Overlapping syndromes, undifferentiated connective tissue disease, and other fibrosing conditions

Many patients presenting with symptoms suggestive of a connective tissue disease do not fulfill criteria for a specific connective tissue disease at initial presentation. Some of these patients with undifferentiated connective tissue disease eventually develop a specific connective tissue disease. Recently, a large cohort of 213 patients from different centers with undifferentiated connective tissue disease of early onset were enrolled in a prospective protocoled study. Baseline characteristics, including antinuclear antibody profiles, were reported. The aim of this study was to define predictors for the development of specific organ-system involvement and connective tissue diseases in early undifferentiated connective tissue disease. Many patients show overlapping features of two or more connective tissue diseases. The presence of autoantibodies to U1-ribonucleoproteins has been associated with a particular overlap syndrome, mixed connective tissue disease. Most anti-U1-ribonucleoprotein-positive patients with undifferentiated connective tissue disease at presentation appear to develop mixed connective tissue disease over the course of disease. Although levels of anti-U1-ribonucleoprotein do not seem to be related to disease activity, this association suggests a pathogenetic relationship between anti-U1-ribonucleoprotein and mixed connective tissue disease. Genetic studies have shown that patients with antibodies against the 70-kD component of U1-ribonucleoprotein share a common epitope within the groove of their DR molecules at antigen-binding region, pointing to a particular antigen involved in the induction of these antibodies that may be relevant in the etiopathogenesis of associated disease.