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

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

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