Correspondence

Reversible Lymphoma in the Setting of Azathioprine Therapy for Crohn's Disease

N Engl J Med 1994; 331:883-884September 29, 1994

Article

To the Editor:

The use of immunosuppressive agents after organ transplantation is associated with an increased risk of lymphoproliferative disorders related to Epstein-Barr virus (EBV)1. The risk of these disorders with immunosuppressive therapy for other conditions, such as inflammatory bowel disease, is not well established. We describe a patient in whom a reversible EBV-related lymphoproliferative disease developed during treatment with azathioprine for Crohn's disease.

A 33-year-old man had a 13-year history of Crohn's disease involving the whole small bowel. Because the disease was steroid-dependent, azathioprine therapy was started (100 mg per day) in April 1988. After steroids were withdrawn, the Crohn's disease remained inactive with azathioprine therapy. Azathioprine was discontinued in March 1993 because of multiple enlarged lymph nodes and an intercostal mass. Surgical biopsies of a lymph node and of the intercostal tumor revealed a polymorphic B-cell lymphoid proliferation associated with extensive necrosis. In situ hybridization detected a large quantity of kappa light-chain messenger RNA. The EBV genome and two EBV transcripts were detected in nearly all tumor cells with nonradioactive BamHI (Figure 1Figure 1EBV DNA Detected by in Situ Hybridization with the BamHI Probe (x 500).), EBER, and BHLF probes, respectively. Four weeks after the cessation of azathioprine therapy, the lymphadenopathy had regressed dramatically and the intercostal mass had disappeared. In March 1994 the patient had no evidence of lymphoma, and Crohn's disease was still inactive with mesalamine treatment (4 g per day).

Malignant lymphomas have been found to occur with unexpected frequency during Crohn's disease2. The cause of the association is obscure, and the possible role of immunosuppressive agents is unknown. Only two brain lymphomas have been reported during therapy for Crohn's disease with mercaptopurine or azathioprine3,4. The lymphoma in our patient had histologic, immunohistochemical, and virologic features similar to those of the B-cell lymphoproliferations that occur after organ transplantation5. The possibility cannot be excluded that a defect in T-cell immunosurveillance for EBV, linked to Crohn's disease itself, might contribute to the development of lymphoproliferative disorders. In our patient, however, the regression of the lymphoma after the withdrawal of azathioprine suggested that immunosuppressive therapy was the chief pathogenic factor.

Loic Larvol, M.D.
Jean-Claude Soule, M.D.
Louis Mourier Hospital, 92701 Colombes, France

Agnes Le Tourneau, M.D.
Hotel-Dieu, 75181 Paris, France

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Citing Articles (47)

Citing Articles

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