{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T22:24:33Z","timestamp":1790029473872,"version":"4.0.1"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T00:00:00Z","timestamp":1707264000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,7,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Lymphoproliferative disorders (LPDs) are serious complications that arise in patients with rheumatoid arthritis (RA) receiving immunosuppressive drugs (ISDs). Here, we reported a 73-year-old woman diagnosed with RA at 60\u2009years of age and treated with methotrexate, bucillamine, prednisolone, and infliximab. She was referred to our hospital, Osaka Metropolitan University Hospital, with general malaise, pancytopenia, a right adrenal mass, and enlarged periaortic lymph nodes. Epstein\u2013Barr virus was detected in serum. We suspected LPD development and performed a bone marrow biopsy, on which no malignant cells could be detected. Upon ISDs withdrawal, her symptoms and blood counts improved, and the right adrenal mass and enlarged lymph nodes regressed. The patient was followed up for clinical LPD. However, 7\u2009months after the initial visit to our hospital, she developed fever and pancytopenia. A repeat bone marrow biopsy confirmed the diagnosis of Epstein\u2013Barr virus\u2013positive diffuse large B-cell lymphoma complicated by haemophagocytic syndrome. After pulse steroid therapy, the patient received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone therapy, which resulted in a complete response. In conclusion, when LPDs develop in patients with RA during ISD treatment, LPDs can progress and complicate haemophagocytic syndrome after partial remission following ISDs withdrawal. Therefore, we should carefully follow up RA patients with LPDs, and aim to achieve an early diagnosis of LPD and promptly initiate chemotherapy.<\/jats:p>","DOI":"10.1093\/mrcr\/rxae007","type":"journal-article","created":{"date-parts":[[2024,2,12]],"date-time":"2024-02-12T07:40:49Z","timestamp":1707723649000},"page":"243-248","source":"Crossref","is-referenced-by-count":3,"title":["Lymphoproliferative disorder progressing after partial remission following immunosuppressive drugs withdrawal in a patient with rheumatoid arthritis"],"prefix":"10.1093","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8576-5816","authenticated-orcid":false,"given":"Kazuo","family":"Fukumoto","sequence":"first","affiliation":[{"name":"Department of Clinical Immunology, Osaka Metropolitan University Graduate School of Medicine , Osaka, Japan"},{"name":"Department of Medical Education and General Practice, Osaka Metropolitan University Graduate School of Medicine , Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryu","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, Osaka Metropolitan University Graduate School of Medicine , Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minako","family":"Tsutsumi","sequence":"additional","affiliation":[{"name":"Department of Hematology, Osaka Metropolitan University Graduate School of Medicine , Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teruhito","family":"Takakuwa","sequence":"additional","affiliation":[{"name":"Department of Hematology, Osaka Metropolitan University Graduate School of Medicine , Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masafumi","family":"Miyamoto","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Ohno Memorial Hospital , Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriyuki","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Ohno Memorial Hospital , Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinsuke","family":"Yamada","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, Osaka Metropolitan University Graduate School of Medicine , Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaka","family":"Furumitsu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Ohno Memorial Hospital , Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Hino","sequence":"additional","affiliation":[{"name":"Department of Hematology, Osaka Metropolitan University Graduate School of Medicine , Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motomu","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, Osaka Metropolitan University Graduate School of Medicine , Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,2,7]]},"reference":[{"key":"2024070814405415400_R1","first-page":"443","volume-title":"WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Immunodeficiency-Associated Lymphoproliferative Disorders","author":"Swerdlow","year":"2017","edition":"4th"},{"key":"2024070814405415400_R2","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1080\/14397595.2020.1866837","article-title":"Overall survival and post-spontaneous regression relapse-free survival of patients with lymphoproliferative disorders associated with rheumatoid