Sunday, April 16, 2017

[考生加油]Dermatological Recall: Chapter 135. Xanthomatoses and Lipoprotein Disorders

Fitzpatrick's Dermatology in General Medicine

Chapter 135. Xanthomatoses and Lipoprotein Disorders

如果要儘快掌握本章重點,不妨看一下筆者仿照Surgical Recall寫的Dermatological Recall。
  • 建議可以先遮住右邊,想一下答案大概是什麼。
  • (5)表示答案有五項。(訣)表示有筆者自編的口訣。

Xanthomatoses and Lipoprotein Disorders: introduction
  1. Xanthoma內有哪種細胞?
Chlesterol & triglycerides in foamy macrophages
  1. Xanthoma會在哪些組織?(3)
Skin, tendons, tonsillar(Tangier dz)
  1. Xahthoma形成有哪些mechanisms (3)
  • Local factors( heat, movement, and friction)→↑LDL capillary leakage→↑ V-CAM & E-selectin引來Mφ
  • Mφs’ scavenger receptors LDL uptake
  • MφIn situ lipid synthesis
  1. Xanthomas型態分為哪四大類?
Eruptive, tubo-eruptive or tuberous, tendinous, or planar.
  1. Xanthomas的病理學特徵為何?
Foam cells: Mφcontain lipid.
Eruptive: foam cells+ lymphoid cells, histiocytes, neutrophils, and free lipid in the dermis.
Tuberous/ Tendonous: foam cells+ cholesterol clefts(doubly refractile)
Xanthelasmata: superficial location/eyelids(striated muscle, vellus hair, and/or a thinned epidermis).
Lipid and Lipoprotein Metabolism
  1. Cholesterol合成的速率決定步驟是哪個酵素?
HMG-CoA reductase
  1. Cholesterol吸收和合成的比例大概多少?
  1. 哪些食物富含Cholesterol?
Eggs, butter, whole milk, and animal fats as found in meat
  1. 植物的Cholesterol叫做?
Plant sterols (β-sitosterol and campesterol)
  1. Cholesterol可做成那些產物?(5)
Bile acids—cholic acid & chenodeoxycholic acid
Steroid hormones: estrogen, testosterone, & cortisol
  1. Cholesterol不能合成Bile acids會產生什麼疾病?
cerebrotendinous xanthomatosis(CTX)
  1. 五種lipoprotein代謝的流程為何?
小腸→Chylomicrons→血管→chylomicron remnant→肝→VLDL→血管→VLDL remnant(IDL) →肝→LDL→肝/adipocyte
Mn: C Cr V Vr L(語法:去過血管變~remnant,去過肝變~LDL)
  1. 五種lipoprotein代謝過程中,哪種成分逐漸降低?
  1. 小腸會製造哪兩種lipoprotein?
Chylomicrons & HDL
  1. 哪些lipid會被ABCG5/8送回腸道?
Cholesterol,β-sitosterol and campesterol
  1. 承上,ABCG5/8異常會造成哪種疾病?
Phytosterolemia(β-sitosterol),會造成tendinous xanthomas.
  1. Chylomicrons有哪四種lipoproteins?哪種會和血管的lipoprotein lipase(LPL)作用?
A, B48, CII, E。CII
  1. Chylomicrons remnant有哪兩種lipoproteins?哪種會和肝的Chylomicrons remnant receptor作用?
B48, E。E
  1. VLDL有哪三種lipoproteins? 哪種會和血管的LPL作用?
B100, CII, E。CII
  1. VLDL remnant(IDL) 有哪兩種lipoproteins?哪種會和肝的LDL receptor作用?
B100, E。B100
  1. LDL有哪種lipoprotein能與肝的LDL receptor作用?
  1. HDL有哪兩種lipoprotein能將cholesterol回收入肝?
apoA-I & apoA-II
  1. 無法代謝chylomicrons and VLDL會造成哪種xanthoma?
Eruptive(severe hypertriglyceridemia)
  1. 無法代謝chylomicron and VLDL remnant會造成哪種xanthoma?
tubo-eruptive xanthomas (combined hyperlipidemia)
  1. HDL deficiency(apoA-I不足) 會造成哪種xanthoma?
tubo-eruptive xanthomas
  1. 無法代謝LDL會造成哪種xanthoma?
tendinous xanthomas(familial hypercholesterolemia)
  1. Cholestanol or plant sterols過多會造成哪種xanthoma?
tendinous xanthomas
  1. 哪些familial lipoprotein disorders容易產生premature CHD?
Familial hypercholesterolemia(IIa)
Familial Lipoprotein (a) Excess(tendinous or tubo-eruptive)
Familial Combined Hyperlipidemia(tendinous or tubo-eruptive)IIb
Familial Dyslipidemia(tubo-eruptive)III
Familial Hypoalphalipoproteinemia(tubo-eruptive)IV
Tangier Disease(yellow/orange hyperplastic tonsils)
  1. 承上,這些疾病是否容易產生xanthoma?


