21 - 126 - XANTHOMAS AND LIPOPROTEIN DISORDERS Flashcards
plaques or nodules consisting of an abnormal excess of lipid primarily in the skin or tendons.
Xanthomas
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).
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).
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).
firm, subcutaneous nodules found in fascia, ligaments, Achilles tendons, or extensor tendons of the hands, knees, and elbows
Tendinous xanthomas
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.
- With the diagnosis in mind, what other noncutaneous symptoms should we watch out for?
a. acute pancreatitis
b. hypertension
c. myocardial infarction
d. xanthoma - What is the mode of inheritance of her disease?
a. autosomal dominant
b. autosomal recessive
c. X-linked dominant
d. X-linked recessive
a. acute pancreatitis
b. autosomal recessive
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
b. recent lipid profile results
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.
- Which of these is LEAST associated with her condition?
a. intake of estrogen
b. use of illicit drugs
c. alcohol intake
d. diabetes - 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 - 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
b. use of illicit drugs
b. there is no age and gender predilection for this disease
d. all of the above
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
a. HMG-CoA reductase inhibitor
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
b. risk for Diabetes
Overweight adults with xanthoma should aim for a _______ kcal/day energy deficit?
a. 250-500
b. 500-750
c. 100-250
d. 75-100
b. 500-750
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
d. Serum cholesterol is elevated when patients are young but decreases over time
- 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
Eruptive xanthomas
nodules that are localized to pressure areas including the extensor surfaces of the elbows, knees, knuckles, and buttocks
Tuberous xanthomas
- 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
Tendinous xanthomas
- yellow macules, soft papules, or plaques found commonly on the upper eyelids near the inner canthus
Planar xanthomas
what do you call planar xanthomas on the eyelids near the inner canthus?
xanthelasma palpebrarum or xanthelasma
what do you call planar xanthomas on the wrist and palms?
xanthoma striatum palmare
T/F
Occurrence of xanthelasmas on the eyelids is usually not associated with coronary heart disease
True
Type of Dyslipidema that may develop a characteristic variant xanthoma characterized by yellow-orange discoloration of the cutaneous creases of the palmar skin
Type III
- 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.
verruciform xanthoma
verruciform xanthomas are associated with what syndrome and condition?
- CHILD (congenital hemidysplasia with ichthyosiform erythroderma and limb defects) syndrome
- epidermolysis bullosa
- 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
Xanthoma disseminatum
sitosterolemia, or a retention and elevation of plant-based sterols in the serum is associated with what mutation?
mutation of the** ABCG5/G8 transporter**
- important for intestinal absorption of sterols
- These patients may develop tendinous xanthomas with the overall clinical picture imitating familial hypercholesterolemia
this type of xanthoma may be the first sign of underlying **hematologic abnormalities **and may be associated with chronic microcytic anemia or hematologic malignancies
planar xanthomas
- 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
Type I hyperlipidemias
- familial lipoprotein lipase [LPL] deficiency or familial hyperchylomicronemia
patients with this type of hypercholesterolemia are prone to developing tendinous xanthomas, especially over the Achilles tendon
Type IIa hyperlipidemia
- commonly caused by familial combined hyperlipidemia, resulting in elevated LDL and VLDL concentrations
Type IIb hyperlipidemia
- referred to as dysbetalipoproteinemia, results in elevated concentrations of remnant lipoprotein particles, either chylomicron 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
Type III hyperlipidemia
most common xanthoma seen with Type III disorders
tuberoeruptive xanthomas
palmar xanthomas are also seen in type III
- 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
Type IV
(familial hypertriglyceridemia)
- consists of elevated VLDL and chylomicrons; consequently, patients are at increased risk of eruptive xanthomas secondary to hypertriglyceridemia
Type V dyslipidemia
the 2 nonheritable types of xanthomas without a predilection for cutaneous manifestations are often seen in normolipemic patients.
- xanthoma disseminatum
- verruciform xanthomas
A triglyceride level of greater than 1000 mg/dL is classified as markedly elevated and is associated with what?
increased risk of pancreatitis, as well as eruptive xanthomas
macrophages that contain lipid and are histopathologically characteristic of xanthomas
Foam cells
first-line pharmacotherapy for lowering LDL-C
Statins
Examples of high-potency, high-intensity statin therapies
rosuvastatin 20 mg or 40 mg and atorvastatin 40 mg or 80 mg daily
rate-limiting enzyme in endogenous cholesterol synthesis
HMG-CoA reductase
- Second-line medication therapy
- specific inhibitor of the Niemann-Pick C-like protein 1 transporter, which is responsible for dietary cholesterol and plant sterol absorption within intestinal cells
ezetimibe
- 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)
Fibrates
approved by the U.S. Food and Drug Administration (FDA) for use in patients with homozygous familial hypercholesterolemia
- Lomitapide
- Mipomersen
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.
PCSK9 inhibitors
evolocumab and alirocumab
- 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
procedures that has been approved by the FDA for patients who are not at LDL-C goals despite standard medical therapy
ApoB lipoprotein apheresis
The process involves extracorporeal removal of apoB particles, including VLDL and LDL on a weekly or biweekly basis through an apoBavid adsorbent column
