CREST Syndrome

Posted by Elaine Moore May 11, 2006

A subset of patients with scleroderma, a systemic autoimmune disorder that causes fibrosis, can have several associated conditions and symptoms that are collectively known as CREST syndrome. CREST is an acronym for these related conditions, which include calcinosis, Raynaud phenomenon, esophageal changes that result in dysmotility, scleroderma-like changes or sclerodactyly, and telangiectasia. Two major forms of scleroderma exist: a diffuse cutaneous subtype and a limited cutaneous subtype, which is associated with a better survival rate than diffuse disease. Most patients with CREST syndrome have the limited cutaneous form of scleroderma. Limited cutaneous scleroderma generally causes thickening of the skin distal (toward the fingers) to the elbows but may include the face. Limited disease generally progresses slowly compared to the diffuse cutaneous form of scleroderma, which is more likely to affect internal organs.

Calcinosis is a condition in which calcium deposits or calcification occurs in soft tissues. These deposits can become painful and lead to ulcerations, which are prone to infection and inflammation. Calcinosis frequently affects the fingers, particularly the knuckle joints, but it can cause calcifications in the elbows and knees and in the spinal column, causing pain and compressing the nerves leading to the arms and legs. Calcium deposits usually occur near the skin surface but they can also occur in the deeper areas of tissue covering any of the body's bones or joints.

Patients with limited scleroderma are more likely to show signs of Raynaud's phenomenon early in the disease course, often before signs of scleroderma appear. Raynaud's phenomenon causes vascular changes that cause the distal extremities, primarily the hands and, less often the feet, to react with extreme sensitivity to cold temperatures and emotional stress. The skin in Raynaud's generally changes colors, reddening and blanching to white. The ears and nose may also be affected. Vascular changes are suspected of also contributing to the development of scleroderma. During episodes of Raynaud's the affected tissue, which may feel painful or numb, feels cold although adjacent tissue remains warm. Raynaud's phenomenon can also occur as a distinct phenomenon with no association to scleroderma or any other autoimmune disorder.

Esophageal dysmotility is a condition in which the esophagus develops erosive changes that interferes with its normal movement. Patients with this condition can have difficulty swallowing and experience heartburn. Esophageal changes in scleroderma can also progress to esophageal adenocarcinoma or affect the lungs, causing diminished pulmonary function.

Sclerodactyly refers to skin thickening primarily affecting the fingers and toes. Thickening in scleroderma occurs in three distinct phases. At first the fingers and toes experience edema, appearing puffy and swollen. Pain and stiffness are common in this phase, which usually lasts several months but occasionally can persist for several years. In the second phase, which is the indurative phase, the skin appears to thicken, becoming shiny and tight as if it is being stretched over bone. Skin creases disappear and the skin often appears reddened or burnt. This phase continues for many years. In the third phase, which occurs late in the disease course, the skin becomes fragile and lax as it begins to atrophy. Although the areas distal to the knees and elbows show the greatest involvement, the skin of the face and neck may also be affected. When the face is affected, the skin near the mouth and over the forehead may appear stretched causing the lips to appear thinner and furrows or puckering to appear around the mouth.

Telangiectasia is a condition causing multiple dilated blood vessels or spider veins. The skin on the face, upper trunk and hands is primarily affected, although telangiectases can occur on mucosal surfaces, such as the inner lips and gastrointestinal tract, where they may cause bleeding.

Most patients with CREST syndrome also have musculoskeletal pain, neurologic changes causing carpal tunnel syndrome, eye and mouth dryness, and weakness of the proximal muscles of the thighs and shoulder girdle. And up to 25 percent of patients also show evidence of pulmonary hypertension, which can cause shortness of breath and couch. Fibrosis can also affect tissue in the heart and kidneys causing cardiac arrhythmias and renal failure.

Lab changes in CREST syndrome are similar to those seen in patients with limited cutaneous scleroderma. The ANA test is positive, showing a pattern of anticentromere antibodies, in 50-90 percent of patients. Antibodies to Scl-70 are usually negative in limited scleroderma and positive in diffuse scleroderma. In patients with CREST syndrome, the platelet count, erythrocyte sedimentation rate, and C-reactive protein level are frequently elevated. Plain radiographic imaging tests are used to determine the presence of calcinosis. Treatment varies depending on the predominant symptoms but primarily consists of immunosuppressants such as methotrexate and cyclosporine, and medications to manage pain such as Neurontin.