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Hyperlipidemias are metabolic disorders of plasma lipoproteins that are associated with an increased risk of atherosclerosis and other abnormalities, especially xanthomatous deposits and pancreatitis. Xanthomas are characterized by plaques, papules, or nodules with accumulation of lipid laden macrophages that develop in the skin and subcutaneous tissue.
A 12-year-old non-obese boy born of second degree consanguineous marriage presented with asymptomatic swellings over the elbows, hands, buttocks, posterior thighs, popliteal fossa, knees, and ankles since 7 years. Lesions started over the buttocks, were initially small and gradually increased in size and number while progressing to other body parts. His maternal uncle had similar complaints. There was no history suggestive of myocardial infarction or stroke in family members. On examination, there were multiple skin-colored nodular lesions, ranging in size from 0.5 cm to 10 cm in diameter and distributed symmetrically [Figure [Figure1a1a and andb].b]. Lesions were non tender, immovable and did not change their size and shape with application of pressure. Lipid profile showed high total cholesterol (619 mg/dl) and high low-density lipoprotein (LDL) (537 mg/dl), with normal high-density lipoprotein (HDL) (60 mg/dl), very low-density lipoprotein (VLDL) (20 mg/dl), and triglycerides (102 mg/dl). Routine hematological investigations were normal. Slit lamp and fundus examination of the eyes were normal. Electrocardiogram was suggestive of left ventricular hypertrophy. Biopsy from the lesion showed foamy macrophages and cholesterol clefts along with collagen bundles in the dermis [Figure [Figure2a2a and andb].b]. Diagnosis of hypercholesterolemia (type IIa) in association with tuberous xanthomas was made based on the above mentioned investigations. Patient was given dietary advice and started on lipid lowering agents (Statins). Patient was advised cardiac evaluation but he did not turn up for follow up. Because the condition can be familial, relevant investigations were advised for the remaining family members.
Xanthomas are usually caused by disturbance in lipoprotein metabolism. They may also be associated with lymphoproliferative malignant neoplasms. Tuberous xanthomas are typically firm, painless, yellow-red nodules seen over the extensor areas of the limbs and buttocks. Pathogenesis is either due to increased uptake of lipids transported through the capillaries or increased lipid synthesis in the dermal macrophages, resulting in the production of foam cells. Heat, movement, and friction increases capillary leakage of LDL which explain the location of tuberous xanthomas, tendinous xanthomas, xanthelasmata.
Frederickson classified hyperlipidemias into five classes based on the electrophoretic banding of plasma lipoprotein fractions. Xanthomas are clinically classified as eruptive, tuberoeruptive, or tuberous, tendinous, or planar. Tendinous xanthomas (40–50% cases) are the most common followed by xanthelasma (23%) and tuberous xanthomas (10–15%) whereas intertriginous plane xanthomas occur occasionally.
There is a remarkable association between each type of xanthoma with elevation of a characteristic lipoprotein and associated genetic disorder. Type IIa hyperlipoproteinemia or familial hypercholesterolemia usually presents with tendinous, tuberous, or planar xanthomas (xanthelesma or intertriginous type). When they occur in children and adolescents, a more severe form of hyperlipidemia should be suspected.
Histopathology shows foam cells, which are macrophages containing lipid. In addition to these, primitive mesenchymal cells, elongated perivascular, fibroblast-like cells, and lysosome filled macrophages can be found, indicating possible stages in the evolution of dermal mesenchymal cells into mature, cholesterol-rich, foam cells. It may reveal cholesterol clefts, as seen in our case. Diagnosis is made by thorough history, lipid profile, and histopathology of the lesions.
Treatment options include lifestyle changes, diet regulation, pharmacologic therapy, invasive procedures including lifelong lipid apheresis, and liver transplantation. Pharmacotherapy includes statins, bile acid sequestrants, ezetimibe, and niacin that affect various steps in the pathways of cholesterol absorption and metabolism. The most common medication is a statin in combination with a cholesterol absorption inhibitor; a third drug such as a bile acid sequestrant is added if needed. Early diagnosis and treatment of this condition helps in preventing the development of early coronary artery disease.
There are no conflicts of interest.