There are varied clinical presentations for cholesterol embolism syndrome depending on the organs involved.

Constitutional symptoms secondary to acute inflammatory reactions may include fever, malaise, anorexia, weight loss, and myalgia

Peripheral skin manifestations such as livedo reticularis, blue toe syndrome, and digital gangrene are among the diagnostic criteria for cholesterol embolism syndrome [3]. Note that blue toe syndrome and other ischemic skin changes occur in approximately one-third of patients [4]. Other common skin findings suggestive of this disease include nodules, purpura, cyanosis, and ulcerations. Ischemic patches, particularly on the legs may also be observed.

In some individuals, the above cutaneous changes may precede systemic complications such as kidney failure [5]. The latter develops in as many as half of all patients with cholesterol embolism [4] [6].

If present, cardiovascular effects may include uncontrolled hypertension, tachycardia, intact peripheral pulses as well as complications such as myocardial infarction and congestive heart failure. Additionally, these patients may exhibit the skin finding known as livedo reticularis, which is indicative of small vessel occlusion.

Patients with gastrointestinal involvement may experience abdominal pain, hemorrhage, intestinal infarction and diseases such as cholecystitis and pancreatitis.

The neurologic clinical picture may be characterized by the acute onset of neurologic deficit and amaurosis fugax. Other findings may include mental status changes (confusion or delirium), ischemic stroke, paraplegia, and/or Hollenhorst plaques in the retinal arteries.

Emboli to the muscles cause myalgia while an inflammatory response in the lungs leads to acute respiratory distress syndrome (ARDS). Additionally, endocrine involvement results in adrenal insufficiency.

• Gangrene of the Toe

  The skin is affected in over one-third of patients resulting in livedo reticularis, gangrene, cyanosis (‘ blue toe syndrome ’ secondary to lack of oxygenated blood supply), ulceration, painful red nodules, and purpura (purple patches). [dermnetnz.org]

  Other cutaneous signs that can occur in cholesterol microembolization syndrome include livedo reticularis, cyanosis, ulceration and even gangrene. 3, 4 In the central nervous system, cholesterol microembolization syndrome may cause strokes with paresthesia [ncbi.nlm.nih.gov]

• Limb Pain

  pain and gastrointestinal pain, [1] resolution of cutaneous lesions, [18] improvement in peripheral symptoms [3] and reversal of pulmonary lesions. [14] During treatment, the side-effects of the corticosteroids should be monitored. [sjkdt.org]

• Abdominal Pain

  Cholesterol emboli can present as renal failure, hypertension, spells of numbness, abdominal pain, and myocardial infarction, or as a multisystem disease that closely approximates the presentation, clinical course, and even biopsy picture of polymyositis [ncbi.nlm.nih.gov]

  pain, nausea, vomiting, oliguria and lower extremity pain. [casereports.bmj.com]

  Full Text A 47-year-old hypertensive woman was admitted to the Intensive Care Unit due to abdominal pain and shock with violet macular skin rash ( Fig. 1 ). [medintensiva.org]

  […] amounts of protein in the urine may cause edema (swelling) of the skin (a combination of symptoms known as nephrotic syndrome ). [3] If emboli have spread to the digestive tract, reduced appetite, nausea and vomiting may occur, as well as nonspecific abdominal [en.wikipedia.org]

• Acute Abdomen

  Acute gastritis. Inflammatory bowel disease. Abdominal angina due to severe mesenteric atheroma. Mesenteric infarction. Adrenal (Addisonian) crisis. Abdominal trauma. Biliary or renal colic or other causes of acute abdomen. [patient.info]

• Hypertension

  Secondary hypertension. Other causes of malignant hypertension. Vasculitides, eg polyarteritis nodosa. Cellulitis. Deep vein thrombosis. Causes of acute neurological dysfunction or delirium. Diabetic vascular disease and leg ulcers. [patient.info]

  Nephropathies The Kidney in Pregnancy References Diagnosis and Management Treatment of Anemia in Chronic Kidney Disease Stages 35 Dyslipidemia in Chronic Kidney Disease Chronic Kidney Disease and Hypertension Recognition and Management of Mineral and [books.google.com]

  Cholesterol emboli can present as renal failure, hypertension, spells of numbness, abdominal pain, and myocardial infarction, or as a multisystem disease that closely approximates the presentation, clinical course, and even biopsy picture of polymyositis [ncbi.nlm.nih.gov]

• Cutaneous Manifestation

  Acute pain in the legs or abdomen occurred in six patients, two of whom had abdominal angina; renal failure was present in six patients, cutaneous manifestations in five, and a cholesterol embolus was seen in the retina in one. [ncbi.nlm.nih.gov]

