AB0398 CASE SERIES OF PATIENTS WITH CHOLESTEROL CRYSTAL EMBOLISM SYNDROME THAT MIMICS SYSTEMIC VASCULITIS

Background:Cholesterol crystal embolism (CCE) syndrome is a multisystemic disorder caused by small arteries cholesterol crystal emboli subsequent to small pieces of atheromatous plaques from the aorta or other major arteries break off. CCE is often overlooked because it mimics symptoms of systemic vasculitis due to its clinical characteristics such as ulceration and gangrene of toes, livedo reticularis, renal insufficiency. Acute inflammatory reactants such as ESR, CRP may elevate in CCE patients since the cholesterol crystals trigger a foreign-body inflammatory reaction around the arterioles.Objectives:This study aimed to explore the clinical characteristics of CCE patients, to make rheumatologists learn more about this disease.Methods:Peer-reviewed articles in the electronic databases Medline, PubMed, Science Citation Index, China Biomedical Literature Database (CBM), China Journal Full Text Database (CNKI), and WANFANG Data were searched using the terms “cholesterol crystal embolism syndrome”, “cholesterol embolism”, “atherosclerotic embolism”, “atherosclerotic nephropathy”, or “CCE”. Only articles or case reports containing detailed medical records of CCE patients were included. We also included CCE patients in our department.Results:A 66-year-old male CCE patient presented with multiple ulceration and gangrene of toes and heels (Figure 1), subacute renal insufficiency, and elevated CRP and ESR. This patient had been considered as “suspected systemic vasculitis” and was referred to our rheumatology department. Another 39 Chinese CCE patients from the above databases were qualified for analysis. Among these 40 patients, 87.5% (35/40) were male and the mean age was 68±6 years. The most common involved was kidney and 90% (36/40) of patients presenting with renal insufficiency including the progressive increase of serum creatinine, hematuria, proteinuria, or sudden (or sharp) aggravation of hypertension. Next common involved was skin that occurred in 87.5% (35/40) of patients, especially in the toes and heels. For skin manifestations, blue toe syndrome occurred in 82.5% (33/40) of patients, ulceration or gangrene in 25% (10/40), and livedo reticularis in 15% (6/40). Additionally, 12.5% (5/40) showed ocular involvement such as visual impairment and visual field defect. In 2 patients, embolized cholesterol crystal in retinal arteries that is called Hollenhorst plaques was detected by fundoscopy. There were 62.5% (25/40) of patients having elevated CRP or ESR. The positive rate for skin or subcutaneous biopsies was 58% (11/19) and for kidney biopsies was 100% (6/6). The precipitating factors preceding the occurrence of classical symptoms such as blue toe syndrome, livedo reticularis and/or subacute renal insufficiency is important for CCE diagnosis especially for patients who had contraindications or were intolerant to biopsy. The precipitating factors include endovascular intervention (80%), vascular surgery (5%), and anticoagulant or thrombolytic therapy (2.5%). Only 12.5% (5/40) of patients were spontaneous and didn’t have any predisposing factors. General interventions of CCE included statins (82.5%), antiplatelets (32.5%), and dialysis (32.5%). Twelve patients (30%) received glucocorticoids and 75% (9/12) of them renal function improved and ulceration healed (Figure 1). Among 36 patients who presented with renal insufficiency, the renal function returned to normal after treatment in 2 patients (5.6%), but 27 patients (75%) still showed abnormal renal function even though somewhat improved, and 7 patients (19.4%) needed renal replacement therapy or dialysis for maintenance.Conclusion:This study reported CCE patients had high prevalence of renal insufficiency, blue toe syndrome, and ulceration or gangrene of toes, as well as elevated CRP or ESR, thus rheumatologists should be alert to this disease as one of the differential diagnosis of systemic vasculitis, especially for elderly patients with evidence of atherosclerosis who undergo a recent cardiovascular procedure.Disclosure of Interests:None declared

