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Clinical Consultation: Smoking and rheumatoid arthritis

Publication
Article
The Journal of Respiratory DiseasesThe Journal of Respiratory Diseases Vol 6 No 9
Volume 6
Issue 9

n epidemiologic studies, cigarette smoking is strongly associated with the development of rheumatoid arthritis (RA), in particular seropositive RA. In 1987, Vessey and colleagues1 first reported an unexpectedly elevated risk of RA among women smokers in the Oxford Family Planning Association contraceptive study.

Smoking and the risk of rheumatoid arthritis: Genes, gender, and the latest data How strong is the evidence that smoking is a risk factor for rheumatoid arthritis?

In epidemiologic studies, cigarette smoking is strongly associated with the development of rheumatoid arthritis (RA), in particular seropositive RA. In 1987, Vessey and colleagues1 first reported an unexpectedly elevated risk of RA among women smokers in the Oxford Family Planning Association contraceptive study.

Since then, 11 case-control and 4 cohort studies have confirmed the increased risk of incident RA associated with cigarette smoking.1-16 In these studies, it appears that the risk is higher in men (odds ratio [OR] range, 1.9 to 4.4 in 6 case-control studies2,5,6,10,12,15) than in women (OR range, 0.6 to 2.5 in 8 case-control studies1,3-6,8,9,12 and 3 cohort studies11,13,16). Among RA patients with first-degree relatives who have RA, the age at onset is younger in smokers than in nonsmokers.17

Smoking intensity (number of cigarettes smoked per day) and duration are both powerful predictors of RA risk, although duration may be more important.11 The risk of incident RA is elevated for current and former smokers and remains elevated for up to 20 years after smoking cessation.13,16

Cigarette smoking primarily increases the risk of seropositive (rheumatoid factor [RF]-positive and anti-cyclic citrullinated peptide [anti-CCP] antibody-positive) RA. An interesting gene-environment interaction exists between cigarette smoking and the HLA-DRB1 shared epitope. A group of HLA-DRB1 alleles strongly associated with susceptibility to RA share a region of sequence similarity--or shared epitope--at amino acid positions 70 to 74 in the third hypervariable region of the HLA-DRB1 molecule.6,14,18 In the Epidemiological Investigation of Rheumatoid Arthritis (EIRA) cohort study in Sweden, current smokers with 2 copies of the shared epitope had a 16-fold increased risk of RF-positive RA (95% confidence interval [CI], 7.2 to 34.2)6 and a 21-fold increased risk of anti-CCP antibody- positive RA (95% CI, 11.0 to 40.2).14

The EIRA group has proposed a new and elegant model for the pathogenesis of anti-CCP antibody-positive RA.14 Cigarette smoking may promote citrullination (the conversion of an arginine to a citrulline residue in certain peptides), and the generation of antibodies to citrullinated proteins (anti-CCP antibodies) may then occur preferentially in persons who have the shared epitope genotypes.14,19

References:

REFERENCES


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