Lymphedema, the excessive accumulation of lymph fluid caused by decreased lymphatic transport, encompasses a set of pathologic conditions. It is a regional, interstitial process, can be primary or secondary (acquired) and usually occurs in the extremities, although it can occur viscerally. Rockson reviews the types, causes, diagnosis and treatment of lymphedema.

Primary lymphedema is often classified by the age of the patient at onset of the edema. Congenital lymphedema occurs at birth or within the first two years of life. Although the edema can involve a single lower extremity, it also occurs in multiple limbs, the genitalia and, sometimes, the face. Bilateral edema of the lower extremities is more common in congenital lymphedema than in any other form of primary lymphedema. It may be transmitted in an autosomal dominant pattern, when cluster cases are found in families. Lymphedema praecox, the most common form of primary lymphedema, occurs around puberty or in young adults. In most cases, edema is evident in one foot and calf. Lymphedema tarda occurs in patients 35 years or older and is uncommon.

Secondary lymphedema, more common than the primary form, usually develops following disruption or obstruction of lymphatic pathways associated with a disease process, or following surgery or radiotherapy. Worldwide, filariasis is the most common cause of secondary lymphedema. In the United States, the most common secondary lymphedema develops in the upper extremity following axillary lymph node dissection. The incidence varies considerably, depending on the definition of edema. Results of one series of published reports reveal a 14 percent rate of secondary lymphedema in postmastectomy patients who also had undergone irradiation therapy.

Precipitation factors for overt lymphedema are unknown. The most common clinical presentation is “puffy” swelling of the affected area. As the lymphedema becomes chronic, the area is likely to become indurated and fibrotic. The maximal increase in girth of an extremity usually occurs during the first year. While the clinical presentation and physical findings of advanced lymphedema are characteristic, this is not the case with early lymphedema, when persons typically present with mild or intermittent swelling. Classic characteristics of early lymphedema versus other chronic edematous states of the extremities include subcutaneous fibrosis (peau d'orange), the Stemmer sign (inability to tent the skin on the dorsum of the toes or digits) and preferential swelling of the dorsum of the foot and the characteristic blunt “squared-off” appearance of the digits of the involved extremity.

The differential diagnosis includes chronic venous insufficiency (CVI) and postphlebitic syndrome, myxedema, lipedema and malignant lymphedema. CVI is characterized by aching in the lower extremities, chronic pruritus and cutaneous varicosities and discoloration. Patients with advanced CVI may develop skin ulceration. Myxedema is the term given to edema that occurs when there is an abnormal deposition of mucinous substances in the extremity as a result of thyroid disease. Pretibial edema occurs in thyrotoxicosis, but generalized myxedema occurs in hypothyroidism. Patients with myxedema present with rough skin of the palms, soles, elbows and knees, and yellow-orange discoloration of the skin, along with other signs of hypothyroidism. Lipedema usually occurs in women and is characterized by fatty accumulation subcutaneously between the pelvis and the ankle, sparing the feet. The patient may complain of painful swelling and may first have noted the problem shortly following onset of puberty—normally one to two years afterward. Stemmer's sign will be absent. Malignant lymphedema, the leading cause of lymphedema in the United States, develops rapidly and progresses relentlessly. Pain, which is absent from the benign form of lymphedema, is present, and the edema tends to begin centrally. In the differential diagnosis of new or worsening lymphedema, recurrent cancer must be considered.

Aggressive decongestive lymphatic therapy, the mainstay of most therapeutic recommendations, reduces limb volume and provides long-term benefit. Other treatment modalities include meticulous skin care, exercise, massage and compression garments. Compression therapy mandates the presence of sufficient arterial flow to the affected limb; otherwise, such treatment may cause ischemia and necrosis. Once decongestive treatments have been successful, compression garments should continue to be used and should be replaced every three to six months (or when the garment has lost its elasticity). Coumarin has been used to stimulate local proteolysis and has been shown to reduce edema volume by more than 50 percent. The oral formulation may cause idiosyncratic hepatitis; however, the topical formulation is still under investigation and is unavailable for clinical trials in the United States. Surgical approaches include excisional procedures to remove part or all of the lymphedematous tissue and microsurgery to create an anastomosis between the lymph system and another vessel. Surgical results have not been uniformly encouraging. Regardless of the surgical intervention chosen, compression therapy will be needed to maintain the reduced volume after surgery.