Skip to Main Content

AT-A-GLANCE

AT-A-GLANCE

  • Xanthomas are plaques or nodules consisting of an abnormal excess of lipid primarily in the skin or tendons.

  • Clinically, xanthomas may be divided into eruptive, tuber-eruptive or tuberous, tendinous, or planar forms. Two traditionally noninherited variations include verruciform and disseminated xanthomas, both of which have a propensity for largely noncutaneous manifestations.

  • Xanthomas are not disease entities themselves but are signs of various lipoprotein disorders, which may be primary lipid disorders or secondary disorders from a variety of causes including hepatic, hematologic, and endocrine sources.

  • The key pathogenesis of xanthoma formation consists of the downstream formation of foam cells, which involves an interplay of various lipoproteins including chylomicrons, very-low-density lipoproteins (VLDLs), chylomicron and VLDL remnant lipoproteins, low-density lipoproteins, and high-density lipoproteins.

  • Primary dyslipidemias, designated as Types I to V, have been historically categorized into various phenotypes described by Fredrickson, Levy, and Lees, based on the elevated lipoprotein fractions found in serum.

  • Diagnosis of xanthoma is based on clinical and morphologic characteristics of the lesions and identifying the underlying lipid disorder.

  • Treatment of xanthoma is aimed at the underlying lipid disorder, and typically involves lifestyle changes (diet, weight loss, smoking cessation) and medications (statins, adjuvant agents, PCSK9 inhibitors).

  • Young patients with xanthomas and those with suspected familial dyslipidemias should be referred for genetic testing and counseling.

DEFINITIONS

Xanthomas are plaques or nodules consisting of an accumulation of excess of lipid primarily in the skin or tendons, resulting in the formation of foam cells. Not a disease entity in themselves, xanthomas are signs of various lipoprotein disorders and are occasionally seen without underlying metabolic effects. Xanthomas may arise from primary dyslipidemias or may be the cutaneous manifestations of systemic disorders resulting in secondary dyslipidemia.

HISTORICAL PERSPECTIVE

Primary dyslipidemias have been traditionally grouped into 6 major phenotypes (Types I, IIa, IIb, III, IV, and V) classified by Fredrickson, Levy, and Lees in a series of seminal papers from the 1960s.1 By visually assessing samples of patient serum and directly measuring cholesterol content through ultracentrifugation, precipitation, and electrophoresis techniques, Fredrickson, Levy, and Lees quantified the size, composition, and density of various lipoproteins, including chylomicrons, low-density lipoprotein (LDL), and very-low-density lipoprotein (VLDL). At the time of publication, 5 phenotypes were proposed based on the predominant lipoprotein present in serum with a sixth phenotype later added to this scheme in the 1970s by Goldstein and colleagues.2

The World Health Organization formally adopted the Fredrickson-Levy-Lees classification in 1972 using a biochemical phenotypic classification and incorporated clinical dyslipidemias associated with the various combinations of elevated apolipoprotein B (apoB) containing lipoproteins. Interestingly, the adoption of the Fredrickson-Levy-Lees classification occurred prior to the recognition of HDL as an important contributor to dyslipidemia. Although the basis of these definitions is rooted in which serum lipoprotein is elevated; as of this writing there is no consensus on absolute values used to define an excess state. ...

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.