Use of Proprotein Converse Subtilisin/Kexin Type 9 Inhibitor to Treat Cholesterol Crystal Embolisms after Catheterization: A Report of Three Cases.

Cholesterol crystal embolism (CCE) is a serious complication that occurs after cardiac and vascular procedures. CCE involves multiple organs, and the prognosis and renal function of patients is poor. Although the efficacy of steroid, statin, and low-density lipoprotein apheresis has been reported, no definitive treatment has been established. We herein report three consecutive cases treated with conventional steroid therapy with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor after catheterization. The renal function was preserved, steroid therapy was stopped, and wound healing of blue toes was achieved. PCSK9 inhibitor therapy was safe in the present patient and may be a potential treatment option for CCE.

Successful treatment of cholesterol crystal embolism with anti-proprotein convertase subtilisin/kexin type 9 (PCSK9) antibody: a case report.

Background: We report a unique case of renal cholesterol crystal embolism (CCE) induced by carotid artery stenting that was successfully treated with evolocumab, a fully human monoclonal antibody against proprotein convertase subtilisin kexin type 9 (PCSK9).Case presentation: A 77-year-old man with hypertension, hyperlipidemia, and chronic kidney disease was referred to our department for decreased estimated glomerular filtration rate (eGFR)-from 32.0 to 13.9 mL/min/1.73 m2-5 weeks after carotid artery stenting. Further examination revealed livedo reticularis in the bilateral toes and eosinophilia (723/µL). Skin biopsy from livedo reticularis tissue in the bilateral toes showed cholesterol clefts in the small arteries. The patient was therefore diagnosed with CCE. After 25 weeks' administration of evolocumab at a dose of 140 mg subcutaneously administered every 2 weeks, his eGFR had improved from 10.7 to 18.1 mL/min/1.73 m2.Conclusion: Evolocumab may have a beneficial effect on renal involvement in patients with CCE.

Atheroembolism to the Breast.

We report the case of a woman presenting with livedo reticularis of the breast who was found to have atheroembolism to the breast following upper extremity percutaneous access. Atheroembolism is the embolization of cholesterol crystals off an atherosclerotic plaque that can occur spontaneously or as a result of vascular intervention. This is a unique presentation of an otherwise well-described complication of vascular catheterization, and we propose that livedo reticularis of the breast can be interpreted as a sign of atheroembolism in the appropriate clinical context.

Cholesterol Crystal Embolism Induced by Direct Factor Xa Inhibitor: A First Case Report.

An 80-year-old man presented at our hospital with renal failure. He had been treated with edoxaban, an oral direct factor Xa inhibitor, for deep vein thrombosis for 10 months prior to admission. Although the pulses in his bilateral pedal arteries were palpable, cyanosis was present in the bilateral toes. Laboratory data indicated azotemia and eosinophilia. A skin biopsy confirmed a diagnosis of cholesterol crystal embolism (CCE). Because no invasive vascular procedure was performed, we assumed that CCE was related to edoxaban. To the best of our knowledge, this is the first case report suggesting CCE induced by an Xa inhibitor.

Platelet NOX, a novel target for anti-thrombotic treatment.

There is a growing body of evidence to suggest that reactive oxidant species (ROS) including O2-, OH- or H2O2 act as second messengers to activate platelets via 1) calcium mobilisation, 2) nitric oxide (NO) inactivation, and 3) interaction with arachidonic to give formation of isoprostanes. Among the enzymes generating ROS formation NOX2, the catalytic core of NADPH oxidase (NOX), plays a prominent role as shown by the almost absent ROS production by platelets taken from patients with hereditary deficiency of NOX2. Experimental and clinical studies provided evidence that NOX2 is implicated in platelet activation. Thus, impaired platelet activation has been detected in patients with NOX2 hereditary deficiency. Similarly, normal platelets added with NOX2 specific inhibitors disclosed impaired platelet activation along with ROS down-regulation. Accordingly, animals prone to atherosclerosis treated with apocynin, a NOX inhibitor, showed reduced platelet adhesion and atherosclerotic plaque. Furthermore, a significant association between NOX2 up-regulation and platelet activation has been detected in patients at athero-thrombotic risk, but a cause-effect relationship needs to be established. These findings may represent a rationale to plan interventional trials with NOX inhibitors to establish if blocking NOX2 or other NOX isoforms may represent a novel anti-platelet approach.

