126: Xanthomas Flashcards
1
Q
What are xanthomas?
A
Xanthomas are plaques or nodules consisting of an accumulation of excess lipid primarily in the skin or tendons, resulting in the formation of foam cells.
2
Q
How are xanthomas classified?
A
Xanthomas are traditionally grouped into 6 major phenotypes (Type I, IIa, IIb, III, IV, and V) classified by Fredrickson, Levy, and Lees.
3
Q
What is the historical significance of the Fredrickson-Levy-Lees classification?
A
The classification provides a biochemical phenotypic classification of dyslipidemias associated with various combinations of elevated apolipoprotein B (apoB) containing lipoproteins.
4
Q
What are the epidemiological findings related to xanthomas and dyslipidemia?
A
Approximately 53% of U.S. adults have some form of lipid abnormalities, and nearly 30% of participants in the Multi-Ethnic Study of Atherosclerosis were characterized with dyslipidemias.
5
Q
What lifestyle changes are recommended for the treatment of xanthomas?
A
The treatment typically involves diet modifications, smoking cessation, and medications (e.g., statins, adjuvants, PCSK9 inhibitors).
6
Q
What is the significance of apolipoprotein B in dyslipidemia?
A
Apolipoprotein B (apoB) containing lipoproteins are associated with various combinations of elevated lipoproteins, contributing to dyslipidemia.
7
Q
What percentage of U.S. adults have some form of lipid abnormalities?
A
An estimated 53% of all U.S. adults have some form of lipid abnormalities.
8
Q
What is the prevalence of xanthelasmas among eyelid tumors?
A
Xanthelasmas constitute 6% of eyelid tumors according to one study.
9
Q
What is the relationship between age and xanthoma disseminatum?
A
Xanthoma disseminatum tends to affect younger males in a 2:1 predilection compared to younger females.
10
Q
What is the role of genetic testing in diagnosing primary dyslipidemias?
A
Genetic testing helps confirm the diagnosis for many patients with primary dyslipidemias by identifying mutations in apolipoproteins.
11
Q
What are the common causes of secondary dyslipidemias?
A
Secondary dyslipidemias can be linked to systemic diseases such as nephrotic syndrome, hepatic abnormalities, and thyroid dysfunction.
12
Q
What is the recommendation for high-risk patients with known atherosclerotic cardiovascular disease?
A
Primary prevention statin-therapy is recommended for high-risk patients.
13
Q
What are the clinical features of eruptive xanthomas?
A
Eruptive xanthomas are characterized by multiple, small, red-yellow papules, usually less than 5 mm in size, arranged in crops on the extensor surfaces of the extremities and buttocks.
14
Q
What are the characteristics of tuberous xanthomas?
A
Tuberous xanthomas are nodules localized to pressure areas, including the extensor surfaces of elbows, knees, knuckles, and buttocks, and are rarely found on the face.
15
Q
Describe tendinous xanthomas and their clinical significance.
A
Tendinous xanthomas are firm, subcutaneous nodules found in fascia, ligaments, and tendons (e.g., Achilles, hands, knees, elbows).
16
Q
What are planar xanthomas and where are they commonly found?
A
Planar xanthomas are yellow macules, soft papules, or plaques commonly found on the upper eyelids near the inner canthus.
17
Q
What factors can aggravate eruptive xanthomas?
A
Eruptive xanthomas can be aggravated by underlying diabetes, obesity, excessive ethanol intake, and certain medications.
18
Q
What is the prevalence of familial combined dyslipidemia (Type IIb)?
A
Familial combined dyslipidemia (Type IIb) is found in 0.5% to 2% of the general population and in upwards of 10% in those with known cardiovascular disease.
19
Q
What is the association between dysbetalipoproteinemia and xanthomas?
A
Dysbetalipoproteinemia, or the Type III phenotype, is reported in 1 in 10,000 adults, and those with dyslipidemia are at risk of developing xanthomas.
20
Q
What are the characteristics of xanthelasma palpebrarum?
A
Xanthelasma palpebrarum typically appears on the eyelids and can occur in patients with elevated LDL-C levels, but is more commonly found in those with relatively normal lipid levels.
21
Q
What are the noncutaneous findings associated with xanthoma disseminatum?
A
Xanthoma disseminatum can affect visceral organs, ocular structures, the CNS, and the skeletal system.
22
Q
What complications can arise from xanthomas and their underlying conditions?
A
Complications can include cosmetic and functional defects, restricted range of motion, and obstructive blindness in cases of xanthelasma.
23
Q
What is the pathogenesis of xanthoma formation?
A
The pathogenesis is primarily due to the accumulation of serum chylomicrons and lipoproteins, leading to the formation of foam cells.
24
Q
How does sitosterolemia relate to xanthomas and its treatment?
A
Sitosterolemia is characterized by the retention and elevation of plant-based sterols in the serum, leading to tendinous xanthomas.
25
What are xanthelasmas and where are they commonly found?
Xanthelasmas are yellowish lesions that typically occur on the eyelids.
