title: Off-label use of azathioprine in dermatology: a systematic review.
abstract: OBJECTIVE
  To summarize evidence regarding the effectiveness, efficacy, and safety of off-label azathioprine use in dermatology.
  
  
  METHODS
  We searched the MEDLINE (1950-2009), EMBASE (1980-2009), and CENTRAL (1996-2009) databases on October 9, 2009. The main search terms were azathioprine and its synonyms. No restrictions were imposed regarding publication date. Only articles in English, French, German, or Dutch were included.
  
  
  METHODS
  Randomized controlled trials, cohorts, and case series concerning the use of azathioprine in an off-label dermatologic setting were independently assessed for eligibility by 2 coauthors. The search retrieved 3870 articles, and 148 articles were selected for detailed review.
  
  
  METHODS
  Forty-three articles matching the inclusion and exclusion criteria were reviewed for methodologic quality by 2 reviewers independently, including an evaluation of components associated with biased estimates of treatment effect.
  
  
  RESULTS
  High-quality evidence (level A) was found for a moderate therapeutic effect in severe atopic dermatitis. Evidence of moderate quality (level B) was found for efficacy in parthenium dermatitis (an airborne plant allergen contact dermatitis), bullous pemphigoid, chronic actinic dermatitis, and leprosy type 1 reaction. Furthermore, favorable therapeutic effects existed for erythema multiforme, lichen planus, and pityriasis rubra pilaris, although the quality of evidence was low (level C).
  
  
  CONCLUSIONS
  A strong clinical recommendation was given for azathioprine in atopic dermatitis. Conclusions regarding safety in an off-label setting could not be reached because of scarce and incomplete data (level C evidence). Long-term registries and prospective studies could add to the existing evidence and provide legal support for off-label drug use in dermatology.
authors.affiliation: Department of Dermatology, Academic Medical Center, Room A0-252, University of Amsterdam, PO Box 22700, 1100 DE Amsterdam, the Netherlands. m.e.schram@amc.uva.nl
authors.forename: Mandy E
authors.initials: ME
authors.lastname: Schram
authors.forename: Rinke J
authors.initials: RJ
authors.lastname: Borgonjen
authors.forename: Cathelijne M J M
authors.initials: CM
authors.lastname: Bik
authors.forename: Jan G
authors.initials: JG
authors.lastname: van der Schroeff
authors.forename: Jannes J E
authors.initials: JJ
authors.lastname: van Everdingen
authors.forename: Phyllis I
authors.initials: PI
authors.lastname: Spuls
mesh_terms: D001379:Azathioprine / Q000627:therapeutic use*; D003879:Dermatologic Agents / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007918:Leprosy / Q000188:drug therapy; D008297:Male; D056687:Off-Label Use; D016032:Randomized Controlled Trials as Topic; D012871:Skin Diseases / Q000188:drug therapy*
chemical_list: D003879:Dermatologic Agents; D001379:Azathioprine