Lymphedema and subclinical lymphostasis (microlymphedema) facilitate cutaneous infection, inflammatory dermatoses, and neoplasia: A locus minoris resistentiae

Abstract

Whether primary or secondary, lymphedema is caused by failure to drain protein-rich interstitial fluid. Typically affecting a whole limb, it has become apparent that lymphedema can also affect localized regions of the skin, or it can be clinically silent but histologically evident, denoted by dilated lymphangiectases (latent lymphedema). Chronic lymph stasis has numerous consequences, including lipogenesis, fibrosis, inflammation, lymphangiogenesis, and immunosuppression. For example, lymphedema’s disruption of immune cell trafficking leads to localized immune suppression, predisposing the area affected to chronic inflammation, infection (cellulitis and verrucosis), and malignancy (angiosarcoma and nonmelanoma skin cancer). The pathogenesis of lymphedema is reviewed and exemplified by describing how a combination of lymph stasis–promoting factors such as trauma, obesity, infection, and inflammatory disorders produces localized elephantiasis; furthermore, the finding of lymphangiectases is found to be common in numerous dermatologic disorders and argued to play a role in their pathogenesis. Lastly, it is discussed how antigen burden, which is controlled by lymphatic clearance, affects the immune response, resulting in immune tolerance, immunopathology, or normal adaptive immunity.