Alikhan 3.8 - Xanthomas
Mainly exogenous production
Are chylomicrons formed from endogenous or exogenous production?
No
Are verruciform xanthomas associated with hyperlipidemia?
Usually >3000 mg/dL
Eruptive xanthomas are associated with what triglyceride levels?
Type I
Familial LPL deficiency is which type of hyperlipoproteinemia?
Type I
Familial hyperchylomicronemia is which type of hyperlipoproteinemia?
Remnant of VLDL after hydrolysis of most of triglycerides by lipoprotein lipase
How is IDL formed?
Product of further triglyceride hydrolysis of IDL (now mainly cholesterol ester core and B-100 on surface)
How is LDL formed?
Type II hyperlipidemia > type III
In which subtype of hyperlipidemia are tendinous xanthomas most often seen?
Mainly endogenous production in the liver
Is VLDL formed from endogenous or exogenous production? Where?
No
Is type I hyperlipoproteinemia associated with increased coronary artery disease?
Type II
Name the hyperlipoproteinemia: Accelerated degradation of LDL receptor due to missense PCSK9 mutations
Type I
Name the hyperlipoproteinemia: Apo C-II deficiency
Type II
Name the hyperlipoproteinemia: Defective LDL receptor adaptor protein 1
Type I
Name the hyperlipoproteinemia: Deficient glycosyl-phosphatidylinositol-anchored HDL-binding protein
Type I
Name the hyperlipoproteinemia: Deficient or abnormal LPL
Type II, Type III
Name the hyperlipoproteinemia: Hypercholesterolemia
Type II
Name the hyperlipoproteinemia: LDL receptor defect
Type I (maybe Type IV, Type V?)
Name the hyperlipoproteinemia: No increased risk of coronary artery disease
Type II
Name the hyperlipoproteinemia: Reduced LDL clearance
Type II
Name the hyperlipoproteinemia: Reduced affinity of LDL for LDL receptor due to dysfunction of apo B-100 (ligand)
Type II, Type III
Name the hyperlipoproteinemia: Tendinous xanthomas
Type I, Type V
Name the hyperlipoproteinemia: decreased LDL and HDL levels
Type I, Type IV, Type V
Name the hyperlipoproteinemia: eruptive xanthomas
Type I, Type III, Type IV, Type V
Name the hyperlipoproteinemia: hypertriglyceridemia
Type I
Name the hyperlipoproteinemia: slow chylomicron clearance
Type II, Type III
Name the hyperlipoproteinemia: tuberoeruptive xanthomas
Type II
Name the hyperlipoproteinemia: xanthelasma
May occur in monoclonal gammopathy (plasma cell dyscrasia usually) with no lipid abnormality favors neck, upper trunk, intertriginous and periocular areas
Plane xanthomas can occur in the setting of no lipid abnormalities in what clinical setting?
Homozygous familial hypercholesterolemia (type II hyperlipidemia)
Plane xanthomas in intertriginous areas and web spaces of fingers are usually diagnostic of what condition?
Neck, upper trunk, intertriginous and periocular areas
Plane xanthomas in the setting of monoclonal gammopathy have what antomic predilection?
Dysbetalipoproteinemia
Plane xanthomas on the palmar/finger creases are nearly pathognomonic for what?
I, IV, and V hyperlipidemias
Primary eruptive xanthomas are associated with which hyperlipidemia subtypes?
Obesity, diabetes, alcohol abuse, medication-induced (ORAL RETINOIDS, protease inhibitors, olanzapine, estrogen replacement)
Secondary eruptive xanthomas are associated with what conditions/drugs?
Type II and III
Tuberous xanthomas are most strongly associated with what subtypes of hyperlipidemias?
ATHEROSCLEROSIS of peripheral and coronary arteries
Type II hyperlipoproteinemia are associated with what systemic complications?
CHILD syndrome; any disorder that causes epidermal damage (epidermolysis bullosa, GVHD, LS&A, pemphigus)
Verruciform xanthomas are associated with what conditions/medical conditions?
50%
What % of patients with xanthelasma have hyperlipidemia?
A-I
What apoprotein on HDL is required to remove cholesterol from tissues?
