Co-existence of acute myeloid leukemia with multilineage dysplasia and Epstein-Barr virus-associated T-cell lymphoproliferative disorder in a patient with rheumatoid arthritis: a case report
© Tokuhira et al; licensee BioMed Central Ltd. 2009
Received: 27 March 2009
Accepted: 30 June 2009
Published: 30 June 2009
Rheumatoid arthritis (RA) is an autoimmune disease mediated by inflammatory processes mainly at the joints. Recently, awareness of Epstein-Barr virus (EBV)-associated T-cell lymphoproliferative disorder (T-LPD) has been heightened for its association with methotraxate usage in RA patients. In the contrary, acute myeloid leukemia with multilineage dysplasia (AML-MLD) has never been documented to be present concomitantly with the above two conditions. In this report we present a case of an autopsy-proven co-existence of AML-MLD and EBV-associated T-LPD in a patient with RA.
Rheumatoid arthritis (RA) is an autoimmune disease mediated by inflammatory processes mainly at the joints; activation of fibroblasts and macrophages of the synovial tissue by a triggering agent(s) is thought to play a role in its pathogenesis, while lymphocytes in these environments may play an important role in the destruction of joint tissue by the RA-associated autoimmunity [1–3]. In the present case, two additional diseases, i.e., acute myeloid leukemia with multilineage dysplasia (AML-MLD) and Epstein-Barr virus (EBV)-associated T-cell lymphoproliferative disorder (T-LPD), developed after the treatment of RA. The patient died with respiratory complications and multiple organ failure with severe infection after steroid pulse therapy and cyclophosphamide. To the best of our knowledge, this is the first report of the simultaneous presence of AML-MLD and EBV-associated T-LPD in a patient with RA.
To the best of our knowledge, this is the first reported case of co-existing AML-MLD and EBV-associated T-LPD in RA. It is possible that the development of AML was secondary to either RA-related treatment or the underlying myelodysplastic syndrome (MDS) [5–8]. In the present case, NSAIDs, PSL and bucillamine were given to the patient as RA treatment. Bucillamine was developed in Japan, and has a cysteine derivative possessing two SH-groups. Its antirheumatic effects are thought to arise from its suppression of the formation of IgM in B cells, the formation of matrix metalloproteinase-3, and the differentiation of osteoclasts [9, 10]. The bone marrow karyotyping revealed an abnormal karyotype of chromosome 7 in the BM cells, which is seen often in MDS. It is therefore most likely that AML-MLD was secondary to MDS. It has been shown that EBV infection can trigger chronic immune inflammatory disease [11, 12]. For instance, the number of infected peripheral B lymphocytes in RA tend to be higher than in normal individuals, and an impairment of specific cytotoxic T lymphocytes against EBV has been noted in RA patients [13, 14]. In addition, EBV DNA was directly detected in RA synovial tissue by polymerase chain reaction method . Balandraud et al demonstrated that RA has a 10-fold systemic EBV overload, very similar to that observed in organ transplant recipients . In the present case, high titers of EBV were seen. Recent attention has been focused on this immunodysregulatory phenomena. It has been demonstrated that the responsible gene is SAP (signaling lymphocytic activation molecule [SLAM]-associated protein), an adaptor protein that mediates signals through SLAM and other immunoglobulin superfamily receptors including 2B4, Ly8, SF2000, and CD84 . It has been suggested that SAP plays an important role in the physiological immunity for viral infections [18, 19]. In regard to RA patients, Takei et al demonstrated that the expression level of SAP transcripts in the peripheral leukocytes of RA patients was significantly lower than in normal individuals, and RA patients had decreased expression of SAP transcripts in peripheral CD2(+) T cells compared to normal individuals. They proposed that decreased SAP gene expression might trigger RA progression [20, 21]. On the other hand, EBV-LPD has often been reported in immunodeficient individuals such as HIV patients, patients post-transplantation, or patients taking immunosuppressants . Methotrexate (MTX) has been implicated to induce LPD in RA patients . The fact that withdrawal of MTX led to improvement of LPD in 30–50% of the patients also suggested a direct MTX interaction with immune system . Several studies have reported that RA itself is not a risk factor of LPD . It remains unclear whether the co-existence of the three conditions are coincidental or there could be an intrinsic mechanism.
The current case with AML-MLD and EBV-associated T-LPD developmedin a RA patient appears to be extremely rare. To the best of our knowledge, this is the first reported case of co-existing AML-MLD and EBV-associated T-LPD in a patient with RA.
Written informed consent was obtained from the patient's wife for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
acute myeloid leukemia with multilineage dysplasia
T-cell lymphoproliferative disorder
white blood cell
anti-non steroid inflammatory drugs
World Health Organization
human T-cell lymphotropic virus type 1
human immunodeficiency virus
anti-Epstein-Barr virus-viral capsid antigen
anti-Epstein-Barr virus nuclear antigen
signaling lymphocytic activation molecule associated protein
signaling lymphocytic activation molecule.
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