Drug-induced hyperpigmentation

Author: Vanessa Ngan, Staff Writer, 2004.

Synonyms:

Drug-induced abnormal pigmentation of skin, Non-melanin pigmentation caused by drugs, Drug-induced hypermelanosis

Categories:

Reaction to external agent, Pigmentary disorder

Subcategories:

Drugs implicated in increasing skin pigmentation, Types of pigmentation caused by drugs, Clinical features of drug-induced skin pigmentation, Outcome of drug pigmentation

ICD-10:

L81.9, L81.8

ICD-11:

ED64

SNOMED CT:

110990003, 403627003, 238998002, 18869009

What is drug-induced skin pigmentation?

Drug-induced skin pigmentation accounts for 10–20% of all cases of acquired hyperpigmentation. Pigmentation may be induced by a wide variety of drugs; the main ones implicated include non-steroidal anti-inflammatory drugs (NSAIDs), phenytoin, antimalarials, amiodarone, antipsychotic drugs, cytotoxic drugs, tetracyclines, and heavy metals.

Some drugs may cause fixed drug eruption, which is followed by localised hyperpigmentation and gradually fades.

Drug-induced pigmentation

What causes drug-induced skin pigmentation?

Several mechanisms may be involved in the drug-induced changes of pigmentation of the skin.

Certain heavy metals, such as iron, silver, and gold, may be deposited in the dermis following damage to dermal vessels. If deposited in sufficient quantities a distinctive change in skin colour may be seen without any significant increase in melanin.
Some drugs react with melanin to form a drug-pigment complex. Exposure to sunlight often stimulates sun-induced melanin synthesis forming these complexes.
Some drugs will induce hypermelanosis (accumulation of melanin) as a non-specific post-inflammatory change in predisposed individuals. This is often worsened by sun exposure.
Some drugs induce pigmentation directly by accumulating and/or reacting with other substances in the skin.

What are the clinical features of drug-induced skin pigmentation?

The clinical features of drug-induced skin pigmentation are very variable according to the drug involved. A large range of patterns and shades may be formed.

Drug/drug group	Clinical features
Heavy metals	Pigmentation from heavy metal toxicity may be permanent Iron can cause a dark brown pigmentation (siderosis) at the site of inadvertent subcutaneous injection Excessive gold, previously used in the treatment of rheumatic diseases, can cause diffuse golden brown pigmentation Ingested silver salts may induce a diffuse greyish pigmentation (argyria)
Tetracyclines (minocycline)	Bluish pigmentation, especially in scars May affect nails and skin Cumulative; pigmentation is more likely on higher doses Affects older patients more than younger ones May take several years to clear once the drug has been stopped
Antipsychotics (chlorpromazine and related phenothiazines)	Bluish-grey pigmentation, especially in sun-exposed areas Pigmentation is cumulative and some areas may develop a purplish tint Pigmentation of the conjunctiva in the eye may also occur, along with cataracts and corneal opacities
Phenytoin/anticonvulsants	10% of patients develop pigmentation of the face and neck resembling melasma (clearly defined, roughly symmetrical dark brown patches) Fades after a few months when the drug has been stopped
Antimalarials	About 25% of patients receiving chloroquine or hydroxychloroquine for several years develop bluish-grey pigmentation on face, neck and sometimes lower legs and forearms Continuous long-term use may lead to blue-black patches, especially in sun-exposed areas Nail beds and corneal and retinal changes may also develop
Cytotoxic drugs	Busulfan, cyclophosphamide, bleomycin and adriamycin have all produced hyperpigmentation to some degree Banded or diffuse pigmentation of nails often occurs
Amiodarone	Blue-grey pigmentation in sun-exposed areas (face and hands) Photosensitivity occurs in 30-57% of patients whilst 1-10% show skin pigmentation Skin pigmentation is reversible but may take up to one year for complete resolution after the drug has been stopped
NSAIDs	Often associated with fixed drug eruptions (drugs that cause a single or few sharply demarcated erythematous lesions which resolve promptly but leave a local brown pigmentation May occur on the face, extremities and genitalia

What is the treatment for drug-induced skin pigmentation?

Drug-induced skin pigmentation can become cosmetically disfiguring. In many cases, once the offending drug has been stopped, fading of the lesions occurs. However, the pigmentation may last a long time or become permanent. Because many drugs that induce skin pigmentation also cause photosensitivity reactions, sun protection is usually recommended.

Laser treatment has been successful in treating amiodarone-induced skin pigmentation.

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Related information

References

Textbook of Dermatology. Ed Rook A, Wilkinson DS, Ebling FJB, Champion RH, Burton JL. Fourth edition. Blackwell Scientific Publications.
Dereure O. Drug-induced skin pigmentation. Epidemiology, diagnosis and treatment. Am J Clin Dermatol 2001;2(4):253-62

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