Your activity: 2 p.v.

Cutaneous xanthomas

Cutaneous xanthomas
Authors:
Karolyn Wanat, MD
Megan H Noe, MD, MPH, MSCE
Section Editors:
Jeffrey Callen, MD, FACP, FAAD
Mason W Freeman, MD
Deputy Editor:
Abena O Ofori, MD
Literature review current through: Nov 2022. | This topic last updated: Nov 22, 2022.

INTRODUCTION — Xanthomas are localized lipid deposits within organs that may manifest as papules, plaques, or nodules in skin. The clinical variants of cutaneous xanthomas include:

Eruptive xanthomas (picture 1A-C)

Tuberous xanthomas (picture 2A-C)

Tendinous xanthomas (picture 3)

Plane xanthomas (including xanthelasma) (picture 4A-C)

Verruciform xanthomas (picture 5)

Cutaneous xanthomas can be idiopathic or a sign of an inherited abnormality of lipoprotein metabolism (primary dyslipidemia), hyperlipidemia secondary to systemic disease or medication, or hematologic disease. The subtype of xanthoma provides a clue to the underlying abnormality. Accurate diagnosis of xanthomas is important because it can lead to the identification and treatment of underlying disease (algorithm 1).

The clinical features, diagnosis, and management of patients with cutaneous xanthomas will be reviewed here. The causes and management of lipid disorders are discussed separately. (See "Inherited disorders of LDL-cholesterol metabolism other than familial hypercholesterolemia" and "Secondary causes of dyslipidemia" and "Hypertriglyceridemia in adults: Management".)

EPIDEMIOLOGY — Epidemiologic data on cutaneous xanthomas are limited. With the exception of xanthelasma, the most common subtype, cutaneous xanthomas are uncommon. Xanthelasma occur both in the presence and absence of hyperlipidemia with estimates of prevalence in the general population ranging from less than 1 to 4 percent [1]. Tuberous, tuberoeruptive, tendinous, and nonxanthelasma plane xanthomas typically occur in association with inherited or acquired dyslipidemia or hematologic disease [2,3]. (See 'Clinical variants' below.)

Cutaneous xanthomas most often present in adulthood. Xanthomas associated with familial hypercholesterolemia are an exception; xanthomas in patients with this disorder often begin to develop prior to the age of 10 years. Cutaneous xanthomas occur in both males and females. There does not appear to be a clear sex predilection.

PATHOGENESIS — Cutaneous xanthomas represent deposition of lipid and associated inflammation in the skin. The pathogenic mechanisms that lead to cutaneous xanthomas are not fully understood and may differ based upon the etiology and type of xanthoma.

For xanthomas occurring in association with hyperlipidemia, it is hypothesized that when serum levels of lipoproteins are substantially elevated, extravasation of lipoproteins through dermal capillary blood vessels with subsequent engulfment by macrophages leads to the lipid-laden cells found in xanthomas, which has been demonstrated using electron microscopy [4,5]. Earlier studies suggested the cutaneous lipid accumulation was a result of de novo lipid synthesis [6,7].

Primary or secondary hyperlipidemic states can lead to xanthoma formation. Primary hyperlipidemia results from genetic defects in receptors, receptor ligands, or enzymes involved in lipid metabolism. Causes of secondary hyperlipidemia include underlying disease states and medications. Examples of diseases and physiologic states associated with hyperlipidemia include obesity, diabetes mellitus, hypothyroidism, nephrotic syndrome, cholestasis, and pregnancy [8-13]. Examples of medications that may lead to hyperlipidemia (often hypertriglyceridemia) include estrogens, tamoxifen, prednisone, oral retinoids, cyclosporine, olanzapine, nilotinib, and protease inhibitors [14-18]. (See "Secondary causes of dyslipidemia" and "Inherited disorders of LDL-cholesterol metabolism other than familial hypercholesterolemia" and "Familial hypercholesterolemia in adults: Overview" and "Hypertriglyceridemia in adults: Approach to evaluation", section on 'Symptoms and signs'.)

Some plane xanthomas occur in the absence of dyslipidemia. Diffuse normolipemic plane xanthoma, a rare subtype of plane xanthoma, often develops in association with monoclonal gammopathy, multiple myeloma, and other hematologic diseases. Immune complex formation between antibodies and lipoproteins leading to lipid accumulation within macrophages is a proposed mechanism for xanthoma formation in the setting of monoclonal gammopathy [19]. The mechanism of xanthelasma (periorbital plane xanthoma) formation in patients without dyslipidemia is unclear. (See 'Plane xanthomas' below.)

Verruciform xanthomas are not associated with hyperlipidemia or underlying disease. Verruciform xanthomas may represent an immune reaction to local trauma or inflammation [20]. (See 'Verruciform xanthomas' below.)

