Xanthomas · What Are They, Causes, Signs, Symptoms, and More

In general, xanthomas are caused by excessive fat, in the form of cholesterol or triglycerides, within the blood. Excessive LDL cholesterol is phagocytosed, or ingested, by macrophages, which then produce foam cells. The foam cells can deposit into the tendons, fascia, periosteum, and skin, forming the characteristic yellow lesions seen with xanthomas. 

The underlying cause for what leads to excessive cholesterol or triglycerides varies and can include genetic causes; lymphoproliferative conditions; hematologic malignancies; and certain medications, such as glucocorticoids, in rare situations. Some types of xanthomas with genetic causes include eruptive xanthomas due to mutations to apolipoprotein B-100, PCSK9 gene, and the LDL receptor; xanthoma tuberosum and xanthoma tendineum due to an autosomal dominant inheritance; cerebrotendinous xanthomatosis (i.e., a condition that affects how lipids are metabolized because of a 27-hydroxylase deficiency), an autosomal recessive condition caused by a mutation in the CYP27A1 gene; and familial β-sitosterolemia (i.e., genetic condition that affects lipid transporters), an autosomal recessive condition caused by mutations in the ABCG5 or ABCG8 genes. 

Next, xanthoma diffusum planum occurs in the setting of lymphoproliferative disorders and hematologic malignancies (e.g., multiple myeloma). Xanthoma disseminatum is believed to occur from histiocytic disorders (e.g., excess white blood cells) such as histiocytosis, histiocytoma, and reticulohistiocytoma. 

Generally, the signs and symptoms of xanthomas include well-circumscribed macules, papules, or plaques that can develop anywhere on the body and are yellow in color due to the carotene found in lipids. 

Specifically, each type of xanthoma has a slightly different presentation. For example, xanthelasma palpebrarum, one of the most commonly found xanthomas, is characteristically seen as yellow plaques over the eyelids. Eruptive xanthomas develop acutely causing multiple 1 to 4 millimeters (mm) yellow nodules to develop and are typically surrounded by an erythematous halo. On the other hand, tuberous xanthomas and tendon xanthomas are both characterized by raised, flat-topped, yellow nodules that can progress to several centimeters in size. These xanthomas are found over joints and tendons, like the hands, knees, and elbows. Tendineum xanthomas, specifically, are often identified over the Achilles tendon.

Xanthomas are diagnosed through a thorough history and physical examination by a healthcare provider. Initially, a medical history may reveal personal or family history of xanthomas, while the physical examination can reveal the characteristic lesions. Blood work may be completed to evaluate for any underlying cause, like hyperlipidemia or hypercholesterolemia. A fasting lipid profile that includes a cholesterol panel and triglyceride level, may provide information as to what specific lipid is elevated and which type of xanthoma may be suspected. Other blood work, such as blood glucose and HbA1C levels, can also be done to evaluate for concurrent disorders, like diabetes mellitus. It may also be helpful to calculate an atherosclerotic cardiovascular disease (ASCVD) risk analysis to assess the 10-year risk of atherosclerotic heart disease. Elevated triglycerides can also increase the risk of pancreatitis; therefore, in the setting of abdominal pain, a lipase level may be drawn to assess pancreatic enzymes.