Smoking as a trigger for inflammatory rheumatic diseases.
OBJECTIVE
This review has two purposes: to describe the known effects of cigarette smoking on the development of inflammatory rheumatic diseases, in particular rheumatoid arthritis and systemic lupus erythematosus, and to review recent research aimed at understanding the mechanisms by which smoking may interact with genes and immunity in triggering these diseases.


RESULTS
Large case-control studies as well as cohort studies have demonstrated that cigarette smoking is a risk factor for RF positive and anti-citrulline antibody with rheumatoid arthritis and that the risk diminishes only several years after cessation of smoking. Evidence exists that smoking is a risk factor also for systemic lupus erythematosus, and that the risk may be related to the presence of anti-dsDNA antibodies. Mechanistic studies are reviewed that suggest that smoking can trigger specific and potentially disease-inducing immune reactions against citrullinated proteins in rheumatoid arthritis, and dsDNA in systemic lupus erythematosus, and it is suggested that the genetic context determines which immune reactions may be triggered by smoking.


CONCLUSIONS
Counselling against smoking should be mandatory in rheumatological practice both to patients and to their relatives. Studies on the mechanisms whereby smoking triggers rheumatoid arthritis and systemic lupus erythematosus may provide fundamental new knowledge about the cause and molecular pathogenesis of these diseases.
Klareskog
Lars
L
Rheumatology Unit, Department of Medicine, Karolinska Institutet at Karolinska University Hospital Solna, Stockholm, Sweden. lars.klareskog@ki.se
Padyukov
Leonid
L
Alfredsson
Lars
L
D000974:Antibodies, Antinuclear / Q000096:biosynthesis; D001172:Arthritis, Rheumatoid / Q000209:etiology / Q000235:genetics / Q000276:immunology; D003093:Colitis, Ulcerative / Q000209:etiology / Q000235:genetics / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000235:genetics / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000209:etiology / Q000235:genetics / Q000276:immunology; D012216:Rheumatic Diseases / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D012907:Smoking / Q000009:adverse effects* / Q000235:genetics / Q000276:immunology
D000974:Antibodies, Antinuclear