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

Author:Georgina Tiarks

Editors:Alyssa Haag,Józia McGowan, DO,Kelsey LaFayette, DNP, ARNP, FNP-C

Illustrator:Jessica Reynolds, MS

What are xanthomas?

Xanthomas are fatty deposits in the skin due to elevated blood lipid levels. These well-circumscribed, yellow (i.e., “xanthos” in Greek translates to yellow) nodules in the skin consist of foam cells. Foam cells are formed from low-density lipoprotein (LDL) cholesterol that is ingested by macrophages. Histologically, foam cells are pathognomonic for certain conditions, such as congenital or acquired hyperlipidemia. While presence of xanthomas can be used as a clinical indicator of a blood lipid disorder, not all individuals with elevated lipid levels will develop xanthomas. Additionally, the presence of xanthomas can be associated with an increased risk of cardiovascular disease and shorter lifespan. There are many types of xanthomas, which are differentiated by their underlying cause and part of the body they affect. 

Yellow-colored fatty nodules.

What causes xanthomas?

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. 

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What are the signs and symptoms of xanthomas?

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.

Diffusum planum xanthomas are usually present over the neck, shoulders, and axilla; while xanthoma intertriginosum may be found over the interdigital spaces. Xanthoma palmare emerges over the palmar surface of the hands. Xanthoma disseminatum appears as blue, red, or orange nodules, occurring most often around the face and flexural areas (e.g., neck, elbows, genitalia). This type of xanthoma may also be disseminated to include extracutaneous manifestations, such as the nervous system, ocular system, and airways. Cerebrotendinosus xanthomatosis can also develop from lipid deposition in the brain and is characterized by neurological dysfunction and gait instability, depending on where exactly the deposits are located. Xanthogranuloma necrobioticum causes necrotic, blue, and violet nodules affecting the head, neck, and trunk.

How are xanthomas diagnosed?

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.

If familial hypercholesterolemia is suspected, genetic testing can also be performed. If lymphoproliferative or hematologic disorders are suspected, an initial complete blood count (CBC) can be ordered. Xanthomas affecting the Achilles tendon can also cause increasing thickness of the tendon itself, which can be diagnosed on an ultrasound.

How are xanthomas treated?

Xanthomas may be treated using a variety of therapies based on the underlying cause. Initially, lifestyle modifications, such as adjusting diet and incorporating exercise, may be utilized to help improve lipid levels. If these are not successful or the lipid levels are significantly elevated, pharmacotherapy may be required. Statins (e.g., atorvastatin, rosuvastatin), ezetimibe, PCSK9 inhibitors (e.g., evolocumab), and bile acid sequestrants (e.g., colesevelam) are primarily used to reduce blood cholesterol levels. If triglycerides are significantly elevated, fibrates (e.g., fenofibrate, gemfibrozil) or omega-3 fatty acids may be recommended. If these therapies are unsuccessful, providers may recommend niacin (i.e., vitamin B3). Lastly, if xanthomas are symptomatic (i.e., causing pain or emotional distress), surgical excision of the lesions can be done.

What are the most important facts to know about xanthomas?

Xanthomas are raised, yellow, nodular lesions that can present anywhere on the body, including the joints (e.g. elbow, knees), eyelids, tendons (e.g., Achilles tendon), interdigital spaces, and flexural areas. The presentation of xanthomas may represent disorders of elevated lipid (i.e., fat) levels. Macrophages ingest low-density lipoprotein (LDL) fat, forming foam cells, which may deposit in the skin giving rise to xanthomas. Diagnosis is made through a thorough history and physical examination followed by blood work to test lipid levels. Treatment for xanthomas consists of targeting the underlying cause and includes medications, such as statins, fibrates, PCSK9 inhibitors, omega-3 fatty acids, and bile acid sequestrants. In severe cases, surgery may be done. 

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Resources for research and reference

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