Minor Revision 3/1/2008
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Scleroderma (means "hard skin") is a rare connective tissue disorder characterized by abnormal thickening of the skin. It is generally considered to be an autoimmune disorder.
There are two major variants of the disease, as well as other less common forms. The more serious form is usually called "diffuse Scleroderma" and is characterized by rapid development of skin thickening beginning with the hands, and face and extending to the arms and trunk. People with diffuse Scleroderma are at greater risk for developing internal organ involvement early in the course of the disease.
The other major form is often called limited Scleroderma or CREST Syndrome. The name CREST is an acronym for its characteristic symptoms: calcinosis, Raynaud's phenomenon, esophageal involvement, sclerodactyly, and telangiectasia (these terms are discussed below). This form progresses more slowly and has a better prognosis.
Scleroderma can also occur in more localized forms without internal organ involvement. These variants are called Morphea and Linear Scleroderma. Scleroderma like symptoms can also appear in conjunction with other disorders such as Mixed Connective Tissue Disorder. These scleroderma-like conditions are discussed in more detail below.
In most cases, diagnosis can be made based on presenting symptoms in combination with a positive anti-nuclear antibody (ANA) test. Specific antibody tests can often be used to confirm or differentiate specific subsets of the disease.
The presence of anti-centromere (ACA) antibodies is very highly correlated with a diagnosis of CREST (limited Scleroderma). However, only about 57% of patients who are diagnosed with CREST by symptoms alone have detectable ACA antibodies. Similarly, the presence of anti-topoisomerase I (anti-SCL-70) antibodies is highly correlated with diffuse Scleroderma, while only about 40% of patients diagnosed with diffuse Scleroderma by symptoms alone have detectable anti-SCL-70 antibodies. It is very rare for an individual to have both antibodies.
Overall, only about 60% of patients diagnosed with Scleroderma have positive specific antibody tests. This means that the lack of specific antibodies does not rule out the diagnosis of Scleroderma. Measurement of these antibodies should be considered secondary to the clinical features when making a diagnosis of Scleroderma.
These findings also suggest that there are at least four different subsets of Scleroderma and possibly more: ACA positive CREST, ACA negative CREST, anti-SCL-70 positive diffuse Scleroderma, and anti-SCL-70 negative diffuse Scleroderma. This has significant implications when interpreting the results of research studies that do not distinguish between the specific subsets of the disease.
Morphea, or localized Scleroderma, usually begins between the ages of 20 to 50 years as patches of yellowish or ivory-colored rigid, dry skin. These are followed by the appearance of firm, hard, oval-shaped plaques with ivory centers that are encircled by a violet ring. These spots generally appear on the trunk, face, and/or extremities. Many patients with localized Morphea improve without treatment. Generalized Morphea is more rare and serious, and involves the skin but not the internal organs.
Linear Scleroderma appears as a band-like thickening of skin on the arms or legs. This type of Scleroderma is most likely to be on one side of the body but may be on both sides. Linear Scleroderma generally appears in young children and is characterized by the failure of one limb (i.e., arm or leg) to grow as rapidly as its counterpart.
Diffuse fasciitis with eosinophilia (DFE; also called eosinophilic fasciitis or Shulmanís syndrome) is a rare condition that mimics Scleroderma with swelling, stiffness, and decreased flexibility of the limbs associated with skin thickening. Although the symptoms can be widespread and involve the trunk and limbs, in contrast to Scleroderma, the fingers, hands, and face are usually not affected. In addition, there is no occurrence of Raynaudís or GI involvement.
Eosinophilia-myalgia syndrome (
Scleroderma-like skin changes have also been associated with insulin-dependent diabetes, carcinoid syndrome, myeloma, scleromyxedema, chronic graft-versus-host disease, porphyria cutanea tarda, Wernerís syndrome, progeria, phenylketonuria, bleomycin exposure, local lipodystrophies, and POEMS syndrome.
is a rare disorder that affects an estimated 40,000 to 165,000 people in the
Scleroderma may occur at any age, but the symptoms most frequently begin in mid-life. The diffuse and limited forms of Scleroderma are very rare in children. The disease is 3 to 4 times more common in women than men. There is some evidence that black women have a significantly greater risk than white women. In addition, diffuse Scleroderma appears to occur more frequently among black women and starts at an earlier age.