  1. 哪些familial lipoprotein disorders容易產生xanthoma?
Familial Hypercholesterolemia(tendinous)IIa
Cerebrotendinous Xanthomatosis(tendinous)
Marked HDL Deficiency(tubo-eruptive)
  1. Tendinous xanthomas好發於何處tendon?
Subcutaneous nodules in fascia, ligaments, extensor tendons of hands, knees, elbows, and Achilles tendons
  1. Tenidnous xanthomas是因為血中哪些成分高?
Sterols: cholesterol,
  1. Tendinous xanthomas與那些疾病有關?
Familial hypercholesterolemia (FH, LDL>300mg/dL), phytosterolemia (plant sterols: β-sitosterol and campesterol), or cerebrotendinous xanthomatosis (cholestanol).
  1. Tendinous xanthomas有哪些治療?
Statins, ezetimibe, anion exchange resins, LDL apheresis
  1. Familial Hypercholesterolemia(IIa)有哪三種類型?
Homozygous familial hypercholesterolemia, heterozygous familial hypercholesterolemia, or defective apoliprotein-B100
  1. Familial Hypercholesterolemia造成哪種xanthoma?
Tendinous or tuberous xanthomas.
  1. Familial Hypercholesterolemia的臨床特徵為何?
Arcus senilis, tendinous xanthomas, xanthelasma
LDL↑, normal TG & HDL.
  1. Homozygous familial hypercholesterolemia另有哪些臨床特徵?
Tubo-eruptive xanthomatous plaques (over the extremities, buttocks, and hands), Intertriginous xanthomas(極具指標性), CHD/aortic stenosis <20y/o, LDL>600mg/dL(heterozygous>300 mg/dL)
  1. Familial Hypercholesterolemia造成的CHD要如何預防?
服用Statins+ ezetimibe,使LDL <130 mg/dL
有必要時LDL apheresis
  1. Phytosterolemia血中那些成分會高?
Elevated LDL cholesterol, plasma β-sitosterol & campesterol
  1. Phytosterolemia的臨床症狀為何?
tendinous and tuberous xanthomas and premature CHD
  1. Phytosterolemia有哪些治療?
  1. CTX血中那種成分會高?
  1. CTX的臨床症狀為何?
Cerebellar ataxia and dementia, tendinous xanthoma
  1. CTX患者為何無法用cholesterol製造bile acid?
Defects in the sterol 27-hydoxylase gene
  1. CTX有哪些治療?
Oral chenodeoxycholate 250 mg TID
  1. Tubo-eruptive, planar, and palmar xanthomas與那些疾病有關?
Combined hyperlipidemia(Cholesterol+ TG) & marked HDL deficiency, monoclonal gammopathies, multiple myeloma
  1. Tubo-eruptive, planar, and palmar xanthomas是因為血中哪些成分高?
Cholesterol+TG= intestinal and liver remnant lipoprotein particles (dysbetalipoproteinemia)
  1. Tubo-eruptive, planar, and palmar xanthomas有哪些治療方式?
Dietary modification, statins, fibrates, and niacin
  1. Dysbetalipoproteinemia(IIb & III)血中那些成分會高?
Chylomicron remnants & VLDL remnants(IDL).
  1. Dysbetalipoproteinemia是哪種lipoprotein缺乏/功能不足?
ApoE deficiency,或apoE2/2(正常為3/3),hepatic lipase deficiency
  1. 用哪種檢體測量hepatic lipase活性?
Postheparin plasma (10 minutes after the injection of 100 units/kg body weight of heparin).
  1. Dysbetalipoproteinemia的臨床症狀為何?
Adult with xanthoma striatum palmare(characteristic) ,
Tubo-eruptive xanthomas on their elbows, hands, and even ears
Premature CHD, gout, and diabetes
  1. Dysbetalipoproteinemia的lab為何?
non HDL cholesterol (total cholesterol—HDL cholesterol>200 mg/dL) and remnant lipoprotein cholesterol (>100 mg/dL)
  1. Dysbetalipoproteinemia有哪些治療?
fibrates, nicotinic acid, or statin
  1. marked HDL deficiency 的LDL與TG如何?
  1. marked HDL deficiency是哪種lipoprotein缺乏?
  1. marked HDL deficiency的臨床症狀為何?
Corneal opacification, premature CHD in their 30s. tubo-eruptive xanthomas, palmar and planar xanthomas
  1. marked HDL deficiency 的lab為何?
HDL cholesterol <10 mg/dL
  1. marked HDL deficiency有哪些治療?
optimizing all CHD risk factors (LDL <70 mg/dL, TG <150 mg/dL, no smoking, BP <130 mmHg, and HbA1c <7.0%),
  1. Xanthomas還與哪些systemic diseases有關?(4)
monoclonal gammopathies, multiple myeloma, lymphoma and various forms of leukemia
  1. 承上,這類xanthoma形成的機轉為何?
Igs bind lipoprotein,延遲chylomicron remnants or VLDL remnants之清除(兩者會高)。
  1. 承上,這類xanthoma多半為哪些類型?
Tubo-eruptive, planar, and palmar xanthomas(同combined hyperlipidemia or dysbetalipoproteinemia)
  1. 承上,這類xanthoma如何治療?
治療underlying disorder, fenofibrate
  1. Xanthomas還與哪類結構性疾病有關
Prolonged obstruction of the biliary tree (primary biliary cirrhosis and secondary biliary obstruction.)
  1. 承上,這類xanthoma的lab為何?
unesterified cholesterol.
  1. 承上,這類xanthoma多半為哪些類型?
Plane xanthomas (plaques on hands, feet, and trunk), xanthelasma, and tuberous xanthomas.
Jaundice, pruritus, and hyperpigmentation of the skin
  1. 承上,這類xanthoma如何治療?
解決obstruction. liver transplantation for stage 4 disease.
  1. Planar xanthoma的臨床特徵為?
Yellow macules, soft papules, or plaques on the upper eyelids (xanthelasma palpebrarum), the wrists and palms (xanthoma striatum palmare), and in intertriginous area.
  1. Xanthelasma好發於何處? 與那些疾病有關?
Eyelids, elevated LDL cholesterol 或完全健康的人
  1. Xanthelasm有哪些治療方式?
Ablative laser therapy(最佳), surgical excision, , trichloroacetic acid, cryotherapy

