FIGURE 15-10 Addison disease A. Hyperpigmentation representing an accentuation of normal pigmenta- tion of the hand of a patient wth Addison cisease. B. Note accentuated pigmentation in the palmar creases. METABOLIC AND NUTRITIONAL CONDITIONS OO CL eho = Cutaneous xanthomas are yellow-brown, pinkish, or orange macules, papules, plaques, nodules, or infiltrations in tendons. 1 Histologically there are accumulations of xan- thome cels-macrophages containing droplets of lpia. 1 Xanthomas may be symptoms of a general meta- bolic disease, e generalized histiocytosis, ora local fat phagocytosing storage process. 1 The dassiication of metabolic xenthomas is based on this prindple: (1) xanthomes due to hypetii- demia and (2) normolipidemic xanthomas. 1 The cause of xanthomas in the fist group may be a primary hypetipideria, mostly genetically determined (Table 15-1), or secondary hypert- pidemia, associated with certain intemal diseases such as biliary cithoss, diabetes melitus, chronic renal failure, alcoholism, hyperthyroidism, and monoclonal gammopathy, or with intake of cer- tain drugs such as beta-blockers and estrogens. '= Some of the xanthomas are associated with high plasma low-density lipoprotein (LDL)-cholesterol levels and therefore with a serious rsk of athero- melosis and myocardial infarction For that reason laboratory investigation of plasma lipid levels is always necessary. In some cases en apopratein deficiency is present. 1 Table 15-2 shows correlations of clinical xanthoma type and lipoprotein disturbances.SECTION 15 ENDOCRINE, METABOLIC NUTRITIONAL, AND GENETIC DISEASES [BB] taste 15-1. Classification of Genetic Hyperlipidemias Frederickson Classification Lipid Profile Type 1 Familial ipoprotein lipase deficiency TG++, Cnonmal, CA++, HDL —fnormal (yperchylomicronemia, hypetrigyceidemia) (FLD) lia Farvilal hypercholesterolemia (FH) 1G normal, C+, LOL ‘ib Familial combined hyperipidemia (FCHL) 1G+, Ct LDL, VDL ‘i Farilaldysbetalpidemia (remnant particle disease) (FD) TG+, C+, IDL+, CM remnants v Famnilial hypertighceridemia (FHTG) TG, C normal/+, LOL-+, VLDLH+ v Familial combined hyperviglyceridemia (FHT) TG+, Ch MUL, CMH ore TG, wighetides;C holes; CO, comions; HDL, high-density ipoproers; LOL, low-densty inopoteins; VLDL, very lon-densty lpoptctens; IDL, intermediate ders lipoproteins: raised; ioneted [EB 1981e 15-2 Clinical Presentations of Xanthomas Type of Xanthoma Genetic Disorders Secondary Disorders Fruptve Familial lipoprotein lipase defidency (ype 1) Obesity Ap0-C2 deficiency (type I) Cholestasis Famiial hypertiglyceridemia (ype M) Diabetes Farle hypertighcerdemia vith chylomicronemia (ype V)_ Medications: Retinoids, estrogen therapy, protease inhibitors Tuberous Familial hypercholesteroleria (ype i) Monoclonal gamimopathies Familial dysbetalipoproteneria (ype I) Phytosterolemia Tendinous Familial hypercholesteroleria (ype i) Familial defective apo-B Familial dysbetalipoproteinemia (type I) Phytosterolemia Cerebrotendinous xanthomatosis Planar Palmar Famiial dysbetalipoproteineria (type Il) intertriginous Familial homozygous hypercholesterolemia (type I) Cholestasis Difuse Monoclonal gammopathies, cholestasis Xenthelasma Famiial hypercholesterolemia (type I) ‘Monoclonal gammopathies Famiial dysbetalipoproteineria (ype Il) Other Commeal arcus __Farnalhypercholesterolemia (type il) Tonsilar Tangier disease apo = apolipoprotein. Source: LE White Yanthomas and lipoprotein disorders in K Wolfe. a. (es) Flzparic's Dermatology in Genera Medicine, 7h ed. New York, McCraw 2008, P1272,La PART Il DERMATOLOGY AND INTERNAL MEDICINE PO CC. ae! Sy ETOH. = Most common of all xenthomas. In most cases an isolated finding unrelated to hypetipideria. Occurs in individuals >50 years; however, when in children or young adults, it is associated with familial hypercholesterolemia (FH) or familial dysbetalipoproteinemia (FD). 1 Skin lesions are asymptomatic. Soft, polygonal yellow-orange papules and plaques localized to upper and lower eyelids (Fig. 15-11) and around inner canthus. Slow enlargement from tiny spots ‘over months to years. = Cholesterol should be estimated in plasma; if enhanced, screening for type of hyperlipidemia (FH or FD). f due to hyperlipidemia, complication with atherosclerotic cardiovascular disease may be expected. m Laser, excision, electrodesiccation, or topical ap- plication of trichloroacetic acid, Recurrences are ‘not uncommon. Synonyms: Xanthelasma palpebrarum, periocular xanthoma, B POCO DLL) IM 1m These subcutaneous tumors are yellow or skin- colored and move with the extensor tendons (Fig. 15-12). 