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Purpose: To determine whether xanthelasma palpebrarum (XP) is associated with dyslipidemia, cardiovascular disease (CVD), and other systemic conditions in a large population., Design: Case-control study conducted at a single tertiary care center., Participants: Individuals who were examined at a medical screening institute from 2001 through 2020., Methods: Medical records were reviewed to extract data on ophthalmic evaluations, blood test results, and systemic diagnoses. Patients identified with XP in at least 1 eye constituted the study group. A control group without XP was established matched by age and sex at a 10:1 ratio to allow robust statistical analysis., Main Outcome Measures: Associations between XP and dyslipidemia and CVD were determined. Lipid profiles and diagnoses of dyslipidemia and CVD were compared between the case and control groups., Results: The database included 35 452 individuals, 24 287 of whom were male (69%), with a mean ± standard deviation age of 52.2 ± 12.2 years. The study population included 203 patients with XP (0.6%) and 2030 matched control participants. The prevalence of dyslipidemia diagnosis was similar between the two groups (42% XP vs. 46% controls, P = 0.29), as were the use rates of statins, fibrates, or other cholesterol-lowering medications (48% XP vs. 47% controls, P = 0.88). Lipid profiles were similar between the groups, including total cholesterol (controls median 187 [IQR, 163-211] vs. XP 192 [166-215], P = 0.093), high-density lipoprotein (controls median 48 [IQR, 41-57] vs. XP 47 [42-57], P = 0.65), low-density lipoprotein (controls median 120 [101-141] vs. XP 125 [104-145], P = 0.17), and triglyceride levels (controls median 111 [81-152] vs. XP 105 [81-139], P = 0.16). The rate of CVD was similar as well (10% control group vs. 8.9% XP group; P = 0.56). The prevalences of related conditions, including hypertension, diabetes mellitus, and history of cerebrovascular accident, were similar between groups (24% control group vs. 23% XP group, 14% control group vs. 10% XP group, and 1.3% control group vs. 1% XP group, respectively; P > 0.05)., Conclusions: Xanthelasma palpebrarum was not associated with increased rates of dyslipidemia or CVD. This questions the extent to which XP serves as an indicative marker for heightened systemic risk., Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Adipocytic tumors are mesenchymal tumors that are commonly reported in psittacine birds; however, large-scale studies evaluating their prevalence and associated risk factors are lacking. A retrospective study of adipocytic tumors in psittacine birds was performed by reviewing pathology submissions from the University of California, Davis-Drury Reavill Pathology Database, containing 26 013 submissions from psittacine birds (1998-2018). Age, sex, genus, anatomic distribution, and pathological diagnosis were collected for each case when available. The prevalence, risk factors, and association with other lipid-accumulation disorders were reported. A total of 450 cases of lipoma, 129 cases of myelolipoma, 35 cases of hemangiolipoma, 31 cases of liposarcoma, and 451 cases of xanthoma were identified. The prevalence of adipocytic tumors and xanthomas on necropsy was 1.3% (158/11 737, 95% confidence interval [CI]: 1.1-1.6). Adipocytic tumors were identified in 27 genera. Amazona (odds ratio [OR] = 1.93, 95% CI: 1.24-2.99, p = 0.004), Myiopsitta (OR = 2.3, 95% CI: 1.0-5.2, p = 0.041), Melopsittacus (OR = 3.4, 95% CI: 2.1-5.5, p < 0.001), and Agapornis (OR = 3.5, 95% CI: 2.0-6.1, p < 0.001) had significantly higher odds of developing adipocytic tumors compared with other genera, whereas Ara had significantly lower odds (OR = 0.5, 95% CI: 0.3-0.9, p = 0.030). Age was also a significant risk factor for many types of adipocytic tumors. There was no significant association between general adipocytic tumor formation and atherosclerosis or hepatic lipidosis. Xanthomas were associated with atherosclerosis (OR = 1.88, 95% CI: 1.01-3.51, p = 0.048), but not hepatic lipidosis ( p = 0.503). On necropsy, the trunk and air sacs were the most common sites of xanthoma formation, whereas the trunk and liver were the most common sites of lipoma and myelolipoma formation, respectively.

Introduction and Objectives: Tendon xanthomas (TX) are lipid deposits highly specific to familial hypercholesterolemia (FH). However, there is significant variability in their presentation among FH patients, primarily due to largely unknown causes. Lipoprotein(a) is a well-established independent risk factor for atherosclerotic cardiovascular disease in the general population as well as in FH. Given the wide variability of lipoprotein(a) among FH individuals and the likelihood that TX may result from a proatherogenic and proinflammatory condition, the objective of this study was to analyze the size of TX in the Achilles tendons of FH participants and the variables associated with their presence, including lipoprotein(a) concentration., Methods: A cross-sectional study was conducted on 377 participants with a molecular diagnosis of heterozygous FH. Achilles tendon maximum thickness (ATMT) was measured using ultrasonography with standardized equipment and procedures. Demographic variables and lipid profiles were collected. A multivariate linear regression model using a log-Gaussian approach was used to predict TX size. Classical cardiovascular risk factors and lipoprotein(a) were included as explanatory variables., Results: The mean low-density lipoprotein cholesterol level was 277mg/dL without lipid-lowering treatment, and the median ATMT was 5.50mm. We demonstrated that age, sex, low-density lipoprotein cholesterol, and lipoprotein(a) were independently associated with ATMT. However, these 4 variables did not account for most the interindividual variability observed (R 2 =0.205)., Conclusions: TX, a characteristic hallmark of FH, exhibit heterogeneity in their presentation. Interindividual variability can partially be explained by age, male sex, low-density lipoprotein cholesterol, and lipoprotein(a) but these factors account for only 20% of this heterogeneity., (Copyright © 2024 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Pituitary xanthogranulomatomas (XG) are a rare pathological entity caused by accumulation of lipid laden macrophages and reactive granuloma formation usually triggered by cystic fluid leakage or hemorrhage. Our aim was to compare clinical characteristics and presenting features of patients with secondary etiology of XG and those with no identifiable founding lesion (primary -"pure" XG) in order to gain new insights into this rare pituitary pathology. In a retrospective review of 714 patients operated for sellar masses, at tertiary center, we identified 16 (2.24%) with histologically confirmed diagnosis of pituitary XG over the period of 7 years (2015-2021). Patients were further analyzed according to XG etiology: "pure"- XG (n = 8) with no identifiable founding lesion were compared to those with histological elements of pituitary tumor or cyst - secondary XG (n = 8). We identified 16 patients (11 male), mean age 44.8 ± 22.3 years, diagnosed with pituitary XG. Secondary forms were associated with Ratke's cleft cyst (RCC, n = 2) and pituitary adenoma (PA, n = 6). The most common presenting features in both groups were hypopituitarism (75%), headache (68.5%) and visual disturbances (37.5%). Predominance of male sex was noted (males 68.75%, females 31.25%), especially in patients with primary forms. Patients with primary pituitary XG were all males (p = 0.0256) and more frequently affected by panhypopituitarism (87.5% vs. 25%, p = 0.0406) compared to patients with secondary causes. Hyperprolactinemia was noted in pituitary tumor group with secondary etiology only (p = 0.0769). Majority of lesions were solid on magnetic resonance imaging - MRI (81.25%). Distinct clinical phenotype was observed dependent on the etiology of XG.

Xanthelasma palpebrarum (XP) is the most common form of cutaneous xanthoma, with a prevalence of 1.1%~4.4% in the population. However, the cause of XP remains largely unknown. In the present study, we used Mendelian randomization to assess the genetic association between plasma lipids, metabolic traits, and circulating protein with XP, leveraging summary statistics from large genome-wide association studies (GWAS). Genetically predicted plasma cholesterol and LDL-C, but not HDL-C or triglyceride, were significantly associated with XP. Metabolic traits, including BMI, fasting glucose, type 2 diabetes, systolic and diastolic blood pressure, were not significantly associated with XP. Furthermore, we found genetically predicted 12 circulating proteins were associated with XP, including FN1, NTM, FCN2, GOLM1, ICAM5, PDE5A, C5, CLEC11A, CXCL1, CCL2, CCL11, CCL13. In conclusion, this study identified plasma cholesterol, LDL-C, and 12 circulating proteins to be putative causal factors for XP, highlighting the role of plasma cholesterol and inflammatory response in XP development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hu, Liu, Lian and Lu.)

