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Melasma consists of dark brown, roughly symmetric patches of hyperpigmentation with irregular borders on the face (usually on the forehead, temples, cheeks, cutaneous upper lip, or nose). It occurs primarily in pregnant women (melasma gravidarum, also called the mask of pregnancy) and in women taking oral contraceptives. Melasma is more prevalent among and lasts longer in people with dark skin.

Melasma can affect the epidermis and dermis.

Мелазма

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Because melasma risk increases with increasing sun exposure, the mechanism probably involves overproduction of melanin by hyperfunctional melanocytes. Other than sun exposure, aggravating factors include

• Autoimmune thyroid disorders

• Photosensitizing medications

• Antiseizure medications

• Sex hormones, including oral contraceptives

In women, melasma fades slowly and incompletely after childbirth or cessation of hormone use. In men, melasma rarely fades.

The mainstay of melasma management is strict photoprotection agents. Patients should use sunscreen with a broad-spectrum (UVA and UVB) sun protection factor (SPF) of 50 or higher, wear sun-protective clothing and hats (UV protection factor 50 or higher), and avoid direct sun exposure. During and after therapy, strict sun protection must be maintained. Because visible light is not blocked by most sunscreens, patients should use a tinted sunscreen (eg, that contains zinc oxide or titanium dioxide). The addition of antioxidants to the sunscreen and oral adjunctive photoprotection agents such as Polypodium leucotomas can enhance protection (1, 2). Because of potential health and environmental toxicities, use of oxybenzone/benzophenone-3 has often been discouraged (3); however, its health effects are unknown because data on clinically meaningful outcomes are limited (4, 5).

Other treatment depends on whether the pigmentation is epidermal or dermal; epidermal pigmentation becomes accentuated with a Wood light (365 nm) or can be diagnosed with biopsy. Only epidermal pigmentation responds to treatment. Most topical melasma treatments are used in combination rather than individually.

Triple topical therapy is first-line treatment that is often effective and consists of a combination of

• Hydroquinone 2 to 4%

• Tretinoin 0.05 to 1%

• A class V to VII topical corticosteroid (see table Relative Potency of Selected Topical Corticosteroids)

Hydroquinone depigments the skin by blocking the enzymatic oxidation of tyrosine 3,4-dihydroxyphenylalanine (DOPA) and inhibiting melanocyte metabolic processes. Hydroquinone should be tested behind one ear or on a small patch on the forearm for 1 week before use on the face because it may cause irritation or an allergic reaction.

Tretinoin promotes keratinocyte turnover and can exfoliate skin that contains epidermal pigment.

Corticosteroids help block synthesis and secretion of melanin.

Two promising technologies being tried in conjunction with triple topical therapy are the Q-switched Nd:YAG (1064 nm) laser modalities (6).

If triple topical therapy is not available, hydroquinone 2 to 4% alone can be used; however, chronic continuous use can theoretically increase the risk of exogenous ochronosis, which is a permanent form of hyperpigmentation. Hydroquinone 2% is useful as maintenance.

Azelaic acid 15 to 20% cream can be used in place of or with hydroquinone and/or tretinoin. Azelaic acid is a tyrosinase inhibitor that reduces melanin production. In addition, topical kojic acid has been increasingly used; it is a chelating agent that blocks tyrosine conversion to melanin.

During pregnancy, azelaic acid 15 to 20% cream and chemical peeling with glycolic acid are safe to use. NOTE: Hydroquinone, tranexamic acid, trichloroacetic acid peels, and tretinoin are not safe to use during pregnancy.

Second-line treatment options for patients with severe melasma unresponsive to topical bleaching agents include chemical peeling with glycolic acid or 30 to 50% trichloroacetic acid. Laser treatments also have been used but are not standard therapy.

A randomized study has shown improvement with oral tranexamic acid in patients with moderate-to-severe melasma (7). However, relapse can occur when treatment is stopped.

Lentigines (singular: lentigo) are flat, tan to brown, oval macules. They are commonly due to chronic sun exposure (solar lentigines; sometimes called liver spots, although they are not related to hepatic dysfunction) and occur most frequently on the face and back of the hands. They typically first appear during middle age and increase in number with age. Although progression from lentigines to melanoma has not been established, lentigines are an independent risk factor for melanoma.

If lentigines are a cosmetic concern, they are treated with cryotherapy or laser; hydroquinone is not effective.

Nonsolar lentigines are sometimes associated with systemic disorders, such as Peutz-Jeghers syndrome (in which profuse lentigines of the lips occur), multiple lentigines syndrome (or LEOPARD syndrome, which stands for multiple Lentigines, Electrocardiogram [ECG] conduction abnormalities, Ocular hypertelorism, Pulmonic stenosis, Abnormal genitals, Retardation of growth, and sensorineural Deafness), or xeroderma pigmentosum.

Lentigo Simplex

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Changes are usually diffuse but sometimes have drug- or substance-specific distribution patterns or hues (see table Hyperpigmentation Effects of Some Medications and Heavy Metals). Mechanisms include

• Increased melanin in the epidermis (tends to be more brown)

• Increased melanin in the epidermis and high dermis (mostly brown with hints of gray or blue)

• Increased melanin in the dermis (tends to be more grayish or blue)

• Dermal deposition of the drug or substance, metabolite, or complex between the drug or substance and melanin (usually slate or bluish gray)

Medications may cause secondary hyperpigmentation. For example, focal hyperpigmentation frequently occurs after medication-induced lichen planus (also known as lichenoid drug eruption).

In fixed drug eruptions, round or oval red plaques or blisters form at the same site each time the causative medication is taken; residual postinflammatory hyperpigmentation usually persists, especially in dark skin types. Typical lesions occur on the face (especially the lips), hands, feet, and genitals. Typical inciting medications include antibiotics (sulfonamides, tetracyclines, trimethoprim, and fluoroquinolones), nonsteroidal anti-inflammatory drugs, and barbiturates.

Treatment of drug- or substance-induced hyperpigmentation involves stopping the causative drug or substance; the hyperpigmentation fades very slowly in some if not all cases.

Because many drugs and substances that cause skin pigmentation also cause photosensitivity reactions, patients should avoid sun exposure. People with dark skin tones are more susceptible to postinflammatory hyperpigmentation and should also practice strict sun protective measures to limit exacerbation of postinflammatory hyperpigmentation.