What is scleroderma?

Scleroderma is an autoimmune disorder that can lead to a tightening or hardening of the skin and other soft, connective tissues. It is a chronic condition in which the immune system mistakenly attacks and damages your own body. This manifests as an overproduction of collagen, a protein that is a building block of connective tissues. This overproduction leads to fibrosis – an increase of tissue volume – of the skin or of tissues of the lungs or other organs.

What causes scleroderma?

As with most autoimmune diseases, the exact cause is unknown, although in many patients it may be multifactorial, arising from a combination of congenital processes and environmental agents.

Some scleroderma-like illnesses have also been associated with environmental exposures, such as an outbreak of scleroderma-like illness in Spain in people who had ingested a toxic rapeseed oil. Other cases of scleroderma-like diseases have developed in people who consumed adulterated food containing L tryptophan (an amino acid that is essential to building our bodily proteins, and which we absorb from food).

In some people, certain scleroderma-like lung diseases have occurred after exposures to certain toxins or chemotherapy agents to treat cancer, such as bleomycin.

Is scleroderma life-threatening?

Mild forms of scleroderma may disrupt quality of life but poses no danger. But systemic scleroderma is the most lethal of all rheumatic conditions due to the way it can affect organ systems. Systemic scleroderma can lead to pulmonary fibrosis (increased tissue in the lung that can disrupt respiration), pulmonary hypertension (high blood pressure in the arteries that carry blood from the heart to the lungs) and scleroderma renal crisis, which can cause kidney failure, heart failure and other deadly conditions.

What are the different types of scleroderma?

There are two basic types, each of which has various subtypes: Localized scleroderma (affecting only the skin) is a milder type, while systemic scleroderma (affecting the internal organs), is much more dangerous. Systemic scleroderma is also known as systemic sclerosis (SSc) or “generalized scleroderma” and can lead to serious or even life-threatening organ damage and complications.

Localized scleroderma

In some patients, the disease is localized and purely a skin disorder, at times characterized by isolated patches of thickened, scarred, tight skin. In other case, the skin involvement becomes more widespread, but the disease still does not extend to affect internal organs or cause vascular (blood vessel) problems.

There are three basic subtypes of localized scleroderma:

• morphea: roundish or irregular-shaped hard patches of skin on the face, hands, feet or trunk
• linear scleroderma: lines or bands of thickened skin on the face, arms or legs
• morphea en coup de sabre: thickened skin causing linear depressions on the forehead only

(Find a localized scleroderma specialist at HSS.)

Systemic scleroderma

Two major forms of systemic sclerosis are recognized: limited systemic scleroderma (also known as CREST syndrome) and diffuse scleroderma. This second form is also known by many other names, including diffuse cutaneous systemic scleroderma (dcSSc), progressive cutaneous systemic scleroderma, and progressive cutaneous systemic sclerosis. (Find a systemic scleroderma specialist at HSS.)

In both forms, vascular (blood vessel) problems such Raynaud’s phenomenon are present. Gastrointestinal problems can occur in both forms as well. The difference between the two depends on the extent of involvement of the skin.

In patients with limited disease, the skin involvement mostly affects the hands, possibly the forearms, but not extending above the elbows and there generally is sparing of the trunk. The face may be involved as well. In patients with diffuse scleroderma, the skin involvement usually affects the upper arms, thighs, chest wall and trunk.

In a much rarer subtype known as systemic sclerosis sine scleroderma (ssSSc), people have unaffected, normal skin but have other manifestations of the systemic scleroderma.

Limited sclerosis

Limited sclerosis is also sometimes called CREST syndrome, which is an acronym of its common features:

• Calcinosis: nodules of calcium that form under the skin
• Raynaud’s phenomenon: color changes of the fingers and toes in the cold
• Esophageal dysfunction: improper functioning of the esophagus, which can cause acid reflux
• Sclerodactyly: Tightened skin on the hands that can cause fingers to flex (curl) involuntarily and impair movement
• Telangiectasia ("spider veins"): dilated or broken blood vessels located near the surface of the skin or mucous membranes

Although lung involvement or even kidney involvement can occur in patients with limited disease, it is less common as a rapidly progressive problem early in the disease course, although it is important not to overlook these potential complications. Pulmonary hypertension in particular, which can be a very serious condition, can occur in patients with limited disease and can arise late in the course of the disease.