  Other suggestive clues to the diagnosis are the systemic nature or, on the other hand, the telltale cutaneous manifestations. Sometimes chronic idiopathic renal failure may actually turn out to be due to CCE. Treatment of CCE is mainly supportive. [angiologist.com]

  The presence of cutaneous manifestations does not appear to predict survival because the features may occur with minor or severe disease. However, patients with peripheral manifestations alone have a 38% mortality rate within 15 months. [emedicine.medscape.com]

  On DermNet NZ Cholesterol emboli pathology Vasculitis Blue toe syndrome Other websites Medscape Reference: Cutaneous Cholesterol Emboli Cutaneous Manifestations of Cholesterol Embolism Cholesterol Embolism Books about skin diseases See the DermNet NZ [dermnetnz.org]

  Radauceanu et al. (12) reported that prostacyclin (prostaglandin I-2) was beneficial for cutaneous manifestations of CCE. [medicaljournals.se]

• Leg Pain

  These have been used recently for treating cholesterol atheroembolisms as they quickly improve distal cyanosis, leg pain and kidney function. 8-10 Figure 1. [revistanefrologia.com]

• Transient Blindness

  Transient ischemic attacks (TIA), or “mini-strokes,” can appear as transient blindness in part or all of one eye and may signal an oncoming stroke. [ucdmc.ucdavis.edu]

  Patients may be asymptomatic, with microvascular disease occurring distal to the macula, or they may report intermittent monocular blindness or amaurosis fugax (transient blindness). [dermaamin.com]

• Stroke

  Transient ischemic attacks (TIA), or “mini-strokes,” can appear as transient blindness in part or all of one eye and may signal an oncoming stroke. [ucdmc.ucdavis.edu]

  Methods – We studied 69 patients with ischemic stroke at low-risk for cardiogenic embolism. [publicacoes.cardiol.br]

  Complex plaques in the proximal descending aorta: an underestimated embolic source of stroke. Stroke. 2010 Jun;41(6):1145-50. DOI 10.1161/STROKEAHA.109.577775. (7.) Heinzlef O, Cohen A, Amarenco P. [aprendeenlinea.udea.edu.co]

  Protruding aortic atheromas predict stroke in elderly patients undergoing cardiopulmonary bypass: experience with intraoperative transesophageal echocardiography. J Am Coll Cardiol. 1992 Jul. 20(1):70-7. [Medline]. [emedicine.com]

Suspicion should be high in patients with a recent history of vascular surgery presenting with skin manifestations, renal failure, and possibly other findings. The clinical evaluation includes a full medical, social, and family history to ascertain the clinical picture and assess for risk factors. Additionally, a detailed physical examination and the appropriate studies are key components of the workup.

Biopsy

The only conclusive diagnostic test is the finding of cholesterol crystals in occluded arterioles in the skin [7]. Biopsy of the kidneys, gastrointestinal tract, muscles, or other tissues may also lead to similar results.

Laboratory tests

Patients suspected to have cholesterol embolism should have a complete blood count done as eosinophilia is present in as many as 80% of individuals with this syndrome. Furthermore, leukocytosis, anemia, and thrombocytopenia are other possible findings.

Additionally, serum chemistry is important as increased blood urea nitrogen (BUN) and creatinine concentrations are ubiquitously observed in these patients.

A urinalysis is very useful since microscopic hematuria, proteinuria, and hyaline casts are prevalent. Moreover, eosinophiluria is highly suggestive of this disease.

Further findings include increased creatine kinase (CK) level suggestive of muscle injury and elevations in cardiac enzymes, hepatobiliary enzymes, and amylase.

Finally, studies measuring inflammatory mediators may yield the presence of antinuclear antibodies, rheumatoid factor, decreased complements and increased C-reactive protein (CRP) [3]. The latter is likely an independent predictor of this syndrome in heart disease patients. Elevated erythrocyte sedimentation rate (ESR) may also be seen.

Imaging

One imaging technique that is becoming more widespread in diagnosing aortic atheromas is the transesophageal echocardiography (TEE) [8] [9]. This tool may be useful in individuals undergoing bypass surgery as mobile atheromatous lesions have been correlated to cholesterol embolism in these patients.

Spiral computed tomography (CT) is also beneficial in the identification of protruding atheroma masses in the aorta [10]. This rapid and noninvasive technique can visualize the aortic arch and the distal ascending portion, two segments that are not clearly portrayed on TEE.

Magnetic resonance imaging (MRI) is likely associated with good sensitivity although there is insufficient data.

Finally, angiography with contrast can be used to assess for causes of tissue ischemia. This test, however, may itself cause atheroembolism.

