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Xanthomatosis: an Insight to Familial Hypercholesterolemia Pathology Section Case Report DOI: 10.7860/NJLM/2016/15619:2093 Xanthomatosis: An Insight to Familial Hypercholesterolemia Pathology Section JAYA MANCHANDA, RITU GOGIA, SANJAY GOGIA, A.K.VERMA ABSTRACT Here the author present a case of 10 years old boy who Familial hypercholesterolemia is a “RECEPTOR DISEASE” presented with xanthomas and an elevated serum low that is the consequence of a mutation in the gene encoding density lipoprotein. His father had similar clinical history. The the receptor for low-density lipoprotein, which is involved in subject was Fredericks Phenotype II A – with increased LDL the transport and metabolism of cholesterol. It is associated cholesterol. This report is to emphasise the need to screen with skin and tendon xanthomas, xanthelasma, premature first-degree relatives and extended family members as early arcus corneae and increased risk of premature coronary heart intervention and diagnosis will save the affected individual from disease. catastrophic cardiac events. Keywords: Lipid laden macrophages, Low density lipoprotein, Xanthomas CASE REPORT thought to be neurofibromatosis, benign mesenchymal A 10 years old boy presented in the Department of lesion or xanthomatosis. There was no history of diabetes Pathology with history of multiple gradually enlarging painless mellitus, hypothyroidism, hepatic disease, or renal disease. nodules over both elbows, both knees, popliteal fossa, On physical examination, multiple nodules of varying size sacrococcygeal area, buttocks, ankles, metacarpophalangeal were observed on the previously mentioned sites. Systemic joints and post auricular regions [Table/Fig-1-3]. His father examination was unremarkable Investigations revealed total had similar complaints with nodules over both elbows and cholesterol of 713 mg/dl, low density lipoprotein cholesterol altered lipid profile. On the basis of clinical finding it was of 635.7mg/dl, high density lipoprotein cholesterol of 36.9 mg/dl and triglyceride of 160 mg/dl. Complete hemogram, blood sugar, renal function test, liver function test and thyroid function test were within normal limits. Electrocardiogram (ECG), treadmill tests (TMT) and echocardiography was done to look for the cardiovascular effects of hypercholesterolemia and they proved to be normal. The chest X-ray was normal, while that of hands and elbows showed multiple soft [Table/Fig-1-3]: Xanthomas over the ankle, metacarpo-phalangeal tissue swellings corresponding to cutaneous lesions and joints,post-aural and gluteal region. [Table/Fig-4]: The xanthoma cells have abundant foamy-appearing cytoplasm and small nuclei [Table/Fig-5]: Touton type of giant cells interspesred in foamy histiocytes (40X) [Table/Fig-6]: Masson’s trichome stain showing collagen bundles interspersed between foamy histiocytes (left to right). 30 National Journal of Laboratory Medicine. 2016 Jan, Vol 5(1): 30-32 www.njlm.jcdr.net Jaya Manchanda et al., Xanthomatosis:An Insight to Familial Hypercholesterolemia PHENOTYPE ELEVATED PARTICLES MAJOR LIPID FREQUENCY I Chylomicron TG Very rare Eruptive xanthomas common II A LDL LDL Common Severe atherosclerosis Tuberous xanthomas Xanthelasmas II B LDL and VLDL LDL, TG Common Adult presentation Tuberous xanthomas Xanthelasmas III IDL TC , TG Rare Premature atherosclerosis Plane (palmar) xanthomas IV VLDL TG Common Eruptive Xanthomas V Chylomicron ,VLDL TG Uncommon Acute pancreatitis Plane xanthomas [Table/Fig-7]: Frederickson classification of dyslipidemia. normal underlying bones. FNAC performed from one of the in patient. Type I was classified as hyperchylomicronemia, nodules yielded scant aspirate and was inconclusive. Biopsy type II as hyper-lipoproteinemia, type III as a combination from one of the nodules over the right elbow and buttock of both hyper and pre-lipoproteinemia, type IV as hyper- showed normal epidermis and aggregates of xanthoma cells pre-lipoproteinemia, and, type V as hyperchylomicronemia separated by fibrocollagenous bundles in the dermis [Table/ in combination with hyper-pre-lipoproteinemia. Moreover, it Fig-4]. A few Touton giant cells were also identified [Table/ was proved that different types of hyperlipoproteinemia had Keywords: Lipid laden macrophages, Low density lipoprotein, Xanthomas Fig-5]. On the basis of histopathological findings, diagnosis different clinical manifestations, responses to therapy and of benign histiocytic lesion, juvenile xanthomas, tuberous diet, and different genetic aspects [7]. xanthomas, reactive proliferation was thought of. In view of Xanthomatosis is a cutaneous manifestation of lipidosis in the microscopic picture and clinical features correlation with which plasma lipoproteins and free fatty acids are qualitatively lipid profile was advised. Masson