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.

Efficacy of LDL apheresis for the treatment of cholesterol crystal embolism: A prospective, controlled study.

This study was performed to evaluate the efficacy and safety of LDL apheresis (LDL-A) for the treatment of cholesterol crystal embolism (CCE) after cardiovascular procedures. We conducted a prospective multicenter study of 34 patients with CCE and 15 historical control patients. The present participants underwent six sessions of LDL-A for 4 weeks and underwent medical therapy with corticosteroids and statins. The mean creatinine concentration and estimated glomerular filtration rate at baseline were 3.82 ± 2.29 mg/dL and 17.8 ± 9.9 mL/min/1.73 m2 , respectively. The prevalence of maintenance dialysis at 24 weeks was significantly lower in the present participants than in the historical controls (3.1% vs. 40.0%, respectively; p < 0.0001), but the mortality rate at 24 weeks was comparable (19% vs. 33%, respectively). Although 45 adverse events occurred in 23 participants, there were no unexpected adverse events. LDL-A for CCE reduces the prevalence of maintenance dialysis 24 weeks later and is well tolerated. This study was registered in the Japan Registry of Clinical Trials (jRCTs022180029) and clinicaltrials.gov (NCT01726868).

[Atheroembolic renal disease: risk factors, diagnostics, histology, and therapeutic approaches].

The increase in patients' average age, the enhancement of anticoagulation therapy and the growth of vascular interventions represent the perfect conditions for the onset of atheroembolic renal disease. AERD is observed in patients with diffuse atherosclerosis, generally after a triggering event such as surgery on the aorta, invasive procedures (angiography, catheterization of the left ventricle, coronary angioplasty) and anticoagulant or fibrinolytic therapy. The clinical signs are heterogeneous, a consequence of the occlusion of downstream small arterial vessels by cholesterol emboli coming from atheromatous plaques of the aorta, or one of its main branches. The proximity of the kidneys to the abdominal aorta, and the high flow of blood they receive, make them a major target organ. For this reason, AERD represents a pathological condition that always needs to be taken into account in the nephropathic patient, although its systemic nature makes the diagnosis difficult. This manuscript presents a review of the existing literature on this pathology, to provide an updated summary of the state of the art: risk factors, diagnostics, histology and therapeutic approaches.

Proportion and risk factors of cholesterol crystal embolization after cardiovascular procedures: a retrospective national database study.

Cholesterol crystal embolization (CCE) is a rare, mainly iatrogenic condition. The proportion of CCE after cardiovascular procedures has not been fully elucidated. The purpose of this study was to determine the proportion of CCE diagnosed after cardiovascular procedures and to identify risk factors for CCE occurrence. Data on patients aged older than 40 years who underwent cardiovascular procedures between July 2010 and March 2017 were extracted from the Japanese Diagnosis Procedure Combination database. Inpatients diagnosed with CCE within 1 year after procedures in the same hospital were identified. Logistic regression analysis was performed to identify factors associated with the occurrence of CCE. There were 962 patients with CCE in 2,190,300 patients who underwent cardiovascular procedures. The overall proportion of CCE after cardiovascular procedures was 4.4 per 10,000 patients (95% confidence interval 4.1-4.7). The overall in-hospital mortality among patients with CCE was 11% (107/962). Older age, male sex, smoking, heart failure, peripheral vascular disease, cerebrovascular disease, renal insufficiency, diabetes mellitus, hypertension, and aortic aneurism and dissection were significantly associated with the higher occurrence of CCE. Compared with cardioangiography, several procedures were significantly associated with higher occurrence of CCE, including intra-aortic balloon pumping, percutaneous transluminal angioplasty of the renal artery, and transcatheter aortic valve implantation or balloon aortic valvuloplasty. CCE is rare but remains a severe complication of cardiovascular procedures. Atherosclerotic risk factors and certain cardiovascular procedures were associated with CCE.

[Update on cholesterol crystal embolism]. / État des lieux de la maladie des emboles de cholestérol.