Use of corticosteroids in the treatment of cholesterol crystal embolism after cardiac catheterization: a report of four Japanese cases.

Cholesterol crystal embolism (CCE) is a serious complication associated with invasive vascular procedures. The prognosis of the renal involvement type of CCE is very poor, and there is currently no established treatment, other than supportive therapy. We herein report four cases of CCE with severe atherosclerosis wherein the renal function progressively deteriorated after cardiac catheterization. In three of the four patients, low-dose corticosteroids (0.3 mg/kg/day) improved the renal function, whereas the fourth patient died from CCE of the digestive system. This report reviews the literature on CCE and discusses possible therapeutic options.

The purple toe syndrome in female with Factor V Leiden mutation successfully treated with enoxaparin.

Purple toe syndrome is a rare complication of warfarin therapy. It occurs usually after 3 to 8 weeks of therapy and it is caused by cholesterol emboli from atheromatous plaque. Sudden onset of pain in affected area, typically in toes and feet, is the main characteristic of the syndrome. We describe a case of a 65-year-old female with purple toe syndrome after 6 weeks of warfarin. Indication of warfarin was a proximal deep venous thrombosis, which developed after prolonged immobilization. Factor V (FV) Leiden and persistent high FVIII activity were found as additional eliciting factors for venous thromboembolism. After warfarin withdrawal and enoxaparin treatment, symptoms disappeared promptly but a slight discoloration of the toe persists.

[Inhibition of platelet aggregation]. / Thrombozytenaggregationshemmer.

Acute atherothrombotic complications, as part of the accelerated atherosclerosis, contribute to cardiovascular morbibity and mortality in diabetic patients. Inhibition of platelet aggregation can reduce the risk for acute atherothrombosis. The present article represents the recommendations of the Austrian Diabetes Association for the use of antiplatelet drugs in diabetic patients according to current scientific evidence.

Ateroembolia de colesterol y tratamiento combinado con esteroides e iloprost / Cholesterol atheroembolism and combined treatment with steroids and iloprost

La ateroembolia de colesterol (AEC) es una enfermedad sistémica cuya incidencia ha aumentado en las últimas décadas y que presenta una elevada morbimortalidad. En el momento actual se desconocen cuáles son las alternativas terapéuticas más efectivas en esta entidad. En este artículo presentamos el caso de una paciente diagnosticada de AEC con afectación cutánea, intestinal y renal, que presentó una buena evolución tras el inicio de terapia combinada con esteroides y análogos de las prostaglandinas. A pesar de que no existen estudios concluyentes, sugerimos esta alternativa para el manejo de AEC con afectación orgánica (AU)

Cholesterol atheroembolism (CAE) is a systemic disorder whose incidence has increased in recent decades and that presents high morbidity and mortality. Although several therapeutic alternatives have been reported, there is no consensus about the best treatment for this disease. In this paper we report the case of a patient with CAE with skin, bowel and kidney involvement who presented a good response to combined therapy with steroids and prostaglandin analogues. Although there are no conclusive studies, we recommend this therapeutic alternative in the management of CAE with organic failure (AU)

Cholesterol atheroembolism and combined treatment with steroids and iloprost.

Cholesterol atheroembolism (CAE) is a systemic disorder whose incidence has increased in recent decades and that presents high morbidity and mortality. Although several therapeutic alternatives have been reported, there is no consensus about the best treatment for this disease. In this paper we report the case of a patient with CAE with skin, bowel and kidney involvement who presented a good response to combined therapy with steroids and prostaglandin analogues. Although there are no conclusive studies, we recommend this therapeutic alternative in the management of CAE with organic failure.

