CREST Syndrome Workup

Updated: Oct 05, 2020
  • Author: Jeanie C Yoon, MD; Chief Editor: Dirk M Elston, MD  more...
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Laboratory Studies

Laboratory studies are as follows:

  • ANAs: Limited scleroderma is associated with an early rise in ANA levels, particularly of the immunoglobulin G3 subclass. The overall sensitivity of ANA in systemic sclerosis is 85%, while the specificity is approximately 54%. Serial testing of ANAs to monitor the progress of disease is not currently recommended. [55]

  • Anticentromere antibodies: These are found in approximately 50-90% of patients with limited forms of scleroderma; Anticentromere antibodies are present in 82-96% of patients with the CREST variant. The specificity of this test is 95%. [56]  Anti-Scl-70 (anti-topoisomerase I) antibody is associated with diffuse scleroderma, early internal organ involvement, and a worse prognosis. Perform this laboratory test early in the course of the patient's presentation to determine if the patient is at risk for this course of scleroderma. Nonspecific indicators of inflammation (eg, mild leukocytosis, normocytic-normochromic anemia, thrombocytosis, elevated erythrocyte sedimentation rate, elevated C-reactive protein) are rare but may be present in persons with limited scleroderma. [57]

  • Calcinosis: Evaluate serum calcium and phosphorus levels to exclude a metabolic disturbance; however, calcinosis resulting from limited scleroderma is not associated with calcium or phosphorus abnormalities.

  • Raynaud phenomenon: The presence of ANA predicts the development of connective-tissue disease. The positive and negative predictive values of ANA values by immunofluorescence are 65% and 93%, respectively.

  • Esophageal dysmotility: Patients who are positive for ANAs and anticentromere antibodies while also being negative for anti-Scl70 antibody appear to have more esophageal involvement. [58]

  • Sclerodactyly: A thyrotropin level may help exclude the presence of thyroid disease as another potential cause of edematous or thickened skin.

  • Telangiectasia: No laboratory data are necessary.


Imaging Studies

Imaging studies are as follows:

  • Calcinosis: The diagnosis of calcinosis (suspected based on physical examination finding of palpable, hard, subcutaneous nodules) is confirmed with plain radiographs demonstrating dermal or subcutaneous radiodense deposits. Computed tomography and bone scanning (skeletal scintigraphy with diphosphate compounds) are more sensitive for identifying calcinosis when plain radiography findings are normal. [59]  Videodermatoscopy may also be a useful tool for diagnosing dystrophic calcifications such as those resulting from CREST syndrome; however, it is not yet widely used. [60]

  • Raynaud phenomenon: Digital ischemia and/or infarction secondary to Raynaud disease may prompt Doppler ultrasonography or angiography to identify anatomic occlusive disease, which may be amenable to angioplasty or bypass surgery.

  • Esophageal dysmotility: Multiple modalities are available to evaluate esophageal dysmotility. The least invasive evaluation involves radiologic barium studies with attention to the esophagus (cine-esophagram). Findings include dilatation with decreased or absent peristalsis in the distal esophagus, indicating advanced disease. Esophageal stricture and ulcerations indicate late findings of erosive esophagitis. The best use of a barium swallow is to exclude a stricture when the patient reports dysphagia. Esophageal transit time can be demonstrated by fluoroscopy, but this is not clinically useful. Radionuclide scanning is specific for gastroesophageal reflux and pulmonary aspiration, but it is expensive and is not sensitive.

  • Sclerodactyly: No imaging studies are necessary.

  • Telangiectasia: No imaging studies are necessary for cutaneous telangiectasia.

  • Cough or fatigue: If patients have cough or fatigue, perform transthoracic echocardiography to look for pulmonary hypertension. More advanced pulmonary hypertension may demonstrate signs of right-sided heart enlargement on chest radiographs.


Other Tests

Other tests that may be needed are as follows:

  • Raynaud phenomenon: Research tools, such as strain plethysmography, laser Doppler flowmetry, thermography, or finger systolic blood pressure, are not useful clinically for diagnosis, monitoring disease progression, or monitoring response to treatment.

  • Esophageal dysmotility: Esophageal manometry is highly sensitive for abnormal motility. Findings include diminished or absent distal peristalsis. LES pressure often is diminished. Manometry is fairly simple and inexpensive; abnormal results predict the development of erosive esophagitis, and findings are more likely to be positive in CREST syndrome patients. [61]  Twenty-four–hour pH monitoring is greater than 90% sensitive for the presence of gastroesophageal reflux; however, this test is more cumbersome and expensive. Esophagogastroduodenoscopy can identify the gross or histologic presence of esophagitis and the complications of esophagitis (eg, ulcers, stricture, Barrett esophagitis, adenocarcinoma). A biopsy is required to make the diagnosis of Barrett esophagitis or adenocarcinoma.