arthritis: a multi-center retrospective cohort study","volume":"32","author":"Saito","year":"2022","journal-title":"Mod Rheumatol"},{"key":"2024070814405415400_R3","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1080\/14397595.2021.1899570","article-title":"Clinicopathological characteristics of lymphoproliferative disorders in 232 patients with rheumatoid arthritis in Japan: a retrospective, multicenter, descriptive study","volume":"32","author":"Takada","year":"2022","journal-title":"Mod Rheumatol"},{"key":"2024070814405415400_R4","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1111\/j.1365-2141.1999.01239.x","article-title":"B-cell lymphoma associated with haemophagocytic syndrome: a clinical, immunological and cytogenetic study","volume":"104","author":"Shimazaki","year":"1999","journal-title":"Br J Haematol"},{"key":"2024070814405415400_R5","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1080\/1042819031000103926","article-title":"Effective anti-viral therapy for hemophagocytic syndrome associated with B-cell lymphoma","volume":"44","author":"Gomyo","year":"2003","journal-title":"Leuk Lymphoma"},{"key":"2024070814405415400_R6","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1046\/j.0954-6820.2003.01249.x","article-title":"Hodgkin\u2019s lymphoma, Epstein\u2013Barr virus reactivation and fatal haemophagocytic syndrome","volume":"255","author":"Hasselblom","year":"2004","journal-title":"J Intern Med"},{"key":"2024070814405415400_R7","first-page":"119","article-title":"Fatal pulmonary lymphomatoid granulomatosis in a patient taking methotrexate for rheumatoid arthritis","volume":"80","author":"Blanchart","year":"2014","journal-title":"Minerva Anestesiol"},{"key":"2024070814405415400_R8","article-title":"Iatrogenic T-cell lymphoma with associated hemophagocytic lymphohistiocyotsis in a patient with long-standing rheumatoid arthritis","volume":"2018","author":"Andrade","year":"2018","journal-title":"Case Rep Hematol"},{"key":"2024070814405415400_R9","article-title":"Hemophagocytic syndrome-associated variant of methotrexate-associated intravascular large B-cell lymphoma in a rheumatoid arthritis patient","volume":"2019","author":"Komeno","year":"2019","journal-title":"Case Rep Hematol"},{"key":"2024070814405415400_R10","doi-asserted-by":"crossref","first-page":"564","DOI":"10.3899\/jrheum.140533","article-title":"Incidence of malignancy and the risk of lymphoma in Japanese patients with rheumatoid arthritis compared to the general population","volume":"42","author":"Hashimoto","year":"2015","journal-title":"J Rheumatol"},{"key":"2024070814405415400_R11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/14397595.2017.1352477","article-title":"Lymphoproliferative disorders in patients with rheumatoid arthritis in the era of widespread use of methotrexate: a review of the literature and current perspective","volume":"28","author":"Harigai","year":"2018","journal-title":"Mod Rheumatol"},{"key":"2024070814405415400_R12","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1080\/14397595.2020.1869370","article-title":"Association of methotrexate use and lymphoproliferative disorder in patients with rheumatoid arthritis: results from a Japanese multi-institutional retrospective study","volume":"32","author":"Honda","year":"2022","journal-title":"Mod Rheumatol"},{"key":"2024070814405415400_R13","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1002\/art.21675","article-title":"Association of chronic inflammation, not its treatment, with increased lymphoma risk in rheumatoid arthritis","volume":"54","author":"Baecklund","year":"2006","journal-title":"Arthritis Rheum"},{"key":"2024070814405415400_R14","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.blre.2008.03.009","article-title":"Immunodeficiency-associated lymphomas","volume":"22","author":"Tran","year":"2008","journal-title":"Blood Rev"},{"key":"2024070814405415400_R15","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1002\/hon.2790","article-title":"Association of Epstein-Barr virus with regression after withdrawal of immunosuppressive drugs and subsequent progression of iatrogenic immunodeficiency-associated lymphoproliferative disorders in patients with autoimmune diseases","volume":"38","author":"Fujimoto","year":"2020","journal-title":"Hematol Oncol"},{"key":"2024070814405415400_R16","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1111\/ejh.12116","article-title":"Methotrexate\/iatrogenic lymphoproliferative disorders in rheumatoid arthritis: histology, Epstein-Barr virus, and clonality are important predictors of disease progression and regression","volume":"91","author":"Ichikawa","year":"2013","journal-title":"Eur J Haematol"},{"key":"2024070814405415400_R17","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1200\/JCO.2006.09.2403","article-title":"Revised response criteria for malignant