Cutaneous Cholesterol Emboli

Updated: Apr 12, 2021
Author: Robert A Schwartz, MD, MPH; Chief Editor: Dirk M Elston, MD 



The general term atheromatous emboli describes the embolization of any atheromatous material. Atheroemboli refers to the dislodgment of relatively large portions of atheromatous plaques containing RBCs and fibrin aggregates, which includes cholesterol crystals of sufficient size to occlude a major systemic artery and potentially result in major organ dysfunction. Cholesterol emboli (CE), on the other hand, result from ulceration of plaques and the subsequent release of cholesterol crystals. These emboli are smaller and usually more numerous, often producing multisystem disease.

Chronic leg ulcer due to cutaneous cholesterol emb Chronic leg ulcer due to cutaneous cholesterol emboli on the leg of a 79-year-old woman.

The term cutaneous CE (CCE) is used when CE result in disease of the skin, as shown in the image below. The terms peripheral emboli, lower extremity atheromatous emboli syndrome, blue toe syndrome, purple toe syndrome, and trash foot refer to special cases of CE to the lower extremities in which cutaneous manifestations are usually present, the latter three occurring in association with anticoagulation or vascular surgery.[1]

In 1945, Flory was the first to suggest that CE may produce skin disease.[2] His hypothesis was later validated by Hoye and associates in 1959, who observed arteries occluded with cholesterol crystals in areas of gangrene on the feet and toes.[3]

It is more commonly associated with iatrogenic manipulation via invasive vascular procedures or therapies (anticoagulation or thrombolytics) and, most commonly, affects the kidneys, gastrointestinal system, and skin.[4] Skin findings can facilitate clinical diagnosis, since about 88% of patients with CCE have them, most commonly livedo reticularis and cyanotic changes of the toes.

CCE is a disease primarily of elderly white men with ulcerous atherosclerosis. Atherosclerotic foci release cholesterol crystals spontaneously or after anticoagulation or endovascular manipulation, inducing the obstruction of small arteries. Cholesterol embolization syndrome is a systemic disease due to distal showering of cholesterol crystals after angiography, major vessel surgery, or thrombolysis. Obstruction of cutaneous vasculature most often results in a clinical picture of livedo reticularis (LR). It is more common in patients with atherosclerotic disease, hypertension, a history of smoking, and elevated baseline plasma C-reactive protein levels.

Gangrene, cyanosis, ulcers, nodules, and purpura can also be observed. In cases of multisystem involvement, CCE may masquerade as many different diseases, but the clinical picture most often mimics a vasculitis. Skin or muscle specimens demonstrate the cholesterol crystals characteristic of this disease.

Treatment is based on the identification of the source of emboli through angiography and on the exclusion of that source from the circulation. Medical therapy has largely been unsuccessful. Gangrene necessitating amputation is the major complication of CCE, but complications may occur in practically any organ system. Without surgery, CCE is a recurrent process with a high mortality rate.


The most likely explanation for the cutaneous manifestation of CCE is trapping of cholesterol crystals in blood vessels leading to occlusion and tissue ischemia. Other contributing factors include underlying lowered arterial pressure from proximal atherosclerosis and the ability of emboli to activate the complement system.

The pattern of LR may be the first clinical sign of CCE and is thought to result from incomplete disturbance of circulation and desaturation of blood that initially occurs with subtotal occlusion of vessels.[5, 6, 7, 8, 9] As spasm and complete occlusion occur, the other signs of CCE become evident. In addition to the blockage of small vascular channels, lower arterial pressure from narrowing of larger proximal arteries may be necessary for the cutaneous manifestations of CCE because intact collateral supply should normally avert it. In one study, injections of a cholesterol suspension in the femoral arteries of dogs produced gangrene, but only in cases with associated thrombosis of the femoral artery. This indicates that embolism is a contributing factor in necrosis with a vascular supply already compromised by atherosclerosis or other occlusive disease. Neither thrombosis alone nor CE alone would produce necrosis.

Other evidence suggests that in addition to a purely mechanical effect, crystalline cholesterol may amplify infarctive tissue damage through the activation of plasma complement, which is capable of potently aggregating polymorphonuclear (PMN) leukocytes and provoking them to damage endothelial cells via toxic oxygen radical release. In both experimental and clinical infarction, evidence of plasma complement activation, often with depletion of complement components, is observed. Animals depleted of complement prior to experimental infarction experience smaller infarcts than controls. In one report, a man suspected of having CE with cutaneous lesions, including LR and digital infarcts, reportedly had plasma with PMN leukocyte–aggregating activity that contained a component of molecular weight and antigenicity consistent with C5a.

