CREST syndrome

(CHEST 2000; 117:584-587)

A 69-year-old nonsmoking woman with a history of CREST (calcinosis, Reynaud's phenomenon, esophageal motility disorders, sclerodactyly, and telangiectasia) syndrome presented with a chief complaint of dyspnea. The patient first noticed telangiectasias on her hands and face 20 years earlier and slowly developed tightness of the skin on her hands and face. Five years before admission, she was evaluated for symptoms of gastroesophageal reflux disease (GERD) and was found to have an esophageal stricture. Her symptoms responded well to stricture dilation and treatment with omeprazole and cisapride. She had no history or symptoms suggestive of aspiration. Serologic testing at that time showed an antinuclear antibody titer of [is greater than] 1:640 with a centromere pattern, negative Scl-70 antibodies, rheumatoid factor of 143 IU/mL, and erythrocyte sedimentation rate of 15 mm/h. The patient did well until 6 months prior to admission when she noticed dyspnea on exertion. She was evaluated by her primary care physician and was referred for further evaluation.

Physical Examination

The patient was afebrile, with a BP of 161/81 mm Hg, pulse of 70 beats/min, and respiratory rate of 20 breaths/min. The lungs were dear to auscultation and percussion bilaterally. The cardiac examination was normal. Sclerodactyly and telangiectasias were present over the dorsum of the hands, wrists, and the proximal phalanges.

Laboratory Findings

The chest radiograph is shown in Figure 1. An arterial blood gas analysis on room air showed a pH of 7.49, [PCO.sub.2], 25 mm Hg; [HCO.sub.3], 19 mEq/L; [PO.sub.2], 46 mm Hg, with oxygen saturation, 86%. Pulmonary function testing revealed the following: FVC, 2.53 L (89%); [FEV.sub.1], 1.78 L (77%); [FEV.sub.1]/FVC, 70%; total lung capacity, 5.10 L (102%); residual volume, 2.57 L (128%); and diffusing capacity of the lung for carbon monoxide, 4.9 mL/min/mm Hg (29%). A high-resolution CT scan is shown in Figure 2.

[Figures 1-2 ILLUSTRATION OMITTED]

What is the most likely diagnosis and what additional studies are indicated?

Diagnosis: Pulmonary hypertension secondary to the CREST syndrome.

DISCUSSION

Dyspnea affecting patients with collagen vascular diseases may be secondary to pulmonary parenchymal disease, airway involvement, or pulmonary vascular disease. Anemia, muscle weakness, diaphragmatic dysfunction, and cardiac involvement may also contribute to dyspnea in these patients. Some agents that are used to treat collagen vascular diseases, such as penicillamine, gold, methotrexate, and cytoxan, may also cause lung injury and dyspnea. Esophageal involvement, as occurs in CREST, leads to GERD. If untreated, GERD may lead to aspiration and consequent lung injury. The CREST syndrome, a variant of scleroderma, is rarely associated with airway or infiltrative disease. CREST can be associated with pulmonary fibrosis, but it has a particular propensity to cause pulmonary hypertension. Dyspnea and hypoxemia in a patient with CREST suggests pulmonary hypertension, but the CT scan can be misleading if it shows a mosaic pattern.

Three different processes may cause a mosaic pattern of lung attenuation: (1) patchy infiltrative disease (airspace filling); (2) diffuse small airway disease (ie, obliterative bronchiolitis), which causes patchy areas of air trapping and hyperlucency; or (3) patchy perfusion secondary to vascular disease. In each of the above pathophysiologic settings, alternating areas of light and dark on the CT are observed and the cause may not be obvious. In fact, one study has shown that although patchy infiltrative disease and airway obstructive disease are often correctly identified, vascular disease is almost invariably misclassified by experienced radiologists. Other findings on the CT scan may be helpful in distinguishing between these three processes (discussed below).

