From the Guidelines
Xanthomas are the classical physical exam finding associated with Familial Hypercholesterolemia (FH). These are yellowish cholesterol deposits that typically appear on tendons (especially the Achilles tendon and extensor tendons of the hands), around the eyes (xanthelasma), or on the eyelids. Xanthomas develop due to the extremely elevated LDL cholesterol levels characteristic of FH, which causes cholesterol to accumulate in tissues. These deposits are pathognomonic for severe hypercholesterolemia and should prompt immediate evaluation for FH, especially when found in younger patients. Other physical findings in FH may include corneal arcus (a white-gray ring around the cornea) in patients under 45 years old and premature cardiovascular disease. Early identification of these physical signs is crucial as FH patients have significantly increased risk of early coronary artery disease, and treatment with high-intensity statins, ezetimibe, PCSK9 inhibitors, or combination therapy should be initiated promptly to reduce cardiovascular risk, as recommended by recent guidelines 1.
The presence of xanthomas is a key diagnostic feature of FH, and their detection can help identify individuals at high risk of cardiovascular disease. According to the International Atherosclerosis Society guidance for implementing best practice in the care of familial hypercholesterolaemia, published in 2023 1, xanthomas are a characteristic physical finding in patients with FH. This guidance emphasizes the importance of early detection and treatment of FH to prevent premature cardiovascular disease.
In contrast, pallor, petechiae, and clubbing are not typically associated with FH. Pallor may be a sign of anemia or other conditions, petechiae are often seen in patients with platelet disorders or vasculitis, and clubbing is commonly associated with respiratory or cardiovascular diseases. While these physical findings may be present in some patients with FH, they are not specific or diagnostic for the condition.
Therefore, xanthomas are the most relevant physical exam finding associated with Familial Hypercholesterolemia (FH), and their presence should prompt further evaluation and treatment to reduce the risk of cardiovascular disease, as supported by the latest evidence 1.
From the Research
Classical Physical Exam Findings in Familial Hypercholesterolemia
The classical physical exam findings associated with Familial Hypercholesterolemia (FH) include:
- Xanthomas: These are cutaneous lesions that can be found on the tendons, hands, and other parts of the body 2, 3, 4.
- Xanthelasmata: These are small, yellowish patches on the skin, often found on the eyelids 2.
- Corneal arcus: This is a white, grey, or blue opaque ring in the corneal margin (peripheral cornea) of the eye, often seen in individuals under the age of 45 years 2.
Comparison with Other Options
In comparison, the other options listed (pallor, petechiae, or clubbing) are not specifically associated with Familial Hypercholesterolemia as classical physical exam findings.
- Pallor refers to pale skin, which can be caused by a variety of conditions, but is not a specific finding in FH.
- Petechiae are small, pinpoint spots on the skin caused by bleeding from small blood vessels, and are not typically associated with FH.
- Clubbing is a deformity of the fingers and fingernails that can be caused by various conditions, including cardiovascular and respiratory diseases, but is not a classical finding in FH.
Diagnosis and Management
The presence of xanthomas, xanthelasmata, and corneal arcus should prompt the physician to request lipid tests and use clinical scores to diagnose FH 2. If the diagnosis of FH is likely, aggressive lipid-lowering therapy should be initiated to reduce the risk of coronary artery disease (CAD) and a cascade screening of family members should also be requested 2, 5.