From the Guidelines
Minocycline, an antibiotic, is the most notable medication that can cause permanent skin pigmentation changes, resulting in blue-black pigmentation on the face, legs, and at sites of inflammation, as reported in a study published in the Journal of the American Academy of Dermatology 1. Several medications can cause permanent skin pigmentation changes, including:
- Amiodarone, used for heart rhythm disorders, which can cause blue-gray discoloration particularly on sun-exposed areas due to drug deposits in the skin
- Minocycline, an antibiotic, which may cause blue-black pigmentation on the face, legs, and at sites of inflammation
- Chloroquine and hydroxychloroquine, used for malaria and autoimmune conditions, which can cause yellow-brown or blue-gray discoloration, especially on the face, legs, and hard palate
- Heavy metals like silver (argyria) and gold (chrysiasis) which can cause slate-gray or blue-gray skin discoloration
- Psychotropic medications including phenothiazines and tricyclic antidepressants which may cause slate-gray pigmentation in sun-exposed areas These changes occur through various mechanisms including drug deposition in the skin, increased melanin production, and formation of drug-melanin complexes. The risk of permanent skin pigmentation changes increases with higher cumulative doses and longer treatment duration, as noted in a study published in the Journal of the American Academy of Dermatology 1. Sun protection is crucial for patients on these medications as UV exposure often worsens the pigmentation changes, as recommended in a study published in Nature Reviews Cardiology 1. It is essential to consider the potential for permanent skin pigmentation changes when prescribing medications, particularly those with a high risk of causing such changes, and to counsel patients on the importance of sun protection and monitoring for any changes in skin pigmentation.
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)
Hydroxychloroquine sulfate can cause permanent skin pigmentation changes, specifically hyperpigmentation. 2
From the Research
Medication-Induced Skin Pigmentation
Medications that can cause permanent skin pigmentation changes include:
- Nonsteroidal anti-inflammatory drugs 3
- Antimalarials, such as hydroxychloroquine 3, 4
- Amiodarone 3
- Cytotoxic drugs 3, 5
- Tetracyclines 3
- Heavy metals 3, 6, 5
- Psychotropic drugs 3, 5
Characteristics of Drug-Induced Pigmentation
The characteristics of drug-induced pigmentation can vary depending on the offending agent, but common features include:
- Accumulation of melanin within the dermis 3, 6
- Drug accumulation 3, 6
- Pigment synthesis 3, 6
- Iron deposition 3, 6
- Photoprotection plays an important role in preventing exacerbation of drug-induced pigmentation 6
Treatment and Prevention
Treatment options for drug-induced pigmentation include:
- Sun avoidance 3
- Interruption of treatment with the offending drug 3
- Laser therapy, such as picosecond alexandrite, Q-switched Nd:YAG, Q-switched alexandrite, and Q-switched ruby lasers 6
- Photoprotection, including applying a broad-spectrum sunscreen, wearing photoprotective clothing, and seeking shade 6