• Creatinine Increased

  He also developed anorexia and malaise and the serum creatinine increased to 7.5 mg/dL. Oral prednisolone was administered at a dose of 1 mg/kg/day. [sjkdt.org]

  Creatinine increased to 8 mg/dl, BUN 250 mg/dl and decreased urine output with water overload led us consider initiating hemodialysis. [oatext.com]

• Creatinine Increased

  He also developed anorexia and malaise and the serum creatinine increased to 7.5 mg/dL. Oral prednisolone was administered at a dose of 1 mg/kg/day. [sjkdt.org]

  Creatinine increased to 8 mg/dl, BUN 250 mg/dl and decreased urine output with water overload led us consider initiating hemodialysis. [oatext.com]

Since there is no definitive treatment for cholesterol embolism, the therapeutic approach for these patients is supportive care for end-organ damage [11]. Depending on which organs are involved, interventions may include cholecystectomy, pancreatitis management, and/or bowel resection. Furthermore, renal failure patients with poor recovery chances will require dialysis and nutritional support while those with ARDS may warrant mechanical ventilation.

Additionally, the medical team must monitor the vital signs and hemodynamic parameters. Individuals managed with vasopressors will likely require pulmonary artery catheterization.

Drug therapy for cholesterol embolism is overall limited. Calcium channel blockers may provide some vasodilator benefit against the vasospasm induced ischemia. However, angiotensin-converting enzyme (ACE) inhibitors are not used due to their physiologic effects on the kidneys. Finally, one study reported that statin therapy helped prevent the recurrence of embolism [12].

Surgical intervention

Procedures such as endarterectomy (aortoiliac, femoral, or popliteal), bypass (aortic, infrainguinal, or upper-extremity) [13] [14], or stent graft placement [15] can be performed to reduce the risk for future embolism.

Other

Since atherosclerosis predisposes the individual for cholesterol embolism, it is paramount to modify existing risk factors. Hence, smoking cessation, control of hypertension, hypercholesterolemia, and diabetes mellitus are key strategies.

Cholesterol embolism can affect every organ. The resulting complications vary in severity as they range from mild impairment to severe organ failure. Individuals with multiorgan involvement tend to have a poor prognosis as the mortality of those with acute multisystem failure is up to 90%. Additionally, there is a 90% fatality rate of patients with severe cholesterol embolism at 3 months.

As embolization of crystals may stabilize, the sequelae may be minor. In cases with kidney insults, renal function may recover although embolism can recur.

The risk factors for cholesterol embolism are the same as those for its precedent disease, atherosclerosis. These include 1) age above 60 years old, 2) male gender, 3) tobacco use, 4) hypertension, 5) diabetes mellitus, 6) hypercholesterolemia, 7) cerebrovascular disease, 8) aortoiliac disease, 9) mitral annular calcification, and 10) family history.

In terms of etiologies, cholesterol emboli can form spontaneously; 20% of cases lack a precipitating event and is likely to be due to aging. More often, iatrogenic trauma can be a cause as vascular manipulations in cardiovascular procedures can dislodge cholesterol crystals from atheromas. Additionally, cholesterol embolism has been noted to occur post thrombolytic treatment in stroke patients [2].

The crystals and other debris migrate to distal vessels, occlude them, and then promote an inflammatory response that leads to organ damage.

The patient demographics is characterized by a minimum age of 50 and ranges from middle age to the elderly. This disease also shows a preference for men.

Epidemiologic data has been ascertained from autopsy research. Evaluation of the following tissue sections has demonstrated the following athero- embolic events in order of decreasing incidence: abdominal aortic aneurysm repair (as much as 77%), aortic aneurysms (31%), and aortic disease (1 to 16%).

Note that up to 30% of patients who undergo angiography and about 3% of those who are treated with percutaneous transluminal coronary angioplasty (PTCA) vein grafts develop cholesterol embolism.

Cholesterol embolism may affect organs through 2 main mechanisms.

Embolization of smaller arteries

In this phenomenon, crystals split and plaque debris from atherosclerotic plaques mechanically occlude small to medium arteries measuring 100 to 200 μm. During this process, cholesterol crystals stimulate an inflammatory foreign body immune response inducing fibrosis of the adventitial layer and occlusion of the lumen of the blood vessels. This eventually leads to tissue ischemia. Additionally, the release of vasospastic mediators following tissue ischemia results in damage to the organs.

Embolization of larger arteries

This mechanism is explained by the separation of larger sized atherosclerotic plaque following 1) trauma caused by angiography or events affecting the aorta, 2) destabilization of clots covering these plaques as a consequence of anticoagulation therapy, or 3) spontaneous event. These smaller plaques go on to occlude large caliber arteries including the internal carotid artery, iliac arteries, or the aorta ultimately leading to tissue infarction and organ impairment.