26
What is the significance of planar xanthomas in relation to systemic diseases?
Planar xanthomas may be the first sign of underlying hematologic abnormalities.
27
What are the potential complications associated with xanthoma disseminatum?
Xanthoma disseminatum can lead to increased morbidity due to GIT involvement, airway issues, ocular involvement, and intracranial lesions.
28
How does cholesterol play a role in the formation of xanthomas?
Cholesterol is a core component of lipoproteins and influences the pathophysiology of xanthomas.
29
What are the noncutaneous findings associated with xanthomas?
Noncutaneous findings may include atherosclerotic disease in any vascular bed.
30
What is sitosterolemia and how is it related to xanthomas?
Sitosterolemia is caused by a mutation in the ABCG5/G8 transporter, leading to retention of plant-based sterols in the serum.
31
What are the clinical implications of xanthomas in patients with dyslipidemia?
Patients with xanthomas stemming from dyslipidemia are at increased risk for clinical atherosclerotic cardiovascular disease.
32
A patient with xanthelasmas but normal lipid levels is concerned about cardiovascular risk. What should you tell them?
Xanthelasmas are often not associated with coronary heart disease when lipid levels are normal.
33
A patient with xanthomas and elevated β-sitosterol levels is diagnosed with phytosterolemia. What is the first-line treatment?
The first-line treatment for phytosterolemia is ezetimibe.
34
A patient with xanthomas and a history of sitosterolemia presents with elevated plant sterol levels. What genetic mutation is responsible?
Sitosterolemia is caused by a mutation in the ABCG5/G8 transporter.
35
A patient with xanthomas and a history of cerebrotendinous xanthomatosis presents with neurologic dysfunction. What is the underlying defect?
Cerebrotendinous xanthomatosis is caused by a defect in the sterol 27-hydroxylase gene.
36
What is the role of Niemann-Pick C-like protein 1 in cholesterol transport?
Niemann-Pick C-like protein 1 is responsible for transporting dietary cholesterol from the intestine.
37
What is the significance of the enzyme HMG-CoA reductase in cholesterol synthesis?
HMG-CoA reductase is the rate-limiting enzyme in cholesterol synthesis and is the target of statin-based therapies.
38
How are lipoproteins classified and what do they consist of?
Lipoproteins are classified based on size and density, consisting of cholesterol, triglycerides, and a surface layer of phospholipids.
39
What are chylomicrons and what is their primary composition?
Chylomicrons are large lipoprotein particles made in the intestine, primarily composed of triglycerides.
40
What happens to chylomicrons after they are released into the lymphatic system?
Chylomicrons pick up additional lipoproteins and are then transported to the serum where they are acted upon by lipoprotein lipase (LPL).
41
What is the difference between VLDL and LDL in terms of composition and function?
VLDLs are rich in triglycerides and synthesized in the liver, while LDLs are the end product of VLDL catabolism and contain a higher proportion of total cholesterol.
42
What is the role of HDL in cholesterol transport?
HDLs participate in reverse cholesterol transport, obtaining cholesterol from peripheral tissues and delivering it to the liver.
43
What is the clinical significance of small dense LDL compared to large LDL?
Small dense LDL is considered more atherogenic than large LDL.
44
What is the function of CETP in relation to HDL and triglycerides?
CETP facilitates the transfer of triglycerides and cholesterol esters between lipoproteins.
45
What is the clinical significance of small dense LDL compared to large LDL?
Small dense LDL is considered more atherogenic than large LDL, but measuring small dense LDL does not significantly improve risk prediction over total LDL particle or apoB concentrations.
46
What is the function of CETP in relation to HDL and triglycerides?
CETP facilitates the transfer of cholesteryl esters from HDL to triglyceride-rich lipoproteins in exchange for triglyceride.
47
What is considered a significant cardiovascular risk factor regarding HDL-C levels?
Decreased HDL-C levels of less than 40 mg/dL are often considered a significant cardiovascular risk factor.
48
What is the role of Niemann-Pick C-like protein 1 in cholesterol transport?
It transports dietary cholesterol from the intestine through the exogenous pathway.
49
What is the primary component of chylomicrons?
Triglycerides, which make up 85% by weight.
50
What happens to chylomicrons after they are released into the lymphatic system?
They pick up additional lipoproteins including apolipoprotein AI (apoAI), apoAIV, and the C apolipoproteins.
51
What is the function of lipoprotein lipase (LPL) in relation to chylomicrons?
LPL cleaves free fatty acids off the glycerol backbones of triglycerides in chylomicrons.
52
What is the significance of the enzyme HMG-CoA reductase in cholesterol synthesis?
It is the rate-limiting step in cholesterol synthesis and the target of statin-based therapies.
53
How are intermediate-density lipoproteins (IDLs) formed?
From remnant VLDL particles after triglyceride is removed by LPL.
54
What is the primary protein found in LDL particles?
ApoB100.
55
What is the difference between large LDL and small dense LDL?
