Xanthoma and xanthelasma — Viva

Q1: Definition and clinical presentation (2 min)

What is a xanthoma, and how are the clinical types classified? Describe the morphology and site of xanthelasma, tendinous, tuberous, eruptive and plane xanthoma, and explain why each type reflects a specific lipoprotein disorder.

Expected: a deposit of lipid-laden macrophages (foam cells) classified by site and morphology; xanthelasma on eyelids (mixed, half normolipidaemic), tendinous on Achilles/extensor tendons (LDL, FH), tuberous on elbows/knees (LDL), eruptive crops on buttocks/thighs (triglyceride-rich, types IV/V), plane palmar = type III, diffuse plane = paraproteinaemia. Cite foam cells and Touton giant cells.

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Q2: Pathophysiology and histology (2 min)

Describe the mechanism of foam cell formation. Why do macrophages accumulate lipid, and how does the lipoprotein species dictate the morphology and tempo of the lesion?

Expected: lipoproteins extravasate through dermal/tendinous capillaries and are taken up by macrophages via non-feedback-regulated scavenger receptors (SR-A, CD36), becoming foam cells; Touton giant cells in tuberous/tendinous types; LDL accumulates slowly (indolent nodules) while chylomicrons flood the dermis rapidly (eruptive crops). Diffuse plane involves Ig-lipoprotein complexing.

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Q3: Differential diagnosis (3 min)

What conditions enter the differential for a nodule on the Achilles tendon, and how would you distinguish each from a tendinous xanthoma? Name two syndromic xanthomatoses and how their management differs from ordinary FH.

Expected: rheumatoid nodule, gouty tophus, ganglion, fibroma, sarcoidosis, granuloma annulare — distinguished by lipid profile, crystal analysis, distribution and histology. Syndromic: cerebrotendinous xanthomatosis (cholestanol, treated with chenodeoxycholic acid) and sitosterolaemia (ABCG5/8, plant sterols, treated with ezetimibe and a low-plant-sterol diet).

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Q4: Investigations (2 min)

What investigations are mandatory in every patient with a xanthoma, and what targeted tests would you arrange for suspected FH, type III, diffuse plane xanthomatosis, and eruptive xanthoma with abdominal pain?

Expected: fasting lipid panel, glucose/HbA1c, TSH, U&E, LFTs, urinalysis in all. FH: DLCNC/Simon Broome criteria, genetic testing (LDLR/APOB/PCSK9), Lp(a). Type III: APOE genotyping (E2/E2), lipoprotein electrophoresis. Diffuse plane: SPEP, free light chains, Bence-Jones, calcium, renal function. Eruptive: amylase, lipase, triglyceride.

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Q5: Management (3 min)

Outline your stepwise management for a patient with heterozygous familial hypercholesterolaemia and tendon xanthomas, and for severe hypertriglyceridaemia with eruptive xanthoma. What cosmetic options exist for xanthelasma, and what is the recurrence rate?

Expected: FH — high-intensity statin (atorvastatin 80 mg) plus ezetimibe, add PCSK9 inhibitor if not at goal, and cascade screening of relatives; homozygous FH adds lomitapide, LDL apheresis, liver transplant. Hypertriglyceridaemia — fibrate plus omega-3, trigger removal, glycaemic and alcohol control; eruptive + pancreatitis is an emergency (NPO, fluids, insulin infusion, consider apheresis). Xanthelasma cosmetic: excision, laser (CO2/Er:YAG), or TCA 50 to 80 per cent; recurrence approximately 40 per cent.

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Q6: Complications and prognosis (2 min)

What are the main complications, and what determines prognosis? Name the four classic pitfalls in managing xanthoma patients.

Expected: atherosclerotic CVD and pancreatitis are the dominant complications; prognosis is driven by the underlying metabolic disease, not the skin lesion. Pitfalls: treating the cosmetic lesion without investigating lipids; failing to cascade-screen FH relatives; missing the paraproteinaemia in diffuse plane xanthoma; and missing pancreatitis behind eruptive xanthoma.^[1][2][5]

References5ShowHide

1. [1]Shrestha A, Bam PK, Pandit A, et al. Eruptive xanthoma as a warning sign of uncontrolled hypertriglyceridemia presenting with acute pancreatitis and uncontrolled type II diabetes mellitus: A case report Clin Case Rep, 2024.PMID 38799544
2. [2]Cota C, Pellacani G, Lora V, et al. Diffuse (Generalized) Plane Xanthoma Misdiagnosed as Carotenoderma: Usefulness of Reflectance Confocal Microscopy Am J Dermatopathol, 2020.PMID 32732688
3. [3]Patni N, Wilson DP Cerebrotendinous Xanthomatosis 2000.PMID 27809439
4. [4]Cota C, Pellacani G, Lora V, et al. Diffuse (Generalized) Plane Xanthoma Misdiagnosed as Carotenoderma: Usefulness of Reflectance Confocal Microscopy Am J Dermatopathol, 2020.PMID 32732688
5. [5]Tada H, Nohara A, Kawashiri MA, et al. Impact of Achilles tendon on diagnosis and phenotypes of familial hypercholesterolemia Curr Opin Lipidol, 2025.PMID 40277332