5th June 2025

Drug induced pigmentation

Pigmentation can be triggered by a range of different drugs: the main ones include non-steroidal anti-inflammatory drugs, phenytoin, antimalarials, amiodarone, antipsychotic drugs, cytotoxic drugs, tetracyclines and heavy metal. 

Some drugs cause a fixed drug eruption where there is a cutaneous allergic reaction at the area of medication exposure which is followed by localised hyperpigmentation that gradually fades.

Causes

The mechanism involved in drug induced hyperpigmentation varies depending on the drug;

• Heavy metals (iron, silver and gold) may be deposited in the dermis following destruction to dermal vessels and can cause skin colour changes.
• Drug-pigment complexes can form with certain drugs that react with melanin. These complexes form by a trigger such as sunlight. 
• Some medication will cause an increase of melanin from non-specific post-inflammatory change in predisposed individuals. This can be aggravated by sunlight. 
• Other medications may cause pigmentation from accumulating and/or reacting with other substances found in the skin.

Clinical features 

The clinical presentation will vary depending on causative drug;

• Heavy metals- iron can cause dark brown pigmentation, gold can cause diffuse golden-brown pigmentation, silver can cause diffuse greyish pigmentation. The pigmentation can be permanent. 
• Tetracycline (minocycline)- blue pigmentation affecting nails, skin, and scars. Older patients with higher doses of tetracycline are likely to experience these skin changes. Can take many years once a drug is discontinued for pigmentation to clear.
• Antipsychotic (chlorpromazine and related phenothiazines)- blue-grey pigmentation on sun exposed sites and conjunctiva of eyes. 
• Phenytoin/ anticonvulsants- Symmetrical dark brown patches like melasma that clear a few months after drug discontinued. Found on the neck and face usually. 
• Antimalarials (chloroquine/ hydroxychloroquine)- blue-grey pigmentation found on face, neck, lower leg and forearms. With prolonged use of medication, blue black patches on sun-exposed areas. May also develop changes on nail bed, cornea and retina. 
• Cytotoxic drugs (busulfan/cyclophosphamide/bleomycin/Adriamycin)- hyperpigmentation on nails usually that is banded or diffuse.
• Amiodarone- Blue-grey pigmentation on sun exposed sites. It reverses on discontinuation of the drug, but this can take up to a year.
• NSAID- Demarcated erythematous lesions from fixed drug eruptions that resolve leaving a brown pigment and are normally found on the face, extremities and genitalia.

Management

The mainstay of management is discontinuing the offending drug so the hyperpigmentation fades. However, the improvement in pigmentation can take months, years or it may be permanent. Sun protection is also advised as medication that causes skin pigmentation may cause photosensitivity reactions. In amiodarone-induced skin pigmentation laser treatment has been successful.