Competing Interests: Conflict of interest: D.C. has participated in educational meetings and/or attended a conferences or symposia (including travel, accommodation, and/or hospitality) with Bristol-Myers Squibb, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Merck Serono, Ferrer, Pfizer, Novartis, and Roche. M.A. reported participation in conferences with Boehringer Ingelheim, AstraZeneca, Bayer, Bristol-Myers Squibb, Grünenthal, Tecnimede, and Merck Sharp & Dohme. The remaining authors do not have any conflict of interests to report.

Aims: Familial hypercholesterolemia (FH) is currently a worldwide health issue. Understanding the characteristics of patients is important for proper diagnosis and treatment. This study aimed to analyze the phenotypic and genetic features, including threshold cholesterol levels, of Korean patients with FH., Methods: A total of 296 patients enrolled in the Korean FH registry were included, according to the following criteria: low-density lipoprotein-cholesterol (LDL-C) ＞190 mg/dL with tendon xanthoma or family history compatible with FH, or LDL-C ＞225 mg/dL. DNA sequences of three FH-associated genes were obtained using whole-exome or target exome sequencing. Threshold cholesterol levels for differentiating patients with FH/pathogenic variant (PV) carriers and predictors of PVs were identified., Results: Of the 296 patients, 104 had PVs and showed more obvious clinical findings, including higher cholesterol levels. PV rates ranged from 30% to 64% when patients were categorized by possible or definite type according to the Simon Broome criteria. Frequent PV types included missense variants and copy number variations (CNVs), while the most frequent location of PVs was p.P685L in LDLR. The threshold LDL-C levels for patient differentiation and PV prediction were 177 and 225 mg/dL, respectively. Younger age, tendon xanthoma, and higher LDL-C levels were identified as independent predictors of PVs, while traditional cardiovascular risk factors were predictors of coronary artery disease., Conclusions: Korean patients with FH had variable PV rates depending on diagnostic criteria and distinctive PV locations. The reported threshold LDL-C levels pave the way for efficient patient care in this population.

Introduction: Xanthelasma palpebrarum refers to lipid deposition that occurs on eyelids and inner canthi. It is an important cutaneous manifestation of hyperlipidemia, atherosclerosis and coronary artery disease. Few studies have been done in Nepal regarding lipid abnormality in xanthelasma patients. The aim of this study was to find out the prevalence of dyslipidemia among patients with xanthelasma palpebrarum visiting the Department of Dermatology of a tertiary care centre., Methods: This is a descriptive cross-sectional study conducted among 80 patients from January, 2021 to February, 2022 in the Department of Dermatology of a tertiary care centre. Ethical approval was taken from the Institutional Review Committee (Reference number: 60512021). Convenience sampling was used. Lipid profile analysis was done among patients with clinical diagnosis of xanthelasma palpabrarum. Data was collected using Microsoft Excel for Mac version 16.16.27 and analyzed using the Statistical Package for the Social Sciences version 22.0. Point estimate at 90% Confidence Interval was calculated along with frequency and proportion for binary data., Results: Out of 80 patients with xanthelasma palpebrarum, the prevalence of dyslipidemia was 64 (80.00%) (74-86 at 90% Confidence Interval). Among them, 29 (45.31%) were males and 35 (54.69%) were females., Conclusions: In our study, the prevalence of dyslipidemia among patients with xanthelasma palpebrarum was found to be higher than in similar studies conducted in similar settings., Keywords: dyslipidemia; gender; lipid.

Background: Xanthogranulomatous cholecystitis is a particularly destructive variant of cholecystitis marked by unique inflammatory changes evident in pathologic specimens. Multiple case series have evaluated this process. However, these often focus on differentiating it from malignancy and have largely been conducted in Asia, where the disease may differ from that seen in the Western hemisphere. This study evaluated surgical outcomes after cholecystectomy for xanthogranulomatous cholecystitis at a high-volume tertiary care institution in the United States. The goal was to determine whether the process can be identified preoperatively and whether modifications should be made to the operative approach in this setting., Methods: Patients with histopathological confirmation of xanthogranulomatous cholecystitis who underwent cholecystectomy between 2002 and 2019 were identified from an updated institutional database. Data regarding demographics, imaging findings, surgical procedures, and perioperative complications were reviewed retrospectively. A cohort of patients undergoing cholecystectomy for more typical diagnoses was also identified for comparison., Results: Twenty-seven patients with a histopathologic diagnosis of xanthogranulomatous cholecystitis were identified. The median age was 64, and 17/27 (63.0%) were male. The majority of cases were done electively on patients admitted that day (17/27). Seventeen patients were evaluated with diagnostic ultrasonography, 21 with computed tomography scan, and 8 with magnetic resonance imaging; 21/27 patients had multiple modality studies. The most common singular finding was gallbladder wall thickening, but the radiographic findings were otherwise inconsistent. Twenty-five patients had planned laparoscopic cholecystectomies, but only 10 were completed. Only 8 of the 15 converted procedures were completed as simple cholecystectomies. Five patients required subtotal cholecystectomy. Median estimated blood loss was 250 cm 3 , and the median time of procedure was nearly 3 hours. Eight patients had complications, including 6 severe complications such as intraoperative bile duct injury., Conclusion: Xanthogranulomatous cholecystitis unfortunately has a nonspecific presentation, which can make it difficult to recognize preoperatively. It is to be suspected in cases featuring a distended, severely inflamed gallbladder that does not match the benign appearance of the patient. When the diagnosis is suspected, an open approach is justified and patients should be counseled as to the increased likelihood of atypical approaches and elevated risk of complication. Referral to a hepatobiliary specialist is to be considered., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background and Aims: Familial hypercholesterolaemia (FH) is associated with high cardiovascular risk and underdiagnosed. Cutaneous manifestations are traditionally used as a major criterion of FH. They are included in the Dutch Lipid Clinic Network or Simon Broome registry criteria. The objective of this study was to evaluate cutaneous manifestations in contemporary FH patients., Methods: We prospectively analysed the clinical presentation of FH patients referred to a University lipid clinic and validated these data in the German FH registry CaRe High., Results: Physical examination revealed that only 14.4% of the FH patients in the lipid clinic cohort (n = 223) showed cutaneous manifestations. An arcus cornealis was present in 0.9%, xanthomata in 1.8%, and xanthelasmata in 12.1%. Xanthelasmata are not part of the clinical scores, but represented 84.4% of all cutaneous manifestations. In 42.6% (n = 95) of the patients, genetic analysis was available. A causal FH mutation was detected in 50.5%. Among carriers, 66.7% had no cutaneous manifestation, 8.3% exhibited an arcus cornealis or xanthomata, and 25.0% had xanthelasmata. In the CaRe High FH registry, data on cutaneous manifestations were available in n = 1274 patients. 3.5% had xanthomata, 5.7% an arcus cornealis, and 7.7% at least one of both; xanthelasmata were present in 10.3%., Conclusions: Cutaneous manifestations are only present in a minority of contemporary patients with FH including the subgroup with monogenic FH mutations. Although rare, the cutaneous signs have value in terms of specificity. However, the clinical characteristics shared by the majority of FH patients may be better suited for screening purposes., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Patients with homozygous familial hypercholesterolemia (HoFH) have a high risk for premature death. Supravalvular aortic stenosis (SVAS) is a common and the feature lesion of the aortic root in HoFH. The relation between SVAS and the risk of premature death in patients with HoFH has not been fully investigated. The present study analysis included 97 HoFH patients with mean age of 14.7 (years) from the Genetic and Imaging of Familial Hypercholesterolemia in Han Nationality Study. During the median (±SD) follow-up 4.0 (±4.0) years, 40 (41.2%) participants had SVAS and 17 (17.5%) participants experienced death. The proportion of premature death in the non-SVAS and SVAS group was 7.0% and 32.5%, respectively. Compared with the non-SVAS group, SVAS group cumulative survival was lower in the HoFH (log-rank test, p <0.001). This result was further confirmed in the multivariable Cox regression models. After adjusting for age, sex, low density lipoprotein cholesterol (LDL&#95;C)-year-score, lipid-lowering drugs, cardiovascular disease, and carotid artery plaque, SVAS was an independent risk factor of premature death in HoFH on the multivariate analysis (hazard ratio 4.45; 95% confidence interval, 1.10 to 18.12; p = 0.037). In conclusion, a significantly increased risk of premature death was observed in HoFH patients with SVAS. Our study emphasized the importance of careful and aggressive management in these patients when appropriate., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Certain conflicting conclusions have been drawn that gastric xanthelasma is related to H. pylori, atrophic gastritis, intestinal metaplasia, and early gastric cancer. The aim of this study was to examine the relationship between gastric xanthelasma and upper gastrointestinal (GI) endoscopic or pathological features. A cross‑sectional study was completed. A total of 8,634 patients who underwent stomach biopsy and who had no gastrectomy history were enrolled in the study. The patients were divided into two groups according to the presence or absence of gastric xanthelasma. The relationship between gastric xanthelasma and demographic characteristics (including age and sex), endoscopic features (including peptic ulcer, bile reflux, and gastric poly), or pathological features (including atrophy, intestinal metaplasia, H. pylori, dysplasia, and gastric cancer) was analyzed. Age/sex matched analysis was also performed to exclude the influence of age and sex. The results revealed that out of the 8,634 patients, 3.54% patients had xanthelasma. Gastric xanthelasma was significantly associated with age (55.76 vs. 49.17 years, P<0.0001), duodenal ulcer (OR 0.860, 95% CI 0.369‑0.923), atrophy (OR 1.839, 95% CI 1.432‑2.362), and intestinal metaplasia (OR 3.296, 95% CI 2.612‑4.159). Binary logistic analysis revealed that age (OR 1.027, 95% CI 1.017‑1.037) and intestinal metaplasia (OR 2.700, 95% CI 2.090‑3.487) were independently related to gastric xanthelasma. Age/sex matched control binary logistic analysis revealed that gastric xanthelasma was significantly associated with presence of intestinal metaplasia (OR 2.338, 95% CI 1.659‑3.297). There was no difference in the number (P=0.427) and location (P>0.05) of gastric xanthelasma for intestinal metaplasia. In conclusion, gastric xanthelasma may be an independent endoscopic warning sign of intestinal metaplasia.