[Case of purpura nephritis accompanied by idiopathic cholesterol embolism].

A 69-year-old man with a history of hypertension was admitted to our hospital because of proteinuria, renal dysfunction, and both purpura and edema in the lower extremities. Laboratory data on admission revealed proteinuria (3.4 g/day), microscopic hematuria (3+), and renal dysfunction (serum creatinine 1.47 mg/dL). In the renal biopsy, all glomeruli showed mild mesangial proliferation. A few glomeruli showed mild segmental endocapillary proliferation. Crescent was not found in any glomeruli. Immunofluorescent study revealed the deposition of IgA and C3 in the mesangial area. In addition, jagged-edged angular cholesterol clefts of atheromatous emboli were seen in a small artery with tubular atrophy and fibrosis. He was diagnosed as Henoch-Schonlein purpura nephritis accompanied by idiopathic cholesterol crystal embolism, because he previously had not undergone any cardiac procedures (e. g., percutaneous coronary intervention and coronary artery bypass grafting) and anticoagulating therapy. Oral prednisolone (40 mg/day) effectively decreased proteinuria and improved his renal dysfunction. In this case, renal dysfunction may be related to the ischemic interstitial damage caused by cholesterol crystal embolism, as well as purpura nephritis.

Cholesterol embolization syndrome.

PURPOSE OF REVIEW: To describe cholesterol embolization syndrome (CES) and its risk factors, pathophysiology, clinical presentation, diagnosis and treatment. RECENT FINDINGS: To date, no specific diagnostic test (other than biopsy) for CES has been developed. Effective treatments for CES are yet to be developed. SUMMARY: CES (also referred to as cholesterol crystal embolization, atheromatous embolization or atheroembolism) occurs when cholesterol crystals and other contents of an atherosclerotic plaque embolize from a large proximal artery to smaller distal arteries, causing ischemic end-organ damage. Clinical manifestations of CES include constitutional symptoms (fever, anorexia, weight loss, fatigue and myalgias), signs of systemic inflammation (anemia, thrombocytopenia leukocytosis, high erythrocyte sedimentation rate, elevated levels of C-reactive protein, hypocomplementemia), hypereosinophilia, eosinophiluria, acute onset of diffuse neurologic deficit, amaurosis fugax, acute renal failure, gut ischemia, livedo reticularis and blue-toe syndrome. CES may occur spontaneously or after an arterial procedure. There is no specific laboratory test for CES. Retinal exam demonstrating Hollenhorst plaques supports the diagnosis of CES. Biopsy of target organs (usually skin, skeletal muscles or kidneys) is the only means of confirming the diagnosis of CES. Treatment consists of supportive care and general management of atherosclerosis and arterial ischemia.

A patient with idiopathic cholesterol crystal embolization: effectiveness of early detection and treatment.

A 72-year-old man was admitted to our hospital because of progressive renal dysfunction persisting for 1.5 months. Physical examination showed livedo reticularis of the toes of both feet, peripheral edema, and gait disturbance due to the toe pain. The levels of blood urea nitrogen (50.0 mg/dL) and creatinine (2.81 mg/dL) were elevated, and eosinophilia (10%, 870/µL) was noted. A biopsy of the area of livedo reticularis revealed cholesterin crystals. The patient had not undergone angiography, anticoagulation therapy, or antithrombotic treatment. Idiopathic cholesterol crystal embolization was diagnosed. Transesophageal echocardiography revealed intimal thickening of the aorta and plaque. Oral steroid therapy was started because of the progressive renal dysfunction. After steroid therapy, the symptoms improved. Early diagnosis and treatment are important. Renal dysfunction is a common symptom in elderly patients. Cholesterol crystal embolization should also be considered as a cause of unexplained renal dysfunction, especially in such patients.