There seems to be a relatively weak genetic link with Scleroderma. Close order relatives of an affected individual are much more likely to have elevated ANA levels, but without any Scleroderma symptoms, than the normal population.
The exact cause of Scleroderma is unknown. There are a number of environmental factors that appear to be related to Scleroderma or Scleroderma-like illnesses, including exposure to silica dust, vinyl chloride, epoxy resins, and other organic solvents. Several studies have shown some evidence of geographic clustering, which is also consistent with possible environmental risk factors
A number of researchers have investigated the possible link between Scleroderma and silicone breast implants. To date, all of these studies have shown no causal link. While there are certainly many reported cases of Scleroderma and other auto-immune disorders among women who have had breast implants, this is the same population which is most likely to develop auto-immune disorders such as Scleroderma in any case, and the incidence of auto-immune disorders among these women is consistent with the expected incidence in this population.
A few studies have suggested that certain viruses may have a causal role in some cases of Scleroderma, but the data is limited.
Clinical Features - General
Scleroderma normally begins with Raynaud's phenomenon - the fingers and toes lose circulation and turn white upon exposure to cold. Raynaud's phenomenon usually (but not always) precedes skin changes by several months with diffuse Scleroderma and often precedes skin changes by several years with limited Scleroderma. Other early symptoms may be painful joints, morning stiffness, red swollen hands, fatigue, and/or weight loss. It is important to note, however, that Raynaudís phenomenon without any underlying disease is quite common in the general population, especially among women. This form of Raynaudís is called "primary Raynaudís". A key distinguishing characteristic is that with primary Raynaudís, the anti-nuclear antibody (ANA) level will normally be negative, while with Raynaudís which accompanies Scleroderma or other auto-immune disorders (secondary Raynaudís), ANA levels are normally positive.
The first specific clinical symptom to suggest a diagnosis of Scleroderma is skin thickening that begins as swelling or "puffiness" of the fingers and hands. Later the skin becomes hard, shiny, and leathery. With diffuse Scleroderma, these areas of hardness are widespread and typically appear on both sides of the body. In the more limited form, skin thickening is often restricted to the hands and face. Eventually, tissue loss occurs and the skin becomes more highly colored.
People with limited Scleroderma usually have Raynaudís symptoms for years (often 5 to 10 years) before other signs of Scleroderma are noted. However, even the limited form can, in rare cases, present with internal organ involvement without Raynaudís. Patients with limited Scleroderma are less likely to develop severe lung, heart, or kidney involvement than patients with diffuse disease, although all of these complications can occur late in the disease process. Most patients with limited Scleroderma eventually develop CREST symptoms. CREST is an acronym for calcinosis, Raynaud's phenomenon, esophageal dysfunction, sclerodactyly and telangiectasia. Calcinosis is the abnormal accumulation of calcium salts under the skin and in many other organs. It presents as small, localized, hard masses on fingers, forearms, or other pressure points. Raynaud's Phenomenon is characterized by the intermittent loss of blood to various parts of the body particularly the fingers, toes, nose, and/or ears after exposure to cold and causes tingling sensations, numbness, and/or pain. This can result in ulceration of the fingertips and in some severe cases, lead to amputation of the affected digits. Dysfunction of the lower esophagus results in chronic heartburn and possible esophageal scarring. If the heartburn symptoms are not well controlled, the repeated acid exposure can eventually lead to a condition know as Barrettís esophagus, a pre-cancerous condition. The esophagus may eventually have areas that are narrowed and swallowing may become difficult. The small intestine may also lose the ability to push food through to the large intestine leading to malabsorption and increased bacterial growth in the small intestine. Sclerodactyly, a condition in which the skin becomes thin, shiny, and bright, results in decreased function of the fingers and toes. Telangiectasia, the appearance of small blood vessels near the surface of the skin, usually on the face, hands, and in the mouth, is unsightly but not debilitating. Patients with CREST Syndrome are at increased risk of developing kidney failure and lung fibrosis leading to pulmonary hypertension, but these complications usually occur at a much later date than with diffuse Scleroderma.
