eMedicine Specialties > Dermatology > Diseases of Pigmentation
Melasma: Treatment & Medication
Updated: Dec 16, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
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.
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.7,8 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.9 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.10
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.11
- 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.12,13 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.14 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.15 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.
- 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.16,17 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.18 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.19
Activity
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.
Medication
The goals of pharmacotherapy are to reduce morbidity and prevent complications.
Depigmenting agents
These agents inhibit key enzymes involved in melanin synthesis.
Hydroquinone USP 4% (Claripel cream with sunscreens)
Produces reversible depigmentation of skin by inhibiting enzymatic oxidation of tyrosine to 3-(3,4-dihydroxyphenyl-alanine [dopa]) and suppression of other melanocyte metabolic processes. Exposure to sunlight or UV light causes repigmentation, which may be prevented by the broad-spectrum sunscreen agents contained in this product.
Adult
Apply to affected areas bid
Pediatric
<12 years: Not established
>12 years: Administer as in adults
None reported
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
May produce unwanted cosmetic effects if not used as directed; physician should be familiar with contents of prescribing insert before prescribing or dispensing medication; test for skin sensitivity before using product by applying to small area of unbroken skin (minor redness is not a contraindication, but discontinue if itching, vesicle formation, or excessive inflammatory response occurs); avoid contact with eyes; do not use for prevention of sunburn; discontinue use if no lightening effect is noted after 2 mo of treatment; on rare occasions, a gradual blue-black darkening of the skin may occur (discontinue if it occurs)
Hydroquinone (Alphaquin HP, Alustra, Eldopaque, Eldopaque Forte, Eldoquin, Eldoquin Forte, Esoterica, Esoterica Sensitive Skin, Glyquin, Glyquin-XM, Lustra, Melanex, Melanol, Melpaque HP, Melquin HP, Melquin-3, Nuquin HP, Solaquin, Solaquin Forte, Viquin Forte)
Suppresses melanocyte metabolic processes, especially enzymatic oxidation of tyrosine to 3,4-dihydroxyphenylamine. Exposure to sun reverses effects and causes repigmentation. Lightens healthy and hyperpigmented skin.
Adult
Apply sparingly and rub bid
Pediatric
<12 years: Not established
>12 years: Administer as in adults
None reported
Documented hypersensitivity; sunburns
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Adverse effects include allergic and irritant contact dermatitis, phototoxic reactions, and exogenous ochronosis (rare); application area should not exceed that of face, neck, hands, or arms
Antibiotic agents
These agents inhibit DNA synthesis and mitochondrial enzymes to interrupt hyperactive melanocytes. Normally functioning melanocytes are not inhibited.
Azelaic acid (Azelex) Cream 20%
May decrease microcomedo formation. May have bleaching effect on skin. May also have antimicrobial effect.
Adult
Wash area and apply sparingly bid
Pediatric
Not established
None reported
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Avoid contact with eyes; discontinue use if severe irritation develops; adverse effects include erythema, stinging or burning sensation, pruritus, and scaling
Retinoids
These agents regulate cell growth and proliferation.
Tretinoin (Avita, Retin-A)
Inhibits microcomedo formation and eliminates lesions. Makes keratinocytes in sebaceous follicles less adherent and easier to remove. Dosage formulations include 0.025%, 0.05%, and 0.1% cream; 0.01%, 0.025%, and 0.1% gel; and 0.05% solution.
Adult
Begin with lowest tretinoin formulation and increase as tolerated; apply hs or qod; lower frequency of application if irritation develops
Pediatric
<12 years: Not established
>12 years: Administer as in adults
Toxicity increases with coadministration of benzoyl peroxide, salicylic acid, and resorcinol; avoid topical sulfur, resorcinol, salicylic acid, other keratolytics, abrasives, astringents, spices, and lime
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Apply sparingly to completely dry skin; adverse effects include erythema, stinging or burning, scaling, and hypopigmentation or hyperpigmentation, especially with increasing concentration; additionally, cream forms are generally less irritating than gels and solution; photosensitivity may occur with excessive sunlight exposure; caution in eczema; do not apply to mucous membranes, mouth, and angles of nose
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 Treatment & Medication: Melasma |
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References
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Further Reading
Keywords
melasma, chloasma, the mask of pregnancy, hypermelanosis
