Scleroderma and Systemic Sclerosis (SSc): An Overview


Jessica K. Gordon, MD

Assistant Attending Physician, Hospital for Special Surgery
Assistant Professor of Medicine, Weill Cornell Medical College

Introduction

The term scleroderma comes from the Greek skleros, meaning hard, and derma, meaning skin. Scleroderma is a group of conditions affecting approximately 300,000 people in the United States.

When scleroderma only affects the skin, it is considered "localized." However, if it affects the skin and internal organs, it is viewed as "systemic," also called Systemic Sclerosis (SSc). SSc affects approximately 100,000 people, or about one third of patients with scleroderma in the United States; this article will focus primarily on SSc.

What is Systemic Sclerosis (SSc)?

There are two main subtypes of SSc – limited and diffuse – which are defined according to the pattern of skin involvement. The third and less prevalent subtype is SSc sine scleroderma, or SSc without hard skin, meaning a person has the internal organ manifestations and perhaps laboratory evidence for the condition, but no skin involvement.

SSc can affect almost any organ in the body. The most commonly affected areas include the following:

  • Skin
  • Blood vessels
  • Gastrointestinal tract
  • Lungs
  • Heart
  • Kidneys
  • Muscles
  • Joints

Scleroderma is an autoimmune disorder, a condition in which the body mistakenly damages normal tissue. In healthy individuals, the immune system protects the body from infections. However, in patients with scleroderma, the immune system is dysregulated and misdirected.

The immune system manufactures antibodies that fight one or more of the individual’s own proteins. Doctors can see evidence of this immune dysregulation when they perform blood tests and look for these "auto-antibodies" in the blood.

What Causes Scleroderma?

The specific cause for the development of scleroderma is unknown. However, it is known that there are multiple factors involving vascular dysfunction, immune alteration, and overproduction of collagen, leading to various manifestations of this disease.

Recent research shows that genetic factors play some role in the development of this scleroderma, but family members of patients with scleroderma are still very unlikely to develop this illness. Many experts believe there is also likely to be some sort of additional unknown stimulus which triggers the development of this condition.

Scleroderma affects people of any age – from young children to elderly adults. However, it most commonly affects people between 30 and 50 years of age. Gender also plays a role in the prevalence of the disorder, as 75% of patients with SSc are women. In addition, race and ethnic background may influence the risk of getting scleroderma and the pattern of disease manifestations. SSc is somewhat more common in persons of African ancestry.

Signs and Symptoms of Scleroderma and SSc

Scleroderma can be difficult to diagnose, especially early in the course of the disease. The symptoms and physical findings early on, including symptoms of Raynaud’s phenomenon, swelling of the hands, and general pain, can overlap with the early symptoms of lupus, rheumatoid arthritis, dermatomyositis, and other conditions. A rheumatologist will usually make this diagnosis, but it may take more than one visit for the rheumatologist to be certain.

Blood Vessels: The first symptom of scleroderma is frequently the development of the Raynaud‘s phenomenon, which is when the fingers and/or toes change color and become numb when exposed to the cold. Usually the fingers turn white, then bluish or purple, and then very red. This can become sufficiently severe enough to cause digital ulceration (sores on the fingers) and/or gangrene of the fingers. Additionally, patients frequently have dilated blood vessels at the nail folds, which doctors can see with magnification and may help with the diagnosis.

Skin: Almost all patients with Systemic Sclerosis (SSc) have thickening of their skin. This is seen especially in the hands but can extend over the whole body. In limited cutaneous SSc, skin involvement is limited to the face, hands, forearms, lower legs, and feet. In diffuse cutaneous SSc, the skin thickening can additionally involve the upper arms, thighs, and the trunk.

It is possible to have Systemic Sclerosis without skin thickening (sine scleroderma), which is when a patient has the internal organ manifestations without the skin findings, but this is very rare. Skin thickening and tightness can lead to contractures of the joints (when a person cannot extend or flex a joint completely) and an inability to open the mouth fully. Other skin findings include the following:

  • Hyper - or hypopigmentation of the skin, when the skin looks darker or lighter than usual
  • Telangiectasia, which are dilated blood vessels that show up as red spots on the skin
  • Calcinosis or hard calcium in the skin, which can be painful

Pulmonary: Patients with SSc may suffer from shortness of breath, decreased exercise capacity, or cough. The leading cause of death in patients with SSc is lung disease, which can either be interstitial lung disease with fibrosis (scarring) of the lungs or pulmonary hypertension, which is elevated pressures in the pulmonary artery.

Patients with SSc need screening for these conditions on a regular basis. This is performed with pulmonary function testing, echocardiography, and chest radiography or CT scans of the chest. If these screening tests are abnormal, referral to a pulmonologist or cardiologist for additional testing is frequently needed.

