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Xanthomatoses and Lipoprotein Disorders at a Glance
  • Several lipoprotein disorders manifest as xanthomas, which contain cholesterol and triglycerides in macrophages.
  • Tendinous xanthomas with thickening of the Achilles tendons and disposition in tendons on the hands, elbows, and knees are observed in familial hypercholesterolemia (FH), phytosterolemia, or cerebrotendinous xanthomatosis (CTX).
  • Familial Hypercholesterolemia is diagnosed by finding a markedly elevated low-density lipoprotein (LDL) cholesterol level (usually >300 mg/dL), which can be treated with statins, ezetimibe, anion exchange resins and, if necessary, LDL apheresis.
  • Xanthelasma on the eyelids are common and can be associated with elevated LDL cholesterol, but more often are seen in patients with normal lipids and treated cosmetically.
  • Phytosterolemia, associated with moderately elevated LDL cholesterol levels and markedly elevated plasma β-sitosterol and campesterol, is best treated with ezetimibe.
  • Cerebrotendinous xanthomatosis is due to markedly elevated plasma levels of cholestanol and therapy consists of oral chenodeoxycholate to prevent progression of xanthomas and neurologic disease.
  • Tubo-eruptive, planar, and palmar xanthomas can be observed with combined hyperlipidemia as well as occasionally with marked high-density lipoprotein deficiency, and can be treated with dietary modification, statins, fibrates, and niacin.
  • Eruptive xanthomas are usually due to severe hypertriglyceridemia (fasting level >1,000 mg/dL, with chylomicrons present), and are often transient.
  • Patients with severe hypertriglyceridemia are at increased risk of pancreatitis and need to restrict dietary fat and sugars, control diabetes if present, and use fibrates and fish oil.
  • Xanthomas are occasionally observed in patients with monoclonal gammopathies or multiple myeloma.

Xanthomas are plaques or nodules consisting of abnormal lipid deposition and foam cells in skin or in tendons. They do not represent a disease but rather are signs of a variety of lipoprotein disorders. Xanthomas are occasionally seen without an underlying metabolic effect. Xanthomas are thought to develop through several mechanisms. Through scavenger receptors for enhanced low-density lipoprotein (LDL) uptake, macrophages (converted from monocytes) incorporate lipid that has been transported through the capillary walls, thus becoming foam cells. Foam cells can also develop as a result of in situ lipid synthesis by the macrophage. Further, lipid that has been extravasated by the capillaries can also recruit additional foam cells into an already established xanthoma. Extravasated and oxidized LDL recruits foam cells by inducing vascular cellular adhesion molecule and E-selectin.1,2 Local factors such as heat, movement, and friction may increase LDL capillary leakage, and, hence, result in the development of xanthomata.3 These local factors help explain the location of tuberous xanthomas, tendinous xanthomas, and xanthelasmata.

Clinical Findings

Cutaneous Lesions

Clinically, xanthomas can be classified as eruptive, tubo-eruptive or tuberous, tendinous, or planar.4 Planar xanthomas include xanthelasma palpebrarum/xanthelasma, xanthoma striatum palmare, and intertriginous xanthomas. There are characteristic clinical phenotypes associated with specific metabolic defects (Tables 135-1 and 135-2 showing older Frederickson classification).

Table 135-1 Clinical Presentations of Xanthomas

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