CLINICAL VARIANTS — The clinical variants of cutaneous xanthoma include eruptive xanthomas, tuberous and tuberoeruptive xanthomas, tendinous xanthomas, plane xanthomas (including xanthelasma), and verruciform xanthomas. Most xanthomas present as erythematous to yellow papules, plaques, or nodules representative of lipid deposition in the skin.

The characteristic histologic feature of cutaneous xanthomas is lipid-laden macrophages, also known as "foam cells." The number of foam cells and the presence of associated findings, such as inflammatory cells, extracellular lipid deposition, and fibrosis vary with the type and age of the xanthoma. Eruptive xanthomas often have prominent extracellular lipid deposition, and tuberous and tendinous xanthomas often have large foam cells with associated fibrosis [2,21].

Eruptive xanthomas

Clinical features – Eruptive xanthomas are 1 to 5 mm erythematous to yellow papules that appear in crops and have an abrupt onset (picture 1A-C). The most common sites of involvement are the extensor surfaces of the extremities and buttocks. Koebnerization (the appearance of eruptive xanthomas at sites of skin trauma) can occur.

Associated disorders – Eruptive xanthomas are highly suggestive of hypertriglyceridemia and are often associated with serum triglyceride levels exceeding 1500 to 2000 mg/dL. Lipid disorders that may result in eruptive xanthomas are those in which very low density lipoprotein (VLDL) levels, chylomicron levels, or both are dramatically increased (table 1). Occasionally, eruptive xanthomas are the initial sign of diabetes [22,23]. Eruptive xanthomas have also occurred in association with hypertriglyceridemia-induced pancreatitis [24]. (See "Hypertriglyceridemia in adults: Management".)

Histopathology – Eruptive xanthomas demonstrate foam cells, a mixed inflammatory cell infiltrate with lymphocytes, neutrophils, and histiocytes, and extracellular lipid deposits. Foam cells may be few in number in early eruptive xanthomas.

Tuberous xanthomas

Clinical features – Tuberous xanthomas are yellow-orange or erythematous papules or nodules located over joints or extensor surfaces of the extremities, especially the elbows and knees (picture 2A-C). They may be solitary or grouped and they can reach sizes up to 3 cm. The term "tuberoeruptive xanthomas" may be used to refer to papular lesions.

Associated disorders – Tuberous xanthomas occur in hypercholesterolemic states, such as with familial hypercholesterolemia (low-density lipoprotein [LDL] levels elevated) or when intermediate density lipoprotein levels are high (familial dysbetalipoproteinemia), in which case the serum cholesterol and triglyceride levels may be similarly increased (eg, each is approximately 400 mg/dL) (table 1). (See "Inherited disorders of LDL-cholesterol metabolism other than familial hypercholesterolemia".)

Histopathology – Tuberous xanthomas demonstrate abundant foam cells (picture 6). A mild inflammatory infiltrate may also be present. Older tuberous xanthomas may exhibit increased fibroblasts and collagen deposition.

Tendinous xanthomas

Clinical features – Tendinous xanthomas are smooth, firm but mobile, skin-colored nodules (picture 3). They appear over tendons or ligaments, most commonly the Achilles tendon. Tendinous xanthomas are incorporated into the tendon and will move as the tendon passes back and forth with joint extension and flexion.

Associated disorders – Tendinous xanthomas commonly occur in genetic hypercholesterolemic syndromes due to elevated LDL levels, either caused by LDL receptor mutations (familial hypercholesterolemia) or defects in the LDL apoprotein, apolipoprotein B-100 (familial defective apo B-100). Tendinous xanthomas also can develop in cerebrotendinous xanthomatosis, a rare autosomal recessive lipid storage disease that leads to the accumulation of cholesterol and cholestanol in tissues and results in neurologic dysfunction [25]. Patients with sitosterolemia, a rare inherited sterol storage disease, may also develop tendinous xanthomas [26]. (See "Cerebrotendinous xanthomatosis" and "Inherited disorders of LDL-cholesterol metabolism other than familial hypercholesterolemia".)

Histopathology – The histopathology of tendinous xanthomas is similar to tuberous xanthomas.

Plane xanthomas

Clinical features – Plane xanthomas are soft yellow thin plaques that are found most commonly around the eyelids (xanthelasma), neck, trunk, shoulders, and axillae (picture 4A-C).

