Systemic sclerosis (SSc), also called scleroderma, is a multisystem connective tissue disease characterized by the excessive production of collagen, glycosaminoglycans and fibrinonectins within connective tissue. This results in the hardening and fibrosis of skin, mucus membranes, vasculature and internal organs. Clinical features include tightening and thickening of skin (skin sclerosis), Raynaud's phenomenon and involvement of various internal organs (particularly in the lungs). There are two major SSc phenotypes, limited cutaneous and diffuse cutaneous form, based on the extension of skin involvement. Prevalence of scleroderma ranges from 4 – 489 cases per million worldwide, with an annual incidence of 0.6 – 122 million. Greater prevalence is seen in the US and Australia than in Europe and Japan. The ratio of women to men affected is 3:1 and it has a peak incidence in the fifth decade of life.