Cholesterol crystal embolization following plaque rupture: a systemic disease with unusual features

Abstract

Cholesterol crystal embolic (CCE) syndrome is often a clinically challenging condition that has a poor prognostic implication. It is a result of plaque rupture with release of cholesterol crystals into the circulation that embolize into various tissue organs. Plaque rupture seems to be triggered by an expanding necrotic core during cholesterol crystallization forming sharp tipped crystals that perforate and tear the fibrous cap. Embolizing cholesterol crystals then initiate both local and systemic inflammation that eventually lead to vascular fibrosis and obstruction causing symptoms that can mimic other vasculitic conditions. In fact, animal studies have demonstrated that cholesterol crystals can trigger an inflammatory response via NLRP3 inflammasome similar to that seen with gout. The diagnosis of CCE syndrome often requires a high suspicion of the condition. Serum inflammation biomarkers including elevated sedimentation rate, abnormal renal function tests and eosinophilia are useful but non-specific. Common target organ involvement includes the skin, kidney, and brain. Various testing including fundoscopic eye examination and other non-invasive procedures such as trans-esophageal echocardiography and magnetic resonance imaging may be helpful in identifying the embolic source. Treatment includes aspirin and clopidogrel, high dose statin and possibly steroids. In rare cases, mechanical intervention using covered stents may help isolate the ruptured plaque. Anticoagulation with warfarin is not recommended and might even be harmful. Overall, CCE syndrome is usually a harbinger of extensive and unstable atherosclerotic disease that is often associated with acute cardiovascular events.

Keywords

cholesterol crystal embolic syndrome / plaque rupture / cholesterol crystal pathogenesis / clinical presentation / diagnosis

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Acknowledgement

Support was provided in part from Michigan State University, The Jean P. Schultz Biomedical Research Endowment; Clinical and Translational ScienceInstitute at Michigan State University; Seed Funds from the Department of Medicine, College of Human Medicine; Graduate Medical Education,Inc. East Lansing, Michigan and Edward W. Sparrow Hospital, Lansing,Michigan.

Conflict of Interest

G.A. is a speaker and recipient of grants from Merck. He is a participant at Merck's US Thrombosis Advisory Board and Atherosclerosis Global Therapeutic Experts Forum. He is a speaker for Amgen, Daiichi Sankyo and consultant for Kowa pharmaceuticals.

F.G., D.V., J.K., S.D. N.T., and S.A. have no conflicts to declare.

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