Associated disorders – Plane xanthomas can occur in both the presence and absence of primary or secondary hyperlipidemia. Xanthoma striatum palmare, plane xanthomas within the creases of the palms, are pathognomonic for familial dysbetalipoproteinemia (picture 7). Interdigital xanthomas, especially between the thumb and index finger, are pathognomonic for homozygous familial hypercholesterolemia [27,28]. Plane xanthomas also can occur in the setting of cholestasis-related hypercholesterolemia in primary biliary cholangitis or in biliary atresia seen in Alagille syndrome [29-31]. These patients often develop xanthomatous plaques on the hands and feet. (See "Inherited disorders of LDL-cholesterol metabolism other than familial hypercholesterolemia" and "Hypercholesterolemia in primary biliary cholangitis (primary biliary cirrhosis)" and "Biliary atresia".)

The relationship between xanthelasma and dyslipidemia has been controversial. A systematic review and meta-analysis of 15 case-control studies that assessed serum lipid levels in individuals with xanthelasma found higher serum levels of total cholesterol (standard mean difference [SMD] 0.612, 95% CI 0.376-0.848) and LDLs (SMD 0.587, 95% CI 0.339-0.836) in patients with xanthelasma than in control patients, supporting an increased risk for dyslipidemia in this population [32]. Patients with xanthelasma also had higher levels of apolipoprotein B (a risk marker of atherosclerosis) and higher carotid intima-media thickness (a surrogate marker of atherosclerosis), suggesting increased risk for atherosclerotic disease. Significant differences in levels of high-density lipoproteins (HDLs), VLDLs, and triglycerides were not detected between the populations. (See 'Laboratory evaluation' below.)

Diffuse normolipemic plane xanthoma is a rare subtype of plane xanthoma characterized by a symmetrical eruption of plane xanthomas on the face, neck, and upper trunk in the absence of hyperlipidemia. These xanthomas most frequently develop in patients with hematologic disorders, such as monoclonal gammopathy, multiple myeloma, chronic myelomonocytic leukemia, myelodysplastic syndrome, and lymphoproliferative disorders (eg, B cell lymphoma, Castleman disease) [33]. The xanthomas may precede the diagnosis of hematologic disease [34].

Histopathology – Plane xanthomas exhibit aggregates of foam cells in the upper dermis. Inflammatory cells may be few or absent. Biopsies of xanthelasma also demonstrate small vellus hairs and superficial, thin muscles, consistent with the eyelid location (picture 8).

Verruciform xanthomas

Clinical features – Verruciform xanthomas are solitary, erythematous, flat or verrucous papules that most commonly develop in the oral cavity or on anogenital skin (picture 5).

Associated disorders Verruciform xanthomas can develop independently [35] or in association with a variety of disorders, including recessive dystrophic epidermolysis bullosa [36], congenital hemidysplasia with ichthyosiform erythroderma and limb defects (CHILD) syndrome [37], chronic lymphedema [38-40], graft versus host disease [41,42], or oral lichen planus [43,44].

Histopathology – Verruciform xanthomas have a characteristic histopathologic appearance, demonstrating a papillomatous epidermis with cup-shaped invaginations of parakeratosis (picture 9A-B). There are neutrophils and foam cells in the dermal papillae [45].

DIAGNOSIS — The diagnosis of cutaneous xanthomas involves determining the type of xanthoma and the underlying cause through the patient history, physical examination, and relevant laboratory studies. Often, the classic yellow or yellow-red color and distribution of eruptive, tuberous, and plane xanthomas (eg, eyelids in xanthelasma) enables a presumptive diagnosis. Correlation of the clinical and pathologic findings confirms the diagnosis.

Clinical assessment — The patient history should include an assessment for risk factors for xanthoma development. We assess patients for:

Underlying diseases (eg, diabetes, thyroid disease, nephrotic syndrome, hematologic disease)

Medications that may cause hyperlipidemia (eg, estrogens, tamoxifen, prednisone, oral retinoids, cyclosporine, olanzapine, nilotinib, and protease inhibitors)

Family history of primary lipid disorders or diseases associated with hyperlipidemia

The physical examination should include an assessment of the morphology and location of the xanthoma(s). Physical findings that suggest particular variants include:

Eruptive xanthomas – Multiple small, yellow to yellow-red papules on the buttocks or extensor extremities (picture 1A-C)

Tuberous xanthomas – Yellow-orange or erythematous papules or nodules on the extensor extremities or joints (picture 2A-C)

Tendinous xanthomas – Skin-colored, mobile nodules over tendons or ligaments (picture 3)

Plane xanthomas – Yellow, thin plaques on the eyelids (xanthelasma), neck, trunk, shoulders, or axillae (picture 4A-C)

Verruciform xanthomas – Verrucous papules in the oral cavity or on anogenital skin (picture 5)

Biopsy — A shave, punch, or excisional skin biopsy can identify histologic features consistent with a cutaneous xanthoma and can confirm the diagnosis when correlated with the clinical findings. (See 'Clinical variants' above and "Skin biopsy techniques".)

