Scleroderma

What is scleroderma?

Scleroderma is a poorly understood illness that causes widespread hardening of the skin, especially on the hands and face. It also can damage the lungs, heart, kidneys, digestive tract, muscles, and joints. It is a long-lasting (chronic) autoimmune disorder, an illness in which the body's immune defenses mistakenly attack the body's own cells rather than protecting them from outside invaders. Scleroderma also is called progressive systemic sclerosis.

There are two types of scleroderma. In the limited form, also called limited systemic sclerosis, the skin is the primary target. In the diffuse form (diffuse systemic sclerosis), the damage not only affects the skin, but also can affect the lungs, kidneys, and other internal organs.

In people with scleroderma, scientists have identified abnormal immune proteins called autoantibodies, which are programmed to attack specific components of body cells. They also have found abnormal accumulations of protective T cells (white blood cells that are part of the immune system) in the skin and elsewhere.

Although scientists don't understand exactly what happens, they believe that the immune system, perhaps involving these autoantibodies or T cells, somehow damages the body's smallest arteries, called arterioles. These damaged arterioles leak fluid, which causes swelling. They also release chemical factors that stimulate cells called fibroblasts to produce too much collagen, a fibrous protein involved in forming scar tissue.

In the skin, this leads to thickening, hardening, and tightness. Elsewhere in the body, the autoimmune attack of scleroderma can damage the digestive tract, the linings of joints, the outside sheaths of tendons, muscles (including the heart muscle), portions of the heart that regulate heart rhythm, the small blood vessels, and the kidneys.

Scleroderma is rare, affecting about 14 in every 1 million people worldwide. It is most common in women ages 35 to 54. The cause is unknown. For some reason, cells called fibroblasts make too much scar-type tissue in the skin and in organs throughout the body.

A number of theories have been proposed to explain this, including abnormalities in blood vessel function, abnormal proteins and antibodies in the circulation, and abnormal amounts of chemical messengers instructing fibroblasts to become overly active. Because scleroderma is more common in women during the childbearing years, researchers have looked for a pregnancy-related factor to explain why scleroderma develops. One theory suggests that leftover fetal cells can still be circulating in the mother's bloodstream decades after pregnancy, and may play some role in triggering the autoimmune changes behind scleroderma. Genetic factors and infectious triggers have also been proposed.

Older studies have linked scleroderma to exposure to certain chemicals, including vinyl chloride, epoxy resins, aromatic hydrocarbons, and ingestion of rapeseed oil adulterated with aniline. Some people who took tryptophan, an amino acid that used to be sold as a dietary supplement, developed a condition similar to scleroderma called eosinophilia myalgia syndrome. Since tryptophan was removed from the market, no further cases of eosinophilia myalgia syndrome have been reported. But the clear link between tryptophan and eosinophilia myalgia syndrome and the scleroderma-like disease associated with contaminated rapeseed oil ingestion raise the possibility that exposure to something in the environment could trigger scleroderma.

Symptoms of scleroderma

The symptoms of scleroderma vary from person to person and can include:

• Raynaud's phenomenon. In people with this condition, blood vessels in the fingers or toes, and sometimes in the tips of the nose and ears, suddenly constrict. The area turns white or blue and becomes cold and numb. This is followed by a flush of redness as the area warms up again, often together with pain or tingling. Raynaud's phenomenon can be triggered by exposure to cold or vibration or by emotional stress.
• Skin symptoms. There can be swelling of the fingers, hands, forearms, and face, and sometimes the feet and lower legs. This is followed by a skin thickening and tightness that can limit body movement. There also can be
  • skin ulcers
  • skin that is lighter or darker than usual
  • loss of hair
  • abnormal skin dryness, including vaginal dryness
  • calcium deposits in the skin (subcutaneous calcinosis)
  • small red spots caused by localized swelling of tiny blood vessels (telangiectasias)
• Joints. Joints can swell and become painful and stiff.
• Muscles. Muscles can become weak, and tendons can become abnormally thick, causing pain and limited joint motion.
• Digestive system. When scleroderma involves the esophagus, it can cause a feeling of fullness or burning pain (heartburn) in the upper abdomen or behind the breastbone, together with difficulty swallowing or keeping food down. Other digestive symptoms include bloating, constipation, lower abdominal pain, or difficulty controlling bowel movements.
• Lungs. Symptoms can include shortness of breath, especially when you exercise, and a dry cough that doesn't bring up sputum or mucus.
• Heart. Problems can include chest pain, abnormal heart rhythms, and heart failure.
• Kidneys. Kidney damage can lead to high blood pressure, headache, seizures, and too little urine being made.
• Other symptoms. Other symptoms can include dry eyes and mouth, sudden episodes of severe facial pain (trigeminal neuralgia), and impotence.

More than 95% of people with scleroderma have both Raynaud's phenomenon and skin thickening (also called sclerodactyly when the fingers are involved). In addition, those with limited scleroderma tend to have telangiectasias, a collection of dilated blood vessels under the skin (85% of patients); digestive problems involving the esophagus (80%); and calcinosis (50%), often called CREST syndrome (calcinosis, Raynaud's, esophageal disease, sclerodactyly, and telangiectasia). High pressure in the blood vessels around the lung (a serious condition called pulmonary hypertension) develops in about 15% of people with limited scleroderma.

Besides having Raynaud's phenomenon and skin thickening, people with the diffuse form of scleroderma can have digestive symptoms involving the esophagus (80%), joint symptoms (70%), muscle weakness (50%), lung symptoms (40%), and heart failure (30%).

