There are two major subgroups of systemic sclerosis based on the extent of skin involvement: limited and diffuse.

Visceral organs, including the kidneys, heart, lungs, and gastrointestinal tract can also be affected by the fibrotic process.

[2] Calcinosis, Raynaud's phenomenon, Esophageal dysfunction, Sclerodactyly, and Telangiectasia (CREST syndrome) are associated with limited scleroderma.

Most patients (over 80%) have vascular symptoms and Raynaud's phenomenon, which leads to attacks of discoloration of the hands and feet in response to cold.

Calcinosis (deposition of calcium in lumps under the skin) is also common in systemic scleroderma, and is often seen near the elbows, knees, or other joints.

[11] This is best initially treated with proton pump inhibitors for acid suppression,[12] but may require bougie dilatation in the case of stricture.

[10] The most common source of decreased motility is the esophagus and the lower esophageal sphincter, leading to dysphagia and chest pain.

If this is left untreated, acid from the stomach can back up into the esophagus, causing esophagitis and gastroesophageal reflux disease.

Further scarring from acid damage to the lower esophagus many times leads to the development of fibrotic narrowing, also known as strictures, which can be treated by dilatation[citation needed].

In patients with neuromuscular disorders, particularly progressive systemic sclerosis and visceral myopathy, the duodenum is frequently involved.

[citation needed] The small intestine can also become involved, leading to bacterial overgrowth and malabsorption of bile salts, fats, carbohydrates, proteins, and vitamins.

[5] Rarer complications include pneumatosis cystoides intestinalis, or gas pockets in the bowel wall, wide-mouthed diverticula in the colon and esophagus, and liver fibrosis.

Prophylactic use of ACE inhibitors is currently not recommended, as recent data suggest a poorer prognosis in patient treated with these drugs prior to the development of renal crisis.

[27] One of the suspected mechanisms behind the autoimmune phenomenon is the existence of microchimerism, i.e. fetal cells circulating in maternal blood, triggering an immune reaction to what is perceived as foreign material.

[27][28] A distinct form of scleroderma and systemic sclerosis may develop in patients with chronic kidney failure.

[33] Bleomycin[34] (a chemotherapeutic agent) and possibly taxane chemotherapy[35] may cause scleroderma, and occupational exposure to solvents has been linked to an increased risk of systemic sclerosis.

[36] Overproduction of collagen is thought to result from an autoimmune dysfunction, in which the immune system starts to attack the kinetochore of the chromosomes.

Stimulation of the fibroblast, in particular, seems to be crucial to the disease process, and studies have converged on the potential factors that produce this effect.

[37] 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.

[39] No cure for scleroderma is known, though treatments exist for some of the symptoms, including drugs that soften the skin and reduce inflammation.

[citation needed] Episodes of Raynaud's phenomenon sometimes respond to nifedipine or other calcium channel blockers; severe digital ulceration may respond to prostacyclin analogue iloprost, and the dual endothelin-receptor antagonist bosentan may be beneficial for Raynaud's phenomenon.

Scleroderma renal crisis (SRC) is a life-threatening complication of systemic sclerosis that may be the initial manifestation of the disease.

[citation needed] The mainstay of therapy for SRC includes ACE inhibitors, which reduce RAAS activity and improve renal function and blood pressure.

[42] Nintedanib was approved for use in the United States Food and Drug Administration on September 6, 2019, to slow the rate of decline in pulmonary function in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD).

[45][46] Some evidence indicates that plasmapheresis (therapeutic plasma exchange) can be used to treat the systemic form of scleroderma.

This is done by replacing blood plasma with a fluid consisting of albumin, and is thought to keep the disease at bay by reducing the circulation of scleroderma autoantibodies.

[53] Comedian and television presenter Bob Saget, a board member of the SRF, directed the 1996 ABC TV movie For Hope, starring Dana Delany, which depicts a young woman fatally affected by scleroderma; the film was based on the experiences of Saget's sister Gay.

Diffuse systemic sclerosis, internal organ complications, and older age at diagnosis are associated with worse prognoses.

These include antithymocyte globulin and mycophenolate mofetil; some reports have shown improvements in the skin symptoms, as well as delaying the progress of systemic disease, but neither has been subjected to large clinical trials.