Small dense LDL is considered more atherogenic than large LDL.
56
What cardiovascular risk is associated with decreased HDL-C levels?
Levels less than 40 mg/dL are considered a significant cardiovascular risk factor.
57
What are the two main pathways of lipid metabolism highlighted in the overview?
The two main pathways of lipid metabolism are exogenous lipid metabolism and endogenous lipid metabolism.
58
What role does capillary lipoprotein lipase (LPL) play in lipid metabolism?
Capillary lipoprotein lipase (LPL) hydrolyzes triglycerides and releases fatty acids for uptake by various tissues, requiring apolipoprotein CII (apoCII) as a cofactor.
59
What happens to chylomicron remnants in the liver?
Chylomicron remnants are recycled by the liver, where they require apoE as a ligand for low-density lipoprotein (LDL) receptors, leading to their transformation into LDL.
60
How does the endogenous pathway of lipid metabolism function?
The endogenous pathway involves the hepatic production of very-low-density lipoprotein (VLDL) and the delivery of free fatty acids to peripheral tissues, with VLDL hydrolyzing triglycerides for tissue uptake.
61
What is the fate of intermediate-density lipoproteins (IDLs) in lipid metabolism?
Intermediate-density lipoproteins (IDLs) may be removed from circulation via the LDL receptor or transformed into LDL by hepatic lipase (HL) in the liver.
62
What is the function of very-low-density lipoprotein (VLDL) in lipid metabolism?
VLDL is produced in the liver and delivers free fatty acids to peripheral tissues.
63
What is the significance of LDL receptors in lipid metabolism?
LDL receptors bind to LDL for clearance or deposit within luminal walls.
64
What is the primary function of chylomicrons in lipid metabolism?
Chylomicrons package triglycerides in the intestines for transport to various tissues.
65
What is the role of apoCII in the function of LPL?
ApoCII acts as a cofactor required for LPL to hydrolyze triglycerides.
66
What are the primary categories of dyslipidemias that can lead to xanthomas?
1. Primary dyslipidemias - carry a heritable or familial component.
2. Secondary dyslipidemias - typically acquired but may unmask an underlying genetic predisposition.
3. Normolipemic states - there is no underlying dyslipidemia, which is much rarer compared to primary and secondary dyslipidemias.
67
What are the clinical manifestations of Type I hyperlipidemias?
- Increased serum chylomicrons due to deficiencies in LPL or apoCII.
- Serum triglyceride levels commonly above 1000 mg/dL.
- Severe hypertriglyceridemia can lead to episodic eruptive xanthomas.
- Other manifestations include:
- Acute pancreatitis
- Neuropathy
- Arthralgias
- Hepatosplenomegaly
- Lipemia retinalis
68
What genetic defects are associated with Type IIa hyperlipidemias?
- Mutations in the LDL receptor, which clears circulating LDL.
- Mutations in apoB, which is a cofactor in the binding between LDL and its receptor.
- Autosomal recessive forms due to defects in LDL receptor adaptor protein 1 (LDLRAP1) or PCSK9, which promotes degradation of LDL receptors.
69
What distinguishes Type IV familial hypertriglyceridemia from Type IIb hyperlipidemia?
- Type IV results in isolated elevation of VLDL without concomitant increase in LDL.
- Type IIb involves elevated levels of both LDL and VLDL.
- Type IV is characterized by increased triglyceride synthesis and secretion, while Type IIb is associated with increased hepatic VLDL production.
70
What are the common clinical features of Type III dysbetalipoproteinemia?
- Elevated concentrations of remnant lipoprotein particles (chylomicron remnants or VLDL remnants).
- A defect in apoE 2/2, which is a major causative factor.
- Characteristic palmar xanthomas and tuberous xanthomas.
- Highly atherogenic due to elevated remnant particle concentration.
71
What is the primary defect in Type I hyperlipidemias?
Deficiencies or functional defects in LPL or apoCII, leading to increased serum chylomicrons.
72
What are common clinical manifestations of Type I hyperlipidemias?
Frequent episodes of acute pancreatitis, neuropathy, arthralgias, hepatosplenomegaly, and lipemia retinalis.
73
What causes Type IIa hyperlipidemias?
Familial hypercholesterolemia resulting in abnormally high circulating levels of LDL-C due to mutations in the LDL receptor or apoB.
74
What is the significance of apoE in Type III dysbetalipoproteinemia?
A defect in apoE2/2 is a major causative factor, affecting the clearance of triglyceride-rich particles and leading to elevated remnant particle concentration.
75
What distinguishes Type IV familial hypertriglyceridemia from Type IIb hyperlipidemia?
Type IV results in isolated elevation of VLDL without concomitant increase in LDL, while Type IIb has elevated levels of both LDL and VLDL.
76
What is a common risk factor associated with Type V dyslipidemia?
Increased risk of eruptive xanthomas secondary to hypertriglyceridemia, often seen in the setting of diabetes.
77
What are the classes of familial hypercholesterolemia?
