Xanthoma and xanthelasma

Meet the patient

A 34-year-old man with poorly controlled type 2 diabetes arrives with sudden crops of tender yellow papules on his buttocks and thighs and a dull epigastric ache that is beginning to bore through to his back. The skin is dramatic; the pancreas behind it is the danger. The first test is not a biopsy — it is a serum amylase, lipase and a fasting triglyceride.[6]

Two questions decide his next six hours, and they decide every xanthoma case: what lipoprotein is raised? (a fasting lipid panel answers) and what is the lesion hiding? (coronary risk, pancreatitis, or a paraprotein). Hold those two questions and the whole topic slots into place.[1]

A yellow signpost — definition and etymology

A xanthoma (Greek xanthos, yellow) is a focal heap of foam cells — macrophages stuffed with lipid — in the dermis, subcutis or tendon. The colour is the lipid; the cell is the macrophage; the disease is whatever sent the lipid there. Treat the skin as a stained-glass window onto the circulation.[1]

Etymology for viva gold: xanthos is Greek for yellow; elasma comes from elassein, "to beat out flat", describing the plaque-like lid lesion. So xanthelasma is literally a "beaten-flat yellow plaque" — a name that paints the lesion.[1]

The unifying histology across all six types is a dermal infiltrate of foam cells: large macrophages whose lipid is dissolved out during tissue processing, leaving clear, finely vacuolated cytoplasm. Tuberous and tendinous lesions add Touton giant cells — multinucleated giants with a peripheral wreath of nuclei ringed by foamy cytoplasm — a pattern the examiner rewards. What changes between types is where the lipid comes from, how much accumulates, and how fast it appears.[1]

The discipline this imposes at the bedside is absolute: every xanthoma of any type, in any patient, begins with a fasting lipid profile and a search for secondary causes. The lesion is the messenger; the threats are atherosclerotic cardiovascular disease, acute pancreatitis and occult haematological malignancy.[1]

The six types — a face-off table

Six types, six messages: read the site and you can name the lipoprotein before the panel returns. This is the table to memorise — each row a morphology, a site, and the one-line discriminator that wins the stem.[1]

[1]

The classic trap: a xanthelasma with a normal lipid panel is not a closed file. About half of xanthelasma patients are normolipidaemic, yet they still carry a small but real independent cardiovascular signal — subclinical atherogenic dyslipidaemia is common. A normal panel raises the threshold for action; it does not lower it. Always complete a formal cardiovascular risk assessment.[8]

The danger trap: eruptive xanthoma is the one lesion that can kill the patient within hours. Sudden crops plus abdominal pain in a hypertriglyceridaemic — usually diabetic — patient is acute pancreatitis from chylomicronaemia until proven otherwise. Check amylase, lipase and triglycerides now, not tomorrow.[6][7]

Mapping type to lipoprotein — the Fredrickson phenotypes

Pair the lesion with the Fredrickson (WHO) phenotype and you can predict the complication at the bedside. The phenotypes relevant to cutaneous xanthoma are IIa, IIb, III, IV and V; type I (pure chylomicronaemia, lipoprotein lipase deficiency) is rare and causes eruptive lesions and lipaemia retinalis in infancy.[1]

[1]

The examinable pattern: IIa and III give the firm, indolent nodules (tendon and tuberous); IV and V give the explosive eruptive crops; III alone gives the palmar crease sign. Read the lipid panel for which class is raised, name the phenotype, predict the complication — coronary disease for IIa and III, pancreatitis for V.[1]

Three entities sit in the differential but are not classic lipid xanthomas, and naming them shows you know the boundary: xanthoma disseminatum (a non-Langerhans cell histiocytosis of flexures and mucosa, with diabetes insipidus and normal lipids); verruciform xanthoma (a solitary wart-like oral or genital lesion, normolipidaemic); and juvenile xanthogranuloma (a benign self-limiting histiocytic lesion of infancy).[1]

How common, who, and the precipitants

[1]

