J Korean Med Sci 2006; 21: 946-9 ISSN 1011-8934 Copyright The Korean Academy of Medical Sciences Etanercept-Induced Systemic Lupus Erythematosus in a Patient with Rheumatoid Arthritis Tumor necrosis factor (TNF) is known to play a critical role in the pathogenesis of rheumatoid arthritis (RA). Etanercept is a recombinant soluble fusion protein of TNF type II receptor and IgG, which acts as a specific TNF- antagonist. Anti-TNF- therapy has been an important advance in the treatment of RA. However, induc- tion of autoantibodies in some proportion of patients treated with TNF inhibitors raised concerns for development of systemic autoimmune diseases such as sys- temic lupus erythematosus (SLE). Although new autoantibody formation is com- mon with anti-TNF therapy, there are only rare reports of overt SLE, most of which manifested without major organ involvement and resolved shortly after discontinu- ation of the therapy. We describe a 55-yr-old Korean woman who developed overt life threatening SLE complicated by pneumonia and tuberculosis following etaner- cept treatment for RA. This case is to our knowledge, the first report of etanercept- induced SLE in Korea. Key Words : Lupus Erythematosus, Systemic; Etanercept; TNFR-Fc fusion protein; Arthritis, Rheumatoid Min-Jung Kang*, You-Hyun Lee*, Jisoo Lee Department of Internal Medicine, Division of Rheumatology Ewha Womans University College of Medicine, Seoul, Korea *equal contribution by both authors Received : 11 April 2005 Accepted : 16 August 2005 Address for correspondence Jisoo Lee, M.D. Department of Internal Medicine, Ewha Womans University College of Medicine, 911-1 Mok-dong, Yangcheon-gu, Seoul 158-710, Korea Tel : +82.2-2650-6164, Fax : +82.2-2655-2076 E-mail : leejisoo@ewha.ac.kr INTRODUCTION Etanercept is a soluble tumor necrosis factor (TNF ) recep- tor fusion protein, which inhibits the biological activity of TNF . Specific therapy targeting TNF has been offered an important advance in the treatment of active rheumatoid arthritis (RA) (1). Although anti-inflammatory and disease- modifying effect of anti-TNF therapy are well known, there are concerns for development of serious side effects such as autoimmune disorder, infection and neoplasm as the physi- ologic actions of TNF are blocked (2, 3). Drug-induced lupus was firstly reported by Hoffman in 1945, in a patient who developed hypersensitivity syndrome similar to acute systemic lupus erythematosus (SLE) after taking sulfadiazine (4). Up to 80 kinds of drugs have been known to induce lupus-like syndrome, composing approxi- mately 10% of the all SLE cases (5). Anti-TNF agents in- cluding etanercept have recently been considered as drugs that can potentially induce lupus, since new autoantibodies such as antinuclear antibodies (ANAs) and anti-double stranded DNA (anti-dsDNA) antibodies were detected in anti-TNF treated patients (6-8). Shakoor et al. described the first SLE case among the RA patients treated with etanercept in 2002 (9). Since then, a few similar cases have been reported, that alarmed the clini- cians for development of SLE in RA patients treated with anti-TNF agents (10-13). However, all of the reported cases of anti-TNF -induced SLE was manifested without major 946 organ involvement and resolved shortly after the discontin- uation of the therapy. Although a case of tuberculous pleurisy following infliximab therapy was reported in Korea, etaner- cept associated SLE was not reported previously (14). Here- in, we describe a 55-yr-old Korean woman who developed overt life threatening SLE complicated by pneumonia and tuberculosis following etanercept treatment for RA. CASE REPORT A 55-yr-old Korean woman presented with fever and gen- eralized weakness which persisted for 3 months. She had no history of pulmonary tuberculosis or diabetes mellitus. She was diagnosed as seropositive RA 20 yr ago, and had been treated with prednisolone, NSAIDs and methotrexate. Since she had continued active joint inflammation, 25 mg of etaner- cept twice weekly subcutaneous injection was added to the treatment 8 months ago. Despite improvement of her arthritic symptoms, she began to experience severe fatigue and malaise 3 months ago. Intermittent high fever, myalgia, oral ulcers, gum bleeding, and 10 kg-weight loss were associated. Phys- ical examination revealed cachexic, chronic ill looking woman with severe wasting. Her blood pressure was 130/75 mmHg, heart rate 88/min, and body temperature 38.1℃. Her hands demonstrated typical changes of RA with ulnar deviation and deformity of her fingers. Conjunctiva was anemic. Shal- low irregular shaped ulcers with hemorrhagic spots were noted