Pathogenesis of acute CPP crystal arthritis (pseudogout)
Crystal shedding explains the occurrence of CPP crystals within the synovial fluid. These crystals may induce inflammation in several ways.
- • Engagement of toll-like receptor 2 in phagocytes and chondrocytes (with subsequent downstream activation of inflammatory pathways).
- • Direct interaction with intracellular NALP-3, resulting in caspase-1 activation and emission of multiple cytokines.
- • Release of neutrophil extracellular traps.
- • Interaction with cell membranes causing nonspecific activation and release of prostaglandins, leukotrienes, and cytokines. Interleukin (IL)-8 is a potent neutrophil chemoattractant, which is critical in bringing more cells into the joint.
Apart from inducing inflammation, CPP crystals have important direct catabolic effects on chondrocytes and synoviocytes via production of metalloproteinases, prostaglandins, and nitric oxide, altering the mechanical properties of cartilage.
