Following the molecular pathways toward an understanding of the pathogenesis of systemic sclerosis.

Systemic sclerosis is a disease of unknown origin characterized by excessive deposition of collagen and other connective tissue macromolecules in skin and multiple internal organs, prominent and often severe alterations in the microvasculature, and humoral and cellular immunologic abnormalities (see Glossary). Systemic sclerosis is a complex and heterogeneous disease. Clinical forms range from limited skin involvement with minimal systemic alterations (limited cutaneous systemic sclerosis) to forms with diffuse skin sclerosis and severe internal organ disease (diffuse cutaneous systemic sclerosis) (1), and occasionally a fulminant course (fulminant systemic sclerosis) (2). The most apparent and almost universal clinical features of systemic sclerosis are related to the progressive