Pain in rheumatoid arthritis: a critical review.

Patients with rheumatoid arthritis (RA) are frequently afflicted by pain, which may be caused by joint inflammation (leading to structural joint damage) or secondary osteoarthritis, and may be increased by central sensitisation. Non-inflammatory pain may also confuse the assessment of disease activity, and so the aim of treatment is not only to combat inflammatory disease, but also relieve painful symptoms. In order to ensure effective treatment stratification, it is necessary to record a patients medical history in detail, perform a physical examination, and objectively assess synovitis and joint damage. The management of pain requires various approaches that include pharmacological analgesia and biological and non-biological treatments. Although joint replacement surgery can significantly improve RA-related pain, it may only be available to patients with the most severe advanced disease.

Immunogenicity and autoimmunity during anti-TNF therapy.

The introduction of anti-tumour necrosis factor (TNF) agents for the treatment of rheumatoid arthritis (RA), Crohn's disease (CD) or spondyloarthritis (SpA) has revolutionised the therapeutic approach to patients with active disease failing to respond to conventional therapy. However, some of the patients treated with selective TNF inhibitors may develop autoantibodies, such as antinuclear antibodies (ANAs) and anti-double-stranded DNA (anti-dsDNA) antibodies. Furthermore, anti-phospholipid antibodies, which are mainly detected by means of anti-cardiolipin assays, have been found in RA patients receiving TNF blockers. There have also been a number of reports of the development of anti-drug antibodies, of which those against infliximab can interfere with the drug's pharmacokinetics (and therefore its effects), and may also cause acute and delayed infusion and injection site reactions. The onset of autoimmune diseases during biological treatment is rare, but it needs to be promptly recognised in order to plan appropriate patient management. The addition of an immunosuppressive drug can reduce the induction of anti-TNF antibodies.

Cardiovascular involvement in psoriatic arthritis.

Psoriasis is a chronic, genetically determined and immunomediated inflammatory skin disease that affects 2-3% of the Caucasian population. A considerable proportion of these patients develop a form of inflammatory arthritis known as psoriatic arthritis (PsA), although the prevalence of this has not been well defined. Patients with PsA have a higher mortality rate than the general population and the risk of mortality is related to disease severity at the time of presentation. Endothelial dysfunction and early atherosclerosis have been found in patients with PsA without any cardiovascular disease (CVD) risk factors, and experts believe that CVD is one of the leading causes of death, as it is in patients with rheumatoid arthritis (RA). Various disease-related mechanisms may be involved in the development of premature vascular damage in both cases, including an increased synthesis of proinflammatory mediators (such as cytokines, chemokines and adhesion molecules), autoantibodies against endothelial cell components, perturbations in T-cell subsets, genetic polymorphisms, hyperhomocysteinemia, oxidative stress, abnormal vascular repair, and iatrogenic factors. In a recent study of 22 patients with PsA without any signs of CVD, we found that the plasma concentration of asymmetric dimethylarginine (ADMA) levels were significantly high and coronary flow reserve (CFR) was significantly reduced. Moreover, there was a significant correlation between CFR and plasma ADMA levels in the PsA group. The significant correlation between the reduced CRF and increased ADMA levels suggests that, like patients with early RA, PsA patients suffer from endothelial dysfunction and impaired coronary microcirculation. Active PsA is a risk factor for CVD, and so PsA patients should be screened for subclinical forms of the disease and its risk factors, and an early treatment approach should be adopted.