Class I: complete absence of LDL receptor synthesis; Class II: defect in transportation of the LDL receptor; Class III: abnormal binding between LDL receptor and LDL; Class IV: correct binding with a defect in endocytosis; Class V: dysregulation in recycling of the LDL receptor.
78
A patient with familial hypercholesterolemia has xanthomas over the Achilles tendon. What genetic mutation is most likely responsible?
The patient likely has a mutation in the LDL receptor, apoB, or PCSK9, which are common genetic defects in familial hypercholesterolemia.
79
A patient with Type III dyslipidemia presents with palmar xanthomas. What is the underlying genetic defect?
The underlying defect is in apoE2/2, which impairs the clearance of remnant lipoprotein particles, leading to elevated remnant particle concentrations.
80
A patient with xanthomas and a history of alcohol abuse presents with elevated triglycerides. What is the likely type of dyslipidemia?
The patient likely has Type IV familial hypertriglyceridemia, which is associated with increased VLDL synthesis and secretion.
81
A patient with xanthomas and a history of obesity presents with elevated VLDL levels. What is the likely mechanism?
Obesity leads to increased free fatty acid delivery to the liver, resulting in increased VLDL production and secretion.
82
A patient with xanthomas and a history of hypothyroidism presents with elevated LDL-C levels. What is the likely type of dyslipidemia?
The patient likely has Type IIa hyperlipidemia, which is characterized by elevated LDL-C levels.
83
A patient with xanthomas and a history of familial combined hyperlipidemia presents with elevated LDL and VLDL levels. What is the likely type of dyslipidemia?
The patient likely has Type IIb hyperlipidemia, which is characterized by elevated LDL and VLDL levels.
84
A patient with xanthomas and a history of dysbetalipoproteinemia presents with palmar xanthomas. What is the likely lipid abnormality?
The patient likely has elevated remnant lipoprotein particles, including chylomicron and VLDL remnants.
85
A patient with xanthomas and a history of hyperchylomicronemia presents with eruptive xanthomas. What is the likely type of dyslipidemia?
The patient likely has Type I hyperlipidemia, which is characterized by elevated chylomicrons.
86
A patient with xanthomas and a history of familial hypertriglyceridemia presents with elevated VLDL levels. What is the likely type of dyslipidemia?
The patient likely has Type IV hyperlipidemia, which is characterized by isolated elevation of VLDL.
87
A patient with xanthomas and a history of familial hypercholesterolemia presents with tendinous xanthomas. What is the likely type of dyslipidemia?
The patient likely has Type IIa hyperlipidemia, which is characterized by elevated LDL-C levels.
88
What are the common causes of secondary hyperlipidemia that can lead to xanthomas?
Common causes of secondary hyperlipidemia include:
1. Hematologic disorders: Conditions like monoclonal gammopathies, multiple myeloma, and lymphoma.
2. Hepatic disorders: Prolonged biliary tree obstruction leading to cholesterol accumulation.
3. Endocrinologic/metabolic disorders: Conditions such as diabetes and thyroid dysfunction.
4. Drug-induced causes: Certain medications can increase lipid levels, leading to xanthomas.
89
How does diabetes contribute to dyslipidemia and the formation of xanthomas?
Diabetes contributes to dyslipidemia and xanthoma formation through several mechanisms:
- Increased VLDL production: Due to decreased peripheral insulin resistance and resultant lipolysis.
- Decreased clearance of chylomicrons: Postprandial chylomicrons may have defective clearance in diabetes.
- Increased triglycerides and LDL levels: Resulting from the combination of insulin resistance and increased hepatic delivery of free fatty acids.
90
What are the expected changes in lipid metabolism during normal pregnancy?
During normal pregnancy, the following changes in lipid metabolism are expected:
1. Hypertrophy of maternal adipocytes: This leads to an increase in insulin and hormonal secretion (estrogen and progesterone).
2. Increased lipogenesis: There is a disproportionate increase in lipogenesis, particularly triglyceride formation, compared to lipolysis.
3. Increased risk for eruptive xanthomas: Pregnant women with predisposed hypertriglyceridemia are at increased risk for developing eruptive xanthomas due to pregnancy-induced triglyceridemia.
91
What are the characteristics of normolipemic xanthomas?
Normolipemic xanthomas are characterized by:
- Nonheritable types: These types do not have a predilection for cutaneous manifestations and are often seen in normolipemic patients.
- Rarity: Xanthoma disseminatum is rare, with few known risk factors.
- Verruciform xanthomas: May arise from chronic inflammatory states and local oromucosal trauma.
- Diffuse normolipemic plane xanthoma: Characterized by symmetric plaques found diffusely in the neck, flexural areas, and upper trunk, often associated with hematologic disorders.
92
What are tuberoeruptive xanthomas associated with?
Marked HDL deficiency.
93
What types of xanthomas are observed in patients with hematologic and oncologic abnormalities?
Tuberoeruptive and planar xanthomas.
