Research Update




Cigarette Smoking and Systemic Lupus Erythematosus: A Smoking Gun?

What problem was studied?
Systemic lupus erythematosus (SLE, or lupus) is an autoimmune disease characterized by inflammation of the joints, skin and internal organs. Although the disease is often severe and disabling, little is known about its cause. Most researchers agree that a combination of genetic and environmental factors play a role in its development.

Cigarette smoke contains hundred of potentially toxic compounds including tars, nicotine, carbon monoxide and polycyclic aromatic hydrocarbons, with many known and unknown effects on the body. The pro-inflammatory effects of cigarette smoke have been well studied in relation to the risk of cardiovascular disease and emphysema. Studies have also have linked cigarette smoke to the development of rheumatoid arthritis, Graves’ disease and primary biliary (liver) cirrhosis.  There are suspicions and limited evidence that cigarette smoke may contribute to the development of lupus as well, but the role of cigarette smoking in the development of lupus remains controversial.

What was done in the study?
To date, three epidemiologic studies have reported significantly increased odds ratios for the development of lupus in smokers, while six other studies have not found a clear association. This paper looked at a previously published meta-analysis of those studies and discussed the strengths and weaknesses of these studies and their findings as well as the potential implication for those findings.

What were the study results?
A meta-analysis of the nine studies on smoking and lupus suggests that current cigarette smoking poses a modest increase in the risk of development, while past smoking does not increase risk. These results suggest that current smoking may be an instantaneous hazard for the development of SLE and that after smoking stop, the risk of SLE returns to that observed in people who have never smoked.

However, the authors of the meta-analysis and this review, Arthritis Foundation-funded researcher Karen H. Costenbader, MD, and Elizabeth W. Karlson, MD, of Brigham and Women’s Hospital in Boston, say there are wide variations among the studies that make such an analysis difficult. These include definition of smoking status (never, past and current), questionnaire response rates in cases (people who developed lupus) and controls (people who did not), the inclusion of potential confounders (factors other than smoking that may have contributed to lupus’ development) and the timing of the study questionnaire in relation to the onset of SLE.  Another problem was that the most of the studies were case-control retrospective studies, in which people with lupus were asked to recall past exposure to cigarette smoke years in the past. Two large prospective studies – in which populations and their health habits are followed before the development of disease and which are generally accepted as more reliable than retrospective studies -- did not observe an association between smoking and the development of lupus, but probably did not have enough people with lupus to definitively detect or rule out such an association.

What’s the relevance to people with lupus?
The current thinking about lupus is that an environmental exposure triggers the disease in genetically susceptible people. Further studies are needed to understand better the potential role of cigarette smoke and its components in triggering the disease. “In the meantime, the possibility that cigarette smoking could increase the risk of developing lupus should be added to the long list of good reasons young women should be dissuaded from starting to smoke and encouraged to stop as soon as possible,” says Dr. Costenbader (see “Portrait in Research,” for more about Dr. Costenbader’s research).

Source: Autoimminuty, Vol. 38, No. 7


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