What is the natural history of rheumatoid arthritis?

Inflammatory polyarthritis can be a self-limiting disease, develop into rheumatoid arthritis (RA) or differentiate into another form of chronic arthritis. It remains a clinical and scientific challenge to understand the relationship between these phenotypes, determine their aetiologies and predict the course and outcome for individual patients. Even patients labelled as having RA show a wide spectrum of clinical phenotypes. Disease definition is a major problem in studying the aetiology of RA as currently used classification criteria were derived using patients with established disease. RA is thought to result from the combination of genetic susceptibility and exposure to an appropriate environmental trigger. The genetic component is probably oligogenic. The association with HLA has been known for over 25 years. RA is now thought to be associated with a conserved sequence of amino acids in a number of HLA-DRB1 alleles, called the RA shared epitope. However, the shared epitope appears to be associated with RA chronicity and severity more than with susceptibility. Other potential RA susceptibility genes include IL-1, aromatase, corticotropin-releasing hormone and a region on the X chromosome. Hormonal and reproductive factors also influence RA susceptibility 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 have long been suspected, no definitive evidence has been obtained. Previous blood transfusion, smoking and obesity are also possible risk factors. Chronicity and remission are important aspects of the natural history of early RA. Although we can identify patients at risk of adverse prognosis with some accuracy, we remain unable to predict remission. Functional disability and radiological damage are the most studied outcomes in RA. Radiological damage often occurs early in the course of RA, but patients may show erosion for the first time several years after symptom onset. Many studies have demonstrated a relationship between HLA and features of severe RA in established patients. This appears to be related to gene dosage.