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

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.

Cholesterol crystal embolism leading to perforation of the gallbladder

BACKGROUND: Cholesterol crystal embolism (CCE) from atherosclerotic arterial disease leading to perforation of the gallbladder is rare. We describe our experience of managing a patient with perforation of gallbladder caused by CCE. METHODS: A 64-year-old man was admitted to this hospital because of acute abdominal pain with clinical features suggestive of peritonitis. He was known to suffer from atherosclerotic peripheral arterial disease and had undergone aortobifemoral bypass 17 years ago. A CT scan showed a collection of peri-hepatic fluid. The gallbladder was normal in appearance but contained multiple calculi. At laparotomy, free bile was observed in the peritoneal cavity, leaking from a pin-hole size peroration of the fundus of the gallbladder. Hence cholecystectomy was performed. RESULTS: The patient made an uneventful recovery. Histological study of the gallbladder showed chronic cholecystitis and obliteration of the lumen of the mural arteries with cholesterol crystals within, indicating CCE. CONCLUSIONS: Although perforation of the gallbladder following CCE of its mural arteries is rare, the diagnosis should be considered in patients with abdominal pain and known atherosclerotic arterial disease. Management should include an early recognition of this condition, prompt institution of treatment, prevention of further insults by discontinuing or avoiding predisposing factors, and modification of cardiovascular risk factors.

Idiopathic cholesterol crystal embolism with atheroembolic renal disease and blue toes syndrome:A case report

BACKGROUND Cholesterol crystal embolization(CCE)is a multisystemic and fatal disease with multiple clinical manifestations;however,there are few cases of idiopathic CCE.Here we report a patient with idiopathic CCE accompanied by atheroembolic renal disease and blue toes who had a relatively good prognosis in the short-term due to early treatment with corticosteroids and statins.CASE SUMMARY A 76-year-old man complained of coldness,numbness and purple color change in his left foot for 7 d.He had a feeling of fatigue,constipation,foamy urine,poor appetite and sleep.He had a lacunar infarction for 5 years and hypertension for 9 mo.Laboratory results showed elevated eosinophils,cholesterol,uric acid,serum creatinine,urea and 24 h urine analysis revealed proteinuria.A renal biopsy revealed atheroembolic renal disease.Taken together,these findings strongly supported the diagnosis of idiopathic CCE and atheroembolic renal disease.CONCLUSION Atheroembolic renal disease and blue toes syndrome can be caused by idiopathic CCE,and early treatment with corticosteroids is effective but requires further investigation.

Clinical analysis of two cases of cholesterol crystal embolism following precutaneous coronary intervention

Cholesterol crystal embolism （CCE） is a serious complication after mechanical manipulation of the aorta during angiography or cardiac vascular surgery1.2. Methods Retrospective analysis of the medical ma- terials of 2 cases of CCE in our hospital and review of some literature were conducted. Results Two cases of CCE had blue toes and renal failure, but cholesterol emboli were found in one patients＇ skin biopsy. Strengthen statins were administered and none received corticosteroids. The renal function in both cases was recovered, and the livedo reticularis was disappeared. Conclusions Since there is currently no established treatment other than supportive therapy to CCE, prevention is very important, and we should avoid aortic manipulating procedures in severely atherosclerotic patients. It＇ s crucial early diagnosis for patients to prevent further development of choles- terol embolism. Our study indicated that statins therapy seems to be a more reasonable and effective therapy.

胆石体外调节人体胆汁的胆固醇结晶途径

背景:胆固醇结晶是胆石形成的一个必要步骤。尽管一些模拟胆汁研究显示,胆石表面与周围水相对于结晶形成过程中的胆固醇分子存在竞争关系;但相关研究尚未在人体胆汁中开展。方法:收集13例行腹腔镜胆囊切除术患者的新鲜胆汁,其中10例为胆固醇结石,3例为胆色素结石。再从其他2例患者收集小的胆固醇结石。应用偏光显微镜观察原始胆汁和超滤胆汁(加入或不加入胆石)中胆固醇结晶的形态,包括螺旋状和针状无水胆固醇结晶,以及片状和块状胆固醇单水结晶。分别于胆石加入胆汁前和加入21天后,称量胆石的重量。结果:在原始胆汁中加入胆石后,无水胆固醇结晶有减少的趋势,但块状胆固醇单水结晶显著增多。在超滤胆汁中加入胆石后,螺旋状结晶和针状结晶的形成有受抑趋势,而片状和块状胆固醇单水结晶数量显著增多。胆汁孵育21天后,胆石重量显著减轻,无论是原始胆汁(-4.5%61.6%,P=0.046)还是超滤胆汁(-6.5%61.5%,P=0.002)。来自胆色素结石患者的胆汁,在未加入胆石前是清亮的;但加入胆固醇胆石后,所有样本均早期出现片状和块状胆固醇单水结晶。结论:无论是在原始胆汁还是超滤胆汁中,加入胆固醇结石均可对胆固醇结晶途径产生重大影响,胆固醇单水结晶的数量增加,而无水胆固醇结晶的形成受抑。固态胆固醇结晶从胆石表面分离或可解释这一现象。

Similarities and differences between biliary sludge and microlithiasis: Their clinical and pathophysiological significances

The terms biliary sludge and cholesterol microlithiasis(hereafter referred to as microlithiasis)were originated from different diagnostic techniques and may represent different stages of cholesterol gall-stone disease.Although the pathogenesis of biliary sludge and microlithiasis may be similar,micro-lithiasis could be preceded by biliary sludge,followed by persistent precipitation and aggregation of solid cholesterol crystals,and eventually,gallstone formation.Many clinical conditions are clearly associated with the formation of biliary sludge and microlithiasis,including total parenteral nutrition,rapid weight loss,pregnancy,organ transplantation,administration of certain medications,and a variety of acute and chronic illnesses.Numerous studies have demonstrated complete resolution of biliary sludge in approximately 40%of patients,a cyclic pattern of disappearing and reappearing in about 40%,and progression to gallstones in nearly 20%.Although only a minority of patients with ultrasonographic demonstration of biliary sludge develop gallstones,it is still a matter of controversy whether micro-lithiasis could eventually evolve to cholesterol gallstones.Biliary sludge and microlithiasis are asymp-tomatic in the vast majority of patients;however,they can cause biliary colic,acute cholecystitis,and acute pancreatitis.Biliary sludge and microlithiasis are most often diagnosed ultrasonographically and bile microscopy is considered the gold standard for their diagnosis.Specific measures to prevent the development of biliary sludge are not practical or cost-effective in the general population.Laparoscopic cholecystectomy offers the most definitive therapy on biliary sludge.Endoscopic sphincterotomy or surgical intervention is effective for microlithiasis-induced pancreatitis.Ursodeoxycholic acid can effectively prevent the recurrence of solid cholesterol crystals and significantly reduce the risk of recurrent pancreatitis.