Laboratory evaluation — A fasting lipid panel to evaluate for dyslipidemia should be performed in all patients with xanthomas, with the exception of patients with verruciform xanthomas (algorithm 1). Verruciform xanthomas are not associated with hyperlipidemia. (See 'Verruciform xanthomas' above.)

Patients with hyperlipidemia should receive further evaluation to identify the cause of dyslipidemia. Patients with eruptive or plane xanthomas and hyperlipidemia warrant evaluations for causes of secondary hyperlipidemia, such as diabetes, thyroid disease, liver disease, or renal disease. We typically begin the evaluation of these patients by obtaining a fasting glucose level, hemoglobin A1C, liver function tests, thyroid-stimulating hormone, and renal function tests, depending on patient history and review of symptoms. If a cause of secondary hyperlipidemia does not become evident in a patient with eruptive or plane xanthomas, the patient should be evaluated for primary (inherited) dyslipidemia. Patients with tendinous or tuberous xanthomas automatically should be evaluated for an inherited dyslipidemia.

While children with sitosterolemia can present with normolipemic xanthomas, in adults without evidence of dyslipidemia, a diagnosis of eruptive, tuberous, or tendinous xanthomas should be reconsidered given the strong association of these subtypes with dyslipidemia. (See "Inherited disorders of LDL-cholesterol metabolism other than familial hypercholesterolemia" and "Secondary causes of dyslipidemia" and "Hypertriglyceridemia in adults: Management" and "Familial hypercholesterolemia in children", section on 'Differential diagnosis'.)

Patients with plane xanthomas can be normolipidemic. Because of the association of diffuse normolipemic plane xanthomas with hematologic disease, these patients should be evaluated for an associated hematologic disease. Reasonable initial laboratory studies include:

Complete blood count

Serum protein electrophoresis and serum immunofixation

Serum free light chain assay

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of xanthomas depends on the clinical variant. When necessary, a skin biopsy can differentiate cutaneous xanthomas from other disorders.

Xanthelasma, the most common type cutaneous xanthoma, should be distinguished from other causes of persistent periocular papules. Examples include:

Sebaceous hyperplasia – Sebaceous hyperplasia presents as single or multiple, yellow-orange, 2 to 6 mm, lobulated papules with a central dell (picture 10A-B). The face is the most common site of involvement. (See "Cutaneous adnexal tumors", section on 'Sebaceous hyperplasia'.)

Juvenile xanthogranuloma – Juvenile xanthogranuloma classically presents as reddish or yellowish skin papules or nodules on the head, neck, or upper trunk (picture 11A-B). Unlike xanthelasma, juvenile xanthogranuloma most commonly occurs in young children. (See "Juvenile xanthogranuloma (JXG)".)

Syringoma – Syringomas usually present as firm, grouped papules on periorbital skin (picture 12). Syringomas are skin-colored and lack the yellow color typical of xanthelasma. (See "Cutaneous adnexal tumors", section on 'Syringoma'.)

Nodular basal cell carcinoma – Nodular basal cell carcinoma commonly occurs on the face, typically manifesting as a pearly papule with arborizing telangiectasias (picture 13). Basal cell carcinomas lack the yellow hue of xanthelasma. (See "Epidemiology, pathogenesis, clinical features, and diagnosis of basal cell carcinoma".)

Plane xanthomas should be distinguished from necrobiotic xanthogranuloma (NXG). NXG is a non-Langerhans histiocytosis that is often associated with monoclonal gammopathy. Patients with NXG typically develop red-brown, violaceous, or yellowish cutaneous papules, plaques, or nodules on periorbital skin or other sites (picture 14A-B). (See "Necrobiotic xanthogranuloma".)

The multiple papules of eruptive xanthomas should be distinguished from generalized granuloma annulare and xanthoma disseminatum. Generalized granuloma annulare manifests with widespread skin-colored to erythematous papules or plaques on the trunk and extremities (picture 15A-B). Xanthoma disseminatum is a form of non-Langerhans cell histiocytosis characterized by red-brown papules and plaques in the flexural areas of the trunk or proximal extremities [46]. (See "Granuloma annulare: Epidemiology, clinical manifestations, and diagnosis", section on 'Generalized granuloma annulare'.)

Tendinous xanthomas and tuberous xanthomas may resemble other nodular eruptions with predilections for sites over joints or tendons. Examples include rheumatoid nodules (picture 16), gouty tophi (picture 17), subcutaneous granuloma annulare (picture 18), and erythema elevatum diutinum (picture 19A-B). Knowledge of underlying medical conditions is useful for narrowing the differential diagnosis.

