Fatal Course of Cutaneous Cholesterol Embolization Syndrome: A Case Report.

Cholesterol embolization syndrome is an increasing but underestimated problem after endovascular intervention or after the start of thrombolytic therapies. Embolies from the aortic wall involves abdominal organs and the skin of the lower extremities or buttocks. In our case a progressive ulceration and necroses occurs spontaneously. Endovascular treatment of the lower extremities was successful for a short period. Due to the progression of necrosis, both legs were amputated. Biopsies were taken from the skin were initially no directions to the diagnosis of Cholesterol embolization syndrome. After a second elliptical excision biopsy the diagnosis of cholesterol embolization syndrome was confirmed. Because the rapid progression of skin necroses despite the treatment of prednisone, patient died due to sepsis and renal failure. This case shows when arterial revascularization is performed and progression in skin necrosis occurs despite optimal arterial vascular status the diagnosis CES should be considered and treated in an early state of disease.

Crystal Clots as Therapeutic Target in Cholesterol Crystal Embolism.

RATIONALE: Cholesterol crystal embolism can be a life-threatening complication of advanced atherosclerosis. Pathophysiology and molecular targets for treatment are largely unknown. OBJECTIVE: We aimed to develop a new animal model of cholesterol crystal embolism to dissect the molecular mechanisms of cholesterol crystal (CC)-driven arterial occlusion, tissue infarction, and organ failure. METHODS AND RESULTS: C57BL/6J mice were injected with CC into the left kidney artery. Primary end point was glomerular filtration rate (GFR). CC caused crystal clots occluding intrarenal arteries and a dose-dependent drop in GFR, followed by GFR recovery within 4 weeks, that is, acute kidney disease. In contrast, the extent of kidney infarction was more variable. Blocking necroptosis using mixed lineage kinase domain-like deficient mice or necrostatin-1s treatment protected from kidney infarction but not from GFR loss because arterial obstructions persisted, identifying crystal clots as a primary target to prevent organ failure. CC involved platelets, neutrophils, fibrin, and extracellular DNA. Neutrophil depletion or inhibition of the release of neutrophil extracellular traps had little effects, but platelet P2Y12 receptor antagonism with clopidogrel, fibrinolysis with urokinase, or DNA digestion with recombinant DNase I all prevented arterial occlusions, GFR loss, and kidney infarction. The window-of-opportunity was <3 hours after CC injection. However, combining Nec-1s (necrostatin-1s) prophylaxis given 1 hour before and DNase I 3 hours after CC injection completely prevented kidney failure and infarcts. In vitro, CC did not directly induce plasmatic coagulation but induced neutrophil extracellular trap formation and DNA release mainly from kidney endothelial cells, neutrophils, and few from platelets. CC induced ATP release from aggregating platelets, which increased fibrin formation in a DNase-dependent manner. CONCLUSIONS: CC embolism causes arterial obstructions and organ failure via the formation of crystal clots with fibrin, platelets, and extracellular DNA as critical components. Therefore, our model enables to unravel the pathogenesis of the CC embolism syndrome as a basis for both prophylaxis and targeted therapy.

Cholesterol crystal embolism to the gastrointestinal tract: a catastrophic case

Cholesterol crystal embolism is a rare and easily overlooked cause of colonic ischemia. The gastrointestinal tract is the third most common organ system affected by cholesterol emboli, second only to kidney and skin. Here we present a catastrophic case of gastrointestinal cholesterol crystal embolism leading to extensive post-operative bowel infarction and ultimately death. For a practicing pathologist, careful attention to the vessels of any ischemic bowel and recognition of the subtle but distinct angular imprint of cholesterol crystals facilitates prompt identification of the atheroemboli. In some cases, early identification may help mitigate further tissue damage. In more acute and severe cases, identification of the cholesterol crystal emboli may be important primarily for documentation of procedural complications.

Visible-free cholesterol crystal emboli adjacent to microinfarcts in myocardial capillaries and arterioles on H&E-stained frozen sections of an autopsied patient.

The number of released free cholesterol crystal emboli (fCCE) and their role during percutaneous coronary intervention (PCI) in acute coronary syndrome (ACS) have not been documented yet. Furthermore, fCCE manifesting in the coronary lumen following plaque rupture has been historically overlooked owing to the standard tissue preparation for light microscopy which uses ethanol as a dehydrating agent that can dissolve fCCE, leaving behind empty tissue. In this case report, we evaluated fCCE released during PCI for ACS and their relationship with myocardial injury and coronary artery obstruction on the H&E-stained sections by using polarised light microscopy. To our knowledge, there has been no mention of the visibility of fCCE on H&E-stained frozen polarised sections before.

Unilateral necrosis of the tongue caused by embolisation of cholesterol crystals.

