21 - 126 - XANTHOMAS AND LIPOPROTEIN DISORDERS

Question 1

plaques or nodules consisting of an abnormal excess of lipid primarily in the skin or tendons.

Answer 1

Xanthomas

Question 2

Answer 2

Eruptive xanthomas are multiple, small, red-yellow papules, usually less than 5 mm in size, that may appear suddenly and are arranged in crops on the extensor surface of the extremities and the buttocks, often forming a confluent rash (Fig. 126-1).

Question 3

Answer 3

They are associated with severe hypertriglyceridemia, usually resulting from accumulation of chylomicrons as in Types I and V dyslipidemia, and may be aggravated by underlying diabetes, obesity, excessive ethanol intake, and drugs such as retinoids, estrogen therapy, and protease inhibitors (Fig. 126-2).

Question 4

Answer 4

Tuberous xanthomas are nodules that are localized to pressure areas including the extensor surfaces of the elbows, knees, knuckles, and buttocks (Figs. 126-3 and 126-4).

Question 5

firm, subcutaneous nodules found in fascia, ligaments, Achilles tendons, or extensor tendons of the hands, knees, and elbows

Answer 5

Tendinous xanthomas

Question 6

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Question 13

Marie came into your clinic due to multiple red-yellow papules in crops on the extensor extremities and buttocks. You suspected Eruptive Xanthoma and requested for lab tests. Her serum triglyceride is 1500mg/dL, there is also an increase in serum chylomicrons and on genetic testing, there was a functional defect in LPL.

1. With the diagnosis in mind, what other noncutaneous symptoms should we watch out for?
   a. acute pancreatitis
   b. hypertension
   c. myocardial infarction
   d. xanthoma
2. What is the mode of inheritance of her disease?
   a. autosomal dominant
   b. autosomal recessive
   c. X-linked dominant
   d. X-linked recessive

Answer 13

a. acute pancreatitis
b. autosomal recessive

Question 14

Faye, a 22 year old female came into your clinic complaining of multiple yellow papules on her extremities. What other pertinent data should you elicit in your history taking?

a. history of coronary heart disease
b. recent lipid profile results
c. both
d. neither

Answer 14

b. recent lipid profile results

Question 15

Queenie, a 30 year old Filipino female came into your clinic complaining of a sudden eruption of multiple red-yellow papules on her extensor extremities.

1. Which of these is LEAST associated with her condition?
   a. intake of estrogen
   b. use of illicit drugs
   c. alcohol intake
   d. diabetes
2. She asked you if this is commonly seen in her age and gender. What will you tell her?
   a. this condition is more commonly seen in females
   b. there is no age and gender predilection for this disease
   c. this disease unusual to be seen at her age group
   d. this disease is commonly seen in Asians and Hispanics
3. She also asked about the noncutaneous manifestations of her condition. Which of these is/are a noncutaneous manifestations of this condition?
   a. intracranial lesions
   b. carotid stenosis
   c. peripheral vascular disease
   d. all of the above

Answer 15

b. use of illicit drugs
b. there is no age and gender predilection for this disease
d. all of the above

Question 16

What is the first line pharmacotherapy for lowering LDL-C levels in patients with xanthoma?

a. HMG-CoA reductase inhibitor
b. HMG-CoA oxidase inhibitor
c. fibrates
d. Omega-3 fatty acids

Answer 16

a. HMG-CoA reductase inhibitor

Question 17

Which of these is a common side effect of HMG-CoA reductase inhibitor

a. headache and diarrhea
b. risk for Diabetes
c. Pruritus
d. flu-like symptoms

Answer 17

b. risk for Diabetes

Question 18

Overweight adults with xanthoma should aim for a _______ kcal/day energy deficit?

a. 250-500
b. 500-750
c. 100-250
d. 75-100

Answer 18

b. 500-750

Question 19

Which is TRUE regarding Alagille syndrome?

a. Cirrhosis develops in 80% of patients
b. They present with characteristic facies such as a prominent forehead, hypotelorism and nasal dystrophy
c. It is a sporadic syndrome of biliary hypoplasia and elevated serum cholesterol
d. Serum cholesterol is elevated when patients are young but decreases over time

Answer 19

d. Serum cholesterol is elevated when patients are young but decreases over time

Question 20

• multiple, small, red-yellow papules, usually less than 5 mm in size, that may appear suddenly and are arranged in crops on the extensor surface of the extremities and the buttocks, often forming a confluent rash

Answer 20

Eruptive xanthomas

Question 21

nodules that are localized to pressure areas including the extensor surfaces of the elbows, knees, knuckles, and buttocks

Answer 21

Tuberous xanthomas

Question 22

• firm, subcutaneous nodules found in fascia, ligaments, Achilles tendons, or extensor tendons of the hands, knees, and elbows
• They may occasionally appear as tophus-like lesions over the great toe and be mistaken for gout, and may be uncovered by direct trauma

Answer 22

Tendinous xanthomas

Question 23

• yellow macules, soft papules, or plaques found commonly on the upper eyelids near the inner canthus

Answer 23

Planar xanthomas

Question 24

what do you call planar xanthomas on the eyelids near the inner canthus?

Answer 24

xanthelasma palpebrarum or xanthelasma

Question 25

what do you call planar xanthomas on the wrist and palms?