Background: Xanthogranulomatous cholecystitis (XGC) is an uncommon, focal, or diffuse destructive inflammatory disease of the gallbladder mimicking or being together with the gallbladder carcinoma. This study aimed to evaluate the diagnosis, treatment, and outcomes of patients with XGC as a single tertiary center experience in the light of literature., Materials and Methods: Data about 34 patients with XGC identified after evaluating 2212 cholecystectomy specimens between January 2013 and December 2018 in a single tertiary center were documented to determine demographics (sex, age), clinical symptoms and findings, biochemical and imaging clues and operative findings, duration of hospitalization, postoperative complications, and histopathologic results., Results: Thirty-four patients with XGC were evaluated (17 male and 17 female patients with a mean age of 53; range, 25 to 78). Preoperative diagnosis was chronic calculous cholecystitis in 5 patients, cholelithiasis in 12 cases, acute calculous cholecystitis in 16 and emphysematous cholecystitis in 1 patient. Ultrasound was performed in all patients, computerized tomography in 11, contrast-enhanced magnetic resonance imaging in 9, and magnetic resonance cholangiopancreatography in 7 patients. None of the patients were diagnosed preoperatively. All patients received laparoscopic cholecystectomy, among whom 9 were converted to open. Partial cholecystectomy was performed in 1 patient. One patient with gallbladder adenocarcinoma was treated with radical cholecystectomy. XGC has nonspecific clinical and radiologic findings; thus, preoperative diagnosis is generally absent. Open cholecystectomy is the recommended treatment modality. Conversion to open is frequently necessary after laparoscopy. Complete cholecystectomy is the ultimate goal; however, partial cholecystectomy may be preferred to protect the structures of the hepatic hilum. Preoperative imaging studies (ultrasound or computerized tomography) of 34 patients showed a gallbladder stone in 18 patients, microlithiazis in 12 patients, sludge in 10 patients, and gallbladder sclerosis in 5 patients., Conclusions: Diagnosis of XGC and differentiation from gallbladder carcinoma may be difficult through preoperative or peroperative studies, even imaging is useful; the definitive diagnosis depends exclusively on pathologic examination. The surgeon should be prepared for every possibility.

Familial hypercholesterolemia (FH) is reportedly associated with the development of coronary artery disease (CAD), especially acute coronary syndrome (ACS). However, the prevalence of FH in patients with stable CAD is still unclear. The aim of this study was to investigate the prevalence of Achilles tendon xanthoma (ATX) and heterozygous FH in patients with stable CAD and ACS undergoing percutaneous coronary intervention (PCI). A total of 423 patients with CAD (273 stable CAD and 150 ACS) undergoing PCI at Chiba University Hospital between June 2016 and February 2018 were enrolled in this study. Soft X-ray radiography of the Achilles tendon was performed in all patients, and a maximum thickness of 9 mm or more is regarded as ATX. Heterozygous FH was diagnosed according to the Japan Atherosclerosis Society Guidelines. In comparisons between stable CAD and ACS patients, ATX was observed in 9.2% vs. 15.3% (p = 0.055), and heterozygous FH was diagnosed in 3.7% vs. 5.3% (p = 0.416), respectively. Among ACS patients, those with ST elevation myocardial infarction (STEMI) showed the highest prevalence of ATX (19.5%) and FH (7.3%). Whereas ATX and heterozygous FH were considerably observed in patients with ACS, a certain number of ATX and heterozygous FH were also detected in stable CAD patients.

Background/aims: Fundic gland polyps (FGPs), hyperplastic polyps (HPs), and xanthomas (XTs) are common benign gastric lesions that can be diagnosed by endoscopic appearance alone in most cases. The aim of this study was to evaluate associations between gastric cancer and these benign lesions., Methods: Two expert endoscopists reviewed a series of gastroscopy images. FGPs, HPs, and XTs were diagnosed by endoscopic appearance, whereas all gastric cancers were confirmed pathologically., Results: Of the 1,227 patients reviewed, 114 (9.3%) had a concurrent or past history of gastric cancer. The overall prevalences of FGPs, HPs and XTs were 9.4%, 6.3% and 14.2%, respectively. HPs and XTs coexisted in 1.6% of patients, whereas other combinations were rarer. XTs were observed in 39.3% and 11.5% of patients with and without gastric cancer, respectively (p<0.001). In contrast, no gastric cancer patients had FGPs, whereas 10.4% of patients without cancer had FGPs (p<0.001). The prevalence of HPs was similar between the two groups (8.8% and 6.0% of patients with and without cancer, respectively, p=0.29). Multivariate and Mantel-Haenszel analyses demonstrated that XTs were positively associated and FGPs were negatively associated with gastric cancer., Conclusions: XTs and FGPs might be useful as endoscopic risk indicators for monitoring gastric cancer.