Verrucous xanthomas on the oral and genital mucosa may be clinically confused with condylomata, oral papillomas, verrucous carcinoma, and squamous cell carcinoma.

TREATMENT — Cutaneous xanthomas are not life-threatening and are usually asymptomatic. Therefore, treatment specifically for cutaneous xanthomas is not mandatory, although it is often desired for cosmetic reasons.

However, pharmacologic treatment of dyslipidemia is usually indicated and often leads to concomitant improvement in eruptive, tuberous, tendinous, and plane xanthomas caused by hyperlipidemia [47-49]. Eruptive xanthomas typically resolve within several weeks when triglyceride levels are reduced. Tuberous and tendinous xanthomas are slower to regress during treatment of dyslipidemia. (See "Low-density lipoprotein cholesterol-lowering therapy in the primary prevention of cardiovascular disease" and "Hypertriglyceridemia in adults: Management", section on 'Treatment goals' and "Management of low density lipoprotein cholesterol (LDL-C) in the secondary prevention of cardiovascular disease".)

Different approaches are necessary for the treatment of xanthomas that are not associated with dyslipidemia. Normolipidemic patients with xanthelasma who desire treatment are primarily treated with surgical excision or destructive interventions. Traditionally, surgical excision has been used, with good cosmetic results [50]. Other effective treatment methods include destruction of xanthelasma with cryotherapy; 70% trichloroacetic acid chemical peels; intralesional bleomycin; and treatment with carbon dioxide (CO2), erbium-doped yttrium aluminium garnet (Er:YAG), or Q-switched neodymium-doped yttrium aluminium garnet (Nd:YAG) lasers [51-56]. Of note, surgical and destructive techniques do not prevent recurrences or new xanthelasma.

Although small normolipemic plane xanthomas, such as xanthelasma, are amenable to surgical or destructive therapies, such treatment is often impractical for patients with more extensive skin involvement, leaving the best approach to treatment of these lesions unclear. A split-face, randomized, controlled trial suggested that fractional CO2 laser therapy was superior to Er:YAG laser therapy, with more patients experiencing clinical improvement with fewer treatments on the side treated with the fractional CO2 laser [57].

Diffuse normolipemic plane xanthomas that occur in association with hematologic disease tend to be persistent. However, remission of the hematologic disease has been associated with improvement of the skin lesions [19].

Verruciform xanthomas are generally treated with surgical excision [58-60]. In addition, case reports have described resolution of a large verruciform xanthoma on the vulva with topical imiquimod and successful treatment of a scrotal verruciform xanthoma with shave debulking followed by fractionated CO2 laser therapy [58,61].

PROGNOSIS AND FOLLOW-UP — Without treatment, xanthomas typically persist. Patients with hyperlipidemia-associated xanthomas require clinical follow up for morbidities associated with hyperlipidemia and underlying causes of hyperlipidemia. In addition, patients with diffuse plane xanthomas who lack evidence for hematologic disease at the time of diagnosis require long-term follow up for the development of hematologic disease [34].

There is uncertainty about the prognostic implications of xanthelasma in the absence of hyperlipidemia. A study of 20 normolipidemic patients with xanthelasma, 20 hyperlipidemic patients with xanthelasma, and 40 normolipidemic participants without xanthelasma found higher (albeit normal) levels of total cholesterol and triglycerides in normolipidemic patients with xanthelasma than control patients [62]. Carotid artery intima-media thickness, a marker for atherosclerosis, also was higher in normolipidemic patients with xanthelasma than controls. These findings suggest that xanthelasma is associated with increased risk for atherosclerosis, independent of lipid concentrations. Larger studies are necessary to confirm this conclusion.

SUMMARY AND RECOMMENDATIONS

Overview – Xanthomas are localized deposits of lipids within the organs that occur most commonly in the setting of an underlying lipid abnormality. The major subtypes of cutaneous xanthomas are eruptive xanthoma, tuberous xanthoma, tendinous xanthoma, plane xanthoma, and verruciform xanthoma. (See 'Clinical variants' above.)

Clinical variants – The clinical variants of cutaneous xanthomas have varying clinical features and disease associations:

Eruptive xanthomas – Eruptive xanthomas manifest as crops of erythematous to yellow 1 to 5 mm papules that usually appear on the extensor surfaces of the extremities and buttocks (picture 1A-C). Eruptive xanthomas occur in the setting of severe hypertriglyceridemia. (See 'Eruptive xanthomas' above.)

Tuberous xanthomas – Tuberous xanthomas are yellow-orange or erythematous papules or nodules that usually appear on skin over joints or extensor surfaces of the extremities (picture 2A-C). Tuberous xanthomas occur in the setting of hypercholesterolemia. (See 'Tuberous xanthomas' above.)

