Cutaneous Manifestations of Cholesterol Embolism Clinical Presentation

Updated: Jun 27, 2019
  • Author: Laura F McGevna, MD; Chief Editor: William D James, MD  more...
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Presentation

History

Once termed the great masquerader for its clinical similarity to several other important systemic diseases (eg, polyarteritis nodosa), cholesterol embolism syndrome is often misdiagnosed. Thus, a high suspicion is needed, especially in patients with suspected atherosclerotic disease and specific precipitating events. In a person older than 50 years, the classic triad of excruciating lower extremity pain, livedo reticularis, and palpable peripheral pulses should be considered cholesterol embolization until proven otherwise.

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Physical Examination

The recognition of physical findings may be delayed by days to months. In a small series published by Jucgla et al, atheroembolism was the admitting diagnosis in only 35% of patients, with a delay in diagnosis of up to 81 days [14] . Cutaneous manifestations are the most common physical findings in patients with cholesterol embolism and the most helpful in establishing a diagnosis. Jucgla et al revealed skin findings in 88% of patients with known disease, [14] and a 2004 report by Manganoni indicated that 50 of 52 patients had recognizable skin findings, often marked erythema of the toes. [16]

Cutaneous manifestations

Skin lesions described in cholesterol embolism in multiple studies are described below.

Livedo reticularis

Livedo is the most common dermatologic manifestation of cholesterol embolism, comprising 50-74% of cholesterol embolism–related skin lesions. [14] This blue-red mottling of the skin in a netlike pattern usually affects the feet, the legs, the buttocks, and the thighs, but can extend to the trunk and the upper extremities. The presence of livedo reticularis may be noted only while the patient is standing; therefore, examining patients in both the supine position and the standing position is imperative when possible. See the image below.

The lower extremities show well-developed livedo r The lower extremities show well-developed livedo reticularis and focal areas of erosion and ulceration.

Gangrene/tissue necrosis

Occurring in 35% of patients, gangrene is the loss of tissue due to ischemia. In cholesterol embolism, it may develop within patches of acrocyanosis or livedo reticularis. Gangrene is often confined to the toes (bilaterally in 50% of patients), and rarely it involves the scrotal area. It has been reported with extensive involvement of the abdomen, lower back, and bilateral hips. See the image below of toe involvement.

Plantar surface of the right foot. The distal half Plantar surface of the right foot. The distal half of the great toe is gangrenous, with a sharp demarcation between the necrotic tissue and the normal proximal skin. Livedo reticularis is present on the distal plantar forefoot, and petechiae are present on the distal pad of the second and fourth toes.

Acrocyanosis or blue toe syndrome

Occurring in 28% of patients, this is a characteristic blue-black or violaceous discoloration of the distal extremities. The lesions are painful, discolored, or even necrotic from ischemia. Blue toe syndrome, a term coined by Karmody et al, [17] refers to acute digital ischemia caused by microembolism from the distal aorta, iliac artery, or femoral artery. See the image below.

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.
Dorsal surface of the toes of the right foot of a Dorsal surface of the toes of the right foot of a patient with discoloration resulting from petechiae. This image shows cyanosis of the fourth toe. The dominant eruption is petechial. Note the pallor of the tip of the great toe and the second toe. This finding indicates acute loss of perfusion.

Ulceration

This occurs in 17-39% of patients [14] and is typically unilateral and located on the toes and the feet. Unusual presentations or refractory and recurrent ulcers of the digits and the lower extremities have also been reported. [18]

Nodules or indurated papules

These are present in 10% of patients and are firm, violaceous, and painful. They can appear on the legs, thighs, toes, or feet as a result of an inflammatory reaction surrounding cholesterol crystals. Isolated case reports describe cholesterol clefts in solitary lesions in unusual locations (eg, a nodule on an ear, red nodules on the chest) with microscopic findings of hemorrhagic panniculitis.

Purpura

Purpura has been described in some 40% patients, most commonly on the legs and the feet. The lesions resemble those of vasculitis, but, quite unlike other features in cholesterol embolism, purpura typically spares the toes.

Petechiae

Small, pinpoint, purpuric spots, petechiae do not blanch on diascopy and may appear in individuals with cholesterol embolism.

Balanitis and necrosis of the penile foreskin, perineal area, and scrotum

This has been reported with cholesterol embolism, reflecting a distal aortic or iliofemoral source.

Punctiform subungual hemorrhages

Subungual hemorrhage has been described in association with cholesterol embolism.

Full-thickness cutaneous infarcts

Mimicking heparin necrosis, full-thickness cutaneous infarct and ulceration may occur.

Extracutaneous manifestations

Extracutaneous manifestations of cholesterol embolism are multifarious. These include constitutional symptoms, such as fever and weight loss, as well as those described below.

Renal manifestations (34%)

Receiving 20-25% of the cardiac output, and distal to the abdominal aorta, renal involvement is common. While the skin has an extensive network of collateral circulation, the blood supply to the renal cortex consists of predominantly end-arterioles. Therefore, embolic events in the kidneys often result in an irreversible loss of glomerular function. This portends a poor prognosis for the patient. The clinical diagnosis of cholesterol embolism can be made when stepwise loss of glomerular function is accompanied by cutaneous involvement. The 2 most common renal manifestations of cholesterol embolism are hypertension and loss of glomerular function.

Hypertension resulting from cholesterol embolism may be intractable. Acute rise in pressure may result from obstruction of vasculature by crystals or high circulating plasma renin and angiotensin levels in the setting of renal damage. Renin is released by the juxtaglomerular cells of the afferent arterioles in response to decreased blood flow, often due to obstruction from cholesterol plaques.

