Psoriatic Arthritis: What is Happening at the Joint?

Abstract

Psoriatic arthritis (PsA) is a heterogeneous and inflammatory disease with diverse clinical manifestations, including psoriasis, nail psoriasis, peripheral joint disease, axial joint disease, enthesitis, and dactylitis. Typically, this varied clinical presentation complicates the clinician’s ability to distinguish PsA from other forms of arthritis. In the synovium of individuals with PsA, upregulation of the genes WNT3A , BMPR2 , and TGFBR1 results in bone erosion and new bone formation, a pattern unique to the disease. Additionally, genes associated with angiogenesis and vascularization such as VEGF and TGFB1 facilitate inflammation and joint damage. Gross pathogenesis of PsA is driven by proinflammatory cytokines, and key cytokines affecting joint structures include tumor necrosis factor-α, interleukin (IL)-6, IL-17A, IL-21, IL-22, and IL-23. Early diagnosis is critical for providing treatment that prevents irreversible disease progression and function loss. This narrative review discusses differentiation of PsA from other forms of arthritis. Additionally, we detail the role of cytokines at the joint in mediating PsA pathogenesis. Funding: Novartis Pharmaceuticals Corporation.

RNAseq-Based Prioritization Revealed COL6A5, COL8A1, COL10A1 and MIR146A as Common and Differential Susceptibility Biomarkers for Psoriasis and Psoriatic Arthritis: Confirmation from Genotyping Analysis of 1417 Italian Subjects

“…The bioinformatic functional analysis revealed that COL10A1 plays a role in maintaining bone homeostasis and cartilage metabolism as well as in the organization and remodeling of ECM. This result supports the potential implication of bone and cartilage metabolism-related processes in the onset and progression of PsA [20]. Accordingly, it has been found that Collagen X metabolism was enhanced in patients affected by PsA and Axial Spondyloarthritis [21].…”

“…Of note, it is known that psoriatic patients may experience an aberrant vascularization of the dermis towards the epidermis, due to an overexpression of proangiogenic factors induced by the alteration of cell proliferation pathways. These vessels are characterized by tortuous capillary loops, which may contribute to exacerbate the disease symptoms in patients affected by Ps and PsA [19,20].…”

Vascular endothelial growth factor‐A as a promising therapeutic target for the management of psoriasis

“…[84] Since angiogenesis and VEGF-A also play a key role in the pathogenesis of psoriatic arthritis, patients with this phenotype may profit from a systemic therapy that targets the vasculature. [85,86] A case report of remission of psoriatic arthritis following bevacizumab therapy [78] supports the concept that anti-VEGF-A therapy may be a potential treatment option for both the skin and joint manifestations of psoriasis.…”

Effectiveness and safety of secukinumab in patients with moderate-to-severe plaque psoriasis – a real life retrospective study

“…PsA affects people heterogeneously with a range of clinical manifestations, like inflammatory arthritis, dactylitis, enthesitis, spondylitis, skin psoriasis and nail disease. The disease has a significant impact on patients' physical function, social participation, and quality of life [5,6].…”