Xanthelasma is the commonest type, affecting roughly 1 per cent of adults, with a predilection for middle-aged women. The epidemiology turns on one counter-intuitive fact: only about half have a measurable dyslipidaemia — which is why a single normal panel never closes the file.[1][8]

Tendinous and tuberous xanthomas point to familial hypercholesterolaemia (FH), an autosomal dominant LDL-clearance defect carried by about 1 in 250 people in its heterozygous form. Tendon xanthomas are essentially absent before age ten, appear progressively thereafter, and are among the strongest single clinical markers of premature coronary disease a dermatologist can find.[2]

Eruptive xanthomas arise when triglyceride-rich lipoproteins accumulate fast. The precipitants — worth memorising — are uncontrolled diabetes, alcohol excess, obesity, exogenous oestrogens, systemic retinoids, glucocorticoids, bile-acid sequestrants, and the familial hypertriglyceridaemias. Recognise the trigger and you have the treatment: remove it, and the lesions often resolve within weeks.[6]

Secondary causes of dyslipidaemia must be excluded in every patient regardless of type, because they are reversible and they change management. The list is short and worth a mnemonic.[1]

[1]

Because excluding a secondary cause changes management, hold the commonest culprits with the lipid pattern each produces.[1]

[1]

The rule that follows: a xanthoma with a clear secondary cause is managed by treating the cause first, adding lipid-lowering therapy only if the abnormality persists. Alcohol-driven eruptive xanthoma resolves with abstinence and a fibrate; a plane xanthoma from biliary obstruction needs the obstruction fixed, not merely a statin.[1]

Pathophysiology — the foam cell is the final common pathway

The shared mechanism is a tissue macrophage turned into a foam cell by lipid it cannot off-load. Circulating lipoproteins — LDL, VLDL remnants, chylomicron remnants, lipoprotein-X — extravasate through dermal and tendinous capillaries. Resident macrophages engulf the lipid through scavenger receptors (SR-A, CD36), and — critically — unlike the regulated LDL receptor, scavenger uptake is not feedback-inhibited: the macrophage keeps ingesting long after it should stop, and cholesterol esters distend its cytoplasm into the clear vacuolated foam cell.[1]

The type of lipoprotein dictates morphology and tempo. In hypercholesterolaemia, insoluble LDL accumulates slowly and persistently in tendons and extensor skin, producing the firm, deep, indolent nodules. In severe hypertriglyceridaemia, bulky chylomicrons and VLDL leak rapidly through capillary walls and flood the dermis, generating the explosive erythematous-haloed crops within days — a different speed and a different biology. In type III, defective remnant clearance (APOE E2/E2) deposits remnants in palmar creases and tuberous sites.[2]

In diffuse plane xanthomatosis the mechanism is different again: a circulating monoclonal immunoglobulin complexes with lipoproteins, and the immune complex deposits in the dermis, generating widespread flat plaques in a patient who may have entirely normal baseline lipids. That is why the lesion mandates a search for a paraprotein, not just a lipid panel.[1]

The clinical corollary: the foam cell is the final common pathway, but the upstream defect determines everything — site, speed, systemic risk, and whether treating the lipids will clear the lesion. Eruptive and tuberous lesions tend to regress with lipid control; tendinous xanthomas shrink only slowly; xanthelasma, once formed, often persist despite statins and need cosmetic removal.[1]

Clinical presentation — six lesions, read by site

Xanthomas are painless (except eruptive, which can be tender), non-pruritic, and yellow-orange from their lipid content; distribution is the single most useful clue. Take them type by type.[1]

Xanthelasma palpebrarum — soft yellow flat or slightly raised plaques on the lids, classically at the medial canthus, becoming bilateral. They grow slowly, cause only cosmetic distress, and are the commonest reason a patient presents. Their importance is systemic: roughly half have a dyslipidaemia, and even the normolipidaemic half carry a small but real cardiovascular signal.[1][8]

Tendinous xanthoma — firm, deep, subcutaneous nodules tethered to the tendon with freely mobile overlying skin. The Achilles is the classic site, then the extensor tendons of hands and feet and the patellar tendon. Painless, growing over years, pathognomonic for FH. A thickened, irregular Achilles in someone under fifty is FH until proven otherwise.[2]

