Lymphoma subtypes in patients with rheumatoid arthritis: Increased proportion of diffuse large B cell lymphoma

Baecklund, Eva; Sundström, Christer; Ekbom, Anders; Catrina, Anca I.; Biberfeld, Peter; Feltelius, Nils; Klareskog, Lars

doi:10.1002/art.11144

Cited by 153 publications

(113 citation statements)

References 29 publications

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“…17 However, an iatrogenic etiology appears more likely, as the incidence of EBV in rheumatoid arthritis-associated lymphomas is low. 18,19 Methotrexate, used to treat rheumatoid arthritis and other autoimmune diseases, has been closely associated with the development of lymphomas in rheumatoid arthritis patients. These methotrexate-associated lymphomas are most often classical Hodgkin lymphoma and diffuse large B-cell lymphoma that are EBV-positive, similar to the most prevalent lymphomas in our series.…”

Section: Discussionmentioning

confidence: 99%

Immunomodulator agent-related lymphoproliferative disorders

Hasserjian

Chen²,

Perkins

et al. 2009

Modern Pathology

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The recent development of inhibitors of key immune response proteins has revolutionized the therapy of autoimmune diseases; these immunomodulator agents include monoclonal antibodies and receptor antagonists. However, as with all therapies, these new agents are not without side effects and complications. In particular, anti-tumor necrosis factor alpha (TNFa) agents have been reported to be associated with an increased incidence of lymphoproliferative disorders, infections, and vasculitis. We evaluated the clinicopathological features of 18 cases of immunomodulator agent-related lymphoproliferative disorders (IAR-LPD) from several institutions. These included 6 cases of B-cell lymphoma, 2 cases of T-cell lymphoma, 3 cases of classical Hodgkin lymphoma, and 7 atypical lymphoid proliferations that did not fulfill diagnostic criteria for lymphoma; two of the latter regressed after discontinuation of the immunomodulator agent therapy. All eight lymphoma patients with available information had also received prior chemotherapy (methotrexate or 6-mercaptopurine). EBV was strongly associated with the B-cell and classical Hodgkin lymphomas. This case series illustrates that a broad range of lymphoid proliferations can occur after immunomodulator agent therapy and that these immunomodulator agent-related lymphoproliferative disorders have considerable overlap with other well-defined lymphoproliferative diseases associated with iatrogenic immunosuppression. Further study is warranted to evaluate how these therapies interact with other immunosuppressive agents and the underlying abnormal immune system to enhance the development of lymphomas and atypical lymphoid proliferations.

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Section: Discussionmentioning

confidence: 99%

Immunomodulator agent-related lymphoproliferative disorders

Hasserjian

Chen²,

Perkins

et al. 2009

Modern Pathology

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“…The same exclusion/inclusion criteria were used for the controls, i.e., of all potential controls whose files were reviewed (n ϭ 507), 65 (13%) were excluded because the patients did not meet the ACR criteria for RA or did not have erosive/deforming polyarthritis and other typical signs of RA. To confirm the lymphoma diagnosis, paraffinembedded lymphoma tissues were reviewed and reclassified according to the World Health Organization (WHO) classification (28), as previously described (29). We tested for Epstein-Barr virus (EBV) in the lymphomas using EBVencoded RNA in situ hybridization (29).…”

Section: Methodsmentioning

confidence: 99%

“…To confirm the lymphoma diagnosis, paraffinembedded lymphoma tissues were reviewed and reclassified according to the World Health Organization (WHO) classification (28), as previously described (29). We tested for Epstein-Barr virus (EBV) in the lymphomas using EBVencoded RNA in situ hybridization (29).…”

Section: Methodsmentioning

confidence: 99%

“…The first, described in reports of our pilot study (6,29), scored overall disease activity for the whole RA disease period as either low, medium, or high (assessed in 376 cases/controls). The overall disease activity score was based on the estimation of a score value for each reported visit, and the final score was the mean of the total scores from all visits ( Table 1).…”

Section: Methodsmentioning

confidence: 99%

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Association of chronic inflammation, not its treatment, with increased lymphoma risk in rheumatoid arthritis