Tendinous xanthomas – Tendinous xanthomas are smooth, skin-colored nodules found over tendons or ligaments (picture 3). Tendinous xanthomas most commonly occur in familial hyperlipidemia syndromes with elevated low-density lipoprotein (LDL) or familial defective apolipoprotein B-100. (See 'Tendinous xanthomas' above.)

Plane xanthomas – Plane xanthomas are soft, yellow plaques found around the eyelids (xanthelasma), neck, trunk shoulders or axillae (picture 4A-C). Plane xanthomas may occur in the presence or absence of hyperlipidemia. Rarely, plane xanthomas are associated with monoclonal gammopathies, multiple myeloma, or other hematologic disease. (See 'Plane xanthomas' above.)

Verruciform xanthomas – Verruciform xanthomas are flat or verrucous papules that most commonly appear on the oral mucosa or anogenital skin. Verruciform xanthomas are not associated with dyslipidemia. (See 'Verruciform xanthomas' above.)

Diagnosis – A diagnosis of cutaneous xanthomas can be suspected based upon the physical findings and confirmed with a skin biopsy. (See 'Diagnosis' above.)

Additional evaluation – All patients with cutaneous xanthomas, with the exception of patients with verruciform xanthomas, should be evaluated for the presence of hyperlipidemia (algorithm 1). Hyperlipidemia in patients with eruptive or plane xanthomas warrants an evaluation for causes of secondary hyperlipidemia. Normolipidemic patients with diffuse plane xanthomas require evaluation for underlying hematologic disease. (See 'Laboratory evaluation' above.)

Treatment – Cutaneous xanthomas associated with hyperlipidemia often improve with treatment of the underlying lipid abnormality. Surgical and destructive treatments are the primary therapeutic options for xanthelasma in normolipidemic patients and for verruciform xanthomas. (See 'Treatment' above.)