Tuberous xanthoma — firm yellow-orange nodules on extensor surfaces: elbows, knees, buttocks, dorsum of hands. Slower and more superficial than tendinous lesions; hypercholesterolaemia (IIa), occasionally type III.[1]

Eruptive xanthoma — the most dramatic tempo. Sudden crops of small (2 to 5 mm) firm yellow papules with an erythematous halo, over days, on buttocks, extensor arms, thighs and back. Tender or pruritic; resolve rapidly once triglycerides are controlled, sometimes leaving a hyperpigmented macule. A warning of severe hypertriglyceridaemia with a real risk of acute pancreatitis — crops plus abdominal pain is an emergency.[6][7]

Plane xanthoma (xanthoma striatum palmaris) — orange-yellow discolouration of the palmar creases, pathognomonic for type III dysbetalipoproteinaemia (APOE E2/E2), with both cholesterol and triglycerides raised. Plane xanthomas also occur in biliary obstruction (especially PBC) via lipoprotein-X, where the palms are typically spared.[1]

Diffuse plane xanthomatosis — widespread flat yellow-orange plaques over face, neck, trunk and intertriginous flexures. Lipids may be normal: deposition is driven by a circulating paraprotein complexing with lipoproteins. The lesion is a dermatological red flag for multiple myeloma.[1]

Atypical and syndromic presentations

A handful of inherited presentations are deliberately tested because they sit at the dermatology-and-metabolic boundary. In cerebrotendinous xanthomatosis (CYP27A1 defect), cholestanol — not cholesterol — accumulates, producing tendon xanthomas with progressive ataxia, dementia, peripheral neuropathy, juvenile cataracts and premature atherosclerosis; the disease-modifying treatment is chenodeoxycholic acid, which the examiner will expect you to name. In sitosterolaemia (ABCG5/ABCG8), plant sterols accumulate and mimic FH with tendon and tuberous xanthomas, but with the clue of haemolytic anaemia and stomatocytes; treat with ezetimibe and a low-plant-sterol diet. In severe hypertriglyceridaemia, lipaemia retinalis — milky salmon-pink retinal vessels — is a striking bedside clue on fundoscopy.[9]

The mimics — distinguish on morphology, site and the lipid panel

The decisive discriminator in every case is the fasting lipid profile, supported by histology where doubt remains. Each lesion type has its own mimics; the panel sorts them.[1]

[1]

A lipid panel that is entirely normal should prompt the paraproteinaemia work-up for diffuse plane xanthoma, and the consideration of xanthoma disseminatum or verruciform xanthoma for the mucosal and flexural forms.[1]

The bedside round — skin, tendons, eyes, heart

Examination is short but systematic, and it hunts deliberately for the systemic associations that determine risk. Begin with the skin, then tendons, then eyes, then the cardiovascular system.[1]

Inspect the eyelids (medial canthus especially), the extensor surfaces (elbows, knees, knuckles), the buttocks and thighs (eruptive crops), the palmar creases (the orange line of xanthoma striatum palmaris), and the intertriginous flexures. Palpate the Achilles and the extensor tendons of hands and feet for nodularity, thickening and symmetry: an irregular, thickened Achilles is the single most reliable bedside sign of FH. Where available, measure Achilles tendon thickness by ultrasound or lateral x-ray — a thickness over 9 mm in an adult strongly suggests FH (normal generally under 5.6 mm).[2]

Examine the eyes for corneal arcus (before age forty-five it supports dyslipidaemia; arcus senilis in the elderly is incidental) and perform fundoscopy for lipaemia retinalis in suspected severe hypertriglyceridaemia. Complete with a focused cardiovascular and metabolic examination: blood pressure, waist circumference, body-mass index, signs of chronic liver disease and hypothyroidism, and a search for peripheral arterial disease. A careful family history of premature coronary disease or sudden death is part of the examination — it drives cascade screening in FH.[1]

[1]