Diagnosing scleroderma

Your doctor will ask about your symptoms and will examine your skin, especially on your fingers, hands, and face. If your doctor suspects you have scleroderma, he or she may want to order blood and urine tests. Occasionally, a skin biopsy may be recommended, during which a small sample of skin is removed and examined in a laboratory. If scleroderma affects internal organs such as the heart, lungs, or digestive organs, a chest x-ray and other tests may be necessary.

Expected duration of scleroderma

Scleroderma is a chronic (long-lasting) disease. Although symptoms may come and go over time, the various forms of this disease usually last a lifetime. The skin swelling that happens first can last for a few weeks or months. This is followed by a gradual thickening of the skin and other skin changes. In the diffuse form of the disease, skin symptoms tend to peak within three years, then stabilize or even improve. If skin changes occur more rapidly, there is often a greater risk that internal organs are being damaged as well. In limited scleroderma, skin symptoms tend to worsen very slowly over a period of many years.

Preventing scleroderma

There is no way to prevent scleroderma.

Treating scleroderma

There is currently no single treatment for scleroderma that is reliably effective. Treatment choices depend on the organ involved, other medications and medical problems, and patient preference.

A host of drugs are commonly prescribed and may have benefit. Among the most commonly prescribed drugs for scleroderma are:

• Mycophenolate mofetil (Cellcept) and mycophenolate sodium (Myfortic) may be especially helpful for people with skin or lung involvement.
• Methotrexate (Rheumatrex, Trexall, others) may be particularly helpful for skin involvement, arthritis, or myositis.
• Hydroxychloroquine may reduce symptoms of arthritis.
• Cyclophosphamide (Cytoxan, Neosar) decreases the activity of the immune system and has been shown to improve lung function when used along with corticosteroids in people with inflammation in the lungs. The risks associated with this powerful medication (including infection, bleeding from the bladder, and an increased risk of cancer) require that its use be highly selective and closely monitored.
• Glucocorticoids can be used to relieve inflammation of the membrane surrounding the heart (pericarditis), arthritis, and inflammation of the lungs (pneumonitis) or muscles (myositis). However, these drugs also can have serious side effects — especially in people with scleroderma, in whom they may cause increased blood pressure and worsened kidney function. For these reasons glucocorticoids are generally prescribed in the lowest effective dose for the shortest possible time or avoided altogether in people with scleroderma.
• Nonsteroidal anti-inflammatory drugs (NSAIDs) may be useful for joint and tendon inflammation.
• Diuretics encourage the body to release excess fluid as urine. They are used to relieve swelling of the hands and feet.
• Omeprazole (Prilosec) or related medications may be quite effective for heartburn related to esophageal disease. Other medications, including metoclopramide (Reglan), prucalopride (Motegrity), and various antibiotics may be helpful for various intestinal problems caused by scleroderma.
• Bosentan (Tracleer), macitentan (Opsumit), ambrisentan (Letairis), epoprostenol (Flolan), treprostinil (Remodulin and others), iloprost (Ventavis), selexipag (Uptravi), riociguat (Adempas), sildenafil (Revatio), and tadalafil (Adcirca) may be at least somewhat effective for pulmonary hypertension. Many of these drugs also may improve symptoms of Raynaud's phenomenon.
• ACE inhibitors, such as enalapril (Vasotec), lisinopril (Prinivil or Zestril), or captopril (Capoten), can reduce elevated blood pressure and may be an effective treatment for severe kidney disease (called scleroderma renal crisis).
• Calcium-channel blockers, including amlodipine (Norvasc), nifedipine (Procardia, Adalat), and diltiazem (Cardizem), may improve symptoms of Raynaud's phenomenon. Other options include fluoxetine (Prozac), hydralazine (Apresoline), prazosin (Minipress), nitroglycerin cream or ointment, losartan (Cozaar), sildenafil (Viagra), and tadalafil (Cialis).

Other immune-suppressing medications that are sometimes recommended for scleroderma include azathioprine, tocilizumab, or rituximab. A promising experimental therapy for severe disease is high-dose immunosuppression with stem cell treatment, although serious side effects (including overwhelming infection and heart problems) have limited its use. When lung or kidney disease is severe and does not respond to treatment, organ transplant may be recommended.

Many patients find relief from Raynaud's phenomenon with nonmedication approaches such as limiting their exposure to cold and by wearing warm clothing, especially mittens and socks. Others find that regular exercise, physical therapy, skin massage, and moisturizing ointments help skin symptoms. If dry skin becomes ulcerated and infected, antibiotics may be needed. In addition, patients with Raynaud's phenomenon are urged not to smoke and to avoid street drugs and certain prescription drugs, including beta blockers, amphetamines, cocaine, and ergotamine (Ergomar and other brand names).

When to call a professional

Call your doctor if you think that you are experiencing episodes of Raynaud's phenomenon or other symptoms of scleroderma, especially if you are a woman of childbearing age.

Prognosis

While many people with scleroderma live long, full lives, the death rate is increased by up to eight times for diffuse disease and two times for limited disease. Pulmonary hypertension and diffuse skin disease are risk factors for poor prognosis. However, longevity in this illness seems to be improving over time. Its rarity and variability make it difficult to accurately predict the prognosis in an individual with scleroderma.

Additional info

American College of Rheumatology
https://www.rheumatology.org/

National Institute of Arthritis and Musculoskeletal and Skin Diseases
https://www.niams.nih.gov/

Scleroderma Foundation
https://www.scleroderma.org/

Scleroderma Research Foundation
https://www.sclerodermaresearch.org