EPSTEIN-BARR-VIRUS AND LYMPHOPROLIFERATION IN METHOTREXATE-TREATED RHEUMATOID-ARTHRITIS

Generalized lymphadenopathy developed in a 60-year-old female receivin g methotrexate and prednisone for treatment of rheumatoid arthritis, H istologic examination of an enlarged right axillary lymph node reveale d effacement of normal architecture by a polymorphic population of lym phocytes. The recognition that the patient was medically immunosuppres sed and the similarity of lymph node histology to that of a polymorphi c post-transplantation lymphoid proliferation led to suspicion that th e adenopathy might represent an immunosuppression-related lymphoid pro liferation, This possibility was supported by regression of the adenop athy on discontinuation of methotrexate, despite continued corticoster oid therapy, which is an outcome reminiscent of the remissions observe d with reduction of immunosuppressive therapy in post-transplantation lymphoproliferative disorders, Subsequent ancillary laboratory studies of lymph node tissue included genetic probe analysis, which revealed a monoclonal population of B-lymphocytes containing clonal Epstein-Bar r virus DNA. In situ hybridization studies performed on lymph node tis sue revealed expression of Epstein-Barr virus-encoded RNA 1 transcript s, and immunohistochemical studies revealed expression of Epstein-Barr virus latent membrane protein 1, These ancillary studies confirmed th e similarity to post transplantation lymphoproliferative disorder. Alt hough immunosuppression-related lymphoproliferative disorders share fe atures with malignant lymphoma, the possibility of resolution in situa tions in which immunosuppression can be reversed provides a distinctio n from true malignancy and is of profound importance in therapeutic de cision making.