Hyperpigmentation has multiple causes and may be focal or diffuse. Most cases are due to an increase in melanin production and deposition.
Focal hyperpigmentation is most often postinflammatory in nature, occurring after injury (eg, cuts and burns) or other causes of inflammation (eg, acne, lupus). Focal linear hyperpigmentation is commonly due to phytophotodermatitis, which is a phototoxic reaction that results from ultraviolet light combined with psoralens (specifically furocoumarins) in plants (eg, limes, parsley, celery). Focal hyperpigmentation can also result from neoplastic processes (eg, lentigines, melanoma), melasma, or café-au-lait macules. Acanthosis nigricans causes focal hyperpigmentation and a velvety plaque most often on the axillae and posterior neck.
Diffuse hyperpigmentation can result from drugs and also has systemic and neoplastic causes (especially lung carcinomas and melanoma with systemic involvement). After eliminating drugs as a cause of diffuse hyperpigmentation, patients should be tested for the most common systemic causes. These causes are Addison disease (see Adrenal Disorders: Addison Disease), hemochromatosis (see Iron Overload: Hereditary Hemochromatosis), and primary biliary cirrhosis (see Fibrosis and Cirrhosis: Primary Biliary Cirrhosis (PBC)). Skin findings are nondiagnostic; therefore, a skin biopsy is not necessary or helpful.
Melasma consists of dark brown, sharply marginated, roughly symmetric patches of hyperpigmentation on the face (usually on the forehead, temples, cheeks, upper lip, or nose). It occurs primarily in pregnant women (melasma gravidarum, or the mask of pregnancy) and in women taking oral contraceptives. Ten percent of cases occur in non-pregnant women and dark-skinned men. Melasma is more prevalent among and lasts longer in people with dark skin.
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
In women, melasma fades slowly and incompletely after childbirth or cessation of hormone use. In men, melasma rarely fades.
Treatment depends on whether the pigmentation is epidermal or dermal; epidermal pigmentation becomes accentuated with a Wood light or can be diagnosed with biopsy. Only epidermal pigmentation responds to treatment. First-line therapy, often effective, includes a combination of hydroquinone 2 to 4%, tretinoin 0.05 to 1%, and a class V to VII topical corticosteroid (Table 1: Principles of Topical Dermatologic Therapy: Relative Potency of Selected Topical Corticosteroids ). Hydroquinone 3 to 4% applied twice daily is usually required for long courses; 2% hydroquinone is useful as maintenance. Hydroquinone should be tested behind one ear or on a small patch on the forearm for 1 wk before use on the face because it may cause irritation or an allergic reaction. Azelaic acid 15 to 20% cream, can be used in place of or with hydroquinone and/or tretinoin. Hydroquinone, tretinoin, and azaleic acid are bleaching agents. Chemical peeling with glycolic acid or 30 to 50% trichloroacetic acid is an option for patients with severe melasma unresponsive to topical bleaching agents. Laser treatments have been used, but none has been established yet as standard therapy. Two promising technologies are the Q-switched Nd:YAG (1064 nm) laser and nonablative fractional resurfacing in conjunction with triple topical therapy as described above. During and following therapy, strict sun protection must be maintained.
Lentigines (singular: lentigo) are flat, tan to brown, oval spots. They are commonly due to chronic sun exposure (solar lentigines; sometimes called liver spots) 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 (Leopard syndrome), or xeroderma pigmentosum.
Changes are usually diffuse but sometimes have drug-specific distribution patterns or hues (see Table 1: Pigmentation Disorders: Hyperpigmentation Effects of Some Drugs and Chemicals). Mechanisms include
Drugs may cause secondary hyperpigmentation. For example, focal hyperpigmentation frequently occurs after drug-induced lichen planus (also known as lichenoid drug reactions).
In fixed drug eruptions, red plaques or blisters form at the same site each time a drug is taken; residual postinflammatory hyperpigmentation usually persists. Typical lesions occur on the face (especially the lips), hands, feet, and genitals. Typical inciting drugs include sulfonamides, tetracycline, NSAIDs, barbiturates, and carbamazepine.
Last full review/revision November 2012 by Peter C. Schalock, MD
Content last modified December 2012