The pathophysiology of lymphedema and the action of benzo-pyrones in reducing it.

The pathogenesis of lymphedema is briefly reviewed. Swelling secondary to lymphostasis shares the common deleterious effects of other edemas, especially those of chronic high protein edema, namely chronic inflammation with excess tissue fibrosis. Benzo-pyrones are the only known drugs which reduce the excess protein in the tissues with high protein edema including lymphedema. Once excess tissue protein is resorbed, edema subsides and the fibrosis slowly resolves by remodeling. Two of these benzo-pyrone drugs have been shown to reduce postmastectomy and primary lymphedema in randomized, double-blind, cross-over, placebo-controlled trials. One of these drugs (which is also inexpensive) has also been shown to reduce filaritic lymphedema and elephantiasis in a similar trial in India. The bigger the leg initially, the more rapid is the reduction. In this extreme condition about a 20% lessening of the excess volume occurs each year. The benzo-pyrones do not work rapidly, but they do convert a rapidly worsening condition into a slowly improving one. In addition, they have extremely low toxicity and are effective orally. They also seem to reduce the incidence of secondary acute inflammation.