Sitosterolemia Exhibiting Severe Hypercholesterolemia with Tendon Xanthomas Due to Compound Heterozygous ABCG5 Gene Mutations Treated with Ezetimibe and Alirocumab.

We herein report a rare case presenting with severe hypercholesterolemia, massive Achilles tendon xanthomas, and multi-vessel coronary artery disease. Initially, the patient was misdiagnosed with familial hypercholesterolemia. However, a genetic analysis using our custom sequencing panel covering genes associated with Mendelian lipid disorders revealed him to have a genetic basis of sitosterolemia with compound heterozygous mutations in the adenosine triphosphate binding cassette subfamily G5 (ABCG5) gene. A comprehensive genetic analysis can be particularly useful for diagnosing cases with severe phenotypes, leading to appropriate and medical therapies. Our patient was refractory to statins, whereas ezetimibe and PCSK9 inhibitor with a low-plant-sterol diet successfully reduced his serum levels of low-density lipoprotein cholesterol.

Extended resection for xanthogranulomatous cholecystitis mimicking gallbladder carcinoma: Cases and review of diagnostic approach.

Xanthogranulomatous cholecystitis is a rare variant of chronic cholecystitis, which can involve adjacent organs including liver, colon and duodenum mimicking gallbladder cancer. Preoperative and intraoperative differentiation of xanthogranulomatous cholecystitis from gallbladder cancer is often difficult and the final diagnosis is made on histopathology of the resected specimen. We hereby report four cases of xanthogranulomatous chol ec ystitis w hich were misdiagnosed as cases of advanced gallbladder cancer based on presentation and radiological findings and underwent radical resections but the final histopathology was a diagnostic surprise. Xanthogranulomatous cholecystitis is still a diagnostic challenge as no single modality has been helpful to diagnose this entity till date. Radical resection seems justified in patients who present with the features mimicking gallbladder cancer.

Clinical and molecular genetic features of cerebrotendinous xanthomatosis patients in Chinese families.

Cerebrotendinous xanthomatosis (CTX) is a lipid-storage disease caused by mutations in CYP27A1. Current publications of Chinese CTX were mainly based on case reports. Here we investigated the clinical manifestations, genetic features in Chinese CTX patients. The clinical materials of 4 Chinese CTX pedigrees were collected. The genetic testing was done by polymerase chain reaction plus Sanger sequencing. The features of Chinese CTX patients reported previously were also reviewed. Three novel mutations of p.Arg513Cys, c.1477-2A > C in family 1 and p.Arg188Stop in family 4 (NM 000784.3) in CYP27A1 were found. The probands in our study manifested cerebellar ataxia, tendon xanthoma and spastic paresis in family 1 and 4, tendon xanthoma plus spastic paraparesis in family 2, asymptomatic tendon xanthoma in family 3. Three known mutations of p.Arg137Gln, p.Arg127Trp and p.Arg405Gln were found respectively in Family 2, 3 and 4. For the Chinese patients reviewed, the most common findings were xanthomatosis (100%), pyramidal signs (100%), cerebellar ataxia (66.7%), cognitive impairment (66.7%), cataracts (50.0%), and peripheral neuropathy (33.3%). Chronic diarrhea was infrequently seen (5.6%). No mutation was found associated with any given clinical features. We identified 3 novel mutations in CYP27A1. In Chinese CTX patients, xanthomatosis was the most common symptom while cataracts and chronic diarrhea were less frequent. The special features in Chinese CTX patients might caused by the lack of serum cholestanol test and should be confirmed in larger number of patients in the future.

Are normolipidaemic patients with xanthelasma prone to atherosclerosis?

