Severe aplastic anemia in a patient with rheumatoid arthritis after introduction of etanercept

Yoshiro Horai 1 , Tomoya Miyamura 1 , Karin Shimada 1 , Motoko Ishida 1 , Soichiro Takahama 1 , Rumi Minami 1 , Masahiro Yamamoto 1 , and Eiichi Suematsu 1
  • 1 Department of Internal Medicine and Rheumatology, Clinical Research Center, National Hospital, Organization Kyushu Medical Center, 1-8-1 Jigyohama Chuo-ku, Fukuoka, 810-8563, Japan


A 73-year-old female, diagnosed with rheumatoid arthritis (RA), complicated with severe levels of joint destruction, started etanercept (ETN) because of high persistent RA disease activity. Although her articular symptoms dramatically improved, she developed marked pancytopenia after the introduction of ETN. Bone marrow aspirate specimen revealed hypocellular marrow in three hematopoietic series without atypical findings, which was compatible with aplastic anemia (AA). This is a rare case of severe pancytopenia due to AA presumably induced by ETN.

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  • [1] van der Heijde D, Klareskog L, et al. Comparison of etanercept and methotrexate, alone and combined, in the treatment of rheumatoid arthritis: two-year clinical and radiographic results from the TEMPO study, a double-blind, randomized trial. Arthritis Rheum, 2006, 54: 1063–1074

  • [2] Katikireddi VS, Whittle SL, Hill CL. Tumour necrosis factor inhibitors and risk of serious infection in rheumatoid arthritis. Int J Rheum Dis, 2010, 13: 12–26

  • [3] Komano Y, Harigai M, Koike R, et al. Pneumocystis jiroveci pneumonia in patients with rheumatoid arthritis treated with infliximab: a retrospective review and case-control study of 21 patients. Arthritis Rheum, 2009, 61: 305–312

  • [4] Jurisic V, Bogdanovic G, Kojic V, Jakimov D, Srdic T. Effect of TNF-alpha on Raji cells at different cellular levels estimated by various methods. Ann Hematol. 2006, 85, 86–94

  • [5] Miyasaka N, Takeuchi T, Eguchi K. Guidelines for the proper use of etanercept in Japan. Mod Rheumatol, 2006, 16: 63–67

  • [6] Koike T, Harigai M, Inokuma S, et al. Postmarketing surveillance of the safety and effectiveness of etanercept in Japan. J Rheumatol, 2009, 36: 898–906

  • [7] Takeuchi T, Amano K. Etanercept (in Japanese). Nippon Rinsho, 2002, 60: 2390–2396

  • [8] Kaushik P, Rahmani M, Ellison W. Membranous glomerulonephritis with the use of etanercept in ankylosing spondylitis. Ann Pharmacother, 2011, 45:e62

  • [9] Baumelou E, Guiguet M, Mary JY. Epidemiology of aplastic anemia in France: a case-control study. I. Medical history and medication use. The French Cooperative Group for Epidemiological Study of Aplastic Anemia. Blood, 1993, 81:1471–1478

  • [10] Pathare SK, Heycock C, Hamilton J. TNFalpha blocker-induced thrombocytopenia. Rheumatology (Oxford), 2006, 45:1313–1314

  • [11] Jurisic V, Terzic T, Pavlovic S, Colovic N, Colovic M. Elevated TNF-alpha and LDH without parathormone disturbance is associated with diffuse osteolytic lesions in leukemic transformation of myelofibrosis. Pathol Res Pract. 2008, 204, 129–132

  • [12] Kuruvilla J, Leitch HA, Vickars LM, Galbraith PF, Li CH, Al-Saab S, et al. Aplastic anemia following administration of a tumor necrosis factor-alpha inhibitor. Eur J Haematol, 2003, 71: 396–398

  • [13] Balandraud N, Guis S, Meynard JB, Auger I, Roudier J, Roudier C. Long-term treatment with methotrexate or tumor necrosis factor alpha inhibitors does not increase epstein-barr virus load in patients with rheumatoid arthritis. Arthritis Rheum, 2007, 57: 762–767

  • [14] Komatsuda A, Wakui H, Nimura T, Sawada K. Reversible infliximab-related lymphoproliferative disorder associated with Epstein-Barr virus in a patient with rheumatoid arthritis. Mod Rheumatol, 2008, 18, 315–318

  • [15] Ueda M, Tateishi T, Shigeto H, Yamasaki R, Ohyagi Y, Kira J. A case of acute disseminated encephalomyelitis associated with Epstein-Barr virus reactivation during infliximab therapy (in Japanese). Rinsho Shinkeigaku, 2010, 50: 461–466

  • [16] Semenzato G, Zambello R, Starkebaum G, Oshimi K, Loughran TP Jr. The lymphoproliferative disease of granular lymphocytes: updated criteria for diagnosis. Blood, 1997, 89:256–260

  • [17] Bowman SJ, Sivakumaran M, Snowden N, et al. The large granular lymphocyte syndrome with rheumatoid arthritis. Immunogenetic evidence for a broader definition of Felty’s syndrome. Arthritis Rheum. 1994, 37, 1326–1330

  • [18] Hart DN, Baker BW, Inglis MJ, et al. Epstein-Barr viral DNA in acute large granular lymphocyte (natural killer) leukemic cells. Blood, 1992, 79: 2116–2123

  • [19] Kim TH, Choi SJ, Lee YH, Song GG, Ji JD. Soluble triggering receptor expressed on myeloid cells-1 as a new therapeutic molecule in rheumatoid arthritis. Med Hypotheses. 2012, 78, 270–272


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