Scleroderma

  • Medical Author:
    William C. Shiel Jr., MD, FACP, FACR

    Dr. Shiel received a Bachelor of Science degree with honors from the University of Notre Dame. There he was involved in research in radiation biology and received the Huisking Scholarship. After graduating from St. Louis University School of Medicine, he completed his Internal Medicine residency and Rheumatology fellowship at the University of California, Irvine. He is board-certified in Internal Medicine and Rheumatology.

  • Medical Editor: Charles Patrick Davis, MD, PhD
    Charles Patrick Davis, MD, PhD

    Charles Patrick Davis, MD, PhD

    Dr. Charles "Pat" Davis, MD, PhD, is a board certified Emergency Medicine doctor who currently practices as a consultant and staff member for hospitals. He has a PhD in Microbiology (UT at Austin), and the MD (Univ. Texas Medical Branch, Galveston). He is a Clinical Professor (retired) in the Division of Emergency Medicine, UT Health Science Center at San Antonio, and has been the Chief of Emergency Medicine at UT Medical Branch and at UTHSCSA with over 250 publications.

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Scleroderma facts

  • Scleroderma is a disease of the connective tissue featuring thickened skin that can involve scarring, blood vessel problems, varying degrees of inflammation and pain, and is associated with an overactive immune system.
  • CREST syndrome is a limited form of scleroderma.
  • Patients with scleroderma can have specific antibodies (ANA, anticentromere, or antitopoisomerase) in their blood that suggest autoimmunity.
  • Treatment of scleroderma is primarily directed toward the particular individual's symptoms.

What is scleroderma?

Scleroderma is an autoimmune condition of the connective tissue characterized by skin thickening, spontaneous scarring, blood vessel disease, and varying degrees of inflammation, associated with an overactive immune system. Autoimmune diseases are illnesses that occur when the body's tissues are attacked by its own immune system. Scleroderma is characterized by the formation of scar tissue (fibrosis) in the skin. This leads to thickness and firmness of involved skin. This may also occur in internal organs such as the kidney.

Scleroderma is classified as localized or widespread (systemic scleroderma with a tendency to affect internal organs). Systemic scleroderma is further divided into limited and diffuse based upon the extent of skin involvement.

What causes scleroderma?

The cause of scleroderma is not known. Researchers have found some evidence that certain genes are important hereditary factors, but the environment seems to also play a role. The result is activation of the immune system in a susceptible individual, causing damage to the inner lining of tiny blood vessels and injury to tissues that result in scar tissue formation and the accumulation of excess collagen.

The fact that genes seem to cause a predisposition to developing scleroderma means that inheritance at least plays a partial role. It is not unusual to find other autoimmune diseases in families of scleroderma patients. Some evidence for the role genes may play in leading to the development of scleroderma comes from the study of Choctaw Native Americans who are the group with the highest reported prevalence of the disease. The condition is more frequent in females than in males.

Scleroderma Elbow Tip Pain

A common area of involvement of this condition is the skin over the tips of the elbows (the olecranon area). When this skin is involved, it can lead to troublesome irritation of the tips of the elbows with tenderness noted when any pressure is applied.

What are risk factors for developing scleroderma?

Because of the known association of certain genes with scleroderma, it may be that combinations of exposures to environmental factors and possibly certain viruses may trigger the development of scleroderma in genetically susceptible people. The precise interplay of pathology leading to blood vessel damage, scar and collagen accumulation, and autoimmunity is unclear.

How is scleroderma classified?

Scleroderma can be classified in terms of the degree and location of the skin and organ involvement. Accordingly, scleroderma has been categorized into two major groups, localized scleroderma and systemic sclerosis. Systemic sclerosis is further subdivided into either diffuse or limited forms based on the location and extent of skin involvement.

Localized scleroderma skin changes are in isolated areas, either as morphea patches or linear scleroderma. Morphea is scleroderma that is localized to a patchy area of the skin that becomes hardened and slightly pigmented. Sometimes morphea can cause multiple lesions in the skin. Morphea is not associated with disease elsewhere within the body, only in the involved skin areas. Linear scleroderma is scleroderma that is localized usually to a lower extremity, frequently presenting as a strip of hardening skin down the leg of a child. Linear scleroderma in children can stunt bone growth of the affected limb. Sometimes linear scleroderma is associated with a "satellite" area of a patch of localized scleroderma skin, such as on the abdomen.

