Pathophysiology of gout flares
Gout flares are triggered by the precipitation of MSU crystals in the joint or surrounding tissues. The initial recognition of “naked” MSU crystals by toll-like receptors 2 and 4 on chondrocytes and macrophage lineage cells appears to be critical to the expression of proinflammatory cytokines and initiation of the inflammatory response. The inflammatory potential of the crystals is thought to be determined by a balance of certain “coating” proteins; crystals coated with IgG bind Fc receptors on cells and promote an inflammatory response, whereas crystals coated with apolipoprotein-B less often undergo phagocytosis and induce less inflammation. MSU crystals stimulate the production of chemotactic factors, cytokines (IL-1β [through activation of the NLRP3 inflammasome], IL-6, IL-8, and tumor necrosis factor [TNF]), prostaglandins, leukotrienes, and oxygen radicals by neutrophils, monocytes, and synovial cells in addition to activating complement and inducing lysosomal enzyme release.
