Apart from TGFβ, connective tissue growth factor (CTGF) has a possible role. Indeed, a common CTGF gene polymorphism is present at an increased level in systemic sclerosis.Damage to endothelium is an early abnormality in the development of scleroderma, and this, too, seems to be due to collagen accumulation by fibroblasts, although direct alterations by cytokines, platelet adhesion, and a type II hypersensitivity reaction  similarly have been implicated. Increased endothelin and decreased vasodilation have been documented.Jimenez and Derk describe three theories about the development of scleroderma:

The abnormalities are primarily due to a physical agent, and all other changes are secondary or reactive to this direct insult. The initial event is fetomaternal cell transfer causing microchimerism, with a second summative cause (e.g. environmental) leading to the actual development of the disease. Physical causes lead to phenotypic alterations in susceptible cells (e.g. due to genetic makeup), which then effectuate DNA changes that alter the cells behavior. Diagnosis
In 1980, the American College of Rheumatology agreed on diagnostic criteria for scleroderma.Diagnosis is by clinical suspicion, presence of autoantibodies (specifically anticentromere and anti-scl70/antitopoisomerase antibodies), and occasionally by biopsy. Of the antibodies, 90% have a detectable antinuclear antibody. Anticentromere antibody is more common in the limited form (80–90%) than in the diffuse form (10%), and anti-scl70 is more common in the diffuse form (30–40%) and in African-American patients (who are more susceptible to the systemic form).Other conditions may mimic systemic sclerosis by causing hardening of the skin.
Systemic scleroderma, or systemic sclerosis, is an autoimmune rheumatic disease characterised by excessive production and accumulation of collagen, called fibrosis, in the skin and internal organs  and by injuries to small arteries. There are two major subgroups of  systemic sclerosis based on the extent of skin involvement: limited and diffuse. The limited form affects areas below, but not above, the elbows and knees with or without involvement of the face. The diffuse form also affects the skin above the elbows and knees and can also spread to the torso. Visceral organs, including the kidneys, heart, lungs, and gastrointestinal tract can also be affected by the fibrotic process. Prognosis is determined by the form of the disease and the extent of visceral involvement. Patients with limited systemic sclerosis have a better prognosis than those with the diffuse form. Death is most often caused by lung, heart, and kidney involvement. The risk of cancer is increased slightly.Survival rates have greatly increased with effective treatment for kidney failure. Therapies include immunosuppressive drugs, and in some cases, glucocorticoids. Signs and symptoms
Calcinosis, Raynauds phenomenon, Esophageal dysfunction, Sclerodactyly, and Telangiectasia (CREST syndrome) are associated with limited scleroderma. Other symptoms include:

Skin symptoms
In the skin, systemic sclerosis causes hardening and scarring. The skin may appear tight, reddish, or scaly. Blood vessels may also be more visible. Where large areas are affected, fat and muscle wastage may weaken limbs and affect appearance. Patients report severe and recurrent itching of large skin areas.