Familial hypercholesterolemia is an autosomal dominant disorder due to mutations in thelow-density lipoprotein receptor gene, characterized by skin and tendonxanthomas,xanthelasma and premature arcus senilis. A female patient presented with multiple large swellings over extensor aspects of both the elbows, inner aspects of both the arms and buttocks which on biopsy were found to be tuberous xanthomas. Her lipid profile revealed severe hypercholesterolemia and markedly raised LDL levels. A diagnosis of Familial Hypercholesterolemia was made. She was advised life style modification; surgical excision was done and treated with Rosuvastatin 40mg OD. As Homozygous FH is an important risk factor for atherosclerosis and premature coronary artery disease in children and young adults, early diagnosis and treatment with screening of first-degree relatives is essential to minimize the progression of cardiovascular disease.
Tuberous xanthomas present asplaques or papules ornodulesover the skin present in lipoprotein metabolism disorders. These are benign andformed by accumulation of lipid laden macrophages that develop in the dermis subcutaneous tissue.[1] Tuberous xanthomas are firm painless yellowish nodules most commonly seen over extensor aspects of limbs and buttocks. [2,4] They are indicative of a derangement in lipoprotein metabolism, in particular familial hypercholesterolemia.
A 17yr oldFemale patient came with the complaints of asymptomatic raised lesions over elbows, arms, buttocks since 10 yrs which started as small asymptomatic peanut sized lesions over both the buttocks since 10 yrs followed by the appearance of similar lesions over both the elbows since 3 yrs which later graduallyprogressed to tumour like growths.Patient noticed similar lesions over both the arms 2yrs back. She is a product of consanguineous marriage.Father died of MI at the age of 38 yrs. Her mother also had hypercholesterolemia. On examination she had bilateral corneal arcus.
Her Cutaneous examination showed 3 to 7 cm sized firm oval nodules of skin colour over both the buttocks.Skin coloured firm plaques of size varying from1 cm to over 8 cm were present over both the elbows.Multiple yellow coloured papules were noticed over both the arms.Palms and soles are normal ;Hair, scalp and nails are normal.
Her Lipid profile showed total cholesterol as 386 mg/dl, low density lipoprotein as 335 mg/dl. Her triglycerides and highdensity lipoproteins are normal.
Biopsy from the nodule revealed infiltration of the dermis with admixture of foam cellshistiocytes and lymphocytes, fibrosis and cholesterol clefts.
Routine investigation were normal. 2D Echo and Thyroid profile are normal. Surgical excision was done and Rosuvastatin 40 mg OD was started. Life style modification was advised.
Familial hypercholesterolemia is an autosomal codominant disorder with raised LDL levels due to increased production and reduced resorption of LDL secondary to dysfunctional LDL receptors due to mutations in LDL receptor gene. Heterozygotes express half the number of LDL receptors and homozygotes have between 0% and 25%.[5]. As Homozygous familial hypercholesterolemia is animportant risk factor for atherosclerosis and premature coronary artery disease in children and young adults[5,8], early diagnosis and treatment of firstdegree relatives is essential to minimize the progression of cardiovascular diseases. Screening of family members in our case revealed hypercholesterolemia in her mother and elder sister.
Xanthomata are cutaneous markers of underlying lipid metabolism disorders, classified by Frederickson into five classes. Tuberous xanthomas are usually found in type IIa familial hypercholesterolemia.[3,6].Histologically, apart from foamy macrophages, they have also been found to contain primitive mesenchymal cells, elongated perivascular, and fibroblast-like cells, and lysosome-filled macrophages, indicating possible stages in the evolution of dermal mesenchymal cells into mature, cholesterol-rich foam cells.[7]
Pharmacologic treatments includes statins, bile acid sequestrants, ezetimibe, 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, and if needed a third drug such as a bile acid sequestrant.[9]The treatment options must include lifestyle and diet modifications also.Pharmacologic treatments and invasive procedures including lifelong lipid apheresis andliver transplantation.[10].
In conclusion, this case was reported for the atypical presentation of multiple giant tuberous xanthomas which are generally <2cm in size and presence of arcus senilis which is considered rare. A thorough workup is essential for all the family members to identify the underlying conditionto start treatment early and to prevent further complications.
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Conflicts of interests: The authors declare no conflicts of interest.
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