Scleroderma

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.