Xanthelasma (xanthelasma palpebrarum)
Xanthelasma (xanthelasma palpebrarum) ICD-9 374.51
Are You Confident of the Diagnosis?
What you should be alert for in the history
Also called xanthelasma palpebrarum, these planar, yellow-to-gray plaques are present on the eyelids and periorbital skin. They are the most common and least specific of all xanthomas. When seen in isolation xanthelasma can present a diagnostic dilemma because one-half of patients with it are normolipemic. However, their presence, especially in a younger patient, warrants a history, physical, and measurement of a fasting plasma lipid profile.
Characteristic findings on physical examination
Xanthelasma are planar, yellow-to-gray plaques present on the eyelids and the periorbital skin (
Xanthelasma presenting as a soft yellow plaque on the periorbital skin (Courtesy of the Betty E. Janes Clinical Image Library, Department of Dermatology, University of Texas Southwestern Medical Center)
Expected results of diagnostic studies
The hallmark histopathologic feature of all xanthomas is the presence of foam cells within the dermis. These cells represent macrophages, which contain lipid. These cells will stain positive for lipid with special stains (Oil-red-O). As a reflection of their periorbital location, a histologic specimen of xanthelasma can contain striated muscle, vellus hairs, and a thin epidermis.
Performing a fasting lipid profile can readily determine if a patient’s xanthelasma are the consequence of an underlying hyperlipidemia. Clinicians should test patients with xanthelasma, especially if they are young or have multiple family members with early atherosclerotic disease.
The location of xanthelasma generates a differential diagnosis that includes appendageal tumors.
Who is at Risk for Developing this Disease?
Xanthelasma can arise in several of the genetic disorders of lipoprotein metabolism including homozygous and heterozygous familial hypercholesterolemia, familial dysbetalipoproteinemia (type III), and in systemic disease (monoclonal gammopathy and paraproteinemia).
What is the Cause of the Disease?
There is good evidence that the lipid found within xanthomas is the same lipid circulating in high concentrations in the plasma of patients. However, the exact mechanisms that induce xanthoma formation are less clear. It has been demonstrated that using scavenger receptors for low density lipoprotein (LDL) macrophages can take-up lipid and become transformed into foam cells. It has also been shown that extravasated lipid can attract foam cells through modulation of vascular endothelial receptors.
Furthermore, oxidized low density lipoprotein has been shown to induce the formation and infiltration of foam cells within the dermis. Local factors like heat, movement, and friction may increase LDL leakage from capillaries and explain the sites of predilection for xanthomas.
Systemic Implications and Complications
Recognition of xanthelasma should prompt the clinician to screen for underlying hyperlipidemia. These patients should be screened for lipid abnormalities and have aggressive treatment of their lipid derangement to slow the progression of atherosclerotic disease.
Lifestyle modifications and prevention
Dietary modification (only modestly helpful)
Systemic medications for hyperlipidemia
HMG CoA reductase inhibitors (statins)
Bile acid sequestrants
Fibric acid derivatives (fenofibrate and gemfibrozil)
Surgical treatments for xanthelasma
Ablative laser therapy
Optimal Therapeutic Approach for this Disease
The first step in the management of xanthelasma should be to determine if there is an abnormality of lipoprotein metabolism contributing to their presence in a particular patient. Patients should have a fasting lipid profile performed. If an abnormality is noted, specific treatment can be aimed at correcting it. Systemic medications to reduce the level of total cholesterol, LDL, and VLDL are utilized to target the specific lipoprotein elevations.
To correct the appearance of xanthelasma surgical and physical modalities that can be employed include excision, ablative laser treatment, trichloroacetic acid (35%), and cryotherapy.
Through recognizing a cutaneous manifestation of hyperlipidemia, patients at high risk of atherosclerotic disease can be identified and treated with cholesterol lowering medications. These patients will need regular and consistent monitoring of their lipid levels and they should be managed in combination with their primary care physician and if necessary a cardiologist.
Unusual Clinical Scenarios to Consider in Patient Management
Some patients with xanthelasma are found to have no overt elevation of lipids levels, but are heterozygous for the apolipoprotein-E2 allele. These patients do not have biochemical or the clinical features of the syndrome of familial dysbetalipoproteinemia. It is unclear if these patients are at an elevated risk of atherosclerosis.
What is the Evidence?
Gómez, JA, Gonzalez, MJ, de Moragas, JM, Serrat, J, Gonzalez-Sastre, F, Perez, M. "Apolipoprotein E phenotypes, lipoprotein composition, and xanthelasmas". Arch Dermatol. vol. 125. 1989. pp. 1281-2.(Though nearly one-half of patients with xanthelasma are normolipemic, some patients are heterozygous carriers of the abnormal apolipoprotein-E2 allele. It is unclear if these patients are at an increased risk of atherosclerosis.)
Elder, DE. "Lever’s Histopathology of the Skin". Wilkins. 2005.(The salient histologic features of xanthelasma are reviewed.)
Cruz, PD, East, C, Bergstresser, PR. "Dermal, subcutaneous, and tendon xanthomas: diagnostic markers for specific lipoprotein disorders". J Am Acad Dermatol. vol. 19. 1988. pp. 95-111.(A review of the dermatologic manifestations of the various types of xanthomas is presented.)
Bergman, R. "The pathogenesis and clinical significance of xanthelasma palpebrarum". J Am Acad Dermatol. vol. 30. 1994. pp. 236-42.(In this study of patients with xanthelasma nearly one-half of patients were found to be hyperlipidemic. This illustrates the need to screen patients with xanthelasma, especially patients that are young.)
Knopp, RH. "Drug treatment of lipid disorders". N Engl J Med. vol. 341. 1999. pp. 498-511.(The treatment of hyperlipidemia is reviewed.)
Elabjer, BK, Busic, M, Sekelj, S, Krstonijevic, EK. "Operative treatment of large periocular xanthelasma". Orbit. vol. 28. 2009. pp. 16-9.(A case series of 63 patients treated with operative resection of large periocular xanthelasma.)
Karsai, S, Czarnecka, A, Raulin, C. "Treatment of xanthelasma palpebrarum using a pulsed dye laser: a prospective clinical trial in 38 cases". Dermatol Surg. vol. 36. 2010. pp. 610-7.(An evaluation of the efficacy of pulsed dye laser in the treatment of xanthelasma. It demonstrates the efficacy of this treatment, especially when multiple sessions are performed.)
Cannon, PS, Ajit, R, Leatherbarrow, B. "Efficacy of trichloroacetic acid (95%) in the management of xanthelasma palpebrarum". Clin Exp Dermatol. vol. 35. 2010. pp. 845-8.(Though we recommend starting with a lower concentration of trichloroacetic acid, this article demonstrates the efficacy of repeated topical TCA application.)
Hawk, JL. "Cryotherapy may be effective for eyelid xanthelasma". Clin Exp Dermatol. vol. 25. 2000. pp. 351.(Cryotherapy can be a useful ablative treatment modality for the treatment of xanthelasma.)
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