Cholesterol crystals and lipids from atheromata incubated with plasma or serum activate complement, as evidenced by immunoelectrophoresis that showed conversion of C3 to C5. On the other hand, serum or plasma depleted of complement or from a patient with congenital C5 deficiency resists activation. PMN leukocytes incubated with endothelial cells to which C5a or cholesterol-incubated plasma was added show evidence of endothelial damage via increased superoxide production, while the addition of plasma alone or cholesterol-incubated plasma without PMN leukocytes does not cause any damage beyond that which spontaneously occurs. This damage is partially inhibited by the addition of superoxide dismutase and catalase.

A related Medscape Reference article is Cutaneous Manifestations of Cholesterol Embolism.


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.[10, 11] 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.[12] 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,[13, 14, 15] and intravenous tissue plasminogen activator.[16, 17, 18] 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. Cholesterol crystal emboli can be induced by factor Xa inhibitor.[19]



United States

The incidence of CCE is rising in association with increased use of interventional vascular procedures, angioplasties, and anticoagulant/thrombolytic therapy.[4] The frequency of CCE is difficult to estimate because routine necropsy is often limited and does not include evaluation of the skin; however, because the abdominal aorta is usually the site of the most advanced intimal disease, one would anticipate that the lower extremities and associated skin and musculature would be one of the most frequently involved sites. In one study, skin and muscle biopsy specimens were obtained from the lower extremities of 100 consecutive autopsies and a 4% rate of CCE was observed. In a large review of 223 patients with all types of CE, 78 (35%) had skin involvement.


In the Netherlands, cutaneous involvement is observed in approximately 24% of cases of CE.[20]


Of 31 cases of CCE in which race was mentioned, all patients were white.


In the same study, 64 (82%) of 78 cases of CCE were in men.


Ages of those affected with CCE in the same study ranged from 26-90 years (mean, 63 y).


CCE is a repetitive process. Untreated patients often have recurrent episodes with significant morbidity and mortality; however, patients with only peripheral involvement, as opposed to both peripheral and visceral involvement, have a much better prognosis. In the most extensive review of CCE cases, the mortality rate was very high. Forty-nine (78%) of 68 patients died.

Patient Education

For patient education resources, see the Cholesterol Center, as well as High Cholesterol and Cholesterol FAQs.




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:

  • Repetitive bouts of sudden spontaneous severe pain: The character of the pain has been described as tightness, burning, stinging, or soreness.

  • Myalgias

  • 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.


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.



Diagnostic Considerations

Also consider the following:

  • Polymyositis
  • Mononeuritis multiplex
  • Giant cell arteritis
  • Heparin necrosis
  • Wegener granulomatosis or an allergic vasculitis
  • Buerger disease
  • Subacute bacterial endocarditis
  • Symmetric peripheral gangrene from sepsis
  • Diabetic vasculitis or neuropathy
  • Other collagen vascular diseases
  • Cryoglobulinemia
  • Immune complex disease
  • Macroglobulinemia
  • Dysproteinemias
  • Raynaud phenomenon
  • Obliterative arteriosclerosis
  • Thrombophlebitis
  • Polycythemia vera
  • Vasculitis [32]

CE may be classified as a cyanotic-infarctive pseudovasculitis due vaso-occlusion by emboli, thrombi, or fibrointimal hyperplasia (endarteritis obliterans).[33] Thus, the differential diagnosis of CE includes purpura fulminans, warfarin (Coumadin) necrosis, antiphospholipid antibody syndrome, cardiac myxoma, calciphylaxis, and radiation arteritis.

CE has been called the great masquerader because of the variety of clinical manifestations. One of the more common clinical pictures simulates a vasculitis. In a study of 73 cases of CCE, 12 (16%) were mistaken for vasculitis, 9 (12%) specifically for polyarteritis nodosa (PAN). Patients with CCE have also been mistakenly diagnosed with polymyositis, mononeuritis multiplex, giant cell arteritis, and heparin necrosis.

In cases simulating PAN, patients often report an abrupt onset of lower extremity pain followed by the appearance of tender nodules and LR in the presence of normal pulses. Systemic symptoms may involve the gastrointestinal and nervous systems. Laboratory findings include hypertension, neutrophilic leukocytosis, eosinophilia, elevation of the sedimentation rate, melena, hematuria, albuminuria, and azotemia.

