Open AccessAzathioprine‐related bone marrow toxicity and low activities of purine enzymes in patients with rheumatoid arthritis
Author(s) -
Kerstens Pit J. S. M.,
Stolk Jan N.,
De Abreu Ronney A.,
Lambooy Lambert H. J.,
Van Putte Leo B. A. De,
Boerbooms Agnes A. M. T.
Publication year - 1995
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.1780380122
Subject(s) - medicine , thiopurine methyltransferase , toxicity , bone marrow , azathioprine , rheumatoid arthritis , purine , purine nucleoside phosphorylase , pharmacology , enzyme , chemistry , biochemistry , disease
Objective . Azathioprine (AZA) metabolism largely parallels the endogenous purine pathways. To date, thiopurine methyltransferase (TPMT) deficiency has been reported as a cause of AZA‐related bone marrow toxicity in 1 patient with rheumatoid arthritis (RA). We therefore studied purine enzyme activities in 3 patients with RA who experienced AZA‐related bone marrow toxicity. Methods . Lymphocyte activity of purine nucleoside phosphorylase and 5′‐nucleotidase (5NT) and erythrocyte activity of TPMT, key enzymes in thiopurine catabolism, were measured in 3 RA patients who had experienced AZA‐related bone marrow toxicity and in 16 RA patients without signs of toxicity despite at least 6 months of treatment with AZA. Results . Two patients with AZA‐related bone marrow toxicity were found to have a TPMT deficiency, 1 partial and 1 total. In the third patient, 5NT activity was found to be well below the lowest level observed in the control subjects. Conclusion . All 3 patients with severe AZA‐related bone marrow toxicity had abnormal purine enzyme activities. Deficiency of purine enzymes, including TPMT and 5NT, may be a cause of AZA‐related bone marrow toxicity in patients with RA.