1/9. Management of lipoprotein-x accumulation in severe cholestasis by semi-selective LDL-apheresis.liver disorders characterized by prolonged bile stasis are often associated with the accumulation of an abnormal lipoprotein, lipoprotein-x (LP-X), in plasma. LP-X is separated in the low-density lipoprotein (LDL) density range, but lacks apolipoprotein B and does not interact with the LDL receptor; LP-X can cause hyperlipidemia, cutaneous xanthomas, and worsening of arterial disease. We report the case of a patient with severe cholestasis, markedly elevated plasma cholesterol levels (26.8 to 31.5 mmol/L), mainly due to a massive accumulation of LP-X in plasma, and diffuse xanthomas. To reduce the elevated cholesterol levels, the patient was given extracorporeal treatment aimed at removing atherogenic lipoprotein (LDL-apheresis). LDL-apheresis was performed at weekly or bi-weekly intervals, either by a semi-selective technique using filters with a defined pore diameter (double filtration, DF) or by a more selective technique using dextran-sulfate-cellulose (DSC) columns able to bind LDL. The semi-selective DF technique proved more effective than DSC, removing 48% of total cholesterol (compared to 30% with DSC), and lowering cholesterol levels to 11.1 mmol/L in 6 weeks. DF removed both LDL and LP-X from plasma, whereas DSC selectively decreased the LDL content. 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.- - - - - - - - - - ranking = 1keywords = xanthoma (Clic here for more details about this article) |
2/9. Gingival and cutaneous xanthomatosis associated with primary biliary cirrhosis. Report of a case.The first comprehensive case report of intraoral xanthomatosis associated with primary biliary cirrhosis is detailed. The lesions were present along the free gingival margin and labial vestibule. Crevicular fluid was noted to be tinged yellow. Generalized cutaneous eruptions were also seen. The xanthomas were attributed to the underlying hyperlipoproteinemia. Advanced progression of the hepatic disease necessitated a liver transplant. Disappearance of both oral and skin lesions were subsequently observed.- - - - - - - - - - ranking = 2keywords = xanthoma (Clic here for more details about this article) |
3/9. Eruptive and tubero-eruptive xanthomas of the skin arising on sites of prior injury. Two case reports.Eruptive and tubero-eruptive xanthomas arising at the site of previous minor skin injury are described in two patients with type IV and type III hyperlipidemia, respectively. In one case, the lesions appeared following a cat scratch, while in the second, massive bee stinging preceded the appearance of a constellation of xanthomas.- - - - - - - - - - ranking = 2keywords = xanthoma (Clic here for more details about this article) |
4/9. Tendon xanthomas associated with cholestanolosis and hyperapobetalipoproteinemia.Large achilles tendon xanthomas of the type found in severe familial hypercholesterolemia were the first manifestation of cholestanolosis (cerebrotendinous xanthomatosis) in our patient, an otherwise asymptomatic normolipidemic 21-year-old woman. Extensive laboratory investigation disclosed the presence of hyperapobetalipoproteinemia which did not resolve with the administration of probucol. Immunofluorescent studies revealed marked accumulation of apolipoprotein B in a xanthoma excised from the tricipital area. This was in contrast to the spotty and weak fluorescence observed in a tuberous xanthoma, from the same anatomical area and histologically otherwise identical, obtained from a patient with heterozygous familial hypercholesterolemia. Hyperapobetalipoproteinemia has been reported before in association with sitosterolemia but not with cholestanolosis. We suggest that cholestanol, like sitosterol, may interfere with the normal uptake and degradation of low-density lipoproteins by peripheral cells.- - - - - - - - - - ranking = 2.6666666666667keywords = xanthoma (Clic here for more details about this article) |
5/9. Perineural xanthoma.A 50-year-old man suffering from cholestatic hepatitis and diabetes mellitus with hyperlipoproteinaemia had small, painful, slightly elevated, reddish, firm indurated plaques on his soles. Histologically, the lesions were composed of a centrally located cutaneous nerve surrounded by concentric layers of xanthoma cells. Electron microscopy showed the cutaneous nerves to be unmyelinated, their axons were vacuolated and contained dense bodies. The xanthoma cells had the same ultrastructural features as those observed in usual xanthomatous lesions. We suggest that this entity be named perineural xanthoma.- - - - - - - - - - ranking = 2.6666666666667keywords = xanthoma (Clic here for more details about this article) |