Cholesterol crystals embolise when an aortic atherosclerotic lesion ruptures and cholesterol crystals are scattered and obstruct small peripheral arterioles. Risk factors include both iatrogenic factors such as intravascular catheterisation, and spontaneous factors for atherosclerosis such as aging, hypertension, dyslipidaemia, and smoking. We describe the case of an 83-year-old Japanese man who developed unilateral, superficial necrosis of the tongue as a result of spontaneous embolisation of cholesterol crystals.

Cholesterol Crystal Embolism and Chronic Kidney Disease.

Renal disease caused by cholesterol crystal embolism (CCE) occurs when cholesterol crystals become lodged in small renal arteries after small pieces of atheromatous plaques break off from the aorta or renal arteries and shower the downstream vascular bed. CCE is a multisystemic disease but kidneys are particularly vulnerable to atheroembolic disease, which can cause an acute, subacute, or chronic decline in renal function. This life-threatening disease may be underdiagnosed and overlooked as a cause of chronic kidney disease (CKD) among patients with advanced atherosclerosis. CCE can result from vascular surgery, angiography, or administration of anticoagulants. Atheroembolic renal disease has various clinical features that resemble those found in other kidney disorders and systemic diseases. It is commonly misdiagnosed in clinic, but confirmed by characteristic renal biopsy findings. Therapeutic options are limited, and prognosis is considered to be poor. Expanding knowledge of atheroembolic renal disease due to CCE opens perspectives for recognition, diagnosis, and treatment of this cause of progressive renal insufficiency.

Late Onset of Cholesterol Embolism Leading to Graft Failure After Renal Transplantation: Report of Two Cases.

Cholesterol-crystal embolization (CE) usually presents as an acute or subacute multisystemic disease. When affecting native kidneys prognosis is poor, often leading to chronic kidney disease. Presentation in renal allografts is a rare condition although probably underdiagnosed. If renal CE originates from the recipient, allograft survival is usually good, whereas if the donor is the origin, graft dysfunction and subsequent graft loss are common. Associated risk factors are common to native and transplanted kidneys. We report 2 renal graft recipients of different cadaveric donors, both male and 68 years old, diagnosed with CE in renal grafts at 19 and 72 months after transplantation, respectively. They presented previous risk factors for CE, including severe atherosclerosis. They presented insidious and asymptomatic impairment of renal function initially. Renal graft biopsy specimens showed CE in the interlobular arteries. Potential triggers for CE were suspended and high doses of steroids were started. However, progressive decline in renal function and requirement of chronic dialysis occurred within the first year after diagnosis in both cases. Herein we discuss the causal or incidental role of CE in the graft failure of these cases, highlighting the serious outcome despite the recipient origin of the CE and the initiation of treatment.

Ateroembolia de colesterol / Cholesterol atheroembolism

La ateroembolia de colesterol (AEC) es una enfermedad sistémica poco conocida y con un pronóstico sombrío. En estas últimas décadas, su incidencia ha aumentado considerablemente. El diagnóstico es difícil y parte de una alta sospecha clínica, dada la inespecificidad de sus síntomas y el frecuente inicio tardío, semanas después de haber estado expuesto a factores predisponentes (procedimientos endovasculares, tratamiento anticoagulante). Se confirma por la biopsia del órgano afectado. A continuación presentamos un caso clínico de una paciente con AEC de origen espontáneo que presentaba manifestaciones cutáneas, donde la sospecha clínica de esta enfermedad fue la clave para su diagnóstico y un temprano manejo terapéutico (AU)

Cholesterol atheroembolism (CAE) is a rarely known systemic disease with bad prognosis. In the last decades, the incidence of this disorder has increased considerably. The diagnosis is difficult and starts with a clinical suspicion, given the lack of specific symptoms and the frequent late onset during the weeks after exposure of the patient to predisposing factors (angiographic procedures or anticoagulant treatments). It is confirmed by biopsy of the affected organ. Below we report the case of a patient with spontaneous CAE who presented skin manifestations, where clinical suspicion of this disease was the key to diagnosis and early therapeutic management (AU)

[Massive rhabdomyolysis: an uncommon complication of cholesterol embolization syndrome]. / Rhabdomyolyse massive: une complication rare de la maladie des emboles de cholestérol.

A 79-year-old man with atherosclerosis presented blue toes and livedo reticularis. The patient had eroded aortic atheromatous plaques, and cholesterol embolization syndrome was suspected. An endovascular technique to exclude sources of cholesterol emboli was however performed. The patient immediately presented with severe muscle pain and total functional disability of lower limbs, new ischemic lesions of toes, anal and genital necrosis, and a livedo extended up to the abdomen. A massive rhabdomyolysis occurred associated with acute kidney injury and hyperkaliemia treated by continuous renal replacement therapy with regional citrate anticoagulation. Steroids have been introduced and renal function improved. Cholesterol crystals were also found on a skin biopsy, performed before endovascular procedure.