Humpath.com - Human pathology

Home > D. General pathology > Therapy, Toxics and drugs > azathioprine

azathioprine

Wednesday 2 July 2008

Azathioprine prodrug is converted to 6-mercaptopurine, which inhibits purine nucleotide synthesis and blocks RNA formation and metabolism.

Oncogenesis

Azathioprine has been implicated to be oncogenic through a number of mechanisms, including the promotion of oxidative DNA damage and the compromise of DNA mismatch repair. The carcinogenic risk of azathioprine has been discussed controversially in the literature.

While autoimmune diseases themselves tend to be associated with a more frequent occurrence of malignancies there appears to be a higher incidence of lymphomas in patients with inflammatory bowel disease, rheumatoid arthritis and transplant recipients treated with this mercaptopurine.

Azathioprine treatment aims at inducing an immunosuppressed state. It can result in leukopenia and lymphopenia, which may impair an effective immune surveillance, and could allow the emergence of neoplastic growth.

Four patients suffering from neurological autoimmune disease (all myasthenia gravis) treated with azathioprine that developed primary CNS non-Hodgkin lymphoma have been reported, and one patient with Crohn`s disease.

It appears reasonable to assume that impaired immunosurveillance iatrogenically induced by azathioprine treatment was causative.

See also

- azathioprine-associated lymphomas

  • hepatosplenic T-gammadelta lymphoma (12688327)
  • reversible Hodgkin lymphoma (# 18469023#)

Case studies

- UPMC #600

References

- Navarro JT, Ribera JM, Mate JL, Granada I, Juncà J, Batlle M, Millá F, Feliu E. Hepatosplenic T-gammadelta lymphoma in a patient with Crohn’s disease treated with azathioprine. Leuk Lymphoma. 2003 Mar;44(3):531-3. PMID: 12688327

- Kandiel A, Fraser AG, Korelitz BI, Brensinger C, Lewis JD (2005) Increased risk of lymphoma among inflammmatory bowel disease patients treated with azathioprine and 6-mercaptopurine. Gut 54:1121-1125.

- Silman AJ, Petrie J, Hazleman B, Evans SJW (1988) Lymphoproliferative cancer and other malignancy in patients with rheumatoid arthritis treated with azathioprine: a 20 year follow up study. Ann Rheum Dis 47:988-992.