Cholesterol embolization syndrome

Cholesterol embolization syndrome is a condition in which cholesterol crystals dislodge from atherosclerotic plaques and enter the bloodstream, blocking small to medium arteries in various organs. Incidence is highest in older individuals with underlying atherosclerosis, particularly after invasive vascular procedures. Clinical features vary depending on the embolism location. Patients typically present with nonspecific systemic inflammatory symptoms and various types of end-organ damage, e.g., acute renal failure, mesenteric ischemia, peripheral skin manifestations (especially in the lower extremities), or stroke. The diagnosis is mostly clinical and may be supported by laboratory and imaging studies. Treatment primarily focuses on prevention of recurrence and includes management of ASCVD and removal of the embolic source, e.g., in patients with abdominal aortic aneurysm.

• Iatrogenic ^[1]
  • Vascular interventions, e.g., percutaneous coronary intervention (PCI) or aortography
  • Abdominal aortic surgery, e.g., abdominal aortic aneurysm repair
  • Cardiac surgery
  • Carotid revascularization
  • Thrombolytic therapy or anticoagulant therapy
• Traumatic
• Spontaneous plaque rupture (rare) ^[1]

Although thrombolytic and/or anticoagulant therapy are widely discussed as causes of cholesterol embolization syndrome, evidence is lacking. ^[1]

Atherosclerosis → rupture of atherosclerotic plaque (most commonly from the aorta) → blockage and inflammation of small to medium arteries by cholesterol crystals → formation of multiple small peripheral, muscular, or visceral emboli → end-organ damage ^[1]

Signs of end-organ damage ^[1]

The type of end-organ damage depends on the location of the emboli.

• Features of renal damage
  • Signs of acute kidney injury
  • Signs of chronic kidney disease
  • Hematuria
• Peripheral skin manifestations
  • Livedo reticularis
  • Necrosis
  • Purpura
  • Cyanosis
  • Ulceration
  • Blue toe syndrome: ischemia due to small vessel occlusion that manifests as toe discoloration (pulses typically remain palpable as large arteries are unaffected)
• Signs of gastrointestinal involvement: (e.g., intestinal ischemia or pancreatitis)
  • Abdominal pain
  • Diarrhea
  • GI bleeding
• Signs of CNS involvement (e.g., ischemic stroke or TIA): Signs of diffuse brain damage (e.g., confusion, memory loss) are more common than focal neurological deficits. ^[1]
• Signs of retinal involvement
  • Hollenhorst plaques on retinal exam
  • Amaurosis fugax

Nonspecific systemic inflammatory symptoms ^[1]

• Fever
• Fatigue
• Myalgia
• Anorexia and weight loss

Diagnosis should be suspected in patients with a combination of end-organ damage, inflammatory response, and a history of atherosclerosis, especially in those with recent vascular intervention or surgery.

• Routine laboratory studies: Findings are nonspecific. ^[1][2]
  • CBC with differential
    • Leukocytosis, eosinophilia
    • Anemia
    • Thrombocytopenia
  • Inflammatory markers: ↑ CRP, ↑ ESR, hypocomplementemia
  • Renal function tests: ↑ BUN, ↑ creatinine
  • Urine studies: proteinuria, hematuria, eosinophiluria ^[3]
• Imaging
  • Imaging of the affected organ showing multiple vessel occlusions can support the diagnosis.
  • TEE, MRA, or CTA of the aorta may identify the source of atheroembolism. ^[2][4]
• Biopsy (of skin, muscle, or affected end-organ) ^[2]
  • Only definitive test; not routinely performed
  • Findings include:
    • Amorphous, eosinophilic material in the vessel lumen
    • Spindle-shaped spaces (cholesterol clefts)

The diagnosis of cholesterol embolization syndrome is mostly clinical and may be supported by laboratory and imaging studies.

• Arterial thromboembolism
• Venous thromboembolism
• Bacterial embolism
• Fat embolism
• Calciphylaxis in chronic kidney disease
• Vasculitis
• Acrocyanosis
• Poor peripheral perfusion due to low cardiac output
• Frostbite

The differential diagnoses listed here are not exhaustive.

There is no specific treatment for cholesterol embolization syndrome. ^[1]

• Treat end-organ damage, e.g.:
  • Management of acute kidney injury
  • Management of ischemic stroke
  • Treatment of acute pancreatitis
  • Management of acute limb ischemia
• The mainstay of management is the prevention of recurrence. ^[1]
  • Optimize management of ASCVD.
    • Mixed evidence for the use of statins, antiplatelets, corticosteroids ^[1]
    • Thrombolytic or anticoagulant therapy is not recommended unless otherwise indicated. ^[1]
  • Consider removal of the embolic source in consultation with a specialist (e.g., vascular surgeon, interventional radiologist). ^[4]
    • Surgical treatment, e.g., vascular bypass surgery, AAA repair, endarterectomy
    • Interventional treatment, e.g., angioplasty, endovascular stent grafting