Limited scleroderma (CREST syndrome)

Introduction

Limited scleroderma, or CREST syndrome, is a condition affecting your connective tissue. Connective tissue is a kind of cellular glue — it's found outside your cells and supports and gives form to tissues and organs throughout your body.

Because it's so pervasive and varied, connective tissue can give rise to a multitude of disorders. One is limited scleroderma, previously known as CREST syndrome. Experts who treat limited scleroderma have mostly stopped using the term "CREST syndrome," because it doesn't accurately reflect all aspects of the disorder. While limited scleroderma usually affects your skin and blood vessels, it can also affect your digestive tract and can cause serious heart and lung disorders.

For some people, the problems caused by limited scleroderma are minor. For others, limited scleroderma can be life altering and even fatal. The disease has no known cure, and treatments focus on managing symptoms and preventing serious complications.

Signs and symptoms

There are two forms of scleroderma: systemic and localized. Systemic scleroderma, also known as systemic sclerosis, is a disorder that leads to thickening, hardening and tightening of your skin and connective tissue. In localized scleroderma, the damage is confined to your skin and the tissue just beneath it. But systemic sclerosis is more far-reaching, affecting blood vessels and internal organs as well.

Systemic scleroderma is broadly divided into subsets based on the degree of skin involvement:

• Diffuse scleroderma. This form of the disease is marked by thickening of the skin of the extremities and trunk. Involvement of the esophagus, intestine, lungs, heart and kidneys can result in serious complications.
• Limited scleroderma. This form usually affects skin only on the lower arms and legs, neck and face. Limited scleroderma tends to progress much more slowly than the diffuse type does. CREST syndrome is associated with the limited form of the disease — so much so that the terms were used interchangeably, though limited scleroderma is the term doctors are now more likely to use.

Signs and symptoms of limited scleroderma (CREST syndrome)
CREST has a distinct set of characteristics that give the syndrome its acronymic name. These characteristics include:

• Calcinosis. In this condition, tiny calcium deposits develop under your skin, mainly on your elbows, knees and fingers, although they can occur almost anywhere, including your legs and spine. You can see and feel these deposits, which sometimes may be tender, drain a chalky fluid or become infected.

• Raynaud's phenomenon. For many people with limited scleroderma, Raynaud's phenomenon, which causes numbness, pain and color changes in your fingers, is the first indication of the disease. Often appearing years before other CREST signs and symptoms, Raynaud's occurs when small blood vessels (capillaries) spasm in response to cold or emotional stress, blocking the flow of blood.

  Although not everyone with Raynaud's experiences the same signs and symptoms during an attack, the areas of affected skin generally turn white before becoming blue, cold and numb. When circulation improves, the skin usually reddens and may throb or tingle. The various changes begin at your fingertips and move toward your wrists, with a clear line of demarcation between normal and affected tissue.

  Attacks of Raynaud's may last from a few minutes to several hours and tend to become worse over time. In severe cases, lack of circulation can lead to sores or ulcers on your fingers or toes.

• Esophageal dysfunction. People with limited scleroderma commonly experience problems with their esophagus — the tube that connects the mouth and stomach. Poor functioning of the muscles in the upper and lower esophagus can make swallowing difficult and allow stomach acids to back up into the esophagus, leading to heartburn, inflammation and scarring of esophageal tissues.

• Sclerodactyly. Thick, hardened skin (sclerodactyly) is the hallmark of scleroderma. In the diffuse form of the disease, skin thickening usually develops quickly and affects much of your body, including your hands, face, arms, legs, chest and abdomen. In people with limited scleroderma, however, skin changes usually occur gradually and affect only the lower arms and legs, including fingers and toes, and sometimes the face and throat.

  At first the affected areas simply look puffy, especially in the morning, but over time the skin thickens and turns shiny as it stretches tightly over the underlying bone. Eventually, you may find that hardened skin makes it difficult to bend or straighten your fingers.

  Tightening of your facial skin sometimes can make speaking more difficult, but more often, the changes are cosmetic — tight skin can make your mouth smaller and narrower and thin your upper lip. Although these changes can't be prevented, plastic surgery may provide improvement.