With diffuse Scleroderma, there is usually a short interval (weeks or months) between the development of Raynaudís and significant additional symptoms. Relatively rapid skin changes often occur in the first few months of the disease and continue to progress over the next 2 to 3 years. This is often followed by a remission of the skin changes and the skin either thins or sometimes returns toward normal thickness. The severe fibrosis of the skin, especially in the fingers and hands, can cause significant disability. Diffuse Scleroderma can also include a wide range of potential complications including inflammation of the muscles, swelling of the fingers and/or hands, microvascular abnormalities, gastrointestinal malfunction, lung fibrosis leading to pulmonary hypertension, progressive kidney failure, and cardiovascular problems. Internal organ involvement often occurs early in diffuse Scleroderma and can be the initial presenting symptom.
Raynaudís phenomenon is characterized by cold hands and feet accompanied by color changes. Upon exposure to cold or emotional stress, the fingers and/or toes (sometimes the nose), lose circulation and turn white (blanch). Once the digits are re-warmed the blood flow returns, commonly 10 to 15 minutes later. The affected portion of the digits will often turn a bluish color or will appear mottled before returning to normal appearance.
Several studies have reported that between 4% and 15% of the general adult population, primarily women, have symptoms of Raynaudís phenomenon. These symptoms are usually quite mild and are not associated with any underlying disease. This form of Raynaudís is known as "primary Raynaudís". It is also associated with a negative ANA. It often first appears at a much younger age than secondary Raynaudís, often before the age of 20. When Raynaudís attacks are intense or long lasting or first occur after the age of 20, there is an increased likelihood that the Raynaudís is secondary to an underlying autoimmune disorder. Note that in addition to Scleroderma, Raynaudís can be associated with a number of other disorders, for example, lupus, mixed connective tissue disorder, polymyositis, dermatomyositis, cold aggultinin disease, hypothyroidism, etc.
With secondary Raynaudís there can also be enlargement of the blood vessels at the base of the fingernails, although this is not always the case.
In the earliest stages of Scleroderma, the skin appears mildly inflamed with swelling and often redness. The skin gradually thickens (more rapidly in the diffuse form) and the patient feels progressive "tightening" of the skin with decreased flexibility. The skin changes are more widespread in the diffuse form and the skin can become "hyperpigmented", giving the skin a salt and pepper appearance.
As the skin changes progress, the skin becomes thicker and the skin can become severely dried with intense itching. This stage can progress for a long period, up to several years. Finally, the inflammation and further thickening stops as the skin begins to thin, although the skin will usually bind with underlying structures. Painful ulcerations can occur at joints.
With the limited form of the disease (CREST), calcium deposits may form under the skin. These can appear as white spots or ulcerations and may be quite painful. Spider veins (telangiectasia) often appear on the fingers, chest, face, lips, and tongue.
Musculoskeletal (Muscles and Joints)
Nonspecific muscle pain and stiffness are often some of the earliest symptoms of Scleroderma. While arthritis can also occur, the pain and stiffness over the joints is greater than would normally be expected based on the degree of inflammation visible. Pain can also occur along tendons and into muscles of the arms and legs. This can occur with movement of the ankles, wrists, knees, or elbows. These symptoms are more common in the diffuse form of the disease.
Often, a grating sound can be heard as the inflamed tissues move over each other, particularly at and below the knees. With diffuse Scleroderma, the fingers, wrists, and elbows can become fixed in flexed positions because of the scarring of the skin. In the limited form, this is usually limited to the fingers.
In later stages of the disease, muscle loss and weakness is the main problem. In some cases, however, some of the symptoms may be caused by some of the drugs commonly used to treat Scleroderma, for example, D-penicillamine or steroids.