Investigations — two goals, one panel

Investigation has two goals: characterise the lipid disorder and find any secondary cause. The fasting lipid panel is the cornerstone and is mandatory in every patient; the rest is selected by type.[1]

Mandatory in all patients

A fasting lipid profile (total cholesterol, LDL-C, HDL-C, triglycerides) is the single most informative test. The pattern names the defect: isolated high LDL suggests FH (IIa); a combined cholesterol and triglyceride rise suggests IIb, or type III with palmar involvement; an isolated very high triglyceride suggests IV and V. Add fasting glucose and HbA1c (diabetes drives eruptive xanthoma), TSH (hypothyroidism is a classic reversible cause), urea, electrolytes and eGFR (renal disease), urinalysis for protein (nephrotic syndrome), and liver function tests (cholestasis and the lipoprotein-X of PBC).[1]

Targeted to the clinical type

For suspected FH, apply a validated clinical score — Dutch Lipid Clinic Network Criteria (DLCNC) internationally or Simon Broome in the UK — and arrange genetic testing for LDLR, APOB, PCSK9. Measure lipoprotein(a) as an independent risk enhancer. For type III, APOE genotyping confirms E2/E2 and lipoprotein electrophoresis shows the broad beta band. For diffuse plane xanthomatosis, SPEP, serum free light chains, urine Bence-Jones, calcium and renal function exclude a monoclonal gammopathy or myeloma. For eruptive xanthoma with abdominal pain, check serum amylase and lipase for pancreatitis.[6]

Named criteria for familial hypercholesterolaemia — DLCNC and Simon Broome

Both named scores reward the tendon xanthoma heavily — which is why a dermatologist's finding is pivotal to the FH diagnosis. Reproduce them verbatim.[1]

Dutch Lipid Clinic Network Criteria (DLCNC) scores family history, personal vascular history, physical signs, untreated LDL-C, with a bonus for a causative mutation:[1]

• Family history: first-degree relative with premature (men under 55, women under 60) coronary or vascular disease, or known high LDL-C — 1 point; first-degree relative with tendon xanthoma or arcus, or a child under 18 with high LDL-C — 2 points.
• Clinical history: premature coronary disease — 2; premature cerebral or peripheral vascular disease — 1.
• Examination: tendon xanthoma — 6; arcus cornealis before age 45 — 4.
• Untreated LDL-C: at or above 8.5 mmol/L — 8; 6.5 to 8.4 — 5; 5.0 to 6.4 — 3; 4.0 to 4.9 — 1.
• Genetic: a functional mutation in LDLR, APOB or PCSK9 — 8.

[1]

The interpretation the examiner expects: a total above 8 is "definite" FH, 6 to 8 "probable", 3 to 5 "possible", under 3 "unlikely". Tendon xanthoma (6 points) plus a high LDL-C can secure "probable" FH even before genetic testing — which is why the bedside finding matters.[1]

Simon Broome (UK) distinguishes definite from possible FH. Definite FH needs a raised lipid level — total cholesterol over 7.5 mmol/L or LDL-C over 4.9 mmol/L in an adult (over 6.7 / over 4.0 in a child under 16) — plus either tendon xanthoma in the patient or a relative, or a confirmed DNA mutation. Possible FH meets the same lipid threshold plus one of: family history of MI under 50 (men) or under 60 (women) in a second-degree relative; family history of total cholesterol over 7.5 mmol/L; or a child under 16 with total cholesterol over 6.7 mmol/L. In both systems, identifying one affected individual obliges cascade screening of the family — the public-health payoff of an accurate clinical diagnosis.[2][5]

Adjuncts

Achilles tendon ultrasound or lateral radiograph documents tendon xanthomas objectively and supports a DLCNC diagnosis when genetic testing is unavailable. Lipoprotein electrophoresis or ultracentrifugation resolves ambiguous mixed dyslipidaemias. Skin biopsy is reserved for genuine diagnostic doubt: dermal foam cells confirm a xanthoma, but histology cannot distinguish the lipid types and so never replaces the panel.[1]

