A hypothesis on the pathogenesis of rheumatoid and other non-specific synovitides based on a combination of observations often overlooked.

In early synovitides the tissue inflammatory cell reaction is often weak and sometimes absent, many alterations being consistent with nonvasculitic exudation (I). Increased permeability to protein may require little, if any, endothelial damage. In rheumatoid arthritis (RA) increased transfer of fluid and protein from vessels is not restricted to joints, suggesting that exudation is more liable to induce inflammation in joints than in other tissues of ambulant individuals (II). At least 17 vascular, rheological and other "primary" mechanisms may contribute to the formation of exudates; combinations of only a few of these may be required to produce joint effusions. Some mechanisms may explain why inflammation in RA favours joints (III). Joint effusions increase intra-articular hydrostatic pressure, contributing to synovial hypoxia, glycolysis and acidosis, which may be important "secondary" mechanisms in synovial inflammation (IV). Only a few of the "primary" mechanisms are strictly local ones, and RA may predominantly be a systemic disease dependent on combinations of minor aberrations in metabolic, endocrine and other functions (V). The combination of contributing mechanisms is not necessarily the same in two patients fulfilling the criteria for RA, and patients with clinically different types of synovitis may share pathogenetic mechanisms (VI).