  1. Eruptive xanthomas有哪些臨床特徵?
Multiple, reddish-yellow papules at extensor surface of extremities & buttocks(Appear suddenly)
  1. Eruptive xanthomas血中哪種成分會高?
Chylomicron and TG (fasting level >1,000 mg/dL, chylomicrons+), 嚴重會pancreatitis
  1. 哪些疾病會造成eruptive xanthomas?
Severe Hypertriglyceridemia(typeI: Familial chylomicronemia; typeV: Mixed hyperlipidemia), obesity, alcohol abuse, diabetes (type 2), and drugs
  1. 遺傳性Severe Hypertriglyceridemia是哪種酵素/lipoprotein缺乏?
Lipoprotein lipase deficiency or apoC2 deficiency
  1. Severe Hypertriglyceridemia的臨床症狀為何?
Eruptivee xanthoma, Lipemia retinalis (milky plasma which can be visualized in retinal veins)
很少coronary atherosclerosis.
  1. Severe Hypertriglyceridemia的lab為何?
LDL <50 mg/dL
chylomicrons and VLDL,導致lipoprotein lipase活性很低
  1. Severe Hypertriglyceridemia有哪些治療?
dietary modification.
  1. 哪些藥物會造成eruptive xanthomas
Retinoids, estrogen, and protease inhibitors.
  1. Eruptive xanthomas有哪些治療方式?
限 fat and sugars, weight loss,control diabetes, fibrates & fish oil.

