Primary lymphedema

Basics and definition

Unlike the common secondary “general edema”, lymphedema is not a consequence of one of many underlying diseases, such as cardiac insufficiency, venous insufficiency or renal insufficiency, but an independent, chronic clinical picture with a tendency to progression. It is based on an insufficiency of the lymphatic drainage system, which may be congenital (primary lymphedema) or acquired (secondary lymphedema).

The transport capacity of the lymphatic vessels is too low to absorb the lymphatic loads that arise. The primary (congenital) or secondary (acquired) damage to the lymphatic drainage system can be present at various levels. This then affects the initial lymphatic vessels (lymphatic capillaries, lymphatic sinuses), the precollectors, the lymphatic collectors, the lymphatic trunks and/or lymph nodes, and also leads to chronic inflammatory damage to the interstitium. This increased and altered fluid in the interstitium is also responsible for the typical fibrosclerotic remodeling process seen in prolonged lymphedema.

The most common form in Europe is secondary lymphedema (acquired through damage/injury to the lymphatic transport system) at approximately 89 percent compared to primary lymphedema (congenital lymphatic transport disorder) accounting for approximately 11 percent.

The incidence of primary lymphedema already manifest at birth is about 1 : 6,000, the prevalence of manifest primary lymphedema in under 20-year-olds is about 1 : 87,000.


Classification of lymphedema according to the cause of lymphovascular and lymphonodular diseases:

Primary lymphedemaSecondary lymphedema

Lymphatic vessel aplasia/atresia

Lymphatic vessel hypoplasia

Lymphatic vessel hyperplasia

Lymph node fibrosis

Lymph node agenesis

“Secondary benign lymphedema”:
after curative oncologic therapy
(status following lymphadenectomy, radiotherapy).

“Secondary malignant lymphedema”:
in the case of active malignancy
(drainage obstruction due to primary, metastasis,
lymphangiosis carcinomatosa).

“Secondary chronic lymphedema”:
following non-oncologic damage to lymphatic transport
(vein harvesting for bypass surgery, post-traumatic,
post-infectious, arthritic, late-stage chronic
venous insufficiency).


Primary lymphedema is the result of a genetic predisposition that is either autosomal-dominant or autosomal-recessive hereditary. For more details see also “Genetic basis”.


Classification of lymphedema according to the time of clinical manifestation:

a) Age of manifestation in primary lymphedemab) Manifestation

“Congenital” (in the sense of inborn)

Lymphedema precox (< 35th LY)

Lymphedema tardum (> 35th LY)






Several genes are now known whose mutation is associated with lymphedema. This can relate to isolated lymphedema or complex syndromes associated with lymphedema. See also “Genetic basis”.

Correct classification of lymphedema is necessary for stage-appropriate therapy. This means that only after the lymphedema stage has been assessed should a decision be made on whether to initiate outpatient therapy or to refer the patient for inpatient therapy.

Stages of lymphedema:

Stage 0: No swelling, but pathological lymphoscintigram (“latency stage”).

Stage I: Edema of soft consistency, elevation reduces swelling (“spontaneously reversible stage”).

Stage II: Edema with secondary increasing tissue changes, elevation has no effect; (“spontaneous irreversible stage”).

Stage III: Hard swelling, often lobular form (“deforming stage III”) with typical skin changes - formerly given the derogatory name “elephantiasis”.

Clinical diagnosis

In recent years, improved diagnostic and therapeutic possibilities and, last but not least, the increasing maturity of patients and their relatives with their demand for appropriate therapy have heightened society’s awareness of the problems of lymphological diseases.

Basic diagnostics are enough to make a clinical diagnosis of lymphedema in the vast majority of cases; this consists of the 3 pillars: history - inspection - palpation.

Checklists aid the diagnostic process and should prevent aspects of the disease being overlooked.

Despite this rather straightforward examination method, there is still a distinct lack of knowledge regarding the diagnostic steps − some of which are very simple −that are needed to confirm the diagnosis and also the corresponding stage-appropriate therapy of lymphedema.

The 3 pillars of basic lymphological clinical diagnostics: history, inspection and palpation.

A workflow with checklists for history, inspection and palpation should be “worked through” in the course of clinical examination of the patient so that the diagnosis of lymphedema can be reinforced and the cause and severity can be determined. In this way, the lymphedema can be correctly classified and subsequently treated according to its stage.

Checklist “history”

  • General medical history: (family history, suspected heredity, previous illnesses, constriction furrows, surgical interventions, accidents, past inflammatory processes - especially erysipelas, immobilization due to orthopedic or neurological diseases, autonomic history).
  • Specific edema history: (time course of edema development, triggering factors, initial localization of edema, duration of reversible stage, progression, trigger factors (such as heat or orthostasis), frequency of erysipelas, history of lymphorrhea or lymphocysts, previous lymphological treatments)

Checklist “inspection”

  • Edema distribution: unilateral or bilateral swelling, (typical) asymmetry of the swelling, possibly difference in length of the extremities, localization of the swelling (distal, proximal, generalized, trunk-related).
  • Skin findings: color, trophic disturbances, ulcerations, pigmentation, scars, constriction furrows, papillomatosis cutis lymphostatica, erythema (erysipelas, erythroderma), hyperkeratosis, ectatic skin lymphatics, lymphocysts, lymphatic fistulas, fungal infestation, skin fold retractions (deepened skin folds that cannot be widened), box toes, disturbed nail growth with dorsal deviation

Checklist “palpation”

  • Edema consistency: soft and doughy, turgid elastic, fibrotic, hard induration
  • Induration (pitting edema):  can be indented, permanent
  • Skin temperature: normal, cool, elevated
  • Stemmer's sign: skinfold can be tented over the proximal phalanx of the second and third toes
  • Tissue induration-fibrosis
  • Lymph nodes (enlarged soft, bulging, stuck together, displaceable, tender on palpation)
  • Vascular status (peripheral pulses, venous filling), orthopedic-neurologic status, and functional limitations

These checklists for history, inspection and palpation are available in the appendix of the AWMF S2k guideline on the diagnosis and treatment of lymphedema (from page 89) (see “Recommended literature”).

