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Lymphedema is defined as “the abnormal accumulation of interstitial fluid and fibroadipose tissues resulting from injury, infection, or congenital abnormalities of the lymphatic system.” It occurs where there is an abnormal accumulation of protein-rich fluid in the interstitial tissue compartment, resulting in inflammation, adipose tissue hypertrophy, and fibrosis.1 The consequent limb edema and induration can result in disfigurement, decreased mobility, and/or limb dysfunction, significantly impacting psychological and social function.


Lymphedema occurs due to an imbalance in the rate of lymph production and/or lymph removal via the lymphatic system. Damage of lymph vessels, nodes, or system malfunctioning contributes to this imbalance – which may be due to primary or secondary lymphatic system disorders (see Pathophysiology).

Primary lymphedema is a rare, inherited condition caused by developmental issues of the lymphatic vessels and has three main forms:

  • Congenital lymphedema (Milroy disease) – recognized within 2 years of birth
  • Lymphedema praecox (Meige’s disease) – puberty up to age 35
  • Late-onset lymphedema or lymphedema tarda – beginning after age 35

Secondary lymphedema has multiple causes and can occur at any time point (see Epidemiology).

Epidemiology including risk factors and primary prevention

Secondary lymphedema is more common than primary lymphedema, with an estimated prevalence of 1 in 1,000, compared to 1 in 100,000 respectively.2 Worldwide, filarial infection is the most common cause of secondary lymphedema, affecting over 120 million people.1 In developed countries including the United States, the most common cause of secondary lymphedema is cancer (breast, gynecologic, urologic, melanoma, lymphoma) and/or its treatment (e.g., axillary lymph node dissection or radiation therapy).

The most common cancer associated with secondary lymphedema is breast cancer, with one in five patients developing it.3 The incidence of lymphedema depends on the extent of tissue and lymph nodes removed, and radiation therapy, as outlined in the table below. 4

Preferentially using sentinel lymph node biopsy over axillary node dissection, using axillary reverse mapping to identify and spare lymphatic vessels during node dissection or lymphatic venous anastomoses (LYMPHA), and immediate breast reconstruction, can reduce the incidence of lymphedema.5

In addition, breast cancer patients with higher BMI, abdominal circumference, low physical activity levels, older age, and Black or Hispanic race are at higher risk of developing lymphedema. Overall, the risk of developing lymphedema peaks around 24 months.6,7,8 Current data suggests that starting surveillance early (screening for symptoms, performing circumferential measures, evaluating arm volume with bioimpedance spectroscopy if available) and providing patient education and early intervention may prevent progression to clinical lymphedema.5,9

While the focus has been largely on breast cancer, other cancers including gynecologic (15-60%), prostate (0-22%), head and neck cancers (>90%) are also associated with high rates of lymphedema.10,11

Other risk factors for developing secondary lymphedema include trauma, infection, and obesity. While edema can occur in any tissue, lower extremity is the most common location.

When lymphedema is recognized early, it is much more easily and successfully managed, though there is no clear data on effective strategies for reducing the risk for lymphedema.11

Patients can reduce their risk of lymphedema by exercising, controlling their weight, using compression garments, and performing self-manual lymphatic drainage.


The rate of lymph production may be accelerated due to increased capillary permeability, venous hypertension, decreased capillary oncotic pressure, or increased lymphatic oncotic pressure. Lymph removal can be adversely affected by inherited lymph vessel malformation (primary lymphedema due to aberrant structural development), and secondary disorders, including lymphatic vessel/node injury or inflammation (e.g., infection, radiation therapy), extrinsic compression, tumor infiltration, or surgical excision of affected lymph nodes or vessels due to malignancy.

The lymphatic load consists of white blood cells, triglycerides, protein, bacteria, cell debris, and water from interstitial spaces collected into the superficial (skin and subcutaneous tissue) or deep (muscles, joints, tendon sheaths and nerves) lymphatic system. The transport capacity is the maximum amount of fluid the lymphatic system can carry. In healthy subjects, the transport capacity exceeds the lymphatic load almost ten times. However, when the transport capacity decreases due to lymphatic system dysfunction (as mentioned above), it can no longer manage the excess lymphatic load, resulting in lymphedema. The associated swelling can be distal (in the extremities) or more proximal (breast, chest, pelvis, face), depending of the region affected and may result in skin discoloration, restricted joint range of motion, impaired sensation, pain, and difficulty wearing clothes.

Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)

Once lymphedema occurs, the emphasis is on slowing/stopping disease progression and preventing complications. Studies demonstrated that prospective surveillance, symptom assessment, and compression intervention during subclinical lymphedema in breast cancer reduce progression to chronic lymphedema.12

Lymphedema has several classification schemes. One is defined by the International Society of Lymphology as follows:

  • Stage 0 (latent or subclinical) – swelling is not evident despite impaired lymph transport; may be months or years before overt edema.
  • Stage 1 (spontaneous, reversible) – mild edema with protein-rich fluid and pitting may occur; subsides with limb elevation.
  • Stage 2 (spontaneously irreversible) – moderate edema persists with or without pitting. The skin may undergo inflammation, hardening, or thickening. Limb elevation alone rarely alleviates edema.
  • Stage 3 (lymphostatic elephantiasis) – severe edema in which the limb can become very large and disfigured. Trophic skin changes (leathery appearance), fat deposits, and warty overgrowths are often present.

Another example is the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE):13

  • Grade 1 – Trace thickening or faint discoloration
  • Grade 2 – Marked discoloration, leathery skin texture, papillary formation, limiting instrumental activities of daily living (ADL)
  • Grade 3 – Severe symptoms limiting self-care and activities of daily living

Lymphedema can also be classified by chronicity:

  • New onset/acute: soft or pitting edema of the affected limb or body region
  • Subacute: edema with transition to subcutaneous fibrosis, and recurrent cellulitis and lymphangitis may occur
  • Chronic/stable: edema with fibrous indurated subcutaneous tissue; recurrent cellulitis and lymphangitis, and hyperkeratosis and skin breakdown
  • Pre-terminal

Specific secondary or associated conditions and complications

Skin breakdown and recurrent cellulitis are the most common complications. Episodes of cellulitis were positively associated with lack of access to specialists and longer duration of lymphedema, indicating a need for improved education and telehealth.14Without appropriate treatment, this can be life-threatening. Furthermore, patients may experience musculoskeletal pain due to lymphedema as well as decreased joint range of motion. Patients may also experience psychosocial dysfunction including impaired body image, sexuality concerns, anxiety, and depression. Chronic lymphedema can result in tumors including lymphangiosarcoma (10% risk after 10 years of lymphedema), Kaposi sarcoma and lymphoma.15

Essentials of Assessment


Lymphedema diagnosis is made primarily clinical, based on history and physical examination. Symptoms include overt swelling or subtle complaints such as “fullness” or “heaviness in a region of the body, usually unilateral.”

Timing of edema onset in relation to risk factors (e.g., prior surgery, radiation, trauma, infection, travel to endemic filariasis region, family history of lymphedema) should be investigated as it may affect the differential diagnosis. Patients should be queried regarding recurrent cellulitis or skin breakdown. In patients with a history of cancer, it is important to know whether lymph node dissection was performed.

Differential diagnosis includes edema related to heart failure, liver cirrhosis, acute deep venous thrombosis, chronic venous insufficiency, post-thrombotic syndrome, cellulitis, renal failure, nephropathy (or other protein-losing condition), lipedema, myxedema (from hypothyroidism), and drug reaction.

Physical examination

  • Soft, pitting edema (early)
  • Fibrosis and induration (later)
  • Hyperkeratosis, papillomatosis, cellulitis
  • Lymphangioma and lymphorrhea
  • Evaluate for visible axillary cording in breast cancer patients16
  • Stemmer sign (inability to grasp skin of dorsum second digit of the foot)
  • Range of motion measurement
  • Limb circumference or volume measurement (20% or less difference between limbs is mild-moderate, greater than 20% is considered severe)
  • Vascular assessment
  • Neurologic exam: strength, sensation 

Functional assessment

Upper limb involvement may affect a patient’s ability to perform activities of daily living, especially if the dominant limb is involved, while ambulation may be impaired with severe lower limb involvement due to disfiguration or increased limb size/weight.

Psychological problems may include impaired body image, loss of self-esteem, social withdrawal, decreased quality of life, and depression.

Laboratory studies

In order to exclude other causes of edema, laboratories and imaging studies may be of help. If an infectious process is suspected, ordering a Complete Blood Count (CBC) and inflammatory markers is recommended. Additionally, a Comprehensive Metabolic Panel (CMP) and thyroid function tests will help in evaluating renal/liver dysfunction or thyroid dysfunction respectively. If thromboembolic disease is suspected, a venous Doppler ultrasound should be ordered.

Supplemental assessment tools

There are various methods available for practitioners to assess lymphedema.

In addition to surveilling for lymphedema and monitoring its progression, it is important to evaluate patient psychosocial and physical quality of life. Standard instruments such as SF-36 can be used but lymphedema-specific ones are presented in the table below.

