Diagnosis:

There are no specific tests for scleroderma. The doctor may suspect scleroderma after taking a history of the symptoms and performing a physical examination. As part of this examination, the doctor does the following:

• Checks the skin for thickened and hardened areas. The major signs of scleroderma are hardening and thickening of the skin in any areas on the fingers and toes.
• Presses affected tendons and joints to detect crackling or grating sensations, which can indicate changes related to scleroderma beneath the skin.
• Examines the fingernails underneath a microscope. The doctor may find changes in capillaries that are characteristic of scleroderma or mixed connective tissue disease.

Tests for Antinuclear Antibodies

Tests may be done to detect immune factors called antinuclear antibodies (ANAs). Detecting specific types of ANAs may help diagnose scleroderma. ANA subtypes include the following:

• Rheumatoid factor, anti-single-stranded DNA, and antihistone antibodies are autoantibodies associated with scleroderma, but they are also common in other autoimmune disorders, such as rheumatoid arthritis and systemic lupus erythematosus. Some ANAs attack RNA or DNA, the genetic material in cells.
• Anti-RNA polymerase III, anti-topoisomerase I (also called anti-DNA topo 1) and anti-centromere antibodies (ACA) are also autoantibodies. Most patients with systemic scleroderma (but not localized scleroderma) have one or more of these autoantibodies. They do not appear at the same time, and seem related to different phases of the disease process. For example, anti-DNA topo 1 often occurs with diffuse skin scleroderma and lung complications. Anti-centromere antibodies usually occur with a less severe form of the disease.
• Higher-than-normal levels of autoantibodies to fibrillin 1, a protein found in muscle and other connective tissues, is more common in patients with both systemic and localized scleroderma. This autoantibody in localized scleroderma is more common in some ethnic groups (such as Japanese and Native Americans) than in others (Caucasians). It is not found in other autoimmune diseases.

These antibodies are also found in other rheumatologic disorders, so detecting them does not necessarily prove that a patient has scleroderma. At the same time, studies have found that specific antibodies are associated with specific aspects of the disease. Therefore, identifying their presence could help diagnose, treat, and monitor people with scleroderma. Here are a few examples:

• Anti-U1-RNP and anti U3-RNP are associated with muscle inflammation.
• ACA is commonly associated with pulmonary hypertension and vascular disease.
• TOPO is associated with pulmonary fibrosis.
• RNA Polymerase III (Pol 3) is rarely linked to severe interstitial fibrosis, although this autoantibody is strongly present in patients with kidney crisis.
• Patients with diffuse scleroderma who have Pol 3 have the best survival rates.

Diagnosing Systemic Complications

Diagnosing Lung Complications. Changes in the lungs may occur early in scleroderma lung disease, and prompt treatment is very important to prevent complications. For this reason, once a diagnosis is made, the doctor will check for lung changes in the following ways:

• Listen to the lungs through a stethoscope. Rales, a crackling sound at the base of the lungs as the patient breathes in, is a sign of pulmonary fibrosis, even if breath function is normal.
• Perform respiratory function tests to determine lung capacity.
• Take a chest x-ray (however, x-rays do not always find lung disease, especially in children).
• Have patients inhale nitric oxide to test the ability of blood vessels to open.
• Perform more extensive tests, such as high-resolution computed tomography (CT) scans and bronchoalveolar lavage, if there is a suspicion of severe lung scarring.

Newer tests showing promise in diagnosing lung complications include:

• The induced sputum test, which looks at cells taken from coughed-up phlegm
• A test that uses an inhaled chemical, technetium-labeled diethylenetriamine pentaacetate (99mTC-DTPA), to detect lung damage

Diagnosing Heart Complications. Patients with suspected heart complications should have the following tests:

• Electrocardiography (ECG): A test of the heart's electrical activity
• Echocardiography: A look at the beating heart through the use of sound waves
• Radionucleotide ventriculography: An evaluation of the working heart using a radioactive dye

Advanced imaging techniques, which provide a more detailed picture of the heart, may also be useful to determine the extent of heart complications in scleroderma patients.

Diagnosing Pulmonary Hypertension. Echocardiography is a noninvasive imaging technique for detecting pulmonary hypertension. (Noninvasive means that neither materials nor equipment are put into the body.) To confirm the diagnosis, doctors sometimes use an invasive procedure called right-heart catheterization. Right-heart catheterization involves the passage of a catheter (a thin flexible tube) into the right side of the heart to get diagnostic information about the heart.

Diagnosing Gastrointestinal (Digestive) Complications. Endoscopy may detect gastrointestinal problems. Endoscopy is an invasive procedure in which a tube is inserted down the esophagus. The tube contains a small camera and other instruments. Another diagnostic test is manometry, which measures the pressure that the muscles in the esophagus apply.

Electrogastrography (EGG) measures the electrical activity in muscles in the stomach, and may be an effective method for detecting stomach problems.

Diagnosing problems in growth of blood vessels. Capillaroscopy is the microscopic examination of blood vessels under the skin. It is now considered a useful tool for identifying problems with the growth of blood vessels, because more than 95% of patients will have some capillary abnormalities. Such problems can show the severity and progression of scleroderma. In a technique called nailfold capillaroscopy, the doctor places a drop of oil on the nailfold (the skin at the base of the fingernails), and then looks at the nailfold under a microscope for signs of changes in the capillaries. These changes may indicate a connective tissue disease such as scleroderma.

Ruling out Other Conditions

Other Autoimmune and Connective Tissue Disorders. Several other autoimmune conditions that affect connective tissue can strongly resemble, or occur together with, scleroderma. They include the following:

• Rheumatoid arthritis
• Systemic lupus erythematosus
• Polymyositis

Symptoms of such diseases may also include fever, arthritis, muscle aches, rash, and lung and heart problems.

Eosinophilic Fasciitis. Eosinophilic fasciitis is a muscle disorder that is known to occur after intense hard work. It can cause symptoms similar to scleroderma, including pain, swelling, and tenderness in the hands and feet, as well as skin thickening. The disorder can be ruled out with blood tests.

Although Raynaud's phenomenon occurs in most scleroderma patients, most of the time Raynaud's phenomenon by itself is not associated with more serious conditions. Following are other problems that might accompany or cause Raynaud's phenomenon:

• Other autoimmune connective tissue diseases
• Diabetes (patients with diabetes may develop Raynaud's phenomenon and other scleroderma-like symptoms)
• Certain drugs, including bleomycin, ergot derivatives (used for migraines), and methysergide
• Hereditary hemorrhagic telangiectasia (a very rare condition that may have skin changes similar to CREST syndrome)

• Repetitive stress injuries (particularly from vibrating tools)
• Hypothyroidism