- I. GENERAL CONSIDERATIONS As a fundamental starting point, lymphedema is an external (or internal) manifestation of lymphatic system insufficiency and deranged lymph transport. It may be an isolated phenomenon or associated with a multitude of other disabling local sequelae or even life-threatening systemic syndromes. In its purest form, the central disturbance is a low output failure of the lymphvascular system, that is, overall lymphatic transport is reduced. This derangement arises either from congenital lymphatic dysplasia (primary lymphedema) or anatomical obliteration, such as after radical operative dissection (e g., axillary or retroperitoneal nodal sampling), irradiation, or from repeated lymphangitis with lymphangiosclerosis (secondary lymphedema) or as a consequence of functional deficiency (e.g., lymphangiospasm, paralysis, and valvular insufficiency) (primary or secondary lymphedema). The common denominator, nonetheless, is that lymphatic transport has fallen below the capacity needed to handle the presented load of microvascular filtrate including plasma protein and cells that normally leak from the bloodstream into the interstitium. Swelling is produced by accumulation in the extracellular space of excess water, filtered/diffused plasma proteins, extravascular blood cells and parenchymal cell products. This process culminates in proliferation of parenchymal and stromal elements with excessive deposition of ground matrix substances. High output failure of the lymph circulation, on the other hand, occurs when a normal or increased transport capacity of intact lymphatics is overwhelmed by an excessive burden of blood capillary filtrate. Examples include hepatic cirrhosis (ascites), nephrotic syndrome (anasarca), and deep venous insufficiency of the leg (peripheral edema). Although the final pathway is the manifestation of tissue edema whenever lymph formation exceeds lymph absorption, the latter entities should properly be distinguished from lymphedema, which is characterized by decreased lymphatic transport. In some syndromes where high output lymphatic transport failure is longstanding, a gradual functional deterioration of the draining lymphatics may supervene and thereby reduce overall transport capacity. A reduced lymphatic circulatory capacity then develops in the face of increased blood capillary filtration. Examples include recurring infection, thermal burns, and repeated allergic reactions. These latter conditions are associated with “safety valve insufficiency” of the lymphatic system and can be considered a mixed form of edema/lymphedema and as such are particularly troublesome to treat. Peripheral lymphedema associated with chylous and non-chylous reflux syndromes is an infrequent but complex condition that requires specific diagnostic measures and treatment methods. In the treatment of “classical” lymphedema of the limbs (that is, peripheral lymphedema), improvement in swelling can usually be achieved by non-operative therapy. Because lymphedema is a chronic, generally incurable ailment, it generally requires, as do other chronic disorders, lifelong care and attention along with psychosocial support. The continued need for therapy does not mean a priori that treatment is unsatisfactory, although often it is less than ideal. For example, patients with diabetes mellitus continue to need drugs (insulin) or special diet (low calorie, low sugar) in order to maintain metabolic homeostasis. Similarly, patients with chronic venous insufficiency require lifelong external compression therapy to minimize edema, lipodermatosclerosis and skin ulceration (treatments may be preventative if initiated early). The compliance and commitment of the patient is also essential to an improved outcome. For example, in a patient with diabetes, poor compliance can result in weight loss, polyuria, and even coma and, long-term, also blindness, renal failure, and stroke. With chronic venous insufficiency, poor patient cooperation may be causally associated with progressive skin ulceration, hyperpigmentation, and other trophic changes in the lower leg. Similarly, failure to control lymphedema may lead to repeated infections (cellulitis/lymphangitis), progressive elephantine trophic changes in the skin, sometimes crippling invalidism and on rare occasions, the development of a highly lethal angiosarcoma (Stewart-Treves syndrome). The recent promulgation of a list of risk factors for secondary lymphedema has become a highlighted issue due to publications of “do’s and don’ts” lists. These are largely anecdotal and without sufficient investigation. While some rely on solid physiological principles (e.g. avoiding excessive heat on an “at risk” limb or trying to avoid infections), others are less supported. It must be noted that most published studies on incidence of secondary lymphedema report less than 50% chance of developing lymphedema and use of some of these methods for “prevention” of lymphedema may not be appropriate and likely subjects patients to therapies which are unsupported until a point in the future when evaluation and prognostication has advanced to identify more clearly specific risks and preventative measures.