun exposure include hats and other forms of shade combined with the application of a broad-spectrum sunscreen at least daily. Sunscreens containing physical blockers, such as titanium dioxide and zinc oxide, are preferred over chemical blockers because of their broader protection. UV-B, UV-A, and visible light are all capable of stimulating melanogenesis. In addition, patients should be forewarned that resolution is gradual and may take many months.