Mechanisms and treatments of lymphedema

Lymphedema refers to the interstitial edema caused by obstruction of lymph drainage. The clinical symptoms of lymphedema include local swelling and pain, thickened and rough skin, limited walking and repeated infection. Genetic mutation, fat deposition, aging and lymphatic filariasis may contribute to the pathogenesis of lymphedema. CD4⁺T cells also promote the development of lymphedema. Cell junctions between adjacent lymphatic endothelial cells (LECs) are crucial to maintain the integrity of lymphatic vessels, and damage of these junctions increases the vessel permeability and induces lymphedema. VEGF-C-VEGFR3 signaling is a key regulator of lymphangiogenesis, whereas inflammatory mediators modulate lymphatic repair in a context-dependent manner. Current management includes conservative therapy and selected surgical approaches, while lymphangiogenic, pharmacologic, and cell-based treatments remain largely investigational. In this review, we summarize pathogenic factors associated with lymphedema, mechanisms regulating lymphatic endothelial permeability and lymphangiogenesis, and emerging therapeutic strategies.