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Lymphedema

by James D. Douketis, MD

Lymphedema is edema of a limb due to lymphatic hypoplasia (primary) or to obstruction or disruption (secondary) of lymphatic vessels. Symptoms and signs are brawny, fibrous, nonpitting edema in one or more limbs. Diagnosis is by physical examination. Treatment consists of exercise, pressure gradient dressings, massage, and sometimes surgery. Cure is unusual, but treatment may lessen symptoms, slow progression, and prevent complications. Patients are at risk of cellulitis, lymphangitis, and, rarely, lymphangiosarcoma.

Etiology

Lymphedema may be primary (due to lymphatic hypoplasia) or secondary (due to obstruction or disruption of lymphatic vessels).

Primary lymphedemas

Primary lymphedemas are inherited and uncommon. They vary in phenotype and patient age at presentation.

Congenital lymphedema appears before age 2 yr and is due to lymphatic aplasia or hypoplasia. Milroy disease is an autosomal dominant familial form of congenital lymphedema attributed to vascular endothelial growth factor receptor-3 ( VEGFR-3 ) gene mutations and sometimes associated with cholestatic jaundice and edema or diarrhea due to a protein-losing enteropathy caused by intestinal lymphangiectasia.

Lymphedema praecox appears between ages 2 and 35, typically in women at the onset of menses or pregnancy. Meige disease is an autosomal dominant familial form of lymphedema praecox attributed to mutations in a transcription factor gene ( FOXC2 ) and associated with extra eyelashes (distichiasis), cleft palate, and edema of legs, arms, and sometimes the face.

Lymphedema tarda occurs after age 35. Familial and sporadic forms exist; the genetic basis of both is unknown. Clinical findings are similar to those of lymphedema praecox but may be less severe.

Lymphedema is prominent in some other genetic syndromes, including Turner syndrome; yellow nail syndrome, characterized by pleural effusions and yellow nails; and Hennekam syndrome, a rare congenital syndrome of intestinal and other lymphangiectases, facial anomalies, and intellectual disability.


Secondary lymphedema

Secondary lymphedema is far more common than primary. It is most commonly caused by surgery (especially lymph node dissection, typically for treatment of breast cancer), radiation therapy (especially axillary or inguinal), trauma, lymphatic obstruction by a tumor, and, in developing countries, lymphatic filariasis. Mild lymphedema may also result from leakage of lymph into interstitial tissues in patients with chronic venous insufficiency.


Symptoms and Signs

Symptoms of secondary lymphedema include aching discomfort and a sensation of heaviness or fullness.

The cardinal sign is soft-tissue edema, graded in 3 stages:

  • In stage 1, the edema is pitting, and the affected area often returns to normal by morning.

  • In stage 2, the edema is nonpitting, and chronic soft-tissue inflammation causes early fibrosis.

  • In stage 3, the edema is brawny and irreversible, largely because of soft-tissue fibrosis.

The swelling is most often unilateral and may worsen when the weather is warm, before menstruation occurs, and after the limb remains for a long time in a dependent position. It can affect any part of the limb (isolated proximal or distal) or the entire extremity; it can restrict range of motion when swelling is periarticular. Disability and emotional distress can be significant, especially when lymphedema results from medical or surgical treatment.

Skin changes are common and include hyperkeratosis, hyperpigmentation, verrucae, papillomas, and fungal infections.

Complications

Lymphangitis (see Lymphangitis) may develop, most often when bacteria enter through skin cracks between the toes as a result of fungal infections or through cuts to the hand. Lymphangitis is almost always streptococcal, causing erysipelas; sometimes it is staphylococcal. The affected limb becomes red and feels hot; red streaks may extend proximally from the point of entry, and lymphadenopathy may develop. Rarely, the skin breaks down. Rarely, long-standing lymphedema leads to lymphangiosarcoma (Stewart-Treves syndrome), usually in postmastectomy patients and in patients with filariasis.


Diagnosis

  • Clinical diagnosis

  • CT or MRI if cause is not apparent

Primary lymphedema is usually obvious, based on characteristic soft-tissue edema throughout the body and other information from the history and physical examination.

Diagnosis of secondary lymphedema is usually obvious from physical examination. Additional tests are indicated when secondary lymphedema is suspected unless the diagnosis and cause are obvious. CT and MRI can identify sites of lymphatic obstruction; radionuclide lymphoscintigraphy can identify lymphatic hypoplasia or sluggish flow. Progression can be monitored by measuring limb circumference, measuring water volume displaced by the submerged limb, or using skin or soft-tissue tonometry; these tests have not been validated. In developing countries, tests for lymphatic filariasis should be done (see Bancroftian and Brugian Lymphatic Filariasis). If lymphedema seems much greater than expected (eg, on the basis of lymph node dissection) or appears after a delay in a woman treated for breast cancer, cancer recurrence should be considered.

Prognosis

Cure is unusual once lymphedema occurs. Meticulous treatment and possibly preventive measures can lessen symptoms, slow or halt disease progression, and prevent complications.

Treatment

  • Sometimes surgical reconstruction for primary lymphedema

  • Mobilizing fluid (eg, by elevation and compression, massage, pressure bandages, intermittent pneumatic compression)

Treatment of primary lymphedema may include surgical soft-tissue reduction (removal of subcutaneous fat and fibrous tissue) and reconstruction if quality of life is significantly reduced.

Treatment of secondary lymphedema involves managing its cause. For lymphedema itself, several interventions to mobilize fluid (complex decongestive therapy) can be used. They include manual lymphatic drainage, in which the limb is elevated and compressed (“milked”) toward the heart; gradient pressure bandages or sleeves; limb exercises; and limb massage, including intermittent pneumatic compression. Surgical soft-tissue reduction, lymphatic reanastomoses, and formation of drainage channels are sometimes tried but have not been rigorously studied.

Preventive measures include avoiding heat, vigorous exercise, and constrictive garments (including blood pressure cuffs) around the affected limb. Skin and nail care require meticulous attention; vaccination, phlebotomy, and IV catheterization in the affected limb should be avoided.

Cellulitis and lymphangitis are treated with β-lactamase–resistant antibiotics that are effective against gram-positive organisms (eg, oxacillin, cloxacillin, dicloxacillin).

Drugs Mentioned In This Article

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  • BACTOCILL IN PLASTIC CONTAINER
  • No US brand name

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