Intended for healthcare professionals

Rapid response to:

Clinical Review Lesson of the week

Azathioprine-induced pancytopenia in a patient with pompholyx and deficiency of erythrocyte thiopurine methyltransferase

BMJ 2005; 330 doi: https://doi.org/10.1136/bmj.330.7487.350 (Published 10 February 2005) Cite this as: BMJ 2005;330:350

Rapid Response:

Re: Regular monitoring of full blood count and liver function tests is still the mainstay of azathioprine monitoring.

As Dr Lewington and colleagues point out, the British Society of Gastroenterology guidelines state that TPMT mesurement "cannot yet be recommended as a prerequisite to therapy" with azathioprine.(1) Three references are cited.(2-4)

The first is in the context of childhood leukaemia treated with 6- mercaptopurine and recommends measuring TPMT prior to therapy.(2) The second (referred to by Dr Lewington and colleagues) suggests not that TPMT status is unimportant but that genotyping rather than phenotyping might provide a strategy to identify it.(3)

The third is a retrospective review of 622 patients with inflammatory bowel disease treated with azathioprine that is relatively reassuring about the long term safety of the drug as long as potential bone marrow toxicity is monitored with regular full blood counts, but TPMT status was not examined.(4) Even so, five per cent of patients had myelosuppression (four episodes of neutropenic sepsis and 29 of leucopenia or pancytopenia). Whilst myelosuppression with azathioprine in inflammatory bowel disease may be multifactorial (see response to Dr de Boer and colleagues, above), it would have been interesting to know whether these cases were related to TPMT deficiency.

As regards the turn around time for TPMT measurement, we agree that this may be longer than is desirable if azathioprine is required promptly. It might be anticipated, however, that it could shorten with an increasing number of requests.

(1) Carter MJ, Lobo AJ, Travis SPL. Guidelines for the management of inflammatory bowel disease in adults. Gut 2004;53:V1-V16.

(2) Lennard L,Gibson BE, Nicole T, et al. Congenital thiopurine methyltransferase deficiency and 6-mercaptopurine toxicity during treatment for acute lymphoblastic leukaemia. Arch Dis Child 1993;69:577–9.

(3) Colombel JF, Ferrari N, Debuysere H, Marteau P, Gendre JP, Bonaz B et al. Genotypic analysis of thiopurine S-methyltransferase in patients with Crohn's disease and severe myelosuppression during azathioprine therapy. Gastroenterology 2000;118(6):1025-30.

(4) Fraser AG ,Orchard TR,Jewell DP.The efficacy of azathioprine for thetreatment of inflammatory bowel disease: a 30 year review. Gut 2002;50:485–9.

Competing interests: None declared

Competing interests: No competing interests

24 February 2005
Andrew W Macfarlane
Consultant Dermatologist
Maria Konstantopoulou, Avinash Belgi, Keith Griffiths, and Jim Seale
Ysbyty Gwynedd, Bangor, Gwynedd LL57 2PW