Cholesterol crystal embolism is a systemic pathology associated with diffuse atherosclerosis. Pathophysiology corresponds to tissue necro-inflammation secondary to arteriolar occlusion associated with microembolism from atherosclerotic plaques of large diameter arteries. The clinical presentation is heterogeneous and polymorphic. Multiple organs may be the targets, but preferential damage is skin, kidneys and digestive system. It is a serious pathology, underdiagnosed, with a poor prognosis. The risk factors for developing the disease remain the same risk factors as atheroma. The factors favouring migration of microembolism remain mainly vascular interventional procedures; easy to diagnose, they oppose spontaneous embolic migrations or secondary to the introduction of antithrombotic treatment, whose diagnosis is more difficult and the prognosis more severe. The diagnosis of the disease remains mostly a diagnosis of elimination and often refers to a bundle of clinical, biological, morphological and histologic arguments. The treatment is poorly codified and the subject of few publications. It will favour both symptomatic treatment (and mainly that of pain) and complications (high blood pressure, renal insufficiency). The aetiological support remains less consensual. The treatment of atherosclerotic plaques consists, of course, in the correction of classical cardiovascular risk factors, the introduction of a statin. It will be discussed in the implementation of surgery or angioplasty to exclude potentially responsible atherosclerotic lesions. Eviction of antithrombotic therapy should be considered in terms of the benefit-risk balance, but often in favour of maintaining it. Finally, other treatments may be proposed in a case-by-case basis, such as oral or intravenous corticosteroid therapy, colchicine or LDL aphaeresis.

Long-term outcome of biopsy-proven cholesterol crystal embolism.

BACKGROUND: Cholesterol crystal embolism (CCE) causes renal damage, and there is an extremely high risk of end-stage renal disease. However, the time course of CCE-related renal deterioration varies and little is known about the subsequent risk of dialysis among patients with biopsy-proven CCE. METHODS: We performed a retrospective cohort study of 38 Japanese patients in whom a histological diagnosis of CCE was made from September 1992 to July 2005. Competing risk regression analysis was used to investigate the association between declining renal function ( ≥ 1.5 elevation of serum creatinine within 26 weeks after CCE) or its subtypes (acute [ < 1 week after CCE], subacute [1 to < 6 weeks], and chronic [6 to < 26 weeks]) and the risk of dialysis, with adjustment for age, baseline serum creatinine, and the precipitating event (iatrogenic or spontaneous). RESULTS: During a median follow-up period of 25.9 weeks, 14 patients (35.9%) started dialysis. Multivariable analysis showed that patients with declining renal function had a higher risk of commencing dialysis than those without declining function (subdistribution hazard ratio [SHR] 9.47; 95% confidence interval [CI] 1.34-66.8). Patients with different renal presentations had a similarly increased risk of commencing dialysis, with the risk being significantly higher for the subacute and chronic patterns of declining renal function (adjusted SHR [95% CI] for acute, subacute, and chronic declining renal function[vs. no decline]: 7.36 [0.85-63.6], 11.9 [1.36-101], and 10.7 [1.49-77.0], respectively). CONCLUSION: Declining renal function after CCE, even later than 6 weeks, was significantly associated with the subsequent risk of dialysis.

A Catastrophic Case of Idiopathic Cholesterol Crystal Embolism with Multiple Lethal Complications: A Labyrinth Underneath the Diagnosis of Skin Ulcers in Chronic Kidney Disease Patients.

A 66-year-old man was admitted to our hospital because of multiple refractory skin ulcers. Based on his severe systemic arterial calcification and severe calcium-phosphate imbalance due to severe kidney dysfunction, we initially considered calciphylaxis. However, a skin biopsy provided a diagnosis of cholesterol crystal embolization. Although we initiated hemodialysis, steroid treatment, and low-density lipoprotein-cholesterol apheresis, he died of multiple intestinal perforation. An autopsy showed cholesterol crystals occluding multiple organ arterioles. This case suggests that skin ulcers in patients with chronic kidney disease may be an important diagnostic hallmark and may be associated with several serious diseases.

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.

Efficacy of low-density lipoprotein apheresis combined with corticosteroids for cholesterol crystal embolism.