Cholesterol crystal embolization (CCE): Improvement of renal function with high-dose corticosteroid treatment.

Cholesterol crystal embolization (CCE) is an important and often under-diagnosed cause of renal insufficiency in patients with atherosclerosis. So far, only statins are the mainstay of therapy and the role of corticosteroids is controversial. We describe a 57-year-old gentleman who presented with accelerated hypertension and renal failure three months after coronary angiogram. Renal biopsy showed cholesterol clefts in the arteriole. Initially, management with anti-hypertensives alone (already receiving statins since angiogram) was unsuccessful. A trial of high-dose corticosteroids resulted in an improvement of the general condition in the next two days, and the serum creatinine reduced gradually to 1.6 mg/dL over the next one month. In conclusion, high-dose corticosteroids are useful in the treatment of CCE associated renal failure, especially in cases with no spontaneous recovery of function.

The effect of low-dose corticosteroids on short- and long-term renal outcome in patients with cholesterol crystal embolism.

BACKGROUND: The effect of corticosteroids on renal cholesterol crystal embolism (CCE) remains uncertain. The aim of the present study was to elucidate the effect of steroid therapy on short- and long-term renal outcome in CCE patients. METHODS: Fifty-one patients diagnosed with renal CCE were included in this retrospective study. The patients were divided into two groups according to whether or not they had received steroid therapy (steroid therapy (+), n = 32; (-), n = 19). Corticosteroids were administered at an initial dose of 10-20 mg/day after CCE diagnosis. The values of the estimated glomerular filtration rate (eGFR) in the two groups were examined at CCE diagnosis, 4 weeks after diagnosis and the last follow-up. Additionally, the % change in eGFR at 4 weeks after diagnosis and % change per year in eGFR at the last follow-up were calculated for each patient. RESULTS: The median values of eGFR at diagnosis in patients with and without steroid therapy were 16.4 and 17.9 mL/min/1.73 m(2), respectively. The median % change in eGFR between diagnosis and 4 weeks after diagnosis was 24% in patients with steroid therapy and 5% in those without, and this difference was statistically significant. On the other hand, there was no significant difference between the two groups in the % change in eGFR per year between diagnosis and the last follow-up. CONCLUSIONS: During the short period after CCE diagnosis, steroid therapy showed a good renal outcome in CCE patients. However, this treatment did not have a favorable effect on long-term renal outcome.

Marked regression of aortic plaque by intensive cholesterol-lowering therapy.

A 65-year-old man with rheumatic combined valvular heart disease showed a persistent fever after cardiac catheterization. He was diagnosed with cholesterol embolism due to multiple mobile plaques in the descending thoracic aorta by transesophageal echocardiography (TEE) along with persistent eosinophilia, deteriorating renal function, and blue toe sign. He was treated with intensive cholesterol-lowering therapy for 3 years, resulting in marked regression of the aortic plaque on TEE.

Embolización cutánea por microcristales de colesterol: presentación de un caso y revisión de la literatura / Cholesterol cutaneous crystal embolization: a case report and literature review

La embolización de cristales de colesterol genera un síndrome multiorgánico inespecífico, severo, relativamente infrecuente y de difícil diagnóstico. Se produce por la oclusión de pequeños vasos en diferentes sistemas, entre ellos la piel, órgano diana frecuente. Se comunica el caso de un varón de 69 años con múltiples factores de riesgo cardiovascular y varios eventos desencadenantes que presentó embolización por microcristales de colesterol con compromiso cutáneo y renal.

Cholesterol crystal embolization is a rare and severe multiorganic syn-drome of diffi cult diagnosis. It occurs as a result of the occlusion of smallvessels in diff erent organs, being the skin a frequent diana.We present the case of a 69 years-old male with multiple cardiovascularrisk factors and many precipitant events. He developed cholesterol em-bolization syndrome with cutaneous and renal involvement.