Like many immunosuppressants, azathioprine, which is a purine analog, was initially developed in the 1960s to prevent organ rejection. It has also been used to treat a number of immunologic diseases including pemphigus vulgaris, rheumatoid arthritis, inflammatory bowel disease, as well as atopic dermatitis.
An increased risk of malignancy (including non-Hodgkin's lymphomas and sarcomas) is a recognized risk of long-term azathioprine treatment in patients receiving treatment to prevent transplant rejection or to manage inflammatory bowel disease. This past year azathioprine received a black box warning about the potential for a rare but frequently lethal lymphoma called hepatosplenic T-cell lymphoma (HSTCL). HSTCL responds poorly to chemotherapy and bone marrow transplantation. Initially, it was thought to occur primarily in young men with Crohn's disease who were also treated with tumor necrosis factor (TNF) antagonists, but a recent review of 25 HSTCL cases indicates the profile of susceptible patients is a bit broader. Over a third of the cases described do not fit this high-risk patient profile. Three of the cases were in patients with rheumatoid arthritis, which indicates that the underlying disease process may play less of a role than the azathioprine. Additionally, 3 of the 25 patients with HSTCL were treated with methotrexate in conjunction with a TNF antagonist (and not azathioprine). Importantly, none of the reported HSTCL cases was in atopic dermatitis patients receiving these drugs. Further studies are warranted to determine whether long-term treatment with azathioprine poses a risk for the development of HSTCL in atopic dermatitis patients.