Heart: The heart can also be affected in SSc, and heart-related symptoms may be similar to lung-related symptoms, including shortness of breath or decreased exercise capacity. Additional symptoms include chest pain or swelling of the legs. Some patients have cardiomyopathy or weakness of the heart muscle, and others may suffer from abnormal cardiac rhythms.

Kidneys: The kidneys can be involved in scleroderma. An uncommon but extremely important condition in SSc is Scleroderma Renal Crisis. This occurs when a patient with SSc suddenly develops very high blood pressure and possibly renal failure. Patients may experience severe headaches, stroke, or seizure if this happens, or they may be asymptomatic. Patients with diffuse SSc, especially early in the course of their illness, should check their blood pressure at home regularly to catch any elevation early when treatment with ACE-Inhibitors would have the best effect.

Gastrointestinal Tract: Any part of the gastrointestinal (GI) tract can be involved in SSc, and the symptoms vary depending on the involvement. Over 90% of patients have GI manifestations of some sort. The most common problem is reflux, which can feel like heartburn or lead to chronic cough. Reflux can also contribute to chronic aspiration, which can then contribute to lung disease. Some patients may experience nausea, vomiting, diarrhea, constipation, or have a difficult time swallowing. Other patients may experience bloating for various reasons or problems absorbing nutrients. Some experience weight loss. Others can experience bleeding from the stomach because of a condition called Gastric Antral Vascular Ectasia (GAVE, also known as “watermelon stomach” because of the way it appears on endoscopy).

Anemia: Low red blood cell counts (anemia) can contribute to many symptoms including fatigue, shortness of breath, or dizziness. This can occur because of low iron or vitamin levels, a chronic inflammatory state, or for other reasons.

Muscle: Patients with SSc may experience muscle weakness because of inflammation of the muscles, while others experience pain in their muscles.

Joints: Many patients with SSc experience pain in their joints, which occurs for many reasons. Sometimes the joints may be inflamed because of an autoimmune process. Other times, patients have an overlapping condition with both SSc and rheumatoid arthritis. Persons with scleroderma may also experience joint pain for the same reasons individuals without this disorder feel discomfort. For example, overuse injuries, osteoarthritis, and degenerative disc disease may result in joint pain.

Neurological: Some patients experience numbness, tingling, and pain from various neuropathies (disorders of the nervous system), including carpal tunnel syndrome and other syndromes as well.

Sexual Dysfunction: This can occur in both men and women with SSc for multiple reasons.

General Symptoms: In addition to the symptoms above, many patients experience fatigue, difficulty sleeping, mood disorders, including depression and anxiety, weight loss, malaise, and pain.
 
Because of the multiple ways by which SSc can manifest itself, it is important for patients to let their physicians know all of their symptoms so they can be addressed.

Localized scleroderma (also known as morphea or linear scleroderma)

Two/thirds of those diagnosed with scleroderma have the localized form, which affects the skin and not the internal organs as detailed above. Localized scleroderma does NOT evolve into systemic scleroderma. Localized scleroderma is seen in all age groups, but is somewhat more common in children. This can affect the growth and development of underlying structures, including muscle and bones. Treatment for this condition includes steroid and vitamin D creams, light (UVA1 or UVB) therapy, and immunosuppressive medications (corticosteroids, methotrexate, and mycophenalate mofetil.)

How Your Doctor Diagnoses Systemic Sclerosis

Systemic Sclerosis is diagnosed based on the presence of various symptoms above and physical examination findings.

The diagnosis can be confirmed by the presence of certain autoantibodies in the blood as well as radiographic studies. Particularly, the ANA, or the antinuclear antibody test, is positive, but not always. An ANA using the immunofluorescence method is sometimes preferable to the ANA performed using ELISA (enzyme-linked immunosorbent assay) methods because of the tendency of ANAs by ELISA to miss nucleolar ANAs.

Commercially available autoantibodies include the anti-centromere antibody seen in limited scleroderma and the antiSCL70 and the anti-RNA Polymerase III antibodies, both seen in diffuse scleroderma. These autoantibodies are also not always positive, so the most important part of the diagnosis is a history and physical examination performed by a rheumatologist experienced in these conditions.

Once the diagnosis is made, certain studies should be performed to screen for internal organ involvement. These include an echocardiogram, pulmonary function testing, and a chest radiograph or CT scan of the chest to screen for heart or lung involvement. Blood and urine tests can show if there are issues with blood counts, kidney, or liver function.

Patients with diffuse systemic sclerosis will frequently be instructed to check their blood pressures regularly, and this is done to catch scleroderma kidney disease at its most early stage – when treatment is the most effective.

Treatment

SSc is a chronic condition that should be treated and monitored by a rheumatologist, and frequently needs the input from physicians in other medical specialties.

Although there is no cure for SSc, there are many treatments which can improve the various symptoms of the disease. Many physicians and scientists across the country are working together to help determine the cause (or causes) of scleroderma and to develop new and improved treatments.

