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Scleroderma is a chronic systemic autoimmune disease (primarily of the skin -"derma") characterized by fibrosis (or hardening -"sclero"), vascular alterations, and autoantibodies. There are two major forms:

Limited systemic sclerosis/scleroderma involves cutaneous manifestations that mainly affect the hands, arms, and face. It was previously called CREST syndrome in reference to the following complications: Calcinosis, Raynaud's phenomenon,Esophageal dysfunction, Sclerodactyly, and Telangiectasias. Additionally, pulmonary arterial hypertension may occur in up to one-third of patients and is the most serious complication for this form of scleroderma.

Diffuse systemic sclerosis/scleroderma is rapidly progressing and affects a large area of the skin and one or more internal organs, frequently the kidneys, esophagus, heart, and lungs. This form of scleroderma can be quite disabling. There are no treatments for scleroderma itself, but individual organ system complications are treated.

Other forms of scleroderma include systemic sine scleroderma (which lacks skin changes but has systemic manifestations) and two localized forms, morphea and linear scleroderma, which affect the skin but not the internal organs.

The prognosis is generally good for limited cutaneous scleroderma patients who escape pulmonary complications, but is worse for those with the diffuse cutaneous disease, particularly in older age, and for males. Death occurs most often from pulmonary, heart, and kidney complications. In diffuse cutaneous disease, five-year survival is 70%, and 10-year survival is 55%.

The cause is unknown. Scleroderma runs in families but the genes have not been identified. It affects the small blood vessels (arterioles) in all organs. First, the endothelial cells of the arteriole die off, along with smooth muscle cells, by a process of apoptosis. They are replaced by collagen and other fibrous material. Inflammatory cells, particularly CD4+ helper T cells, infiltrate the arteriole, and cause further damage. Many of the inflammatory and destructive protein signals have been identified and they are potential targets for drugs that could interrupt the process.

Typical scleroderma is classically defined as symmetrical skin thickening, with about 90% of cases also presenting with Raynaud's phenomenon, nail-fold capillary changes, and antinuclear antibodies. Patients may or may not experience systemic organ involvement. Atypical scleroderma may show any variation of these changes without skin changes or with finger swelling only. Additional symptoms of scleroderma typically present themselves within two years of Raynaud's phenomenon.

Laboratory testing can show antitopoisomerase antibodies, like anti-scl70 (causing a diffuse systemic form), or anticentromere antibodies (causing a limited systemic form, and the CREST syndrome). Other autoantibodies can be seen, such as anti-U3 or anti-RNA polymerase.

Severe complications from scleroderma include:

  • Heart: Untreated high blood pressure strains the heart; irregular heart rhythm and enlargement of the heart lead to heart failure.
  • Kidney: Scleroderma renal crisis in which malignant hypertension develops and causes acute renal failure was once a common cause of death, but is now treatable with ACE inhibitors.
  • Lung: Two-thirds of all patients suffer from respiratory problems, such as shortness of breath, coughing, difficulty breathing, alveolitis (inflammation of lung air sacs), pneumonia, and cancer.
  • Digestive: Esophagus damage can make it difficult to swallow food, and acid reflux is common. The stomach can develop gastric antral vascular ectasia (GAVE), which occasionally may bleed profusely. A sluggish intestine may cause pain and bloating; undigested food can result in diarrhea, flatulence, weight loss, and anemia.
  • Skin and joints: Carpal tunnel syndrome is common, as are muscle weakness, joint pain, and stiffness.
  • Mouth: Flat white patches, loss of attached gingival mucosa, gingival recession, and diffuse widening of the periodontal ligament (PDL) space are seen. Dysphagia may result from collagen deposition in the lingual and esophageal submucosa. Resorption of the posterior ramus of themandible, the coronoid process, and the condyle are seen due to pressure from abnormal collagen production in adjacent areas. Inelasticity of the mouth may make dentures or dental prostheses difficult to insert and remove.


There is no direct cure for scleroderma. Because the exact cause is unknown, any treatment is patient-specific and aimed at ameliorating symptoms of the disease. For example, patients who experience Raynaud's phenomenon may be treated with agents to increase blood flow to the fingers, including nifedipine, amlodipine, diltiazem, felodipine, or nicardipine.

Fibrosis of the skin has been treated with varying degrees of success with agents such as D-penicillamine, colchicine, PUVA, relaxin, cyclosporine, and EPA (omega-3 oil derivative).

Because scleroderma is an autoimmune disease, one of the major pillars of treatment involves the use of immunosuppressive agents. These drugs include methotrexate, cyclophosphamide, azathioprine, and mycophenolate.

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