Xanthomas in Children

  1. 哪些原因會導致小孩出現xanthomas? (4)
homozygous FH, phytosterolemia/sitosterolemia, CTX, and Alagille syndrome
  1. Alagille syndrome原因為何?
an inherited syndrome of biliary hypoplasia
  1. Alagille syndrome有哪些臨床特徵?
A characteristic facies (a prominent forehead, hypertelorism, pointed chin, and nasal dystrophy), Cirrhosis,
  1. Alagille syndrom是哪種血脂增加?
  1. Alagille syndrom如何治療?
liver transplantation

Verruciform Xanthoma(VX)

  1. VX好發於何處?
oral cavity
  1. VX的病理特徵為?
foamy histiocytes within elongated dermal papillae
  1. Nonmucosal VX要小心何種疾病?
congenital hemidysplasia with ichthyosiform erythroderma and limb defects (CHILD)
  1. 還有哪種遺傳疾病會長VX?
Epidermolysis bullosa
Laboratory of xanthomas
  1. 完整的lab須包含哪些項目?
urine protein, serum creatinine(排除nephrotic syn.) and a hepatic panel(排除肝炎TG↑ & 膽道阻塞: LDL&Alp), fasting glucose(排除DM), thyroid function tests(排除hypothyroidism), a fasting lipid profile, lipoprotein(a), apoE genotyping, β-sitosterol, campesterol, and cholestanol.
  1. Lipid profile抽血須注意何事?
fasts overnight
  1. 如何辨別β-sitosterol , campesterol, cholestanol?
gas chromatography
  1. 血脂異常的標準為何?
LDL cholesterol (>160 mg/dL) or triglycerides (>150 mg/dL), or decreased levels of HDL cholesterol (<40 mg/dL)
  1. Diabetes, renal disorders(nephrotic syndrome), anabolic steroid使用的lab特色為?
  1. Hypothyroidism and obstructive liver disease的lab特色為?
  1. estrogens and alcohol intake的lab特色為?
  1. Lifestyle Therapy如何進行?
physical activity /weight control( preventing diabetes, triglycerides, and HDL)
Dietary management: saturated fat/trans fats, cholesterol to <200 mg/day, vegetable oils, fish intake.
  1. ↓LDL & TG, ↑HDL有哪些藥物選擇?
↓LDL: Statins > ezetimibe>resins.
TG: Fibrates(fenofibrate)> fish oil>niacin therapy.
HDL: Niacin
  1. Statin的主要機轉為?
inhibit HMG-CoA reductase
  1. Statin的主要副作用為?
dyspepsia, headaches, muscle or joint aches, liver transaminitis,severe myopathy leading to rhabdomyolysis.
  1. Fibrate有哪兩個藥?
gemfibrozil and fenofibrate((不像gemfibrozil和statin交互作用
  1. Fibrates的主要機轉為?
  1. Fibrates的主要副作用為?
dyspepsia, gallstones(cholesterol secretion into bile)
會增強warfarin and certain hypoglycemic作用
  1. Niacin以哪種藥最常用?
Niaspan: extended release product (less flushing 2 g/day taken at bedtime)
  1. Niacin的主要副作用為?
flushing(先服aspirin), gastric irritation, and uric acid, glucose, and liver enzymes
  1. 哪兩種病人不宜用niacin?
liver disease, gastric ulcer.
  1. Ezetimibe的主要機轉為?
NPC1L1 inhibitor
Cholesterol and plant sterols經由 Niemann-Pick C-like protein 1 (NPC1L1) transporter吸收入腸
  1. 哪種人適合用Ezetimibe?
  1. Ezetimibe和statin用有何特效?
  1. 有哪些Anion Exchange Resins可降血脂?
cholestyramine, colestipol, and colesevelam
  1. Anion Exchange Resins機轉為何?
bind bile acids in intestine→↑conversion of liver cholesterol to bile acids/LDL receptors in liver→↓LDL
  1. Anion Exchange Resins有哪些副作用?
bloating and constipation, TG,阻礙digoxin, tetracycline, d-thyroxine, phenylbutazone, and coumadin吸收
  1. Fish Oil Capsules的機轉為何?
eicosapentanoic acid (EPA) :消炎 immune response(IL-1, 6 and TNF-α), helper T cells & delayed hypersensitivity response
decohexanoic acid (DHA): 降血脂TG, HDL
  1. Fish oil還可減少哪些疾病?
dementia and Alzheimer disease
CHD, death from MI