94
What is a common cause of chronic biliary obstruction leading to hypercholesterolemia?
Primary biliary cirrhosis and secondary biliary obstruction.
95
What metabolic condition is linked to increased triglyceride formation during pregnancy?
Pregnancy-induced triglyceridemia.
96
How does hypothyroidism affect lipid metabolism?
It may promote increased concentrations of serum.
97
How does hypothyroidism affect lipid metabolism?
It may promote increased concentrations of serum lipid subfractions and increase insulin resistance.
98
What is the relationship between diabetes and lipid disorders?
Diabetes can lead to increased rates of production and secretion of VLDL and other lipid disorders.
99
What are normolipemic xanthomas?
Types of xanthomas without a predilection for cutaneous manifestations, often seen in normolipemic patients.
100
What are some postulated risk factors for verruciform xanthomas?
Poor oral hygiene, prior dental abscesses, mechanical stimuli, tobacco abuse, and alcohol exposure.
101
What is the rare diffuse normolipemic plane xanthoma associated with?
Hematologic disorders, including multiple myeloma and monoclonal gammopathies.
102
A patient with a history of hypothyroidism presents with tendinous xanthomas. What is the likely mechanism behind the xanthoma formation?
Hypothyroidism may promote increased concentrations of serum lipid subfractions by decreasing thyroid hormone levels, which reduces LDL receptor activity and increases insulin resistance, leading to elevated LDL-C levels.
103
A patient with diabetes presents with eruptive xanthomas. What lipid abnormalities are likely contributing to this presentation?
The patient likely has hypertriglyceridemia due to increased VLDL production and defective clearance of postprandial chylomicrons, which are common in diabetes.
104
A patient with xanthomas and a history of multiple myeloma is found to have elevated LDL-C levels. What is the likely mechanism?
Monoclonal gammopathies in multiple myeloma may bind to plasma lipoproteins, delaying clearance and resulting in combined hyperlipidemia.
105
A patient with xanthomas and a history of biliary obstruction presents with elevated cholesterol levels. What is the likely cause?
Prolonged biliary obstruction leads to the accumulation of serum cholesterol, which may manifest as plane xanthomas or xanthelasma.
106
A patient with xanthomas and a history of pregnancy-induced hypertriglyceridemia presents with eruptive xanthomas. What is the likely mechanism?
Pregnancy-induced hypertriglyceridemia results from increased lipogenesis due to hormonal changes, leading to eruptive xanthomas in predisposed individuals.
107
A patient with xanthomas and a history of metabolic syndrome presents with elevated triglycerides. What is the likely mechanism?
Metabolic syndrome leads to increased VLDL production and secretion due to insulin resistance and increased free fatty acid delivery to the liver.
108
What are the traditional methodologies used for diagnosing primary hyperlipidemias?
The traditional methodologies include:
1. **Direct lipid fractionation** through electrophoresis.
2. **Ultracentrifugation**.
3. **Plasma lipid profile** measurement, which assesses total cholesterol, triglycerides, HDL-C, and calculated LDL-C.
109
What cholesterol levels are classified as optimal and associated with increased cardiovascular risk?
- **Optimal cholesterol levels**:
- Total cholesterol: less than 200 mg/dL
- LDL-C: less than 100 mg/dL
- **Increased cardiovascular risk**:
- Total cholesterol: greater than 240 mg/dL
- LDL-C: greater than 160 mg/dL
110
What is the significance of a triglyceride level greater than 1000 mg/dL?
A triglyceride level greater than 1000 mg/dL is classified as **markedly elevated** and is associated with an increased risk of:
- **Pancreatitis**
- **Eruptive xanthomas**
111
What are foam cells and their significance in pathology related to xanthomas?
Foam cells are **macrophages that contain lipid** and are histopathologically characteristic of xanthomas. They indicate the presence of lipid accumulation and can vary in associated cells and surrounding material depending on the type of xanthoma.
112
How can tuberous and tendinous xanthomas be differentiated histopathologically?
- **Tuberous xanthomas**: Characterized by foam cells and cholesterol clefts.
- **Tendinous xanthomas**: Histopathologically similar to tuberous xanthomas but may have associated fibrosis, indicating older lesions.
113
What imaging techniques may be considered when the diagnosis of xanthomas is unclear?
In cases where the diagnosis is unclear, the following imaging techniques may be considered:
1. **Ultrasonography**: Xanthomas typically appear as hypoechoic nodules with a heterogeneous pattern.
2. **MRI**: Xanthomas appear as hyperintense lesions on T1-weighted and T2-weighted images with possible diffuse reticulate patterns.
3. **Positron emission tomography**: Used in cases of xanthoma disseminatum to aid in prognosticating the extent of disease.
114
What is the significance of accurate diagnosis in hyperlipidemia?
It can point to underlying systemic disease or hyperlipidemia and help identify early lifestyle and treatment options to slow cardiovascular disease progression.
115
What is the initial standard approach to assess lipid levels in modern medicine?
To order a plasma lipid profile.
