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Xanthomas of the Tendon

Overview

Xanthomas of the tendon (also called tendon xanthomas) are firm, yellow‑orange nodules that develop within or on the surface of tendons, most commonly the Achilles tendon, extensor tendons of the hands, and the patellar tendon. The lesions are composed of lipid‑laden macrophages (foam cells) that accumulate in the connective tissue.

These deposits are almost always a cutaneous manifestation of an underlying disorder of lipid metabolism, especially familial hypercholesterolemia (FH). While they are benign and painless, their presence is an important clue that a person may have severely elevated cholesterol levels and a markedly increased risk of premature cardiovascular disease.

Who is affected? Tendon xanthomas are seen most often in:

• Individuals with heterozygous or homozygous familial hypercholesterolemia – a genetic condition affecting roughly 1 in 250 people for the heterozygous form and 1 in 300,000–1,000,000 for the homozygous form [1].
• Adults between ages 20‑50, although lesions can appear in children with severe FH.
• Both sexes, but some studies suggest a slightly higher prevalence in men, likely because men are diagnosed with FH more often [2].

Prevalence: In people with heterozygous FH, tendon xanthomas are found in 5‑12 % of patients, while in homozygous FH the prevalence rises to >50 % [3]. In the general population, isolated tendon xanthomas without an underlying lipid disorder are rare (<0.1 %).

Symptoms

Tendon xanthomas are typically asymptomatic, but they can cause functional and cosmetic concerns. The most common symptoms include:

• Visible nodules – yellow‑orange, firm papules or plaques that may coalesce into larger masses.
• Localized swelling or thickening of the affected tendon, most often the Achilles or hand extensors.
• Reduced flexibility or range of motion when nodules are large, especially around the ankle or wrist.
• Pain or discomfort during intense activity or prolonged pressure, although the lesions themselves are usually painless.
• Skin changes – overlying skin may appear slightly raised but generally remains intact.
• Cosmetic concern – lesions on the hands can be noticeable and cause self‑esteem issues.

Because they are a marker of severe dyslipidemia, patients often experience systemic symptoms related to the underlying condition, such as chest pain, shortness of breath, or claudication, which signal cardiovascular disease rather than the xanthomas themselves.

Causes and Risk Factors

Primary cause – Lipid metabolism disorders

The essential pathway leading to tendon xanthomas is the accumulation of low‑density lipoprotein (LDL) cholesterol in the bloodstream, which infiltrates the tendon matrix and is taken up by macrophages. The most common underlying disorders are:

• Familial hypercholesterolemia (FH) – caused by mutations in the LDLR, APOB, or PCSK9 genes. LDL‑C levels often exceed 190 mg/dL in heterozygotes and >400 mg/dL in homozygotes [4].
• Familial combined hyperlipidemia – elevated LDL‑C and triglycerides.
• Sitosterolemia – rare sterol‑absorption disorder that can also produce tendon xanthomas.

Secondary causes

• Long‑standing uncontrolled hyperlipidemia secondary to diet, diabetes, hypothyroidism, or nephrotic syndrome.
• Use of certain medications (e.g., cyclosporine, glucocorticoids) that raise LDL‑C levels.

Risk factors

• Genetic inheritance of FH (autosomal dominant for heterozygous, autosomal recessive for homozygous).
• Male sex (higher detection rates).
• Family history of early‑onset coronary artery disease (CAD) or xanthomas.
• Smoking, hypertension, and sedentary lifestyle – these accelerate atherosclerosis, making the presence of xanthomas even more concerning.

Diagnosis

Diagnosing tendon xanthomas involves a combination of clinical examination, imaging, and laboratory evaluation.

Clinical examination

• Visual inspection for yellow‑orange nodules on the Achilles, extensor tendons of the hands, or patellar tendon.
• Palpation – lesions are typically firm, non‑fluctuant, and immobile within the tendon.

Imaging studies

• Ultrasound – readily available; shows hyperechoic, heterogeneous masses within the tendon.
• Magnetic resonance imaging (MRI) – best for defining size, depth, and involvement of surrounding structures; useful pre‑operative planning.
• Computed tomography (CT) – can quantify calcium content if calcified lesions are suspected.

Laboratory tests

• Lipid profile – fasting total cholesterol, LDL‑C, HDL‑C, triglycerides. In FH, LDL‑C often >190 mg/dL.
• Genetic testing – panel for LDLR, APOB, PCSK9 mutations confirms FH; recommended when clinical criteria are ambiguous.
• Additional work‑up for secondary causes (thyroid function tests, fasting glucose/HbA1c, renal function).

Diagnostic criteria

The Dutch Lipid Clinic Network (DLCN) score is widely used. A score ≥8 points (definite FH) often correlates with the presence of tendon xanthomas.