Table 135-1 Clinical Presentations of Xanthomas
Type of Xanthoma
Genetic Disorders
Secondary Disorders
Familial lipoprotein lipase deficiency

ApoC-II deficiency

ApoA-I and apoA-I/C-III deficiency

Familial hypertriglyceridemia
Medications: retinoids, estrogen therapy, protease inhibitors

Familial hypertriglyceridemia with chylomicronemia

Familial hypercholesterolemia
Monoclonal gammopathies

Familial dysbetalipoproteinemia
Multiple myeloma

Familial hypercholesterolemia

Familial defective apoB

Familial dysbetalipoproteinemia


Cerebrotendinous xanthomatosis


Familial dysbetalipoproteinemia

Homozygous apoA-I deficiency

Familial homozygous hypercholesterolemia

Monoclonal gammopathies, cholestasis

Familial hypercholesterolemia

Familial dysbetalipoproteinemia
Monoclonal gammopathies

Corneal arcus
Familial hypercholesterolemia

Tangier disease

Table 135-2 Frederickson Classification of Familial Hyperlipidemias (Only Occasionally Used)
Frederickson Classification
Lipoprotein Increase
Type of Xanthoma
Type I
Familial chylomicronemia
Decreased lipoprotein lipase or altered apoC-II
Chylomicrons (and VLDL)
Eruptive xanthomata
Type IIa
Familial hypercholesterolemia
LDL receptor or apoB deficiency
Tendon, tuberous, plane xanthomas (xanthelasma and intertriginous) 15% with xanthoma by second decade
Xanthomata by age 6 years
Type IIba
Familial combined hypercholesterolemia
Decreased LDL receptor and increased apoB
Usually absent, but can have xanthomas as in type IIa
Type III
Familial dysbetalipoproteinemia
Defective apoE-2 synthesis
Palmar, tuberous, tubo-eruptive xanthoma, xanthelasma
Type IVb
Familial hypertriglyceridemia (pure)
Increased VLDL production and decreased elimination
Rare eruptive xanthomas
Type V
Mixed hyperlipidemia
Increased VLDL production and decreased LPL
VLDL and chylomicrons
Eruptive xanthomas
Most familial hyperlipidemias associated with xanthomas are rare.

Box 135-1 Differential Diagnosis of Xanthomas
  • Eruptive xanthomas
    • Sarcoid
    • Interstitial granuloma annulare
    • Xanthoma disseminatum
    • Juvenile xanthogranulomas
  • Tuberous or tendinous xanthomas
    • Cyst
    • Lipoma
    • Neurofibroma
  • Plane xanthomas
    • Pseudoxanthoma elasticum
    • Amyloidosis
    • Sarcoidosis
  • Xanthelasma
    • Syringoma
    • Sebaceous hyperplasia
    • Adnexal neoplasms

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