Baecklund

Iliadou

Askling

et al. 2006

Arthritis & Rheumatism

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795

562

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Objective. Chronic inflammatory conditions such as rheumatoid arthritis (RA) have been associated with malignant lymphomas. This study was undertaken to investigate which patients are at highest risk, and whether antirheumatic treatment is hazardous or protective.Methods. We performed a matched case-control study of 378 consecutive Swedish RA patients in whom malignant lymphoma occurred between 1964 and 1995 (from a population-based RA cohort of 74,651 RA patients), and 378 controls. Information on disease characteristics and treatment from onset of RA until lymphoma diagnosis was abstracted from medical records. Lymphoma specimens were reclassified and tested for Epstein-Barr virus (EBV). Relative risks (odds ratios [ORs]) for lymphomas (by subtype) associated with deciles of cumulative disease activity were assessed, as were ORs associated with drug treatments.Results. The relative risks of lymphoma were only modestly elevated up to the seventh decile of cumulative disease activity. Thereafter, the relative risk increased Conclusion. Risk of lymphoma is substantially increased in a subset of patients with RA, those with very severe disease. High inflammatory activity, rather than its treatment, is a major risk determinant.

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“…Six of those patients had 2 of these ATM. Total accumulated disease activity was analyzed from retrospective data by calculation of the number of joints affected by arthritis, erythrocyte sedimentation rate (mm/h), and the physician's global assessment as described by Baecklund, et al 35 . Treatments (≥ 6 months) with corticosteroids, diseasemodifying antirheumatic drugs (DMARD), anti-TNF treatment, and statins were registered.…”

Section: Methodsmentioning

confidence: 99%

Polymorphisms of the Genes EncodingCD40and Growth Differentiation Factor 15 and in the 9p21.3 Region in Patients with Rheumatoid Arthritis and Cardiovascular Disease

Ärlestig¹,

Rantapää-Dahlqvist²

2012

J Rheumatol

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Objective.Genes or gene products associated with coronary artery disease in the general population were analyzed in rheumatoid arthritis (RA) patients with atherothrombotic manifestations (ATM).Methods.A cross-sectional study of 681 individuals (498 women; 183 men) with RA (American College of Rheumatology criteria), a mean age of 60.6 ± 13.2 years, and mean disease duration of 15.5 ± 12.6 years who were consecutively recruited and followed for 6 years. The prevalence of ATM [i.e., myocardial infarction, angina pectoris with intervention, deep vein thrombosis/pulmonary embolism (DVT/PE), and/or stroke/transient ischemic attack (TIA)] was recorded. Polymorphisms were analyzed in the genes coding for growth differentiation factor 15 (GDF15)/monocyte inhibitory cytokine-1 (MIC-1; rs1058587),CD40(rs1535045 and rs3765459), and the 9p21.3 locus (rs1333049). Controls were randomly selected (n = 687; matched for age and sex).Results.The distribution of genotypes ofGDF15/MIC-1differed significantly between patients with RA and controls (chi-squared = 6.40, 2 df, p = 0.041). ATM were associated with polymorphism of theGDF15/MIC-1G allele (OR 2.21, 95% CI 1.17–4.18), and with CC genotype of the 9p21.3 locus (rs1333049; OR 1.92, 95% CI 1.15–3.19). Stroke/TIA in women was associated withGDF15/MIC-1GG genotype (OR 3.75, 95% CI 1.06–13.33), while stroke/TIA in men was associated withCD40homozygous major alleles (OR 6.48, 95% CI 1.31–32.0 and OR 2.78, 95% CI 0.78–9.91, respectively). DVT/PE was associated with polymorphism in theGDF15/MIC-1gene (rs1058587) minor allele (OR 3.53, 95% CI 1.30–9.58).Conclusion.The gene polymorphisms analyzed were associated with different ATM in RA. TheGDF15/MIC-1gene polymorphism was also associated with RAper se, suggesting a common etiology for RA and ATM.

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Lymphoma subtypes in patients with rheumatoid arthritis: Increased proportion of diffuse large B cell lymphoma

Cited by 153 publications

References 29 publications

Immunomodulator agent-related lymphoproliferative disorders

Immunomodulator agent-related lymphoproliferative disorders

Association of chronic inflammation, not its treatment, with increased lymphoma risk in rheumatoid arthritis

Polymorphisms of the Genes EncodingCD40and Growth Differentiation Factor 15 and in the 9p21.3 Region in Patients with Rheumatoid Arthritis and Cardiovascular Disease

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