This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on Web of Science (89)  • Contact me when this article is cited  Related Content  • Related letters  • Similar articles in this journal  Topic Collections  • Otolaryngology/ Head & Neck Surgery  • Inflammatory Disease of Head & Neck  • Salivary Gland Disorders  • Evidence-Based Medicine  • Musculoskeletal Syndromes (Chronic Fatigue, Gulf War)  • Rheumatology, Other  • Review  • Rheumatoid Arthritis  • Immunologic Disorders  • Alert me on articles by topic  Social Bookmarking   What's this?

A Meta-analysis

Elias Zintzaras, PhD; Michael Voulgarelis, MD, PhD; Haralampos M. Moutsopoulos, MD, FACP, FRCP

Arch Intern Med. 2005;165:2337-2344.

Background  The risk of development of non-Hodgkin lymphoma (NHL) in autoimmune patients has been investigated in several cohort studies. These studies revealed inconclusive results. To shed some light on this controversy, we conducted a meta-analysis of all available cohort studies linking systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and primary Sjögren syndrome (pSS) to the risk of NHL development.

Methods  We searched the PubMed database (1974 to April 2005) for English-language cohort studies using the key words systemic lupus erythematosus, SLE, rheumatoid arthritis, RA, Sjögren syndrome, or SS; non-Hodgkin lymphoma; and relative risk, RR, standardized incidence rate, or SIR. All cohort studies that used established diagnostic criteria for SLE, RA, and pSS; had histologic confirmation of NHL; and provided standardized incidence rates (SIRs) were included in the meta-analysis.

Results  The 20 studies chosen for the analysis included 6 for SLE, 9 for RA, and 5 for pSS. Overall, the meta-analysis suggested extreme heterogeneity among the studies (P<.01; I²>70%), high risk of NHL development for pSS (random effects SIR, 18.8; 95% confidence interval [CI], 9.5-37.3); moderate risk for SLE (random effects SIR, 7.4; 95% CI, 3.3-17.0); and lower risk for RA (random effects SIR, 3.9; 95% CI, 2.5-5.9). In RA, the random effects SIRs of NHL with conventional antirheumatic treatment, cytotoxic treatment, and treatment with a biological agent were 2.5 (95% CI, 0.7-9.0), 5.1 (95% CI, 0.9-28.6), and 11.5 (95% CI, 3.7-26.9), respectively.

Conclusions  Rheumatic disease may present a potential risk factor for development of NHL. In this regard, we focused on the underlying pathophysiologic mechanisms related to lymphomagenesis in pSS, SLE, and RA, to justify the varying potential for and background of NHL development.

Author Affiliations: Department of Biomathematics, University of Thessaly School of Medicine, Larissa, Greece (Dr Zintzaras); and Department of Pathophysiology, National University of Athens School of Medicine, Athens, Greece (Drs Voulgarelis and Moutsopoulos).

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

RELATED LETTERS

Risk of Lymphoma in Autoimmune Rheumatic Conditions
Sasha Bernatsky, Ann Clarke, MD, MSc, and Rosalind Ramsey-Goldman
Arch Intern Med. 2006;166(11):1233-1234.
EXTRACT | FULL TEXT  

Risk of Lymphoma in Autoimmune Rheumatic Conditions—Reply
Elias Zintzaras, Michael Voulgarelis, and Haralampos M. Moutsopoulos
Arch Intern Med. 2006;166(11):1234.
EXTRACT | FULL TEXT  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Genetic and immune-related factors in the pathogenesis of lymphoproliferative and plasma cell malignancies
Kristinsson et al.
haematol 2009;94:1581-1589.
ABSTRACT | FULL TEXT  

Adverse events and efficacy of TNF-{alpha} blockade with infliximab in patients with systemic lupus erythematosus: long-term follow-up of 13 patients
Aringer et al.
Rheumatology (Oxford) 2009;48:1451-1454.
ABSTRACT | FULL TEXT  

Inflammatory bowel disease and lymphoproliferative disorders: the dust is starting to settle
Sokol and Beaugerie
Gut 2009;58:1427-1436.
ABSTRACT | FULL TEXT  

Lupus and cancer
Gayed et al.
Lupus 2009;18:479-485.
ABSTRACT  

TNF inhibition in SLE: where do we stand?
Aringer and Smolen
Lupus 2009;18:5-8.
 

