Reversible infliximab-related lymphoproliferative disorder associated with Epstein-Barr virus in a patient with rheumatoid arthritis

Atsushi Komatsuda1, Hideki Wakui1, Takashi Nimura2, Ken-ichi Sawada1
1Third Department of Internal Medicine, Akita University School of Medicine, Akita, Japan
2Department of Internal Medicine, Senboku General Hospital, Daisen, Japan

Tóm tắt

A 63-year-old woman with active rheumatoid arthritis (RA) had been treated with methotrexate and prednisolone. She developed cervical lymph node swelling 30 months after the initiation of infliximab therapy. A computed tomography revealed cervical and mediastinal lymph node swelling and multiple nodules (up to 13 mm in diameter) in the lungs. A lymph node biopsy showed infiltration of numerous Hodgkin-like and Reed-Sternberg-like cells. Immunohistological studies showed that these cells were positive for CD15, CD30, and Epstein-Barr virus (EBV) latent membrane protein. In site hybridization revealed the presence of EBV RNA in the nuclei of these cells. EBV DNA was detected in the biopsy specimen by southern blot analysis. She was diagnosed as having EBV-associated lymphoproliferative disorder (LPD). Immunodeficiency-associated LPD related with infliximab therapy was considered. Cessation of infliximab therapy only led to dramatic regression of LPD. This case illustrates that EBV-associated LPDs can occur as part of infliximab adverse effects in patients with RA.

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Tài liệu tham khảo

Ekström K, Hjalgrim H, Brandt L, Baecklund E, Klareskog L, Ekbom A et al. Risk of malignant lymphomas in patients with rheumatoid arthritis and in their first-degree relatives. Arthritis Rheum. 2003;48:963–70.

Baecklund E, Iliadou A, Askling J, Ekbom A, Backlin C, Granath F et al. Association of chronic inflammation, not its treatment, with increased lymphoma risk in rheumatoid arthritis. Arthritis Rheum. 2006;54:692–701.

Wolfe F, Michaud K. Lymphoma in rheumatoid arthritis: the effect of methotrexate and anti-tumor necrosis factor therapy in 18,572 patients. Arthritis Rheum. 2004;50:1740–51.

Harris NL, Swerdlow SH. Immunodeficiency associated lymphoproliferative disorders. In: Jaffe ES, Harris NL, Stein H, Vardiman JW, editors. World Health Organization classification of tumours: pathology and genetics of tumours of haematopoietic and lymphoid tissues. Lyon: IARC Press; 2001. p. 255–71.

Brown SL, Greene MH, Gershon SK, Edwards ET, Braun MM. Tumor necrosis factor antagonist therapy and lymphoma development: 26 cases reported to the Food and Drug Administration. Arthritis Rheum. 2002;46:3151–8.

Wolfe F, Michaud K. The effect of methotrexate and anti-tumor necrosis factor therapy on the risk of lymphoma in rheumatoid arthritis in 19,562 patients during 89,710 person-years of observation. Arthritis Rheum. 2007;56:1433–9.

Baecklund E, Sundström C, Ekbom A, Catrina AI, Biberfeld P, Feltelius N, et al. Lymphoma subtypes in patients with rheumatoid arthritis. Increased proportion of diffuse large B cell lymphoma. Arthritis Rheum. 2003;48:1543–50.

Kamel OW, van de Rijn M, Weiss LM, Del Zoppo JD, Hench PK, Robbins BA, et al. Reversible lymphomas associated with Epstein-Barr virus occurring during methotrexate therapy for rheumatoid arthritis and dermatomyositis. N Engl J Med. 1993;328:1317–21.

Hoshida Y, Yamamoto S, Wada N, Xu J-X, Sasaki T, Aozasa K. Infliximab-associated lymphoproliferative disorders. Int J Hematol. 2005;81:356–7 (letter).

Oyama T, Ichimura K, Suzuki R, Suzumiya J, Ohshima K, Yatabe Y, et al. Senile EBV+ B-cell lymphoproliferative disorders: a clinicopathologic study of 22 patients. Am J Surg Pathol. 2003;27:16–26.