Rheumatology 2001; 40: 1426-1427
© 2001 British Society for Rheumatology
Letters to the Editor |
Cigarette smoking and severity of rheumatoid arthritis
Department of Medicine, Clinical Sciences Centre, University Hospital Aintree, Longmoor Lane, Liverpool L9 7AL, UK
SIR, We read with great interest the paper by Masdottir et al. [1] reporting that women with rheumatoid arthritis (RA) and considerable exposure to cigarette smoke were more likely to have severe disease and nodules than women who smoked modestly. However, we propose that heavy prolonged smoking is also associated with the development of seropositive RA rather than simply disease severity (in terms of joint damage) and that the development of rheumatoid factor (RF) in heavy smokers partly underlies this important association.
The presence of RF in healthy individuals is perhaps more significant than generally understood, as persistence of both IgM and IgA RF is associated with a seven-fold risk of developing seropositive RA [2]. Of the known environmental risk factors associated with the development of RF in healthy individuals, cigarette smoking is by far the most important [3]. Whilst the association between pack-yr smoked and the presence of RF has not been studied in healthy individuals, healthy current smokers are significantly more likely to be positive for both IgM and IgA RF than non-smokers [4]. Furthermore, Heliovaara et al. [3] demonstrated that healthy individuals who had previously smoked had an increased risk of developing high-titre IgM RF (odds ratio 2.78) than individuals who had never smoked and that individuals smoking fewer than 15 cigarettes per day had a very modestly increased risk of developing seropositive RA (relative risk 1.28) compared with the much higher risk of smoking 25 or more cigarettes per day (relative risk 3.43). They also observed that former smokers were more likely to develop seropositive RA than lifelong non-smokers (relative risk 1.76). These data suggest that RF production is associated with high-intensity cigarette smoking and that, once smoking has induced RF production, this process continues despite the cessation of cigarette smoking. In their study, Masdottir et al. observed an association between pack-yr smoked and IgM and IgA RF in female patients, and likewise Wolfe [5] observed a significant association between an increased concentration of IgM RF and pack-yr smoked in RA, independent of the smoking status of the patient.
We propose that, in healthy individuals, as in RA patients, heavy prolonged smoking (but not smoking per se) is associated with RF production and the subsequent development of seropositive RA. Indeed, we have reported a striking association between heavy smoking (40–50 pack-yr) and RA, but only a modest association for ever having smoked [6]. Although cigarette smoking has been consistently associated with RA, a study of pre-menopausal RA patients observed an apparent protective effect for current smoking [7]. However, this might be explained by their young age (20–50 yr); the majority of women studied would not have accumulated the sufficiently high exposure required to provide the susceptibility factor. In keeping with this, we have observed that lifelong non-smoking RA cases develop RA at a significantly younger age than RA cases smoking at disease onset [6], and we note that a similar trend is observed by Masdottir et al. [1].
Regarding heavy smoking and increased RA disease severity, we suggest that the association observed by Masdottir et al. [1] is principally the result of comparing seropositive RA with seronegative RA. We note that in their study group half the women were seronegative; the majority of this group are likely to have never smoked [8]. To investigate the role of heavy smoking in RA, they compared those who had smoked less than 20 pack-yr with those who had smoked more than 20 pack-yr. However, as they included women who had never smoked in the group who had smoked less than 20 pack-yr, this group was biased because as many as 51% had actually never smoked. Therefore, heavy smokers were effectively compared with lifelong non-smokers rather than modest smokers. As suggested above, heavy smoking is associated with the development of RF, predisposing individuals to seropositive rather than seronegative RA. The differences in severity observed between the two groups studied may simply reflect the clinical differences that exist between seropositive and seronegative RA. Saag et al. [8] compared lifelong non-smokers with heavy smokers and observed an increased risk of seropositivity, erosions and nodules. Wolfe [5] did observe an association between increasing pack-yr smoked and increasing joint damage, but this was only apparent at a smoking intensity of above 40 pack-yr.
If there is a true dose response with pack-yr smoked and RA joint disease, a comparison between those smoking between 1 and 20 pack-yr and those who have smoked more than this should reveal a difference in severity. We would be interested to know if this is the case.
Notes
Correspondence to: D. Hutchinson. 
References
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Masdottir B, Jonsson T, Manfreosdottir V, Vikingsson A, Brekkan A, Valdimarsson H. Smoking, rheumatoid factor isotypes and severity of rheumatoid arthritis. Rheumatology2000;39:1202–5.
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Halldorsdottir HD, Jonsson T, Thorsteinsson J, Valdimarsson H. A prospective study on the incidence of rheumatoid arthritis among people with persistent increase of rheumatoid factor. Ann Rheum Dis2000;59:149–51.
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Heliovaara M, Aho K, Knekt P, Impivaara O, Reunanen A, Aromaa A. Coffee consumption, rheumatoid factor, and the risk of rheumatoid arthritis. Ann Rheum Dis2000;59:631–5.
[Abstract/Free Full Text] - Jonsson T, Thorsteinsson J, Valdimarsson H. Does smoking stimulate rheumatoid factor production in non-rheumatic individuals? APMIS1998;106:970–4.[Web of Science][Medline]
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Hutchinson D, Shepstone L, Moots R, Lear JT, Lynch MP. Heavy cigarette smoking is strongly associated with rheumatoid arthritis (RA), particularly in patients without a family history of RA. Ann Rheum Dis2001;60:223–7.
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Hazes JMW, Dijkmans BAC, Vandenbroucke JP, de Vries RRP, Cats A. Lifestyle and the risk of rheumatoid arthritis: smoking and alcohol consumption. Ann Rheum Dis1990;49:980–2.
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Saag KG, Cerhan JR, Kolluri S, Hunninghake GW, Schwartz DA. Cigarette smoking and rheumatoid arthritis severity. Ann Rheum Dis1997;56:463–9.
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