Established rheumatoid arthritis. The pathogenic aspects

The development of rheumatoid arthritis (RA), at least in its autoantibody-positive subset, evolves through a series of events starting well before the appearance of synovitis. The distinction between 'early' and 'established' RA is, therefore, an evolving concept. In routine practice, however, the management of RA still starts with the occurrence of clinically detectable synovitis. As such, the synovial membrane remains a major target for the exploitation of possible stage-specific drivers of the disease. The recognition of a 'window of opportunity', in which treatment is more likely to succeed, raises the hypothesis that there might be a period in which the biological processes of RA are less mature and potentially reversible. The present review aims to provide a general picture of the modifications occurring in RA synovium, analysing the contribution of both infiltrating immune cells and stromal cells. When available, differences between early and established RA will be discussed.