Some reduction of lung functioning occurs in almost all cases of Scleroderma, both in the limited and diffuse forms. However, unless closely monitored, there can be no symptoms until later stages of the disease, at which point lung problems can become a major cause of death. The most common initial symptom is shortness of breath after exercise or other exertion. Later, a persistent non-productive cough can develop. Usually, there is no chest pain caused by the lung involvement, although chest pain can occur from other causes such as muscle pain or heartburn.
The first detectable symptom is usually impaired gas exchange, caused by progressive fibrosis of the lungs. With the diffuse form, lung fibrosis is the more common serious problem to develop, while with the limited form, isolated pulmonary hypertension is more common, although both conditions often co-exist with either form.
Pulmonary disease is best detected by a pulmonary function test (PFT) or by computerized axial tomography (CAT scan). Chest x-rays are usually normal during the early stages of lung involvement. In addition to reduced gas exchange, low lung volumes are also often detected upon testing. The most serious complications of lung disease are seen with pulmonary hypertension or a low gas exchange (less than 40% of normal).
While the course of lung involvement is highly variable, most patients have an early but limited decline in lung functioning and then either stabilize or improve. About one third of patients have a more severe progression for several years before stabilizing. While other lung problems can develop secondary to other complications, these are much less common. In addition, there is an increased risk of lung cancer with Scleroderma.
Some of the most common symptoms of Scleroderma are various difficulties with the gastrointestinal tract. This occurs with both forms of the disease. Difficulty swallowing along with moderate to severe heartburn is common. If untreated or undertreated, this can lead to erosion of the esophagus resulting in bleeding, strictures with narrowing of the esophageal opening, and Barrettís esophagus, a pre-cancerous condition. In addition to direct problems of the esophagus itself, delayed stomach emptying can aggravate heartburn as well as cause bloating, nausea, and vomiting.
Skin thickening on the face can lead to a small mouth opening, mouth dryness, and dental problems. This in turn can result in difficulties in chewing food, loss of teeth, and poor nutrition.
Gradual loss of small intestine functioning may initially occur with any symptoms, but it can also lead to partial obstruction of the intestines, resulting in abdominal pain and vomiting. The decrease in small bowel absorption can lead to cramping, diarrhea, weight loss, and in severe cases malnutrition.
Cardiac involvement in Scleroderma can be quite variable, usually without many overt symptoms early in the disease process. In fact, overt clinical symptoms early in the course of the disease are a poor prognostic indication. Cardiac involvement tends to be more serious and more common in the diffuse form of Scleroderma. Abnormal findings, including irregular heart beats and conduction problems, are often present without any associated clinical symptoms, at least early in the course of the disease.
Kidney involvement is common in Scleroderma although there may no obvious clinical problems. Kidney problems tend to be more serious and more common in the diffuse form of the disease, although sudden increases in blood pressure which (if untreated) can result in kidney failure can occur early in the course of limited Scleroderma in a small percentage of cases. Approximately 80% of all major kidney problems occur within the first 4 to 5 years of the disease. For unknown reasons, serious kidney problems are more common in men and with patients with an older age of disease onset.
Recent studies have shown that about 50% of all Scleroderma patients develop moderate to major depression. However, in almost all cases the depression is responsive to treatment with medications commonly used to treat depression.
A significant number of Scleroderma patients also suffer from SjŲgrenís syndrome. The primary symptoms are dry mouth and eyes. This can result in dental complications and the need to use lubricating eye drops to prevent eye problems.
Hypothyroidism (reduced function of the thyroid) has been reported because of either fibrosis of the thyroid or thyroid auto-immune disorder. Hypothyroidism causes many bodily functions to slow down. Some of the more common symptoms include: hoarse voice, slowed speech, eye and face puffiness, weight gain, cold intolerance, coarse, dry, sparse hair, dry skin and carpal tunnel syndrome.
Other symptoms that have been linked to Scleroderma include: severe chronic chilling even in the absence of hypothyroidism ,trigeminal neuralgia (sudden painful spasms in the lower portion of he face), sexual dysfunction (mostly male impotence), and liver damage.