BACKGROUND: When patients with xanthelasma are found to have normal lipid levels, dermatologists usually proceed with their treatment without further investigations. However, there is some evidence that normolipidaemic patients with xanthelasma (NPX) have a similar cardiovascular risk to hyperlipidaemic patients with xanthelasma (HPX). AIM: To evaluate the risk of atherosclerosis in Egyptian NPX compared with HPX and controls. METHODS: In total, 20 NPX, 20 HPX and 40 normolipidaemic controls were enrolled. All participants were matched for age and sex. Diabetes was an exclusion factor. Carotid ultrasonography was used to measure intima-media thickness (IMT). Other risk factors of atherosclerosis such as high blood pressure, obesity and smoking were also assessed, as well as atherosclerotic markers, including total leucocytic count (TLC), C-reactive protein and lipoprotein a. RESULTS: Although still within the normal range, total cholesterol and triglycerides were significantly higher in NPX compared with controls. IMT was significantly higher in NPX compared with controls, but lower than that of HPX. The increased IMT in NPX was not related to any of the studied risk factors. Apart from significantly higher body mass index and TLC, NPX showed no significant differences from controls for other risk factors of atherosclerosis or for atherosclerotic markers. CONCLUSION: NPX seem to have a higher risk of atherosclerosis independent of lipid concentrations, and should therefore be fully investigated in order to allow detection and early management of such risk.

Xantomas planos diseminados normolipémicos asociados a gammapatía monoclonal de significado incierto / Diffuse normolipemic plane xanthomas associated with monoclonal gammopathy of undetermined significance

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Primary xanthofibroma in the calcaneus: a case report.

Xanthoma or xanthofibroma is a lesion, characterized by foamy histiocytes (xanthoma cell) and is mostly seen in soft tissue. Xanthoma may also occur in in the skeletal system of patients with an abnormal lipid metabolism. We present a 22-year-old man with primary xanthofibroma in the calcaneus, who was treated by curettage and grafting of the lesion.

Fibroxantoma atípico pigmentado o hemosiderótico / Pigmented or Hemosiderotic Atypical Fibroxanthoma

El fibroxantoma atípico pigmentado es una variante rara de fibroxantoma atípico caracterizada por áreas extensas de hemorragia, eritrofagocitosis y depósitos de hemosiderina en el citoplasma de las células neoplásicas. Afecta a pacientes de edad avanzada, y se manifiesta como nódulos cupuliformes o placas pigmentadas, de coloración heterogénea, en áreas de piel fotoexpuesta. Se presenta un caso de fibroxantoma atípico pigmentado de localización malar en un varón de 81 años de edad. Seis años después de la extirpación quirúrgica de la lesión, el paciente permanece en remisión completa, sin que se aprecien signos clínicos de persistencia tumoral o metástasis. Se revisan los 9 casos de fibroxantoma atípico pigmentado publicados en la literatura y se discuten las características histopatológicas y el diagnóstico diferencial de esta rara entidad (AU)

Pigmented atypical fibroxanthoma is a rare variant of atypical fibroxanthoma and is characterized by extensive areas of hemorrhage, erythrophagocytosis, and hemosiderin accumulation in the cytoplasm of the neoplastic cells. It affects elderly individuals and presents as irregularly pigmented, dome-shaped nodules or plaques on areas of skin exposed to the sun. We present a case of pigmented atypical fibroxanthoma on the cheek of an 81-year-old man. Six years after excision of the lesion, the patient remains in complete remission, with no signs of residual tumor or metastasis. The 9 cases of pigmented atypical fibroxanthoma reported in the literature are reviewed, and the histopathological features and differential diagnosis are discussed (AU)

Xanthelasma palpebrarum and its relation to atherosclerotic risk factors and lipoprotein (a).

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.

The potential anti-xanthoma and anti-atherosclerotic effects of proton pump inhibitors.

Xanthoma and atherosclerosis are similar in having infiltrations of macrophages that have transformed into foam cells. The oxidized low-density lipoprotein (LDL) promotes adhesion of monocytes to endothelial cells by inducing expression of adhesion molecules on vascular endothelial cells. Macrophages transform into foam cells by incorporating oxidized LDL using several kinds of scavenger receptors. Very recently, it has been shown that LDL oxidation occurs within lysosomes in macrophages in atherosclerotic lesions and the increase of intra-lysosomal PH can prevent LDL oxidation. Given that proton pump inhibitors can decrease the intra-lysosomal acidicty through inhibition of the lysosomal membrane H+/K+ATPase, theses agents could afford protection against atherosclerosis and xanthoma formation.