Numerous red-yellow papules on EXTENSOR SURFACES, BUTTOCKS, intertriginous areas and orally
What are the clinical features of eruptive xanthomas?
May be localized or diffuse; occurrence in INTERTRIGINOUS AREAS AND WEB SPACES OF FINGERS usually diagnostic of HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA (TYPE II HYPERLIPIDEMIA); occurrence on PALMAR/FINGER CREASES (xanthoma striatum palmare) is nearly pathognomonic for DYSBETALIPOPROTEINEMIA
What are the clinical features of plane xanthomas?
Firm nodules on ACHILLES TENDON and extensor tendons of fingers/hands that develop in third decade
What are the clinical features of tendinous xanthomas?
Yellow-pink indurated nodules mainly on ELBOWS AND KNEES
What are the clinical features of tuberous xanthomas?
Benign verrucous plaque (s) typically occurring in MOUTH or GENITAL AREA; often confused for warts clinically and histologically; not a/w hyperlipidemia
What are the clinical features of verruciform xanthoma?
Skin, tendons, eyes
What are the common locations for xanthomas?
Chylomicrons, VLDL, IDL, LDL, HDL
What are the different types of lipoproteins?
Decreased LDLs and HDLs; hypertriglyceridemia
What are the lab abnormaliteis seen in type V hyperlipoproteinemia?
Familial LPL deficiency; familial hyperchylomicronemima
What are the other names for type I hyperlipoproteinemia?
Familial dysbetalipoproteinemia, remnant removal disease, broad beta disease, apo E deficiency
What are the other names for type III hyperlipoproteinemia?
ORAL RETINOIDS, protease inhibitors, olanzapine, estrogen replacement
What drugs are associated with secondary eruptive xanthomas?
Lecithin-cholesterol acyltransferase
What enzyme esterfies free cholesterol?
Foam cells = macrophages w/ lipidized cytoplasm in dermis; Foam cells located more superficially in plane xanthomas and deper in dermis/SQ in tuberous and tendinous xanthomas
What is seen on histology in plane, tuberous and tendinous xanthomas?
Unique histology; papillomatous epidermal hyperplasia w/ FOAM CELLS IN DERMAL PAPILLAE
What is seen on histology in verruciform xanthomas?
3rd decades
What is the age predilection for tendinous xanthomas?
EXTENSOR SURFACESS, BUTTOCKS, intertriginous areas and orally
What is the anatomic predilection for eruptive xanthomas?
Achilles tendon and extensor tendons of fingers/hands
What is the anatomic predilection for tendinous xanthomas?
ELBOWS AND KNEES
What is the anatomic predilection for tuberous xanthomas?
Mouth or genital area
What is the anatomic predilection of verruciform xanthomas?
Inner core (triglycerides + cholesterol esters) + outer shell (phospholipids, free cholesterol, and apoproteins (bind receptors and activating enzymes))
What is the basic structure of lipoproteins?
Surgical treatment
What is the best treatment option for xanthelasma?
Xanthoma striatum palmare
What is the name for plane xanthomas on the palmar/finger creases?
Xanthelasma
What is the name of a plane xanthoma on the eyelids?
Familial hypercholesterolemia or familial defective apo B-100
What is the other name for type II hyperlipoproteinemia?
Endogenous familial hypertriglyceridemia
What is the other name for type IV hyperlipoproteinemia?
Deficient or abnormal LPL; Apo C-II deficiency or Deficient glycosyl-phosphatidylinositol-anchored HDL-binding protein
What is the pathogenesis of type I hyperlipoproteinemia?
LDL RECEPTOR DEFECT; Reduced affinityy of LDL for LDL receptor due to dysfunction of apo B-100 (ligand); Accelerated degradation of LDL receptor due to missense PCSK9; Defective LDL receptor adaptor protein 1 (required for receptor internalization)
What is the pathogenesis of type II hyperlipoproteinemia?
Hepatic remnant clearance impaired due to apo E abnormality; patients only express the apo E2 isoform that interacts poorly with the apo E receptor
What is the pathogenesis of type III hyperlipoproteinemia?
Elevated production of VLDL associated with glucose intolerance and hyperinsulinemia
What is the pathogenesis of type IV hyperlipoproteinemia?