1 They are a symptom of familial hypercholeste- Tolemia (FH) that presents as type lla hypetipi- demi. = This condition is autosomal recessive with a differ- ent phenotype in the heterorygote and homozy- sole. 1 In the homozygote, the xanthomata appear in eatly childhood and the cardiovascular complica tions in early adolescence; the elevation of the LDL content of the plasma is extreme. These patents rarely attain ages above 20 years = Management: A diet low in cholesterol and saturated fats, supplemented by cholestyramine or statins. In extreme cases, measures such as portacaval shunt or liver transplantation have to be considered. Synonym: Tendinous xanthoma, XANTHOMA TUBEROSUM 1 This condition comprises yellowish nodules (ig 15-13) located especially onthe elbows and knees by confluence of concomitant eruptive xantho- mas. 1 They are to be found in patients with FD, far ial hypertighceridemia with chylomicronemia (ypeV) and FH (Table 15.2). 'm In homozygous patients with FH, the tuberous xanthomas are flatter and skin colored. They are not accompanied by eruptive xanthomas = Management: Treatment ofthe underlying condi tion. Synonym: Tuberous xanthoma, 2. FIGURE 15-13 Tuberous xanthoma erythematous margin. (Across facing page) Flattopped, yellow, firm nodule with an437 FIGURE 15-11 Xanthelasma Multiple reamy-orange, slighty ele- vated dermal papules on the eyelids ‘of a normolipemic individual. FIGURE 15-12 Tendinous xanthoma Large subcutaneous tumor adherent tothe Achilles tendon. FIGURE 15-13,an COL) alee ea SDE! 1 These discrete inflammetorytype papules “erupt” mt Lesions may be scattered, discrete, in a localized suddenly and in showers, appearing typicaly on region feg, elbows, knees (Fig. 15-14), buttocks) the buttocks, elbows, lower arms (Fig. 1:14) and or appear as “tight” clusters that become confiu- knees ent to form nodular “tuberoeruptive” xenthomas. 1A sign of FHT, FD, the very rare familial ipopro- = Management: React very favorably to a low:cal: tein lipase deficiency (FLD) (Table 152), and —_ovie and lowfat diet. dlabetes out of contro 1 Papules are dome-shaped, discrete, intlly red, then yellow center with ted halo (Fig. 15-14) A B FIGURE 15-14 Papular eruptive xanthomas A. Muligle, discrete, red-to-yellow papules becoming contlu- ent on the knees of an individual with uncontrolled diabetes melitus; lesions were present on both elbows and buttocks. B. Higher magnification of xanthomas on the trunk of another patient. 1 This condition is characterized by yellow-orange, mt Patients with FD are prone to atherosclerotic flat or elevated infiltrations ofthe volar creases of _—_cardiovascular disease, especialy ischemia of the palms and fingers (Fig 15-15), legs and coronary vessels = Pathognomonic for FD (ype Ill) (Table 15-2). = Management: Patents with FD react very favo- Next to xanthoma striatum palmare, FD also ably to @ diet low in fats and carbohydrates. If presents with tuberous xanthoma (Fig. 15-13) and _ necessary this may be supplemented with stains, xanthelasma palpebrarum (Fig. 15-1). fbrates, or nicotinic aceSECTION 15 ENDOCRINE, METABOLIC NUTRITIONAL, AND GENETIC DISEASES FIGURE 15-15 Xanthoma striatum palmare The palmar ceases are yelow, often a subte lesion noticeable only upon dose ‘examination Ate Ts ee Cre = Xanthoma planum is a normolipemic xanthoma leukemia, but the most common association is that consists of difuse orange-yellow pigmenta- with mutiple myeloma, tion and slight elevations of the skin (Fig. 15-16) There is a recognizable border. 1 These lesions can be idiopathic or secondary to 1 The lesions may precede the onset of multiple myeloma by many years FIGURE 15-16 Plane xanthoma Yello red, sightly elevated plaques on the neck, notice- able mainly because of the accentuation of the ski texture in a normoliperic patent wih Isr phoma, Plane xanthomas occur most commonly ‘on the upper trunk and neck and alsa accur in individuals with myeloma