bubble_chart Overview

Xanthoma is a lipid deposition disease characterized by prominent skin lesions. Lipid-laden cells accumulate locally in the dermis and tendons, clinically manifesting as yellow, orange, or brownish-red papules, nodules, or patches. It is often associated with systemic lipid metabolism disorders and damage to the cardiovascular system, and can be either primary or secondary to other systemic diseases.

bubble_chart Etiology

Hyperlipoproteinemia is the primary cause of xanthoma formation, where excessively elevated plasma lipids such as cholesterol, triglycerides, and phospholipids tend to deposit locally in the dermis of the skin. This is observed in various types of primary and secondary hyperlipoproteinemia.

Xanthomas can also occur in individuals with normal plasma lipids, known as normolipoproteinemic xanthoma. In such cases, the condition arises due to abnormal plasma protein disorders or abnormal proliferation of tissue cells, leading to secondary localized deposition of plasma lipids. Examples include patients with multiple myeloma, hypergammaglobulinemia, macroglobulinemia, lymphoma, leukemia, as well as those with primary histiocytic proliferative disorders or Langerhans cell histiocytosis (histiocytosis X). Additionally, xanthomatous lesions may also be seen in patients with hereditary enzyme deficiencies such as glucocerebrosidosis and sphingolipidosis.

bubble_chart Pathological Changes

The histological features of various types of xanthomas are similar. They primarily involve the accumulation of lipid-laden histiocytes (foam cells), also known as xanthoma cells, within the dermis. In the early stages, inflammatory cells are often present, while the regression stage shows fibroblast proliferation. Occasionally, multinucleated giant cells with nuclei arranged in a ring-like pattern (Touton cells) can be observed. Frozen sections stained with scarlet red or Sudan red can reveal the presence of cholesterol and cholesterol esters within the foam cells.

bubble_chart Clinical Manifestations

According to the morphology and location of xanthomas, the following clinical types are mainly observed.

(1) Plane xanthoma: These are flat papules or patches, slightly elevated above the skin surface, ranging from pale yellow to orange-yellow in color, and vary in size from rice grains to broad beans with clear boundaries. The most common clinical type occurs around the eyelids and is called xanthelasma palpebrarum, frequently seen in middle-aged women. It typically appears on the inner canthus of the upper eyelid, either as a single or multiple lesions, progressing slowly and potentially spreading to both upper and lower eyelids, forming a distinctive yellow ring around the eyelids. If this type of xanthoma appears after the age of 40, lipid abnormalities are often undetectable, whereas in adolescents, it is usually associated with type II hyperlipoproteinemia. Plane xanthomas may rarely present symmetrically and diffusely around the eyelids, neck sides, trunk, and limbs, seen in middle-aged or elderly individuals or patients with various dysproteinemias, termed generalized normolipemic plane xanthoma. Plane xanthomas may also appear linearly along the palmar creases and the palmar surfaces of the fingers, known as striate palmar xanthoma, often associated with type III hyperlipoproteinemia.

(2) Tuberous xanthoma: These are papules or nodules ranging in size from soybeans to walnuts or even eggs, initially soft and pale yellow to orange-yellow, later becoming firm and brownish-red due to fibrosis. They may slowly enlarge and fuse into distinctly elevated, lobulated patches with clear boundaries. They commonly occur on the extensor surfaces of the elbows, knees, finger joints, hips, and buttocks, often associated with types II, III, and IV hyperlipoproteinemia. Tuberous xanthomas may also develop on tendons, ligaments, and fascial membranes, referred to as tendon xanthomas, most commonly seen in the Achilles tendon, presenting as deep, firm nodules. These are frequently observed in patients with severe type II hyperlipoproteinemia or secondary hyperlipoproteinemia.

(3) Eruptive xanthoma: These are multiple soft small papules, ranging from pinhead to matchhead size, initially orange-yellow with a red halo, later turning yellowish-brown. They erupt suddenly in batches on the upper trunk, buttocks, and extensor surfaces of the limbs, and may involve the lips and oral mucosa. They often resolve quickly without leaving traces. Patients usually have type I or V hyperlipoproteinemia, occasionally type III or secondary hyperlipoproteinemia.

(4) Disseminated xanthoma: This is a rare normolipemic, non-familial xanthoma, commonly seen in young males, presenting as multiple small eruptive papules and nodules that transition from orange-yellow to reddish-yellow and then mahogany in color. They cluster without merging and are symmetrically distributed on the neck, armpits, elbow creases, groin, popliteal fossa, and flexural surfaces of the trunk. Approximately one-third of patients have mucosal lesions, which may involve the mouth, tongue, nose, throat, and even the trachea; another one-third may develop hypothalamic-posterior pituitary involvement, leading to diabetes insipidus. The course is chronic but may spontaneously remit.

bubble_chart Auxiliary Examination

The examination items should include serum appearance, lipid measurement, and lipoprotein electrophoresis to identify hyperlipoproteinemia and its type. Sometimes, protein electrophoresis, serum protein, immunoglobulin measurement, cardiovascular system function tests, and histopathological examination of xanthoma are also required.

bubble_chart Diagnosis

The diagnosis is easily made based on the characteristics of the skin lesions, particularly the color and distribution of the lesions. The key lies in determining whether there are accompanying systemic diseases. By considering the type of xanthoma, the age of onset, family history of the disease, as well as relevant symptoms and examinations of various systems, combined with necessary laboratory test results, further judgment can be made regarding the presence of other systemic disorders.

bubble_chart Treatment Measures

After systemic diseases associated with xanthomas are treated and controlled, the xanthomas often gradually regress. For disseminated xanthomas and some eruptive xanthomas, no treatment is necessary as they may resolve spontaneously.

For localized lesions such as xanthelasma palpebrarum and tendon xanthomas, which may affect appearance or function, local treatments are the main approach. These include topical application of 33% trichloroacetic acid, carbon dioxide laser therapy, liquid nitrogen cryotherapy, or surgical excision. Larger nodular xanthomas that require treatment can be surgically removed.