We recently used transthoracic and transesophageal echocardiography to examine a patient with pseudoxanthoma elasticum who had experienced sudden monocular blindness that we believed to be the result of embolization from extensive intracardiac fibroelastosis and calcification.

Case Report

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A 54-year-old Hispanic woman with a history of pseudoxanthoma elasticum had episodes of transient, and later persistent, blindness in her left eye. Three years before hospitalization, a biopsy of papular skin lesions on the lateral aspect of the neck showed elastic fiber fragmentation and calcification within the papillary dermis. The patient reported a 2-year history of lower-extremity claudication and upper-extremity paresthesias but denied previous visual problems, transient cerebral ischemic events, headache, and stroke. No history of hypertension, lipid disorder, cigarette smoking, or family history of early atherosclerosis was reported. Our patient was 1 of 10 siblings, and 2 sisters were known to have similar skin lesions. Physical examination showed many small yellow papules in the flexor regions of the neck and axillae typical of pseudoxanthoma elasticum. Funduscopic examination at the time of hospitalization showed angioid streaks in both eyes. Subsequent evaluation by an ophthalmology consultant 6 weeks later showed marked pallor of the optic disc of the left eye that was indicative of retrograde degeneration of the inner retinal layer resulting from an ischemic insult (Figure 1). The patient's blood pressure, cardiac examination, and peripheral pulses were normal. Her electrocardiogram was also normal. The chest roentgenogram showed a normal cardiac silhouette with marked calcification in the region of the left atrium and mitral valve. Forearm and hand roentgenograms were notable for calcification of the radial and ulnar arteries.

View larger version (129K): [in this window] [in a new window]   Figure 1. Photograph of the left retina. Marked pallor of the temporal disc is indicative of retrograde degeneration of the inner layer of the retina after an ischemic insult. Note the prominent angioid streak in the superior nasal retinal field (arrows).

To exclude other causes of embolic disease, neurologic and hematologic evaluations were undertaken. Duplex scanning showed minimal narrowing at the origin of both internal carotid arteries, but no calcification was found. Results of computed tomographic scan of the head without contrast, a 24-hour ambulatory cardiac evaluation, a coagulation profile including proteins C and S, and an assessment of antithrombin III levels were all normal.

Echocardiography

Transthoracic echocardiography Figure 2 showed normal chamber sizes and normal left ventricular function. Marked mitral annular calcification involving the posterior leaflet of the mitral valve extended to the endocardium of the left ventricular posterior wall. The entire left atrial cavity appeared to be encircled with calcific endocardial plaques. A small, densely echogenic mass with independent motion was also seen in the left atrium. Its point of attachment was not apparent. Doppler examination showed mild tricuspid and mitral regurgitation. No abnormal intracardiac gradients were detected. Indices of diastolic function were normal.

View larger version (71K): [in this window] [in a new window]   Figure 2. Transthoracic two-dimensional echocardiogram. Left. Parasternal long-axis view. Extensive calcification of the left atrial endocardium (\#10152;) and the aortomitral annulus is evident. Calcification of the posterior mitral annulus involves the posterior leaflet of the mitral valve () and extends onto the endocardial surface of the left ventricular posterior wall. LV = left ventricle; RV = right ventricle. Right. Parasternal short-axis view at the level of the left atrium and the aortic root. Circumferential calcification of the left atrial endocardium is indicated by arrows. AO = aortic root; RA = right atrium.

To better evaluate the left atrial findings, transesophageal echocardiography was done (Figure 3). The left atrial endocardium appeared to be extensively calcified with raised plaques in the left atrial appendage, overlying the aortomitral annulus, and in the posterior left atrium. Calcification extended from the mitral annulus along the posterior left ventricular endocardium. A 5-mm mobile calcific echodensity was attached to the junction of the left atrial appendage and the left atrium. The posterior mitral leaflet was markedly calcified and immobile. Due to the widespread and dense echogenicity of these cardiac structures, extensive ultrasonic "shadowing" obscured much of the far-field anatomy. The thoracic aorta was free of disease. Doppler examination showed only mild mitral regurgitation.

View larger version (134K): [in this window] [in a new window]   Figure 3. Transesophageal echocardiogram. The horizontal plane at the level of the left atrium (LA) and left atrial appendage (A) is shown. Calcified endocardial plaques (small arrows) outline the left atrial appendage. A mobile calcific mass 5 mm in diameter is seen at the junction of left atrial appendage and the body of the left atrium (large arrow).