BACKGROUND: Corticosteroids have been widely used in patients with cholesterol crystal embolism (CCE) and low-density lipoprotein apheresis (LDL-A) was reported to reduce the risk of end-stage renal disease in patients with CCE. This study was designed to evaluate the renoprotective effects of LDL-A in combination with corticosteroids in patients with CCE. METHODS: Thirty-five patients with CCE who, between 2008 and 2013, had shown renal deterioration after vascular interventions were retrospectively evaluated. All patients received corticosteroids; of these, 24 also received LDL-A and 11 did not, designated LDL-A and control groups, respectively. Differences in eGFR (ΔeGFR), 3 months and 1 year after CCE diagnosis, were compared in the two groups. RESULTS: The median estimated glomerular filtration rate (eGFR) in all patients was 38.9 [interquartile range (IQR) 31.9-49.4] ml/min/1.73 m2 at baseline (before vascular intervention). At diagnosis, it was 14.4 (IQR 11.3-21.8) ml/min/1.73 m2. The initial corticosteroid dose was 0.34 ± 0.10 mg/kg/day. The mean number of LDL-A treatment sessions in the LDL-A group was 4.3 ± 1.8. eGFR was increased significantly after LDL-A treatments, from 15.0 (IQR 12.3-20.1) to 19.6 (IQR 14.3-23.6) ml/min/1.73 m2 (P < 0.05). ΔeGFR tended to be higher in the LDL-A than in the control group at 3 months [median 6.5 (IQR 5.1-9.3) vs. 2.6 (IQR -0.6 to 6.3) ml/min/1.73 m2, P = 0.095] and was significantly higher at 1 year [median 7.5 (IQR 5.4-8.7) vs. 2.2 (IQR -3.8 to 5.1) ml/min/1.73 m2, P = 0.019]. CONCLUSIONS: LDL-A plus corticosteroids may restore deteriorated renal function better than corticosteroids alone in patients with CCE.

Multisystem diseases affecting the skin and eye.

There exist a wide variety of multisystem diseases that can affect both the eyes and skin. The skin and eyes may be the initial sites affected, leading to a new diagnosis of a systemic illness, or severe skin and eye involvement can drive treatment for patients with multisystem disease. It is important for physicians to be aware of how to recognize and diagnose these conditions, to evaluate patients for extent of disease, and to initiate appropriate therapies to combat these potentially severe diseases. This contribution will discuss the following diseases with a special emphasis on the mucocutaneous and ophthalmologic manifestations: reactive arthritis, sarcoidosis, necrobiotic xanthogranuloma and other granulomatous diseases, amyloidosis, Behçet disease, cholesterol emboli, Vogt-Koyanagi-Harada syndrome, and the primary vasculitides. In each case, a thorough understanding of the cutaneous manifestations and ocular manifestations are critical to help guide appropriate evaluation of these patients, and managing the ocular and cutaneous manifestations are critical to prevent morbidity and potentially devastating long-term sequelae.

Low-Density Lipoprotein Apheresis Ameliorates Renal Prognosis of Cholesterol Crystal Embolism.

Drugs such as corticosteroids and statins have been used to treat cholesterol crystal embolism (CCE), but the prognosis remains poor. This study evaluated the efficacy of low-density lipoprotein apheresis (LDL-A) in patients with CCE. Patients with CCE who showed renal deterioration after vascular interventions were studied retrospectively. Information on demographic variables, clinical measurements, and medication use was collected. The outcomes were incidence of maintenance dialysis and mortality at 24 weeks. A total of 49 patients with CCE were included, among whom 37 (76%) were diagnosed pathologically and the remainder were diagnosed clinically. The median estimated GFR at baseline and at diagnosis were 40.5 and 13.4 mL/min per 1.73 m(2) , respectively. Corticosteroids were used in 42 patients (86%), statins in 30 patients (61%), and angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in 29 patients (59%). LDL-A was performed in 25 patients (LDL-A group), and not in 24 patients (control group). Smoking (100% vs. 72%, P = 0.02), white blood cell count (8900/mm(3) vs. 7000/mm(3) ) and corticosteroid use (96% vs. 75%) were higher in the LDL-A group compared with the control group, but there were no differences in other demographic and clinical parameters between the groups. Patients in the LDL-A group had a lower incidence of maintenance dialysis (2/25 (8%) vs. 8/24 (33%), P < 0.05), and a trend towards lower mortality (2/25 (8%) vs. 7/24 (29%), P = 0.074). These results suggest that LDL-A decreases the risk of maintenance dialysis in severe renal CCE patients after vascular interventions.

Low-density lipoprotein apheresis ameliorates monthly estimated glomerular filtration rate declines in patients with renal cholesterol crystal embolism.

