Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy associated with psoriasis and included in seronegative spondyloarthropathy. PsA has several unique characteristics different from rheumatoid arthritis (RA), such as enthesopathy, dactylitis, and abnormal bone remodeling. As compared with synovitis of RA (pannus), proliferation of PsA synovium is mild and characterized by hypervascularity and increased infiltration of polymorphonuclear leukocytes in the synovial tissues. Angiogenesis plays a crucial role in cutaneous psoriasis, and several angiogenic factors such as vascular endothelial growth factor, interleukin-8, angiopoietin, tumor necrosis factor-
Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy in association with psoriasis. PsA is classified as one of the seronegative spondyloarthropathy characterized by joint destruction with extra-articular involvement (i.e., eye, gut, and bowel). The involved joints present swelling, redness, and deformity to the end, which are usually periphery (main involvements are distal interphalangeal joints), but sacroiliac joints are less frequently affected. In nearly 70% of patients, cutaneous lesions precede the onset of joint pain, in 20% arthropathy starts before skin manifestations, and in 10% both are contemporary. Results of laboratory examination show elevated levels of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) which reflect acute-phase inflammation. Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) antibodies are usually negative. HLA-B27 is found chiefly in patients with spondylitis type PsA. Radiographic features of joint space narrowing, erosions, osteolysis, new bone formation, enthesitis, spur formation, pencil-in-cup appearance, and bamboo spine. Although, in general, patients with severe cutaneous psoriasis often complain of arthralgia, skin severity and joint lesions are not always parallel. A number of studies have suggested genetic, environmental, and immunological aspects in the development of PsA. Although the pathophysiology of synovium of PsA is still not fully elucidated [
A number of studies have demonstrated that angiogenesis is crucial in the pathogenesis of psoriasis [
In mice, VEGF overexpressed selectively in basal keratinocytes exhibited a chronic skin inflammation with increased numbers of tortuous capillaries and expression of VEGFR-1 and VEGFR-2 [
Previous studies showed that synovial T-cells in PsA are functionally active, which may migrate also into the psoriatic skin as well as inflamed enthesis. T-cells, cytokines, chemokines, and matrix metalloproteinases (MMPs) are supposed to play important roles in the inflammatory process leading to the destruction of joint tissues. Not only T-cells but also B-cells are seen in the synovium, occasionally forming primitive germinal centers; however the implication of B-cell infiltration is unclear. Abundant T-cells, both CD4+ and CD8+ with clonal or oligoclonal expansions, are infiltrated in the synovial tissues of PsA [
Infiltration of CD68+ macrophages was less in synovium of PsA as compared with RA, but expression of macrophage-derived cytokines such as TNF-
Neutrophils play an important role in the lesional skin of psoriasis, and also neutrophil infiltration is seen in the synovium. As compared with rheumatoid synovial membranes, infiltration of polymorphonuclear cells is prominent [
Dendritic cells (DCs) populations are Langerhans cells, myeloid DCs, and plasmacytoid DCs. Myeloid CD11c+DCs are subdivided into resident and myeloid inflammatory DCs, depending on their expression of CD1c, and in the psoriatic skin, CD11c+CD1c− population is increased in number [
Mast cells are increased in number in the synovium in PsA as well as enhanced expression of stem cell factor, a mast cell growth factor [
Synovial angiogenesis is central to synovial proliferation. Angiogenic mediators secreted by synovial tissue cells and/or synovial tissue infiltrating cells are involved in neovascularization. Morphological vascular changes such as tortuous and elongated features are shown by microscopic examination in the blood vessels of synovial membrane of PsA [
Immunohistological localization of angiogenesis markers (a) VEGF, (b) flt-1, (c) flk-1, (d) angiopoietin, (e) HIF-1
In the inflamed synovium, synovial fibroblasts are stimulated by proinflammatory cytokines and may change the phenotype which secret inflammatory mediators, matrix-degrading enzymes, and chemotactic molecules. Toll-like receptors (TLRs) play an important role in the regulation of innate and adaptive immune responses. Recent findings demonstrate functionally active TLRs on synovial fibroblasts are involved in the regulation of inflammatory responses in the synovial tissues of RA and spondylarthropathy [
CD8+ T-cells are significantly increased with clonal expansions in synovial fluids, but CD4+ T-cells are few [
Angiogenic pathways are implicated to play an important role in the pathogenesis of PsA, which drives inflammation, synovial fibroblasts activation, and joint damages. Inhibition of angiogenesis targeting or controlling of angiogenic molecules or angiogenesis-induced cellular events may lead to the novel therapies for PsA.
The author states no conflict of interests.