A 45-year-old woman is evaluated for progressive exertional dyspnea and fatigue. She also reports episodic pain and bluish discoloration of the fingers and toes on cold exposure that improve with rewarming. Physical examination shows skin tightening over the fingers. Cardiac examination reveals an accentuated S2 over the upper left sternal border. The abdomen is soft with mild hepatomegaly. There is bilateral lower extremity pitting edema. Pulmonary function test results are as follows: Which of the following is the most likely cause of this patient's dyspnea?

Question

A 45-year-old woman is evaluated for progressive exertional dyspnea and fatigue.  She also reports episodic pain and bluish discoloration of the fingers and toes on cold exposure that improve with rewarming.  Physical examination shows skin tightening over the fingers.  Cardiac examination reveals an accentuated S2 over the upper left sternal border.  The abdomen is soft with mild hepatomegaly.  There is bilateral lower extremity pitting edema.  Pulmonary function test results are as follows:  Which of the following is the most likely cause of this patient's dyspnea?

Quizplus · Accepted Answer

11ec160b_3a20_9dcb_9249_657d34df8ba8_MD0001_00 This patient's skin tightening on the fingers and Raynaud phenomenon (cold-induced digital vasospasm) are suggestive of CREST syndrome (calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia), which is strongly associated with systemic sclerosis. Vascular manifestations are common in systemic sclerosis, and some patients will develop pulmonary arterial hypertension (PAH). In this patient, PAH is suggested by progressive dyspnea and a loud pulmonic component (P2) of S2; hepatomegaly and peripheral edema suggest consequent right-sided heart failure. PAH results from progressive remodeling of the small and medium-sized pulmonary arteries/arterioles. In systemic sclerosis the remodeling is likely triggered by increased proliferation of T cells with secretion of a variety of cytokines (eg, TGF-beta), which stimulate fibroblasts to increase the production of collagen and extracellular matrix proteins. There is also endothelial dysfunction due to an excess of vasoconstrictive, proproliferative mediators (eg, endothelin, thromboxane A2) relative to vasodilative, antiproliferative mediators (eg, nitric oxide, prostacyclin). Consequent vasoconstriction and smooth muscle proliferation with intimal thickening of the vascular walls lead to increased pulmonary vascular resistance and elevated pulmonary arterial pressure. Over time, the right ventricle is unable to pump against the increased afterload, and right-sided heart failure develops. (Choices A and E) Pulmonary interstitial fibrosis occurs in interstitial lung disease, which is a common complication of systemic sclerosis and can lead to pulmonary hypertension due to hypoxia-induced vasoconstriction. However, this patient's normal pulmonary function testing rules out significant lung disease. (Choice C) Myocardial amyloid deposition occurs in amyloidosis and can lead to heart failure due to restrictive cardiomyopathy. Although patients can have progressive dyspnea, Raynaud phenomenon and digital skin tightening are not typical. (Choice D) Pericardial fibrosis can occur in systemic sclerosis and typically manifests as right-sided heart failure due to impaired diastolic filling of the right ventricle. However, pulmonary arterial pressure is not typically elevated and a loud P2 is not expected. (Choice F) Pulmonic stenosis, when severe, can lead to right-sided heart failure; however, a soft P2 would be expected. Educational objective: Pulmonary arterial hypertension is a common complication of systemic sclerosis, likely resulting from proliferation of T cells with release of cytokines (eg, TGF-beta) and consequent progressive thickening and occlusion of the small and medium-sized pulmonary arteries/arterioles. Patients typically have progressive dyspnea and a loud pulmonic component of S2 and may develop signs of right-sided heart failure (eg, hepatomegaly, peripheral edema).

A 45-Year-Old Woman Is Evaluated for Progressive Exertional Dyspnea and Fatigue