Elevated chylomicrons and VLDLs; subset related to apo A-V defect
What is the pathogenesis of type V hyperlipoproteinemia?
ABNORMALITIES IN LIPID METABOLISM (primary or secondary; may be a/w atherosclerosis) or MONOCLONAL GAMMOPATHY (e.g. MGUS, multiple myeloma, CLL, Waldenstrom disease; usually IgG, but can be IgA or IgM)
What is the pathogenesis of xanthomas?
IDL
What is the remnant of VLDL after hydrolysis of most of triglycerides by lipoprotein lipase?
Removes cholesterol from tissues
What is the role of HDL?
Transport plasma lipids to peripheral cells
What is the role of lipoproteins?
Central core of mainly triglycerides; outer shell contains B-100, E, and C-II
What is the structure of VLDL?
Central core of mainly triglycerides; outer shell contains various apoproteins (B-48, E, A-I, A-II, C-II) --> becomes chylomicron remnant after most of the triglyceride content is hydrolyzed
What is the structure of a chylomicron?
Treat underlying lipoprotein disorder and contributing factors - correct via various interventions (dietary modifications, lipid-lowering medications, surgical excision, and chemotherapy in certain monoclonal gammopathies)
What is the treatment of xanthomas?
Slow chylomicron clearance (if deficient or abnormal LPL); Reduced LDL and HDL levels (if Apo C-II deficiency); Hypertriglyceridemia (if deficient glycosyl-phosphatidylinositol-anchored HDL-binding protein)
What lab abnormalities are associated with type I hyperlipoproteinemia?
Reduced LDL clearance; HYPERCHOLESTEROLEMIA
What lab abnormalities are associated with type II hyperlipoproteinemia?
Elevated levels of chylomicron remnants and IDLs; HYPERCHOLESTEROLEMIA; hypertriglyceridemia
What lab abnormalities are seen in type III hyperlipoproteinemia?
Increased VLDLs; Hypertriglyceridemia
What lab abnormalities are seen in type IV hyperlipoproteinemia?
Frequently associated with type 2 non-insulin-dependent diabetes mellitus, obesity, alcoholism
What systemic abnormalities are associated with type IV hyperlipoproteinemia?
Diabetes mellitus
What systemic abnormalities are associated with type V hyperlipoproteinemia?
ATHEROSCLEROSIS of peripheral and coronary arteries
What systemic features are associated with type III hyperlipoproteinemia?
Type III
What type of hyperlipoproteinemia is apo E deficiency?
Type III
What type of hyperlipoproteinemia is broad beta disease?
Type IV
What type of hyperlipoproteinemia is endogenous familial hypertriglyceridemia?
Type II
What type of hyperlipoproteinemia is familial defective apo B-100?
Type III
What type of hyperlipoproteinemia is familial dysbetalipoproteinemia?
Type II
What type of hyperlipoproteinemia is familial hypercholesterolemia?
Type III
What type of hyperlipoproteinemia is remnant removal disease?
TENDINOUS, TUBEROERUPTIVE, TUBEROUS, PLANE (xanthelasma, intertriginous areas, interdigital web spaces)
What type of xanthomas are associated with type II hyperlipoproteinemia?
ERUPTIVE
What type of xanthomas are associated with type IV hyperlipoproteinemia?
ERUPTIVE
What type of xanthomas are associated with type V hyperlipoproteinemia?
Verruciform xanthomas
What type of xanthomas are not associated with hyperlipidemia?
ERUPTIVE
What types of xanthomas are associated with type I hyperlipoproteinemia?
Tuberoeruptive, tuberous, plane (palmar creases) - most characteristics; tendinous
What xanthomas are associated with type III hyperlipoproteinemia?
Uptake into hepatocytes by apo B-100/E
Where is LDL taken up in the body? With what apoproteins?
C-II
Which apoprotein on VLDL is needed for lipoprotein lipase activation?
Apoproteins (part of the outer shell)
Which portion of the lipoprotein binds receptors and activating enzymes?
Intracellular and dermal lipid deposition
Why do xanthomas appear yellow?
Plane xanthoma
Xanthelasma is a type of what kind of xanthoma?
