Our patient had xanthelasma, or xanthelasma palpebrarum, oval or elongated yellowish plaques just beneath the periorbital skin. The plaques occur most commonly near the inner canthus of the eyelid, more often on the upper lid than the lower lid. Frequently, the lesions are symmetrical; often all four lids are involved. On palpation, xanthelasma may have a soft, semisolid, or calcified texture. The lesions are neither inflammatory nor painful, and there is no tendency toward malignancy. Xanthelasma plaques have a tendency to progress, coalesce, and become permanent.
Histologically, xanthelasma lesions reveal accumulations of lipid-laden macrophages, termed “histiocytes” and/or “xanthoma cells.” These foamy histiocytes reside primarily within the upper reticular dermis. The main lipid stored in both hyperlipidemic and normolipidemic xanthelasmas is cholesterol, most of which is esterified.
Our patient related an episode of allergic dermatitis with the onset of her xanthelasma. Although no precipitating factor is normally associated with this condition, xanthelasma has been reported following erythroderma and inflammatory skin disorders. For example, two prominent British dermatologists reported the condition in a patient following severe facial allergic contact dermatitis from p-phenylenediamine in a black eyelash-tinting product.1 The mechanism by which macrophage accumulation, cholesterol uptake, and foam-cell formation would occur following an inflammatory condition is not understood; however, it has been suggested that increased plasma lipid peroxidation, derived from oxidized low-density lipoprotein, may lead to accumulation of cholesterol in macrophages and formation of foam cells.1
Xanthelasma lesions are the most common type of cutaneous xanthoma. Prevalence, which increases with age, is estimated to be 1.1% in women and 0.3% in men. In most cases, no other xanthomas of any type are found anywhere else on the body.
Approximately one half of patients with xanthelasma have elevated plasma lipid levels. Some affected individuals may have type II hyperlipidemia. Others may have primary genetic disease, such as familial dyslipoproteinemia, familial hypertriglyceridemia, and familial lipoprotein lipase deficiency. Two common causes of secondary hyperlipidemia are diabetes and cirrhosis. As a rule of thumb, patients with xanthelasma in the absence of a family history of the disorder are more likely to have elevated serum cholesterol and atherosclerotic disease.
The other 50% of xanthelasma patients are normolipidemic, although they may demonstrate some minor alteration in lipoproteins, such as abnormal distribution of apolipoprotein (apo) E phenotypes, excessive production of apo B, decreased levels of HDL cholesterol, and/or a decrease in the ratio of HDL-to-LDL cholesterol.
Patients with xanthelasma are typically in their fourth or fifth decade of life, but age at onset can range from 15 to 75 years. Of note, younger individuals with xanthelasma have a proportionally greater likelihood of hyperlipidemia and hypercholesterolemia than their older counterparts.
Most patients with xanthelasma are asymptomatic, and their complaints generally concern esthetics. Rarely, abnormally large xanthelasmas can affect eyelid function, causing ptosis or lagophthlamos.
Xanthelasma is usually an obvious clinical diagnosis, but other lesions can simulate its appearance and may be associated with disorders of a more serious nature. If there is any doubt, surgical excision and pathologic analysis should be performed. A differential diagnosis of xanthelasma could include: necrobiotic xanthogranuloma, tuberous xanthomata, diffuse planar xanthoma, orbital lipogranulomata, juvenile xanthogranulomata, Wegener granulomatosis, lipoid proteinosis, primary systemic amyloidosis, necrobiosis lipoidica, sarcoid, and atypical lymphoid infiltrate
In terms of medical workup, a serum lipid profile is recommended, including LDL and HDL cholesterol levels. Because other metabolic disorders, particularly diabetes and cirrhosis of the liver, can lead to increased serum lipids, determinations of fasting plasma glucose and liver function tests should also be considered.
Recently, ultrasonographic measurement of intima-media thickness has revealed premature carotid atherosclerosis in patients with normolipidemic and hyperlipidemic xanthelasma.2 These findings suggest that patients with xanthelasma should be considered to have an increased risk of cardiovascular disease independent of their plasma lipid levels.2
Another report did not concur that normolipidemia with xanthelasma had a significant association with carotid atherosclerosis, but this group of patients did demonstrate some adverse cardiovascular profiles, namely higher BMI, waist circumference, and LDL cholesterol.3 Dietary restriction and pharmacologic reduction of serum lipids, although important in the overall care of a patient with abnormal lipids, show only limited response in cases of xanthelasma.
Treatment of xanthelasma is primarily for cosmetic reasons. Numerous options are available for the removal of xanthelasma palpebrarum, including surgical excision, argon or carbon dioxide laser ablation, chemical cauterization (i.e., trichloroacetic acid peel), electrodesiccation, and cryotherapy. Surgical treatments can potentially cause scarring, irritation of the conjunctiva, and cutaneous pigment changes. No single technique has emerged as the most effective. Moreover, recurrence rates of about 40% are common regardless of removal method. Of these failures, 25% of cases recurred within the first year; recurrences were more likely in patients with hyperlipidemia syndromes and in those whose xanthelasma involved all four eyelids.
Our patient’s blood lipids revealed cholesterol and triglyceride levels within normal limits. Because of the present
confusion as to whether normolipidemic patients with xanthelasma have an increased risk of carotid atherosclerosis, I wrote to her primary-care clinician regarding the patient’s possible need for cardiac workup. In terms of treatment, the patient did not want chemical removal, but she was interested in obtaining more information on laser therapy. I provided her with the names of two clinicians who had a Q-switched neodymium:yttrium-aluminum-garnet laser and an argon laser, respectively.
Dr. Burkhart is clinical professor of dermatology at the University of Toledo College of Medicine in Ohio and clinical assistant professor of dermatology at Ohio University College of Osteopathic Medicine in Athens.
1. Bhat J, Smith AG. Xanthelasma palpebrarum following allergic contact dermatitis from para-phenylenediamine in a black eyelash-tinting product. Contact Dermatits. 2003;49:311.
2. Noël B. Premature atherosclerosis in patients with xanthelasma. J Eur Acad Dermatol Venereol. 2007;21:1244-1248.
3. Chan CC, Lin SJ, Hwang JJ, et al. Xanthelasma is not associated with increased risk of carotid atherosclerosis in normolipidaemia. Int J Clin Pract. 2008;62:221-227.