116
What total cholesterol level is classified as elevated and associated with increased cardiovascular risk?
Greater than 240 mg/dL.
117
What triglyceride level is classified as markedly elevated and associated with increased risk of pancreatitis?
Greater than 1000 mg/dL.
118
What are the histopathological features of eruptive xanthomas?
They often consist of lymphoid cells, histiocytes, neutrophils, and free lipid in the dermis.
119
How can tuberous xanthomas be differentiated from other types of xanthomas?
Tuberous xanthomas contain foam cells and cholesterol clefts.
120
What is the typical appearance of xanthomas on ultrasonography?
They typically appear as hypoechoic nodules with an overall heterogeneous pattern.
121
A patient with xanthomas undergoes a biopsy. What histopathological feature is characteristic of xanthomas?
Xanthomas are characterized by foam cells, which are macrophages containing lipid.
122
A patient with xanthomas and a history of nephrotic syndrome presents with elevated triglycerides. What is the likely mechanism?
Nephrotic syndrome is associated with elevated triglycerides due to increased hepatic VLDL production and decreased clearance.
123
A patient with xanthomas and hypothyroidism has elevated LDL-C levels. What laboratory tests should be ordered to confirm the diagnosis?
Tests should include thyroid-stimulating hormone (TSH) and free thyroxine (T4) levels to confirm hypothyroidism.
124
A patient with xanthomas and a history of rheumatoid arthritis presents with nodules on the extensor surfaces of their elbows. What is the differential diagnosis?
The differential includes tendinous xanthomas, rheumatoid nodules, and gouty tophi.
125
A patient with xanthomas and a history of hypertriglyceridemia presents with acute pancreatitis. What is the likely lipid abnormality?
The patient likely has markedly elevated triglycerides (>1000 mg/dL), which increase the risk of pancreatitis.
126
What imaging techniques are used to evaluate thyroid abnormalities in dyslipidemia diagnosis?
Diagnostic algorithms involve the use of both **thyroid ultrasonography** and **sestamibi scans**.
127
What is the cornerstone of xanthoma therapy?
The cornerstone of xanthoma therapy is addressing the underlying **hyperlipidemia**, typically through **lifestyle changes** and **medication management**.
128
What lifestyle changes are recommended for managing lipid disorders?
Recommended lifestyle changes include:
1. **Increased aerobic physical activity** (at least 30 min/day).
2. **Weight control** to lower total cholesterol and LDL-C levels.
3. **Dietary modifications** as reflected in clinical guidelines from major health organizations.
129
How does tobacco use affect lipid levels?
Tobacco use may lower **HDL-C levels** while increasing **total cholesterol**, **LDL-C**, and **triglyceride levels**. It also reduces the activity of **LPL**, exacerbating hypertriglyceridemic dyslipidemias.
130
What dietary management strategies are recommended for patients with elevated LDL-C?
Dietary management strategies include:
- Referral to a **nutritionist** for dietary restrictions.
- Following therapeutic diets like the **Mediterranean diet** and the **Portfolio Diet**.
- Targeting specific diets to lower **chylomicron concentrations** and triglycerides, typically involving a **fat-restricted diet**.
131
What is the role of statins in managing dyslipidemia?
Statins are the **first-line pharmacotherapy** for lowering LDL-C. They competitively inhibit **HMG-CoA reductase**, decreasing cellular cholesterol synthesis and enhancing the clearance of LDL particles from the bloodstream.
132
What are the common side effects associated with statin therapy?
Common side effects of statin therapy include:
- Increased propensity for **diabetes** (especially in predisposed individuals).
- Rarely, **hemorrhagic stroke** and **rhabdomyolysis**.
133
What is the cornerstone of xanthoma therapy?
Addressing the underlying hyperlipidemia through lifestyle changes and medication management.
134
What lifestyle changes are recommended for all lipid disorders?
Increased aerobic physical activity and weight control.
135
What dietary management goals are set for patients with elevated LDL-C?
Goals include following therapeutic diets like the Mediterranean diet and the Portfolio Diet.
136
What is the recommended weight loss percentage for beneficial effects on triglyceride and blood glucose levels?
Sustained weight losses of 3% to 5% are recommended.
137
What is the first-line pharmacotherapy for lowering LDL-C?
Statins.
138
What enzyme do statins inhibit to decrease cholesterol synthesis?
HMG-CoA reductase.
139
What are common side effects of statin therapy?
Increased propensity for diabetes and, rarely, hemorrhagic stroke and rhabdomyolysis.
140
What is the effect of physical inactivity on lipid values?
It may result in the opposite trends in lipid values.
141
A patient with xanthomas and a history of diabetes is found to have elevated VLDL levels. What lifestyle modifications should be recommended?
Lifestyle modifications include increased aerobic physical activity, weight management, and a low glycemic, carbohydrate-restricted diet.
142
What are the three groups of patients recommended for statin therapy according to the American College of Cardiology and American Heart Association guidelines?
