title: Increased incidence of squamous cell carcinoma of the skin after long-term treatment with azathioprine in patients with auto-immune inflammatory rheumatic diseases.
abstract: BACKGROUND
  Auto-immune inflammatory rheumatic diseases (AIRD) are often successfully treated with the immunosuppressant azathioprine for years. Treatment with azathioprine has been proven to increase the risk of non-melanoma skin cancer (NMSC) in transplant patients and possibly in patients with inflammatory bowel disease as well. Little is known about the risk of NMSC in AIRD patients treated with azathioprine.
  
  
  OBJECTIVE
  The aim of this study is to determine the incidence of NMSC in patients with AIRD treated with azathioprine for at least 1 year, as compared with the general Dutch population.
  
  
  METHODS
  Data were extracted from a historical cohort of patients with AIRD in a tertiary care centre. We compared the incidence to an age-matched control population and analysed risk factors for NMSC with univariate logistic regression.
  
  
  RESULTS
  Fifty-nine patients were analysed. No patients were diagnosed with basal cell carcinoma and four patients with a single squamous cell carcinoma (SCC). Patients with SCC had a higher cumulative dose of azathioprine (≥ 500 g: OR 30.0 [95% CI 2.6-345.1]) and longer treatment duration (≥ 11 years: OR 13.5 [95% CI 1.3-143.6]). The risk of SCC compared with the general Dutch population was increased (standardized incidence ratio of 16.0 [95% CI 0.3-31.7]).
  
  
  CONCLUSIONS
  In this cohort of patients with AIRD treated with azathioprine for at least 1 year, the risk of SCC was increased, as compared with the general population. An individual cumulative dose of at least 500 g azathioprine and a treatment duration of at least 11 years were quantified as risk factors.
authors.affiliation: Department of Dermatology, Radboud University Nijmegen Medical Centre, NijmegenDepartment of Rheumatology, Rijnstate Hospital, ArnhemDepartment of Primary and Community Care, Radboud University Nijmegen Medical CentreDepartment of Epidemiology and Biostatistics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: J M P A
authors.initials: JM
authors.lastname: van den Reek
authors.forename: P P M
authors.initials: PP
authors.lastname: van Lümig
authors.forename: M
authors.initials: M
authors.lastname: Janssen
authors.forename: H J
authors.initials: HJ
authors.lastname: Schers
authors.forename: J C M
authors.initials: JC
authors.lastname: Hendriks
authors.forename: P C M
authors.initials: PC
authors.lastname: van de Kerkhof
authors.forename: M M B
authors.initials: MM
authors.lastname: Seyger
authors.forename: E M G J
authors.initials: EM
authors.lastname: de Jong
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D001379:Azathioprine / Q000008:administration & dosage* / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000453:epidemiology*; D002648:Child; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D012878:Skin Neoplasms / Q000139:chemically induced / Q000453:epidemiology*; D055815:Young Adult
chemical_list: D001379:Azathioprine