To examine and explore the potential relationships among the following: the incidence/severity of rheumatoid arthritis (RA), the extra-articular manifestations of RA, vascular disease, certain specific malignancies, the p53 tumor suppressor gene, and cigarette smoking.
The medical literature was reviewed from 1985 to 2001 with the assistance of a MEDLINE search using the key words vascular disease, smoking, protein p53, RA, rheumatoid vasculitis, cancer, and malignancies. A qualitative review was performed after all articles were abstracted and new information summarized.
Cigarette smoking has been increasingly shown in epidemiologic and case-control studies to be an important risk factor for both the incidence and severity of RA, especially in seropositive men. Further, there is evidence of a downward trend in incidence of extra-articular manifestations of RA, especially RA vasculitis, observed with a decrease in worldwide tobacco use and overall improved mortality in RA. The association of cigarette smoking with lung and other cancers and its link to vascular disease (including Buerger's disease) and atherosclerosis appears secure. Mutations or alterations in p53, a suppressor gene that regulates cell growth, have been found in certain cancers, cigarette smokers, and in patients with RA.
Cigarette smoking appears to have an undeniable link to the pathogenesis of vascular disease of many types, including the possibility of a strong causal connection to rheumatoid vasculitis. The observations worldwide of decreasing tobacco use along with secular trends of diminished RA vasculitis and extra-articular manifestations, and with improved survival, points to a better outcome for our patients. The example of p53 may be a first step in the discovery of additional links between environmental triggers and phenotypic expression of chronic illness.