Rheumatology Advance Access originally published online on May 9, 2008
Rheumatology 2008 47(7):1103-1104; doi:10.1093/rheumatology/ken188
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Reversible Hodgkin's lymphoma associated with Epstein–Barr virus occurring during azathioprine therapy for SLE
1Department of Rheumatology and 2Department of Haematology, Wrexham Maelor Hospital, North East Wales NHS Trust, Wrexham, UK
Correspondence to: J. Evans, Rheumatology Department, Wrexham Maelor Hospital, Croesnewydd Road, Wrexham, LL13 7TD, UK. E-mail: jayneevans{at}tesco.net
SIR, We report the case of a 47-yr-old Caucasian female with a 20-yr history of SLE who had been treated with AZA, cyclosporin and prednisolone in 1998 for lupus pneumonitis. From 2005, AZA had been continued at a dose of 150 mg daily. In April 2007, she presented with weight loss and a mass on her tongue. MRI scan of the head and neck revealed a locally invasive mass associated with lymphadenopathy (Fig. 1). Histological examination showed a mixed lymphoid infiltrate consisting of T- and B-cell blasts, with strong positivity for the EBV marker EBER (EBV-encoded RNA). The infiltrate also appeared pleomorphic, and subsequent clonality studies confirmed classical Hodgkin's lymphoma (HL) of the nodular sclerosing type. AZA was stopped and after 6 weeks the lesion had regressed significantly (assessed by a repeat MRI scan), and after a further 4 months had almost completely resolved without requiring chemotherapy.
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EBV has been shown to transform B lymphocytes in vitro into immortal proliferating lymphoblastoid cell lines. In vivo, this is counteracted by EBV-specific cytotoxic T-lymphocytes (CTLs). In immunosuppressed hosts, loss of EBV-specific CTLs can enable unchecked viral proliferation predisposing to the development of lymphoma [1]. EBV-related lymphoproliferative disorders occur in immunosuppressed transplant recipients as well as patients with rheumatological disorders treated with MTX and other steroid-sparing agents. Withdrawal of these agents can lead to tumour regression [2].
The increased risk of lymphoproliferative cancer has been suggested in AZA-treated patients with RA, resulting in one extra case in 1000 patient-years of observation in one study [3]. Lymphomas associated with AZA tend to be EBV negative, and are more aggressive responding poorly to AZA withdrawal [4]. Previous reports of HL in AZA-treated SLE patients have all required combination chemotherapy and an association with EBV was not identified.
To summarize, our case illustrates that, albeit rarely, AZA can be associated with EBV-positive HL in SLE. Disappearance of the tumour after the withdrawal of AZA suggests that in this case the therapy was a major factor in the generation of this tumour. AZA remains an effective and important agent in the treatment of SLE. However, our case illustrates an extremely rare but potentially serious complication of this drug.
Disclosure statement: The authors have declared no conflicts of interest.
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- Klein E, Kis LL, Klein G. Epstein-Barr virus infection in humans: from harmless to life endangering virus-lymphocyte interactions. Oncogene (2007) 26:1297–1305.[CrossRef][Web of Science][Medline]
- Kamel OW, Van de Rijn M, Weiss LM, et al. Brief report: reversible lymphomas associated with Epstein-Barr virus occurring during methotrexate therapy for rheumatoid arthritis and dermatomyositis. New Eng J Med (1993) 328:1317–21.
[Free Full Text] - Silman AJ, Petrie J, Hazleman B, Evans SJW. Lymphoproliferative cancer and other malignancy in patients with rheumatoid arthritis treated with azathioprine: a 20 year follow up study. Ann Rheum Dis (1988) 47:898–992.
[Abstract/Free Full Text] - Au WY, Ma ESK, Choy C, et al. Therapy-related lymphomas in patients with autoimmune diseases after treatment with disease-modifying anti-rheumatic drugs. Am J Hematol (2006) 81:5–11.[CrossRef][Web of Science][Medline]
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