• Telangiectasia. This is a collection of dilated blood vessels on the surface of your skin, usually so closely packed that they appear as solid red marks rather than as individual vessels. Although telangiectasia can develop almost anywhere, people with limited scleroderma are most likely to have them on the face, hands, lips and lining of the intestinal tract.

You don't have to have all of the above signs and symptoms to be diagnosed with limited scleroderma. Some doctors believe only two of the five are necessary for a diagnosis. This means that many variations on the general CREST theme can exist — for example:

• CRST, which means you have all the signs and symptoms of CREST except esophageal problems
• REST, which is CREST without calcinosis

Additionally, people with limited scleroderma may also experience interstitial lung disease and high blood pressure in the lungs (pulmonary hypertension).

Some people also have what's known as "overlap disease," in which limited scleroderma occurs in conjunction with other autoimmune conditions, such as polymyositis, lupus and rheumatoid arthritis.

Causes

Connective tissue is an extensive and complex structural scaffold that surrounds and supports cells. It acts as a kind of mesh that holds your body together, rather like the wire framework on a screen, with your cells filling in the screen's holes.

Connective tissue, which is found in your skin, bones, ligaments and tendons, is made up of two major proteins — collagen and elastin. Collagen is particularly important: It's the most abundant protein in your body and the main component of ligaments and tendons. It also helps make your skin elastic and resilient.

In people with limited scleroderma, the immune system appears to stimulate cells called fibroblasts to produce excess amounts of collagen. Normally, fibroblasts synthesize collagen to help heal wounds, but in this case, the protein is produced even when it's not needed, forming thick bands of connective tissue around the cells of your skin, blood vessels and in some cases, your internal organs.

Although an abnormal immune system response and the resulting production of excess collagen appears to be the main cause of limited scleroderma, researchers suspect that other factors may play a role, including:

• Genetic makeup. In rare cases, it appears that genetic defects may make people more susceptible to scleroderma.

• Pregnancy. Normally, a predisposition to certain diseases is passed from parent to child. But in an ironic genetic twist, women who have been pregnant may be more prone to limited scleroderma because of cells they receive from their fetuses. These cells, which pass from a baby to its mother through the placenta, can linger in the mother's body for years after a child's birth.

  Because the mother's immune system perceives the cells as foreign substances, it may initiate a response in which immune cells attack healthy tissue. Exactly how and even if this process occurs isn't known, but researchers are continuing to study the potential link between fetal cells and scleroderma.

• Hormones. Women are far more likely to develop limited scleroderma than men are, especially during their childbearing years. Scientists suspect that the female hormone estrogen may be involved, but haven't yet established a clear link.
• Environmental factors. Exposure to viral infections and some environmental toxins may trigger scleroderma in people who are genetically predisposed to develop the disease.

Risk factors

Because it's not entirely clear just what causes limited scleroderma, all the risk factors for the disease may not yet be known. Researchers do know that women, and black women in particular, are far more likely to develop the disease than men are. The gender disparity may be linked to the effects of female hormones or to fetal cells acquired during pregnancy.

Other factors that may make you more susceptible to limited scleroderma include:

• Age. Most people who develop limited scleroderma are between 30 and 65 years old.
• Race. Choctaw American Indians and people of Thai descent also have higher rates of limited scleroderma than other races.
• Genetic factors. If someone in your family has an autoimmune disease — that is, a disease in which the immune system turns against the body's own tissues — you have an increased risk of developing limited scleroderma.
• Exposure to toxins. Toxic substances, such as polyvinyl chloride, benzene, silica and trichloroethylene, may trigger scleroderma in people with a genetic predisposition to the disease.

When to seek medical advice

See your doctor if you're experiencing any of the early signs of CREST — numbness, pain or color changes in your fingers, or gradual thickening or tightening of your skin. It's important to establish a diagnosis before the disease progresses and to determine if the condition has affected your internal organs.

Screening and diagnosis

Like other unusual and complex disorders, limited scleroderma can be difficult to diagnose. Signs and symptoms vary widely and often resemble those of other connective tissue and autoimmune diseases. Further complicating matters is that limited scleroderma sometimes occurs with other conditions.

