Mixed connective tissue diseases: new aspects of clinical picture, prognosis and pathogenesis.

pulmonary involvement – either pulmonary fibrosis or pulmonary hypertension – has emerged as an important prognostic factor in MCTD [11-15]. In 2005, Bodolay and co-authors [13] reported a 66.6% prevalence of active interstitial lung disease in consecutive patients with MCTD. In a recent study, Gunnarsson et al. [14] reported at least one abnormality compatible with lung fibrosis in 52% of MCTD patients, with severe lung fibrosis observed in 19% assessed with high resolution computed tomography. Importantly, severe lung fibrosis was associated with increased mortality [14]. On the other hand, Gunnarsson et al. [15] recently reevaluated an unselected cohort of MCTD patients and found that the prevalence of pulmonary arterial hypertension was only 3.4%. Interestingly, the presence of antibeta-2 glycoprotein I antibodies was associated with pulmonary arterial hypertension in a small cohort of MCTD patients [16]. Recent data have suggested that antiU1RNP autoantibodies may play a central role in the disease pathogenesis. In fact, anti-U1RNP autoantibodies were found to interact with lung tissue, contributing significantly to disease manifestations [17]. Although the presence of anti-U1RNP autoantibodies is mandatory for the diagnosis, the coexistence of other autoantibody specificities is a common finding in MCTD patients, with a significant influence on disease expression. Szodoray and collaborators [18] described three different clinical and serological sub-phenotypes of disease; the first subgroup appears to be characterized by patients with anti-endothelial cells and antiphospholipid antibodies in association with pulmonary arterial hypertension, Raynaud’s phenomenon, livedo reticularis and vascular thrombosis. t The term “mixed connective tissue disease” (MCTD) was coined in 1972 by Sharp et al. [1-6] to refer to a distinct systemic autoimmune disease characterized by overlapping features of systemic lupus erythematosus, systemic sclerosis, polymyositis/dermatomyositis and rheumatoid arthritis, in association with antibodies against the U1 small nuclear ribonucleoprotein autoantigen (U1snRNP) as a serological hallmark. The initial belief that MCTD1 represents a relatively benign condition with a good response to corticosteroid therapy was subsequently challenged by a number of observations. In fact, the lengthy follow-up of the originally described patients and long-term data on other cohorts of patients have shown that about one-third of MCTD patients have a favorable outcome, one-third have a good outcome but require continuous therapy with either corticosteroids or immunosuppressive drugs, and the remaining third have a more aggressive disease [5,7-10]. Recent studies have confirmed that polyarthritis, Raynaud’s phenomenon, puffy fingers and sclerodactyly are the most common presenting symptoms. However, long-term follow-up has shown that patients accrue new symptoms – such as esophageal hypomotility, nervous system manifestations, pulmonary arterial hypertension and interstitial lung disease. In many studies,