Xanthomas Clinical Presentation

Updated: Jun 09, 2021
  • Author: Kara Melissa Torres Culala, MD; Chief Editor: Dirk M Elston, MD  more...
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Usually patients seek consult from specialists because of the clinically visible lesions, and then they would undergo further workup and discover they have underlying metabolic conditions.

A family history of xanthomas, history of myocardial infarction, aortic regurgitation, atherosclerosis, and even pancreatitis may be encountered in patients with cutaneous xanthomas. [21, 22, 23, 24] Normolipemic forms of tuberous xanthomas and drug-induced tuberous and tendinous xanthomas are uncommon but may occur. [25, 26, 27] Large solitary planar xanthomas may rarely be associated with chronic myelomonocytic leukemia, non–Langerhans cell disease, mastocytoma, and ultraviolet irradiation exposure. [28, 29, 30, 31] Rarely, xanthomas may be associated with the POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein skin changes) syndrome, systemic sarcoidosis, and nonsyndromic paucity of interlobular bile ducts. [32, 33, 34] Cutaneous manifestations may also precede a diagnosis of hyperlipidemia, which may be primary or secondary. If diagnosed in children with pruritus as a symptom, clinicians should investigate the possibility of cholestasis of the liver. [35]

Patients with xanthoma disseminatum may present with symptoms of dysphagia, dyspnea, and obstructive blindness, depending on the involved site. [36, 37, 38] There may be rare gastrointestinal, central nervous system, musculoskeletal, and intracranial involvement. [39, 40, 41, 42] Exceptional cases are those forms that are multisystemic yet asymptomatic and those associated with the Koebner phenomenon. [43, 44] The disease may be persistent and progressive, or it may be self-limited with spontaneous resolution. [45, 20] Diffuse plane xanthomatosis is most commonly associated with lymphoproliferative disorders, monoclonal gammopathies, and hematological malignancies. [46, 47] Xanthoma disseminatum without any underlying abnormality is rare but may occur. [48] It may be infrequently linked with mycosis fungoides, Budd-Chiari syndrome, Hand-Schüller-Christian disease, or rheumatoid arthritis. [49, 50, 51, 52]

Verruciform xanthoma may be associated with lichen planus, Paget disease, epidermal nevus, discoid lupus erythematosus (DLE), pemphigus vulgaris, recessive dystrophic epidermolysis bullosa (RDEB), chronic graft versus host disease (GVHD), actinic keratosis, squamous cell carcinoma, CHILD (congenital hemidysplasia with ichthyosiform nevus and limb defects (CHILD) syndrome, post psoralen with ultraviolet A (PUVA) phototherapy, post radiation therapy, chronic lymphedema, and post hematopoietic stem cell transplantation (HSCT). [53, 10, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64] Rarely, they may occur without an underlying disease or syndrome. [65]

Patients with cerebrotendinous xanthomas may present with bilateral cataracts and chronic diarrhea during childhood.


Physical Examination

Cutaneous xanthomas associated with hyperlipidemia can be clinically subdivided into xanthelasma palpebrarum, tuberous xanthoma, tendinous xanthoma, eruptive xanthoma, planar xanthoma, and generalized plane xanthoma. A combination of the different types may occur. [66] A rare “cauliflower xanthoma” type may also be seen. [67] Cutaneous xanthomas may also raise the suggestion of the presence of cerebrotendinous xanthomatosis. [68]

Xanthelasma palpebrarum is the most common type of xanthoma. The lesions are asymptomatic and symmetric soft, velvety, yellow, flat, polygonal papules. They occur most commonly in the upper eyelids near the inner canthus. Giant xanthelasma palpebrarum may demonstrate extensive involvement of all four eyelids. [69] See the image below.

Xanthelasma. Courtesy of Duke University Medical C Xanthelasma. Courtesy of Duke University Medical Center.

Tuberous xanthomas are firm, painless, red-yellow nodules. The lesions can coalesce to form multilobulated tumors and can be extensive. [70] Tuberous xanthomas usually develop in pressure areas, such as the extensor surfaces of the knees, the elbows, and the buttocks. They may rarely occur on the cheeks and nasal bridge. [71] See the image below.

Tuberous xanthomas. Courtesy of Duke University Me Tuberous xanthomas. Courtesy of Duke University Medical Center.

Tendinous xanthomas appear as slowly enlarging subcutaneous nodules related to the tendons or the ligaments. Atypical gout-tophi–like lesions over the great toe may occur. [72] The most common locations are the extensor tendons of the hands, the feet, and the Achilles tendons. The lesions are often related to trauma.

The lesions of eruptive xanthomas typically erupt as crops of small, red-yellow papules on an erythematous base in a period of several weeks. Pruritus is common, and the lesions may be tender. Eruptive xanthomas most commonly arise over the buttocks, shoulders, and extensor surfaces of the extremities. Rarely, the oral mucosa or the face may be affected. Koebner phenomenon has been described. Spontaneous resolution may occur, but recurrence is common. See the image below.

Eruptive xanthomas. Courtesy of Duke University Me Eruptive xanthomas. Courtesy of Duke University Medical Center.

Plane xanthomas are mostly yellowish macules; less frequently, they are thin plaques. They can occur in any site. Involvement of the palmar creases is characteristic of type III dysbetalipoproteinemia. Patients with diffuse-plane xanthomatosis have yellow, symmetric, plaque lesions over periorbital areas, neck, upper trunk, buttocks, and flexures. Unusual forms may present as oral lesions. [51, 73]

Xanthoma disseminatum and verruciform xanthoma are particular forms of xanthomas that occur in normolipemic patients. [74, 75]

Xanthoma disseminatum presents in adults most commonly as red-yellow papules and nodules with a predilection for the flexures. Lesions may also occur over the face, trunk, proximal extremities, and, unusually, extensive eyelid involvement. [38, 16] It may rarely present as large plaques with indurated borders and as plaques with surrounding papules. [76] The mucosa is involved 40-60% of the time. [36]

Verruciform xanthoma predominantly occurs in the gingiva of adults as a solitary and an asymptomatic papillomatous yellow lesion. Extra-oral manifestation is rare but cases have been reported with localization at the sole, forearm, digits of hand and foot, anogenital area, and esophagus. [53, 65, 77, 78, 79, 80, 81] In 2021, a verruciform xanthoma over the ventral aspect of the tongue was also reported. [82]



Abnormalities in the lipid profile constitute the complications in untreated cases.

In xanthoma disseminatum, complications may arise from involvement of the upper respiratory tract (difficulty of breathing), conjunctiva and cornea (blindness), and meninges with infiltration to the hypothalamus and pituitary gland (diabetes insipidus).

Complications from associated lymphoproliferative diseases may occur in diffuse normolipemic plane xanthomas; thyroid dysfunctions in some xanthelasmas [83] ; and neurologic, cardiovascular, and skeletal abnormalities in cerebrotendinous xanthoma. [13]