Secondary lymphedema: Pathogenesis

Secondary lymphedema follows an acquired defect in the lymphatic system. The common causes leading to a defective lymphatic function include infection, inflammation, malignancy, trauma, obesity, immobility, and therapeutic interventions. Understanding the pathogenesis of lymphedema is of prime importance in offering effective treatment. The pathogenetic mechanisms such as lymphatic valvular insufficiency, obliteration/ disruption of lymphatic vessels, and decreased lymphatic contractility aggravate lymphatic hypertension and lymphstasis. Accumulation of lymph, interstitial fluid, proteins, and glycosaminoglycans within the skin and subcutaneous tissue eventually stimulates collagen production by fibroblasts, causes disruption of elastic fibers, and activates keratinocytes, fibroblasts, and adipocytes. These result in thickening of skin and cause fibrosis of subcutaneous tissue. However, the sequence of these pathomechanisms, their inter-relationship and progression vary depending on the specific etiology of the lymphedema. In this article, we discuss the possible cellular and molecular mechanisms involved in the pathogenesis. Further studies to delineate the exact sequence of pathogenic processes surrounding the primary triggering event can help to formulate tailored therapeutic approaches.