A 34-year-old man with poorly controlled type 2 diabetes mellitus (HbA1c 12.4%) presents with a 3-week eruption of multiple small, firm, yellow-orange papules on extensor surfaces of elbows, knees, and buttocks. Serum triglycerides are 4,800 mg/dL, and skin biopsy confirms eruptive xanthomas with lipid-laden foamy macrophages. He has a history of recent pancreatitis. The management strategy marked **A** in the diagram — fibrates combined with dietary triglyceride control — is the most appropriate long-term approach because it addresses which of the following pathophysiologic mechanisms?
A. Mechanical removal of lipid-laden macrophages through surgical excision and topical keratolytic therapy
B. Activation of PPAR-alpha and induction of lipoprotein lipase, reducing triglycerides by 30–50% while restricting dietary fat intake to <15% of total calories
C. Inhibition of HMG-CoA reductase and direct reduction of VLDL particle secretion from hepatocytes
D. Suppression of apolipoprotein B synthesis and enhancement of LDL receptor expression on hepatic cells
Explanation
Why option 1 is right
Fibrates (fenofibrate, gemfibrozil) are the first-line agents for predominant hypertriglyceridemia in eruptive xanthomas. They work by activating PPAR-alpha, which induces lipoprotein lipase and reduces triglycerides by 30–50% — the mechanism essential for resolving severe hypertriglyceridemia (>1,000 mg/dL) and preventing acute pancreatitis. Combined with dietary fat restriction (<15% of calories), alcohol abstinence, and optimal glycemic control, this approach addresses the root cause of eruptive xanthomas and allows complete resolution of skin lesions within 6–12 weeks of triglyceride normalization, without surgical intervention (AHA/ACC Hypertriglyceridemia Guidelines; Habif Clinical Dermatology, 7th ed.).
Why each distractor is wrong
Option 2: HMG-CoA reductase inhibitors (statins) are appropriate when LDL is also elevated, but they are NOT first-line for predominant hypertriglyceridemia. Statins primarily lower LDL and have modest effects on triglycerides; they are added as adjuncts, not as monotherapy for this presentation.
Option 3: Surgical excision of papules does not address the underlying hypertriglyceridemia and is not indicated. Eruptive xanthomas resolve spontaneously with lipid control; surgical removal is unnecessary and does not prevent pancreatitis risk.
Option 4: Apolipoprotein B synthesis inhibition and LDL receptor upregulation are mechanisms of statins and PCSK9 inhibitors, not fibrates. These are relevant for familial hypercholesterolemia with elevated LDL, not for isolated severe hypertriglyceridemia.
High-YieldNEET PG
Eruptive xanthomas = cutaneous marker of severe hypertriglyceridemia (>1,000 mg/dL) → fibrates first-line → complete resolution with TG normalization, no surgery needed.
