Association of chronic inflammation, not its treatment, with increased lymphoma risk in rheumatoid arthritis.
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 dramatically (OR ninth decile 9.4 [95% confidence interval 3.1-28.0], OR tenth decile 61.6 [95% confidence interval 21.0-181.0]). Most lymphomas (48%) were of the diffuse large B cell type, but other lymphoma subtypes also displayed an association with cumulative disease activity. Standard nonbiologic treatments did not increase lymphoma risk. EBV was present in 12% of lymphomas.


CONCLUSIONS
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.
Baecklund
Eva
E
Department of Rheumatology, Akademiska Hospital, Uppsala, Sweden. Eva.Baecklund@swipnet.se
Iliadou
Anastasia
A
Askling
Johan
J
Ekbom
Anders
A
Backlin
Carin
C
Granath
Fredrik
F
Catrina
Anca Irinel
AI
Rosenquist
Richard
R
Feltelius
Nils
N
Sundström
Christer
C
Klareskog
Lars
L
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018501:Antirheumatic Agents; D001172:Arthritis, Rheumatoid / Q000150:complications* / Q000188:drug therapy; D016022:Case-Control Studies; D002908:Chronic Disease; D005260:Female; D004854:Herpesvirus 4, Human / Q000302:isolation & purification; D006801:Humans; D007249:Inflammation / Q000150:complications*; D008223:Lymphoma / Q000209:etiology* / Q000821:virology; D008297:Male; D008875:Middle Aged; D012307:Risk Factors
D018501:Antirheumatic Agents