The incidence of cholesterol crystal embolism (CCE) has increased along with increases in the prevalence of atheromatous diseases and intravascular procedures. CCE frequently results in the deterioration of renal function, which sometimes leads to end-stage renal failure. Although there has been no established therapy for CCE, the possibility that low-density lipoprotein apheresis (LDL-A) is an effective therapy for renal CCE was previously reported. However, whether LDL-A improves renal CCE remains uncertain. This study aimed to evaluate the effectiveness of LDL-A in renal CCE patients. Twelve renal CCE patients (9 men and 3 women, mean age 70.6 ± 1.7 years) were included in this retrospective study. All patients had received LDL-A therapy, and estimated glomerular filtration rate (eGFR) values were examined before and after LDL-A. In addition, monthly changes in eGFR before and after LDL-A were calculated for each patient. At initial diagnosis of renal CCE, the eGFR was 35.2 ± 4.8 mL/min/1.73 m(2). At the initiation of LDL-A, the eGFR significantly decreased to 11.0 ± 1.2 mL/min/1.73 m(2), and monthly changes in eGFR reached -7.2 ± 2.5 mL/min/1.73 m(2)/month. After the initiation of LDL-A, the progression of renal dysfunction stabilized in nearly two-thirds of patients, and monthly changes in eGFR after LDL-A significantly diminished to -0.3 ± 0.7 mL/min/1.73 m(2)/month (p < 0.05 vs. before LDL-A). Although 4 patients had to undergo hemodialysis, all patients were alive over 1 year after the initiation of LDL-A. LDL-A therapy ameliorated renal dysfunction in renal CCE patients.

The cholesterol emboli syndrome in atherosclerosis.

Cholesterol emboli syndrome is a relatively rare, but potentially devastating, manifestation of atherosclerotic disease. Cholesterol emboli syndrome is characterized by waves of arterio-arterial embolization of cholesterol crystals and atheroma debris from atherosclerotic plaques in the aorta or its large branches to small or medium caliber arteries (100-200 µm in diameter) that frequently occur after invasive arterial procedures. End-organ damage is due to mechanical occlusion and inflammatory response in the destination arteries. Clinical manifestations may include renal failure, blue toe syndrome, global neurologic deficits and a variety of gastrointestinal, ocular and constitutional signs and symptoms. There is no specific therapy for cholesterol emboli syndrome. Supportive measures include modifications of risk factors, use of statins and antiplatelet agents, avoidance of anticoagulation and thrombolytic agents, and utilization of surgical and endovascular techniques to exclude sources of cholesterol emboli.

[Atheroembolism renal disease: diagnosis and etiologic factors]. / La malattia renale ateroembolica: diagnosi ed eziologia.

Atheromatous renal disease is the major cause of renal insufficiency in the elderly, and cholesterol embolism is a manifestation of this disease. Cholesterol embolism occurs in patients suffering from diffuse erosive atherosclerosis, usually after triggering causes, such as aortic surgery, arterial invasive procedures (angiography, left heart catheterization and coronary angioplasty) and anticoagulant or thrombolytic therapy. It is characterized by occlusion of small arteries with cholesterol emboli deriving from eroded atheromatous plaques of the aorta or large feeder arteries. The proximity of the kidneys to the abdominal aorta and the large renal blood supply make the kidney a frequent target organ for cholesterol atheroembolism. The exact incidence of atheroembolic renal disease (AERD) is not known. The reported incidence AERD varied in the literature because of the differences in study design and the different criteria used for making the diagnosis. Retrospective data derived from autopsy or biopsy studies may exaggerate the frequency by including many subclinical cases. Clinical observations that are based on a short duration of follow-up after an invasive vascular procedure and the infrequency of the confirmatory renal biopsies can lead to an underestimation of the true incidence of AERD. The initial signs and symptoms in patients diagnosed with cholesterol embolism were blue toes syndrome, livedo reticularis, gangrene, leg, toe or foot pain, abdominal pain and flank or back pain, gross haematuria, accelerated hypertension and renal failure. Cholesterol embolism may also be associated with fever, increased erythrocyte sedimentation rate and eosinophilia. Thus, in the cases of spontaneous cholesterol embolism, differential diagnosis includes, polyarteritis nodosa, allergic vasculitis and subacute bacterial endocarditis. Skin and renal biopsy specimens are the best sample for histologic diagnosis. There is, at present, no pharmacological treatments shown to be effective in altering the course of the disease. Management is limited to supportive therapy and avoidance of anticoagulation; aortic procedures should be postponed.

Cutaneous cholesterol embolization syndrome: A case report.

An 81-year-old woman with chronic kidney disease, systemic hypertension, and a large infra-renal abdominal aortic aneurysm, developed bilateral calf muscle pain, altered sensorium, and deterioration of renal function following endovascular aneurysmal repair. On the third post-operative day she developed symmetrical purpuric macules with erythematous margins on the gluteal region and bluish reticulated patches on the soles and tips of toes. This was followed by melena development on the seventh post-operative day. Histology of the skin confirmed the diagnosis of cutaneous cholesterol embolization syndrome (CES). She was treated with hemodialysis and supportive management and she recovered.