Diffuse scleroderma

Patients with diffuse scleroderma seem to be at higher risk for early lung involvement, and doctors will generally screen for this proactively. These patients also seem to be higher risk for kidney involvement. This can be dangerous or life-threatening if left unrecognized, but it can be easily screened for by frequent analysis of urine samples and checking blood pressure regularly (several times a week), particularly early in the course of the disease.

What are the symptoms of scleroderma?

Symptoms vary but can include:

• Raynaud’s phenomenon (color changes of the fingers and toes in the cold)
• arthritis or joint pain
• thickened or tightened skin on different parts of the body
• acid reflux, heartburn and other gastrointestinal problems

More serious manifestations (for systemic scleroderma or systemic sclerosis) include:

• interstitial lung disease
• pulmonary hypertension
• breathing difficulties and chest pain
• anemia
• heart problems
• kidney problems

What are the early signs and symptoms of systemic sclerosis?

Often, the first symptom of systemic sclerosis (systemic scleroderma) is Raynaud’s phenomenon. This is when the fingers turn white, red, and/or blue in response to the cold or stress. However, it is important to note that most people who have Raynaud’s phenomenon do not have scleroderma. Up to 15% of certain populations may have the Raynaud’s phenomenon, while less than 0.001% have systemic sclerosis.

Who is most at risk for scleroderma?

Like lupus and rheumatoid arthritis, scleroderma affects women more frequently than men. About 80% of patients with systemic scleroderma are women. This rare disease can develop at age but usually starts to affect adults between their 20s to 50s. Localized scleroderma may be seen in adults or children alike. In most patients with scleroderma, there is no clear underlying predisposing risk factor.

Is scleroderma genetic? Does it run in families?

There are some genetic issues which may be associated with a slightly higher risk for scleroderma, but in general, scleroderma does not seem to be a strongly genetically determined disease. The overwhelming majority of patients with scleroderma have no family members with the disorder. A very small number of scleroderma patients (about 1.5%) will have an affected first-degree family member (meaning parent, child or sibling.) These families are being studied by researchers to learn more about scleroderma genetics.

Is scleroderma triggered by environmental factors?

A host of environmental exposures have been associated with the development of scleroderma-like illnesses, but this is relevant in only a minority of patients who ultimately develop scleroderma. Smoking seems to be a risk factor for vascular disease associated with scleroderma and with more severe expression of the disease in general. It is not clear, however, whether tobacco or nicotine use increases the risk of developing scleroderma.

Should I see a dermatologist or rheumatologist if I think I have scleroderma?

A diagnosis of scleroderma frequently requires consultation between several different specialists, including a dermatologist and a rheumatologist. A good place to start might be your primary care doctor, who can help refer you to the correct specialists. Scleroderma can cause symptoms that are like those of other chronic, rheumatic diseases, and it can be confused with other conditions that involve the development of thick and itchy skin. A rheumatologist can help distinguish between them.

Because it is such a rare disease, many physicians are not aware of the screening recommendations nor of available treatment options. People with systemic sclerosis, especially, need a rigorous evaluation for cardiac and lung disease, as well as counseling on how to monitor for the more serious signs and symptoms of this condition. If you are concerned about getting a correct diagnosis or if another physician has diagnosed you with systemic scleroderma (systemic sclerosis), it is very important to be seen by a rheumatologist with special expertise in systemic sclerosis. (Find a systemic scleroderma specialist at HSS.)

How is scleroderma diagnosed?

The scleroderma diagnosis is based on a combination of clinical feature (symptoms) certain laboratory findings. A thorough examination and blood tests are needed to determine whether you have scleroderma. Diagnosis can be difficult, because the disease shares many similarities with other autoimmune disorders. It is very important to consult a rheumatologist who has expertise in scleroderma. (Find a scleroderma expert at HSS.)