Background: Tendon xanthomas are accumulations of collagen and macrophages, which contain cholesterol esters and a marker of high risk for coronary artery disease (CAD)., Objective: The aim of the article was to clarify whether the presence of Achilles tendon thickening (ATT) was associated with disease severity and plaque vulnerability in patients with CAD., Methods: A total of 241 consecutive patients who underwent percutaneous coronary intervention and ATT assessment were analyzed. ATT was defined as Achilles tendon thickness of ≥9 mm on radiograph. The severity of CAD and plaque vulnerability was assessed by the findings on angiogram and optical coherence tomography, respectively., Results: ATT was found in 44 patients (18.2%). The frequency of multivessel disease (79.6% vs 58.4%, P = .009) and left main lesion (13.6% vs 3.1%, P = .004) was significantly higher in patients with ATT (ATT group) than in patients without ATT (no ATT group). Multivariate logistic regression analyses demonstrated that the presence of ATT was independently associated with the presence of multivessel disease (odds ratio, 2.33; 95% confidence interval, 1.08-5.46; P = .031). The ATT group had a higher prevalence of intimal vascular channels (50.0% vs 24.7%, P = .018) and macrophage accumulation (58.3% vs 33.3%, P = .028) in culprit plaque than the no ATT group., Conclusions: Patients with the presence of ATT had a higher prevalence of multivessel coronary disease and left main coronary artery disease than with patients without ATT. The presence of ATT was also associated with vulnerable features, including intimal vascular channels and macrophage accumulation in culprit plaques., (Copyright © 2018 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Prevalence of familial hypercholesterolemia (FH), a common genetic disorder with a high risk for coronary artery disease (CAD), is high among CAD patients; however, data on FH prevalence among acute coronary syndrome (ACS) patients are limited. EXPLORE-J is the largest registry to diagnose FH among Japanese ACS patients using the 2012 Japan Atherosclerosis Society guidelines., Methods: This prospective study consecutively recruited patients between April 2015 and August 2016 at 59 sites. Low-density lipoprotein cholesterol (LDL-C) levels, family history of premature CAD, presence of tendon xanthomas, and Achilles tendon radiograms were recorded at baseline. The prevalence rate of FH in patients with ACS was estimated with 95% CI., Results: Of 1944 analyzed patients (mean age, 66.0 years; men, 80.3%), 52 (2.7% [95% CI: 2.0-3.5]) had FH. Thirty-one (1.6%) had LDL-C ≥180 mg/dL and Achilles tendon thickness (ATT) ≥9 mm, 8 (0.4%) had LDL-C ≥180 mg/dL and family history of premature CAD, 10 (0.5%) had ATT ≥9 mm and family history of premature CAD, and 3 (0.2%) met all the criteria. FH patients were younger than those without FH (59.5 [12.5] vs. 66.2 [12.1] years; p < 0.001). More patients with premature ACS (men, <55 years; women, <65 years) than without (4.7% [95% CI: 2.9-7.2] vs. 2.1% [1.4-3.0]) had FH., Conclusions: FH prevalence is at least five-fold higher in ACS patients than in the general population, especially in patients with premature ACS onset and ATT ≥9 mm. FH screening in ACS patients is therefore clinically important and critical., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Achilles tendons are the most common sites of tendon xanthomas that are commonly caused by disturbance of lipid metabolism. Achilles tendon thickening is the early characteristic of Achilles tendon xanthomas. The relationship between Achilles tendon thickness (ATT) and LDL-C levels, and risk factors of ATT in patients with hypercholesterolemia, have thus far been poorly documented., Methods: A total of 205 individuals, aged 18-75 years, were enrolled from March 2014 to March 2015. According to the LDL-C levels and the "Chinese Guidelines on Prevention and Treatment of Dyslipidemia in Adults", all subjects were divided into 3 groups: normal group (LDL-C < 3.37 mmol/L, n = 51); borderline LDL-C group (3.37 mmol/L ≤ LDL-C ≤ 4.12 mmol/L, n = 50); and hypercholesterolemia group (LDL ≥ 4.14 mmol/L, n = 104). ATT was measured using a standardized digital radiography method and the results were compared among the 3 groups. The correlation between ATT and serum LDL-C levels was analyzed by Pearson's correlation, and the risk factors of ATT were determined by the logistic regression model., Results: ATT in borderline LDL-C group was 8.24 ± 1.73 mm, markedly higher than 6.05 ± 0.28 mm of normal group (P < 0.05). ATT in hypercholesterolemia group was 9.42 ± 3.63 mm which was significantly higher than that of normal group (P < 0.005) and that of borderline LDL-C group (P < 0.05). There was a positive correlation between the serum LDL-C levels and ATT (r = 0.346, P < 0.001). The serum LDL-C level was a risk factor (OR = 1.871, 95% CI: 1.067-3.280) while the levels of HDL-C (OR = 0.099, 95% CI: 0.017-0.573) and Apo AI (OR = 0.035, 95% CI: 0.003-0.412) were protective factors of ATT., Conclusions: ATT might serve as a valuable auxiliary diagnostic index for hypercholesterolemia and used for the assessment and management of cardiovascular disease.

Background: Xanthelasma palpebrarum is a common periorbital lesion that occurs in middle-aged woman. Dyslipidemia was strongly associated with the occurrence of xanthelasma. Different treatment methods for xanthelasma were applied with comparable results., Materials and Methods: This was a retrospective chart review series performed at a single institute. The surgical pathology of 69 patients who received surgical excision from 1994 to 2012 was obtained. In addition, International Classification of Diseases, Ninth Revision, Clinical Modification code of xanthelasma (374.51) of 44 patients who underwent nonsurgical treatment at an outpatient department was acquired from 2006 to 2012. The serum lipid levels, comorbidities, recurrence, and treatment methods were obtained and analyzed with Statistical Analysis System (SAS) 9.4., Results: Of a total of 113 identified patients, 50 had lipid profile data. Of these 50 patients, 25 (50%) had dyslipidemia, which is higher than general population in Taiwan. The recurrence rate was 17.5%, and there was no statistical difference in the recurrence rate between the different treatment methods., Conclusions: Xanthelasma was found to be associated with dyslipidemia. Thus, we recommend patients with xanthelasma to check their lipid profile and receive diet control and lipid-lowering medications for lipid abnormalities.

Background: Visible age-related signs indicate biological age, as individuals that appear old for their age are more likely to be at poor health, compared with people that appear their actual age. The aim of this study was to investigate whether alcohol and smoking are associated with four visible age-related signs (arcus corneae, xanthelasmata, earlobe crease and male pattern baldness)., Methods: We used information from 11 613 individuals in the Copenhagen City Heart Study (1976-2003). Alcohol intake, smoking habits and other lifestyle factors were assessed prospectively and visible age-related signs were inspected during subsequent examinations., Results: The risk of developing arcus corneae, earlobe crease and xanthelasmata increased stepwise with increased smoking as measured by pack-years. For alcohol consumption, a high intake was associated with the risk of developing arcus corneae and earlobe crease, but not xanthelasmata., Conclusions: High alcohol consumption and smoking predict development of visible age-related signs. This is the first prospective study to show that heavy alcohol use and smoking are associated with generally looking older than one's actual age., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Aim: To gain knowledge of xanthelasma, a large population-based study was conducted., Methods: Patients who underwent upper gastrointestinal endoscopy at the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China during Jan 2009 to Nov 2016 were included. General characteristics as well as clinical data were collected, including blood routine, serum biochemical analysis, endoscopic findinds, histological evaluation and comorbiditie. Statistical analyses was performed using SPSS 20.0 software for Windows (IBM Inc., Chicago, IL, United States) using Student's t -test, Mann-Whitney U test, χ 2 test, univariable and multivariable logistic analysis. 2-tailed P value less than 0.05 was considered to be statistically significant., Results: A total of 176006 endoscopies were retrieved and we included 1370 xanthelasma participants (703 men, 667 women) in this study. Prevalence of xanthelasma was 0.78% with average age of 56.6 ± 11.2 years. Chief complaint of xanthelasma consisted abdominal pain (24.2%), up-abdominal discomfort (14.1%), abdominal distention (10.1%), dyspepsia (9.1%), et al. Most xanthelasma occurred as single lesion in gastric antrum. Xanthelasma patients witnessed higher Helicobacter pylori ( H. pylori ) infection rate, more of other gastric lesions including atrophy, intestinal metaplasia and dysplasia ( P < 0.01). In xanthelasma patients, serum carcinoembryonic antigen, triglyceride, fasting glucose, neutrophil, neutrophil-to-lymphocyte ratio were significantly higher, and high density lipoprotein-cholesterol, lymphocyte was lower ( P < 0.05). Xanthelasma accompanied with more fatty liver disease and hepatic cyst, but fewer gallbladder polyp ( P < 0.05). In logistic regression, it revealed that fasting plasma glucose (OR = 3.347, 1.170-9.575, P < 0.05), neutrophil (OR = 1.617, 1.003-2.605, P < 0.05), and carcinoembryonic antigen (OR = 2.011, 1.236-3.271, P < 0.01) were all independent risk factors in xanthelasma., Conclusion: Current study described a large xanthelasma cohort in Chinese population, revealed its relationship with H. pylori infection, carcinogenesis, metabolic dysfunction and inflammation as well., Competing Interests: Conflict-of-interest statement: All authors have no any conflict of interest to declare.

