title: Association of skin hyperpigmentation and drug use: a systematic review.
abstract: BACKGROUND
  Part of the acquired hyperpigmentations of the skin are interpreted as adverse effect of drugs. However, systematic studies are rare in the literature, as case reports have predominantly been published. The present systematic review attempts to provide a contribution to the body of evidence for a causal relation.
  
  
  METHODS
  The reports on an association of hyperpigmentation and drugs from 1970 until April 2016 found in Medline and EMBASE were rated according to the SIGN grading system for clinical studies.
  
  
  RESULTS
  A total of 352 evaluated publications were found, which mainly consist of reports of single cases, only a small number of larger case series were available. Case-control-studies and randomized controlled studies have rarely been found. The level of evidence for a causal relation to hyperpigmentation is low for the major part of drugs as quoted in order to the Anatomical Therapeutic Chemical Classification System with Defined Daily Doses. A causal relation is likely only for prostaglandins, minocyclin, phenothiazine, nicotine, and anti-malaria drugs.
  
  
  CONCLUSIONS
  There is paucity of evidence for an induction of hyperpigmentation by drugs. A causal relationship is likely only in a small number of drugs.
authors.affiliation: Department of Dermatology and Allergology, Gießen and Marburg University Clinic, Marburg, Germany - krause@med.uni-marburg.de.
authors.forename: Walter
authors.initials: W
authors.lastname: Krause
mesh_terms: D003875:Drug Eruptions / Q000453:epidemiology*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology*; D006801:Humans; D017495:Hyperpigmentation / Q000139:chemically induced* / Q000453:epidemiology; D016032:Randomized Controlled Trials as Topic