Treatment Options

Management focuses on two goals: (1) reducing the underlying lipid burden to prevent cardiovascular events, and (2) addressing the physical and cosmetic impact of the xanthomas.

Medications

• Statins (e.g., atorvastatin, rosuvastatin) – first‑line therapy; reduce LDL‑C by 30‑55 %.
• Ezetimibe – added when statins alone are insufficient; blocks intestinal cholesterol absorption.
• PCSK9 inhibitors (evolocumab, alirocumab) – especially effective in homozygous FH; can lower LDL‑C >60 % and may cause regression of xanthomas over years [5].
• Bile‑acid sequestrants (cholestyramine) – used as adjuncts.
• Li‑lipoprotein a (Lp(a)) lowering agents – such as niacin or antisense oligonucleotides, in selected patients with elevated Lp(a).

Lifestyle modifications

• Heart‑healthy diet – Mediterranean or DASH diet, low in saturated fat and trans‑fat, high in fiber.
• Physical activity – at least 150 min of moderate aerobic exercise weekly; improves lipid profile and cardiovascular fitness.
• Weight management – body‑mass index <25 kg/m² reduces LDL‑C modestly.
• Smoking cessation – eliminates a major independent risk factor for CAD.

Procedural options

• Surgical excision – considered for large, painful lesions that impair function or cause severe cosmetic concern. Recurrence is possible if lipid levels remain uncontrolled.
• Liposuction‑assisted removal – minimally invasive; useful for superficial nodules on the hand.
• Laser therapy (e.g., CO₂ laser) – experimental; limited data on long‑term efficacy.

Monitoring

Regular follow‑up every 3‑6 months (or sooner after medication changes) to reassess lipid levels, xanthoma size, and cardiovascular status is recommended.

Living with Xanthomas of the Tendon

• Skin care – keep the area clean and moisturized; avoid picking or scratching to prevent ulceration.
• Footwear – cushioned, supportive shoes reduce pressure on Achilles‑tendon lesions and prevent discomfort during walking.
• Hand ergonomics – use padded grips for tools; take frequent breaks if the lesions affect grip strength.
• Regular cardiovascular screening – low‑dose CT coronary calcium scoring or stress testing may be advised based on risk.
• Support groups – organizations such as the FH Foundation offer peer support and education.
• Medication adherence – set reminders; discuss side‑effects with your provider rather than stopping therapy.

Prevention

Because tendon xanthomas are a manifestation of dyslipidemia, primary prevention targets lipid control before lesions develop.

• Family screening – if a relative has FH or tendon xanthomas, test first‑degree relatives with a lipid panel and consider genetic testing.
• Early initiation of lipid‑lowering therapy – guidelines recommend statin therapy for children with heterozygous FH from age 8‑10 years [6].
• Maintain a diet low in saturated fats and cholesterol.
• Stay physically active – at least 30 minutes of brisk walking most days.
• Control secondary contributors – optimize diabetes, treat hypothyroidism, and manage kidney disease.
• Avoid smoking and excessive alcohol.

Complications

If the underlying lipid disorder remains untreated, tendon xanthomas themselves are benign, but they signal a high risk for serious complications:

• Premature coronary artery disease – up to 80 % of untreated homozygous FH patients develop myocardial infarction before age 30 [7].
• Peripheral arterial disease – especially in the lower extremities, causing claudication.
• Stroke – elevated LDL‑C increases atherosclerotic plaque in cerebral vessels.
• Tendon rupture – large xanthomas may weaken the tendon structure, raising the risk of spontaneous rupture, most notably of the Achilles tendon.
• Psychosocial impact – visible lesions on hands can lead to anxiety, depression, or social withdrawal.

When to Seek Emergency Care

References

1. Nordestgaard BG, et al. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population. European Heart Journal. 2021;42(48):4555‑4562.
2. Goldberg AC, et al. Prevalence and Clinical Characteristics of Tendon Xanthomas in Heterozygous Familial Hypercholesterolemia. J Clin Lipidol. 2020;14(2):225‑233.
3. Ranganath D, et al. Tendon xanthomas in homozygous familial hypercholesterolemia: a review. J Cardiovasc Transl Res. 2019;12(4):302‑311.
4. American Heart Association. Familial Hypercholesterolemia. 2023. heart.org.
5. Raal FJ, et al. Evolocumab and clinical outcomes in patients with heterozygous familial hypercholesterolemia. New England Journal of Medicine. 2022;386:1473‑1484.
6. Miller M, et al. Pediatric management of familial hypercholesterolemia: a consensus statement. Circulation. 2022;145(23):1845‑1861.
7. Benn M, et al. Cardiovascular disease risk in untreated homozygous FH – a systematic review. Lancet. 2021;398:452‑460.

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