History
Cholesterol emboli is a rare potentially devastating complication of atherosclerosis, usually appearing as an iatrogenic event in a vascular procedure in the course of anticoagulant or thrombolytic therapy or after trauma. [21] Waves of emboli may produce end-organ failure, and include the blue toe syndrome. [22] In addition to describing the typical cutaneous signs of CCE, patients also often report the following:
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Repetitive bouts of sudden spontaneous severe pain: The character of the pain has been described as tightness, burning, stinging, or soreness.
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Myalgias
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Claudication in the lower half of the body that may be exacerbated by cold or dependency
Numbness, coolness, and paresthesias of the extremities have also been reported.
According to Fukumoto in 2003, the diagnosis of CCE can be made when patients who undergo left-sided heart catheterization have peripheral cutaneous involvement (LR, blue toe syndrome, and digital gangrene) or renal dysfunction. [23] Elevated preprocedure plasma levels of C-reactive protein are linked with subsequent CCE in patients who undergo vascular procedures.
Cholesterol emboli may also be evident as the purple toes syndrome following stroke thrombolysis and warfarin therapy. [24]
Thus, the cholesterol embolization syndrome is a rare, potentially fatal disorder due to emboli of cholesterol crystals from atherosclerotic plaques, the signs and symptoms of which may be initially insidious and unrecognized. [25] However, it may occur in a less dramatic form as a mild cutaneous subtype. [26] It can be viewed as one of the syndromes affecting both skin and eye. [27] Multiple refractory cutaneous ulcers with chronic kidney disease may be a diagnostic sign of widespread, potentially lethal cholesterol embolization. [28]
Physical Examination
The most comprehensive review of CCE is by Falanga and associates from 1986. [29] The cutaneous findings in 78 patients with CE were LR in 38 (49%), gangrene in 27 (35%), cyanosis in 22 (28%), ulceration in 13 (17%), purple toes in 11 (14%), nodules in 8 (10%), and purpura in 7 (9%). Many of these signs are exacerbated with limb dependency. Rarely, CCE may appear as a solitary persistent painful ulcer on the elbow [21] or an a pruritic patch on the flank. [30]
LR was usually bilateral and almost always involved the feet and legs, extending to the thighs, trunk, and even upper extremities in some. In one review, it was observed as late as 5-16 weeks after an inciting event. Gangrene was neither consistently unilateral nor bilateral and primarily occurred in the toes. Toe findings may be striking. [31] Cyanosis was usually bilateral and located on the toes but also involved the feet and, rarely, the upper extremities. Ulceration was more often unilateral and occurred mostly on the toes and feet but was also observed on the legs. Nodules occurred exclusively on the lower extremities, mostly from the ankles to the waist. Purpura was always below the knee, mostly on the legs and feet.
Several reports have emphasized involvement of the genitals. Findings have included scrotal ischemia and necrosis and penile necrosis with ulceration of the glans. Balanitis may progress to preputial necrosis.
Other associated cutaneous findings include splinter and subungual hemorrhages.
Distal pulses are often reported to be normal in persons with CCE, especially early in the disease. However, in a review of 51 cases of CCE in which pulses were mentioned, 29 (57%) were normal, 20 (39%) were bilaterally decreased, and 2 (4%) were absent.
The most common noncutaneous findings in patients with CCE are fever, myalgia, weight loss, altered mental status, and the sudden onset of arterial hypertension.
Complications
The main complication of CCE is gangrene necessitating extremity amputation. In cases of penile ischemia and necrosis, circumcision and even penectomy has been required. In 73 patients with CCE, amputation was performed in 11 (15%).
Patients with CCE frequently have emboli to other systems and the attendant complications. The most common sites of embolization that result in clinical disease are the renal, cardiac, and gastrointestinal systems. Findings include hypertension, renal failure, myocardial infarction, and a multitude of gastrointestinal disorders, including hemorrhage, ulcers, infarction, obstruction, perforation, and stricture formation.
Death most often results from multiple factors or from renal or cardiac complications.
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Chronic leg ulcer due to cutaneous cholesterol emboli on the leg of a 79-year-old woman.
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Skin biopsy specimen demonstrating ulceration and an occluded vessel at the right border of the specimen within the fat. Hematoxylin and eosin stain at 22X magnification.
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Higher magnification of the same biopsy specimen, demonstrating cholesterol clefts within an occluded arteriole. Hematoxylin and eosin stain at 297X magnification.