1) Patients with LDL-C levels equal to or greater than 190 mg/dL, especially those with a high suspicion of familial hypercholesterolemia.
2) Patients with diabetes aged 40 to 75 years with LDL-C values ranging between 70 and 189 mg/dL.
3) Patients with a 10-year estimated risk of 7.5% or greater for developing a clinical atherosclerotic event, including myocardial infarctions or strokes.
143
What is the mechanism of action of ezetimibe and its recommended use in dyslipidemia treatment?
Ezetimibe is a specific inhibitor of the Niemann-Pick C-like protein 1 transporter, responsible for dietary cholesterol and plant sterol absorption in intestinal cells. It is recommended for patients with LDL-C equal to or greater than 190 mg/dL who are on statin therapy for secondary prevention and have failed to achieve at least a 50% reduction in LDL-C levels on maximally tolerated statins.
144
What are the common side effects associated with fibrates used in dyslipidemia treatment?
Common side effects of fibrates include:
- Dyspepsia
- Myopathy
- Headaches
- Diarrhea
145
How do PCSK9 inhibitors function in the treatment of dyslipidemias?
PCSK9 inhibitors work by blocking the action of PCSK9, which normally binds to LDL receptors on the surface of cells, mainly hepatocytes, leading to their degradation. By inhibiting PCSK9, these medications increase the availability of LDL receptors, thereby enhancing the clearance of circulating LDL.
146
What are the adverse effects associated with the use of PCSK9 inhibitors?
Adverse effects of PCSK9 inhibitors include:
- Myalgia
- Ophthalmologic complaints
- Headaches and neurologic dysfunction
- Injection-site reactions
147
What is the role of omega-3 fatty acids in managing dyslipidemia?
Omega-3 fatty acids can help reduce triglycerides by 25% to 50% but may increase LDL-C levels by 5% to 10%. They are thought to be anti-inflammatory mediators and direct inhibitors of hepatic VLDL secretion through decreased triglyceride synthesis and other mechanisms.
148
What is the significance of recognizing secondary causes of dyslipidemia?
Recognition of secondary causes and their associated treatments should be initiated in any patient with overt dyslipidemia to ensure appropriate management and treatment strategies are applied.
149
What do the American College of Cardiology and American Heart Association recommend for individuals with established atherosclerotic cardiovascular disease?
The use of statin therapy.
150
What is the role of ezetimibe in the treatment of dyslipidemia?
It is a specific inhibitor of the Niemann-Pick C-like protein 1 transporter, used in patients with high LDL-C levels who are on statin therapy.
151
How do fibrates affect HDL-C levels?
They may raise HDL-C levels by 15% to 25% depending on triglyceride levels.
152
What is the mechanism of action of niacin in dyslipidemia treatment?
It may lower the release of adipose free fatty acids and increase the activity of LPL.
153
What is the FDA-approved use of Lomitapide?
For patients with homozygous familial hypercholesterolemia, inhibiting microsomal triglyceride transfer protein.
154
What are the adverse effects associated with Mipomersen?
Injection-site reactions, flu-like symptoms, and increase in transaminases.
155
What should be recognized in any patient with overt dyslipidemia?
Secondary causes and their associated treatments should be initiated.
156
A patient with severe hypertriglyceridemia and recurrent pancreatitis is being treated with fibrates. What is the mechanism of action of fibrates?
Fibrates activate nuclear peroxisome-proliferator-activated receptors (PPARs), which induce genes responsible for triglyceride catabolism, increase LPL activity, and raise HDL-C levels.
157
A patient with xanthomas and elevated LDL-C levels is started on statins. How do statins lower LDL-C?
Statins inhibit HMG-CoA reductase, the rate-limiting enzyme in cholesterol synthesis, leading to increased LDL receptor activity and enhanced clearance of LDL particles.
158
What is the mechanism of action of fibrates?
Fibrates activate nuclear peroxisome-proliferator-activated receptors (PPARs), which induce genes responsible for triglyceride catabolism, increase LPL activity, and raise HDL-C levels.
159
How do statins lower LDL-C?
Statins inhibit HMG-CoA reductase, the rate-limiting enzyme in cholesterol synthesis, leading to increased LDL receptor activity and enhanced clearance of LDL particles.
160
What is the mechanism of action of PCSK9 inhibitors?
PCSK9 inhibitors block the degradation of LDL receptors, increasing their availability and enhancing LDL clearance.
161
What are the characteristics of the Fredrickson-Levy-Lees dyslipidemias?
| Fredrickson-Levy-Lees Phenotype | Defect | Lipoprotein Excess | Xanthoma Type |
|-------------------------------|--------|-------------------|----------------|
| Type I (lipoprotein lipase deficiency) | Decreased LPL or apolipoprotein CII deficiencies | Chylomicrons | Eruptive |
| Type IIa (familial hypercholesterolemia) | Low-density lipoprotein (LDL) receptor defect | LDL | Tendinous |
| Type IIb (familial combined dyslipidemia) | LDL receptor defect | LDL + very-low-density lipoprotein (VLDL) | Rarely seen |
| Type III (dysbetalipoproteinemia) | Apoprotein E2 defect | Remnant particles | Palmar, Tuberoeruptive |
| Type IV (familial hypertriglyceridemia) | Increased VLDL production | VLDL | Rarely eruptive |
| Type V | Apolipoprotein CII deficiency and increased VLDL | VLDL + chylomicrons | Rarely palmar |
162
What are the surgical options for managing xanthomas?
