A 24-year-old Japanese woman with one year history of active rheumatoid arthritis (RA) who complained in March 2007 with pain and swelling of bilateral wrists, elevation of the inflammatory markers such as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and matrix metalloproteinase-3 (MMP3). The blood examination showed anti-agalactosyl IgG antibody CARF positive, which is known as the early diagnosis marker for RA (Das et al.). X-ray imaging showed particular bone erosions in the carpal bones of the hands and partially ankylosis of the carpal bones (Figure 1). RA diagnosis was met with the 1987 Rheumatoid Arthritis Classification. The combination of MTX (6-8 mg/week) and PSL (3 mg/day) was selected as an initial therapy for RA in September 2007. After that, however, disease activity was increased up to DAS28-CRP 5.1 (over right fingers, bilateral knees, right index middle ring PIP, and right ankle) and x-ray showed rapid destructive joints and high disease activity progression to Steinbrocker stage classification 3 within half a year after RA diagnosis. Then, she was referred to Takatsuki Red Cross Hospital for administration of anti-TNF-alpha inhibitor. Screening test was examined by included laboratory data with ECG, chest x-ray for excluding tuberculosis (Tbe), hepatitis C viruses (HCV) and hepatitis B viruses (HBV). Immunological examinations were tested for rheumatoid factor (RF) 22 U/ml, MMP-3 654 ng/ml, CRP 7.65 mg/dl, and ESR 35 mm/h. In August 2008, ADA (40 mg every other week) was administrated with MTX (8 mg/week). Seven days after receiving first administration of ADA, she showed rapid progression of sore throat, high fever and general lymph nodes swelling. Laboratory tests showed an elevated white blood cell count (WBC) 31800 (20.6% neutrophils and 63.7% lymphocytes without atypical lymphocytes), high level of CRP (3.3 mg/dl) and elevated liver-function tests with alanine aminotransferase level (53 U/L), aspartate aminotransferase (65 U/L), and gamma-glutamyltransferase (138 U/L). Evaluation of diagnosis with computed tomography (CT) and ultrasonography showed cervical and mediastinal lymph node swelling, multiple nodules measuring up to 13 mm in diameter in the lungs and mild hepatosplenomegary (Figure 2). An inguinal lymph node biopsy staining with hematoxylin and eosin staining (H&E staining) showed proliferation of the lymphatic cells without tumor cell phenotype (Figure 3A) and immunohistological studies with this examined inguinal lymph node revealed the lympho-proliferative CD20 positive cells (Figure 3B). H&E staining in high power filed showed the full range of mature lymphatic cells with polymorphous pattern and phagocytic macrophages included condensed small nuclear cells suggested apoptotic cell (Figure 3C). Besides, many lymphatic cells in the inguinal lymph node were positive with cleaved caspase 3 staining (Figure 3D). Moreover, EBV RNA in situ hybridization with the biopsy specimen revealed positive signals in the nucleus of large cells, and EBV DNA was detected by southern blot analysis (data not shown). Flow-cytometric analysis of infiltrating lymphocytes in lymph node showed an abundant population of CD38 positive B cell. In addition to routine blood test and urine cultures, the histories of infection were collected (e.g., HCV, HBV, tuberculosis, cytomegalovirus, parvovirus, varicella-zoster virus, HIV, EBV). The examinations for all these infections agents were negative except for high titers of anti-EBV antigen IgG (Table 1). Taken together these examinations, we diagnosed EB virus related B-cell LPD after the treatment with TNF-alpha inhibitor plus MTX, and that was in accordance with the 2008 WHO classification. Combination therapy with ADA plus MTX was terminated and pulse treatment with methylprednisolone was started. Steroid treatment for 7 days resulted in dramatic regression of LPD. Moreover, 10 days treatment with methylprednisolone reached to the complete remission of arthritis with below detection limits in ESR (3 ~ 11 mm/h), CRP (<0.3 mg/dl), and low level of MMP-3 (17.3 ~ 59.7 ng/ml) (Figure 4A and B). After the improvement of clinical symptoms and laboratory data, the administration of PSL was tapered off. She achieved drug-free with the reduction of EBV VCA-IgG titers (160 U/ml) 12 months after the emergent admission, and delivered healthy baby 2 years after discharge. She has completely attained drug-free Boolean remission for 5 years.