A 47-year-old woman comes to the office due to progressive exertional dyspnea and fatigue. She also reports painful episodes of bluish discoloration of the fingers and toes that are triggered by cold exposure and improve with rewarming. Medical history is significant for severe gastroesophageal reflux disease. Physical examination shows skin tightening over the fingers. The oral aperture is small, and scattered telangiectasias are present over the lips. Cardiac examination demonstrates an increased intensity of S2 over the upper left sternal border. Lungs are clear to auscultation with normal air movement and no crackles. The abdomen is soft with mild hepatomegaly. There is bilateral lower extremity pitting edema. Chest x-ray reveals no abnormalities. Results of office spirometry are as follows:
| Forced vital capacity (FVC) | Normal |
| Forced expiratory volume in 1 second (FEV1) | Normal |
| FEV1/FVC ratio (%) | Normal |
Which of the following is the most likely cause of this patient's dyspnea?
Show Explanatory Sources
This patient displays Raynaud phenomenon (cold-induced painful digital vasospasm), sclerodactyly (skin tightening of the hands/ feet), telangiectasias, gastroesophageal dysfunction. These findings suggest systemic sclerosis (ie, scleroderma), specifically the limited cutaneous variant, or CREST (Calcinosis cutis, Raynaud phenomenon, Esophageal dysmotility, Sclerodactyly, Telangiectasia) syndrome.
Systemic sclerosis frequently involves multisystem vasculopathy affecting several vessel beds, including distal extremities (digital ischemia), kidneys (renal crisis), and pulmonary arteries. Pulmonary arterial hypertension (PAH), a leading cause of mortality in patients with systemic sclerosis, is driven by abnormal inflammatory and fibroproliferative signaling (eg, transforming growth factor beta), leading to neointimal/medial thickening and luminal narrowing. Histologically, vessels have a concentric onion-skin, sclerotic appearance.
Pulmonary vascular remodeling is progressive and relentless. Over time, the right ventricle cannot pump against the increased afterload, leading to right ventricular failure. In this patient, PAH is suggested by a prominent pulmonic component of S2 (ie, loud P2, reflecting high pressure in pulmonary artery) with signs of right-sided venous congestion (eg, hepatomegaly, lower extremity edema).
(Choice A) Systemic sclerosis can induce extrapulmonary restriction via chest wall skin tightening that limits thoracic expansion. Clear lungs are expected on auscultation and imaging; however, pulmonary function testing would show a restrictive pattern (ie, low FVC).
(Choice B) Fibrotic interstitial lung disease is another pulmonary complication of systemic sclerosis (particularly the diffuse cutaneous variant), characterized by lung parenchymal inflammation and collagen deposition. However, inspiratory crackles, reticular interstitial thickening on chest x-ray, and a restrictive pattern on pulmonary function testing are expected.
(Choice C) Pericardial fibrosis, occasionally a complication of systemic sclerosis, typically manifests as right-sided heart failure due to impaired diastolic filling of the right ventricle. However, this impaired filling prevents elevation of pulmonary artery pressure; therefore, a loud P2 is not expected.
(Choice E) Pulmonic stenosis can lead to right-sided heart failure. However, right ventricular outflow obstruction leads to low pulmonary artery pressures, resulting in a soft P2. In addition, pulmonic stenosis (almost always a congenital lesion) does not explain the additional findings of CREST syndrome.
Educational objective:
Pulmonary arterial hypertension, a vascular complication of systemic sclerosis, involves fibroproliferative remodeling of the vessel wall, leading to increased pulmonary vascular resistance and right-sided heart failure.