Imaging diagnosis

Additional imaging diagnostics are only necessary if a diagnosis or clear classification of the lymphedema cannot be deduced from the basic clinical diagnostics (e.g., in early-stage lymphedema without signs of fibrosis, or when there are edema-inducing or aggravating comorbidities).

If complex syndromes or involvement of internal organs are suspected, advanced diagnostic tests are necessary, i.e., imaging and further examinations for fluid accumulation in the body cavities: chylothorax, chylopericardium, chylous ascites, joint effusions. In addition, imaging diagnostics for vascular malformations and dysmorphic syndromes, e.g., by means of duplex sonography, CT, MR angiography, DSA, supplemented by genetic investigations.

Advanced instrumental and imaging diagnostics include edema sonography, indirect lymphangiography, magnetic resonance imaging, functional lymphoscintigraphy, indocyanine green (ICG), near-infrared fluorescent imaging (NIRF).

Edema sonography: Sonography uses a high-resolution (> 13 MHz) ultrasound probe to measure cutis and subcutis thickness, determine the compressibility of the subcutis by probe pressure (sonoelastography), and examine sonomorphologic criteria of chronic lymphedema such as widening of the subcutis with increased echogenicity.

Indirect lymphography: Indirect lymph(angi)ography using water-soluble contrast medium visualizes the peripheral lymphatic vessels with assessment of the contrast pattern. The value of this is controversial.

Magnetic resonance lymphography: MR lymphography can also be used to detect subfascial fluid and to visualize the major lymphatics in the body cavities (cisterna chyli, thoracic duct). However, few data are currently available.

Direct lymphography: Either after dissection of a lymphatic vessel in the foot (pedal lymphography) or via puncture of a lymph node in the groin (intranodal lymphangiography), direct visualization of the lymphatic vessels by direct injection of oily contrast medium, which drains through the lymphatic ducts and can be visualized under fluoroscopy.

Lymphoscintigraphy: This is less a morphologic imaging study and rather a functional study of lymphatic transport. Lymphoscintigraphy is currently considered the gold standard in functional diagnosis. However, it is limited by the fact that uniform measurement standards and protocols including static and dynamic phase, depth or BMI correction, etc., are essential for comparability of measured results, but are not always met. Subclinical lymphedema (in latency stage 0) can so far only be detected by lymphoscintigraphy (pathologically restricted lymphatic transport in the absence of clinical signs).

Fluorescence microlymphography: Examination with FITC (fluorescein isothiocyanate) under –incident light fluorescence microscope provides information about the morphology of the lymph capillaries. It allows visualization of the initial lymphatic vessels (lymph capillaries) and gives indications of their pathology (off-label in the EU).

Near-infrared fluorescent imaging (NIRF): NIRF imaging is based on intradermal injection of the fluorescent dye indocyanine green (ICG), which is absorbed via the initial lymphatic vessels in the dermis and transported centripetally via the superficial lymphatic channels towards the lymph nodes. This allows near real-time visualization of lymphatic drainage.

Conservative therapy

The gold standard in lymphedema therapy is CPD (complex physical decongestive therapy).

It consists of two phases, where phase 1 (decongestion phase) aims to mobilize the increased interstitial fluid and achieve a certain degree of fibrosis loosening.

In phase 2 (maintenance phase) the achieved therapeutic success is conserved and optimized if possible.

The decision as to whether outpatient therapy is possible or whether inpatient therapy is necessary must be made on a case-by-case basis. In general, the lymphedema stage, the localization of the lymphedema, comorbidities and age of the patient are guiding factors.

Young children should receive inpatient treatment at least initially. This enables their parents to be involved in the intensive training so that they can continue the learned therapeutic measures  at home consistently and in the long term.

Treatment under inpatient observation is required in cases of concomitant chylothorax, chylopericardium, protein-losing enteropathy or pronounced lymphocysts/lymphatic fistulas.

Therapy goals of CPD

  • Skin rehabilitation
  • Edema and volume reduction
  • Reduction of future fibrosis
  • Increased joint mobility
  • Training of patients/relatives in self-management, correct use of compression therapy, self-bandaging and decongestive exercises

Further goals are the prevention of late complications such as hyperkeratosis, papillomatosis cutis lymphostatica (lymphangioma circumscriptum) and the avoidance of skin infections caused by fungi or bacteria (erysipelas).

Inpatient lymphological rehabilitation treatment involves 3 weeks of an intensive daily “phase 1” of the two-phase CPD.

“Phase 1” includes the 5 pillars of CPD:

  • Skin rehabilitation/skin care
  • Manual lymphatic drainage
  • Compression bandaging
  • Decongestive exercises
  • Training/empowerment of patients/relatives for self-treatment

At the end of “phase 1” of the two-phase CPD, custom-made, flat-knitted individual compression garments are individually fitted in the decongested state. The type and strength of compression (CCL 1-4) must be determined individually. In infancy, only bandaging is applied. Compression class 1 custom-made stockings are started from the 2nd year of life, and a higher compression class is applied from school age onwards. The supply intervals (2 stockings for hygiene purposes) are usually 3 to 6 months on account of the child's growth.