HYPERLIPIDEMIA Block 5 Santo 08-23-10

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CASE PRESENTATION: MARCUS H Marcus is a 54-year-old man with a chief complaint of hypercholesterolemia, xanthelasma and xanthoma. As a teenager the patient had noticed thickening of his Achilles tendons. In 1973, at age 20, he was found to have a fasting total cholesterol level at 396 mg/dL (normal < 200), a LDL cholesterol level of 333 mg/dL (normal range: 60-180), triglycerides 68 mg/dL (normal range: 40-160), and HDL-cholesterol 49 mg/dL (normal > 45). On the basis of these findings and a family history of hypercholesterolemia and premature coronary heart disease in her father, heteroxygous familial hypercholesterolemia was diagnosed.

CASE PRESENTATION: MARCUS H On physical examination his temperature is 36.2°C (97.1°F), blood pressure 130/68 mm Hg. However, xanthoma in the bilateral dorsal extensors of the hand, tuberous xanthomas in the bilateral knees and xanthoma in the bilateral Achilles tendons were noted. Xanthelasma was also noted in the bilateral eyelids. Soft X-rays for the Achilles tendons revealed that the thickness of right and left Achilles tendons were 21 mm and 23 mm respectively (average thickness is 6±1 mm).

AUTOSOMAL RECESSIVE HYPERCHOLESTEROLEMIA Definition. Autosomal recessive hypercholesterolemia (ARH) is a disorder of lipid metabolism characterized by impaired LDL receptor function and caused by mutations in a gene that encodes a phosphotyrosine binding domain protein called ARH. Clinical presentation. ARH clinically resembles hymozygous FH and is characterized by hypercholesterolemia, tendon xanthomas, premature atherosclerosis and ischemic heart disease. Plasma cholesterol levels are intermediate between the levels seen in FH homozygotes and FH heterozygotes.

XANTHOMAS INTRODUCTION. Xanthomas are lesions characterized by the deposition of yellowish cholesterol-rich material in skin or tendons. Xanthomas are a common manifestation of disorders of lipoprotein metabolism. Histologically, there is an accumulation of lipids in large foam cells (lipid-laden macrophages). Cutaneous xanthomas are mostly cosmetic disorders. Their presence simply suggests an underlying disorder of lipoprotein metabolism. Morbidity and mortality in disorder of lipoprotein metabolism are related to premature atherosclerosis (ischemic heart disease) and pancreatitis.

XANTHOMAS: CLASSIFICATION Xanthelasma. Xanthelasma is the most common of the xanthomas. A xanthelasma is a sharply demarcated yellowish collection of cholesterol underneath the skin, usually on or around the eyelids. The lesions are soft, yellow, polygonal papules around the eyelids and usually bilateral and symmetric. Xanthelasmas are most common in the upper eyelid near the inner canthus. Usually, the lesions have evolved for several months and enlarged slowly from a small papule. Xanthelasma may be associated with hyperlipidemia. When associated with hyperlipidemia, any type of primary hyperlipoproteinemia can be present. Some secondary hyperlipoproteinemias, such as cholestasis, may also be associated with xanthelasmas.

XANTHOMAS: CLASSIFICATION Tuberous xanthomas. Tuberous xanthomas are located over the joints. Tuberous xanthomas are firm, painless, red-yellow nodules. The lesions can coalesce to form multilobated tumors. Tuberous xanthomas usually develop in the extensor surfaces of the knees, the elbows, and the buttocks. Tuberous xanthomas are particularly associated with hypercholesterolemia and increased levels of LDL. They can be associated with familial dysbetalipoproteinemia and familial hypercholesterolemia, and they may be present in some of the secondary hyperlipidemias (e.g., nephrotic syndrome, hypothyroidism).

XANTHOMAS: CLASSIFICATION Tendinous xanthomas. Tendinous xanthomas appear as slowly enlarging subcutaneous nodules related to the tendons or the ligaments. The most common locations are the extensor tendons of the hands, the feet, and the Achilles tendons. Tendinous xanthomas are associated with severe hypercholesterolemia and elevated LDL levels, particularly in familial hypercholesterolemia. They can also be associated with some of the secondary hyperlipidemias, such as cholestasis.

XANTHOMAS: CLASSIFICATION Eruptive xanthomas. Eruptive xanthomas most commonly arise over the buttocks, the shoulders, and the extensor surfaces of the extremities. The lesions typically erupt as crops of small, red-yellow papules on an erythematous base, and they may spontaneously resolve over weeks. Pruritus is common, and the lesions may be tender. Eruptive xanthomas are associated with hypertriglyceridemias, particularly those associated with high concentrations of VLDL and chylomicrons. They may also appear in secondary hyperlipidemias, particularly in diabetes.