The first step in getting treatment is to find a rheumatologist with whom you can build a strong relationship. The care of patients with scleroderma frequently requires a team approach. Depending on your symptoms, you will likely also need to be referred to other specialists including pulmonologists, cardiologists, gastroenterologists, nephrologists, or dermatologists. The treatment depends on the organ system involvement.

Raynaud’s phenomenon and digital ulceration: Prevention is key, so it is essential to avoid triggers like the cold (wear gloves, dress in layers, keep the whole body warm, avoid rapid changes in temperature, etc.), tobacco, and stress.

The first step in treatment of this issue is usually a calcium channel blocker (amlodipine or nifedipine) and an aspirin. If symptoms persist, additional therapy with nitroglycerin, endothelin antagonists, or phosphodiesterase inhibitors may be added. IV prostaglandins can be used in severe Raynaud’s. Wound care is also important in the treatment of ulcers. Various ointments may be prescribed, and if the ulcers become infected the physician will prescribe antibiotics.

Gangrene can occur and is a medical emergency. If a finger becomes blue and painful, and does not return to normal color upon rewarming, the patient should call his or her rheumatologist immediately for escalated and urgent treatment. 

GI - Reflux: Proton pump inhibitors and H2 Receptor antagonists are very effective for the treatment of reflux. Some patients with SSc require higher doses than usual. Esophageal Dysmotility can be treated with pro-motility medications like Reglan. The alternative, domperidone, is not available in the United States. This frequently requires evaluation with swallowing studies and endoscopy.

Bacterial overgrowth can cause bloating and diarrhea. If this is diagnosed, it is treated with antibiotics. Bleeding due to GAVE (Gastric Antral Vascular Ectasia, or watermelon stomach) can be treated with endoscopic laser ablation therapy.

Pulmonary: Interstitial lung disease is frequently treated with immunosuppressive therapies including cyclophosphamide, Cellcept (mycophenolate mofetil), or different therapies. Clinical trials are ongoing to determine which of these therapies is the most effective.

Pulmonary hypertension is diagnosed by right heart catheterization. Cardiologists and pulmonologists, in conjunction with rheumatologists, treat patients with pulmonary hypertension with a variety of medications including endothelin antagonists, phosphodiesterase inhibitors, calcium channel blockers, and prostacyclin analogues. Sometimes anticoagulants are used as well.

Muscle Disease: Muscle disease in scleroderma can be noninflammatory or inflammatory. Inflammatory muscle disease can be treated with immunosuppressant medications (methotrexate, azathioprine, corticosteroids) or IVIG (intravenous immune globulin). Physical therapy is an extremely important part of the treatment of any muscle disease, including scleroderma.

Arthritis: Patients with systemic sclerosis can have inflammatory arthritis, which can respond to low dose steroids, plaquenil, methotrexate or other therapies. Joints can hurt for any number of reasons, so it is important for patients to notify their rheumatologists about their pain so this can be addressed.

Skin: Immunosuppressive agents like methotrexate and mycophenalate are frequently employed. Some experts use D-penicillamine, although a clear benefit was not shown in clinical trials. Many trials are ongoing to find additional treatments for the skin. Because thickening and tightening of the skin can lead to restriction of range of motion, physical therapy and occupational therapy are essential as a part of the treatment of the skin manifestations of SSc.

Other immunosuppressive regimens: Ongoing clinical trials are now assessing the efficacy of other immunosuppressive regimens, including high dose chemotherapy with stem cell transplantation for patients with the most severe forms of scleroderma. The results of these trials are key to understanding the benefits and risks of these treatments.

Rehabilitation/Physical and occupational therapy (PT/OT): This is essential to overall health and maintenance function. The PT focus is on the larger muscle groups and the OT focus is on the fine motor skills – especially the hands. There is an important role for PT and OT in the treatment of skin disease, arthritis, and muscle disease.

Take-Home Points

  • Scleroderma is a rare condition, and patients with scleroderma need specialized care from a rheumatologist familiar with their condition.
  • The care of patients with scleroderma requires a team approach. Many patients with scleroderma will input from different medical specialties including gastroenterology, pulmonary, cardiology, and others.
  • Educate yourself. Become an expert about your condition, and you will be your own best advocate. Ask your doctors, seek sources on the web, go to educational forums and support groups.
  • Communicate with your doctor. Let your doctor know what is bothering you so he/she can address your concerns.
  • Prepare for your visits – be sure to bring medical records, bring an updated medication list , and be sure to write down your questions beforehand, so you don’t forget them when the time comes for your appointment. If you are using complementary or alternative therapies, be sure to keep your physician informed. Seek the support you need. Whether it is from your family, friends, or a scleroderma support group, everyone with chronic illness needs to be able to count on others for support.
  • Consider participating in research. Although there are many treatments for SSc, there is no cure. You can be a part of the search for a cure by participating in research studies.
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