trichome staining was altered, resulting in morphologic change as lipids accumulate done for the same [Table/Fig-6]. A final diagnosis of multiple in foam cells in the tissues. Lipoprotein form by the combination xanthomas –tuberous and tendinous was given. of insoluble circulating lipids (cholesterol, cholesterol esters, triglycerides and phospholipids) and proteins and any alteration DISCUSSION in the metabolism leads to an increased risk of cardiovascular Xanthomas occur due to accumulation of lipid laden disease, pancreatitis or xanthomas [8]. macrophages. They develop when systemic lipid metabolism Increased uptake of lipids transported through the capillaries is altered or as a result of local cell dysfunction and may appear or increased lipid synthesis in the dermal macrophages as first clinical presentation of familial hyperlipoproteinemia [1]. leads to the formation of foam cells which adhere and form These patients are at high risk for development of premature xanthomas [9]. coronary atherosclerosis as early stages of disease begin in childhood [2]. If premature development of cardiovascular Increase in E- selectin positive endothelial cells and decrease disease can be anticipated during childhood, the disease might in intracellular cell adhesion molecule cells play a vital role in be prevented [3]. Fredrickson classified familial hyperlipidemia promoting macrophage migration into xanthomatic lesions into five main types based on the changes in plasma lipoprotein [10,11]. spectrum and other associated changes [4]. Our case was Fredericks Phenotype II A – with increased Increased concentrations of plasma lipoproteins leads to LDL cholesterol. Phenotype II A includes various disorders hyperlipidemia. Genetic defects alterations are classified as including Familial hypercholesterolemia, Familial defective Apo primary disorders of lipoprotein metabolism. B, Autosomal recessive hypercholesterolemia, Autosomal dominant hypercholesterolemia, Sitosterolemia. Distinction of Alternatively, other contributing factors, such as diabetes these entities requires molecular diagnosis and LDL receptor mellitus, hypothyroidism, obesity, pancreatitis, nephrotic studies. From clinical view there is no compelling reason to syndrome, cholestatic liver disease, dysglobulinemia and perform them since the treatment remains the same as an adverse effect of using certain medications (e.g., estrogens, corticosteroids, systemic retinoid agents) lead to CONCLUSION altered plasma lipoprotein concentration and are classified as This report highlights the pre-requisite of early intervention, secondary disorders of lipid metabolism [5,6]. pre-prophylaxis and diagnosis to prevent the affected Traditionally, hyperlipidemias have been classified in 6 individual and extended family members from impending phenotypes [Table/Fig-7] described by Frederickson based cardiac events. on electrophoretic patterns of elevated lipoprotein levels National Journal of Laboratory Medicine. 2016 Jan, Vol 5(1): 30-32 31 Jaya Manchanda et al., Xanthomatosis:An Insight to Familial Hypercholesterolemia www.njlm.jcdr.net REFERENCES Philadelphia: W.B. Saunders Co; 1998. p. 1099-153. [1] Goldstein JL and Brown NS: Familial Hypercholestrolemia. [6] Shreeya et al. Skin–a mirror of metabolic disorders–a case report. In Scriber CR, Beaudet AL, Sly WS and Valle D. (eds.). The Indian Journal of Medical Case Reports. 2015; 4 (3) :36-38 metabolic basis of inherited disease. New York , Mc Graw – Hill [7] Fredrickson DS, Lees RS. A system for phenotyping pp. 1225-1250,1989. hyperlipoproteinemia. Circulation.1965, 31: 321-27. [8] Kumar B, Dogra S. Metabolic Disorders. In Valia RG, Valia AR, [2] Aggoun Y, Bonnet D, Sidi D, et al. Arterial mechanical changes in rd children with familial hypercholesterolemia. Arterioscler Thromb editors. IADVLTextbook of dermatology. 3 edition.India: Bhalani Vasc Biol. 2000;20(9):2070-75. Publishing House; 2010, p. 1300 [3] Cortner JA, Coates PM, Liacouras CA, Jarvik GP. Familial [9] White LE. Xanthomatoses and lipoprotein disorders. In: Wolff combined hyperlipidemia in children: clinical expression, k,Goldsmith LA, katz SI, Glichrest BA, Pallee AS, Leffell DJ, th metabolic defects, and management. Curr Probl Pediatr. editors. Fitzpatrick’s Dermatology in general Medicine. 7 1994;24(9):295-305. edition, New York:Mgraw-Hill; 2008, p. 1272-81 nd [4] Mahajan VK, Sharma NL, Sood S. Xanthoma tendinosum [10] Weedon D. Weedon’s skin Pathology, 2 edition. London: and familial hypercholesterolemia. Indian J Dermatology. churchill Livingstone Elsevier; 2010, p. 961-65. 2003;48(2):116-18. [11] Pai VV, Shukla P and Bhobe M. Combined planar and eruptive [5] Manley RW, Weisgraber KH, Farese RV. Disorders of lipid xanthoma in a patient with type lla hyperlipoproteinemia. Indian metabolism. In:
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