The time-critical scenario — eruptive xanthoma plus pancreatitis

The only genuinely time-critical situation in the xanthoma family is eruptive xanthoma complicated by acute pancreatitis from chylomicronaemia. The skin lesions are the warning; the threat is the inflamed pancreas behind them.[1]

[1]

The skin lesions themselves need no acute treatment — they resolve as the triglycerides fall, usually within weeks.[7]

Management — definitive, two parallel strands

Two strands must both be pursued: treat the underlying dyslipidaemia (to prevent cardiovascular disease and pancreatitis) and remove or ablate the lesion cosmetically when it causes distress. The cosmetic strand is never a substitute for the metabolic one — a patient whose xanthelasma is excised but whose FH is left untreated has been failed.[1]

Treating the underlying dyslipidaemia

For heterozygous FH, the backbone is a high-intensity statin — atorvastatin 80 mg once daily, or rosuvastatin 20 to 40 mg once daily, by mouth — combined with ezetimibe 10 mg once daily. If LDL-C remains above target, add a PCSK9 inhibitor (alirocumab or evolocumab, subcutaneous). The diagnosis obliges cascade screening of first-degree relatives — each has a one-in-two chance of carrying the same mutation and benefits from early treatment.[5][10]

For homozygous FH, which presents in childhood with cutaneous and tendon xanthomas and aggressive aortic and coronary disease, management is specialist and intensive: high-dose statin plus ezetimibe, a PCSK9 inhibitor, the microsomal triglyceride transfer protein inhibitor lomitapide, and in selected patients LDL apheresis; liver transplantation for the most refractory.[5]

For severe hypertriglyceridaemia, the ladder is a fibrate (fenofibrate 200 mg once daily, or gemfibrozil) with omega-3 ethyl esters 2 to 4 g daily, plus nicotinic acid where tolerated — and, most importantly, removal of the precipitant: strict glycaemic control, alcohol cessation, a very-low-fat diet, withdrawal of oestrogens or retinoids. Type III responds well to a statin-fibrate combination plus lifestyle.[1]

Cosmetic treatment for xanthelasma

Xanthelasma, once established, often persists despite statins and is removed for cosmetic reasons. No single modality is clearly superior, and the recurrence rate after any treatment is roughly 40 per cent — warn the patient.[1][4]

[4]

Consultant confession: I quote the 40 per cent recurrence figure to every xanthelasma patient before I lift a scalpel or reach for the TCA — it sets expectations and protects the therapeutic relationship when the plaque returns.[3][4]

Treat the underlying dyslipidaemia before or alongside cosmetic removal, because untreated hyperlipidaemia drives recurrence and the cardiovascular risk is the more important outcome. A 2024 study of 80 per cent TCA and a comprehensive contemporary review confirm that while multiple modalities are effective, none eliminates the substantial recurrence rate, and combination approaches are increasingly advocated for extensive disease.[3][4]

Specific subtypes and scenarios — the rarer drawers

A viva will probe the rarer xanthomatous disorders that mimic the classic lipid types but have distinct mechanisms and management. Hold them in a separate mental drawer.[1]

Cerebrotendinous xanthomatosis (CTX) — autosomal recessive CYP27A1 defect blocking bile-acid synthesis; cholestanol accumulates. Tendon xanthomas plus progressive neurological disease (ataxia, spasticity, dementia, neuropathy), juvenile cataracts, premature atherosclerosis. The disease-modifying treatment is chenodeoxycholic acid — start early to halt neurological decline. The answer is NOT a statin.[1]

Sitosterolaemia — ABCG5/ABCG8 defect causing intestinal hyperabsorption and impaired biliary excretion of plant sterols. Mimics FH with tendon and tuberous xanthomas and a high LDL-C, but the clues are haemolytic anaemia (stomatocytes), childhood xanthomas, and a strong response to dietary plant-sterol restriction. Cornerstone treatment is ezetimibe plus a low-plant-sterol diet; statins are relatively ineffective.[9]

