Hyperlipoproteinemia type III

Xanthomas are associated with a variety of systemic diseases and genetic disorders (Table 1). These lesions can be classified as tendinous, planar, tuberous or eruptive. Histologically, they are localized infiltrates of lipid-containing histiocytes, usually within the dermis or tendons. [1] Although similar in their histologic composition (primarily foam cells) xanthomas differ in their clinical manifestations.

Tendinous Xanthomas

Tendinous xanthomas (Figure 1) are firm, subcutaneous nodules that arise from tendons, ligaments and fascia. The overlying skin appears normal and can easily be moved over the nodules. These xanthomas frequently occur in extensor tendons of the hands, knees and elbows, and in the Achilles tendons. [1-3] Small lesions may not be visible and may be detected only by palpation.

Tendinous xanthomas usually develop in patients with elevated cholesterol levels. The most common cause of tendinous xanthomas is familial hypercholesterolemia, an autosomal dominant trait with a heterozygous incidence in the general population of one case in 500. [2-5] Patients with this disorder develop premature coronary artery disease. In the homozygous form of familial hypercholesterolemia, atherosclerotic manifestations are seen much earlier, with myocardial infarction reported as early as age 18 months [4] and life expectancy rarely beyond the third decade. [5]

Tendinous xanthomas can also be seen in patients with normal serum cholesterol levels and other, less common genetic disorders. These rare conditions are listed in Table 1.

Because therapy for tendinous xanthomas depends on the underlying disorder, a thorough physical examination, family history and serum lipid evaluation are essential in the initial assessment. Tendinous

[TABULAR DATA OMITTED]

xanthomas may resolve slowly over years and rarely cause problems, although tenosynovitis and mechanical instability have been reported and treated surgically. [2]

Planar Xanthomas

Planar xanthomas, the most common type of xanthoma, may appear clinically as xanthelasmas, intertriginous xanthomas, palmar crease xanthomas or diffuse planar xanthomas.

XANTHELASMAS

Xanthelasmas are the most common type of planar xanthoma, typicaly occurring on or around the eyelids (Figure 2). About one-half of patients have associated hypercholesterolemia; the incidence is greater in patients who develop xanthelasmas at age 40 to 50 years. [1] A family history of lipid disorders or atherosclerosis should be sought. On physical examination, the clinician should look for other xanthomas; serum lipid determinations are important.

Xanthelasmas may be cosmetically unacceptable to some patients. Topical applications of 35 percent trichloroacetic acid solution may be effective. [6] Repeat applications (three to four times over several weeks) may be necessary for optimal results.

INTERTRIGINOUS XANTHOMAS

Intertriginous xanthomas appear as raised yellow plaques, often having a coblestone-like surface. They tend to occur in the interdigital web spaces (Figure 3), but may also be seen in other pressure points or at sites of trauma. [4,5] Intertriginous xanthomas are pathognomonic for homozygous familial hypercholesterolemia, a rare disorder affecting only one in 1 million persons. [1-4]

PALMAR CREASE XANTHOMAS

These planar xanthomas have the appearance of a macular yellow-orange discoloration of the palmar and finger creases (Figure 4) and can easily be missed. They are found frequently in patients with type III familial hyperlipoproteinemia and occur only rarely in other forms of hyperlipoproteinemia. [7]

DIFFUSE PLANAR XANTHOMAS

This yellow-orange xanthoma (Figure 5) usually involves the face, neck and upper truncual areas. It is associated with dysglobulinemias, paraproteinemias and other disease states (Table 1). Because the type of xanthoma may precede the associated diseases by several years, patients with these lesions should be carefully evaluated and followed. [1,2,8-10]

Tuberous Xanthomas

Tuberoeruptive xanthomas begin as small, soft papules that become yellow-red nodules. These may coalesce to become larger, firmer lesions involving the subcutaneous tissue. The larger, non-inflammatory nodular lesions are referred to as tuberous xanthomas (Figure 6).

Tuberous and tuberoeruptive xanthomas most commonly develop as extensor surfaces, such as the elbows, knees and knuckles, and on the buttocks. They occur frequently in patients with type III familial hyperlipoproteinemia. These patients have elevated cholesterol and triglyceride levels and are at increased risk for premature atherosclerosis, which is seen charasterically in the peripheral vasculature. [2,7]

Treatment of the underlying disorder usually produces resolution of the lesions over a period of months. Surgery is reserved for large, refractory lesions.

