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

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.

P0742ASSOCIATION BETWEEN EOSINOPHILIA AND RENAL PROGNOSIS IN PATIENTS WITH CHOLESTEROL CRYSTAL EMBOLISM

Background and Aims Approximately, 20%-70% of patients with cholesterol crystal embolism (CCE) have eosinophilia. However, it remains unknown how eosinophilia influences on renal prognosis in patients with CCE. In this study, we investigated an association between eosinophil count (Eo) and renal prognosis in CCE patients on steroid therapy. Method The present study is a single-center retrospective cohort study in patients with pathological proven CCE and Chronic kidney disease from April 2007 to May 2018. This study included the patients who are not treated with maintenance dialysis nor steroid, and moreover followed until November 2019. We analyzed the validity of eosinophil counts using receiver operating characteristic (ROC) curve analysis. In the statistical analysis, renal survival was calculated with the Kaplan– Meier method, and comparisons between higher and low Eo groups were made with the log-rank test. Results Thirty-two patients with pathological diagnosed CCE were enrolled and followed-up for 11.0 (4.7-43.6) months. There were significant differences in the white blood cell (p=0.03), hemoglobin (p=0.007), serum creatinine levels (p=0.03), phosphate (p=0.045), Calcium×Phosphate (p=0.03), and Eo (p=0.016) between the renal survival and renal death groups. Using the receiver operating characteristic curve analysis with Youden index, Eo of 810/µL showed the sensitivity and specificity 71% and 88% for detecting renal death, respectively (area under the carve; 0.789). Comparing the outcomes in patients having Eo ≥ and <810/µL by using the log-rank test, there are significantly higher renal death rate in CCE patients with Eo ≥810/µL (p=0.004). Conclusion Higher eosinophilia was a prognostic risk factor for renal death in the patients with CCE.

P0513NECROINFLAMMATION VERSUS CRYSTAL CLOTS AS THERAPEUTIC TARGET IN CHOLESTEROL CRYSTAL EMBOLISM-RELATED KIDNEY INFARCT

Background and Aims Cholesterol crystal embolism (CCE) is usually a consequence of the rupture of atheromatous plaques in patients with advanced atherosclerosis. We hypothesized that necroinflammation contributes to CCE-related kidney injury/disease (AKI/AKD). Method Injection of cholesterol crystal (CC) into C56BL/6 WT mice kidney via the left kidney artery induced vascular obstruction, kidney infarction, and GFR loss (measured by transcutaneous monitoring of sinistrin clearance in awake and unrestricted mice). GFR recovered to baseline at 2 weeks despite persistent kidney injury and scarring, probably because the non-injected right kidney developed compensatory hypertrophy. To study the role of necroinflammation in this process, we injected CC to either Mlkl-/- mice or WT mice pre-treated with PBS, the necroptosis inhibitor Nec-1s or the NLRP3 inhibitor MCC950 30 min before CC injection. Results At 24h, Nec-1s, MCC950 treatment had significantly reduced infarct size, kidney injury, neutrophil infiltration, and vascular injury compared to PBS control group. Reduced infarct size, e.g. with Nec-1s persistented until day 14. CC injection into Mlkl-/- mice gave the same results. However, none of these interventions had an effect on GFR loss, i.e. AKI because they did not affect crystal clot formation in the arteria afferent to glomerular perfusion. In contrast, anticoagulant treatment prevented infarcts and GFR loss. Conclusion In this new model of unilateral CCE-induced AKI/AKD global kidney function recovers within 14 d, presumably due to adaptive responses in the contralateral kidney as the post-infarct tissue injury persists and leads to kidney atrophy. As both the NLRP3 inflammasome as well as necroptosis are involved in kidney infarct formation, we conclude on necroinflammation as the central mechanism of CCE-induced AKI/AKD. However, what defines AKI is renal function. We found that crystal clot formation is upstream of kidney infarction but independent of necroinflammation. We conclude, despite necroinflammation is central in kidney infarct formation, crystal clots are the better therapeutic target to prevent CCE-related AKI.

P0764STUDY OF 15 CASES OF CHOLESTEROL CRYSTAL EMBOLISM WITH LOW-DENSITY LIPOPROTEIN APHERESIS

Background and Aims Cholesterol crystal embolism (CCE) causes renal damage, and there is a high risk of end-stage renal disease. Corticosteroids, statins and low-density lipoprotein apheresis (LDL-A) have been used to treat CCE, but the prognosis remains poor and treatment not yet established. This study evaluated the efficacy of LDL-A in patients with CCE. Method We performed a retorospective study of 15 Japanese patients in clinical and histological diagnosis of CCE was made April 2015 to December 2017. 10(67%) patients were diagnosed pathologically on skin biopsy and others were diagnosed clinically. All patients had shown CKD with eGFR <60 mL/min/1.73m2 before being diagnosed with CCE. All patients received LDL-A; of these, 13 (87%) also received corticosteroids. The median estimated GFR diagnosis (at baseline) were 13.4 mL/min/1.73m2, and were analyzed stratified into High eGFR group(H) and Low eGFR group(L). Differences in eGFR, 1 month, 3 months and 1 year after LDL-A, were compared in these groups. Results High eGFR group was significantly higher than Low eGFR group over all observation periods (at 1 month; H:21.3 ± 8.9 vs L:15.9 ± 5.6, P=0.023, at 3 months; H:25.9 ± 10.3 vs L:15.4 ± 5.4, P=0.035, at 1 year; H:21.7 ± 8.9 vs L:13.2 ± 5.7, P=0.01). In high eGFR group, eGFR was no change during the observation period and no decrease significantly. In Low eGFR group, eGFR increased significantly at 1 month and 3 months compared to baseline (10.5 ± 2.1 at baseline, 15.9 ± 5.6 at 1month, P=0.007, 15.4 ± 5.4 at 3month, P=0.01), but was comparable to baseline at 1 year. Conclusion In this study, introduction of LDL-A may have the effect of maintaining renal function over the long term at 1year regardless of eGFR at diagnosed as CCE.