Type III hyperlipoproteinemia with xanthomas and multiple myeloma

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Background

Type III hyperlipoproteinemia usually results from an inherited defect in the composition of apolipoprotein E and is associated with atherosclerosis. An acquired form of the type III phenotype may rarely be associated with myeloma and immunoglobulin-lipoprotein complexes.

Observation

We present the case of a 72-year-old man with a history of well-controlled, unclassified hypercholesterolemia and hypertriglyceridemia, without evidence of atherosclerotic disease. He subsequently developed refractory dyslipidemia, palmar crease, and tuberous xanthomas. Type III hyperlipoproteinemia was confirmed, and nonclassic defective apolipoprotein E. Common secondary causes of hyperlipidemia were ruled out. A workup for malignancy revealed monoclonal IgA gammopathy. Immunostaining confirmed IgA antibodies complexed to the patient's very low-density lipoprotein (VLDL) fraction, causing gross impairment of VLDL metabolism. Conventional therapy for type III hyperlipoproteinemia was attempted but ineffective. Thus, chemotherapy was initiated for his myeloma, with subsequent lowering of his IgA, cholesterol, and triglyceride levels, and improvement of his xanthomas.

Conclusion

There are several unusual features to this case. Planar xanthomas can be associated with myelomas, but usually in the setting of normal lipids. Type III hyperlipoproteinemias are not usually refractory to standard therapy and are only rarely associated with IgA myeloma. IgA antibodies complexed to the patient's VLDL caused gross impairment of VLDL metabolism. The patient's apolipoprotein E genotype (heterozygote E2/E3) is not typical for expression of the heritable type III phenotype (homozygote E2/E2). These features support a causal relationship between this patient's multiple myeloma and type III hyperlipoproteinemia rather than two independent, coexistent conditions.

Section snippets

Case report

A 72-year-old Caucasian man with a history of unclassified hypercholesterolemia and hypertriglyceridemia, which had been well controlled on simvastatin (20 mg/d), subsequently developed a refractory dyslipidemia. Baseline total cholesterol and triglyceride levels during the past 3 years had been in the range of 155 to 209 mg/dL and 164 to 223 mg/dL, respectively. Total cholesterol levels increased ranging from 394 to 499 mg/dL and triglyceride levels increased ranging from 569 to 893 mg/dL

Discussion

There are several unusual features to this case. First, myelomas can be associated with planar xanthomas, but usually in the setting of normal lipids.2, 3, 4, 5, 6, 7 Although the patient was given the diagnosis of paraproteinemia, he also had evidence of both tuberous and palmar crease xanthomas, pathogonomic of type III hyperlipoproteinemia. Second, type III hyperlipoproteinemias are only rarely associated with myeloma.8, 9, 10, 11, 12, 13, 14, 15, 16 Third, type III hyperlipoproteinemias are

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    Supported by Stiefel Laboratories.

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    Conflicts of interest: None identified.

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