Azathioprine-related bone marrow toxicity and low activities of purine enzymes in patients with rheumatoid arthritis.
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.


CONCLUSIONS
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.
Kerstens
P J
PJ
Department of Rheumatology, University Hospital Nijmegen, The Netherlands.
Stolk
J N
JN
De Abreu
R A
RA
Lambooy
L H
LH
van de Putte
L B
LB
Boerbooms
A A
AA
D015720:5'-Nucleotidase / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000201:enzymology*; D001379:Azathioprine / Q000009:adverse effects* / Q000633:toxicity*; D001853:Bone Marrow / Q000187:drug effects*; D005260:Female; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000378:metabolism; D008297:Male; D008780:Methyltransferases / Q000378:metabolism; D008875:Middle Aged; D011683:Purine-Nucleoside Phosphorylase / Q000378:metabolism
D008780:Methyltransferases; C022745:thiopurine methyltransferase; D011683:Purine-Nucleoside Phosphorylase; D007041:Hypoxanthine Phosphoribosyltransferase; D015720:5'-Nucleotidase; D001379:Azathioprine