Lymphoedema

• Lymphoedema is chronic swelling caused by failure of lymphatic drainage; fluid and, later, fibrous and fatty tissue accumulate in the skin and subcutaneous tissue.
• Most cases are secondary (acquired): cancer surgery or radiotherapy, filarial infection, venous disease, obesity, trauma or repeated infection; primary (inherited) lymphoedema is uncommon.
• Early disease is soft, pitting and reversible with elevation; later it becomes firm, non-pitting and irreversible, with skin thickening, hyperkeratosis and papillomatosis. A positive Stemmer sign (skin on the dorsum of the toe or finger cannot be pinched) points to lymphatic rather than venous oedema.
• The international standard is complex decongestive therapy followed by lifelong compression, skin care, exercise and elevation. There is no drug cure.
• Lymphatic filariasis, transmitted by mosquitoes, remains a major cause worldwide and is treated in communities by mass drug administration (diethylcarbamazine or ivermectin plus albendazole, depending on co-endemicity).

By the end of this page you should be able to:

1. Explain normal lymph drainage in simple terms and why its failure produces lymphoedema rather than simple oedema.
2. Classify lymphoedema as primary or secondary and name the principal secondary causes, including filariasis.
3. Recognise the clinical stages of lymphoedema (ISL stages 0–III) and elicit the Stemmer sign.
4. Distinguish lymphoedema of the leg from heart failure, nephrotic syndrome, venous disease, lipoedema and other causes of swelling.
5. Outline investigation and treatment, including complex decongestive therapy, cellulitis management and prophylaxis, surgery and filariasis mass drug administration.
6. Recognise complications such as recurrent cellulitis/erysipelas and lymphangiosarcoma, and apply the principles in a low-resource setting.

A review of the German S3 guideline describes it as a physically and mentally stressful, chronically progressive disease, and notes that the lymphatic system is quantitatively the decisive drainage route in most organs: about 5 litres of fluid are filtered from the blood vessels each day in a 70 kg person, of which roughly half reaches the venous angle through the lymphatic trunks.^[1] Transport capacity normally balances lymphatic load; insufficiency arises when load exceeds capacity, or the lymphatics are damaged outright.^[1][3]

Chronic oedema is defined as swelling lasting more than 3 months. Lymphoedema is a form of chronic oedema that is minimally responsive to overnight leg elevation or diuretics, and is accompanied by skin changes such as thickened or fibrotic skin, hyperkeratosis and papillomatosis.^[3]

Every tissue is bathed in interstitial fluid. Under normal conditions, fluid filters out of capillaries into the tissue spaces; most is handled by the lymphatic system rather than reabsorbed directly into veins.^[1][3] Lymph starts in blind-ended lymphatic capillaries, passes through precollectors and larger lymph collectors with valves, is filtered in lymph nodes, and finally drains via lymphatic trunks into the venous system near the great veins of the neck.

If this drainage fails, fluid persists in the tissues. Macromolecules that are not cleared promote inflammation, adipose deposition and fibrosis, and the loss of lymphocyte trafficking makes the affected limb more prone to infection.^[3]

Primary lymphoedema is rare: incidence at birth is about 1 in 6,000, with a prevalence of roughly 1 in 87,000 in people under 20; women are affected far more often than men.^[1] Secondary lymphoedema is much commoner in industrialised countries; it makes up the great majority of cases, and malignant disease with its treatment is the leading cause.^[1][3]

Secondary lymphoedema after cancer treatment varies with the surgery:

• Breast cancer: 19.9% at 12–24 months after axillary lymph node removal, versus 5.6% after sentinel lymph node biopsy.^[1]
• Gynaecological cancers: about 20% after lymph node removal, with rates up to 47–60% reported after some procedures.^[1]
• Multimodal therapy (chemotherapy, radiotherapy, node dissection), advanced disease and a higher body mass index increase the risk.^[1]

Worldwide, lymphatic filariasis affects an estimated 15 million people with lymphoedema and 25 million men with hydrocele, while 657 million people in 39 countries still need preventive chemotherapy.^[6] Since 2000, 9.7 billion drug treatments have been delivered and 21 countries and territories have been validated as having eliminated lymphatic filariasis as a public health problem.^[6]

