Xanthomas: clinical and pathophysiological relations

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.