CREST syndrome

A 48-year-old man is evaluated in the office for progressive exertional dyspnea and a nonproductive cough. He is an ex-smoker (30-pack-years) and has gastroesophageal reflux disease, hypertension, and hypothyroidism. His medications are a proton pump inhibitor, an angiotensin-converting enzyme inhibitor, and thyroid hormone replacement.

On physical examination, blood pressure is 140/88 mm Hg, heart rate is 86/min, and respiration rate is 16/min. The skin on the hand is shown (Figure 27). He has localized areas of skin thickening on the arms and chest. Bibasilar mid- to late-inspiratory crackles are audible. There is no peripheral edema.

High-resolution CT scan of the chest shows reticular lines that are most prominent in the periphery of the lower lobes, accompanied by patchy, ground-glass opacities. Pulmonary function testing shows an FEV1 84% of predicted, an FVC 78% of predicted, and a DLCO 39% of predicted. Antinuclear antibody titer is 1:160.

Which of the following is the most likely diagnosis?
A Hypersensitivity pneumonitis
B Idiopathic pulmonary fibrosis
C Systemic sclerosis (scleroderma)
D Systemic lupus erythematosus


Key Points

* Lung disease is the most common cause of morbidity and mortality in patients with systemic sclerosis (scleroderma).
* In systemic sclerosis, both interstitial lung disease and pulmonary hypertension can develop (independently or together) and have an adverse effect on outcome.

Answer and Critique (Correct Answer = C)

In patients with systemic sclerosis (scleroderma), the lung is commonly involved, and lung disease is now the most common cause of scleroderma-related morbidity and mortality. Scleroderma is suggested by the typical skin findings. Pigment changes appear first, followed by skin thickening, digital pitting, and ulceration. Skin changes can extend proximally; patients with skin findings proximal to the elbows have diffuse scleroderma, as does this patient. In patients with scleroderma, both interstitial lung disease and pulmonary hypertension can develop (either independently or together) and have an adverse impact on outcome. Pulmonary disease can also be the initial clinical manifestation of scleroderma and is most commonly associated with diffuse scleroderma. Pulmonary hypertension is more commonly associated with limited scleroderma (CREST syndrome: calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia). A comprehensive history and physical examination are necessary to identify and confirm the underlying cause. In this patient, the presence of gastroesophageal reflux disease, sclerodactyly, proximal skin findings, late crackles on examination, abnormal high-resolution CT scan findings, a restrictive pulmonary physiologic defect, and the positive antinuclear antibody titer suggest the presence of scleroderma-related interstitial lung disease.

Idiopathic pulmonary fibrosis is an idiopathic interstitial pneumonia (i.e., it occurs in the absence of other explanations for the lung disease). The presence of features suggestive of scleroderma excludes this diagnosis. Various intrathoracic complications occur in patients with systemic lupus erythematosus; however, classic interstitial lung disease is uncommon. The clinical diagnosis of hypersensitivity pneumonitis requires a specific exposure that is temporally related to the development of the lung disease, and the high- resolution CT scan pattern is generally one of centrilobular nodules with areas of focal air-trapping. In addition, hypersensitivity pneumonitis cannot explain the patient's skin findings and gastroesophageal reflux disease.
Bibliography

1. Steen VD. The lung in systemic sclerosis. J Clin Rheumatol. 2005;11:40-6. [PMID: 16357695] [PubMed]