Acute renal failure is common in cholesterol embolism, and one study estimated it to account for 5-10% of all cases of acute renal failure. Loss of glomerular function in cholesterol embolism is a progressive process, occurring over 4-6 weeks. It results from periodic showering of emboli and causes renal insufficiency in approximately 30-50% of patients. A delay of as long as 2-6 weeks may occur between precipitating events and the onset of renal dysfunction. In fact, if renal impairment occurs immediately after an invasive procedure, the clinician must first rule out other causes, including contrast-induced nephropathy.

A 2007 study of 354 patients by Scolari et al demonstrated that patients with iatrogenically acquired cholesterol embolism were more likely to develop acute or subacute renal failure and have a worse outcome than patients with spontaneous forms. [19] In this study, 32.7% of patients required dialysis after the development of cholesterol embolism, with the largest risk occurring within the first 6 months of the event.

Other features of renal cholesterol embolism may include flank or back pain, gross or microscopic hematuria, pyuria, and/or urinary casts.

Risk factors for renal insufficiency are the presence of heart failure, lower limb or GI tract involvement, and age older than 70 years.

Visualization of cholesterol crystal clefts in a renal biopsy specimen is pathognomonic for cholesterol embolism. The crystals embolize in the arcuate and interlobular arteries of the kidneys, producing an acute inflammatory reaction with endothelial proliferation and occlusion of the lumen, leading to infarction and the formation of a wedge-shaped scar in the kidney.

Pulses

Pedal pulses are palpable in more than 60% of patients. Pulses are purported to be present in cholesterol embolism, even in patients at risk for peripheral vascular disease, because emboli and microthrombi travel to the most distal, small vessels, sparing the dorsal pedalis and posterior tibial arcades.

GI manifestations (30%)

Cholesterol embolism causes ischemia or infarction of the bowel. Unfortunately, GI symptoms may be nonspecific and, thus, are often misattributed to other conditions.

Symptoms include abdominal pain, diarrhea, and GI bleeding. Jucgla et al [14] noted that all patients with GI manifestations in their study had concomitant renal involvement. Indeed, patients with bowel disease frequently have concurrent evidence of embolism to other sites, including the spleen (57%), the liver (15%), and the gallbladder (8%).

Ischemic cholecystitis has been reported, along with perforation of the gallbladder after cholesterol embolism. [20]

Of patients with GI involvement, 10-30% have hemorrhage, which was found to be the cause of death in at least 1% of patients with fatal cholesterol embolism.

Digestive involvement is known to be associated with a poor outcome. A 2007 study demonstrated that the hazard ratio indicating risk for patient death was considerably elevated at 2.57 in patients with any degree of GI involvement. [19] This high degree of tragic complication is thought to be due to nonspecific presentation and resulting diagnostic delay.

Ophthalmic manifestations (6%)

Retinal cholesterol crystals (Hollenhorst plaques) are bright-yellow, glittering intravascular plaques situated at the bifurcation of the narrow arterioles of the retina. These are often readily apparent on funduscopic examination and are refractile on fluorescein angiography. Patients may be asymptomatic, with microvascular disease occurring distal to the macula, or they may report monocular amaurosis fugax (transient blindness). Retinal infarction resulting from complete occlusion of the vasculature also may occur. Patients with carotid or vertebrobasilar atherosclerosis who undergo endarterectomy are at high risk.

Musculoskeletal manifestations

Cholesterol embolization to muscular arterioles can cause intense myalgia at rest and/or weakness with exertion. Involvement of lower extremity muscles with upper limb sparing is characteristic in cholesterol embolism.

Development of rhabdomyolysis after cholesterol embolism is uncommon; however, reports describe this disastrous complication, underscored by Sarwar's [12] report of a patient with extensive myonecrosis and compartment syndrome which led to bilateral below-the-knee amputations.

CNS manifestations

CNS cholesterol embolism may occur after vascular procedures such as carotid angiography or endarterectomy. The most frequent sources of emboli are the carotid arteries, the thoracic aorta, or the aortic trunk. Case reports have described delirium and dementia attributable to cholesterol embolism. [21] Case reports also describe spinal cord infarction following cholesterol embolism, as well as other symptoms resulting from anterior spinal artery involvement.

Pulmonary manifestations

Alveolar hemorrhage, presumably resulting from cholesterol embolism, has been rarely reported. One patient with severe atherosclerosis was noted to develop hemoptysis, renal failure, and purpura after vascular surgery. Another case report documented pulmonary-renal syndrome in a patient with hemoptysis, respiratory distress, and radiographic alveolar shadowing. [22] Although pulmonary symptoms have been considered rare in the past, Jucgla et al [14] reported 57% of patients developed pulmonary edema secondary to cardiac failure.

Endocrine manifestations

Postmortem examination of adrenal glands has demonstrated cholesterol embolism. [14] One study reported the presumed death of a patient with visceral cholesterol embolism resulting from necrosis of the adrenals.

Reproductive manifestations

Cholesterol embolism has also been demonstrated in postmortem examinations of the prostate, apparently asymptomatic in the patient. [14]

Hematopoietic manifestations

Reuter et al reported a case of spontaneous cholesterol crystal embolization to the bone marrow in a 77-year-old woman with fever, mild anemia, and leukocytosis. [10] Bone marrow biopsy revealed an absence of abnormality, with the exception of the presence of cholesterol crystals. Pierce reported the presence of cholesterol embolism to bone marrow in a premortem patient with anemia and other clinical findings. [23] Muretto also reported a case of cholesterol embolism to bone marrow. [24] Although his patient was quite ill, anemia was not reported. It remains unknown whether anemia is a nonspecific finding in cholesterol embolism.

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Complications

Cholesterol embolism is a destructive disease, and even patients who survive the initial insult may have damaging consequences that preclude return to baseline functioning levels. Stroke, amputation, and the need for long-term dialysis are frequent sequelae.

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