A fairly recent development in the UK is the use of blood tests to determine the optimum dose of azathioprine, or whether to avoid it altogether. This also applies to the closely related drugs mercaptopurine and tioguanine. Azathioprine is often prescribed in ulcerative colitis, Crohn’s disease, severe eczema, rheumatoid arthritis and some other autoimmune conditions.

An enzyme, thiopurine methyltransferase (TPMT), acts in a separate pathway in the breakdown of azathioprine so less is available to be converted to the active form. The activity of the enzyme in individuals varies considerably according to a range of inherited genetic factors. This variation is an example of genetic polymorphism and explains why even small doses are highly toxic in some people with low levels of TPMT while others tolerate relatively high doses. 

The main toxic effects of excess azathioprine activity are severe anaemia and myelosuppression (dangerously low white blood cell counts). TPMT polymorphism that results in relatively decreased enzyme activity affects approximately five to 10 per cent of the general population who thus require lower doses. In up to one in 300 patients, TPMT is absent and so azathioprine should be avoided. Measuring TPMT activity using a blood test is therefore now recommended to identify these patients prior to commencing therapy.