While there is no definitive treatment for Scleroderma, specific treatments can often relieve symptoms and improve functioning. Scleroderma patients should be under the care of a rheumatologist and may need the attention of other specialists to deal with specific symptoms. It is important to monitor blood pressure, blood counts, urinalysis, kidney, and lung function on a regular basis.
Raynaud's phenomenon is very common with Scleroderma. Prevention is very important - patients should dress warmly and limit outdoor activities in cold weather. If it is possible, it may make sense for patients in cold climates to move to a warmer climate! A number of medications can be prescribed to reduce Raynaud's symptoms, including calcium channel blockers such as nifedipine (Procardia). However, calcium channel blockers can reduce lower esophageal sphincter pressure and make heartburn symptoms worse. Ketanserin has also been shown to be effective. Some patients can be taught to control the temperature of their hands using biofeedback.
Intravenous Iloprost has been shown to be effective in treating Raynaudís. However, this form of administration is not practical for general usage. Unfortunately, experimental results with an oral form of Iloprost have had mixed results.
Many medications have been tried for reducing the skin thickening and delaying internal organ involvement. D-penicillamine appears to have some limited effectiveness in improving skin thickening, as well as improved 5-year survival rates. However, D-penicillamine can be quite toxic and patients receiving this treatment must be closely monitored. Steroids, for example, Prednisone, do not appear to effective in Scleroderma and are usually used only if arthritic symptoms develop.
Dryness of the skin may be reduced by frequent use of lubricating creams. Regular exercise can help to maintain flexibility of joints and pliability of skin. Fingertip ulcerations are often treated with local nitroglycerine paste or topical antibiotics; however, systemic antibiotics may be needed in some cases.
Musculoskeletal (Muscles and Joints)
Joint and tendon related pain is usually helped by nonsteroidal anti-inflammatory drugs (NSAIDS), but relief is usually more difficult to achieve than in other auto-immune disorders. In some cases, low-dose corticosteroids such as prednisone may be necessary to control musculoskeletal pain. Physical therapy with emphasis on range of motion and stretching is very important to retain as much joint movement as possible.
Most patients with lung involvement have a mild, nonprogressive course that does not require treatment. When it occurs, lung fibrosis leasing to pulmonary hypertension is one of the major complications of Scleroderma. No medicines have proven effective in managing advanced lung fibrosis, although some success has been reported with the use of corticosteriods and cyclophosphamide. Pulmonary infections require prompt treatment with antibiotics. Supplemental oxygen may also be needed. With advanced lung fibrosis or pulmonary hypertension, the only option may be a single or double lung transplant, sometimes including a heart transplant if heart problems are severe.
Chronic heartburn (reflux) is a common problem with Scleroderma. This can often be reduced by preventive measures such as elevation of the head of the bed, eating smaller meals more frequently, taking antacids, and avoiding eating late at night. Some foods such as alcohol, regular coffee or tea can increase heartburn and should be avoided. Foods such as chocolate or fats can reduce the pressure of the lower esophageal sphincter and should be avoided at night. If stronger measures are required, treatments of choice are drugs known as H2 blockers such as Tagamet or Pepcid. These work by reducing stomach acidity. Prilosec (omeprazole), which is significantly more effective at reducing stomach acidity may also be used. Drugs that increase the speed that the stomach empties, for example, Propulsid (cisapride) have also been shown to be beneficial. Surgical interventions may also be indicated in some cases to increase the pressure of the lower esophageal sphincter. This option has recently become more feasible because of new laparoscopic techniques that significantly reduce recovery time and reduce the risks associated with open surgery.
Bloating, diarrhea, weight loss, and malabsorption symptoms caused by bacterial overgrowth in the small intestine are usually successfully treated with broad-spectrum antibiotics such as ampicillin, tetracycline, Bactrim, metronidazole, or ciprofloxacin. The use of cisapride to increase the speed of food passage through the GI system can also be helpful.
When abnormalities of the heart occur as a result of Scleroderma, the drugs nifedipine and dipyridamole may be administered. Nonsteroidal anti-inflammatory or corticosteroid drugs are typically used to treat the symptoms relating to the inflammation of the membranes of the heart (pericarditis). Generally, heart complications with Scleroderma patients are treated the same as for non-Scleroderma patients.
