Idiosyncrasy

Abstract: Clinical characteristics and circumstantial evidence suggest that idiosyncratic drug reactions are caused by reactive metabolites and are immune-mediated; however, there are few definitive data and there are likely exceptions. There are three principal hypotheses for how reactive metabolites might induce an immune-mediated idiosyncratic reaction: the hapten hypothesis, the danger hypothesis, and the PI hypothesis. It has been proposed that some idiosyncratic reactions, especially those involving the liver, represent metabolic idiosyncrasy; however, there are even less data to support this hypothesis. The unpredictable nature of these reactions makes mechanistic studies difficult. There is a very strong association with specific human leukocyte antigen (HLA) genes for certain reactions, but this has only been demonstrated for very few drugs. Animal models represent a very powerful tool for mechanistic studies, but the number of valid models is also limited. There may be biomarkers of risk; however, much more work needs to be done.

Abstract: Summary Analgesic challenge was employed to identify fifty patients with aspirin idiosyncrasy. No serious reactions were observed using the method described. Patients with a history of the condition were highly sensitive and reacted to small doses of aspirin or to paracetamol. Patients with a positive challenge test, but previously unaware of aspirin idiosyncrasy, were less sensitive: they required larger challenge doses of aspirin and did not respond to paracetamol challenge. In the absence of an in vitro test, analgesic challenge is the only means of confirming the presence of aspirin idiosyncrasy.