Eruptive Xanthomas - pediagenosis
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Monday, May 11, 2020

Eruptive Xanthomas

Eruptive Xanthomas
Abnormal accumulation of triglycerides in various tissues, including the skin, may lead to the cutaneous finding of eruptive xanthomas. The xanthomatous diseases are a diverse group of conditions with unique clinical, laboratory, and systemic findings. An abnormality in lipid and cholesterol metabolism is what links these conditions together. Fatty acids provide the body with more than 40% of its daily energy requirements. The majority of fatty acids are supplied directly by the normal diet. Proteins and carbohydrates, when present in excess, can be converted to triglycerides to be stored as a future energy source. This process makes up the remaining source of free fatty acids and triglycerides supplied to the body.

Normal metabolism of triglycerides occurs through complex biochemical pathways. Triglycerides are converted into free fatty acids, which are broken down into acetyl-coenzyme A (acetyl-CoA). Acetyl-CoA then enters the Krebs cycle to be oxidized and turned into adenosine triphosphate (ATP), one of the main forms of energy used in cellular processes.

Ingested triglycerides are broken down into free fatty acids in the lumen of the intestine by bile acids. The free fatty acids are then transported across the gut lining as chylomicrons. This process is very rapid and occurs within 6 hours after eating. The chylomicrons are absorbed by many tissues and are converted back into free fatty acids and glycerol by the enzyme lipo- protein lipase. The free fatty acids can be converted to acetyl-CoA, converted to triglyceride and stored as an energy source for later use, or used to make various phospholipids. The storage of triglycerides for future energy use is ideal, because it yields higher amounts of energy than either proteins or carbohydrates. Triglycerides can yield 9 kcal/g of energy, whereas proteins and carbohydrates produce about 4 kcal/g. This is an efficient means of storing energy. Abnormalities in the production, breakdown, or storage of triglycerides may lead to complications resulting in cutaneous and systemic findings.
Eruptive xanthomas are one of the cutaneous findings caused by an abnormality in lipid metabolism. They can be caused by various familial hyperlipoproteinemias (types I, III, and V), by medications, or as a complication of diabetes. The cutaneous findings are identical in all of these conditions. Eruptive xanthomas should not be confused with tuberoeruptive, tendinous, or planar xanthomas, because these conditions have different biochemical bases and other systemic features that are unique. Treatment of eruptive xanthomas requires a team approach including endocrinology, car- diology, and dermatology specialists.

Clinical Findings: Eruptive xanthomas, as the name implies, have a rapid eruptive onset (hours to a few days). The most common location to be involved is the buttocks, but these eruptions can be seen anywhere on the body, including the mucous membranes. They have a predilection for the extensor surfaces of the skin.
They appear as yellow to slightly red-orange, domeshaped papules with an erythematous base. Patients often complain of mild pruritus, but occasionally they describe a painful sensation when the lesions are palpated. Eruptive xanthomas are rare in both children and adults, but they are more commonly seen in adulthood. There are no racial or sexual differences in incidence.
Patients diagnosed with eruptive xanthomas that are found to be caused by a deficiency in the enzyme lipoprotein lipase are classified as having type I hyperlipoproteinemia. This is a rare form of hyperlipoproteinemia with onset in childhood. Systemic involvement is significant, with recurrent bouts of pancreatitis and hepatosplenomegaly. These patients have extremely elevated triglyceride and chylomicron levels but normal cholesterol levels. The eye may also be affected with lipemia retinalis. Lipemia retinalis can be seen only by means of a funduscopic examination. Vision is typically normal, and the patient is unaware of any eye abnormalities. The blood vessels within the eye have a creamy white color because of the excess lipid in the blood-stream. The arteries and veins are equally affected, and the only way to differentiate the two is by comparing the caliber of the vessel. The arterial light reflex is lost. The vessels appear flat, and the rest of the fundus is a uniform creamy color. Lipoprotein lipase enzyme activity can be measured, and this test is used to help diagnosis type I hyperlipoproteinemia. Eruptive xanthomas can also be seen as part of hyperlipoproteinemia type III (familial dysbetalipoproteinemia) and hyperlipoproteinemia type V. Type III has been found to be caused by a defect in the APOE gene, which encodes the apolipoprotein E protein. This protein is particularly important in clearing chylomicrons and intermediatedensity lipoproteins.
Multiple medications have been implicated in the production of hypertriglyceridemia. They include isotretinoin, glucocorticoids, olanzapine, protease inhibitors (especially ritonavir), and indomethacin. Alcohol abuse can also be a cause of hypertriglyceridemia. Patients presenting with eruptive xanthomas who are taking any of these medications should have the medication discontinued or another substituted and should be reevaluated after treatment.
Diabetes is the most common cause of hypertriglyceridemia, and it probably is also the most common cause of eruptive xanthomas. Insulin is required for normal functioning of the lipoprotein lipase enzyme. Diabetic patients who are deficient in insulin have lower activity levels of lipoprotein lipase and increased levels of chylomicrons and triglycerides as a result.
On laboratory evaluation, the patient has triglyceride levels that are extremely elevated, in the range of 2000 mg/dL sometimes even surpassing the laboratory’s ability to quantify it. If a sample of blood is centrifuged for a few minutes, the white to creamycolored triglycerides will become evident and will take up a considerable amount of the specimen. On occasion, there are so many triglycerides present that the blood sample is a light creamy color even before centrifugation.

Histology: The histological findings from biopsies of early lesions of eruptive xanthomas can mimic those of granuloma annulare. Neutrophils can be evident during the formation of an eruptive xanthoma. The neutrophilic infiltrate lessens and disappears once the lesion has had time to establish itself. It is recommended that the biopsy specimen be taken from an established lesion (one that has been present for a day or two) so that more characteristic findings will be seen. Foam cells are present with a stippled cytoplasm. The number of foam cells is not as prominent as in tuberous or tendinous xanthomas. One unique finding is the presence of extracellular lipid, which is seen between bundles of collagen.

Pathogenesis: The varying conditions that can manifest with eruptive xanthomas all have unique ways of causing hypertriglyceridemia. The final common pathway in the pathogenesis of eruptive xanthomas is the presence of significantly elevated triglyceride levels. Treatment: The main goal of therapy is to return the triglyceride level back to a normal range. Medications that can cause hypertriglyceridemia need to be discontinued. Underlying diabetes needs to be treated aggressively to get better control of glucose metabolism and insulin requirements. Those patients with familial causes need to institute dietary changes (to avoid medium-chain triglycerides), increase their activity level, and take triglyceride-lowering medications. These medications can be used for all causes of hypertriglyceridemia. The medications most commonly used to low r triglyceride levels are fenofibrate and gemfibrozil.

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