What causes lymphedema?

Causes of Lymphedema

Lymphedema is primarily caused by blockage or damage to the lymphatic system, resulting in impaired lymphatic drainage and subsequent fluid accumulation in tissues. 1, 2

Primary vs. Secondary Lymphedema

Primary Lymphedema

• Caused by developmental lymphatic vascular anomalies 3
• May appear at any age but most commonly presents at puberty 4
• Results from congenital abnormalities in the lymphatic system

Secondary Lymphedema (More Common)

• Acquired due to damage to the lymphatic system from:
  • Cancer treatments (most common cause in developed countries) 5
    • Surgery - particularly lymph node dissection/removal 1
    • Radiation therapy - especially to supraclavicular lymph nodes or axilla 1
  • Infection - filariasis (most prevalent worldwide cause, common in Southeast Asia) 4
  • Trauma to lymphatic vessels 3
  • Underlying systemic diseases 3

Pathophysiology of Lymphedema

• Impaired lymphatic drainage leads to retention of lymphatic fluid in the interstitial compartment 3
• After lymph node removal:
  • Immediate disruption of lymph flow occurs in collecting lymphatic vessels 6
  • Abnormal lymphatic drainage patterns develop, including lateral and retrograde lymph flow 6
  • Lymph stasis results in accumulation of protein-rich interstitial fluid 7
• Chronic lymphedema progression:
  • Initial fluid accumulation leads to swelling
  • Over time, inflammation develops
  • Fibrotic and fatty tissue deposition occurs
  • Limited mobility ensues
  • Risk of bacterial infections increases 5

Risk Factors for Lymphedema Development

• Surgical factors:

  • Full axillary lymph node dissection carries higher risk than sentinel lymph node biopsy 1
  • Number of lymph nodes removed (five or more significantly increases risk) 1

• Radiation-related factors:

  • Radiation to supraclavicular lymph nodes 1
  • Radiation to axilla 1
  • Radiation to internal mammary lymph nodes 1

• Patient-related factors:

  • Obesity/overweight status 1, 2
  • Infections (can exacerbate existing lymphedema) 1

Timing of Lymphedema Development

• May occur immediately after treatment 1
• Can develop after many years (late effect) 1
• Progression is often chronic without proper management 3

Pathological Changes in Lymphatic Vessels

• Dysfunction of lymphatic valves may contribute to impaired lymph flow 5
• Chronic lymph stasis impairs local immune surveillance 7
• Stimulates vicarious angiogenesis (development of collateral lymphatic and hematic networks) 7
• Immunological vulnerability develops in the affected area, potentially predisposing to malignancy 7

Clinical Implications

• The degree of swelling varies widely even among patients with similar treatments 1
• Lymphedema can range from mild to severe, potentially causing significant disability 1
• Symptoms range from mild discomfort to overt pain 1
• Increased risk of cellulitis in the affected area 1
• No definitive cure exists, but proper management can limit progression and complications 3

Understanding these causes and mechanisms is essential for implementing effective prevention strategies and management approaches for patients at risk of or experiencing lymphedema.