Rheumatic manifestations in inflammatory bowel disease.

Musculoskeletal symptoms (articular, periarticular and muscular involvement, osteoporosis and related fractures, and fibromyalgia) are the most common frequent extra-intestinal manifestations of inflammatory bowel disease (IBD) and affect 6-46% of patients. IBD-related arthropathy is one of a group of inflammatory arthritides known as seronegative spondyloarthropathies (SpA), which also includes idiopathic ankylosing spondylitis (AS), reactive arthritis, psoriatic arthritis, and undifferentiated SpA. The articular involvement in IBD significantly affects the patients' quality of the life. Although magnetic resonance imaging (MRI) is still the gold standard for assessing entheseal involvement, ultrasonography (US) is a non-invasive and easily reproducible means of detecting early pathological changes in SpA patients. It can identify characteristic features of SpA such as enthesitis, bone erosions, synovitis, bursitis, and tenosynovitis and is therefore helpful for diagnostic purposes. Anti-TNF drugs should be used to treat AS patients with axial and peripheral symptoms (arthritis and enthesitis) who have persistently high levels of disease activity despite conventional treatment, and adalimumab and infliximab can also be beneficially used in patients with IBD.

Interleukin 6 blockade: tocilizumab in psoriatic arthritis.

Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy of unknown etiology that is associated with psoriasis. Joint destruction is often progressive: almost half of the patients attending an early arthritis clinic showed radiological damage 2 years after diagnosis. Proinflammatory cytokines are major mediators of systemic and local inflammation, and high levels of interleukin 1 (IL-1), IL-6, and tumor necrosis factor have been found in psoriatic skin lesions and the synovial tissue of patients with rheumatoid arthritis and PsA. IL-6 is a pleiotropic cytokine that mainly signals by membrane (neutrophil and lymphocyte) or soluble (endothelial cell) IL-6 receptors. IL-6 was originally identified as a factor in B cell differentiation, but is now known to influence T cell development: in the presence of IL-6 and transforming growth factor-ß (TGF-ß), naive T cells develop into Th17 cells, which are important mediators in PsA. IL-6 may also directly contribute to the epidermal hyperplasia seen in psoriatic epithelium and affect the function of dermal inflammatory cells. However, there are no data concerning the use of tocilizumab in patients with PsA, although a pilot study is currently being carried out because the role of IL-6 in the pathogenesis of PsA supports the idea that targeted treatments against IL-6 might be effective.

Antiphospholipid antibodies are associated with an increased risk for chronic renal insufficiency in patients with lupus nephritis.

BACKGROUND: Previous studies have documented the high frequency of thrombosis and fetal loss in patients with lupus nephritis and antiphospholipid (aPL) antibodies, but there is little information on the impact of aPL antibodies on the outcome of lupus nephritis. The aims of this study are to evaluate the prevalence of aPL antibodies in patients with lupus nephritis and assess their prognostic value for thrombosis and pregnancy morbidity and impact on long-term renal outcome. METHODS: One hundred eleven patients with lupus nephritis followed up for a mean of 173 +/- 100 months were tested regularly for immunoglobulin G (IgG) and IgM anticardiolipin antibodies and lupus anticoagulant. RESULTS: The overall prevalence of aPL antibodies was 26%. In follow-up, 79% of aPL antibody-positive patients experienced thrombotic events and/or fetal losses, and aPL antibodies were associated significantly with arterial or venous thrombosis (P = 0.00001), pregnancy morbidity (P = 0.045), thrombocytopenia (P = 0.0015), and persistent arterial hypertension (P = 0.028). aPL antibodies were significantly more frequent in patients with biopsy-proven membranous lupus nephritis (P = 0.01). A strong association between aPL antibodies and the development of chronic renal insufficiency in the long-term outcome also was found (P = 0.01). With multivariate analysis, aPL antibody positivity (P = 0.02), high plasma creatinine level at presentation (P = 0.01), and chronicity index (P = 0.00004) were independent predictors of chronic renal function deterioration. CONCLUSION: Detection of aPL antibodies in patients with lupus nephritis is useful not only to identify patients at risk for vascular and obstetric manifestations, but also for their potential deleterious impact on renal outcome.

Anti-inflammatory and immunomodulating properties of statins. An additional tool for the therapeutic approach of systemic autoimmune diseases?

Cardiovascular diseases secondary to accelerated atherosclerosis are now accepted as a cause of mortality and morbidity in patients suffering from systemic lupus erythematosus and rheumatoid arthritis. More recently, atherosclerosis is emerging as one of the most serious complications in the anti-phospholipid syndrome, although large epidemiological studies, such as those performed in lupus and rheumatoid arthritis patients, have not been performed up to now. Classical risk factors (dislipidemia, hypertension, diabetes, smoking, etc.) and steroid therapy cannot completely explain the high prevalence of cardiovascular complications in systemic autoimmune diseases. Since the modern view defines atherosclerosis as a chronic inflammatory disorder, it has been suggested that systemic inflammation and soluble immune mediators (circulating autoantibodies, immune-complexes, complement activation products) might play a role in accelerating vessel pathology. The main target appears to be the endothelium because of its ability to switch to a pro-adhesive, pro-inflammatory and pro-coagulant surface in response to these mediators. Recent advances in the knowledge of the pharmacology of statins have indicated that these drugs rather than to be simple cholesterol lowering molecules display a pleiotropic effects on several mechanisms involved in the atherosclerotic plaque formation. Their anti-inflammatory activity and particularly their ability to downregulate endothelial cell activation induced by different stimuli strongly suggest their possible use in conditions in which the systemic inflammation and the endothelial activation/damage are thought to represent key pathogenic mechanisms.