Disease relevance of Xanthomatosis

• In the present report we describe a patient with multiple myeloma and long-standing paraproteinemia who developed xanthoma in the absence of an elevation in plasma cholesterol or triglyceride concentrations [1].
• Type III hyperlipoproteinemia is characterized by increased plasma levels of triglycerides and cholesterol, palmar-tuberoeruptive xanthoma, and premature cardiovascular disease [2].
• Long-term colestipol therapy in conjunction with diet may reduce xanthoma size, arrest progression of coronary artery atherosclerosis, and may reduce mortality from coronary heart disease [3].
• Intramuscular injection of a plasmid vector expressing human apolipoprotein E limits progression of xanthoma and aortic atheroma in apoE-deficient mice [4].
• Alagille syndrome (AGS) causes intractable pruritus and disfiguring xanthomas because of retained bile acids and cholesterol [5].

Psychiatry related information on Xanthomatosis

• Patients with the disorder present with tendon xanthomas, juvenile cataracts, dementia, and pyramidal and cerebellar abnormalities but have normal plasma cholesterol [6].

High impact information on Xanthomatosis

• Despite a calculated sterol loss of 560 g over 14 months in one patient and 400 g over 10 months in the other, neither plasma cholesterol nor xanthoma size decreased [7].
• Bone marrow transplantation experiments demonstrated that ACAT1 deficiency in macrophages was sufficient to cause dermal xanthomas in hyperlipidemic LDLR-deficient mice [8].
• Consequently, people who suffer from this disease have very elevated plasma plant sterol levels and develop tendon and tuberous xanthomas, accelerated atherosclerosis, and premature coronary artery disease [9].
• An atherogenic diet, high in fat and cholesterol, exacerbates development of atherosclerosis and xanthomas in the 2/2 mice [10].
• High density lipoprotein deficiency with xanthomas. A defect in reverse cholesterol transport caused by a point mutation in the apolipoprotein A-I gene [11].

Chemical compound and disease context of Xanthomatosis

• Competitive inhibition of bile acid synthesis by endogenous cholestanol and sitosterol in sitosterolemia with xanthomatosis. Effect on cholesterol 7 alpha-hydroxylase [12].
• Sitosterolemia and xanthomatosis together are a disease characterized by premature cardiovascular disease, and by elevated plasma concentrations of total sterols and of plant sterols, especially sitosterol which is hyperabsorbed [13].
• Xanthomas appeared in all mice fed the high-cholesterol diet alone but not in those receiving L-arginine [14].
• Cerebrotendinous xanthomatosis was diagnosed on the basis of increased cholestanol levels in his plasma, red cells and xanthoma, changes in bile acid composition due to the defective synthesis of chenodeoxycholic acid [15].
• Xanthomas exhibited marked regression only during the last 6 years, after 16 years of diet and the addition of clofibrate for 7 years [16].

Biological context of Xanthomatosis

• This report presents the clinical features of the patients with sitosterolemia and xanthomatosis and also demonstrates that heterozygotes with this disorder have increased plasma levels of plant sterols as well as cholestanol, and suggests that this rare disease might be inherited as an autosomal co-dominant trait in certain cases [17].
• The whole population was divided into normolipidemic (NL), type IIa without xanthoma (type IIa), type IIa with xanthoma (FH), type IIb and type IV phenotypes [18].
• We conclude that the lack of apo E results in atypical disseminated xanthomatosis, suggesting that apo E has an important role in determining the tissue distribution of cholesterol deposition [19].
• Xanthomas reflect the status of glucose and lipid metabolism [20].
• All in all the results suggest FDB to be a severe genetic disorder with early penetrance, associated with substantial elevations in plasma and LDL cholesterol and with an increased frequency of premature coronary artery disease and of tendon xanthomas [21].

Anatomical context of Xanthomatosis

• Tendon xanthomas, multiple generation transmission, and the appearance of bimodality in the distributions of total and low-density lipoprotein cholesterol were found [22].
• Comparisons were made with a number of measures of disease severity, including cholesterol-year score, calcium score on electron-beam CT (EBCT), and size of Achilles tendon xanthomas [23].
• Even though only a proportion of an RE population is catalase-positive, the results accord with the majority of current opinion that most of the cells in atherosclerotic lesions are derived locally, whereas the phagocytes in lipid implants and xanthomas are of RE origin [24].
• Analysis of monocytes from familial hypercholesterolemic (FH) subjects, who frequently develop xanthomatosis, revealed a significant number of subjects with elevated STAT1alpha and IP-10 expression [25].
• The persistence of the xanthoma may be due to a lack of acceptors, such as high-density lipoproteins, that remove the cholesterol from the foam cells [26].

Gene context of Xanthomatosis

• Hypotheses to account for the palmar xanthomas were that oxidative modification of triglyceride (TG)-rich lipoproteins occurred due to increased plasma residence time, or that their apolipoprotein E (apoE) content was abnormally elevated [27].
• A woman with primary lipoprotein lipase (LPL) deficiency developed marked hypertriglyceridemia, pancreatitis, eruptive xanthomas, and unusual palmar xanthomas during pregnancy [27].
• The xanthomatous lesions found in the Apoe knock-out mouse clearly differed in location from xanthomas previously found in low density lipoprotein receptor-deficient mice [19].
• OBJECTIVE: To analyze the 3beta-hydroxysteroid dehydrogenase (NSDHL) gene in verruciform xanthoma (VX) to elucidate its potential role in the histogenesis of this lesion [28].
• Massive xanthomatosis and atherosclerosis in cholesterol-fed low density lipoprotein receptor-negative mice [29].

Analytical, diagnostic and therapeutic context of Xanthomatosis

• The xanthoma and elevated plasma cholesterol and triglyceride levels in patients with type III hyperlipoproteinemia respond to dietary and drug therapy [2].
• The reduction of plasma cholesterol levels was associated with a complete regression of the xanthomas, supporting DF apheresis as a first-choice treatment for patients with massive LP-X accumulation due to cholestasis [30].
• Despite the architectural resemblance of verruciform xanthoma to verrucous mucocutaneous lesions related to human papillomavirus infection, it was not detected by either immunohistochemistry, in situ hybridization, polymerase chain reaction, or Southern blot analysis in any case [31].
• However, analysis of cutaneous xanthoma and plasma by thin-layer and gas-liquid chromatography revealed that cholesterol was the principal lipid in xanthoma and that there were no unusual sterols in plasma or tissue [32].
• METHODS: Fifty-two cutaneous clear cell lesions including xanthomas (CX), xanthelasmas (XA), xanthogranulomas (XG), balloon cell nevi (BCN), nodular/clear cell hidradenomas (CCH), and MRCC were examined by immunohistochemistry for the expression of CD10, noting frequency and pattern of labeling [33].

References