  1. Zak A, Zeman M, Slaby A, Vecka M. Xanthomas: clinical and pathophysiological relations. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2014; 158:181.
  2. Love JR, Dubin HV. Xanthomas and lipoproteins. Cutis 1978; 21:801.
  3. Cruz PD Jr, East C, Bergstresser PR. Dermal, subcutaneous, and tendon xanthomas: diagnostic markers for specific lipoprotein disorders. J Am Acad Dermatol 1988; 19:95.
  4. Parker F. Normocholesterolemic xanthomatosis. Arch Dermatol 1986; 122:1253.
  5. Parker F, Bagdade JD, Odland GF, Bierman EL. Evidence for the chylomicron origin of lipids accumulating in diabetic eruptive xanthomas: a correlative lipid biochemical, histochemical, and electron microscopic study. J Clin Invest 1970; 49:2172.
  6. Wilson JD. Studies on the origin of the lipid components of xanthomata. Circ Res 1963; 12:472.
  7. Hu CH, Ellefson RD, Winkelmann RK. Lipid synthesis in cutaneous xanthoma. J Invest Dermatol 1982; 79:80.
  8. Hubert HB, Feinleib M, McNamara PM, Castelli WP. Obesity as an independent risk factor for cardiovascular disease: a 26-year follow-up of participants in the Framingham Heart Study. Circulation 1983; 67:968.
  9. Smellie WS. Hypertriglyceridaemia in diabetes. BMJ 2006; 333:1257.
  10. Wheeler DC, Bernard DB. Lipid abnormalities in the nephrotic syndrome: causes, consequences, and treatment. Am J Kidney Dis 1994; 23:331.
  11. Appel G. Lipid abnormalities in renal disease. Kidney Int 1991; 39:169.
  12. O'Brien T, Dinneen SF, O'Brien PC, Palumbo PJ. Hyperlipidemia in patients with primary and secondary hypothyroidism. Mayo Clin Proc 1993; 68:860.
  13. Walsh BW, Schiff I, Rosner B, et al. Effects of postmenopausal estrogen replacement on the concentrations and metabolism of plasma lipoproteins. N Engl J Med 1991; 325:1196.
  14. Crook D, Cust MP, Gangar KF, et al. Comparison of transdermal and oral estrogen-progestin replacement therapy: effects on serum lipids and lipoproteins. Am J Obstet Gynecol 1992; 166:950.
  15. Kasiske BL, Ma JZ, Kalil RS, Louis TA. Effects of antihypertensive therapy on serum lipids. Ann Intern Med 1995; 122:133.
  16. Hilbrands LB, Demacker PN, Hoitsma AJ, et al. The effects of cyclosporine and prednisone on serum lipid and (apo)lipoprotein levels in renal transplant recipients. J Am Soc Nephrol 1995; 5:2073.
  17. Klör HU, Weizel A, Augustin M, et al. The impact of oral vitamin A derivatives on lipid metabolism - What recommendations can be derived for dealing with this issue in the daily dermatological practice? J Dtsch Dermatol Ges 2011; 9:600.
  18. Sayin I, Ayli M, Oğuz AK, Seval GC. Xanthelasma palpebrarum: a new side effect of nilotinib. BMJ Case Rep 2016; 2016.
  19. Szalat R, Arnulf B, Karlin L, et al. Pathogenesis and treatment of xanthomatosis associated with monoclonal gammopathy. Blood 2011; 118:3777.
  20. Hegde U, Doddawad VG, Sreeshyla H, Patil R. Verruciform xanthoma: A view on the concepts of its etiopathogenesis. J Oral Maxillofac Pathol 2013; 17:392.
  21. Cutaneous infiltrates - Non-lymphoid. In: Weedon's Skin Pathology, 4th ed, Patterson JW, Hosler GA, Weedon D (Eds), Churchill Livingstone Elsevier, 2015. p.1129.
  22. Ravić-Nikolić A, Mladenović V, Mitrović S, et al. Generalized eruptive xanthomas associated with diabetic dyslipidemia. Eur J Dermatol 2014; 24:394.
  23. Solak B, Kara RO, Acikgoz SB, Kosem M. First and only symptom of undiagnosed diabetes mellitus: eruptive xanthoma. BMJ Case Rep 2015; 2015.
  24. Bounouar M, Mernissi F. [Eruptive xanthomas announcing severe acute pancreatitis]. Pan Afr Med J 2014; 17:225.
  25. Moghadasian MH. Cerebrotendinous xanthomatosis: clinical course, genotypes and metabolic backgrounds. Clin Invest Med 2004; 27:42.
  26. Bhattacharyya AK, Connor WE. Beta-sitosterolemia and xanthomatosis. A newly described lipid storage disease in two sisters. J Clin Invest 1974; 53:1033.
  27. Raal FJ, Santos RD. Homozygous familial hypercholesterolemia: current perspectives on diagnosis and treatment. Atherosclerosis 2012; 223:262.
  28. Sil A, Bhanja DB, Biswas SK. Intertriginous Xanthomas-Pathognomonic Cutaneous Markers of Homozygous Familial Hypercholesterolemia. JAMA Dermatol 2021; 157:1228.
  29. Baila-Rueda L, Mateo-Gallego R, Lamiquiz-Moneo I, et al. Severe hypercholesterolemia and phytosterolemia with extensive xanthomas in primary biliary cirrhosis: role of biliary excretion on sterol homeostasis. J Clin Lipidol 2014; 8:520.
  30. Macías-Rodríguez RU, Torre-Delgadillo A. Xanthelasmas and xanthomatas striatum palmare in primary biliary cirrhosis. Ann Hepatol 2006; 5:49.
  31. Weston CF, Burton JL. Xanthomas in the Watson-Alagille syndrome. J Am Acad Dermatol 1987; 16:1117.
  32. Chang HC, Sung CW, Lin MH. Serum lipids and risk of atherosclerosis in xanthelasma palpebrarum: A systematic review and meta-analysis. J Am Acad Dermatol 2020; 82:596.
  33. Lynch MC, Wood L, Anderson BE, Clarke LE. JAAD Grand Rounds. Asymptomatic dermal plaques. J Am Acad Dermatol 2015; 72:922.
