Chronic disease that hardens the skin and fixes it to underlying structures. Swelling and collagen buildup lead to loss of elasticity. The cause is unknown. It usually begins at age 25–55, more often in women, with severe inflammation of underlying tissue and stiffness, pain, and skin tautness and thickening. Systemic problems that may arise years later include fever, trouble in breathing, fibrous tissue in the lungs, inflammation of heart muscle or membranes, gastrointestinal disorders, and kidney malfunction. Calcium deposits build up under the skin. The disease may finally stabilize or gradually regress. Steroids may help, and physical medicine and rehabilitation with heat, massage, and passive exercise (movement of the limbs by the therapist) help prevent limb fixation and deformity.
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Scleroderma is a chronic autoimmune disease characterized by a hardening or sclerosis in the skin or other organs. The localized type of the disease, forms of which also known as "morphea", while disabling, tends not to be fatal. The systemic type or systemic sclerosis, the generalized type of the disease, can be fatal as a result of heart, kidney, lung or intestinal damage.
Diffuse scleroderma can affect any part of the gastrointestinal tract. The most common manifestation in the esophagus is reflux esophagitis, which may be complicated by peptic stricturing, or benign narrowing of the esophagus. This is best initially treated with proton pump inhibitors for acid suppression, but may require bougie dilatation in the case of stricture.
Scleroderma can decrease motility anywhere in the gastrointestinal tract. The most common source of decreased motility involvement is the esophagus and the lower esophageal sphincter, leading to dysphagia and chest pain. As Scleroderma progresses, esophageal involvement from abnormalities in decreased motility may worsen due to progressive fibrosis (scarring). If this is left untreated, acid from the stomach can back up into the esophagus causing esophagitis, and GERD. 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 dilitation, and Barrett's esophagus. The small intestine can also become involved, leading to bacterial overgrowth and malabsorption, of bile salts, fats, carbohydrates, proteins, and vitamins. The colon can be involved, and can cause pseudo-obstruction or ischemic colitis.
Rarer complications include pneumatosis cystoides intestinalis, or gas pockets in the bowel wall, wide mouthed diverticula in the colon and esophagus, and liver fibrosis. Patients with severe gastrointestinal involvement can become profoundly malnourished.
Scleroderma may also be associated with gastric antral vascular ectasia (GAVE), also known as watermelon stomach. This is a condition where atypical blood vessels proliferate usually in a radially symmetric pattern around the pylorus of the stomach. GAVE can be a cause of upper gastrointestinal bleeding or iron deficiency anemia in patients with scleroderma.Kidneys Renal involvement, in scleroderma, is considered a poor prognostic factor and frequently a cause of death.
The most important clinical complication of scleroderma involving the kidney is scleroderma renal crisis. Symptoms of scleroderma renal crisis are malignant hypertension (high blood pressure with evidence of acute organ damage), hyperreninemia (high renin levels), azotemia (kidney failure with accumulation of waste products in the blood) and microangiopathic hemolytic anemia (destruction of red blood cells). Apart from the high blood pressure, hematuria (blood in the urine) and proteinuria (protein loss in the urine) may be indicative.
In the past scleroderma renal crisis was almost uniformily fatal. While outcomes have improved significantly with the use of ACE inhibitors the prognosis is often guarded, as a significant number of patients are refractory to treatment and develop renal failure. Approximately 5-10% of all scleroderma patients develop renal crisis at some point in the course of their disease. Patients that have rapid skin involvement have the highest risk of renal complications. It is most common in diffuse cutaneous scleroderma, and is often associated with antibodies against RNA polymerase (in 59% of cases). Many proceed to dialysis, although this can be stopped within three years in about a third of cases. Higher age and (paradoxically) a lower blood pressure at presentation make it more likely that dialysis is needed.
Treatments for scleroderma renal crisis include ACE inhibitors, which are also used for prophylaxis, and renal transplantation. Transplanted kidneys are known to be affected by scleroderma and patients with early onset renal disease (within one year of the scleroderma diagnosis) are thought to have the highest risk for recurrence.
In typical cases of limited scleroderma, Raynaud's phenomenon may precede scleroderma by several years. Raynaud's phenomenon is due to vasoconstriction of the small arteries of exposed peripheries - particularly the hands and feet - in the cold. It is classically characterised by a triphasic colour change - first white, then blue and finally red on rewarming. The scleroderma may be limited to the fingers - known as sclerodactyly.
The limited form is often referred to as CREST syndrome. "CREST" is an acronym for the five main features:
CREST is a limited form associated with antibodies against centromeres and usually spares the lungs and kidneys.
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.
A distinct form of scleroderma and systemic sclerosis may develop in patients with chronic renal failure. This entity, nephrogenic fibrosing dermopathy or nephrogenic systemic fibrosis, has been linked to the exposure to gadolinium-containing radiocontrast.
A significant player in the process is transforming growth factor (TGFβ). This protein appears to be overproduced, and the fibroblast (possibly in response to other stimuli) also overexpresses the receptor for this mediator. An intracellular pathway (consisting of SMAD2/SMAD3, SMAD4 and the inhibitor SMAD7) is responsible for the secondary messenger system that induces transcription of the proteins and enzymes responsible for collagen deposition. Sp1 is a transcription factor most closely studied in this context. Apart from TGFβ, connective tissue growth factor (CTGF) has a possible role. Indeed, a common CTGF gene polymorphism is present at an increased rate 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 have similarly been implicated. Increased endothelin and decreased vasodilation has been documented.
Jimenez & Derk describe three theories about the development of scleroderma:
While still experimental (given its high rate of complications), hematopoietic stem cell transplantation is being studied in patients with severe systemic sclerosis; improvement in life expectancy and severity of skin changes has been noted.
Scleroderma affects approximately 300,000 people in the United States. It is four times as common in women than in men. Incidence rates are estimated at 2-20 per million per year in the United States.
Juvenile scleroderma affects approximately 7000 children in the United States. The most common form of juvenile scleroderma is localized scleroderma, morphea and/or linear.
In the US, the Scleroderma Research Foundation is dedicated to raise awareness of the disease and assist those who are affected. The Scleroderma Research Foundation sponsors research into the condition. 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.