Helpful in distinguishing between the two is a history of hypersensitivity in patients with PAN or a history of intra-arterial manipulation in patients with CCE. Clinically, PAN has a more generalized distribution than CE, which favors the lower half of the body because of the severity of abdominal aortic disease. Ischemic neuropathy and joint involvement are also common in patients with PAN but are rare in persons with CE.

Histologically, PAN may involve larger arteries or veins, while in CE, adventitial fibrosis is insignificant, vascular lumina and fibrinoid necrosis are eccentric, and necrosis usually involves only a portion of the wall. The principal cellular reaction is endothelial and mononuclear with few acute inflammatory cells. Most importantly, close inspection should reveal cholesterol clefts. Finally, a response to steroids may also help differentiate PAN from CE.

Two patients with presentations similar to polymyositis have been described who experienced the sudden onset of leg pain, cool legs with normal peripheral pulses, petechiae, LR, and elevated tender nodules that represented muscle necrosis (after biopsy). Laboratory abnormalities included elevation of the sedimentation rate, serum aspartate aminotransferase level, lactate dehydrogenase level, and creatine kinase and aldolase values and a myopathic pattern on electromyography.

Cholesterol embolism should be distinguished from cutaneous reactive angiomatosis, a proposed term to describe a group of reactive cutaneous vascular proliferation caused by various diseases.[34]

Cholesterol emboli were described in one patient in whom the emboli were so widespread as to account for an erythroderma and concern about the presence of drug rash with eosinophilia and systemic symptoms (DRESS) syndrome.[35]

Differential Diagnoses



Laboratory Studies

The most common findings in one group of patients with CCE were an elevated erythrocyte sedimentation rate, blood eosinophilia, and rising serum urea nitrogen and creatinine values. Others have reported positive findings for antinuclear antibodies, rheumatoid factor, perinuclear antineutrophil cytoplasmic antibodies with antimyeloperoxidase specificity, and hypocomplementemia.

Imaging Studies

Angiography is useful for identifying arterial lesions that may represent the source of emboli. Studies should include the entire abdominal aorta with iliac, femoral, popliteal, and tibial arteries.

Some also recommend digital arteriography, which may demonstrate a sharp cutoff pattern representing embolization to digital arteries. Biplanar arteriography, including lateral projection, is recommended to detect anterior and posterior lesions that may be missed with the standard frontal projection.

Ultrasonography is a useful noninvasive method to assess for aortic aneurysms.

Transesophageal echocardiography can be especially useful in identifying thoracic aortic sources of CE but is limited in its ability to visualize the abdominal portion.

Other Tests

This diagnosis may be confirmed by funduscopic examination.[36] Ophthalmoscopy may reveal bright orange or yellow plaques in the retinal arterioles, representing CE.

Careful palpation of the abdomen and auscultation for pulsations, thrills, and bruits should be performed to assess for aneurysms.


A skin or muscle biopsy is the most effective method used to diagnose CCE. Its efficacy has been proven in an autopsy study of 20 patients with confirmed CE. Random biopsy specimens from the gastrocnemius and quadriceps muscle groups were positive for emboli in 19 cases. Seven of 7 patients with clinical symptoms suggestive of CCE had a positive diagnosis antemortem after muscle biopsy. In a review of CCE, diagnosis was possible in 22 (92%) of 24 cases in which a skin biopsy was performed. Many have emphasized the need for deep biopsies (eg, incisional), in order to obtain vessels of sufficient size that are likely to be occluded with emboli, and the need for subserial sectioning of specimens. Note the images below.

Skin biopsy specimen demonstrating ulceration and 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.
Higher magnification of the same biopsy specimen, Higher magnification of the same biopsy specimen, demonstrating cholesterol clefts within an occluded arteriole. Hematoxylin and eosin stain at 297X magnification.

Percutaneous renal biopsy and endoscopic gastrointestinal biopsy are more invasive methods of diagnosing CE and are used in cases of systemic embolization.

Amputated limbs or toes can be scrutinized for emboli in the vessels.

Embolectomy specimens can also be examined for cholesterol crystals.

Although rare, cholesterol clefts have been found in bone marrow biopsy samples and remnants from prostatic curettage.

Histologic Findings

When examined with polarized light, cholesterol crystals in frozen section appear as birefringent rhomboids. They can also be identified by the Schultz modification of the Lieberman-Burchard reaction for cholesterol. Crystals are green within a few minutes and then brown at 30 minutes. Paraffin embedding used in routine histologic processing dissolves cholesterol crystals, replacing them with characteristic biconvex or lenticular clefts or spaces.