Early predictions of outcomes

Starting lifestyle interventions for at-risk patients (i.e., high BMI, sedentary) could reduce rates of lymphedema. Early identification is an important predictor of successful management.33,31 Certain surgical strategies such as sentinel lymph node biopsy, as opposed to axillary, can help with primary prevention.30,32

The National Comprehensive Cancer Network (NCCN), a non-profit alliance of leading comprehensive cancer centers in the United States provides guidelines that are recognized as standard for clinical guidance in oncologic care. In March 2023, the survivorship guidelines for lymphedema were updated, recommending regular screening for lymphedema, including objective measurements such as bioimpedance spectroscopy if available.33

Social role and social support system

The National Lymphedema Network (www.lymphnet.org) is a non-profit organization providing education for patients and health professionals regarding risk reduction and management of lymphedema. The website includes a search function for identifying certified lymphedema therapists. The lymphedema schools of North America (Academy of Lymphatic Studies (ACOLS), KLOSE training, Norton School of Lymphatic Therapy) and the Lymphology Association of North America also provide a list of certified lymphedema therapists in the United States. The American Cancer Society (www.cancer.org) provides educational material as well.

Rehabilitation Management and Treatments

Available or current treatment guidelines

Earlier treatment is optimal in order to obtain the best results in the management of lymphedema. Further studies are needed to evaluate and compare therapeutic approaches. Currently, the standard of care includes complex decongestive therapy (CDT) which consists of a reductive phase (decrease edema) that lasts approximately 4-12 weeks and the maintenance phase (goal is to prevent edema exacerbation or complications), which is life-long. CDT includes the following:

  • Manual lymphatic drainage (MLD): Massage performed by a certified lymphedema therapist, performed distal to proximal in the affected region of the body. The goal is to stimulate and direct lymphatic flow to reduce edema. Some studies demonstrated that MLD may not have preventive effects on lymphedema and that patients with chronic breast cancer-related lymphedema demonstrated no significant benefit of MLD over placebo MLD.34-36
  • Short stretch/inelastic compression bandaging: Works in concert with muscle activity to improve lymph clearance and prevent re-accumulation of fluid.
  • Compression garment/sleeves: These may be prefabricated (off-the-shelf) or custom-fit pressure garments (20-30 mmHg or 30-40 mmHg are the most commonly prescribed) and can be flat knitted or circular knitted. They are worn after maximizing volume reduction, for prevention of exacerbations. The compression sleeves have a high resting and low working pressure, and therefore, nighttime use is contraindicated. They are highly recommended during exercise. 
  • Skin hygiene to minimize infection risk: Patients should be educated to maintain the skin moisturized with emollients or low-pH moisturizers. When exposed to sunlight, it is recommended to use long sleeves or apply sunscreen. Additionally, though non-definitive evidence is available, patients are recommended to avoid blood draws or blood pressure measurements taken in the affected arm.
  • Exercises: Decongestive exercises in conjunction with individualized MLD therapy, including active range of motion and stretching exercises.
  • Intermittent pneumatic compression (IPC): sequential compression devices are used adjunctively with MLD in the maintenance phase. This may be appropriate in selective patient populations after a thorough clinical evaluation. IPC can help reduce the feeling of heaviness or tightness in patients with pitting edema. Risks may include increasing fibrosis due to increased removal of fluid and genital swelling.37

The combination of manual lymphatic drainage and exercise in the early postoperative period in patients with breast cancer who underwent axillary node dissection has been associated with lower risk of secondary lymphedema 1 year after surgery. Physical therapy should be encouraged in subclinical lymphedema (stage 0) to improve arm mobility. Additionally, patients should be educated to avoid skin trauma and to ensure appropriate skin care and hygiene to avoid infections.38

Mild lymphedema (stage 1) is managed with compression garments and manual lymphatic drainage (MLD).

Moderate to severe lymphedema (stage 2 and 3) is managed with a more aggressive regimen with complete decongestive therapy (CDT). Surgical interventions may be required if no response to conservative treatments.

For breast cancer-associated lymphedema, applying nighttime compression with bandages or nighttime compression garments, significantly improved limb volume compared to standard treatment.39

A recent study found that significant limb volume reduction after 4 weeks of decongestive lymph therapy was associated with large initial limb volume, longer duration (4 weeks compared with 2), in the presence of PAD.40

Surgical procedures

Surgical interventions could be either reconstructive with the goal of restoring the lymphatic system (i.e., lymphatic venous anastomosis (LVA) or vascularized lymph node transplant (VLNT)) or reductive, with the goal of removing excess fatty tissue (liposuction).

LVA results in limb volume reduction, symptom improvement, and decreased rate of cellulitis; however, patients should continue prior conservative measures for maintenance. The resulting decrease in limb volume persists for at least five years.41

VLNT uses jejunal mesenteric, groin, lateral thoracic omental or submental nodes as donor sites and grafts them to the receptor site, leading to reduced limb volume, cellulitis episodes and improved QoL, and possibly reduces the need for continuing conservative measures.42 However, the effects of VLNT are slow and it carries a risk for developing lymphedema at the donor site.43 Current studies suggest that QOL improvement is greater with VLNT, compared to LVA, and that VLNT may result in greater reduction in limb circumference and episodes of cellulitis.44,45

Reductive techniques are generally used for chronic non-pitting lymphedema, when there is predominance of fatty tissue deposition in the affected arm. These patients experience significant improvement in QoL. The goal is to reduce the size of the extremity by removing excess fatty tissue. However, these patients also require continuing use of compression garments.