Primary lymphoedema results from intrinsic damage to the lymphatic vessels or nodes. It may be isolated or part of a syndrome (for example Noonan syndrome or overgrowth syndromes).^[1][4]

Clinically, several classic forms are recognised, often described by age of onset:^[4]

• Congenital lymphoedema (before age 1 year): Milroy disease (hereditary lymphoedema type IA, caused by mutations affecting vascular endothelial growth factor receptor 3, VEGFR3) and Milroy-like disease (type ID, VEGFC mutations), plus other syndromic forms.
• Lymphoedema praecox (ages 2–35 years): Meige disease (hereditary lymphoedema type II) is the commonest non-syndromic form; it classically produces bilateral lower-limb lymphoedema in adolescence or young adulthood, often in females, without other syndromic features. Five syndromic causes also arise at this age (lymphoedema-distichiasis, Emberger syndrome, hereditary lymphoedema type IC, hypotrichosis-lymphoedema-telangiectasia and yellow nail syndrome).
• Lymphoedema tarda (after age 35 years): classically appearing in adult life and thought to be precipitated by a secondary insult such as infection or trauma unmasking a mild lymphatic defect.^[4]
• Hereditary lymphoedema in its various forms is rare, with an estimated prevalence of 0.001%.^[4]

Genes such as CELSR1 have been implicated in some non-syndromic primary lymphoedema with female-predominant penetrance, but no single gene explains most Meige disease, and genetic testing is increasingly used to refine diagnosis.^[4]

Secondary lymphoedema arises from damage to lymphatics or nodes outside the vessel itself:^[1][3]

• Cancer treatment: lymph node dissection and radiotherapy (axillary, groin/iliac, pelvic, para-aortic, neck dissection). This is the commonest cause in industrialised countries.
• Lymphatic filariasis: a major cause worldwide, and the dominant one in tropical Africa, Asia and the Pacific (see below).
• Infection: recurrent cellulitis/erysipelas with lymphatic damage.
• Trauma and surgery: accidents, burns, direct lymphatic injury.
• Obesity: induces and aggravates lymphoedema independently.
• Chronic venous disease / venous insufficiency: longstanding lymphatic overload can lead to mixed oedema with a lymphatic component.
• Podoconiosis, recurrent allergic reactions and prolonged immobility are further recognised contributors.

Lymphatic failure may be dynamic (overload of an intact system), mechanical (damaged or obstructed vessels) or a mixture.^[3] When clearance fails, fluid is not merely excess water: the interstitium accumulates proteins, growth factors and signalling molecules that drive chronic inflammation, adipose deposition and fibrosis.^[1][3] Over time the skin thickens, loses elasticity and develops hyperkeratosis and papillomatosis; macrophage and lymphocyte trafficking falls, explaining the increased infection risk.^[1][3]

In essence, lymphoedema begins as a fluid (pitting) problem and becomes, if untreated, a tissue (fibrotic/fatty, non-pitting) problem. This single observation explains almost every subsequent clinical and staging distinction.

Patients usually describe a gradual, often painless swelling of one limb (sometimes both, or the genitalia), worse after standing or at the end of the day, that may ease overnight in early disease. Secondary symptoms include heaviness, tightness, reduced joint movement and repeated skin infections. Lymphoedema is usually a clinical diagnosis made from history and examination.^[3][4]

Use the approach in cardiac physical examination for the general survey, including assessment of oedema and the cardiac signs that matter in the differential diagnosis.

