Drug-induced hperpigemntation: a systematic review

Area of Science:

• Dermatology
• Pharmacology
• Evidence-based Medicine

Background:

• Acquired skin hyperpigmentation is often attributed to drug side effects.
• Systematic reviews on this topic are scarce, with most existing literature comprising case reports.
• This review critically evaluates the evidence linking drug use to hyperpigmentation.

Purpose of the Study:

• To assess the strength of evidence for a causal relationship between drug administration and acquired hyperpigmentation.
• To identify drugs with a likely causal association with hyperpigmentation based on available literature.

Main Methods:

• A systematic literature search was conducted for reports from 1970 to June 2012 in MEDLINE and EMBASE.
• Included studies were evaluated using the Scottish Intercollegiate Guidelines Network (SIGN) grading system for evidence quality.
• The highest grade of evidence for each implicated drug was identified.

Main Results:

• 306 publications were analyzed, predominantly consisting of case reports with limited case series.
• Very few case-control studies and randomized controlled trials (RCTs) were identified.
• Low-level evidence supported a causal link for most drugs; a likely causal relationship was identified for prostaglandins, minocycline, phenothiazine, nicotine, and antimalarial drugs.

Conclusions:

• The scientific evidence supporting drug-induced hyperpigmentation is generally weak.
• A causal association between hyperpigmentation and drug intake is probable for a restricted list of medications.