Cutaneous Xanthoma Lesions

Cutaneous xanthomas are dermal accumulations of lipid-laden macrophages (foam cells) producing distinctive yellow to orange papules, plaques, or nodules. They reflect either primary genetic dyslipidemia (familial hypercholesterolemia, familial dysbetalipoproteinemia/type III, familial chylomicronemia, sitosterolemia, cerebrotendinous xanthomatosis) or secondary disorders of lipid metabolism (uncontrolled diabetes, hypothyroidism, cholestatic liver disease, nephrotic syndrome, monoclonal gammopathy, retinoid or HIV protease inhibitor therapy).

Subtypes are recognized by morphology and location: eruptive xanthomas (small yellow papules on buttocks, shoulders, extensors with severe hypertriglyceridemia >1000 mg/dL); tuberous xanthomas (firm yellow nodules on extensor surfaces, elbows, knees, with familial hypercholesterolemia or type III); tendinous xanthomas (Achilles, extensor tendons of hands, with familial hypercholesterolemia); planar xanthomas (palmar/striate in type III dysbetalipoproteinemia, intertriginous in homozygous familial hypercholesterolemia); xanthelasma palpebrarum (eyelid plaques, often normolipidemic but warrant lipid screening); and verruciform xanthoma (oral mucosa, usually nonlipid-related).

Diagnosis is clinical with confirmatory lipid panel (total cholesterol, LDL, HDL, triglycerides, apolipoprotein B, lipoprotein(a)), thyroid function, glucose, liver function, and serum protein electrophoresis when relevant. Genetic testing is considered for premature/heterozygous presentations. Histopathology shows lipid-laden macrophages within the dermis. Management focuses on treating the underlying dyslipidemia: statins, ezetimibe, PCSK9 inhibitors, fibrates for hypertriglyceridemia, lifestyle modification, and treatment of secondary causes; cosmetic removal can be performed for xanthelasma after lipid optimization.