Key findings:

• Pitting early, non-pitting later. Early on, firm finger pressure leaves a pit that refills slowly. With chronicity the tissues harden and pitting disappears.^[3][2]
• Positive Stemmer sign. The skin just proximal to the toes or fingers is pinched and lifted. If it cannot be lifted from the underlying tissue, the sign is positive and supports lymphatic oedema (it is negative in venous oedema). It is a sensitive clue (about 92%) but only moderately specific (about 57%), and it is more likely to be falsely negative in stage 1 disease or in slim patients; false positives occur in obesity and muscle disease (for example spinal muscular atrophy).^[4][5]
• Skin changes: thickened, hardened skin; hyperkeratosis; papillomatosis; deepened skin folds; papules or "knobs"/nodules in advanced disease; sometimes hyperpigmentation or papillomatous/"mossy" changes. Pure lymphoedema rarely ulcerates, unlike chronic venous disease.^[1][3]
• Limb shape. Swelling is often distal and may involve the dorsum of the foot or hand. Lipoedema, by contrast, often spares the feet.
• Episodes of cellulitis/erysipelas. These are very common. Most are caused by group A beta-haemolytic streptococci, sometimes Staphylococcus or other organisms. Typical features are pain, warmth, redness, swelling, lymphangitis, lymphadenitis and sometimes blistering; severe cases bring fever, rigors, headache or vomiting and may need admission. Triggers include tinea pedis, ingrown nails, scratches, bites and eczema, so skin care matters.^[3]

Where lymphatic filariasis is endemic (tropical Africa, Asia and the Pacific), chronic lymphoedema of the limb, breast or genitalia (elephantiasis) develops years after childhood infection. Living adult worms in the lymphatics disrupt drainage; acute attacks (adenolymphangitis) may be due to the parasite or, more often, secondary bacterial skin infection in a limb with damaged defences.^[6]

A swollen leg has many causes. Lymphoedema is usually unilateral or markedly asymmetric, chronic, pitting early and non-pitting later, with a positive Stemmer sign and eventual skin changes; venous and systemic causes tend to pit, improve overnight and leave the Stemmer sign negative.^[3][4][5]

Lymphoedema is usually diagnosed clinically. Investigations are used to confirm the diagnosis, seek a cause or exclude mimics.^[3][4]

• Routine screening for mimics: clinical assessment; for suspected systemic oedema, check renal, hepatic and thyroid function and serum albumin; for filariasis, a travel/exposure history and appropriate filarial testing (blood smear for microfilariae, or antigen tests where available).^[4][6]
• Duplex ultrasound of the leg when DVT or chronic venous insufficiency is suspected; it also excludes venous causes of swelling.^[4]
• Lymphoscintigraphy (radionuclide imaging of lymph uptake and transport) is the most accurate test when diagnosis is equivocal; roughly 96% sensitive and 100% specific. Abnormal findings include delayed tracer transit and dermal backflow. Obtain it before treatment in uncertain cases.^[5]
• MRI lymphangiography / MR lymphography characterises lymphatic anatomy and is useful in primary lymphoedema or when surgical planning is needed.
• Ultrasound of soft tissues is widely available and helps assess skin/subcutaneous changes and rule out DVT.
• Bioimpedance spectroscopy can detect subclinical fluid accumulation in at-risk limbs (for example after breast cancer) but is not universally available.^[4]

There is no blood test that diagnoses lymphoedema itself.^[3]

The international standard (International Society of Lymphology, ISL) recognises a subclinical stage plus stages I–III.^[1][2] Staging is largely clinical: history, pitting test, Stemmer sign, skin changes and response to elevation.^[2]

Filariasis services and much tropical practice use other staging (often the Dreyer seven-stage system), collapsed clinically to mild/moderate/severe, and podoconiosis has its own system.^[2] These systems agree on the essentials: reversal with elevation divides early from late disease, and skin change defines the most advanced stage.^[2]

There is no medication that cures lymphoedema.^[3] Management is lifelong and aims to prevent progression, control volume, protect skin, treat infection and preserve function. Best practice comprises:^[3]

1. Compression therapy (bandaging for decongestion, then garments for maintenance) — the single most essential element.
2. Meticulous skin and nail care.
3. Education and self-management.
4. Manual lymphatic drainage (MLD).
5. Exercise and elevation.

In the acute phase a trained therapist delivers intensive "phase 1" CDT, which combines:

• Compression bandaging with short-stretch (low-elasticity) systems that generate high working pressure with muscle use and lower resting pressure, mobilising tissue fluid more effectively than simple elastic wraps. Compression enhances venous and lymphatic return, lowers net filtration and stimulates the muscle pump.^[3]
• Manual lymphatic drainage to move fluid from congested regions to functioning lymphatics.
• Skin and nail care (cleansing, moisturising, treating tinea pedis and fissures, meticulous foot hygiene) to close the entry points for infection.
• Decongestive exercise and limb elevation.