lymphoma","volume":"25","author":"Cheson","year":"2007","journal-title":"J Clin Oncol"},{"key":"2024070814405415400_R18","doi-asserted-by":"crossref","first-page":"2508","DOI":"10.1080\/10428194.2019.1585841","article-title":"Clinicopathological features of clinical methotrexate-related lymphoproliferative disorders","volume":"60","author":"Tokuhira","year":"2019","journal-title":"Leuk Lymphoma"},{"key":"2024070814405415400_R19","doi-asserted-by":"crossref","DOI":"10.1097\/MD.0000000000001270","article-title":"Primary adrenal lymphoma possibly associated with Epstein-Barr virus reactivation due to immunosuppression under methotrexate therapy","volume":"94","author":"Ohkura","year":"2015","journal-title":"Medicine"},{"key":"2024070814405415400_R20","first-page":"201","article-title":"A case of bilateral adrenal incidentaloma in which MTX-related lymphoproliferative disease could be diagnosed by computed tomography-guided biopsy and MTX administration history","volume":"63","author":"Kitakaze","year":"2017","journal-title":"Hinyokika Kiyo"},{"key":"2024070814405415400_R21","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1002\/iju5.12429","article-title":"Epstein-Barr virus-related diffuse large B-cell lymphoma type methotrexate-associated lymphoproliferative disorders presenting in the adrenal gland","volume":"5","author":"Doi","year":"2022","journal-title":"IJU Case Rep"},{"key":"2024070814405415400_R22","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1080\/10428194.2017.1369073","article-title":"Clinicopathologic investigation of methotrexate-induced lymphoproliferative disorders, with a focus on regression","volume":"59","author":"Tokuhira","year":"2018","journal-title":"Leuk Lymphoma"},{"key":"2024070814405415400_R23","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1097\/PAS.0000000000001271","article-title":"Methotrexate-associated lymphoproliferative disorders in patients with rheumatoid arthritis: clinicopathologic features and prognostic factors","volume":"43","author":"Kurita","year":"2019","journal-title":"Am J Surg Pathol"},{"key":"2024070814405415400_R24","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1080\/14397595.2021.1879362","article-title":"Characteristics of rheumatoid arthritis with immunodeficiency-associated lymphoproliferative disorders to regress spontaneously by the withdrawal of methotrexate and their clinical course: a retrospective, multicenter, case-control study","volume":"32","author":"Kuramoto","year":"2022","journal-title":"Mod Rheumatol"},{"key":"2024070814405415400_R25","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1093\/rheumatology\/kex002","article-title":"Distinct patterns of lymphocyte count transition in lymphoproliferative disorder in patients with rheumatoid arthritis treated with methotrexate","volume":"56","author":"Saito","year":"2017","journal-title":"Rheumatology"},{"key":"2024070814405415400_R26","doi-asserted-by":"crossref","first-page":"3045","DOI":"10.3109\/10428194.2015.1022769","article-title":"Methotrexate-associated lymphoproliferative disorders: management by watchful waiting and observation of early lymphocyte recovery after methotrexate withdrawal","volume":"56","author":"Inui","year":"2015","journal-title":"Leuk Lymphoma"},{"key":"2024070814405415400_R27","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/S0925-5710(97)00584-7","article-title":"Differencial diagnosis of hemophagocytic syndrome: underlying disorders and selection of the most effective treatment","volume":"66","author":"Imashuku","year":"1997","journal-title":"Int J Hematol"},{"key":"2024070814405415400_R28","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1007\/s002770000155","article-title":"B-cell lymphomaassociated hemophagocytic syndrome: clinicopathological characteristics","volume":"79","author":"Miyahara","year":"2000","journal-title":"Ann Hematol"}],"container-title":["Modern Rheumatology Case Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/mrcr\/advance-article-pdf\/doi\/10.1093\/mrcr\/rxae007\/56676585\/rxae007.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/mrcr\/article-pdf\/8\/2\/243\/58470439\/rxae007.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/mrcr\/article-pdf\/8\/2\/243\/58470439\/rxae007.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,8]],"date-time":"2024-07-08T14:43:06Z","timestamp":1720449786000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/mrcr\/article\/8\/2\/243\/7606453"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,7]]},"references-count":28,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2024,2,7]]},"published-print":{"date-parts":[[2024,7,8]]}},"URL":"https:\/\/doi.org\/10.1093\/mrcr\/rxae007","relation":{},"ISSN":["2472-5625"],"issn-type":[{"value":"2472-5625","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,7]]},"published":{"date-parts":[[2024,2,7]]}}}