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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.