The widespread type of scleroderma involves internal organs in addition to the skin. This type, called systemic sclerosis, is subcategorized by the extent of skin involvement as either diffuse or limited. The diffuse form of scleroderma (diffuse systemic sclerosis) involves symmetric thickening of skin of the extremities, face, and trunk (chest, back, abdomen, or flanks) that can rapidly progress to hardening after an early inflammatory phase. Organ disease can occur early on and be serious and significantly decrease life expectancy. Organs affected include the esophagus, bowels, and scarring (fibrosis) of the lungs, heart, and kidneys. High blood pressure can be troublesome and can lead to kidney failure (renal crisis).

The limited form of scleroderma tends to have far less skin involvement with skin thickening confined to the skin of the fingers, hands, and face. The skin changes and other features of disease tend to occur more slowly than in the diffuse form. Because characteristic clinical features can occur in patients with the limited form of scleroderma, this form has taken another name that is composed of the first initials of the common components. Thus, this form is also called the "CREST" variant of scleroderma. CREST syndrome represents the following features:

C...Calcinosis refers to the formation of tiny deposits of calcium in the skin. This is seen as hard whitish areas in the superficial skin, commonly overlying the elbows, knees, or fingers. These firm deposits can be tender, can become infected, and can fall off spontaneously or require surgical removal. This is the least common of the CREST scleroderma variant features.

R...Raynaud's phenomenon refers to the spasm of the tiny arterial vessels supplying blood to the fingers, toes, nose, tongue, or ears. These areas turn white, then blue, then red after exposure to extremes of cold, or even sometimes with extremes of heat or emotional upset. This can lead to tiny areas of damage to the tips of the fingers (digital ulcers) or larger areas of dead skin on the ends of the fingers.

E...Esophagus disease in scleroderma is characterized by poorly functioning muscle of the lower two-thirds of the esophagus (the swallowing tube through which food passes from the mouth to the stomach). This can lead to an abnormally wide esophagus that allows stomach acid to backflow into the esophagus to cause heartburn, inflammation, and potentially scarring that narrows the esophagus. This can eventually lead to difficulty in passing food from the mouth through the esophagus into the stomach. Symptoms of heartburn are treated aggressively in patients with scleroderma in order to prevent injury to the esophagus.

S...Sclerodactyly is the localized thickening and tightness of the skin of the fingers or toes. This can give them a "shiny" and slightly puffy appearance. The tightness can cause severe limitation of motion of the fingers and toes. These skin changes generally progress much slower than those of patients with the diffuse form of scleroderma.

T...Telangiectasias are tiny red areas, frequently on the face, hands, and in the mouth behind the lips. These areas blanch when they are pressed upon and represent widened (dilated) capillaries.

Patients with limited systemic sclerosis can have variations of CREST with differing manifestations, for example, CRST, REST, or ST. Occasionally, patients can have initial illness with features of CREST that evolve into the diffuse form of scleroderma. Some patients have "overlaps" of scleroderma and other connective tissue diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and polymyositis. When features of scleroderma are present along with features of polymyositis, systemic lupus erythematosus, and certain abnormal blood tests, the condition is referred to as mixed connective tissue disease (MCTD).

What are scleroderma symptoms and signs?

The symptoms of scleroderma depend on the type of scleroderma present and the extent of external and internal involvement in the individual affected. Because scleroderma can involve the skin, esophagus, blood vessels, kidneys, lungs, blood pressure, and bowels, the symptoms it causes can affect many areas of the body.

Scleroderma affects the skin to cause local or widespread signs of inflammation (redness, swelling, tenderness, itching, and pain) that can lead to skin tightness or hardening. These skin changes can be widespread, but it's most common for them to affect the fingers, feet, face, and neck. This can lead to decreased range of motion of the fingers, toes, and jaw. Tiny areas of calcification (calcinosis), while not common, can sometimes be noticed as hard nodules at the tips of the elbows, knees, in the fingers, or over joints.

Scleroderma commonly affects the esophagus leading to heartburn. This is directly a result of stomach acid flowing back up into the esophagus. Sometimes this can lead to scarring of the esophagus, resulting in narrowing with difficulty swallowing food and/or localized pain in the central chest.

Blood vessels that can be affected include the tiny arterioles of the finger tips, toes, and elsewhere. These vessels can have a tendency to spasm when the areas are exposed to cold, leading to whiteness, blueness, and redness of involved fingers, toes, and sometimes nose or ears. These color changes are referred to as Raynaud's phenomenon. This may precede the development of other features of scleroderma by years. It should be noted that Raynaud's phenomenon can be an isolated disease without any other disease such as scleroderma developing. Raynaud's phenomenon can cause inadequate supply of oxygen to the involved tips of fingers or toes, causing tiny ulcers or blackened (dead) skin. Sometimes Raynaud's phenomenon is also associated with tingling. Other blood vessels that can be involved in scleroderma are the tiny capillaries of the face, lips, mouth, and fingers. These capillaries widen (dilate), forming tiny, red blanching spots, called telangiectasias. Rarely, telangiectasias in the stomach (called "watermelon stomach" because of its appearance) can present a serious risk of bleeding and require close monitoring by gastroenterologists.