As if that weren't confusing enough, limited scleroderma can often look like undifferentiated connective tissue disease, a catch-all disorder for people who have signs and symptoms of several related connective tissue diseases but who don't fall into any clear diagnostic category. It may take years to reach a diagnosis in such cases.

Getting to a diagnosis
To help diagnose limited scleroderma, your doctor will take a complete medical history and perform a physical exam, looking especially for changes in the texture, color and appearance of your skin. Sometimes doctors take a small sample of skin (biopsy) that's then examined under a microscope in a laboratory. But although biopsies can be helpful, they can't definitively diagnose limited scleroderma or even distinguish between localized and systemic scleroderma.

You may also have laboratory tests to look for antibodies that are frequently found in the blood of people with scleroderma, especially the anti-centromere antibody, which occurs in most people with limited scleroderma. Yet even this isn't definitive because not everyone with limited scleroderma has these antibodies.

In addition to tests that may help diagnose limited scleroderma itself, your doctor may recommend additional tests to identify any lung, heart or gastrointestinal complications.

Complications

The visible signs of limited scleroderma — tight, thick skin on your fingers, hands and face — can affect the way you feel about your appearance, make everyday tasks such as opening a jar or shaving more difficult, and even affect your speech. But the most serious complications tend to occur beneath your skin. Some of those complications include:

• Gastrointestinal problems. Although limited scleroderma can affect tissue anywhere along your digestive tract, damage to your esophagus is the most common gastrointestinal complication. Changes in the functioning of esophageal muscles can cause difficulty swallowing and chronic heartburn, which in turn can lead to Barrett's esophagus, a serious pre-malignant condition, and to an increased risk of esophageal cancer.

  When limited scleroderma affects your intestine, you may develop constipation or diarrhea, bloating after meals, and gas. More severe tissue damage can affect your ability to absorb nutrients from your food, leading to weight loss and malnutrition.

• Digital ulcers. Severe Raynaud's phenomenon can obstruct blood flow to your extremities and may cause ulcers of the fingers and toes. These ulcers can be difficult to heal. Additionally, abnormal or narrowed blood vessels combined with severe Raynaud's phenomenon can lead to gangrene of fingers or toes, which may require amputation.

• Lung damage. Excess collagen can cause interstitial lung disease and scarring of the tissue between the air sacs in your lungs. Scarring of the lung tissue is known as pulmonary fibrosis, and it interferes with the transfer of oxygen from your lungs to your bloodstream, leading to breathing problems and a reduced capacity for exercise.

  Limited scleroderma can also cause high blood pressure in the arteries in your lungs (pulmonary hypertension), a progressive and potentially fatal condition. Pulmonary hypertension is a more frequent complication than is interstitial lung disease for people with limited scleroderma.

  Both pulmonary hypertension and interstitial lung disease may not cause symptoms until they're advanced and severe. Possible signs and symptoms of these complications include shortness of breath with exertion without chest pain or a dry cough.

• Heart problems. Scarring of heart tissue can lead to abnormal heart rhythms (arrhythmias) and in rare cases to an inflamed heart muscle (myocarditis).
• Arthritis and arthralgia. Although arthritis is far less likely to occur with limited scleroderma than it is with diffuse scleroderma, many people with limited scleroderma experience joint pain (arthralgia) without having the inflammation that characterizes arthritis.
• Dental problems. Severe tightening of facial skin can cause your mouth to become smaller and narrower (microsomia), putting you at risk of serious dental problems. A measurably smaller mouth makes it hard to brush your teeth or have them professionally cleaned, increasing your risk of tooth decay. And because people with limited scleroderma often don't produce normal amounts of saliva, the risk of decay increases even more. In addition, acid reflux can destroy tooth enamel, and changes in gum tissue may cause your teeth to become loose or even fall out.
• Sicca syndrome. Affecting about a third of people with limited scleroderma, sicca syndrome causes dry eyes, a dry mouth and sometimes dry airways.
• Depression and anxiety. Living with a chronic illness can be difficult. As many as two-thirds of people with limited scleroderma develop anxiety at some point and slightly less than half will experience depression.