6/9. Plexiform xanthomatous tumor. A report of three cases.We describe three cases of plexiform xanthomatous tumor in middle-aged men. The tumors shared some morphological features with xanthoma, cholesterotic fibrous histiocytoma, and plexiform fibrohistiocytic tumor. However, no hyperlipoproteinemia was found in our cases, and many morphological features distinguish the plexiform xanthomatous tumor from all the other entities.- - - - - - - - - - ranking = 2.3333333333333keywords = xanthoma (Clic here for more details about this article) |
7/9. Flexural planar xanthomas: report of four cases.Four patients with primary hyperlipoproteinemia, Frederickson's type IIb, were observed to have symmetrical planar xanthomas affecting flexures: finger webs, antecubital and popliteal fossae, axillae, and intergluteal cleft. Other types of xanthomas were also present and serum lipid electrophoresis showed type IIb pattern. We draw attention to the peculiar pattern of symmetrical planar xanthomatosis hitherto described only with type III disease and some forms of normolipemic xanthomatoses.- - - - - - - - - - ranking = 2.6666666666667keywords = xanthoma (Clic here for more details about this article) |
8/9. A 10-bp deletion in the apolipoprotein epsilon gene causing apolipoprotein E deficiency and severe type III hyperlipoproteinemia.Type III hyperlipoproteinemia (HLP) is usually associated with homozygosity for apolipoprotein (apo) E2. We identified a 30-year-old male German of Hungarian ancestry with severe type III HLP and apo E deficiency. The disease was expressed in an extreme phenotype with multiple cutaneous xanthomas. Apo E was detectable only in trace amounts in plasma but not in the different lipoprotein fractions. Direct sequencing of PCR-amplified segments of the apo epsilon gene identified a 10-bp deletion in exon 4 (bp 4037-4046 coding for amino acids 209-212 of the mature protein). The mutation is predictive for a reading frameshift introducing a premature stop codon (TGA) at amino acid 229. By western blot analysis, we found small amounts of a truncated apo E in the patient's plasma. family analysis revealed that the proband was homozygous--and 10 of 24 relatives were heterozygous--for the mutation. Heterozygotes had, as compared to unaffected family members, significantly higher triglycerides (TG), very low-density lipoprotein (VLDL) cholesterol and a significantly higher VLDL cholesterol-to-serum TG ratio, which is indicative of a delayed remnant catabolism. We propose that the absence of a functionally active apo E is the cause of the severe type III HLP in the patient and that the mutation, even in a single dose in heterozygotes, predisposes in variable severity to the phenotypic expression of the disease.- - - - - - - - - - ranking = 0.33333333333333keywords = xanthoma (Clic here for more details about this article) |
9/9. Characterization of a novel variant of apolipoprotein E, E2 Fukuoka (Arg-224 --> Gln) in a hyperlipidemic patient with xanthomatosis.A new variant of apolipoprotein (apo) E, designated apo E2 Fukuoka, was identified in a 54-year-old Japanese woman who suffered from hyperlipoproteinemia (total cholesterol 29.7 mmol/l, triglyceride 12.0 mmol/l, when she was 48-year-old) with the presence of xanthoma in the palms, bones, and ocular fundi, and other sites. Foam-cell macrophages were observed in bone marrow specimens. Analysis of apo E phenotype showed the E3/E2 isoform on isoelectric focusing performed on plasma, but the E3/E3 isoform on restriction-fragment-length polymorphism of the apo E gene. This discrepancy indicated that the apo E had an amino-acid substitution outside of amino-acid residues at 112 and 158. sequence analysis of the patient's dna, which was amplified by PCR and subcloned, revealed a single substitution from arginine (CGG) to glutamine (CAG) at residue 224, thereby adding one negatively charged unit to apo E3. Recombinant apo E2 Fukuoka produced in COS-1 cells showed almost the same binding activity to the LDL receptor on human skin fibroblasts as compared with recombinant apo E3. Recombinant apo E2 Fukuoka showed the same heparin binding ability than recombinant apo E3. Findings indicated that apo E2 Fukuoka was not the primary cause of the hyperlipoproteinemia observed in this case.- - - - - - - - - - ranking = 1.6666666666667keywords = xanthoma (Clic here for more details about this article) |