Xanthoma disseminatum — a rare non-Langerhans cell histiocytosis of children and young adults: yellow-brown papules and plaques in flexures, eyelids and mucosa, frequently with diabetes insipidus from pituitary infiltration, and normal lipids. Not a metabolic xanthoma; management is entirely different (observation, systemic therapy for aggressive disease).[1]

Verruciform xanthoma — a solitary, wart-like, normolipidaemic lesion of oral or genital mucosa; simple excision, no lipid implication. Normolipidaemic xanthelasma is the common practical scenario: even with normal lipids, complete a formal cardiovascular risk assessment, because subclinical atherogenic dyslipidaemia is common and the lesion itself carries a small independent cardiovascular signal.[8]

Complications — the four that justify taking every xanthoma seriously

[1]

Four named pitfalls, each a recurring failure mode. Every one is avoided by the same discipline: a fasting lipid profile and a search for secondary causes before any cosmetic procedure.[1]

• Cosmetic without metabolic — excising the xanthelasma without investigating the lipids; the patient leaves cosmetically improved but metabolically untreated.
• FH without cascade screening — recognising FH clinically but failing to screen relatives; affected family members who would benefit from early statins remain undiagnosed.
• Diffuse plane mistaken for a lipid lesion — missing the underlying paraproteinaemia.
• Eruptive xanthoma mistaken for primary skin disease — missing the pancreatitis behind it.

[1]

Prognosis, disposition and follow-up

The prognosis of a xanthoma is the prognosis of the disorder behind it — explain the two strands to the patient separately. The skin lesions behave predictably by type: eruptive resolve within weeks to months once triglycerides are controlled; tuberous regress slowly over months to years; tendinous shrink only slowly and may persist; xanthelasma usually persist and recur in roughly 40 per cent after cosmetic removal. Tell the patient that clearing the lipids improves eruptive and tuberous lesions but may not clear the xanthelasma.[1]

The systemic prognosis is set by cardiovascular risk. FH with tendon xanthomas carries a markedly elevated lifetime risk of premature coronary disease, substantially reduced — though never normalised — by early, sustained, high-intensity statin therapy. Severe hypertriglyceridaemia carries the dual threat of pancreatitis and accelerated atherosclerosis. Diffuse plane xanthomatosis carries the prognosis of its underlying haematological disease.[1]

[1]

Disposition: most patients are managed outpatient with the dermatologist coordinating alongside the primary physician and, where relevant, a lipidologist or endocrinologist. Admit for eruptive xanthoma with pancreatitis or refractory severe hypertriglyceridaemia. Genetic referral for confirmed FH to organise cascade testing; haematology referral for any paraproteinaemia-driven diffuse plane xanthoma.[1]

Follow-up and monitoring

Once the underlying disorder is identified, follow-up is structured around lipid targets and lesion behaviour. For FH, recheck LDL-C at 4 to 12 weeks after any therapy change and titrate toward the regional goal (a greater than 50 per cent reduction in the UK; LDL-C under 1.4 mmol/L in very-high-risk patients under European guidance). Lipid-lowering is lifelong, and adherence plus attention to all modifiable cardiovascular risk factors matters more than the precise drug. For severe hypertriglyceridaemia, monitor triglycerides until they fall below the pancreatitis-risk zone (generally below 10 mmol/L), with rescreening for diabetes, alcohol intake and adherence.[5]

The safety-net for every xanthoma patient is the cardiovascular system. A baseline 12-lead ECG, consideration of coronary artery calcium scoring in selected intermediate-risk patients, and a structured cardiovascular risk assessment are appropriate at diagnosis. Patients with FH should carry the diagnosis forward into every future encounter — it changes the threshold for investigating cardiac symptoms. The dermatologist who diagnoses a xanthoma has opened a lifelong cardiovascular risk-reduction pathway.[1]

Special populations

In children, a xanthoma is an alarm bell. FH can be screened from as early as age two when a parent is affected, and a statin is typically initiated from age 8 to 10 under specialist guidance. CTX and sitosterolaemia both present in childhood with tendon xanthomas and a high LDL-C, and both demand a specific (non-statin-led) diagnosis because their management differs fundamentally from ordinary FH. Any child with a xanthoma warrants specialist metabolic referral, not cosmetic reassurance.[9]

