Pathogenesis of psoriatic arthritis

Psoriatic arthritis is an inflammatory arthritis associated with psoriasis that is more common and severe than initially appreciated. The success of biologic agents in psoriatic arthritis has sparked great interest in this disorder, although the disease pathogenesis is poorly understood. This review focuses on recent advances in the genetic factors and immune pathways that have been implicated in susceptibility to disease. In addition, recent studies examining the mechanisms that underlie angiogenesis, enthesitis, and bone resorption in psoriatic arthritis are discussed.

Studies performed on several different populations indicate that the MHC class I allele Cw6 is associated with both early-onset psoriasis and psoriatic arthritis. Mutations in the caspase-activating recruitment domain 15 locus on chromosome 16 are also associated with psoriatic arthritis, providing support for a model involving innate immune mechanisms. Evidence for a CD8 antigen-driven acquired immune response in psoriatic synovium and blood was reported. The finding of elevated levels of vascular endothelial growth factor and angiopoietin 2 in psoriatic arthritis synovial vasculature may provide insights into events responsible for the tortuous vessel morphology, a histologic feature characteristic of psoriatic joints. Tumor necrosis factor (TNF)-alpha is a critical factor mediating inflammation in the synovium, enthesis, and bone. In particular, osteoclasts resorb bone via a receptor activator of nuclear factor kappaB-receptor activator of nuclear factor kappaB ligand signaling pathway that is potentiated by TNF-alpha. The lessening of bone marrow edema after anti-TNF therapy provides further support for the importance of this cytokine in disease pathogenesis.

Recent studies provide additional support for distinct pathogenetic mechanisms in psoriatic arthritis that arise from a complex interplay between genetic and environmental factors. Histopathologic data and results from clinical trials highlight the predominance of TNF-mediated inflammation in psoriatic joint tissues.