FC 003HYPERURICEMIA HAS VASOACTIVE EFFECTS IN CHOLESTEROL CRYSTAL-INDUCED ACUTE KIDNEY INJURY

Background and Aims Numerous observational studies have reported an association between hyperuricemia (HU) and cardiovascular disease where atherosclerosis is a leading cause. In advanced atherosclerosis, cholesterol crystal (CC) embolism is a life-threatening complication with an average mortality of 62.8%. Clinical manifestations include skin necrosis, intestinal injury and acute kidney injury (AKI). Autopsies and tissue biopsies reveal CC inside the arterial lumen. In a new model of CC-induced AKI, we recently found that fibrin clots formed around CC obstruct peripheral arteries and cause tissue infarction and organ failure. However, the role of asymptomatic HU in CC-induced AKI is currently unknown. Thus, we hypothesized that asymptomatic HU improves the outcomes after CC-induced AKI. Method In vivo, 6 weeks old Alb-creERT2;Glut9lox/lox and Glut9lox/lox control mice were intraperitoneally injected with tamoxifen to deplete hepatic Glut9 expression. Both groups of mice were placed on a standard chow diet enriched with inosine for two weeks. Afterward, a solution of CCs was injected into the left kidney arteries of mice to induce AKI. Serum and kidneys were collected 24 hours later, and kidney function, infarct size and kidney injury evaluated using GFR measurement, colorimetric assays, ELISA and immunohistochemistry of kidney sections. For in vitro studies, we isolated platelets from healthy mice and cultured them in the presence or absence of soluble uric acid (sUA) prior to CC activation. After stimulation, platelet aggregation assays and flow cytometry were performed. Results Our in vivo data showed that Alb-creERT2;Glut9lox/lox mice developed asymptomatic HU without kidney impairment (serum UA levels 9-15 mg/dL), while Glut9lox/lox control mice remained healthy. HU mice displayed a rapid decline in GFR of approx. 80% as compared to only 30% in healthy mice after CC-induced AKI, which was in line with increased serum BUN and IL-6 levels. The rapid GFR decline was due to vasoconstriction in arteries of the contralateral kidney as determined by αSMA/fibrin staining and a reduced ratio of lumen versus artery area in mice with HU after AKI. HU mice also had significantly less kidney infarct size as well as reduced kidney injury (necrosis and edema) and arterial occlusion. The in vitro data showed that sUA had no impact on platelet aggregation, activation and degranulation as compared to medium control in response to CCs. Conclusion We now show that HU has vasoconstrictive effects in the contralateral kidney by reducing GFR, while at the same time protects mice from CC-induced AKI suggesting a compensatory physiological mechanism of autoregulation to protect nephrons. On the other hand, in patients with chronic kidney disease, HU-related vasoconstriction might lead to increased arterial blood pressure; thus, increasing the risk for cardiovascular complications due to platelet activation and aggregation.

Ischemic small bowel perforation caused by cholesterol crystal embolism following transcatheter arterial chemoembolization for recurrent hepatocellular carcinoma: a case report

Background Cholesterol crystal embolism (CCE) following transcatheter arterial chemoembolization (TACE) is rare. Case presentation A 71-year-old man underwent TACE for recurrence of hepatocellular carcinoma (HCC). On postoperative day (POD) 5, he developed abdominal pain and fever. Computed tomography revealed intraperitoneal free air. The patient was diagnosed with gastrointestinal perforation with peritonitis, for which partial intestinal resection and covering ileostomy were performed. Histological examination revealed perforation of the small intestine caused by CCE. The patient made a satisfactory recovery and was discharged on POD 30. The patient showed no recurrence of cholesterol crystal embolism or HCC for 2 years after surgery. Conclusion We reported a successfully treated case of ischemic small bowel perforation due to cholesterol crystal embolism following transcatheter arterial chemoembolization for recurrent HCC.