CDT reduces limb volume and softens the tissues; it is then followed by a maintenance ("phase 2") programme. In practice, hospital-based CDT is often reserved for severe or complicated disease (for example heart failure, extreme obesity or infected limbs that make outpatient work impossible).^[3]

• Compression garments fitted after volume reduction (stockings, sleeves, sometimes gloves), worn daily and replaced regularly. Compression is the cornerstone of maintenance.
• Continued skin care, exercise (walking, swimming, repetitive muscle contraction) and elevation where helpful.
• Weight management: obesity worsens lymphatic function and lymphoedema; weight reduction improves outcomes.^[1][5]
• Multidisciplinary support (occupational therapy, psychosocial support), since chronic oedema carries a substantial quality-of-life burden.

Acute episodes are usually streptococcal; they are treated with antibiotics according to local guidance, covering group A streptococci (and Staphylococcus where suspected). Good skin care, early treatment and protecting entry points reduce recurrence. After repeated episodes, long-term low-dose prophylactic antibiotic strategies are used in some guidelines; agree the regimen with the treating team and follow the local formulary. Urgent referral is warranted if necrotising infection or systemic sepsis is suspected.^[3]

Surgery has evolved from debulking alone to modern physiological microsurgery, and it is generally reserved for disease that is refractory or advanced. Options include:

• Physiological microsurgery: lymphovenous bypass (anastomosing lymphatics to small veins) and vascularised lymph node transfer, aiming to restore lymphatic transport.
• Reductive/debulking surgery: liposuction or excisional debulking for chronic fibrofatty overgrowth, used in combination with compression and continued self-management.
• In practice, compression and skin care remain essential after surgery.

Older reviews reported limited evidence for surgery in lymphoedema and stressed the need for continued conventional therapy.^[3] Current reviews describe these microsurgical and reductive techniques as active, evolving fields; selection and timing should be handled by a specialist team.

For an individual with lymphatic filariasis, acute adenolymphangitis is treated symptomatically with rest, elevation, antibiotics for secondary bacterial infection and simple local care; adult worms can be killed with diethylcarbamazine where appropriate, under specialist supervision.

At the population level, the WHO strategy is annual mass drug administration (MDA) of all at-risk people for at least 4–6 years, with regimens chosen by co-endemicity:^[6]

• Loiasis-endemic areas: albendazole 400 mg twice yearly.
• Onchocerciasis-endemic (Africa/Sudan-Sahel) areas: ivermectin 200 micrograms/kg plus albendazole 400 mg.
• Areas without onchocerciasis: diethylcarbamazine (DEC) 6 mg/kg plus albendazole 400 mg.
• Selected areas without onchocerciasis meeting programme conditions: ivermectin 200 micrograms/kg plus DEC 6 mg/kg plus albendazole 400 mg (triple therapy).

MDA reduces microfilariae but has limited impact on established adult worms. Established (chronic) lymphoedema management in filariasis is morbidity management: hygiene, skin care, exercise and elevation to prevent acute attacks and progression, plus surgery for hydrocele.^[6] DEC-fortified salt has been used in some unique settings.^[6]

Lymphoedema is chronic and, left untreated, progresses inexorably to fibrotic change, disability and recurrent infection.^[3] Early, well-managed disease can be kept stable and the affected limb can remain soft and functional; this saves hospital admissions (an earlier UK survey estimated that each £1 spent on lymphoedema treatment saved £100 in admission costs).^[3] Compliance with compression and self-care is the main determinant of outcome.

Lymphoedema after cancer treatment is a lifelong risk; specialist lymphoedema therapists, well-fitted garments and ready access to antibiotics for cellulitis improve prognosis. Primary lymphoedema cannot be cured but is managed on the same principles.

