Systemic scleroderma

Synonyms

6

Overview

Systemic scleroderma is an autoimmune disorder that affects the skin and internal organs. Autoimmune disorders occur when the immune system malfunctions and attacks the body's own tissues and organs. The word "scleroderma" means hard skin in Greek, and the condition is characterized by the buildup of scar tissue (fibrosis) in the skin and other organs. The condition is also called systemic sclerosis because the fibrosis can affect organs other than the skin. Fibrosis is due to the excess production of a tough protein called collagen, which normally strengthens and supports connective tissues throughout the body.

The signs and symptoms of systemic scleroderma usually begin with episodes of Raynaud phenomenon, which can occur weeks to years before fibrosis. In Raynaud phenomenon, the fingers and toes of affected individuals turn white or blue in response to cold temperature or other stresses. This effect occurs because of problems with the small vessels that carry blood to the extremities. Another early sign of systemic scleroderma is puffy or swollen hands before thickening and hardening of the skin due to fibrosis. Skin thickening usually occurs first in the fingers (called sclerodactyly) and may also involve the hands and face. In addition, people with systemic scleroderma often have open sores (ulcers) on their fingers, painful bumps under the skin (calcinosis), or small clusters of enlarged blood vessels just under the skin (telangiectasia).

Fibrosis can also affect internal organs and can lead to impairment or failure of the affected organs. The most commonly affected organs are the esophagus, heart, lungs, and kidneys. Internal organ involvement may be signaled by heartburn, difficulty swallowing (dysphagia), high blood pressure (hypertension), kidney problems, shortness of breath, diarrhea, or impairment of the muscle contractions that move food through the digestive tract (intestinal pseudo-obstruction).

There are three types of systemic scleroderma, defined by the tissues affected in the disorder. In one type of systemic scleroderma, known as limited cutaneous systemic scleroderma, fibrosis usually affects only the hands, arms, and face. Limited cutaneous systemic scleroderma used to be known as CREST syndrome, which is named for the common features of the condition: calcinosis, Raynaud phenomenon, esophageal motility dysfunction, sclerodactyly, and telangiectasia. In another type of systemic scleroderma, known as diffuse cutaneous systemic scleroderma, the fibrosis affects large areas of skin, including the torso and the upper arms and legs, and often involves internal organs. In diffuse cutaneous systemic scleroderma, the condition worsens quickly and organ damage occurs earlier than in other types of the condition. In the third type of systemic scleroderma, called systemic sclerosis sine scleroderma ("sine" means without in Latin), fibrosis affects one or more internal organs but not the skin.

Approximately 15 percent to 25 percent of people with features of systemic scleroderma also have signs and symptoms of another condition that affects connective tissue, such as polymyositis, dermatomyositis, rheumatoid arthritis, Sjögren syndrome, or systemic lupus erythematosus. The combination of systemic scleroderma with other connective tissue abnormalities is known as scleroderma overlap syndrome.

Symptoms

Some types of scleroderma affect only the skin, while others affect the whole body.

  • Localized scleroderma usually affects only the skin on the hands and face. It develops slowly, and rarely, if ever, spreads throughout the body or causes serious complications.
  • Systemic scleroderma, or sclerosis, may affect large areas of skin and organs such as the heart, lungs, or kidneys. There are two main types of systemic scleroderma: Limited disease (CREST syndrome) and diffuse disease.

 Skin symptoms of scleroderma may include:

  •  Fingers or toes that turn blue or white in response to hot and cold temperatures (See: Raynaud's phenomenon)
  •  Hair loss
  •  Skin hardness
  •  Skin that is abnormally dark or light
  •  Skin thickening, stiffness, and tightness of fingers, hands, and forearm
  •  Small white lumps beneath the skin, sometimes oozing a white substance that looks like toothpaste
  •  Sores (ulcers) on the fingertips or toes
  •  Tight and mask-like skin on the face

 Bone and muscle symptoms may include:

  • Joint pain
  • Numbness and pain in the feet
  • Pain, stiffness, and swelling of fingers and joints
  • Wrist pain

Breathing problems may result from scarring in the lungs and can include:

  •  Dry cough
  •  Shortness of breath
  •  Wheezing

Digestive tract problems may include:

  • Bloating after meals
  • Constipation
  • Diarrhea
  • Difficulty swallowing
  • Esophageal reflux or heartburn
  • Problems controlling stools (fecal incontinence)

Other Symptoms:

  • Abnormality of the gastric mucosa
  • Acrocyanosis
  • Arthralgia
  • Arthritis
  • Atypical scarring of skin
  • Autoimmunity
  • Chest pain
  • Chondrocalcinosis
  • Edema
  • Hyperkeratosis

Causes

The exact, underlying cause of systemic sclerosis is unknown. The cause appears to involve some injury to the cells that line blood vessels, resulting in excessive activation of dermal connective tissue cells, called fibroblasts. Fibroblasts normally produce collagen and other proteins. Build-up of collagen in the skin and other organs causes the signs and symptoms of the condition.