Answer 25

xanthoma striatum palmare

Question 27

T/F Occurrence of xanthelasmas on the eyelids is usually not associated with coronary heart disease

Answer 27

True

Question 28

Type of Dyslipidema that may develop a characteristic variant xanthoma characterized by yellow-orange discoloration of the cutaneous creases of the **palmar skin**

Answer 28

Type III

Question 29

* this variant mainly have **oral mucosal involvement **with lesions appearing in polypoid or sessile forms * Cutaneous lesions are largely limited to the** perineum and scrotum in males**, and are associated with the **CHILD** (congenital hemidysplasia with ichthyosiform erythroderma and limb defects) syndrome or **epidermolysis bullosa.**

Answer 29

verruciform xanthoma

Question 30

verruciform xanthomas are associated with what syndrome and condition?

Answer 30

* CHILD (congenital hemidysplasia with ichthyosiform erythroderma and limb defects) syndrome * epidermolysis bullosa

Question 31

* this variant involves xanthoma formation and histiocyte proliferation within **common mucocutaneous sites,** but also can involve **visceral organs, ocular structures, the CNS, and the skeletal system**

Answer 31

Xanthoma disseminatum

Question 32

sitosterolemia, or a retention and elevation of plant-based sterols in the serum is associated with what mutation?

Answer 32

mutation of the** ABCG5/G8 transporter** ## Footnote * important for intestinal absorption of sterols * These patients may develop tendinous xanthomas with the overall clinical picture imitating familial hypercholesterolemia

Question 32

this type of xanthoma may be the first sign of underlying **hematologic abnormalities **and may be associated with **chronic microcytic anemia or hematologic malignancies**

Answer 32

planar xanthomas

Question 33

* characterized by an **increase** in serum **chylomicrons** * **Deficiencies** or functional defects in **LPL or apoCII**, both of which have autosomal recessive inheritance, are common genetic mutations underlying this disorder

Answer 33

Type I hyperlipidemias * familial lipoprotein lipase [LPL] deficiency or familial hyperchylomicronemia

Question 34

patients with this type of hypercholesterolemia are prone to developing **tendinous** xanthomas, especially over the Achilles tendon

Answer 34

Type IIa hyperlipidemia

Question 35

* commonly caused by familial combined hyperlipidemia, resulting in **elevated LDL and VLDL concentrations**

Answer 35

Type IIb hyperlipidemia

Question 36

* referred to as **dysbetalipoproteinemia**, results in elevated concentrations of **remnant lipoprotein particles**, either c**hylomicron remnants or VLDL remnants** including **IDL** * A **defect in apoE 2/2 is a major causative factor **and has implications in the development of hyperlipidemia and eventual atherosclerosis

Answer 36

Type III hyperlipidemia

Question 37

most common xanthoma seen with Type III disorders

Answer 37

tuberoeruptive xanthomas ## Footnote palmar xanthomas are also seen in type III

Question 38

* results in an isolated elevation of **VLDL**. * This phenotype is relatively common and, as a result of increased triglyceride synthesis, results in increased VLDL synthesis and secretion * There is no concomitant increase in LDL (difference from Type IIb) * Most patients are without cutaneous manifestations of the dyslipidemia

Answer 38

Type IV (familial hypertriglyceridemia)

Question 39

* consists of elevated **VLDL and chylomicrons**; consequently, patients are at increased risk of eruptive xanthomas secondary to hypertriglyceridemia

Answer 39

Type V dyslipidemia

Question 40

the 2 nonheritable types of xanthomas without a predilection for cutaneous manifestations are often seen in normolipemic patients.

Answer 40

* xanthoma disseminatum * verruciform xanthomas

Question 41

A triglyceride level of greater than 1000 mg/dL is classified as markedly elevated and is associated with what?

Answer 41

increased risk of pancreatitis, as well as eruptive xanthomas

Question 42

macrophages that contain lipid and are histopathologically characteristic of xanthomas

Answer 42

Foam cells

Question 43

first-line pharmacotherapy for lowering LDL-C

Answer 43

Statins

Question 44

Examples of high-potency, high-intensity statin therapies

Answer 44

rosuvastatin 20 mg or 40 mg and atorvastatin 40 mg or 80 mg daily

Question 45

rate-limiting enzyme in endogenous cholesterol synthesis

Answer 45

HMG-CoA reductase

Question 46

* Second-line medication therapy * specific i**nhibitor of the Niemann-Pick C-like protein 1** transporter, which is responsible for dietary cholesterol and plant sterol absorption within intestinal cells

Answer 46

ezetimibe

Question 47

* common agents used to help lower triglyceride levels by 40% to 60%, and are especially useful in patients with elevated VLDL and chylomicrons * activation of nuclear peroxisome-proliferator-activated receptors (PPARs)

Answer 47

Fibrates

Question 48

approved by the U.S. Food and Drug Administration (FDA) for use in patients with homozygous familial hypercholesterolemia

Answer 48

* Lomitapide * Mipomersen

Question 49

The FDA has approved a new class of injectable medications for the treatment of dyslipidemias in patients refractory to standard medical therapy. FDA indications currently are limited to patients with familial hypercholesterolemia or those with established atherosclerotic cardiovascular disease who are on diet therapy and maximally tolerated statin therapy, and in need of additional LDL-C lowering.

Answer 49

PCSK9 inhibitors evolocumab and alirocumab ## Footnote * PCSK9 normally binds to LDL receptors on the surface of cells, mainly hepatocytes, and induces their clearance via phagocytosis and subsequent degradation. * By blocking the action of PCSK9, these inhibitors increase the availability of surface LDL receptors, thereby helping to clear circulating LDL

Question 50

procedures that has been approved by the FDA for patients who are not at LDL-C goals despite standard medical therapy

Answer 50

ApoB lipoprotein apheresis ## Footnote The process involves extracorporeal removal of apoB particles, including VLDL and LDL on a weekly or biweekly basis through an apoBavid adsorbent column