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As a part of the initial work-up before diagnosing lymphedema, it may be necessary to exclude other potential causes of lower extremity swelling such as renal failure, hypoalbuminemia, congestive heart-failure, protein-losing nephropathy, pulmonary hypertension, obesity, pregnancy and drug-induced edema.
Other conditions characterized by damage to lymph nodes can also cause lymphedema, including infiltration of lymph nodes by cancer or damage due to trauma, burns, radiation, compression, or infection.