Smoking inflames joints. (Environmental Disease).

After years of researching the effects that cigarette smoking has on rheumatoid arthritis, Derek Mattey has some advice, especially for women: Don't start smoking! In his most recent research, Mattey, a senior scientist at the Staffordshire Rheumatology Centre in Stoke-on-Trent, England, determined that if a woman has ever smoked cigarettes, even if she has since quit, she is more likely to have a more severe form of rheumatoid arthritis than women who have never smoked. This is especially true if she, like millions of other people, lacks a key gene.

"This is an important study," says John Klippel, medical director of the Atlanta, Georgia-based Arthritis Foundation. "It confirms that cigarette smoking plays a role in rheumatoid arthritis." Klippel says the suggestion of a genetic role in the severity of rheumatoid arthritis also makes Mattey's work important for understanding how the disease begins and progresses.

Mattey and his colleagues, reporting in the March 2002 issue of Arthritis & Rheumatism, say that the reason why smoking increases the severity of the disease appears to hinge on the relationship between smoking, rheumatoid arthritis, and glutathione S-transferase M1 (GSTM1). This enzyme helps convert environmental toxicants, such as those found in cigarette smoke, to less toxic, more hydrophilic products that can be more easily metabolized and excreted. About half of all people lack the GSTM1 gene, Mattey says, making it a very common polymorphism. But the bad news for women smokers is that lacking the GSTM1 gene and having rheumatoid arthritis combines for a more debilitating course of the disease.

The researchers used polymerase chain reaction-genotyping to determine who among 164 women with rheumatoid arthritis had the GSTM1 gene. They also tested the women for rheumatoid factor, an immune complex found in the blood and synovial fluid of patients with rheumatoid arthritis. About 80% of patients with rheumatoid arthritis test positive for rheumatoid factor, and the level of rheumatoid factor correlates positively with the severity of the disease. The women underwent radiologic tests to determine the extent of their rheumatoid arthritis damage (their "Larsen score"), and took the Health Assessment Questionnaire to determine how the disease had affected their capacity to perform common activities of daily living.

The researchers found that 58.5% of the women did not have the GSTM1 gene. They also ascertained that 51.3% of the women had never smoked, and 29.9% were current smokers. Women who lacked the GSTM1 gene and had ever or currently smoked were three times more likely to be rheumatoid factor positive than women who lacked the gene and had never taken up cigarettes. Patients who lacked the GSTM1 gene and had ever smoked also had significantly higher Larsen and Health Assessment Questionnaire scores than did those who lacked the gene and had never smoked.

"We were able to show that the combination of smoking and lack of the GSTM1 gene was correlated with a greater likelihood to be rheumatoid factor positive, and the questionnaires and radiology studies confirmed that these same individuals have more advanced, more severe rheumatoid arthritis," Mattey says.

The researchers aren't sure which smoke toxicants are responsible, or how they work. They are now trying to determine if smoking somehow induces the production of rheumatoid factor, and if ambient cigarette smoke also impacts rheumatoid arthritis. "It is difficult to say from this study if secondhand smoke has an effect on the severity of rheumatoid arthritis," Mattey says. "We are trying to make that determination at the moment."