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Rheumatoid arthritis (RA) is a chronic disease that requires long-term administration of immunomodulatory drugs with a greater risk of side effects like malignancies, serious infections and cardiovascular diseases. Furthermore, patients with RA are more prone than the general population to these manifestations. Safety of rituximab has been evaluated in the short-term (6 months) and in the medium-term (up to 10 years) in patients who had been previously treated with antagonists of tumor necrosis factor (a-TNF) and/or with methotrexate (MTX) and in patients who were not. Data obtained from clinical trials demonstrated that rituximab is well tolerated either after a single course or after multiple courses. The overall rate of adverse events (AEs) was stable after the first three courses. The most frequent adverse event was infusion-related reactions (IRR). Serious infections did not increase after multiple courses. Data from "real life" confirm that treatment with rituximab is well tolerated.

In systemic sclerosis (SSc) occurrence of recurrent digital ulcers (DU) is cause of pain and functional disability of hands. Treatment with vasodilator agents, such as calcium channel blockers, ACE inhibitors, prostanoids, has not shown to be an effective therapy. There is evidence that endotelin-1 (ET-1) is a key mediator in regulation of vascular tone and its enhanced production in SSc is believed to lead to vasoconstriction, vessel remodelling, local ischemia and ulcers of fingertips. Recently, an oral endothelin receptor antagonist, bosentan, has been proved to be effective in the treatment of SSc associated pulmonar arterial hypertension (PAH) and to decrease the development of new DU in patients with SSc. In this study, we assessed the occurrence of new DU in eight patients with SSc associated PAH and one SSc patient with recurrent DU refractory to standard vasodilatation therapy. All patients received bosentan at dosage of 62.5 mg bid for 4 weeks and 125 mg bid thereafter for one year. All patients had 3-4 DU of hands at baseline and one patients had also ulcers at lower limbs. In seven out of nine patients we did not record the occurrence of new DU and we also observed a 50% reduction of existing DU, whereas new DU occurred only in two patients. These data suggest that ET-1 plays a key role in DU induction in SSc patients and that ET-1 inhibition by bosentan can be an effective therapeutic strategy.

Joint involvement in systemic sclerosis (SSc) commonly occurs as arthralgias, while a true arthritis is less frequent. The most common arthritis developing in SSc is rheumatoid arthritis (RA) and its diagnosis may be misled by concomitant joint contracture or tendon sheath involvement due to SSc. Anti-citrullinated cyclic peptide (CCP) antibodies are an emerging tool to diagnose RA and have shown to be more specific than rheumatoid factor. We assessed the prevalence of anti-CCP antibodies in SSc patients and evaluated their sensitivity and specificity for associated RA. Searching for RF and anti-CCP antibodies and joint examination were carried out in sixty consecutive SSc patients. Hands and feet standard x-rays were performed in patients complaining with arthralgia and/or arthritis. Six out of sixty (10%) SSc patients had RA according to 1987 ARA revised criteria. Anti-CCP were detected in 5 patients (sensitivity 83%) and RF was present in all RA patients (sensitivity 100%). However, anti-CCP antibodies had a much higher specificity (94%) than RF (41%) for RA. Our study suggests that anti-CCP antibodies are a useful test to identify patients with SSc having also RA. This is crucial in the management of SSc because may allow an adequate therapy of RA and prevent further joint damage in patients who already have a poor quality of life.

Objective: Uveitis is a severe manifestation of rheumatic diseases since it can lead to visual impairment and even blindness. Ocular involvement is frequently a clinical challenge because its occurrence often requires changes of the therapeutic strategy. There are growing evidence that tumor necrosis factor alpha (TNFalpha) inhibitors may be an effective treatment of refractory uveitis. Purpose of this study was to evaluate the efficacy and safety of TNFalpha blocking agents in patients with seronegative spondylo-arthropathies (SNSA) and Behcet disease (BD) associated relapsing uveitis., Methods: Five consecutive patients with chronic or relapsing uveitis were prospectively studied. Two patients with SNSA had recurrent anterior uveitis and three patients had BD associated uveitis (one anterior, two posterior uveitis). All of the patients were taking systemic and topical corticosteroids and three of them were also treated with DMARDs (methotrexate, cyclosporine, sulphasalazine) without clinical benefit. Four patients received infliximab, an anti-TNFalpha monoclonal antibody, at a dosage of 5 mg/kg body weight and one patient was treated with etanercept, a TNFalpha receptor p75-Fc fusion protein, at a dosage of 25 mg twice weekly., Results: Both infliximab and etanercept induced a marked improvement in uveitis and none relapse was observed throughout all the study. Systemic corticosteroids were progressively tapered and stopped in all patients. Also methotrexate and sulphasalazine were discontinued, while cyclosporine dose has been reduced by 30%. No side effects were observed., Conclusions: Therapy with TNFalpha blockers, infliximab and etanercept, was effective and safe in the treatment of rheumatic disease associated uveitis. A complete remission was achieved even in patients with severe steroid resistant uveitis. Further controlled studies on larger number of patients are needed to better define the different forms of ocular involvement that can benefit from the therapy with TNFalpha inhibitors.

The association of Systemic Sclerosis (SSc) and Psoriatic Arthritis (PsA) is unfrequent; only few cases are reported in literature. We describe a case of a patient with SSc following the onset of PsA. The disease begun with tenosynovitis, polyarthritis in association with psoriasis. After two years, Raynaud's phenomenon and sclerodactyly appeared, and, later, pulmonary interstitial fibrosis and esophageal dysfunction. The existence of a common pathogenesis of the two diseases, SSc and PsA, is discussed.