Pathologic manifestations

Cholesterol emboli of the ascending aorta may lead to small infarcts with neurologic sequelae while those of the descending thoracic aorta and abdominal aorta can cause kidney failure, bowel ischemia, dermatological findings, and musculoskeletal involvement.

Lifestyle adjustment is very important to help prevent cholesterol embolism and its preceding pathology, atherosclerosis. All individuals are highly encouraged to cease smoking, control blood pressure, lower cholesterol levels, and achieve glycemic control.

Also, routine medical care in addition to eating healthy, exercising and maintaining weight are essential for overall well-being.

Cholesterol embolism is a disorder in which cholesterol crystals and other debris released from atherosclerotic plaques found on the walls of larger arteries [1] embolize to smaller arteries thereby occluding them. This process triggers an inflammatory response which gives rise to ischemic end-organ damage.

The causes of plaque destabilization and rupture can be spontaneous, traumatic, or iatrogenic. More frequently, cholesterol embolism is triggered by vascular interventions that disrupt the plaques. Additionally, this condition may result as a consequence of anticoagulation therapy.

Cholesterol embolism may affect any organ including the skin, kidneys, lungs, gastrointestinal tract, skeletal muscles and the cardiovascular and neurologic systems. The overall presentation is reflective of the involved sites.

The clinical workup consists of a complete history, thorough physical examination, and key studies. The only definitive test is a biopsy of the arteries of the skin, kidneys, or muscle demonstrating cholesterol crystals. Some of the common laboratory findings include eosinophilia and eosinophiluria among others. Finally, imaging techniques may be beneficial in identifying cholesterol emboli.

The therapeutic approach aims to provide supportive care of the end-organ damage. Hemodialysis, bowel resection, and cholecystectomy are some of the examples of these supportive measures. Moreover, certain vascular surgeries may help prevent recurrent episodes of cholesterol emboli.

Since cholesterol embolism is a manifestation of atherosclerosis, it has the shared risk factors such as older age, smoking, hypertension, hypercholesterolemia, etc. Hence preventative strategies include lifestyle modifications that address the above.

What are cholesterol emboli?

These are small particles of cholesterol that break away from larger cholesterol masses and then migrate to blood vessels where they cause occlusion and narrowing of the vessels in the skin or other organs. This cuts off oxygen to tissues causing damage to the organs.

This may occur spontaneously. Often, this condition develops after intravascular procedures that disrupt plaques and release cholesterol crystals into the bloodstream. Examples of these procedures include vascular surgery, angiography, angioplasty, intra-aortic balloon pumps, and cardiopulmonary resuscitation. Patients may experience symptoms hours to days after surgery.

Cholesterol embolism is also seen in patients who are treated with anticoagulation therapy.

Who is affected by this?

There a number of risk factors that increase the possibility of having cholesterol embolism :

• Having heart disease
• Older age
• Smoking
• High blood pressure
• High cholesterol
• Obesity
• Diabetes mellitus

What are the signs and symptoms?

Patients will have different clinical presentations depending on which organ is affected. Below are signs and symptoms that patients may develop.

General

• Fever
• Fatigue
• Low appetite
• Weight loss
• Muscle pain

Skin

• Livedo reticularis
• Blue toe syndrome
• Purpura, ulcers, gangrene

Heart

• High blood pressure
• Rapid heart rate
• Heart attack
• Congestive heart failure

Neurology

• Confusion, delirium
• Weakness

Kidney

• Kidney failure

Muscle

• Weakness and pain

How is it diagnosed?

For patients suspected to have cholesterol embolism and those who have a variety of the above symptoms, the medical team will ask appropriate questions, perform a full physical examination, and obtain important studies. The blood tests include a complete blood count, serum chemistries. renal function tests, and important enzyme levels. A majority of patients with cholesterol embolism will have high levels of immune cells known as eosinophils in the blood and urine.

The only confirmatory test is the biopsy of vessels in the skin, kidneys, or muscles showing cholesterol crystals.

Imaging techniques such as transesophageal echocardiography, spiral computed tomography, and magnetic resonance imaging may be beneficial in diagnosing this disease.

How is this treated?

There is no specific treatment for cholesterol emboli as the treatment consists of managing the organ damage in the patient. For example, patients with renal failure may need dialysis.

There are certain cardiovascular surgeries that may help prevent the recurrence of cholesterol emboli.

How can it be prevented?

To prevent this, one must prevent or slow down atherosclerosis by making key lifestyle changes such as:

• Quit smoking
• Control blood pressure
• Lower cholesterol
• Control sugar levels
• Maintain healthy weight

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