Lymphedema

Lymphedema is a chronic, progressive condition resulting from impaired lymphatic transport capacity, causing accumulation of protein-rich interstitial fluid (lymph) in the affected tissue. Unlike edema from venous insufficiency or heart failure (which is protein-poor transudate), lymphedema fluid has high protein content (greater than 1.5 g/dL) that triggers a cascade of pathological changes: chronic inflammation, fibroblast activation, adipose tissue deposition, and eventually irreversible fibrosis and tissue remodeling. Lymphedema is classified as primary or secondary. Primary lymphedema results from congenital malformation or dysfunction of the lymphatic system: lymphedema praecox (most common, onset before age 35, often at puberty or pregnancy -- associated with mutations in VEGFR3/FLT4), lymphedema congenita (present at birth, Milroy disease -- hereditary disorder of VEGFR3), and lymphedema tarda (onset after age 35). Secondary lymphedema is far more common and results from acquired damage to previously normal lymphatic vessels or nodes: cancer-related lymph node dissection (axillary dissection for breast cancer is the most common cause in developed countries, with 20-40% lifetime incidence after axillary lymph node dissection), radiation therapy (fibrosis of lymphatic vessels), infection (recurrent cellulitis causes progressive lymphatic damage;...