Cutaneous Manifestations of Cholesterol Embolism

Updated: Jun 27, 2016
  • Author: Laura F McGevna, MD; Chief Editor: William D James, MD  more...
  • Print
Overview

Background

Cholesterol embolism (CE), also known as atheroembolism, is a condition that has historically been a diagnostic challenge. It is defined by the occlusion of small- and medium-caliber arteries (100-200 μ m in diameter) by cholesterol crystals (see the image below). Although it was first reported by Panum nearly 150 years ago, clinicians have only recently become aware of its potentially devastating and rather frequent consequences. Too often, the diagnosis of cholesterol embolism is missed or overlooked, with its nonspecific symptoms misattributed to other, more common entities. In 1987, Fine et al described recognizable skin findings in patients with cholesterol embolism, thereby linking cholesterol embolism to conclusive, conspicuous signs and symptoms. [1] In 1999, Belenfant et al described a successful treatment regimen, unleashing breakthrough advances for the disease. [2]

Aorta with an ulcerated plaque (black arrowhead) o Aorta with an ulcerated plaque (black arrowhead) on the luminal side photographed under water to enhance reflection of cholesterol crystals (white arrowhead).

Despite these advances, cholesterol embolism is still a challenge to diagnose and effectively treat. Fine’s description of livedo reticularis or blue toes (as shown below) in the presence of good peripheral pulses remains invaluable in recognizing cholesterol embolism. However, a high index of suspicion is imperative because symptoms of cholesterol embolism are often atypical, unrecognized, not temporally correlated with the onset of physical findings, or not reported by the patient. Additionally, to date, there is no laboratory testing that is specific for cholesterol embolism. The characteristic needle-shaped cholesterol clefts and intravascular microthrombi may be absent and do not always correlate with clinical disease.

Symmetric involvement of the feet with livedo reti Symmetric involvement of the feet with livedo reticularis on the plantar surface of the forefoot and cyanosis of the left fifth toe. The painful cyanotic toe is typical of blue toe syndrome.
Next:

Pathophysiology

Atherosclerosis is a necessary prerequisite for cholesterol embolism.  The embolic process is often triggered by events or procedures that disrupt unstable atherosclerotic plaques, most frequently during invasive vascular procedures, be they surgical or radiographic, and the administration of anticoagulants or thrombolytics. Diagnosis is suggested by progressive increases in blood urea nitrogen and creatinine levels following the invasive arterial procedure. Although rare, reports describe spontaneous cholesterol embolism in patients with likely unstable atheromatous plaques. [3, 4, 5]

Regardless of proximate cause, the rupture of atheromatous arterial plaques releases a shower of cholesterol crystals into the bloodstream. These crystals migrate distally until they lodge in small arterioles, where they provoke an acute inflammatory response. This response triggers a cascade of events culminating in intravascular thrombus formation, endothelial proliferation, and, finally, vessel fibrosis. Microvascular ischemia eventuates in tissue loss, organ dysfunction, and, in some cases, catastrophic organ failure.

The precise clinical syndrome depends on the location of the source of embolism and the pattern and distribution of flow downstream. The most common sites for severe atheromatous disease are the abdominal aorta and the iliac and femoral arteries. Accordingly, signs and symptoms more commonly result from embolism to the lower half of the body. In fact, 80% of cases are associated with aortoiliac atheromatous plaques. When the source of crystals is in the aortic arch, signs and symptoms of embolization may occur in the eyes and the CNS. [6]

Clinical manifestations may be immediate, or a delay of several months may occur after the inciting event. A 1999 study by Belenfant et al of patients with cholesterol emboli found that the precipitating event occurred an average of 2 months prior to recognition of fulminant disease. [2]

Previous
Next:

Epidemiology

Frequency

The true incidence of cholesterol embolism is unknown, and estimates vary widely among populations. Reasonable estimation is complicated by discrepancy between histologic and clinical disease. Published estimates approximate an average incidence of 2-4%, with reports ranging widely. The largest epidemiological study performed was by Moolenaar and Lamers, using the Dutch National Pathology Information System. [7] They estimated an incidence of 6.2 cases per million per year in the general population in the Netherlands, and a prevalence of only 0.31% in all autopsies. However, this result is not generalizable given the supposed low prevalence of both atherosclerosis and invasive vascular procedures in the Dutch population.

Race

Cholesterol embolism is much more commonly described in white populations than in other racial groups. This observation may be related to ascertainment bias and the failure to detect the subtle cutaneous findings in darkly pigmented skin. Additionally, evidence suggests that access to health care, including invasive vascular procedures (ie, inciting events), may be more limited in black populations, and this may contribute to the sizeable epidemiological difference.

Sex

Cholesterol embolism occurs more often in males than in females, with a male-to-female ratio of approximately 3.4:1, reflecting the excess risk of cardiovascular disease due to atherosclerosis conferred by male sex.

Age

The reported age range for cholesterol embolism is 26-90 years; the mean age is 66-72 years.

Previous
Next:

Prognosis

Despite advances in both diagnosis and treatment, the prognosis remains poor for cholesterol embolism.

Cholesterol embolism is a marker of severe atherosclerosis; the associated morbidity and mortality reflect the gravity of the diagnosis. Mortality rates are reported up to 65-87% within 1 year of diagnosis in some studies, worse than those associated with acute myocardial infarction, which often has a dramatic clinical presentation.

Death from cholesterol embolism may occur via ruptured aortic aneurysm, myocardial or gastrointestinal infarction, sepsis, cerebrovascular disease, critical limb ischemia, and cachexia.

Preexisting renal disease is a known marker for higher mortality. [8] Additionally, longstanding, poorly controlled hypertension is a recognized marker for the development of end-stage renal disease in these patients (P <.001). [9]

Patients with visceral involvement (many of whom also present with skin findings) are reported to have mortality rates of 50% and 65% within 6 and 12 months, respectively.

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.

Those who survive may be left with chronic renal insufficiency requiring hemodialysis, [8] stroke resulting in paraplegia, unstable angina, amputation of the affected extremity (5-15% of patients), and malnutrition or significant weight loss (70% of patients).

Previous
Next:

Patient Education

For excellent patient education resources, visit eMedicineHealth's Cholesterol Center. Also, see eMedicineHealth's patient education articles High Cholesterol, Cholesterol FAQs, and Simvastatin (Zocor).

Previous