Emboli have been observed in the lumina of arteries ranging from 55-900 mm in external diameter but favor vessels in the 150- to 200-µm range. Initially, cholesterol clefts with or without hyaline material and rarely an aggregate of lipid-filled histiocytes are observed. Thrombosis superimposed on the embolus is variable. Shortly thereafter, reactive hyperplasia of the intima occurs with dense infiltration of the media and adventitia or surrounding tissue with neutrophils and, occasionally, eosinophils. Fibrinoid necrosis of the vessel walls and interruption of the internal elastic membrane are also variable findings.

In older lesions, the infiltrate is replaced by mononuclear and foreign body giant cells and prominent fibrosis. The crystals may persist, disappear, or extrude through vessel walls. In heavily infarcted areas, coagulative and early liquefactive necrosis of the epidermis, dermis, and panniculus may be observed.

While generally considered pathognomonic for CCE, the presence of intravascular cholesterol crystals has recently been described in biopsy and excision specimens of nonmelanotic skin cancers from patients with no evidence of CCE. The authors of one paper suggest that in such cases, this finding may be artifactual and perhaps related to wound healing.



Medical Care

Medical treatment of CCE has largely been unsuccessful, with the exception of a few anecdotal reports. The early goals of treatment are to augment the circulation and to try to prevent occlusion. Some believe this can be achieved with drugs that inhibit coagulation, platelet aggregation, and RBC sludging. Vasodilators and corticosteroids have also been used. Variable results have been reported with the use of heparin, streptokinase, urokinase, tissue plasminogen activator, warfarin, bishydroxycoumarin, aspirin, pentoxifylline, dipyridamole, prostaglandins, prostacyclin, intra-arterial papaverine, sulfinpyrazone, low–molecular-weight dextran, nifedipine, prednisone, and methylprednisolone. Some have also recently reported success with hemostatic and lipid-lowering agents (eg, vitamin K, carbazochrome, tranexamic acid, reptilase, lovastatin, cholestyramine, probucol).

Although anticoagulants have been observed to cause CCE and many reports indicate the cessation of symptoms upon discontinuation, in 2 patients, heparin resulted in resolution of their myalgias, tenderness, and pregangrene. Furthermore, they did not have any recurrence of symptoms or signs. Another group reported clinical and radiographic improvement following therapy with intra-arterial streptokinase, heparin, and prostacyclin. Iloprost, a prostacyclin analog, has also been reported to improve renal function and peripheral symptoms in patients with CE. Subcutaneous heparin, which is intermittently administered through the tissue to provide trough periods, may allow more effective healing of plaques than the intravenous form.

Some recommend a trial of corticosteroids for their anti-inflammatory effect to limit arteritis and the subsequent fibrotic occlusion of vessels; however, in 9 patients with CCE thought to have vasculitis who were treated with corticosteroids, 7 died.

Lovastatin may effect healing by inducing the regression of atherosclerosis and by decreasing plaque cholesterol content, which is linked to an increased incidence of emboli.

One group used the combination of hemostatic (ie, vitamin K, carbazochrome, tranexamic acid, reptilase) and antihyperlipidemic (ie, cholestyramine, probucol) drugs and had positive results.

The clinical effect of circulator boot therapy in patients with cholesterol embolization syndrome of the lower extremities in patients following cardiac or vascular procedures may be an effective noninvasive therapeutic option.[37]

Surgical Care

Removal of the source of the emboli using thromboendarterectomy or excision and replacement of the prosthesis has resulted in resolution of CCE. Because gangrene is more likely to occur in persons whose circulation is already compromised, reconstruction of the stenotic proximal artery, which may or may not be the source of emboli, is also advised. Other forms of surgical treatment include embolectomy, sympathectomy, and primary excision of necrotic tissue, possibly involving amputation.

Thoracoabdominal repair is the criterion standard of treatment. Bypass without vessel ligation is contraindicated because it does not remove the source of emboli. Improvement and healing of cutaneous lesions was observed in 2 of 3 patients after resection of abdominal aortic aneurysms. Another group reported that 4 of 5 patients with ischemic lesions from toe gangrene or necrosis benefited from arterial reconstruction. For multilevel occlusive disease, proximal reconstructions are performed prior to distal ones, but the reverse may be appropriate for blue toe syndrome.

