(See also Overview of the Lymphatic System.)
Lymphedema may be
Primary lymphedemas are inherited and uncommon. They vary in phenotype and patient age at presentation.
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) 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
Secondary lymphedema is far more common than primary.
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 (in developing countries)
Mild lymphedema may also result from leakage of lymph into interstitial tissues in patients with chronic venous insufficiency.
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:
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 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.
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.
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.
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.
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 beta-lactamase–resistant antibiotics that are effective against gram-positive organisms (eg, dicloxacillin, cephalexin).
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.
Cure is unusual, but treatment can decrease symptoms, slow or halt disease progression, and prevent complications.
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