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

Arthritis Rheum. 1995 Jan;38(1):142-5. doi: 10.1002/art.1780380122.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5'-Nucleotidase / metabolism
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / enzymology*
  • Azathioprine / adverse effects*
  • Azathioprine / toxicity*
  • Bone Marrow / drug effects*
  • Female
  • Humans
  • Hypoxanthine Phosphoribosyltransferase / metabolism
  • Male
  • Methyltransferases / metabolism
  • Middle Aged
  • Purine-Nucleoside Phosphorylase / metabolism


  • Methyltransferases
  • thiopurine methyltransferase
  • Purine-Nucleoside Phosphorylase
  • Hypoxanthine Phosphoribosyltransferase
  • 5'-Nucleotidase
  • Azathioprine