In pregnancy, statins are contraindicated (teratogenic concern). Pregnancy itself, with physiological hypertriglyceridaemia amplified by oestrogen, can precipitate eruptive xanthoma and even pancreatitis, particularly in the third trimester in a patient with baseline hypertriglyceridaemia or gestational diabetes; management is conservative — diet and glycaemic control — and the lesions typically resolve post partum.[1]

In the elderly, xanthelasma is common and often isolated; reassess cardiovascular risk and balance cosmetic benefit against lid complications. In the immunocompromised, or any patient with diffuse plane xanthomatosis, the work-up for an occult monoclonal gammopathy is non-negotiable — the lesion may precede a myeloma by months or years.[1]

Evidence, guidelines and regional differences

The evidence base is mature, and the regional guidelines agree on principles while differing on thresholds and tactics.[1]

[1] [1]

Three regional deltas. First, LDL-C target philosophy differs: Europe and the UK specify explicit values or percentage reductions; the US favours intensity-based therapy. Second, TCA strength for xanthelasma ranges from the conventional 50 to 70 per cent up to 80 per cent reported effective in a 2024 study, with practice varying by operator.[3] Third, the age of paediatric statin initiation for FH varies modestly, typically 8 to 10 years, deferred to specialist judgement.[1]

Exam pearls — the facts the fellowship examiner rewards

[1]

The ward-round test

Which type fits each clue?

• Yellow plaques on the medial canthus of the eyelids in a normolipidaemic woman — xanthelasma palpebrarum (still assess cardiovascular risk).
• Nodular thickening of the Achilles tendon in a man with LDL-C 6.5 mmol/L and a father who had an MI at 42 — tendinous xanthoma and familial hypercholesterolaemia.
• Sudden crops of tender yellow papules on the buttocks of a poorly controlled diabetic with epigastric pain — eruptive xanthoma; exclude pancreatitis.
• Orange discolouration of the palmar creases with raised cholesterol and triglycerides — plane xanthoma and type III (APOE E2/E2).
• Widespread flat yellow plaques on face and trunk with a normal lipid panel — diffuse plane xanthomatosis; screen for a paraprotein.

[1] [1]

Red flags — when a xanthoma must never be dismissed as cosmetic

[1]

The mantra

The discipline that runs through the whole topic is simple, and worth carrying into the exam: the lesion is the messenger — treat the lipid. Read the site for the lipoprotein, confirm with the lipid panel, treat the underlying disorder to prevent cardiovascular disease and pancreatitis, and only then turn to cosmetic removal — accepting that the xanthelasma, at least, will probably recur.[1]

References

1. [1]Nair PA, Singhal R Xanthelasma palpebrarum - a brief review Clin Cosmet Investig Dermatol, 2018.PMID 29296091
2. [2]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
3. [3]Sapra S, Tran JV, Gurm H, et al. Treatment of Xanthelasma Palpebrarum Using Trichloroacetic Acid 80 J Clin Aesthet Dermatol, 2024.PMID 39758222
4. [4]Yee DA, Zhou AE, Khachemoune A Examining treatment strategies for xanthelasma palpebrarum: a comprehensive literature review of contemporary modalities Arch Dermatol Res, 2024.PMID 38724802
5. [5]Cuchel M, Bruckert E, Ginsberg HN, et al. Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society Eur Heart J, 2014.PMID 25053660
6. [6]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
7. [7]Stark M, Stuart J Eruptive xanthoma in the setting of hypertriglyceridemia and pancreatitis Am J Emerg Med, 2018.PMID 29716801
8. [8]Blair K, Shah SS Xanthelasma Palpebrarum 2026.PMID 30285396
9. [9]Tada H, Kojima N, Takamura M, et al. Sitosterolemia Adv Clin Chem, 2022.PMID 36210074
10. [10]Nohara A, Tada H, Ogura M, et al. Homozygous Familial Hypercholesterolemia J Atheroscler Thromb, 2021.PMID 33867421