Xanthomatous lesions of the sellar region have traditionally been divided into two separate categories, xanthomatous hypophysitis (XH) and xanthogranuloma (XG) of the sellar region. The seminal article on XH, a condition typified by foamy histiocytes and lymphoplasmacytic infiltrates in the pituitary gland/sellar region, but usually little or no hemosiderin pigment, detailed three patients. However, most reports since that time have been single cases, making understanding of the entity difficult. In contrast, the seminal report on XG, characterized by sellar region cholesterol clefts, lymphoplasmacytic infiltrates, marked hemosiderin deposits, fibrosis, multinucleated giant cells around cholesterol clefts, eosinophilic granular necrotic debris, and accumulation of macrophages, included 37 patients, allowing more insights into etiology. Few examples could be linked to adamantinomatous craniopharyngioma, and although ciliated epithelium similar to that of Rathke cleft cyst (RCC) was identified up to 35% of the 37 cases, it could not be proven that XG was related to hemorrhage into RCC. Case reports since that time, however, occasionally linked XG to RCC when an etiology could be identified at all, and a few recognized that a spectrum exists in xanthomatous lesions of the sella. They review literature, adding 23 cases from our own experience, to confirm that overlap occurs between XH and XG, and that the majority-but not all-can be linked to RCC leakage/rupture/hemorrhage. It was suggested that progressive accumulation of hemosiderin pigment in the lesion, possibly caused by the multiple episodes of bleeding, could account for the transition of at least some cases of XH to XG., (© 2017 International Society of Neuropathology.)

Familial hypercholesterolemia (FH) is characterized by high low-density lipoprotein (LDL) cholesterol with co-dominant transmission and high risk of cardiovascular disease (CVD), although with high variability among subjects. Currently, CVD stratification tools for heterozygous FH (HeFH) are not available. A definition of severe HeFH has been recently proposed by the International Atherosclerosis Society (IAS), but it has not been validated. Our study aims to see clinical characteristics and prevalence of CVD in subjects defined as severe HeFH by IAS criteria. Probable or definite HeFH introduced in the Dyslipidemia Registry of Spanish Arteriosclerosis Society were analyzed by the IAS criteria. Univariate and multivariate analysis was used to assess the association of CVD with the IAS criteria. About 1,732 HeFH cases were analyzed. Severe HeFH had higher prevalence of familial history of CVD, personal history of tendon xanthomas, LDL cholesterol, and CVD than nonsevere HeFH. A total of 656 (77.1%) and 441 (50.1%) of men and women, respectively, fulfilled the IAS criteria of severe HeFH. In the univariate analysis, subjects defined as severe HeFH showed odds ratio 3.016 (95% CI 3.136 to 4.257, p <0.001) for CVD. However, when traditional risk factors were included in the multivariate analysis, only the presence of cholesterol >400 mg/dl had a statistically significant association with CVD odds ratio 8.76 (95% CI 3.90 to 19.69, p <0.001). In conclusion, the IAS definition of severe HeFH is not significantly associated with CVD when adjusted for classic risk factors. Risk stratification in HeFH is an important issue, but the proposed criteria do not seem to solve this problem., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Xanthelasma palpebrarum (XP) is associated with increased risk of ischemic heart disease and myocardial infarction independent of other well-known cardiovascular risk factors. Cardio-ankle vascular index (CAVI) is a novel index of arterial stiffness and important marker of subclinical atherosclerosis. The purpose of this study was to investigate the association between XP and CAVI in asymptomatic subjects., Methods: Consecutive 50 subjects with XP and age-gender matched 50 control subjects were enrolled. Patients with known atherosclerotic vascular disease were excluded. Arterial stiffness was assessed by CAVI and defined as abnormal if CAVI is ≥ 8., Results: Subjects with XP had higher mean CAVI than control subjects (8.05 ± 1.72 vs. 6.76 ± 1.18, p < 0.001). Frequency of abnormal CAVI was higher in subjects with XP (n = 27) compared to those without XP (n = 9, 54 vs. 18 %, p < 0.001). There was a significant correlation between XP and CAVI (r = 0.42, p < 0.001). Conditional logistic regression analysis showed that XP (odds ratio OR 8.80, 95 % confidence interval CI 2.63-29.49, p < 0.001) and age (OR 1.17, 95 % CI 1.08-1.26, p < 0.001) were independent predictors for abnormal CAVI., Conclusion: The study suggests that XP is associated with increased arterial stiffness in asymptomatic subjects.

Few studies have evaluated the prevalence of skin tumours in the geriatric population and none have analysed different skin aging parameters for whole-body skin in this population. To evaluate the prevalence of skin tumours and global skin aging in a French cohort of elderly people. In total, 209 subjects, 105 women and 104 men (mean age: 77.5; range: 74-81 years), were enrolled from the PROOF (PROgnostic indicator OF cardiovascular and cerebrovascular events) cohort. SCINEXA (SCore for INtrinsic and EXtrinsic skin Aging) was used to assess the degree of skin aging and the prevalence of skin tumours. Some additional cutaneous parameters were also studied. Skin aging in women and men was compared. Mean global SCINEXA was 24.3 (SD: 4.7; range: 8.2-35.3). Solar elastosis and lax appearance were more severe in women (t test; p<0.0001), whereas pseudoscars (t test; p = 0.0312) and coarse wrinkles (t test; p = 0.0479) were more severe in men. Erythrosis coli (chi-square test; p <0.0001) was more frequent in men, whereas varicous veins (chi-square test; p = 0.0026) and eyelid xanthomas (chi-square test; p = 0.0282) were more frequent in women. Twelve patients presented with cutaneous carcinomas and two patients had early melanomas. This research describes in detail the main indices of skin aging in an old population and the differences related to gender. Moreover, it highlights the utility of systematic screening of old patients by dermatologists in order to diagnose skin cancers early.

Purpose: Adult-onset xanthogranuloma (AOX) of the corneoscleral limbus is a rare inflammatory condition of unknown aetiology. Similar to limbal juvenile xanthogranuloma (JXG), it presents as a growing mass at the corneoscleral junction. Limbal AOX and JXG can lead to sight-threatening complications if not managed in a timely manner. This systematic review summarises the main clinical and histopathological features of limbal AOX/JXG and discusses the management of this uncommon disease., Methods: We performed a literature search in the MEDLINE database for all historical entries, using the search terms "limbus", "limbal" and "xanthogranuloma", and retrieved all articles reporting on limbal xanthogranuloma. After refining the search to articles relevant to limbal AOX, we were able to identify ten adult cases of limbal AOX and compare those with all reported cases of limbal JXG., Results: Clinically, AOX usually presents as an isolated smooth, yellowish, dome-shaped nodule at the corneoscleral junction, similar to an ocular presentation of JXG, with which it also shares similar histopathological features., Conclusion: Limbal JXG and AOX may represent the same disease entity. Diagnosis relies on the clinical presentation, pathology and immunohistochemical profile. Spontaneous regression is unlikely, and thus prompt surgical intervention should be considered to prevent sight-threatening complications. Xanthogranuloma should be included in the differential diagnosis of corneoscleral limbal masses in patients of all age groups.

Background: Skin problems in the elderly population have rarely been the subject of scientific research., Objectives: The present study aimed to determine the prevalences of the most common dermatological conditions in elderly subjects and to investigate their associations with systemic diseases., Methods: The study involved a group of 198 consecutive patients aged ≥ 65 years who were admitted to the Departments of Dermatology and Geriatrics at the study institution. All participants were thoroughly evaluated in a clinical interview and physical examination in which special emphasis was placed on dermatological issues., Results: All subjects presented at least one dermatological condition. A significant correlation was found between the number of systemic diseases and the number of different skin lesions observed. The most common skin disorders included solar lentigines, senile angiomas, xerosis, seborrheic warts, varicose veins, edema of the lower legs, and pruritus. Patients aged ≥ 75 years demonstrated solar lentigines, edema of the lower legs, clavi, solar keratoses, and onychomycosis significantly more often, whereas patients aged < 75 years suffered more frequently from psoriasis. Diabetes was associated with the development of onychomycosis; hypercholesterolemia promoted the incidence of xanthomas and drug-induced skin reactions; chronic obstructive pulmonary disease was associated with senile purpura; and hypothyroidism favored the occurrence of varicose veins in the lower legs and telogen effluvium., Conclusions: Skin disorders are common in elderly people. Systemic diseases promote the development of dermatological conditions. A comprehensive approach to health problems in elderly subjects requires knowledge of dermatology., (© 2015 The International Society of Dermatology.)