Elevated blood pressure is potentially serious and can lead to kidney damage (renal crisis). Symptoms include headache, fatigue, and in severe cases, stroke. Blood pressure monitoring and control is essential.

Inflammation of the lungs in scleroderma can cause scarring, resulting in shortness of breath, especially with physical exertion. Elevated pressure in the arteries to the lungs (pulmonary hypertension) can also cause shortness of breath and difficulty getting an adequate breath with activity.

Scleroderma involvement in the heart can lead to damage to heart muscle, irregular heart rhythms, abnormal electrical activity of the heart, and inflammation around the heart (pericarditis).

Scleroderma affecting the large bowel (colon) most often causes constipation but can also lead to cramping and diarrhea. When this is severe, complete stool blockage (fecal impaction) can result.

How do health care professionals make a diagnosis of scleroderma?

The diagnosis of the scleroderma syndrome is based on the detection of the clinical features of the illness. In addition, nearly all patients with scleroderma have blood tests that suggest autoimmunity and antinuclear antibodies (ANAs) are usually detectable. A particular antibody, the anticentromere antibody, is found almost exclusively in the limited, or CREST, form of systemic sclerosis. Anti-Scl 70 antibody (antitopoisomerase I antibody) is most often seen in patients with the diffuse form of systemic sclerosis.

Other tests are used to evaluate the presence or extent of any internal disease. These may include upper and lower gastrointestinal tests to evaluate the stomach and bowels, chest X-rays, lung function testing (pulmonary function test), and CAT scanning to examine the lungs, EKG and echocardiograms, and sometimes heart catheterization to evaluate the pressure in the arteries of the heart and lungs for pulmonary hypertension.

What are medical treatments for scleroderma?

Treatment of scleroderma is directed toward the individual features affecting different areas of the body.

Aggressive treatments of elevations in blood pressure have been extremely important in preventing kidney failure. Blood pressure medications, particularly the angiotensin converting enzyme (ACE) inhibitor class of drugs, such as lisinopril, are frequently used.

Some research indicates that colchicine can be helpful in decreasing the inflammation and tenderness that periodically accompanies the calcinosis nodules in the skin. Skin itching can be relieved with lotions (emollients) such as Eucerin, Lubriderm, and Curel.

Mild Raynaud's phenomenon may require only hand warming and protection. Low-dose aspirin is often added to prevent tiny blood clots in the fingers, especially in patients with a history of fingertip ulcerations. Moderate Raynaud's phenomenon can be helped by medications that open up the arteries, such as nifedipine (Procardia, Adalat), nicardipine (Cardene), and diltiazem (Cardizem), or with topical nitroglycerin applied to the most affected digit (most effective on the sides of the digit where the arteries are). Gently applied finger splinting can protect tender tissues. (It is important to not constrict the tiny arteries on the sides of the fingers when protecting them with splints, braces, or band aid materials.) A class of medications that is typically used for depression, called serotonin reuptake inhibitors, such as fluoxetine (Prozac), can sometimes improve the circulation of the affected digit. Drugs that constrict blood vessels, such as pseudoephedrine (Sudafed decongestant), should be avoided. Severe Raynaud's phenomenon can require surgical procedures, such as those to interrupt the nerves of the finger that stimulate constriction of the blood vessels (digital sympathectomy). Ulcerations of the fingers can require topical or oral antibiotics.

Esophagus irritation and heartburn can be relieved with omeprazole (Prilosec), esomeprazole (Nexium), or lansoprazole (Prevacid). Antacids can also be helpful. Elevating the head of the bed can reduce the back flow of acid into the esophagus that causes inflammation and heartburn. Avoiding caffeine and cigarette smoking also helps. Of note, there is an increased risk of developing lung cancer in people with scleroderma. This cancer risk is even greater in those who smoke.

Constipation, cramping, and diarrhea are sometimes caused by bacteria that can be treated with tetracycline (Sumycin), erythromycin (E-Mycin, Eryc, Ery-Tab, Pce, Pediazole, Ilosone), ciprofloxacin (Cipro), or metronidazole (Flagyl). Increased fluid intake and fiber intake are good general measures to take to reduce these symptoms. A variety of medications that promote movement of the bowels are available.

