Hepatotoxicity associated with sulfasalazine in inflammatory arthritis: A case series from a local surveillance of serious adverse events.
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.
Jobanputra
Paresh
P
Department of Rheumatology, Selly Oak Hospital, University Hospital Birmingham NHS Foundation Trust, Raddlebarn Road, Birmingham, B29 6JD, UK. p.jobanputra@bham.ac.uk
Amarasena
Roshan
R
Maggs
Fiona
F
Homer
Dawn
D
Bowman
Simon
S
Rankin
Elizabeth
E
Filer
Andrew
A
Raza
Karim
K
Jubb
Ronald
R
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*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D012460:Sulfasalazine