Cutaneous Manifestations of Cholesterol Embolism Workup
- Author: Laura F McGevna, MD; Chief Editor: William D James, MD more...
Laboratory abnormalities in cholesterol embolism are nonspecific. However, the basic metabolic panel, a complete blood cell count with differential, a urinalysis with microscopic evaluation of the sediment, an erythrocyte sedimentation rate, and a C-reactive protein level may all prove helpful in diagnosing cholesterol embolism. Other laboratory studies should be ordered based on the patient's underlying disease and the clinical picture.
Eosinophilia (>300 cells/µL or 3-18% total WBCs) develops within 3 days of embolization in 70-80% of patients and may remain elevated for up to 1 month after a new diagnosis of cholesterol embolism. Cholesterol crystals in tissue initiate a cascade of reactions, including the systemic release of interleukin 5. T lymphocytes are thought to release interleukin 5 in order to induce eosinophil production, chemotaxis, and maturation.
Eosinophiluria may indicate cholesterol embolism when identified in patients with other findings of cholesterol embolism. One study found that 8 of 9 patients with biopsy-proven cholesterol embolism had positive Hansel staining for eosinophiluria. However, like many other findings in cholesterol embolism, eosinophiluria is nonspecific. In addition to cholesterol embolism, the differential diagnosis of eosinophiluria includes acute interstitial nephritis.
Leukocytosis is found in 50% of patients.
The presence of elevated blood urea nitrogen levels, creatinine levels, proteinuria, pyuria, hematuria, and various urinary casts (in order of descending frequency: granular, hyaline, white blood cell, red blood cell, and oval fat bodies) are further indications that glomerular damage is occurring.
The erythrocyte sedimentation rate is often elevated (>30 mm/h) in persons with cholesterol embolism.
Elevated preprocedural plasma levels of C-reactive protein are associated with subsequent cholesterol embolism in patients who undergo vascular procedures, according to Fukumoto et al.
Hypocomplementemia and antineutrophil cytoplasmic antibody positivity have been reported in persons with cholesterol embolism. It is suspected that this may result from neutrophil activation.
Because pancreatitis may be a complication of cholesterol embolism, serum amylase should be evaluated in any patient with abdominal pain. Similarly, transaminase levels should be monitored because of the potential for hepatic involvement.
Fecal occult blood and digital rectal examination should also be performed in a patient with symptoms of cholesterol embolism and severe abdominal pain.
Establishing the source of cholesterol emboli remains a formidable challenge, especially in patients with diffuse atherosclerotic disease. Noninvasive procedures should be performed first, if possible.
A transthoracic echocardiography may aid in excluding an intracardiac source of embolism.
Transesophageal studies may exclude small valvular thrombi, which may be below the resolution capacity of transthoracic ultrasonography.
Doppler ultrasonography of the aorta may exclude aortic aneurysm.
Magnetic resonance imaging and CT scanning offer alternative means to effectively evaluate thoracic and abdominal aortic sources of embolism. The image below shows a CT scan of the abdomen, demonstrating the infrarenal aorta with an aneurysm and a mural thrombus. Obviously, efforts to avoid intravascular contrast should be undertaken.
Unfortunately, angiography may be necessary before surgical intervention can be performed, despite the risk of exacerbating cholesterol embolism by mechanical trauma. Peripheral angiography is the best test for establishing a diagnosis of atheroembolism involving the abdominal aorta and the lower extremity arteries.
Definitive diagnosis of the presence of cholesterol embolism is made by performing a biopsy on affected tissue. Skin and muscle are the most accessible sites for obtaining a biopsy specimen and seem to offer the most reliable specificity and favorable sensitivity. Include symptomatic skin or muscle in the biopsy site whenever possible, but even asymptomatic extremities in patients with visceral disease may yield positive biopsy results. Biopsy incisions should probe to subcutaneous fat, if possible, to sample the small vessels, in which cholesterol embolism commonly occurs. Instruct the laboratory to cut sections at multiple levels through the tissue block because changes may be present in only short segments of affected arteries. In one instructive case report, premortem diagnosis of cholesterol embolism was missed when the first sections of a muscle biopsy were interpreted as being consistent with vasculitis. Cholesterol clefts were found in the tissue at postmortem examination, and further sectioning of the original muscle biopsy sample revealed cholesterol crystals amid the vasculitic lesions.
In evaluating a patient with suspected cholesterol embolism, the consulting dermatologist is often faced with the daunting prospect of performing a skin biopsy on an already compromised extremity. Biopsy should be selectively performed. In unfavorable circumstances, biopsy is recommended if one or more of the following criteria for diagnosis is lacking:
A patient with documented diffuse atherosclerosis and exposure to a known cholesterol embolism–precipitating factor or factors
Acute renal failure with an increase in creatinine levels of more than 150% of the baseline
Characteristic cutaneous lesions or retinal embolism
An understanding of cholesterol embolism is predicated on recognizing the relationship with atherosclerosis. Atherosclerotic lesions develop in the walls of vasculature that has undergone diffuse intimal thickening, a process carried out by smooth muscle cells and involving elastin and proteoglycans. Earliest lesions are thought to be apolipoprotein B–containing lipids in macrophages, known as foam cells, in the outer layers of these thickened vessel walls. Grossly, these can be identified as fatty streaks. As the lesion progresses, lipids continuously accumulate and deposit, forming a lipid core. Fibrous, collagenous caps, as shown below, cover these lesions, which usually conceal denuded, friable endothelium. When the fibrin caps rupture, cholesterol embolization may occur.
Cholesterol embolism is histologically defined by the presence of birefringent crystals with polarized light or biconvex needle-shaped ghostly clefts within the arterial lumen, corresponding to cholesterol crystals dissolved during the fixation process. On frozen sections, the Schultz test stains the acicular (ie, needle shaped) cholesterol crystals green within a few minutes and brown within 30 minutes; however, in the clinical setting, demonstration of the characteristic biconvex cholesterol clefts suffices to establish a diagnosis of cholesterol embolism. In the skin, the artery is usually located at the dermal-subcutaneous junction. In the muscle, the findings occur in small arteries adjacent to areas of patchy myocyte atrophy and necrosis with surrounding infiltrate.
Lesions in different stages of evolution may be found in the same patient, and this is considered evidence of recurrent showers of emboli. The earliest lesions typically reveal the cholesterol clefts surrounded by nonagglutinated red blood cells, reflecting partial occlusion of the arterial lumen. The cutaneous livedo reticularis pattern is believed to be secondary to this local incomplete disturbance of circulation. Macrophages and foreign body giant cells may surround the cholesterol clefts, usually within 24-48 hours. Later, a more complete occlusion may occur as encasement of clefts by intimal proliferation and fibrosis ensues. A vasculitic pattern may be seen in biopsies performed well after initial tissue injury. This final stage most likely underlies tissue necrosis and gangrene. Even in late disease and with recanalization, cholesterol crystals may still be found in affected tissue. See the images below.
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