• Recurrent cellulitis/erysipelas (the most frequent, driving admissions and costs).^[3]
• Chronic skin changes, fissuring, fungal infection and eczema, which provide portals of entry for infection.^[3]
• Lymphangiosarcoma (Stewart–Treves syndrome): in chronic lymphoedema of 10 years' duration the risk is about 10%. Typically after mastectomy/radiotherapy for breast cancer. It appears as a non-resolving bruise or reddish-purple discolouration progressing to ulceration and necrosis; it is aggressive, spreads readily and has a very poor prognosis. Radical surgery may be required. Any suspicious new lesion in a long-standing lymphoedema needs urgent assessment. Other neoplasms (squamous carcinoma, Kaposi sarcoma, lymphoma) can also arise.^[3]
• Psychological and functional burden, including stigma in filariasis-endemic settings.^[6]

• Cancer services: avoid unnecessary node dissection; use sentinel node biopsy where appropriate; baseline limb measurement and patient education reduce progression in those at risk.^[1]
• Filariasis: MDA and vector control; hygiene and skin care to prevent progression in those already affected.^[6]
• Maintain a healthy weight; obesity is an important aggravating factor.^[1][5]

• Children: primary lymphoedema in a child often signals a hereditary form; assess for syndromic features and refer for genetic testing and family counselling where available.^[4]
• Pregnancy: lymphoedema may first present or worsen; management principles remain (compression, skin care, appropriate antibiotics), with high-risk obstetric input as needed. Specific data are limited; individualise care.
• Older adults: higher prevalence and comorbidity (heart failure, chronic venous disease, diabetes, obesity) make mixed oedema common; treat the vascular and medical contributors as well.

Practical points where tests or specialist care are scarce:

• The diagnosis can usually be made at the bedside. A chronic, firm, non-pitting limb swelling with a positive Stemmer sign and skin change is lymphoedema until proved otherwise. In obesity or muscle disease the Stemmer sign can be misleading; if diagnosis is genuinely uncertain and lymphoscintigraphy is unavailable, a careful trial of compression plus weight optimisation and re-assessment may help, but red flags must be excluded first.
• Compression need not be expensive: multilayer short-stretch bandaging can be improvised and garments can be tailored; the key is sustained pressure and daily use.
• Cellulitis: treat early with the best available antibiotic covering streptococci; keep patients off their feet during an acute attack, then restart compression. Recurrent attacks usually mean breached skin (tinea pedis, cracks), so fix the feet rather than just repeating antibiotics.^[3]
• Treat venous insufficiency, heart failure and malnutrition where present; mixed oedema is common.^[3]
• Refer for specialist microsurgery only when disease is refractory and a centre is accessible; until then, conservative care preserves function.
• Hypothesis-free reassurance is inappropriate where podoconiosis or filariasis is endemic: combined prevention programmes (MDA, footwear) must run alongside individual care.

• Lymphoedema is chronic interstitial swelling from lymphatic failure; it progresses from a fluid (pitting) problem to a tissue (fibrotic, non-pitting, skin-changing) problem.
• It is classified as primary (inherited; Milroy, Meige, lymphoedema tarda and syndromic forms are rare) or secondary (cancer treatment, filariasis, infection, trauma, obesity, chronic venous disease).
• Worldwide, lymphatic filariasis is a leading cause; mass drug administration and morbidity management are the pillars of control.
• Cancer-related lymphoedema is common after node dissection, less so after sentinel biopsy.
• Clinical diagnosis rests on gradual swelling, pitting early/non-pitting later, positive Stemmer sign and characteristic skin change.
• The Stemmer sign is sensitive (about 92%) but only moderately specific (about 57%).
• ISL stages 0–III and the Dreyer/WHO/podoconiosis systems share the same essence: reversal with elevation early, skin change late.
• There is no drug cure. Complex decongestive therapy and lifelong compression, skin care, exercise and elevation are the standard.
• Cellulitis/erysipelas is common (mostly streptococcal) and drives admissions; skin care and early antibiotics are essential.
• Chronic lymphoedema of 10 years' duration carries about a 10% risk of lymphangiosarcoma; any suspicious new lesion needs urgent assessment.
• Prevention means avoiding unnecessary node dissection, managing weight, and delivering filariasis programmes where endemic.

• heart failure
• cardiac physical examination

See front matter. Every reference above is cited in the text.