Clinical features of scleroderma

The overwhelming majority of patients with scleroderma had Raynaud’s phenomena, a condition where upon cold exposure extremities can become whitish, bluish, or ultimately even reddish and uncomfortable. Raynaud’s phenomena, however, is common in the general population. In patients with Raynaud’s phenomena in the context of scleroderma, other findings are usually present, including changes that can be observed by an experienced clinician looking closely at the nail beds, skin changes which generally define scleroderma (the typical “hardened skin” that one would see in scleroderma), and the presence of internal organ issues.

Blood tests for scleroderma

A rheumatologist will often order a panel of laboratory tests including autoantibodies, which are markers that can help predict one pattern of disease or another.

Typically, the rheumatologist will order an test for ANA (antinuclear antibody, an antibody commonly found in many of the autoimmune diseases), as well as for Scl-70 antibody (positive in some patients with diffuse scleroderma), anticentromere antibody (generally felt to be a marker for limited scleroderma), and an antibody called RNA polymerase III, which seems to be a marker for diffuse scleroderma, and often predicts patients with more rapidly progressive skin disease, and also possibly higher risk for kidney involvement in whom blood pressures should be monitored with even greater vigilance.

A skin biopsy is usually not necessary to make the diagnosis.

Screening for organ involvement (systemic sclerosis)

There is no single algorithm as to how patients with established or even suspected scleroderma should be screened for organ involvement. The most important screening tool is a comprehensive history, which is a discussion between the patient and the physician, as well as a careful physical examination. Further tests that likely will be ordered will include blood tests and a urine analysis to assess basic parameters of health including whether or not anemia is present, the status of renal function, and usually also muscle blood tests to assess for whether there is any muscle inflammation which can occur in these disorders.

Tests of lung and heart function are often requested, including pulmonary function studies (where a patient breathes into a tube and their lung function is assessed), often a chest X-ray or even high resolution chest CT scan, and usually an echocardiogram which can assess both the heart function, as well as the pressure in the arteries going from the heart to the lung (which helps screen for pulmonary hypertension).

At times, various gastrointestinal (GI) tract tests may be ordered, depending on the patient's symptoms. These tests are all done with an eye towards identifying problems while they are still in an early stage and possibly more easily treatable.

How is scleroderma treated?

There is no cure for this chronic illness, but treatments are available which can help improve pain, various disease manifestations, and improve quality of life. Depending on the severity of the disease, aggressive physical and occupational therapy may be required to prevent disability in some patients.

Several blood-vessel-dilating medications that have been developed have been recognized as being helpful in patients with scleroderma and Raynaud’s phenomena complicated by digital ulcers. There have also been trials demonstrating that immunosuppressive therapies can be helpful in terms of progression of lung disease in patients with scleroderma and progressive interstitial lung disease.

Drug research for scleroderma therapies

A tremendous amount of research is ongoing to find improved treatments and to better understand systemic sclerosis. The question of whether there is a true disease modifying antirheumatic drug (DMARD) for scleroderma, however, remains a difficult one.

There are no drugs that have been unequivocally proven in controlled trials to treat scleroderma. Encouragingly, there are a number of agents of interest looking at a variety of strategies including immunosuppressive strategies with drugs such as mycophenolate or cyclophosphamide, antifibrotic therapies with drugs such as tyrosine kinase inhibitors, and even the development of newer biologics which may hold promise in terms of treating the underlying disease.

The scleroderma clinical research community has become much more sophisticated and integrative in our ability to perform the clinical trials necessary to assess these newer medications. Moreover, advances in understanding the basic underlying immune and vascular system abnormalities in scleroderma holds promise for developing newer therapies in the near future. Patients with systemic sclerosis should consider whether they would like to involve themselves in research and be part of finding a cure for this disease.

Can altering my diet help improve scleroderma symptoms?

There is no strong scientific evidence to recommend a specific diet to treat scleroderma, but in general it is good to eat a healthy and balanced diet. However, specific clinical manifestations of scleroderma may improve with dietary modification. Certain foods can trigger gastroesophageal reflux disease (GERD) and avoiding them can improve symptoms. Other issues which may respond to dietary changes include gastrointestinal or esophageal dysmotility, severe weight loss and constipation. Patients with heart or kidney disease as part of scleroderma may require a low salt diet. Sometimes a consultation with a nutritionist is helpful. Be sure to discuss your diet and your concerns with your physician as well.