  34. Marcoval J, Moreno A, Bordas X, et al. Diffuse plane xanthoma: clinicopathologic study of 8 cases. J Am Acad Dermatol 1998; 39:439.
  35. Blankenship DW, Zech L, Mirzabeigi M, Venna S. Verruciform xanthoma of the upper-extremity in the absence of chronic skin disease or syndrome: a case report and review of the literature. J Cutan Pathol 2013; 40:745.
  36. Curto-Barredo L, Segura S, Barranco C, et al. Verruciform xanthoma developing in recessive dystrophic epidermolysis bullosa: A sheep in wolf's clothing. Am J Dermatopathol 2014; 36:506.
  37. Xu XL, Huang LM, Wang Q, Sun JF. Multiple verruciform xanthomas in the setting of congenital hemidysplasia with ichthyosiform erythroderma and limb defects syndrome. Pediatr Dermatol 2015; 32:135.
  38. Chyu J, Medenica M, Whitney DH. Verruciform xanthoma of the lower extremity--report of a case and review of literature. J Am Acad Dermatol 1987; 17:695.
  39. Huguet P, Toran N, Tarragona J. Cutaneous verruciform xanthoma arising on a congenital lymphoedematous leg. Histopathology 1995; 26:277.
  40. Romaní J, Luelmo J, Sáez A, et al. Localized xanthomas associated with primary lymphedema. Pediatr Dermatol 2012; 29:113.
  41. Mannes KD, Dekle CL, Requena L, Sangueza OP. Verruciform xanthoma associated with squamous cell carcinoma. Am J Dermatopathol 1999; 21:66.
  42. Shahrabi Farahani S, Treister NS, Khan Z, Woo SB. Oral verruciform xanthoma associated with chronic graft-versus-host disease: a report of five cases and a review of the literature. Head Neck Pathol 2011; 5:193.
  43. Polonowita AD, Firth NA, Rich AM. Verruciform xanthoma and concomitant lichen planus of the oral mucosa. A report of three cases. Int J Oral Maxillofac Surg 1999; 28:62.
  44. Miyamoto Y, Nagayama M, Hayashi Y. Verruciform xanthoma occurring within oral lichen planus. J Oral Pathol Med 1996; 25:188.
  45. Harris L, Staines K, Pring M. Oral verruciform xanthoma. BMJ Case Rep 2015; 2015.
  46. Gong HZ, Zheng HY, Li J. Xanthoma disseminatum. Lancet 2018; 391:251.
  47. Yamamoto A, Matsuzawa Y, Yokoyama S, et al. Effects of probucol on xanthomata regression in familial hypercholesterolemia. Am J Cardiol 1986; 57:29H.
  48. Fujita M, Shirai K. A comparative study of the therapeutic effect of probucol and pravastatin on xanthelasma. J Dermatol 1996; 23:598.
  49. Inazu A, Koizumi J, Kajinami K, et al. Opposite effects on serum cholesteryl ester transfer protein levels between long-term treatments with pravastatin and probucol in patients with primary hypercholesterolemia and xanthoma. Atherosclerosis 1999; 145:405.
  50. Lee HY, Jin US, Minn KW, Park YO. Outcomes of surgical management of xanthelasma palpebrarum. Arch Plast Surg 2013; 40:380.
  51. Mourad B, Elgarhy LH, Ellakkawy HA, Elmahdy N. Assessment of efficacy and tolerability of different concentrations of trichloroacetic acid vs. carbon dioxide laser in treatment of xanthelasma palpebrarum. J Cosmet Dermatol 2015; 14:209.
  52. Esmat SM, Elramly AZ, Abdel Halim DM, et al. Fractional CO2 laser is an effective therapeutic modality for xanthelasma palpebrarum: a randomized clinical trial. Dermatol Surg 2014; 40:1349.
  53. Güngör S, Canat D, Gökdemir G. Erbium: YAG laser ablation versus 70% trichloroacetıc acid application in the treatment of xanthelasma palpebrarum. J Dermatolog Treat 2014; 25:290.
  54. Labandeira J, Vázquez-Osorio I, Figueroa-Silva O, et al. Tolerability and effectiveness of liquid nitrogen spray cryotherapy with very short freeze times in the treatment of xanthelasma palpebrarum. Dermatol Ther 2015; 28:346.
  55. Heng JK, Chua SH, Goh CL, et al. Treatment of xanthelasma palpebrarum with a 1064-nm, Q-switched Nd:YAG laser. J Am Acad Dermatol 2017; 77:728.
  56. Lin X, Hu H, Qian Y, et al. Intralesional injection of bleomycin in the treatment of xanthelasma palpebrarum: A clinical study. J Cosmet Dermatol 2020; 19:2125.
  57. Tuan H, Chen Y, Yang S, et al. A Comparison of Efficacy and Safety of Fractional Carbon Dioxide Laser and Fractional Er:YAG Laser for the Treatment of Xanthelasma Palpebrarum: A Two-Center Randomized Split-Face Controlled Trial. Photobiomodul Photomed Laser Surg 2021; 39:131.
  58. Guo Y, Dang Y, Toyohara JP, Geng S. Successful treatment of verruciform xanthoma with imiquimod. J Am Acad Dermatol 2013; 69:e184.
  59. Connolly SB, Lewis EJ, Lindholm JS, et al. Management of cutaneous verruciform xanthoma. J Am Acad Dermatol 2000; 42:343.
  60. Mohsin SK, Lee MW, Amin MB, et al. Cutaneous verruciform xanthoma: a report of five cases investigating the etiology and nature of xanthomatous cells. Am J Surg Pathol 1998; 22:479.
  61. Joo J, Fung MA, Jagdeo J. Successful treatment of scrotal verruciform xanthoma with shave debulking and fractionated carbon dioxide laser therapy. Dermatol Surg 2014; 40:214.
  62. Esmat S, Abdel-Halim MR, Fawzy MM, et al. Are normolipidaemic patients with xanthelasma prone to atherosclerosis? Clin Exp Dermatol 2015; 40:373.
Topic 13786 Version 10.0

References