Since kidney failure can be life threatening, close monitoring of kidney function is necessary. Reduction in kidney function is often accompanied by high blood pressure. Current drugs of choice to treat kidney disease associated with Scleroderma are ACE inhibitors such as Captopril or enalapril. Other drugs to reduce blood pressure have also been used with some success. Sudden onset of high blood pressure and kidney failure is called 'Scleroderma renal crisis'. This occurs in about 20% of people with diffuse Scleroderma and can also occur with CREST. It can result in kidney failure within days to weeks. Anyone with diffuse Scleroderma should be measuring his/her own blood pressure at home every day or two. If it is elevated over a certain point (to be determined by your physician since it must be individualized) you should call your physician immediately. CREST patients should measure their blood pressure at least once a month.
Some Scleroderma patients suffer from excessive dryness of the mouth and eyes (Sjogren's Syndrome). Lubricating drops and ointments as well as artificial saliva products can relieve these symptoms. Good oral hygiene is important because gum disease is common in Scleroderma.
Scleroderma related depression seems to respond well to standard medical treatments using medications such as Prozac, Wellbutrin, Serzone, or Paxil.
Hypothyroidism is readily treated using by replacing the deficient thyroid hormone, using one of several oral medications. The preferred form is synthetic thyroid hormone, T4.
A Note About Scleroderma Research
It is very difficult to do research on treatments for Scleroderma, as is the case with most rare disorders. The small number of patients means that it is difficult to locate enough patients in a single geographical area to do appropriate, well controlled research. This usually means that multi-center research is required, which is costly and difficult to coordinate.
An additional complication for doing Scleroderma research is the fact that Scleroderma appears to be a general term for a cluster of related diseases, as noted above. It is quite possible that some treatments may be effective for some forms of Scleroderma, but ineffective or less effective in other forms. And, since each subset of Scleroderma affects an even smaller population than the total Scleroderma patient population, research on subsets is even harder to do. Historically, most Scleroderma research performed over the past 20 years has not been done on specific disease subsets, but usually on a heterogeneous population which includes diffuse and limited Scleroderma patients, some of which are specific antibody positive while others are antibody negative. By mixing the patient population, results may appear to be negative overall, yet still might be positive for a subset of the patients. For example, since CREST (limited Scleroderma) generally progresses much more slowly than the diffuse form of the disease, it is quite conceivable that certain treatments which show limited results for diffuse patients may be more effective for CREST patients. Also, the slower progression means that it may take much longer to show positive results for experimental therapies than might be the case for the more rapidly progressing diffuse form. Unfortunately, little research has been done that takes this into consideration.
When considering investigational or alternative therapies, it is important to keep these limitations in mind. Since there are no generally accepted systemic treatments for Scleroderma (although specific treatments for various symptoms may be quite effective), some physicians may decide to try alternative or experimental treatment approaches on an individual basis even though there is no clear research support for these treatments. When positive results follow such treatments, it is very easy to believe that these treatments caused the improvements. In some cases this may be the case, however, it is important to realize that it is difficult to establish a cause an effect relationship between a treatment and a result with a single patient. In some cases it may be desirable to withdraw an experimental treatment from a patient to see if improved symptoms worsen. If this occurs and the symptoms again improve when the treatment is resumed, this makes it much more likely that the treatment may be causing the improvement. Nevertheless, without well controlled, double blind research, cause and effect cannot be clearly established.
A number of experimental treatments are currently being evaluated for use in treating people with Scleroderma. More information about many of these experimental programs can be found by contacting the National Organization for Rare Disorders (NORD) (see Resource list below).
A number of alternative treatments are also being used for treating Scleroderma. The effectiveness of these alternative approaches is based mostly on anecdotal reports, although research is underway for some of these alternative treatments.
For more information on Scleroderma, please contact:
The information in this F.A.Q has been obtained from a variety of sources, including:
3/1/08: Updated link to Road Back Foundation
© Copyright 1998-2008 Edward S. Harris All Rights Reserved
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