(See also Overview of the Lymphatic System Overview of the Lymphatic System Plasma, along with some white blood cells, routinely moves out of capillaries into the interstitial space. Most of the fluid and its constituents is taken up by tissue cells or reabsorbed into... read more .)
Etiology of Lymphedema
Lymphedema may be
Primary: Due to lymphatic hypoplasia
Secondary: Due to obstruction or disruption of lymphatic vessels
Primary lymphedemas are inherited and account for < 5% of cases of lymphedema. They vary in phenotype and patient age at presentation but mostly involve the lower extremities.
Congenital lymphedema appears before age 2 years 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) that causes 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
Yellow nail syndrome Nail deformities and dystrophies associated with systemic problems Deformities are often considered together with dystrophies, but the two are slightly different; deformities are generally considered to be gross changes in nail shape, whereas dystrophies are... read more , characterized by pleural effusions and yellow nails
Hennekam syndrome, a rare congenital syndrome of intestinal and other lymphangiectases, facial anomalies, and intellectual disability
Secondary lymphedema accounts for > 95% of cases.
Most common causes are
Surgery (especially lymph node dissection, typically for treatment of breast cancer)
Radiation therapy (especially axillary or inguinal)
Lymphatic obstruction by a tumor
Lymphatic filariasis Bancroftian and Brugian Lymphatic Filariasis Lymphatic filariasis is infection with any of 3 species of Filarioidea. Acute symptoms include fever, lymphadenitis, lymphangitis, epididymitis, and funiculitis (inflammation of the spermatic... read more (present in some tropical and subtropical areas)
Mild lymphedema may also result from leakage of lymph into interstitial tissues in patients with chronic venous insufficiency Chronic Venous Insufficiency and Postphlebitic Syndrome Chronic venous insufficiency is impaired venous return, sometimes causing lower extremity discomfort, edema, and skin changes. Postphlebitic (postthrombotic) syndrome is symptomatic chronic... read more .
Symptoms and Signs of Lymphedema
Symptoms of lymphedema include aching discomfort and a sensation of heaviness or fullness.
The cardinal sign is soft-tissue edema, graded in 3 stages:
Stage 1: The edema is pitting, and the affected area often returns to normal by morning.
Stage 2: The edema is nonpitting, and chronic soft-tissue inflammation causes early fibrosis.
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.
Rarely, an affected limb becomes extremely large, and the hyperkeratosis is severe, giving the appearance of elephant skin (elephantiasis). This manifestation is more common with filariasis than with other causes of lymphedema.
Lymphangitis Lymphangitis Lymphangitis is acute bacterial infection (usually streptococcal) of peripheral lymphatic channels. (See also Overview of Bacterial Skin Infections and Lymphadenitis.) Typical causes of lymphangitis... read more 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. Infrequently, the skin breaks down, which may lead to local infection or cellulitis.
Rarely, long-standing lymphedema leads to lymphangiosarcoma (Stewart-Treves syndrome), usually in postmastectomy patients and in patients with filariasis.
Diagnosis of Lymphedema
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 (to measure resistance to compression); these tests have not been validated.
Tests for lymphatic filariasis Bancroftian and Brugian Lymphatic Filariasis Lymphatic filariasis is infection with any of 3 species of Filarioidea. Acute symptoms include fever, lymphadenitis, lymphangitis, epididymitis, and funiculitis (inflammation of the spermatic... read more should be done in n tropical and subtropical areas where the infecting microfilariae are present.
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 for Lymphedema
Cure is unusual once lymphedema occurs. Meticulous treatment and possibly preventive measures can lessen symptoms, slow or halt disease progression, and prevent complications.
Treatment of Lymphedema
Sometimes surgical soft-tissue reduction and 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 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.
Pearls & Pitfalls
Cellulitis and lymphangitis are treated with beta-lactamase–resistant antibiotics that are effective against gram-positive organisms (eg, dicloxacillin).
Secondary lymphedema (due to obstruction or disruption of lymphatic vessels) is far more common than primary lymphedema (which is due to lymphatic hypoplasia).
Elephantiasis (extreme hyperkeratosis of skin in a limb affected by lymphedema) is a severe manifestation of lymphedema usually due to lymphatic filariasis.
Cure is unusual, but treatment can decrease symptoms, slow or halt disease progression, and prevent complications.