What is the natural history of rheumatoid arthritis?

Inflammatory polyarthritis can be a self-limiting disease, develop into rhe umatoid arthritis (RA) or differentiate into another form of chronic arthri tis. It remains a clinical and scientific challenge to understand the relat ionship between these phenotypes. determine their aetiologies and predict t he course and outcome for individual patients. Even patients labelled as ha ving RA show a wide spectrum of clinical phenotypes. Disease definition is a major problem in studying the aetiology of PA as currently used classific ation criteria were derived using patients with established disease. RA is thought to result from the combination of genetic susceptibility and exposu re to an appropriate environmental trigger. The genetic component is probab ly oligogenic. The association with HLA has been known for over 25 years. R A is now thought to be associated with a conserved sequence of amino acids in a number of HLA-DRBI alleles, called the RA shared epitope. However, the shared epitope appears to be associated with PA chronicity and severity mo re than with susceptibility. Other potential RA susceptibility genes includ e IL-I, aromatase, corticotropin-releasing hormone and a region on the X ch romosome. Hormonal and reproductive factors also influence RA susceptibilit y and severity. RA is more common in women than men, especially before the menopause. Men may be protected by hormonal factors and require a stronger genetic component to develop disease. Although infectious triggers of RA ha ve long been suspected, no definitive evidence has been obtained. Previous blood transfusion, smoking and obesity are also possible risk factors, Chro nicity and remission are important aspects of the natural history of early PA. Although we can identify patients at risk of adverse prognosis with som e accuracy, we remain unable to predict remission. Functional disability an d radiological damage are the most studied outcomes in RA. Radiological dam age often occurs early in the course of RA, bur patients may show erosion f or the first time several years after symptom onset. Many studies have demo nstrated a relationship between HLA and features of severe RA in establishe d patients. This appears to be related to gene dosage.