Treatment

Limited scleroderma has no known cure, but the signs and symptoms of the disease can often be effectively managed using both medical and nonmedical therapies. Success rates vary from person to person.

Some medications used to treat limited scleroderma may not have been specifically approved for that purpose by the Food and Drug Administration (FDA). This is known as "off-label" use and is not an uncommon practice, especially for rarer diseases. Discuss the benefits and risks of any treatment with your doctor.

Treatments for the various aspects of limited scleroderma include:

• Calcinosis. Doctors have tried a number of drugs to treat calcium deposits with little success, although the antibiotic minocycline can sometimes reduce inflammation and ulcers in severe calcinosis. Very large or painful calcium deposits are sometimes surgically removed. A few doctors report that treatment with a carbon dioxide laser may be effective at relieving symptoms and preventing deposits from returning.

• Raynaud's phenomenon. Although drug and even surgical options exist for treating Raynaud's, self-care measures are often highly successful and are usually tried first. These measures include keeping your body's core temperature elevated and protecting your hands and feet from cold, both indoors and out. Biofeedback, a technique that teaches you to control certain body responses; autogenics training, a type of progressive muscle relaxation; and hypnosis may help improve blood flow to the extremities.

  If these methods fail, your doctor may prescribe a vasodilator, such as a long-acting calcium channel blocker, a drug that can open small blood vessels and increase circulation. Side effects, especially in the short-acting versions of the drug, include swelling, headache, dizziness and increased acid reflux.

  Topical nitroglycerin, which can help heal skin ulcers, is another possible treatment for Raynaud's, though you should not apply it directly to the ulcer. Bosentan (Tracleer), which is used to treat pulmonary hypertension, has been reported to enhance healing of digital ulcers in people with scleroderma and its effectiveness in preventing ulcers is being studied. Bosentan hasn't been approved by the FDA for this indication, however.

• Esophageal dysfunction. Certain lifestyle changes can help reduce problems with swallowing and especially with acid reflux. These measures include eating small meals that emphasize soft-textured foods; waiting two to three hours after a meal before lying down; and avoiding alcohol, caffeine, chocolate and spicy foods, which can aggravate heartburn. Your doctor may also suggest an H-2 blocker, such as famotidine (Pepcid), cimetidine (Tagamet) or ranitidine (Zantac), or a proton pump inhibitor, such as esomeprazole (Nexium), omeprazole (Prilosec) or lansoprazole (Prevacid), to help relieve pain and burning by reducing the production of stomach acid.
• Sclerodactyly. For many people with limited scleroderma, an altered appearance may be the most challenging aspect of the disease. In the past, treatments for tight, thick skin were largely superficial — moisturizers for dryness and cortisone creams for inflammation. Light therapy (phototherapy) may prove more therapeutic. Researchers are investigating the use of ultraviolet light to treat scleroderma-related skin problems. Ultraviolet light works by breaking down collagen or by decreasing the production of collagen. In some cases, plastic surgery may be an option.
• Telangiectasia. Dilated capillaries can be hidden with makeup or reduced or eliminated with laser therapy.

• Lung complications. Interstitial lung disease and pulmonary hypertension are the most serious manifestations of limited scleroderma. These areas are also the focus of a great deal of clinical research, and numerous advances in treatment have been made.

  One such advance is the use of cyclophosphamide (Cytoxan) for the treatment of scleroderma-related interstitial lung disease. A 2006 study found that the use of cyclophosphamide resulted in a very modest improvement in lung function compared with placebo. The long-term benefits and side effects of treatment with cyclophosphamide in those with scleroderma are unknown.

  In addition, several medications are available for treating pulmonary hypertension, including epoprostenol (Flolan), iloprost (Ventavis), treprostinil (Remodulin), bosentan (Tracleer) and sildenafil (Revatio). Epoprostenol, iloprost, treprostinil and sildenafil work by opening up the blood vessels in your lungs. Bosentan is an endothelin receptor antagonist, which means it counteracts the effect of endothelin, a substance that causes blood vessels to constrict and narrow.

  There's a risk of serious liver complications with bosentan. If you're taking this medication, your doctor will want to monitor your liver function monthly.