Other therapies:

  • Benzopyrones: This agent is known for its effect on reducing vascular permeability and reducing the amount of fluid forming in the subcutaneous tissues. However, studies are variable and do not support its efficacy for the management of lymphedema or lymphedema-associated symptoms.
  • Vascular endothelial growth factors (VEGF): VEGF has a role in lymphangiogenesis and gene mutations in VEGF have been identified in congenital forms of lymphedema. A clinical trial was reported in 2020, where VGEF-C Lymfactin was used in breast cancer-related lymphedema but results have not been published.46
  • Anti-inflammatory treatments: The pathophysiology of lymphedema includes acute inflammation, fibrosis, and oxidative stress. Specifically, the effect of non-steroidal anti-inflammatory agent ketoprofen has been evaluated in preclinical studies, specifically patients with breast cancer-related lymphedema (BCRL). The study showed significant improvements in skin pathology but not significant differences in limb volume or bioimpedance studies.47
  • Immune pathways: Studies have demonstrated infiltration of T helper cells in lymphedematous tissues. Specifically, higher density of CD4+ cells have been associated with clinical severity of lymphedema.48Interleukins are necessary for the differentiation of CD4+ cells. In a preclinical study, IL3/IL4 neutralizing antibodies were studied in patients with BCRL and they found improvement in quality of life, skin stiffness and histologic changes. However, there were not significant differences in volume measures or bioimpedance scores.49
  • Diuretics: The use of diuretics has not been generally effective.
  • Photobiomodulation or low-level laser therapy (650 to 1000 nm wavelength) has anti-inflammatory properties, can improve lymphatic mobility, promote lymph vessel regeneration, and prevent tissue fibrosis.50 It may provide some improvement in arm circumference and symptoms; however, research is ongoing.
  • Aquatic therapy: No evidence of improved efficacy has been found when compared to standard care.51

At different disease stages

  • Includes potential curative interventions (see above)
  • Includes symptom relief (see above)
  • Includes rehabilitation strategies that intend to stabilize or optimize function or prepare for further interventions at later disease stages (see above)

Subacute (see above)

  • Self-management: includes self-MLD, skin hygiene, routine self-examination (e.g., for infection, increased edema), consistent wearing and proper fit of compression garments, weight control and exercise, and may also include intermittent use of IPC.


  • Resistive and aerobic/cardiovascular exercise should be added to regain strength and endurance.

Pre-terminal or end of life care

  • Focused on aggressive management of distressing symptoms. Includes pain management, assistive equipment for mobility and performance of activities of daily living. Hospice providers can be guided on basic therapeutic alternatives such as compression therapy.

Weight control, skin care and hygiene should be advised during all stages of the disease.

Patient & family education

Since self-management is key to successful control of lymphedema, proper patient and family education and training in long-term self-management is crucial. This includes self MLD, self-bandaging, wearing schedule for compression garments, hygiene, and monitoring for signs and symptoms of cellulitis.

Lymphedema is associated with impaired limb function and pain, poorer psychological well-being and quality of life, impaired body image, impaired sexual interest or sexual activity, impaired social confidence, employment concerns and economic burden. Thus, it is important to assess the patient holistically as well as provide caregiver education. The psychosocial impact of lymphedema in males should be further studied.52

Emerging/unique interventions

Cell therapies (including differentiated or progenitor cells), gene therapies and lymph node-targeting nanoparticles have shown promising results in non-human studies and should be further investigated as a possible treatment of lymphedema.53-55

Cutting Edge/Emerging and Unique Concepts and Practice

Randomized controlled trials have shown that resistance exercises are safe. A 2020 systematic review looked at 16 studies and concluded that resistance exercise seems to be safe and does not increase risk of recurrent lymphedema.56 General contraindications include worsening edema (concern for acute VTE) or signs of new/active infection.

Gaps in the Evidence-Based Knowledge

Further studies are needed to evaluate if MDL contributes to the formation of collateral pathways and improved lymphatic flow. Additionally, most of the studies are focused on breast cancer-related lymphedema (BCRL), for which other types of lymphedema should be further studied.57


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Original Version of the Topic

Patrick Kortebein, MD. Lymphedema. 11/102011.

Previous Revision(s) of the Topic

Roshni Durgam, MD, Anna Lasak, MD. Lymphedema. 5/5/2016

Arpit Arora, MD. Lymphedema. 5/12/2021

Author Disclosure

Ady Correa, MD
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Rosalynn Conic, MD, PhD, MPH
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