Sharply demarcated areas of heterogeneous attenuation in the pulmonary parenchyma that predominantly conform to the boundaries of secondary pulmonary lobules characterize the mosaic pattern. Small airways disease can cause a mosaic pattern of lung attenuation due to air trapping, and expiratory CT scans are frequently helpful in these patients to confirm the air trapping. The CT in airway disease is characterized by lung regions that retain air during exhalation and thus remain more lucent and show less decrease in volume than lung supplied by normal airways. The distribution of air trapping is often patchy and dependent on the level and the severity of airway obstruction. Lung regions that retain air show a decrease in caliber and number of pulmonary vessels compared with normal lung. In primary parenchymal disease (infiltrative process--airspaces filled with fluid, cells, or fibrosis), the CT attenuation of the affected lung increases compared with that of normal parenchyma. The caliber and number of vessels are not appreciably different between the normal and abnormal regions of lung. In vascular lung disease, which was suspected in our patient, regions of hyperemic (higher attenuation) lung mimic ground-glass infiltrates when seen adjacent to oligemic (lower attenuation) regions of lung. This pattern results from regional perfusion differences in the lung. The oligemic lung shows a decrease in the caliber and number of pulmonary vessels compared with normal or hyperemic lung.

A CT mosaic pattern of lung attenuation has many causes and therefore is difficult to interpret. Other findings on the CT scan may point toward the cause. A decrease in the caliber of blood vessels going to the "light" areas suggests airway disease or vasculopathy. An expiratory CT (often not obtained initially) may demonstrate air trapping, indicating airway disease. In addition, CT determination of pulmonary artery diameter may be helpful. In a recent series of 36 patients undergoing evaluation for pulmonary hypertension, a main pulmonary artery diameter (MPAD) [is greater than or equal to] 29 mm had a sensitivity of 87% and specificity of 89% for identifying patients with mean pulmonary artery pressures [is greater than or equal to] 20 mm Hg. Our patient's MPAD was 30 mm by CT scan, suggesting significant pulmonary hypertension. It should be pointed out that the above study did not take patient size or body surface area into account. A recent study proposed a scoring system for the degree of pulmonary disease in scleroderma patients. Ground-glass opacities were assigned a low score when evaluating interstitial disease. This system should not be applied to CREST patients with vascular diseases who have severe impairment, despite the CT findings.

The present patient's severe hypoxemia, clear chest radiograph, and nearly normal spirometric findings strongly suggested pulmonary vasculopathy, but the mosaic CT pattern was confusing. The additional CT features and an echocardiogram helped to clarify the situation. The Doppler echocardiogram showed a calculated right ventricular systolic pressure of 86 mm Hg; the right ventricle was dilated, and the left ventricle appeared normal. There was a moderate degree of tricuspid regurgitation. A biopsy procedure in this setting would be hazardous. Our patient received supplemental oxygen and supportive therapy for her severe pulmonary hypertension. Vasodilator therapy and anticoagulation are efficacious in the treatment of primary pulmonary hypertension, but their role in secondary pulmonary hypertension is still under investigation. Four weeks after evaluation, the patient suffered a cardiac arrest at home. She was taken to another hospital, where she died. An autopsy was not performed.

CLINICAL PEARLS

1. Pulmonary hypertension and/or pulmonary fibrosis should be considered in the differential diagnosis of patients with CREST who present with dyspnea. Pulmonary hypertension is more common in the CREST variant, while fibrosis is more common with scleroderma.

2. The mosaic attenuation pattern on the CT scan may be secondary to small airways disease, infiltrative disease, or pulmonary vasculopathy. Pulmonary function tests and other clinical data can help to differentiate pulmonary vasculopathy from small airways disease and infiltrative disease. Doppler echocardiography should be obtained to estimate pulmonary artery pressures.

3. Additional findings on the CT scan may point to the specific cause of a mosaic pattern. An increase in MPAD ([is greater than or equal to] 29 mm) is indicative of significant pulmonary hypertension.

SUGGESTED READINGS

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(*) From the Miami Valley Hospital, Medical Education Department, One Wyoming St, Dayton, OH 45409. Manuscript received April 20, 1999; revision accepted May 12, 1999.

Correspondence to: Ritu Madan, DO, Miami Valley Hospital, Medical Education Department, One Wyoming St, Dayton, OH 45409

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