Figure 1.

Evolution toward rheumatoid arthritis (RA) can be considered as a disease continuum encompassing pathogenic phases which conclude in the development of arthritis. Preclinical phases can comprise of a symptomatic at-risk individuals with genetic risk (e.g. an affected first degree relative), environmental risk (including smoking and mucosal inflammation), and RA-related systematic autoimmunity (e.g. ACPA antibodies). Subclinical synovitis is more often found in symptomatic at-risk individuals, either in the presence of RA associated autoantibodies, or clinically suspect arthralgia (CSA).