Irritated, itchy dry skin can be helped by emollients such as Lubriderm, Eucerin, or Curel.

Telangiectasias, such as those on the face, can be treated with local laser therapy. Sun exposure should be minimized as it can worsen telangiectasias. Telangiectasias from watermelon stomach can require laser treatments to the stomach.

Approximately 10% of patients with the CREST variant develop elevated pressures in the blood vessels to the lungs (pulmonary hypertension). Abnormally elevated blood pressure of the arteries supplying the lungs is often treated with calcium antagonist medications, such as nifedipine (Procardia), and blood-thinning drugs (anticoagulation). More severe pulmonary hypertension can be helped by continuous intravenous infusion or inhalation of prostacyclin (Iloprost). Taken by mouth, bosentan (Tracleer) is used to treat pulmonary hypertension. In addition, sildenafil (Revatio) and tadalafil (Cialis) are approved to treat pulmonary hypertension.

Additionally, medicines are used to suppress the overly active immune system that seems to be spontaneously causing the disease in organs. Medications used for this purpose include penicillamine, azathioprine (Imuran, Azasan), and methotrexate (Rheumatrex, Trexall). Serious inflammation of the lungs (alveolitis) can require immune suppression with cyclophosphamide (Cytoxan) along with prednisone (Deltasone, Liquid Pred). The optimal treatment of scleroderma lung disease is an area of active research. Stem-cell transplantation is being explored as a possible option.

No medicine has been found to be universally effective for patients with scleroderma. In an individual patient, the illness may be mild and not require treatments. In some, the disease is ravaging, relentless, and can lead to death. Because blood vessel damage is a primary part of the pathology of scleroderma, patients with this condition must not smoke.

What is the prognosis (outlook) for patients with scleroderma?

A patient's prognosis is optimized with close monitoring of overall health status and treatment of complications, especially elevated blood pressure. This can involve medical subspecialists, including rheumatologists, pulmonologists, gastroenterologists, nephrologists, and cardiologists. Research indicates that the critical period of organ risk is generally within the first three years of skin involvement. This means that patients can be reassured that their risk of organ-threatening complications is significantly less after three years of having skin symptoms and not having internal organ problems.

Patients with diffuse skin involvement tend to do worse than those with limited skin involvement. Those with limited disease of the skin can develop serious lung scarring and pulmonary artery hypertension even after a decade of disease. Lung disease is the leading cause of death. Those with poor pulmonary function tests can have worse outcomes.

Scleroderma continues to challenge medical scientists. Researchers are evaluating the effectiveness of thalidomide (Thalomid) for the treatment of scleroderma. More sensitive tests to detect early lung disease of scleroderma are also being evaluated. Ongoing research into new medications for pulmonary hypertension are in clinical trials. Researchers are also evaluating the possible role of stem-cell transplantation for certain serious forms of scleroderma.

Many researchers are investigating the roles of various cell messengers, called cytokines, in causing scleroderma. Researchers are also currently studying a hormone of pregnancy, called relaxin, for the treatment of scleroderma. Preliminary results suggest that it may improve scleroderma. Relaxin normally loosens the ligaments of the pelvis and ripens the womb for childbirth. How it might work in scleroderma is unclear.

It is clear that our understanding of the effects of the immune system in scleroderma is greatly improving. Many clinical research trials are under way to evaluate potential treatments for various aspects of the disease to improve the prognosis for patients with scleroderma. Further research supported by the Scleroderma Foundation, Arthritis Foundation, and the National Institutes of Health will lead to better understanding the illness and more optimal care for patients with scleroderma.

Is it possible to prevent scleroderma?

There is no prevention method or diet to avoid or decrease the risk of scleroderma.

REFERENCES:

Arnett, F. C., et al. "Increased prevalence of systemic sclerosis in a Native American tribe in Oklahoma. Association with an Amerindian HLA haplotype." Arthritis and Rheumatism 39.8 (1996): 1362-1370.

Klippel, J. H., et al. Primer on the Rheumatic Diseases, 13th Edition, Springer, 2008.

Last Editorial Review: 6/8/2017

Reviewed on 6/8/2017
References
REFERENCES:

Arnett, F. C., et al. "Increased prevalence of systemic sclerosis in a Native American tribe in Oklahoma. Association with an Amerindian HLA haplotype." Arthritis and Rheumatism 39.8 (1996): 1362-1370.

Klippel, J. H., et al. Primer on the Rheumatic Diseases, 13th Edition, Springer, 2008.

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