If the entire aorta is diffusely ulcerative, the source of emboli is inaccessible, or the patient is a poor surgical candidate, then thoracoabdominal repair may not be possible. Palliative treatment for such patients is axillobifemoral bypass with external iliac ligation. Four patients with peripheral emboli who underwent this procedure had cessation of new lesions, healing, and pain relief. Embolization to the pelvic circulation may be controlled by iliac ligation at the aortic bifurcation or by individual interruption of the internal iliac arteries. Another group had similar success with this technique and was able to salvage 12 limbs in 6 patients, apart from the loss of a fifth toe.

Embolectomy may be effective in cases of the larger atheroemboli.

Peripheral nerve blockade or lumbar sympathectomy has been used to deter cutaneous breakdown and promote healing. They are advocated for patients with persistent areas of pain, cyanosis, or cutaneous gangrene in the involved limb. Sympathetic blockade influences the microcirculation of the skin through a direct effect on arteriovenous communications that are almost entirely made of smooth muscle.

If peripheral circulation is intact, hard eschars from infarcted skin and/or muscle on the legs should be excised primarily.

If circulation is inadequate, amputation may be the only way to stop the advance of ascending gangrene.


CE can cause severe dysfunction of practically any organ, but renal emboli resulting in hypertension and renal insufficiency or failure is the most common complication. Management by a nephrologist, with possible referral to a dialysis service, may be necessary.


During aortic surgery, gentle clamping, no reclamping, and minimal handling of the aorta are recommended. Smaller, less rigid catheters and less manipulation of them is important, as is the avoidance of high-pressure injectors. For aortography, consider a transaxillary approach instead of a translumbar approach if aortic plaques are present; however, the transaxillary approach is technically more difficult, with an increased risk of thrombosis, hematoma, and possible brachial plexus injury.

Avoid anticoagulants, which can cause hemorrhage within the walls of sclerotic arteries, with subsequent thrombosis and elevation of an atheromatous plaque.

During aortoiliac reconstruction, the downward flush is a maneuver in which, following the proximal and one distal anastomosis, a gush of blood is allowed to escape through the unanastomosed limb of the prosthesis, while the other artery is clamped, to remove debris. In a variation on this technique, one group was able to prevent peripheral emboli during aortoiliac reconstruction with the placement of a blood filter and perfusion cannula between the unanastomosed limb and unattached distal artery, allowing a larger gush of blood and more atheromatous debris to be flushed out.

Some authorities have suggested that CABG surgery should be contraindicated in patients with a known history of CE.



Medication Summary

Little success has been achieved with medical treatment of CCE. General strategies involve the use of anticoagulants, antiplatelet and antisludging drugs, vasodilators, corticosteroids, and lipid-lowering agents to prevent or reduce vascular occlusion, augment circulation, decrease inflammation, and help induce the regression of atherosclerotic plaques. None of these therapies has been proven effective in controlled trials, and, in most cases, the rationale for using them is based on anecdotal reports, such low-density lipoprotein apheresis (LDL-A) followed by steroids, which has been suggested as beneficial, especially in patients with cutaneous involvement.[38]

Anticoagulant/antithrombolytic agents

Class Summary

Anticoagulant/antithrombolytic agents prevent, limit, or degrade thrombosis to reestablish blood flow.

Heparin (Hep-Lock)

Heparin augments the activity of antithrombin III and heparin cofactor to inhibit thrombin and factor Xa. It prevents conversion of fibrinogen to fibrin. It does not actively lyse but is able to inhibit further thrombogenesis. Heparin prevents reaccumulation of clot after spontaneous fibrinolysis, and it prolongs the aPTT.

Warfarin (Coumadin)

Warfarin interferes with hepatic synthesis of vitamin K–dependent coagulation factors (eg, II, VII, IX, X, proteins C and S). It is used for prophylaxis and treatment of venous thrombosis, pulmonary embolism, and thromboembolic disorders. Tailor the dose to maintain an INR of 2-3.

Antiplatelet/antisludging agents

Class Summary

Antiplatelet/antisludging agents prevent vascular occlusion.

Aspirin (Anacin, Bayer, Empirin)

Aspirin inhibits prostaglandin synthesis, preventing the formation of platelet-aggregating thromboxane A2. It may be used in a low dose to inhibit platelet aggregation and improve complications of venous stases and thrombosis.

Pentoxifylline (Trental)

Pentoxifylline may alter the rheology of RBCs, which, in turn, reduces blood viscosity.

