Merck Manual

Please confirm that you are a health care professional

honeypot link

Hyperpigmentation

By

Shinjita Das

, MD, Harvard Medical School

Last full review/revision Dec 2020| Content last modified Dec 2020
Click here for Patient Education
Topic Resources

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 Lacerations Lacerations are tears in soft body tissue. Care of lacerations Enables prompt healing Minimizes risk of infection Optimizes cosmetic results read more and burns Burns Burns are injuries of skin or other tissue caused by thermal, radiation, chemical, or electrical contact. Burns are classified by depth (superficial and deep partial-thickness, and full-thickness)... read more Burns ) or other causes of inflammation (eg, acne Acne Vulgaris Acne vulgaris is the formation of comedones, papules, pustules, nodules, and/or cysts as a result of obstruction and inflammation of pilosebaceous units (hair follicles and their accompanying... read more Acne Vulgaris , lupus Systemic Lupus Erythematosus (SLE) Systemic lupus erythematosus is a chronic, multisystem, inflammatory disorder of autoimmune etiology, occurring predominantly in young women. Common manifestations may include arthralgias and... read more Systemic Lupus Erythematosus (SLE) ). 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—see Photosensitivity is a cutaneous overreaction to sunlight. It may be idiopathic or occur after exposure to certain toxic or allergenic drugs or chemicals, and it is sometimes a feature of systemic... read more ). Focal hyperpigmentation can also result from neoplastic processes (eg, lentigines Lentigines Hyperpigmentation has multiple causes and may be focal or diffuse. Most cases are due to an increase in melanin production and deposition. (See also Overview of Pigmentation Disorders.) Focal... read more Lentigines , melanoma Melanoma Malignant melanoma arises from melanocytes in a pigmented area (eg, skin, mucous membranes, eyes, or central nervous system). Metastasis is correlated with depth of dermal invasion. With spread... read more Melanoma ), melasma Melasma (chloasma) Hyperpigmentation has multiple causes and may be focal or diffuse. Most cases are due to an increase in melanin production and deposition. (See also Overview of Pigmentation Disorders.) Focal... read more Melasma (chloasma) , freckles, or café-au-lait macules An extensive language has been developed to standardize the description of skin lesions, including Lesion type (sometimes called primary morphology) Lesion configuration (sometimes called secondary... read more . Acanthosis nigricans causes focal hyperpigmentation and a velvety plaque most often on the axillae and posterior neck.

Melasma (chloasma)

Melasma consists of dark brown, sharply marginated, roughly symmetric patches of hyperpigmentation 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 Oral Contraceptives Oral contraceptives (OCs) mimic ovarian hormones. Once ingested, they inhibit the release of gonadotropin-releasing hormone (GnRH) by the hypothalamus, thus inhibiting the release of the pituitary... read more . Ten percent of cases occur in nonpregnant 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

  • Autoimmune thyroid disorders

  • Photosensitizing drugs

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 sun protection Prevention The skin may respond to sunlight with chronic (eg, dermatoheliosis [photoaging], actinic keratosis) or acute (eg, photosensitivity, sunburn) changes. The sun emits a wide range of electromagnetic... read more . Patients should use sunscreen with a sun protection factor (SPF) of 30 or higher, wear protective clothing and hats, and avoid direct sun exposure. During and after therapy, strict sun protection must be maintained.

Other treatment depends on whether the pigmentation is epidermal or dermal; epidermal pigmentation becomes accentuated with a Wood light Wood light Diagnostic tests are indicated when the cause of a skin lesion or disease is not obvious from history and physical examination alone. These include Patch testing Biopsy Scrapings Examination... read more 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 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 and nonablative fractional resurfacing.

If triple topical therapy is not available, then hydroquinone 3 to 4% applied twice daily for up to 8 weeks at a time (chronic continuous use can theoretically increase the risk of exogenous ochronosis, which is a permanent form of hyperpigmentation) may be considered; 2% hydroquinone 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 (and is considered safe for use during pregnancy). In addition, topical kojic acid has been increasingly used; it is a chelating agent that blocks tyrosine conversion to melanin.

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.

Oral therapies have been studied. A recent randomized study has shown improvement with oral tranexamic acid in patients with moderate-to-severe melasma (1 Melasma reference Hyperpigmentation has multiple causes and may be focal or diffuse. Most cases are due to an increase in melanin production and deposition. (See also Overview of Pigmentation Disorders.) Focal... read more Melasma reference ).

Melasma reference

Lentigines

Lentigines (singular: lentigo) are flat, tan to brown, oval macules. They are commonly due to chronic sun exposure (solar lentigines; sometimes called liver spots but 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 Melanoma Malignant melanoma arises from melanocytes in a pigmented area (eg, skin, mucous membranes, eyes, or central nervous system). Metastasis is correlated with depth of dermal invasion. With spread... read more 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 Peutz-Jeghers Syndrome Peutz-Jeghers syndrome is an autosomal dominant disease with multiple hamartomatous polyps in the stomach, small bowel, and colon along with distinctive pigmented skin lesions. Most (66 to 94%)... read more 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.

Drug-induced hyperpigmentation

  • 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, metabolite, or drug–melanin complexes (usually slate or bluish gray)

Table
icon

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

Key Points

  • Common causes of focal hyperpigmentation include injury, inflammation, phytophotodermatitis, lentigines, melasma, freckles, café-au-lait macules, and acanthosis nigricans.

  • Common causes of widespread hyperpigmentation include melasma, drugs, cancers, and other systemic disorders.

  • Test patients who have widespread hyperpigmentation not caused by drugs for disorders such as primary biliary cholangitis, hemochromatosis, and Addison disease.

  • Treat melasma initially with a combination of hydroquinone 2 to 4%, tretinoin 0.05 to 1%, and a class V to VII topical corticosteroid.

  • If lentigines are a cosmetic concern, treat with cryotherapy or laser.

Drugs Mentioned In This Article

Drug Name Select Trade
CYTOXAN (LYOPHILIZED)
CYKLOKAPRON
No US brand name
AZELEX, FINACEA
CARAC
COSMEGEN
TRI-LUMA
NORPRAMIN
MINOCIN
CORDARONE
TOFRANIL
Tretinoin
MYLERAN
Click here for Patient Education
NOTE: This is the Professional Version. CONSUMERS: Click here for the Consumer Version
Professionals also read

Test your knowledge

Bullous Pemphigoid
Bullous pemphigoid is a chronic autoimmune skin disorder that occurs more often in patients > 60 years of age. Which of the following is the most common initial symptom?
Download the Manuals App iOS ANDROID
Download the Manuals App iOS ANDROID
Download the Manuals App iOS ANDROID
Download the Manuals App iOS ANDROID
Download the Manuals App iOS ANDROID
Download the Manuals App iOS ANDROID

Also of Interest

Download the Manuals App iOS ANDROID
Download the Manuals App iOS ANDROID
Download the Manuals App iOS ANDROID
TOP