Adult xanthogranuloma presents most commonly as an orange-tan firm solitary nodule with no systemic manifestations. Recently, some cases have been reported in conjunction with lymphoproliferative disorders. Adult reticulohistiocytosis classically presents as red to yellow-red dermal nodules. In the multicentric form, lesions have a predilection for hands and elbows, with a classic coral bead periungual presentation, and are often associated with symmetric erosive arthritis, particularly of the hands and wrists. The presentation and course of Rosai-Dorfman disease, or sinus histiocytosis with massive lymphadenopathy, can vary. The classic presentation is extensive, painless bilateral cervical lymphadenopathy, but some cases have been entirely extranodal., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Adult orbital xanthogranulomatous diseases are rare entities and encompass a group of disorders with varying manifestations that are poorly understood. Taken as a group, there are non-Langerhans histiocytic disorders (type II) that are diagnosed histologically by the presence of foamy histiocytes, Touton giant cells, and varying degrees of fibrosis. Based on the accompanying systemic associations, there are 4 main categories of adult xanthogranulomatous disease: adult-onset xanthogranuloma, adult-onset asthma and periocular xanthogranuloma, necrobiotic xanthogranuloma, and Erdheim-Chester disease. Herein, we discuss the etiopathogenesis, systemic associations, methods of diagnosis, and treatment options for these disorders., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Xanthomas are well circumscribed lesions in the connective tissue of the skin, tendons or fasciae that predominantly consist of foam cells; these specific cells are formed from macrophages as a result of an excessive uptake of low density lipoprotein (LDL) particles and their oxidative modification., Results: Until recently, xanthelasma was considered to be only a cosmetic lesion; however, according to the results of recent prospective studies it is connected with an increased cardiovascular risk and reduced average lifespan. Pathogenetic mechanisms involved in the development of xanthomas resemble early stages of atherogenesis. In clinical practice, xanthomas can signalise various congenital or acquired dyslipidemias. The most prevalent form of xanthomas is xanthelasma palpebrarum. Tendinous and tuberous xanthomas are typical for autosomal dominant hypercholesterolemia, as well as for some rare conditions, such as cerebrotendinous xanthomatosis and familial β-sitosterolemia. In patients with familial hypercholesterolemia, the presence of tendinous xanthomas has been shown to be associated with a two to four times higher risk for cardiovascular disease. Eruptive xanthomas are skin manifestations of a severe hypertriglyceridemia and implicate an elevated risk for acute pancreatitis or type 2 diabetes mellitus. Xanthoma striatum palmare is pathognomic for primary dysbetalipoproteinemia, whereas diffuse plane xanthomas are frequently associated with paraproteinemia and lymphoproliferative disorders., Conclusion: Thorough familiarity with the clinical presentation of xanthomas helps in the diagnosis and follow-up of different forms of dyslipidemia. Moreover, xanthelasma palpebrarum, the most prevalent form of xanthomas, is connected with increased risk of atherothrombotic disease independently of conventional cardiovascular risk factors. To fully understand the pathogenesis, further experimental and clinical research is required.

Introduction: Xanthogranulomatous cholecystitis (XGC) is often mistaken for, and may predispose to, gallbladder carcinoma (GB Ca). This study reviews the worldwide variation of the incidence, investigations, management and outcome of patients with XGC., Methods: Data from 29 studies, cumulatively containing 1599 patients, were reviewed and results summarized by geographical region (Europe, India, Far East and Americas) with 95% confidence intervals (CIs) to present variability within regions. The main study outcomes were incidence, association with GB Ca and treatment of patients with XGC., Results: Overall, the incidence of XGC was 1.3-1.9%, with the exception of India where it was 8.8%. The incidence of GB Ca associated with XGC was lowest in European studies (3.3%) varying from 5.1-5.9% in the remaining regions. Confusion with or undiagnosed GB Ca led to 10.2% of patients receiving over or under treatment., Conclusions: XGC is a global disease and is associated with GB Ca. Characteristic pathological, radiological and clinical features are shared with GB Ca and contribute to considerable treatment inaccuracy. Tissue sampling by pre-operative endoscopic ultrasound or intra-operative frozen section is required to accurately diagnose gallbladder pathology and should be performed before any extensive resection is performed., (© 2013 International Hepato-Pancreato-Biliary Association.)

Background and Aim: The significance of gastric xanthelasma in relation to gastric disease still remains unclear. We investigated the prevalence and significance of gastric xanthelasma in patients with atrophic gastritis and gastric cancer., Methods: A total of 3238 patients who underwent endoscopic examinations of the upper gastrointestinal tract were enrolled. We retrospectively investigated the presence of gastric xanthelasma, the severity of gastric atrophy, and the presence of gastric cancer, and examined the relationship between gastric xanthelasma and various clinicopathological features., Results: Gastric xanthelasma was detected in 249 (7.7%) of the 3238 patients and was significantly associated with age ≥ 65 years, male gender, open-type atrophy, and the presence of gastric cancer (P < 0.0001, P = 0.0002, P < 0.0001 and P < 0.0001, respectively). Multivariate analysis revealed that the presence of gastric cancer was independently related to the presence of gastric xanthelasma (odds ratio 6.19 [3.95-9.70], P < 0.0001). Age/sex/atrophy-matched control analysis demonstrated that the presence of gastric xanthelasma was significantly associated with the presence of gastric cancer (P < 0.0001). Moreover, the presence of xanthelasma in the upper region of the stomach was significantly associated with gastric cancer (P = 0.002). Gastric xanthelasma was observed in 50 (47.6%) of 105 patients with gastric cancer., Conclusion: Gastric xanthelasma may serve as a warning sign for the presence of gastric cancer., (© 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.)

The behavior of atypical fibroxanthoma is benign, if strict diagnostic criteria are applied. Tumors with similar pathologic features but deep subcutaneous invasion, necrosis, and/or lymphovascular or perineural invasion are thought to be associated with adverse outcome and are better regarded as pleomorphic dermal sarcoma or undifferentiated pleomorphic sarcoma of skin. This tumor group is not well documented in the literature, and its characteristics are only poorly defined. To study the clinical and pathologic spectrum more comprehensively, we retrieved 32 pleomorphic dermal sarcomas from our departmental files. The tumors were large (median: 25 mm) and exclusively presented on sun-damaged skin with a strong predilection for the head. Typically, elderly men were affected (median age: 81 y). Histologically, these often ulcerated tumors were poorly marginated, asymmetrical, and deeply invasive into deep subcutaneous, muscular, and/or fascial tissues. The tumors were cellular and composed of pleomorphic epithelioid cells, atypical spindle cells, and multinucleated tumor giant cells in varying proportions. Mitotic count was brisk and often atypical. Tumor necrosis was observed in 53%, lymphovascular invasion in 26%, and perineural infiltration in 29%. The majority of tumors showed a predominance of atypical spindle cells in a fascicular arrangement. A sheet-like growth of pleomorphic epithelioid cells or mixed spindle and epithelioid cell features were less frequently observed. Myxoid and keloidal change, a desmoplastic stromal response, pseudoangiomatous and storiform growth patterns, and admixed osteoclast-like giant cells were additional morphologic features in some cases. No immunoreactivity was noted for multiple cytokeratins, S100, HMB-45, desmin, and CD34. Smooth muscle actin was expressed in 70%, CD31 in 48%, epithelial membrane antigen in 16%, Melan A in 6%, and p63 in 1 case. CD10 was expressed in all cases stained. Follow-up (available for 29 patients; median: 24 mo) showed local recurrence in 28% and a metastatic rate of 10%, mainly in the skin. Progressive metastatic disease was observed in 2 patients. Remission was achieved in 1 patient using systemic chemotherapy. The second patient died in the setting of advanced-stage non-Hodgkin lymphoma. No disease-related mortality was noted. Our data underscore the importance of recognizing adverse histologic features in tumors otherwise resembling atypical fibroxanthoma. Deep subcutaneous invasion, tumor necrosis, and perineural and/or lymphovascular invasion confers at least low-grade malignant potential.