Dipyridamole (Persantine)

Dipyridamole is used to complement usual warfarin therapy. It is a platelet adhesion inhibitor that possibly inhibits RBC uptake of adenosine, itself an inhibitor of platelet reactivity. In addition, it may inhibit phosphodiesterase activity, leading to increased cyclic-3',5'-adenosine monophosphate within platelets and formation of the potent platelet activator thromboxane A2.


Class Summary

Vasodilators relax blood vessels to help reestablish blood flow.

Papaverine (Pavabid, Pavatine)

Papaverine is a benzylisoquinoline derivative with direct nonspecific relaxant effect on vascular, cardiac, and other smooth muscle.


Nifedipine inhibits calcium influx into vascular smooth muscle and myocardium. It relaxes coronary smooth muscle and produces coronary vasodilation, which, in turn, improves myocardial oxygen delivery and increases blood flow.


Class Summary

Corticosteroids have anti-inflammatory properties and cause profound and varied metabolic effects. They modify body's immune response to diverse stimuli and reduce vascular inflammation.

Prednisone (Deltasone, Orasone, Meticorten)

Prednisone is an anti-inflammatory agent that suppresses the function of inflammatory cells and stabilizes lysosomal membranes.

Methylprednisolone (Medrol, Solu-Medrol)

Methylprednisolone is an anti-inflammatory agent that suppresses the function of inflammatory cells and stabilizes lysosomal membranes.

Cholesterol-lowering agents

Class Summary

Cholesterol-lowering agents induce regression of atherosclerotic plaques.

Lovastatin (Mevacor)

Lovastatin competitively inhibits 3-hydroxyl-3-methylglutaryl-coenzyme A reductase, which catalyzes the rate-limiting step in cholesterol synthesis.

Cholestyramine (Questran)

Cholestyramine forms a nonabsorbable complex with bile acids in the intestine, which, in turn, inhibits enterohepatic reuptake of intestinal bile salts.


Questions & Answers


What are cutaneous cholesterol emboli (CCE)?

What is the pathophysiology of cutaneous cholesterol emboli (CCE)?

What causes cutaneous cholesterol emboli (CCE)?

What is the prevalence of cutaneous cholesterol emboli (CCE) in the US?

What is the global prevalence of cutaneous cholesterol emboli (CCE)?

What are the racial predilections of cutaneous cholesterol emboli (CCE)?

What are the sexual predilections of cutaneous cholesterol emboli (CCE)?

Which age groups have the highest prevalence of cutaneous cholesterol emboli (CCE)?

What is the prognosis of cutaneous cholesterol emboli (CCE)?


Which clinical history findings are characteristic of cutaneous cholesterol emboli (CCE)?

Which physical findings are characteristic of cutaneous cholesterol emboli (CCE)?

What are the possible complications of cutaneous cholesterol emboli (CCE)?


Which conditions are included in the differential diagnoses of cutaneous cholesterol emboli (CCE)?

What are the differential diagnoses for Cutaneous Cholesterol Emboli?


What is the role of lab tests in the workup of cutaneous cholesterol emboli (CCE)?

What is the role of imaging studies in the workup of cutaneous cholesterol emboli (CCE)?

How is the diagnosis of cutaneous cholesterol emboli (CCE) confirmed?

How are patients with cutaneous cholesterol emboli (CCE) assessed for aneurysms?

What is the role of biopsy in the workup of cutaneous cholesterol emboli (CCE)?

Which histologic findings are characteristic of cutaneous cholesterol emboli (CCE)?


How is cutaneous cholesterol emboli (CCE) treated?

What is the role of surgery in the treatment of cutaneous cholesterol emboli (CCE)?

Which specialist consultations are beneficial to patients with cutaneous cholesterol emboli (CCE)?

What precautions should be taken during aortic surgery of a patient with cutaneous cholesterol emboli (CCE)?

How are cholesterol emboli (CE) prevented during aortoiliac reconstruction?

What are the surgical contraindications in patients with cholesterol emboli (CE)?


What is the role of medications in the treatment of cutaneous cholesterol emboli (CCE)?

Which medications in the drug class Cholesterol-lowering agents are used in the treatment of Cutaneous Cholesterol Emboli?

Which medications in the drug class Corticosteroids are used in the treatment of Cutaneous Cholesterol Emboli?

Which medications in the drug class Vasodilators are used in the treatment of Cutaneous Cholesterol Emboli?

Which medications in the drug class Antiplatelet/antisludging agents are used in the treatment of Cutaneous Cholesterol Emboli?

Which medications in the drug class Anticoagulant/antithrombolytic agents are used in the treatment of Cutaneous Cholesterol Emboli?