What is xanthomatosis of the palm?

Xanthomatosis of the Palm: A Clinical Marker for Underlying Metabolic Disorders

Palmar xanthomatosis is a distinctive dermatological condition characterized by yellowish-brown papules or plaques on the palms, particularly along the palmar creases, that strongly indicates underlying dyslipidemia, most commonly type III hyperlipoproteinemia (dysbetalipoproteinemia). Palmar xanthomas, especially those following the creases of the palm (xanthoma striatum palmare), are pathognomonic for dysbetalipoproteinemia and require immediate evaluation for serious cardiovascular and metabolic disorders 1, 2.

Clinical Presentation and Diagnosis

• Appearance: Yellowish-brown, firm nodules or plaques along the palmar creases
• Symptoms: Usually asymptomatic, though some patients may report pain 3
• Associated findings: May coexist with other types of xanthomas:
  • Tuberous xanthomas (over joints and pressure points)
  • Tendinous xanthomas (especially Achilles tendon)
  • Xanthelasma palpebrarum (around eyelids)

Underlying Pathophysiology

Palmar xanthomas develop due to:

• Accumulation of lipid-laden macrophages (foam cells) in the dermis
• Excessive uptake of lipoproteins, particularly remnant lipoproteins
• Pathogenesis similar to early stages of atherosclerosis 4

Associated Conditions

1. Type III Hyperlipoproteinemia (Dysbetalipoproteinemia):

   • Most strongly associated condition
   • Characterized by defective clearance of remnant lipoproteins
   • Often requires additional factors (obesity, diabetes, hypothyroidism) for clinical expression 5
   • Near-equivalent cholesterol and triglyceride values (typically 300-600 mg/dL)

2. Other Metabolic Disorders:

   • Familial hypercholesterolemia
   • Severe hypertriglyceridemia
   • Diabetes mellitus type 2 3

3. Systemic Diseases:

   • Erdheim-Chester disease (rare non-Langerhans cell histiocytosis) 5
   • Multiple myeloma and other paraproteinemias

Diagnostic Evaluation

When palmar xanthomas are identified, the following workup is essential:

1. Comprehensive Lipid Profile:

   • Total cholesterol, LDL, HDL, triglycerides
   • Lipoprotein electrophoresis (to identify beta-VLDL)
   • Apolipoprotein E phenotyping (Apo E2/E2 in type III hyperlipoproteinemia) 6

2. Additional Laboratory Tests:

   • Fasting blood glucose or HbA1c
   • Thyroid function tests
   • Liver function tests
   • Serum protein electrophoresis (if paraproteinemia suspected)

3. Cardiovascular Risk Assessment:

   • Carotid ultrasound
   • Echocardiogram
   • Stress testing if indicated

Clinical Significance and Prognosis

Palmar xanthomas are not merely cosmetic concerns but important clinical markers:

• Indicate significantly increased cardiovascular risk 4
• May precede diagnosis of serious metabolic disorders 3, 7
• Can be an early warning sign for potentially life-threatening conditions

Management

Treatment focuses on the underlying metabolic disorder:

1. Lipid-Lowering Therapy:

   • Low-carbohydrate diet (patients with type III hyperlipoproteinemia are often extremely responsive) 5
   • Statins as first-line pharmacotherapy
   • Fibrates for hypertriglyceridemia
   • Combination therapy may be necessary

2. Management of Comorbidities:

   • Diabetes control
   • Thyroid hormone replacement if hypothyroid
   • Weight reduction if obese

3. Direct Treatment of Xanthomas:

   • Surgical excision for symptomatic or cosmetically concerning lesions
   • Note: Xanthomas often regress with successful treatment of underlying dyslipidemia

Key Clinical Pearls

• Palmar xanthomas warrant immediate lipid profile testing, even in normocholesterolemic patients 6
• The presence of palmar xanthomas should prompt evaluation for peripheral vascular disease and coronary artery disease
• Some patients may develop xanthomatous neuropathy with painful lesions 3
• Regular monitoring of lipid profiles and cardiovascular risk is essential for patients with xanthomas

Palmar xanthomatosis represents a visible manifestation of systemic metabolic derangement and should never be dismissed as a mere dermatological curiosity. Early recognition and appropriate management can significantly reduce morbidity and mortality from associated cardiovascular disease.