Purpose: To evaluate the association between xanthelasma palpebrarum (XP) and atherosclerosis by the measurement of carotid intima media thickness (CIMT). In addition, the concurrent association between metabolic syndrome, dyslipidaemia and dyslipoproteinaemia was also assessed., Study Design: A cross-sectional study was conducted from January 2008 to April 2009 involving 40 patients of XP and an equal number of age, sex and body mass index matched controls. All study subjects underwent CIMT estimation by ultrasonography and were evaluated for metabolic syndrome (obesity, blood pressure, blood glucose, serum lipid profile), non-alcoholic fatty liver disease, apolipoprotein A1 and apolipoprotein B., Results: The mean CIMT was significantly higher in XP patients as compared with controls. However, there was no correlation with the extent or the duration of the XP lesions. Prevalence of metabolic syndrome was similar in both groups while non-alcoholic fatty liver disease was more frequent in XP patients as compared with controls (p=0.001). The mean serum cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglyceride levels were similar in the two groups. However, there was significant increase in the mean pro-atherogenic apolipoprotein B and decrease in the anti-atherogenic apolipoprotein A1 levels in XP patients., Conclusions: Alteration in apolipoprotein levels (A1 and B) in XP patients may predispose to cutaneous and systemic deposition of lipids, including atherosclerosis. Therefore, XP patients irrespective of their lesion size or serum lipid levels should be screened using CIMT for detection of subclinical atherosclerosis.

Objective: To test the hypothesis that xanthelasmata and arcus corneae, individually and combined, predict risk of ischaemic vascular disease and death in the general population., Design: Prospective population based cohort study., Setting: The Copenhagen City Heart Study., Participants: 12,745 people aged 20-93 years free of ischaemic vascular disease at baseline and followed from 1976-8 until May 2009 with 100% complete follow-up., Main Outcome Measures: Hazard ratios for myocardial infarction, ischaemic heart disease, ischaemic stroke, ischaemic cerebrovascular disease, and death; odds ratios for severe atherosclerosis., Results: 563 (4.4%) of participants had xanthelasmata and 3159 (24.8%) had arcus corneae at baseline. During 33 years' follow-up (mean 22 years), 1872 developed myocardial infarction, 3699 developed ischaemic heart disease, 1498 developed ischaemic stroke, 1815 developed ischaemic cerebrovascular disease, and 8507 died. Multifactorially adjusted hazard/odds ratios for people with versus those without xanthelasmata were 1.48 (95% confidence interval 1.23 to 1.79) for myocardial infarction, 1.39 (1.20 to 1.60) for ischaemic heart disease, 0.94 (0.73 to 1.21) for ischaemic stroke, 0.91 (0.72 to 1.15) for ischaemic cerebrovascular disease, 1.69 (1.03 to 2.79) for severe atherosclerosis, and 1.14 (1.04 to 1.26) for death. The corresponding hazard/odds ratios for people with versus those without arcus corneae were non-significant. In people with versus those without both xanthelasmata and arcus corneae, hazard/odds ratios were 1.47 (1.09 to 1.99) for myocardial infarction, 1.56 (1.25 to 1.94) for ischaemic heart disease, 0.87 (0.57 to 1.31) for ischaemic stroke, 0.86 (0.58 to 1.26) for ischaemic cerebrovascular disease, 2.75 (0.75 to 10.1) for severe atherosclerosis, and 1.09 (0.93 to 1.28) for death. In all age groups in both women and men, absolute 10 year risk of myocardial infarction, ischaemic heart disease, and death increased in the presence of xanthelasmata. The highest absolute 10 year risks of ischaemic heart disease of 53% and 41% were found in men aged 70-79 years with and without xanthelasmata. Corresponding values in women were 35% and 27%., Conclusion: Xanthelasmata predict risk of myocardial infarction, ischaemic heart disease, severe atherosclerosis, and death in the general population, independently of well known cardiovascular risk factors, including plasma cholesterol and triglyceride concentrations. In contrast, arcus corneae is not an important independent predictor of risk.

Background: Severe hypertriglyceridemia (HTG) is one cause of acute pancreatitis, yet the level of plasma triglycerides likely to be responsible for inducing pancreatitis has not been clearly defined., Methods and Results: A retrospective cohort study was conducted on patients presenting non-acutely to the Healthy Heart Program Lipid Clinic at St. Paul's Hospital with a TG level > 20 mM (1772 mg/dl) between 1986 and 2007. Ninety-five patients with TG > 20 mM at the time of referral were identified, in who follow up data was available for 84. Fifteen patients (15.8%), with a mean outpatient TG level of 38.1 mM, had a history of acute pancreatitis. Among 91 additional patients with less severe HTG, none had a history of pancreatitis when TG were between 10 and 20 mM. Among patients with TG > 20 mM on presentation, 8 (8.5%), with a mean TG level of 67.8 mM, exhibited eruptive xanthomata. A diet high in carbohydrates and fats (79%) and obesity (47.6%) were the two most frequent secondary causes of HTG at initial visit. By 2009, among patients with follow up data 53% exhibited either pre-diabetes or overt Type 2 diabetes mellitus. Upon referral only 23 patients (24%) were receiving a fibrate as either monotherapy or part of combination lipid-lowering therapy. Following initial assessment by a lipid specialist this rose to 84%, and remained at 67% at the last follow up visit., Conclusions: These results suggest hypertriglyceridemia is unlikely to be the primary cause of acute pancreatitis unless TG levels are > 20 mM, that dysglycemia, a diet high in carbohydrates and fats, and obesity are the main secondary causes of HTG, and that fibrates are frequently overlooked as the drug of first choice for severe HTG.

Background: Autosomal Dominant Hypercholesterolemia (ADH) is an autosomal dominant disease caused by mutations in the low density lipoprotein receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin type 9 (PCSK9) genes. Xanthomas and coronary heart diseases (CHD) at an early age are the major clinical manifestations of the disease., Methods: 16 families with familial hypercholesterolemia from different regions in Tunisia participated in the study. Mutations within the LDLR gene were screened through DNA sequencing. Lipids values were measured by standard enzymatic methods., Results: We present here thirty five homozygotes and fifty six heterozygotes. Homozygotes presented extensive xanthomatosis, variable clinical manifestations of CHD, and total cholesterol levels in males and females of 17.26+/-4.18 and 17.64+/-2.59 mmol/L respectively. HDL-cholesterol levels were 0.62+/-0.24 and 1.00+/-0.61 mmol/L for males and females, respectively. None of the heterozygotes had tendon xanthomas (except for one female aged 62), eight had corneal arcus, and nine developed CHD mean between 46 and 88 years old. Total cholesterol levels in males and females ranged from 4.60 to 8.90 and from 4.30 to 10.50 mmol/L, respectively., Conclusion: Tunisian FH heterozygotes are characterized by a moderate clinical and biological expression of the disease., (Copyright 2010 Elsevier B.V. All rights reserved.)

Objectives: To investigate the association between xanthelasma, atherosclerotic risk factors, and lipoprotein (Lp) (a), and to determine whether xanthelasma may be a cutaneous marker for atherosclerosis., Methods: One hundred consecutive patients with xanthelasma and 100 age- and sex-matched patients without xanthelasma, seen during the same time period (controls), were included in this study. The prevalence of cardiac risk factors, the rates of atherosclerotic disease, Framingham risk scores, and Lp (a) levels were compared between the patient groups., Results: Hyperlipidemia was found to be significantly more common in patients with xanthelasma (P = 0.001); however, the rate of clinically overt cardiovascular disease and future cardiovascular risk, assessed by the Framingham risk score, were similar between the groups. No significant difference was observed in serum Lp (a) levels between the groups., Conclusions: In patients with xanthelasma, no increase was observed in the rate or risk of cardiovascular disease. Moreover, no relationship was found between Lp (a) levels and xanthelasma.