Endocardial resection to excise the presumed embolic source was considered, but the attending physician elected to manage the patient expectantly. The patient was treated with 325 mg of aspirin daily and has had no recurrent embolic events after 10 months of follow-up.

Discussion

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The diagnosis of pseudoxanthoma elasticum in our patient was based primarily on the physical and histologic findings of typical skin lesions at flexor sites and was supported by the ocular findings as well as the arterial calcifications and the intrafamilial clustering of similar skin lesions [4].

The complications of pseudoxanthoma elasticum are often secondary to calcific arteriopathy. It has been postulated that calcification of the elastic media is the primary event, with subsequent disruption of the intima and atheromatous plaque formation [4]. When the cerebral circulation is affected, ischemia and stroke can ensue. Renovascular disease may cause hypertension and may secondarily result in congestive heart failure, renal failure, or stroke. In a review of the neurologic complications of pseudoxanthoma elasticum, Messis and Budzilovich [5] reported cases of subarachnoid and intracerebral hemorrhage, cortical atrophy, seizures, dementia, cerebral infarction, and Korsakoff-like psychosis, all ascribed to intrinsic vascular disease. This vascular disease may also involve arterioles, and such changes in the bowel may be responsible for the increased incidence of gastrointestinal hemorrhage in patients with pseudoxanthoma elasticum [4, 6].

Visual disturbances in patients with pseudoxanthoma elasticum are typically not vaso-occlusive. The funduscopic finding of angioid streaks in this patient and others with pseudoxanthoma elasticum derives from elastic fiber degeneration and resultant breaks in the Bruch membrane [4]. Neovascularization, hemorrhage, and scarring may follow and can lead to visual impairment, which can be acute and severe. Our patient had no evidence of such sequelae. In their absence, the sudden and complete loss of vision in one eye argues strongly for arterial occlusion. The funduscopic findings are consistent with a diagnosis of ischemic retinal infarction.

Neurologic evaluation of our patient with carotid duplex and computed tomographic scanning of the head did not show arterial calcification or obstruction. Transesophageal echocardiography showed no evidence of aortic calcification or protruding debris, signs known to be associated with embolic stroke [7]. Echocardiography, however, showed marked endocardial calcification as previously described in pathologic reports [3]. The finding of a mobile calcific density within the left atrium strongly suggested a cardiac source for the retinal embolus, a previously unreported complication of pseudoxanthoma elasticum.

Cardiac manifestations of pseudoxanthoma elasticum include premature coronary artery disease and fibrous thickening of the endocardium of the ventricles, atria, and atrioventricular valves. The resulting clinical syndromes range from heart failure and angina to myocardial infarction and sudden death [1-3].

Echocardiographic findings in patients with pseudoxanthoma elasticum have included the presence of atrial and ventricular endocardial calcification in a patient with congestive heart failure, as described by Fang and colleagues [8]. Challenor and colleagues [9] saw endocardial thickening, abnormal left ventricular diastolic wall motion, and atrial enlargement in a patient with pseudoxanthoma elasticum and a restrictive cardiomyopathy. A report by Lebwohl and colleagues [10] suggesting an association between pseudoxanthoma elasticum and mitral valve prolapse was subsequently questioned by Pyeritz [11].

Widespread calcification of the left atrial endocardium can be seen with rheumatic heart disease [12]. Large segments of the left ventricular endocardium may calcify after myocardial infarction and aneurysm formation [13]. Our patient had no evidence of rheumatic heart disease or myocardial infarction. Her left ventricular wall motion was entirely normal. The echocardiographic finding of endocardial calcification involving such extensive areas of both the left atrium and ventricle correlated with pathologic and radiologic findings previously described in this condition.

The proper management of this presumed cardioembolic disorder is not clear. Although the formation of a thromboembolus on an endocardial plaque might be prevented by anticoagulant therapy, the calcific nature of the mobile intracardiac density suggests that warfarin treatment might be ineffective. In addition, the risk for gastrointestinal hemorrhage in patients with pseudoxanthoma elasticum is a relative contraindication. At least one report has described a patient with pseudoxanthoma elasticum who was treated successfully with endocardial resection for a syndrome of restrictive cardiomyopathy [9]. The utility of such a procedure in preventing embolization in this disorder is unknown.