Cutaneous Cholesterol Emboli Clinical Presentation
- Author: Robert A Schwartz, MD, MPH; Chief Editor: Dirk M Elston, MD more...
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. Waves of emboli may produce end-organ failure, and include the blue toe syndrome. In addition to describing the typical cutaneous signs of CCE, patients also often report the following:
Repetitive bouts of sudden spontaneous severe pain: The character of the pain has been described as tightness, burning, stinging, or soreness.
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. 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.
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. However, it may occur in a less dramatic form as a mild cutaneous subtype. It can be viewed as one of the syndromes affecting both skin and eye.
The most comprehensive review of CCE is by Falanga and associates from 1986. 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 or an a pruritic patch on the flank.
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. 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.
Ulcerated atherosclerosis is the primary risk factor for CCE and is especially prevalent in persons with aortic aneurysms; however, the size of the aneurysm does not correlate with the risk of emboli. Single cases of fibromuscular dysplasia of the external iliac arteries and aortic dissection leading to emboli have also been reported. In the latter 2 cases, abnormal turbulence near the diseased artery and disruption of an atheromatous plaque in the area of dissection were thought to be the cause of embolization. In all these patients, CCE can be spontaneous or precipitated by anticoagulant therapy, vascular procedures or surgery, or, rarely, trauma.
In one series of patients with CCE, 26 (36%) of 73 were taking anticoagulants and 31% had undergone vascular procedures. In a series of 15 cases of peripheral emboli, 13 were spontaneous and 2 followed infrarenal aortic operations. In a series of 13 patients with spontaneous CCE, 4 had aortic aneurysms, 2 had femoral aneurysms, and 7 had severe ulcerative atherosclerosis of the aortoiliac segments. In a larger review of 85 cases of peripheral atheroemboli, 38 (45%) were from proximal aneurysms, 37 (43%) were unexplained, 4 were from a nonaneurysmal source, 3 were from other sources, and 3 were iatrogenic.
While the abdominal aorta has traditionally been considered the source of embolization, some have observed embolization from more distal vessels of the arterial tree. In one study, patients with blue toe syndrome were found to have aortoiliac and peripheral (superficial femoral or popliteal artery) atherosclerosis. Surgical exploration of the peripheral lesions revealed ulcerated plaques or focal stenosis, both of which had adherent white thrombi that were interpreted as evidence of these lesions being the source of the emboli. Surgical correction of the peripheral lesions prevented recurrence at 8-24 months of follow-up. In another study on the source of peripheral emboli, 14 were from the aortic or iliac vessels and 28 were below the inguinal ligament. On the other hand, a smaller study showed 8 (57%) aortoiliac lesions versus 6 (43%) femoropopliteal lesions. Thoracic disease, which is more common in conditions such as syphilis or gout, has also been shown to lead to peripheral emboli.
Vascular manipulation, either for radiographic or surgical purposes, results in embolization through the mechanical disruption of atherosclerotic plaques by needles, wires, catheters, or clamps and is especially common after prolonged or difficult catheterizations.[20, 21] Less often, a stream of injected contrast material may dislodge material. Implicated vascular procedures and surgeries include angiography (most often aortography), heart catheterization, coronary artery bypass graft (CABG) surgery, and percutaneous transluminal coronary angioplasty. Procedures near vascular structures that may involve manipulation of such structures can also result in CE; this has been reported after transhiatal esophagectomy.
Anticoagulants are frequently a cause of CCE. Such occurrences are often designated blue or purple toe syndrome. Anticoagulants are speculated to cause CE by preventing or removing adequate thrombosis over ulcerated atheromatous lesions. In one study, embolization was observed to occur 3 weeks to several months after initiation of therapy. Agents reported to cause CE include heparin, bishydroxycoumarin, warfarin sodium, streptokinase,[23, 24, 25] and intravenous tissue plasminogen activator.[26, 27, 28] In an attempt to define the role of anticoagulation in CE, a prospective study examined 60 patients with acute myocardial infarction who underwent CABG surgery. Twenty-nine received thrombolytic therapy for myocardial infarction, and 31 were treated conservatively. During the CABG surgeries, two muscle biopsy specimens and one skin biopsy specimen were taken from vein harvest sites. CE was observed in 4 of 29 and 3 of 31 specimens, respectively.
Embolization following blunt abdominal trauma from an automobile accident has been reported to precede CE. Vibration of the aortic wall may have dislodged the atheroma.
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