Eruptive Xanthomas

Eruptive xanthomas appear suddenly in crops of capsules, 1 to 4 mm in size most commonly as extensor surfaces of the hands, arms and knees (Figure 7) and the buttocks. They may also appear on pressure points and trauma areas (Koebner's phenomenon). [10-12] In their acute state, eruptive xanthomas may be inflamed, pruritic and tender, with an erythematous base. These xanthomas develop almost exclusively in the presence of hypertriglyceridemia; the triglyceride level is often in the range of 2,000 mg per dL (22.58 mmol per L). Most commonly, the underlying cause is uncontrolled diabetes mellitus, alcohol ingestion or exogenous estrogen therapy in conjunction with a genetic predisposition to hypertriglyceridemia. [4]

Because of the magnitude of the triglyceride elevation, eruptive xanthomas may be seen along with other signs and symptoms of hyperlipidemia. Other manifestations of the chylomicronemic syndrome include abdominal pain, acute pancreatitis, lipemia retinalis, paresthesias, hepatomegaly and splenomegaly. [3] The presence of milky plasma (Figure 8) is noteworthy.

Eruptive xanthomas resolve over several weeks if serum triglyceride levels decrease.

RICHARD P. VINSON, CPT, MC, USA is currently on staff at the 543rd General Dispensary, Camp Walker, Korea. After graduating from Louisiana State University School of Medicine, New Orleans, Dr. Vinson completed a residency in family practice at Martin Army Hospital, Fort Benning, Ga.

ALLAN C. HARRINGTON, MAJ, MC, USA is completing a Mohs cutaneous and micrographic surgery fellowship at New England Medical Center, Boston. Dr. Harrington graduated from Dartmouth School of Medicine Hanover, N.H., and completed a residency in determatology at Fitzsimmons Army Medical Center, Aurora, Colo.

REFERENCES

[1] Parker F. Xanthomas and hyperlipidemias. J Am Acad Dermatol 1985;13:1-30.

[2] Cruz PD Jr, East C, Bergstresser PR. Dermal, subcutaneous, and tendon xanthomas: diagnostic markers for specific lipoprotein disorders. J Am Cad Dermatol 1988;19(1 Pt 1): 95-111.

[3] Brunzell SD. The hyperlipoproteinemias. In: Wyngaarden JB, Smith LH Jr, eds. Cecil Textbook of medicine. 17th ed. Philadelphia: Saunders, 1985:1109-16.

[4] Brown MS, Goldstein JL. The hyperlipoproteinemias and other disorders of lipie metabolism. In: Braunwald E, ed. Harrison's Principles of internal medicine. 11th ed. New York: Mc raw-Hill, 1987:1651-61.

[5] Brewer HB Jr, Frederickson DS. Dyslipoproteinemias and xanthomatosis. In: Fitzpatrick TB, ed. Dermatology in general medicine: textbook and atlas. 3d ed. New York: McGraw-Hill, 1987:1722-38.

[6] Fitzpatrick TB, Polano MK, Suurmond D. Color atlas and synopsis of clinical dermatology. New York: McGraw-Hill, 1983:150-1.

[7] Morganroth J, Levy RI, Frederickson DS. The biochemical, clinical, and genetic features of type III hyperlipoproteinemia. Ann Intern Med 1975;82:158-74.

[8] Lynch PJ, Winkelmann RK. Generalized plane xanthoma and systemic disease. Arch Dermatol 1966;93:639-46.

[9] Feiwel M. Xanthomatosis in cryoglobulinaemia and other paraproteinemias with report of a case. Br J Dermatol 1968;80:719-29.

[10] Parker F. Normocholesterolemic xanthomasis. Arch Dermatol 1986;122:1253-7.

[11] Goldstein GD. The Koebner response with eruptive xanthomas [Letter]. J Am Acad Dermatol 1984;10:1064-5.

[12] Roederer G, Xhignesse M, Davignon J. Eruptive and tubero-eruptive xanthomas of the skin arising on sites of prior injury. Two case reports. JAMA 1988;260:1282-3 [Published erratum appears in JAMA 1989;261:1280].

COPYRIGHT 1991 American Academy of Family Physicians
COPYRIGHT 2004 Gale Group