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

Mixed connective disease is the prototype of an overlapping connective tissue disease. Based on the presence of a specific autoantibody directed against U1-snRNP (U1 small ribonucleoprotein), the syndrome has been considered a distinct disease entity. Patients with anti-U1-snRNP antibodies, however, do not present with a homogeneous clinical syndrome, and the majority develop a classified connective tissue disease within 5 years of presentation. Signs of scleroderma predominate in most patients. The immune response resulting in anti-U1-snRNP seems antigen driven and may result from molecular mimicry between U1-snRNP and certain viral proteins. Fibrotic conditions related to extrinsic factors have been described as human adjuvant disease. Case reports suggest that Swanson silastic joint prostheses can induce granulomatous reactions at a distance from the joints due to leaking of silicone from the implants. Much attention recently has been given to the possible induction of scleroderma-like syndromes in relation to silicone gel breast implants. However, the presently available data do not show convincing evidence that women with silicone gel breast implants are significantly at risk for developing a connective tissue disease.