Self-care

Limited scleroderma can be frustrating — it's difficult to diagnose, has no known cure, and its wide-ranging signs and symptoms tend to become progressively worse. Still, your own efforts can play a key role in managing your symptoms, preventing complications and making the disease easier to live with.

• Stay active. Regular exercise helps control your weight; reduces the risk of dozens of serious diseases including heart attack, stroke, diabetes and some cancers; relieves depression; and even helps reduce chronic pain. It can also boost the circulation in your hands and feet and reduce stress — crucial factors in managing Raynaud's phenomenon.

  If you have lung complications that affect your breathing, exercise is still important, although your doctor may recommend less strenuous activities such as walking or swimming. And if you have trouble with range of motion in your fingers, a physical or occupational therapist can suggest new ways to perform everyday activities or recommend assistive devices to make tasks more manageable.

• Don't smoke. If you smoke, talk to your doctor about the best ways to quit. Nicotine constricts your blood vessels, making Raynaud's phenomenon worse. Smoking can cause permanent narrowing of your blood vessels over time in addition to the damage that it causes to the lungs.

• Protect yourself from cold. Good circulation is essential for preventing the discomfort and complications of Raynaud's phenomenon. Although medications can help keep blood vessels open, you can take steps that may be equally if not more effective.

  First, protect your hands and feet from cold temperatures. Wear gloves or mittens outdoors when the weather is cool and indoors when you reach into the freezer or have your hands in cold water.

  But warm hands aren't enough — to keep blood vessels open, you also need to maintain your body's core temperature. In chilly weather, dress in layers and wear a hat or scarf, thermal socks, and well-fitting boots or shoes that don't cut off your circulation.

  Finally, consider biofeedback, relaxation exercises or hypnosis to help improve blood flow.

• Take care of your digestive tract. Because limited scleroderma can affect any part of your digestive system, you may experience problems ranging from heartburn to diarrhea and malnutrition. You can help minimize acid reflux by eating small, frequent meals, by avoiding spicy or fatty foods, chocolate, caffeine and alcohol, by not exercising immediately before or after eating, and by sitting upright for two or three hours after a meal.

  If you have difficulty swallowing, choose soft, moist foods and chew them well. Your doctor may recommend fiber supplements for constipation, antibiotics or over-the-counter remedies for diarrhea, and dietary supplements for malabsorption.

• Find ways to manage stress. Stress contributes to a host of diseases, and it's detrimental for people with Raynaud's because of its effect on circulation. No one approach or technique is right for every person, but many people have been helped by meditation, deep breathing, guided imagery or other relaxation techniques, by massage or by regular exercise. In addition, family ties, friendships and involvement in social activities can offer a psychological buffer against stress and help you cope better with illness.

• Keep your skin moist. Excess collagen destroys sweat and oil glands, leaving your skin stiff and dry. To help soften your skin, keep it as moist as possible. Bathe just once a day or every other day, and take short baths and showers, using warm rather than hot water. Less is more when it comes to washing your face, too. Although it may be difficult to break the habit of cleansing your face morning and evening, once a day should be enough to remove dirt and oil.

  Whenever you bathe, avoid harsh soaps and detergents. Instead choose cleansing creams or gentle skin cleansers and bath or shower gels with added moisturizers. Apply a rich oil-based moisturizer immediately after washing your hands or bathing, while your skin is still damp.

  It's important to moisturize your house, too, using a humidifier to increase moisture levels in your home.

• Practice good oral hygiene. If you have trouble brushing and flossing your teeth because of stiffness in your fingers and hands, ask your dentist or an occupational therapist about special toothbrushes and flossing devices. An occupational therapist can also recommend exercises that help keep your mouth more flexible. Be sure to have regular checkups and use any special rinses or toothpastes your dentist recommends.

  If your mouth is chronically dry, try drinking more water and sucking on ice chips or hard, sugarless candy. However, some artificial sweeteners such as sorbitol can cause diarrhea when consumed in large amounts, since they're not absorbed by the gastrointestinal tract. When these measures fail, your dentist may prescribe a medication to stimulate the flow of saliva.