From the Guidelines
Several drugs can cause hyperpigmentation of the skin, with tetracycline antibiotics, particularly minocycline, being a common culprit, as noted in a 2024 study 1. The mechanisms of hyperpigmentation vary by drug class but often involve either direct deposition of the drug or its metabolites in the skin, stimulation of melanin production, or post-inflammatory changes. Some of the key drugs that can cause hyperpigmentation include:
- Antimalarials like chloroquine and hydroxychloroquine, which can cause blue-gray discoloration
- Tetracycline antibiotics, particularly minocycline, which may cause slate-gray or blue-black pigmentation, as reported in a study published in the Journal of the American Academy of Dermatology 1
- Amiodarone, an antiarrhythmic that can lead to slate-gray or blue-gray discoloration in sun-exposed areas, as noted in a 2022 study 1
- Heavy metals such as silver, gold, and bismuth
- Chemotherapy agents like bleomycin, busulfan, cyclophosphamide, and 5-fluorouracil, which frequently cause hyperpigmentation
- Hormonal medications including oral contraceptives and hormone replacement therapy, which can trigger melasma-like pigmentation
- Phenothiazines (like chlorpromazine), anticonvulsants, and certain HIV medications, which may also cause skin darkening. Hyperpigmentation typically develops after weeks to months of treatment and may be more pronounced in sun-exposed areas. While often benign, drug-induced hyperpigmentation can cause significant cosmetic concerns for patients and may gradually fade after discontinuation of the causative medication, though complete resolution doesn't always occur, as noted in a study published in the Journal of the American Academy of Dermatology 1.
From the FDA Drug Label
Skin and subcutaneous tissue disorders: Alopecia, hair color changes, rash, pruritus, photosensitivity, psoriasis exacerbation, hyperpigmentation, exfoliative dermatitis, erythema multiforme, acute generalized exanthematous pustulosis, Drug Rash with Eosinophilia and Systemic Symptoms (DRESS syndrome), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN)
The drug hydroxychloroquine can cause hyperpigmentation 2 2.
- Key points:
- Hydroxychloroquine is associated with hyperpigmentation.
- This adverse reaction is listed under skin and subcutaneous tissue disorders.
From the Research
Drugs Causing Hyperpigmentation
- Minocycline, a tetracycline derivative antibiotic, is known to cause hyperpigmentation, particularly after long-term therapy with at least 100 mg/day 3, 4, 5, 6, 7
Types of Hyperpigmentation
- Type I: blue-black discoloration in areas of previous inflammation and scarring 3, 6
- Type II: blue-gray pigmentation of previously normal skin, commonly affecting the legs 3, 6
- Type III: diffuse muddy-brown discoloration predominantly on sun-exposed skin 3, 6
Characteristics of Hyperpigmentation
- The discoloration can vary from blue, slate-gray, or brown, and typically occurs in a dose-dependent fashion 4
- Hyperpigmentation may be cosmetically disfiguring and prompt identification is essential 3
- Without treatment, symptoms may take several months to years to resolve after discontinuation of the drug, and the pigmentation may never completely disappear 3, 5