Oral involvement in primary Sjogren syndrome
Fox et al.
Journal of the American Dental Association 2008;139:1592-1601.
ABSTRACT | FULL TEXT  

Diabetes and Risk of Non-Hodgkin's Lymphoma: A meta-analysis of observational studies
Mitri et al.
Diabetes Care 2008;31:2391-2397.
ABSTRACT | FULL TEXT  

Chronic Immune Stimulation and Subsequent Waldenstrom Macroglobulinemia
Koshiol et al.
Arch Intern Med 2008;168:1903-1909.
ABSTRACT | FULL TEXT  

Novel Insights in Chronic Lymphocytic Leukemia: Are We Getting Closer to Understanding the Pathogenesis of the Disease?
Caligaris-Cappio and Ghia
JCO 2008;26:4497-4503.
ABSTRACT | FULL TEXT  

Autoimmune disorders and risk of non-Hodgkin lymphoma subtypes: a pooled analysis within the InterLymph Consortium
Ekstrom Smedby et al.
Blood 2008;111:4029-4038.
ABSTRACT | FULL TEXT  

Intravascular Large B-Cell Lymphoma With Acute Abdomen As a Presenting Symptom in a Patient With Systemic Lupus Erythematosus
Ishii et al.
JCO 2008;26:1553-1555.
FULL TEXT  

Inciting inflammation: the RAGE about tumor promotion
Dougan and Dranoff
JEM 2008;205:267-270.
ABSTRACT | FULL TEXT  

Emerging biological therapies in primary Sjogren's syndrome
Ramos-Casals and Brito-Zeron
Rheumatology (Oxford) 2007;46:1389-1396.
ABSTRACT | FULL TEXT  

Immune Mechanisms in Non-Hodgkin Lymphoma: Joint Effects of the TNF G308A and IL10 T3575A Polymorphisms with Non-Hodgkin Lymphoma Risk Factors
Wang et al.
Cancer Res. 2007;67:5042-5054.
ABSTRACT | FULL TEXT  

Tolerance and efficacy of rituximab and changes in serum B cell biomarkers in patients with systemic complications of primary Sjogren's syndrome
Seror et al.
Ann Rheum Dis 2007;66:351-357.
ABSTRACT | FULL TEXT  

Sleep-Disordered Breathing and Blood Pressure in Children: A Meta-analysis
Zintzaras and Kaditis
Arch Pediatr Adolesc Med 2007;161:172-178.
ABSTRACT | FULL TEXT  

Malignant Lymphomas in Autoimmunity and Inflammation: A Review of Risks, Risk Factors, and Lymphoma Characteristics.
Smedby et al.
Cancer Epidemiol. Biomarkers Prev. 2006;15:2069-2077.
ABSTRACT | FULL TEXT  

Mycophenolate mofetil: an overview
Sinclair and Baildon
Lupus 2006;15:70-77.
 

Increased risks of lymphoma and death among patients with non-hepatitis C virus-related mixed cryoglobulinemia.
Saadoun et al.
Arch Intern Med 2006;166:2101-2108.
ABSTRACT | FULL TEXT  

The Risk of Cancer following Hospitalization for Infection in Infancy: A Population-Based Cohort Study.
Paltiel et al.
Cancer Epidemiol. Biomarkers Prev. 2006;15:1964-1968.
ABSTRACT | FULL TEXT  

Autoimmunity and susceptibility to Hodgkin lymphoma: a population-based case-control study in Scandinavia.
Landgren et al.
JNCI J Natl Cancer Inst 2006;98:1321-1330.
ABSTRACT | FULL TEXT  

Risk of Lymphoma in Autoimmune Rheumatic Conditions--Reply
Zintzaras et al.
Arch Intern Med 2006;166:1234-1234.
FULL TEXT  

Risk of lymphoma in autoimmune rheumatic conditions.
Bernatsky et al.
Arch Intern Med 2006;166:1233-1234.
FULL TEXT  

The role of epithelial cells in the initiation and perpetuation of autoimmune lesions: lessons from Sjogren's syndrome (autoimmune epithelitis)
Mitsias et al.
Lupus 2006;15:255-261.
ABSTRACT