Insights into mechanisms

Rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) are all associated with a probably distinct immune-mediated pathogenesis that is central to the pathophysiology of each disease but ultimately leads to a chronic infl ammatory response as a fi nal common pathway. Th is fundamental infl ammatory response is characterised by an overproduction of pro infl ammatory cytokines, particularly TNF, IL-1 and IL-6 [1]. TNF is a dominant proinfl ammatory cytokine in RA, AS and PsA. Th e cytokine has both a direct eff ect and an indirect eff ect on the infl ammatory events in these conditions [2-4]. TNF induces macrophages and other cells to secrete other proinfl ammatory cytokines (for example, IL-1, IL-6, IL-8), leads to T-cell activation and induces endothelial cells to express both adhesion molecules that increase T-cell infi ltration and vascular growth factors that promote angiogenesis and keratinocyte proliferation. TNF is also involved in the diff erentiation and maturation of osteoclasts, the pivotal cells engaged in bone destruction in arthritis [5], and stimulates fi broblasts, osteoclasts and chondrocytes to release protein ases, which destroy articular cartilage and bone [1,3,6,7]. Typical infl ammatory symptoms in RA include joint swelling and pain, systemic malaise and morning joint stiff ness. As RA progresses, continued infl ammation leads to permanent damage to the cartilage, bone, tendons and ligaments and, subsequently, to joint destruction and disability [1]. AS is primarily a disease of the axial skeleton that involves the sacroiliac joints and spine [8]. Infl ammatory back pain with stiff ness is the main clinical symptom [9]. Nonaxial involvement may include peripheral joint arthritis (most commonly of the knees), enthesitis and dactylitis [10,11]. Extra-articular manifestations are fairly common in AS patients [12-14] and can aff ect the eyes, gastrointestinal tract, lungs, heart and bones. PsA is characterised by joint damage with associated pain and swelling. Th e disorder is similar to RA but with less severe symptoms. Nail abnormalities, psoriatic skin lesions, enthesitis and dactylitis are common in PsA [15]. Nail psoriasis is associated with a higher prevalence of joint involvement and a more progressive form of the disease [16,17]. Th e skin lesions usually manifest before arthritic symptoms [18].