1. Surgical resection: Definitive management for xanthomas causing functional impairment.
2. Cosmetic surgery: Pursued mainly for aesthetic reasons, especially for xanthelasmas.
3. Ablative laser therapy or cryotherapy: Other treatment options for xanthelasmas.
4. Lipid-lowering therapy: Lesions may improve, but will recur if underlying dyslipidemia is untreated.
5. Surgical options for homozygous familial hypercholesterolemia: Include ileal bypass, portacaval shunt, and liver transplantation in severe cases.
6. ApoB lipoprotein apheresis and PCSK9 inhibitors: Considered in refractory cases.
163
What is the role of ApoB lipoprotein apheresis in treating dyslipidemia?
- FDA Approval: Used for patients not meeting LDL-C goals despite standard therapy.
- Indications: Typically for homozygous familial hypercholesterolemia and severe lipoprotein(A) elevation.
- Procedure: Involves extracorporeal removal of apoB particles (VLDL and LDL) on a weekly or biweekly basis.
- Expected Outcomes: 50% to 75% reduction in LDL-C per session, with a 30% reduction over several months.
- Access: Patients often have venous access through a port or arteriovenous fistula.
- Side Effects: Hypotension, anemia, and headaches.
164
What are the key components of counseling and screening for dyslipidemia?
- Nutritional and smoking cessation counseling: Essential components of management.
- Genetic screening: Individual and family screening for dyslipidemia.
- Familial hypercholesterolemia: Most commonly tested primary dyslipidemia.
- Genetic defects: Over 1500 identified in LDL receptor, apoB100, and PCSK9.
- Cascade genetic testing: Involves testing second-degree relatives if first-degree members test positive.
- Clinical suspicion: Genetic testing may still be performed even if overt criteria are not met.
- Type III phenotype: Commonly investigated with apoE genotyping in suspected cases.
165
What are the differential diagnoses for xanthomas in children?
| Condition | Description |
|-----------|-------------|
| Homozygous familial hypercholesterolemia | Genetic disorder leading to high cholesterol levels. |
| Phytosterolemia/Sitosterolemia | Rare genetic disorders affecting cholesterol absorption. |
| Cerebrotendinous xanthomatosis | A metabolic disorder leading to cholesterol accumulation. |
| Alagille syndrome | Inherited syndrome causing biliary hypoplasia and elevated cholesterol. |
166
What is the primary method for diagnosing xanthomas?
Diagnosis is primarily made on a clinical basis, but biopsies may help depending on suspicion for alternate etiologies.
167
What is the significance of genetic testing in familial hypercholesterolemia?
It helps identify mutations in the LDL receptor and can guide treatment options for affected individuals and their families.
168
What is the relationship between xanthomas and liver transplantation?
Xanthomas have been found to resolve after liver transplantation.
169
What advanced treatment options are available for homozygous familial hypercholesterolemia?
Advanced options include PCSK9 inhibitors, apoB lipoprotein apheresis, or lomitapide, which inhibit LDL receptor degradation or reduce LDL-C levels.
170
What is the underlying cause of elevated cholesterol levels in a patient with xanthomas and Alagille syndrome?
Alagille syndrome is caused by biliary hypoplasia, leading to elevated serum cholesterol levels.
171
What is the defect associated with Type I Frederickson-Levy-Lees phenotype?
Decreased LPL or apolipoprotein CII deficiencies.
172
What lipoprotein excess is associated with Type IIa familial hypercholesterolemia?
LDL receptor defect.
173
What is the xanthoma type associated with Type IIa familial hypercholesterolemia?
Tendinous, Tuberosus, Xanthelasma, Intertriginous.
174
What is the defect associated with Type IIb familial combined dyslipidemia?
LDL + VLDL.
175
What is the defect associated with Type III dysbetalipoproteinemia?
Remnant particles.
176
What is the defect associated with Type IV familial hypertriglyceridemia?
Increased triglycerides.
177
What is the defect associated with Type V Frederickson-Levy-Lees phenotype?
Apolipoprotein CII deficiency and increased VLDL.
178
Which pharmacotherapy is especially useful in patients with elevated VLDL and chylomicrons?
Fibrates.
179
What is the first line pharmacotherapy for lowering LDL-C?
Statins.
180
Which treatment is FDA approved for homozygous familial hypercholesterolemia?
Mipomersen.
181
What treatment reduces triglycerides but increases LDL-C?
Niacin.
182
What treatment increases the level and activity of surface LDL receptors?
PSK9 inhibitors.
