Xanthoma (Xanthelasma)

Xanthoma is a dermatological condition characterized by the deposition of lipids within macrophages in the skin, and in some cases, the subcutaneous layer. It often serves as a visible marker of underlying disorders of lipid metabolism, known as dyslipidaemias, though it may also occur in certain histiocytic disorders. While xanthomas most frequently appear in adults, children with familial hypercholesterolaemia can also present with these lesions. The prevalence across age, sex, and ethnic groups depends largely on the associated underlying condition.

Dyslipidaemias associated with xanthomas are broadly categorized as primary or secondary. Primary dyslipidaemias include inherited disorders such as familial hypercholesterolaemia, combined dyslipidaemia, hypertriglyceridaemia, cerebrotendinous xanthomatosis, and sitosterolaemia. Secondary dyslipidaemias can develop as a consequence of conditions like obesity, diabetes mellitus, insulin resistance, cholestatic liver diseases such as primary biliary cirrhosis, or nephrotic syndrome, as well as from certain medications including oestrogens, tamoxifen, oral retinoids, prednisolone, and ciclosporin. Rare variants such as diffuse plane xanthomatosis have been linked to paraproteinaemia, while xanthoma disseminatum is a rare form related to histiocytosis.

The clinical manifestations of xanthomas are diverse, with subtypes defined by their morphology and location. Xanthelasma, the most common form, presents as soft yellow or yellow-orange macules or plaques typically located symmetrically on the upper and lower eyelids, particularly near the medial canthus. These lesions may develop gradually and are often associated with lipid disorders, though they can occur in individuals with normal serum lipid levels. Other plane xanthomas are flat yellow patches that can develop anywhere on the body; their appearance in the web spaces of fingers and toes is particularly indicative of homozygous familial hypercholesterolaemia. Palmar xanthomas, recognized by yellow-orange pigmentation in palmar creases, are diagnostic of Type III hyperlipoproteinaemia. Tuberous xanthomas form firm, painless nodules over pressure points like the knees, elbows, and heels, sometimes merging into large multilobulated masses. Tendon xanthomas, often found over the Achilles tendon or finger joints, are firm, mobile subcutaneous nodules associated primarily with familial hypercholesterolaemia. Eruptive xanthomas manifest as crops of small yellow papules with erythematous halos, frequently linked to severe hypertriglyceridaemia, while verruciform xanthomas are rare, wart-like lesions typically unrelated to lipid disorders and often found on oral or genital mucosa.

The significance of diagnosing xanthomas extends beyond cosmetic concerns, as these lesions often signal systemic metabolic disturbances with potential complications such as cardiovascular disease or pancreatitis. Xanthelasma itself is considered an independent risk factor for ischemic heart disease. Diagnosis is typically clinical, supported by a lipid profile and other relevant laboratory investigations such as liver, renal, and thyroid function tests, fasting glucose, and in certain cases, serum and urine protein electrophoresis. A skin biopsy may be performed, revealing lipid-filled macrophages in the dermis.

Treatment focuses primarily on addressing the underlying lipid disorder, which can result in the resolution of some xanthomas, including tuberous, eruptive, plane, and palmar lesions. Cosmetic removal may be pursued for persistent or bothersome lesions, using techniques such as topical trichloroacetic acid application, electrodessication, cryotherapy, laser ablation, or surgical excision. Verruciform xanthomas are typically managed surgically and rarely recur. The overall prognosis depends on the successful management of the underlying condition, underscoring the importance of early detection and intervention.