Researchers have identified variations in several genes that may influence the risk of developing systemic scleroderma. The most commonly associated genes belong to a family of genes called the human leukocyte antigen (HLA) complex. The HLA complex helps the immune system distinguish the body's own proteins from proteins made by foreign invaders (such as viruses and bacteria). Each HLA gene has many different normal variations, allowing each person's immune system to react to a wide range of foreign proteins. Specific normal variations of several HLA genes seem to affect the risk of developing systemic scleroderma.

It is suspected that scleroderma may develop from a variety of factors, which may include:

  • Abnormal immune or inflammatory activity
  • Genetic susceptibility: while no specific genes are thought to cause scleroderma, certain genes (or combination of genes) may increase a person's risk to be affected. However, the condition is not passed directly from parents to children.
  • Environmental triggers: suspected triggers may include infections; injury; drugs (e.g. vitamin K, cocaine, penicillamine, appetite suppressants and some chemotherapeutic agents); and chemicals (e.g. silica, organic solvents, pesticides, aliphatic hydrocarbons and epoxy resin).
  • Hormones: because women develop scleroderma more often than men, researchers suspect that hormones may play a role. However, the role of female hormones has not been proven.

Widespread scleroderma can also occur in association with other autoimmune diseases, including systemic lupus erythematosus and polymyositis.

Most cases of systemic scleroderma are sporadic and are not inherited. This means the condition typically occurs in people with no history of the condition in their family. Some people with systemic scleroderma have relatives with other autoimmune disorders, and a few cases of the condition have been reported to run in families. However, the condition is not caused by a single gene that is passed on to offspring. Multiple genetic and environmental factors likely interact to put someone at an increased risk to develop the condition.

Prevention

There is no known prevention. Reducing your exposure to silica dust and polyvinyl chloride may lower your risk for this disease.

Diagnosis

Because systemic scleroderma is not caused by a mutation in any one specific gene, clinical genetic testing to confirm a diagnosis or identify a "carrier" is not currently available. Even if someone is known to carry a version of a gene that may make them susceptible to the condition, it does not mean they will definitely develop the condition.

The health care provider will perform a physical exam. The exam may show hard, tight, thick skin.

Your blood pressure will be checked. Scleroderma can cause severe inflammation of small blood vessels, such as those in the kidneys. Problems with your kidneys can lead to high blood pressure.

Blood tests may include:

  • Antinuclear antibody (ANA) panel
  • Antibody testing
  • ESR (sed rate)
  • Rheumatoid factor

Other tests may include:

  • Chest x-ray
  • CT scan of the lungs
  • Echocardiogram
  • Urinalysis
  • Tests to see how well your lungs and gastrointestinal (GI) tract are working
  • Skin biopsy

Prognosis

Some people with scleroderma have symptoms that develop quickly over the first few years and continue to get worse. However, in most patients, the disease slowly gets worse.

People who only have skin symptoms have a better outlook. Widespread (systemic) scleroderma can damage the heart, kidney, lungs, or GI tract, which may cause death.

Lung problems are the most common cause of death in patients with scleroderma.

Treatment

There is no specific treatment for scleroderma.

Your doctor will prescribe medicines and other treatments to control your symptoms and prevent complications.

Medicines used to treat scleroderma include:

  • Power anti-inflammatory medicines called corticosteroids
  • Immune-suppressing medications such as methotrexate and Cytoxan
  • Nonsteroidal anti-inflammatory drugs (NSAIDs)

Other treatments for specific symptoms may include:

  • Medicines for heartburn or swallowing problems
  • Blood pressure medications (particularly ACE inhibitors) for high blood pressure or kidney problems
  • Light therapy to relieve skin thickening
  • Medicines to improve breathing
  • Medications to treat Raynaud's phenomenon

Treatment usually also involves physical therapy.

Resources

  • NIH
  • Genetic Home Reference