Familial hypercholesterolaemia (FH), an autosomal dominantly inherited disorder characterised by elevated plasma low-density lipoprotein (LDL) cholesterol levels, tendon xanthomata and premature ischaemic heart disease, is amenable to treatment with modern medication. The clinical and biochemical details of 1 031 patients with FH were analysed. FH is the most common monogenic disorder of lipoprotein metabolism presenting to the Lipid Clinic at Groote Schuur Hospital, accounting for about 20% of consultations. The hospital classified 55% of the FH patients as white, 43% as coloured, 1.5% as Asian and 0.5% as black. In the FH cohort (whose mean age at presentation was 44 years), 80% had tendon xanthomata, 36% had arcus cornealis, and 14% had xanthelasma. Tendon xanthomata was present in almost 90% of patients by the age of 50 years. Arcus cornealis was present in about 45% by the age of 40 years, further increasing in frequency with age. Cardiovascular complications included ischaemic heart disease (43%), stroke (1.5%), transient ischaemic attacks (1.3%), and peripheral vascular disease (3.7%). The mean age of death was 55 (+/-13) years; 51 ( +/-10) years in men and 61 ( +/-12) years in women. In 46% of the cohort, a defective gene was identified by testing for locally prevalent mutations.

Lipoprotein lipase deficiency causes severe hypertriglyceridaemia due to chylomicronaemia, and leads to recurrent and potentially life-threatening pancreatitis. This disorder can only be managed by dietary fat restriction as drugs are ineffective. We review the experience with familial chylomicronaemia in patients who attended the lipid clinics at Groote Schuur Hospital and Red Cross Children's War Memorial Hospital in Cape Town. Criteria for inclusion were an initial plasma triglyceride concentration of >15 mmol/l and a typical type I Fredrickson hyperlipidaemia pattern on plasma lipoprotein electrophoresis. A total of 29 patients were seen over 25 years. The mean age of presentation was 10 years, but ranged from 0 to 43 years. The modes of presentation differed: pancreatitis (N=16), eruptive xanthomata (N=2), coincidental detection of hypertriglyceridaemia (N=2), screening relatives (N=7), and after death from pancreatitis (N=1). Plasma triglycerides responded rapidly and dramatically to dietary fat restriction, and some patients sustained good control of the hyperlipidaemia. The onset of pancreatitis was earlier in patients of Indian ancestry, suggesting a genotype/phenotype interaction within this disorder. Genetic work-up indicated founder effects in the Afrikaner and Indian patients. Lipaemic plasma should be taken seriously at all ages, and necessitates work-up at specialised clinics where the diagnosis of chylomicronaemia or type I hyperlipidaemia facilitates appropriate dietary management that can prevent pancreatitis.

Aim: The retrospective analysis of prevalence, peculiarities of duration of biliary calculosis without gall bladder cholesterosis, biliary calculosis with gall-bladder cholesterosis and xanthogranulematous cholecystitis among persons who underwent cholecystectomy using clinical, instrumental and morphological data. MATERIAL AND METHODS. The data was evaluated obtained from medical cards of 4073 inpatients operated for cholelithiasis in 1999-2005. Preoperative clinical condition, body mass index, the results of abdominal ultrasonography, morphology of removed gall-bladders were evaluated. Statistical processing was made by Student's criterion and correlation analysis., Results: After cholecystectomy the diagnosis of cholelithiasis was confirmed in 4020 patients (98.7%). 1177 patients had concomitant gall-bladder cholesterosis (GBC), 38 patients-- xanthogranulematous cholecystitis (XC). GBC and XC were diagnosed morphologically only in the postoperative stage. The patients were divided into three groups: cholelithiasis without GBC (32 patients), cholelithiasis with GBC (68 patients), XC (38 patients). Diseases of the gall-bladder occur more frequent in women and older patients. XC in males occurred 2 times more frequently, cholelithiasis without cholesterosis and XC ran 2 times less. The above diseases are related with disorders of metabolism and lipid transport. GB dyskinesia has different causes in each of the diseases., Conclusion: The analysis determined peculiarities of duration of cholelithiasis without gall-bladder cholesterosis, cholelithiasis with GBC and XC. This necessitate differential therapy.

Aim: To investigate the relationship among gastric xanthomatosis (GX), H pylori, dyslipidemia, and gastritis in Korea, a well-known H pylori endemic area., Methods: A total of 771 patients who had undergone gastroduodenoscopy by one endoscopist were included in this study. Among them, 54 patients with GX were assessed for H pylori infection and their endoscopic characteristics and serum lipid profiles. The findings were compared with 54 age- and sex-matched control subjects without GX., Results: The prevalence of GX was 7% (54/771) with no sex difference. GX was mainly single (64.8%) and located in the antrum (53.7%). The mean diameter was 7 +/- 3 mm. Mean body mass index (BMI) of patients with GX was 23.1 +/- 2.8 and no one was above 30. Compared with the controls, lipid profiles of GX group showed significantly lower HDL-cholesterol (48.8 +/- 12.3 vs 62.9 +/- 40.5, P = 0.028) and higher LDL-cholesterol (112.9 +/- 29.9 vs 95.9 +/- 22.4, P = 0.032). The level of total serum cholesterol, triglyceride and the existence of dyslipoproteinemia were not related to the presence of GX. However, GX showed a close relationship with endoscopically determined atrophic gastritis and histologic severity (24/53, 44.4% vs 8/54, 14.8%, P = 0.0082). H pylori infection and bile reflux gastritis were not significantly related with GX., Conclusion: The prevalence of GX is 7% and it may be an increasing entity in Korea. Moreover, dyslipidemia and atrophic gastritis are found to be related to GX, but H pylori infection is not.

There were studied the peculiarities of the state of patients with xantogranulomatous cholecystitis (XGC) using clinical and instrumental diagnostics performed in preoperative period as well as morphological state of the wall of removed gall-bladders. It was established that the prevalence of XGC among patients after cholecystectomy because of biliary calculosis is 0,93%. The frequency of XGC in women is three times higher than in men. There is prevalence of patients older than 50 years. The clinical period of XGC in men is twice shorter than among women and a polimorbid pathology is more often found in men than in women. XGC has no specific clinical signs. Morphologically the xantogranulomes are the combination of xanthom cells, lymphocytes and plasmocytes. To detail this process it is necessary to determine subpopulations of T- lymphocytes presented in the xantogranulome.

Background/purpose: Oral verruciform xanthoma (VX) is an uncommon oral mucosal lesion. This retrospective study evaluated the clinical and histopathologic features of 15 oral VXs occurring in Taiwanese patients., Methods: Fifteen consecutive cases of oral VX were collected from January 1988 to December 2005. Clinical data and microscopic features of these cases were reviewed and analyzed., Results: The mean age of patients was 45 years (range, 18-79 years). There were eight male and seven female patients. Seven (46.6%) cases occurred on the gingiva, four (26.7%) on the tongue, and four (26.7%) on the buccal or vestibular mucosa. The greatest mean dimension of the lesions was 0.8 cm (range, 0.3-2.0 cm). Three patients had concomitant other oral mucosal lesions such as oral submucous fibrosis, squamous cell carcinoma, and erosive oral lichen planus. Microscopically, all specimens showed varying degrees of surface parakeratosis and the accumulation of numerous foam cells in the connective tissue papillae among uniformly elongated epithelial ridges. Individuals or aggregates of foam cells were also found underneath the epithelial ridges in nine (60%) cases. When the oral VX lesions were further classified into three types according to the microscopic surface architecture, seven (47%) lesions were of the verrucous type, three (20%) the papillary type, and five (33%) the flat type. All patients received surgical excision of the lesions and no recurrence was noted during follow-up of up to 18 years., Conclusion: Oral VXs occur more frequently in the fifth decade of life. The more commonly affected site is the gingiva. The treatment of choice for oral VXs is surgical excision. The prognosis is excellent and recurrence was not seen in this study.