title: Hepatotoxicity associated with sulfasalazine in inflammatory arthritis: A case series from a local surveillance of serious adverse events.
abstract: BACKGROUND
  Spontaneous reporting systems for adverse drug reactions (ADRs) are handicapped by under-reporting and limited detail on individual cases. We report an investigation from a local surveillance for serious adverse drug reactions associated with disease modifying anti-rheumatic drugs that was triggered by the occurrence of liver failure in two of our patients.
  
  
  METHODS
  Serious ADR reports have been solicited from local clinicians by regular postcards over the past seven years. Patients', who had hepatotoxicity on sulfasalazine and met a definition of a serious ADR, were identified. Two clinicians reviewed structured case reports and assessed causality by consensus and by using a causality assessment instrument. The likely frequency of hepatotoxicity with sulfasalazine was estimated by making a series of conservative assumptions.
  
  
  RESULTS
  Ten cases were identified: eight occurred during surveillance. Eight patients were hospitalised, two in hepatic failure - one died after a liver transplant. All but one event occurred within 6 weeks of treatment. Seven patients had a skin rash, three eosinophilia and one interstitial nephritis. Five patients were of Black British of African or Caribbean descent. Liver enzymes showed a hepatocellular pattern in four cases and a mixed pattern in six. Drug-related hepatotoxicity was judged probable or highly probable in 8 patients. The likely frequency of serious hepatotoxicity with sulfasalazine was estimated at 0.4% of treated patients.
  
  
  CONCLUSIONS
  Serious hepatotoxicity associated with sulfasalazine appears to be under-appreciated and intensive monitoring and vigilance in the first 6 weeks of treatment is especially important.
authors.affiliation: Department of Rheumatology, Selly Oak Hospital, University Hospital Birmingham NHS Foundation Trust, Raddlebarn Road, Birmingham, B29 6JD, UK. p.jobanputra@bham.ac.uk
authors.forename: Paresh
authors.initials: P
authors.lastname: Jobanputra
authors.forename: Roshan
authors.initials: R
authors.lastname: Amarasena
authors.forename: Fiona
authors.initials: F
authors.lastname: Maggs
authors.forename: Dawn
authors.initials: D
authors.lastname: Homer
authors.forename: Simon
authors.initials: S
authors.lastname: Bowman
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Rankin
authors.forename: Andrew
authors.initials: A
authors.lastname: Filer
authors.forename: Karim
authors.initials: K
authors.lastname: Raza
authors.forename: Ronald
authors.initials: R
authors.lastname: Jubb
mesh_terms: D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000453:epidemiology; D044383:Black People / Q000706:statistics & numerical data; D056486:Chemical and Drug Induced Liver Injury; D004739:England / Q000453:epidemiology; D005260:Female; D006801:Humans; D008107:Liver Diseases / Q000208:ethnology / Q000401:mortality; D017093:Liver Failure / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D012460:Sulfasalazine / Q000009:adverse effects*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D012460:Sulfasalazine