Archives of Clinical Microbiology

  • ISSN: 1989-8436
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Follow-Up Study of Epstein-Barr Virus-Associated Hodgkin's Lymphoma (HL) Developed in a Patient with Rheumatoid Arthritis (RA) and Analysis of Circulating Cytokines and Clinical Parameters: Clarithromycin Coupled with Prednisolone is Effective for Preventing Relapse of HL and Controlling RA

Nobuo Takemori, Hiroyuki Kaneko, Toshio Fukuda and Masaru Kojima

We conducted a follow-up study of Epstein-Barr virus (EBV)-associated Hodgkin’s Lymphoma (HL) in a patient with rheumatoid arthritis (RA) in whom a drastic complete remission (CR) was achieved after withdrawing methotrexate (MTX) together with administration of clarithromycin (CAM). CAM was administered for 1 year after the first admission but typical HL relapsed 4 months after suspending CAM treatment. The relapse was successfully treated with standard chemotherapy and led to CR. After achieving CR, treatment of CAM coupled with low-dose prednisolone (PSL) was restarted as a maintenance therapy. This combination treatment was found to be effective for preventing the relapse as well as controlling RA. Neither MTX nor other anti-rheumatic drugs except for PSL have been used since initial presentation. To date, no relapse has occurred and RA symptoms are fairly well controlled. Clinical parameters for EBV, RA and HL and circulating cytokines during the course of illness showed elevated levels of soluble interleukin-2 receptors, interleukin (IL)-1β, IL-6 and tumor necrosis factor-α in initial phase of the disease as well as in relapse phase, and returned to normal in CR phase. Copies of EBV-DNA in circulating lymphocytes were increased in relapse phase but returned to normal in CR phase. Since relapse occurred without MTX, this drug is thought not to have caused the HL. Rather, immunodeficiency due to RA itself or PSL (more than 10mg/day) administration might have resulted in reactivation of EBV, leading to HL. Immunomodulatory and immunosuppressive effects of CAM coupled with low-dose PSL on cytokine networks might be involved in maintaining CR and controlling RA. This combination treatment is recommended as a maintenance treatment from the perspective of simplicity, safety and cost-effectiveness in such a situation.