Venous and lymphatic diseases of the limbs: Lymphoedema
Lymphoedema is the consequence of abnormal amounts of fluid and protein in the interstitial spaces of the skin and subcutaneous tissues particularly with respect to the limbs. The high protein content of the fluid distinguishes this type of swelling, or brawny oedema, from that seen occurring as a result of filtration oedema of heart and kidney failure, venous obstruction and hypoproteinaemia (pitting oedema).
This is an unusual cause of limb swelling. There are two principal types:
- a congenital abnormality of the lymphatic channels (primary lymphoedema)
- secondary lymphatic obstruction resulting from infection, trauma (including surgery and radiotherapy), secondary metastatic tumours and, occasionally, primary tumours such as lymphoma.
The brain and the spinal cord are the only body tissues that do not have significant lymphatic vessels. For all other structures, lymphatic vessels function to collect lymph - tissue fluid including protein that leaks from the capillary bed - and then convey this to the regional lymph nodes, to the major lymphatic trunks and ultimately into the thoracic duct, which terminates by joining the junction of the subclavian and internal jugular vein in the left side of the neck.
The lymphatic capillaries are thin-walled endothelial tubes, the endothelium being supported on collagen with occasional smooth muscle cells. The onward progression of the lymph in these channels is maintained by the presence of valves and the compression applied by neighbouring structures, such as the contraction of muscles and the varying pressure and movement of the gut in the abdominal cavity. The onward flow is also enhanced by the changes in the intrathoracic pressure generated by respiration. The composition of the lymph will vary with the drainage site. If this is the intestine, it will contain chylomicrons. In all cases there is a high concentration of albumin. The lymph flow in the thoracic duct varies from 1 to 4 L per day and the proportions of its final composition will depend on the relative flow from the various sites of the body and the food intake at the time.
Pathogenesis and pathology
The pathogenesis of lymphoedema is invariably a consequence of inadequate lymphatic flow, either because the lymph vessels are congenitally abnormal or deficient, or because of obstruction to the vessels or the draining lymph nodes. Less frequently, temporary lymphoedema can occur in a limb on account of muscle inactivity, as occurs with prolonged sitting, but resolves swiftly with muscle activity.
Primary or idiopathic lymphoedema refers to swelling due to intrinsic abnormalities of the lymphatic vessels. This can be a familial abnormality and is often bilateral and symmetrical. The lymphatic vessels are aplastic in 15% and hypoplastic in 65% of patients, being fewer and smaller in calibre than is normal. They may be varicose, dilated and incompetent in 20% due to fibrosis in the draining lymph nodes. In this group with an intrinsic abnormality present at birth, lymph may reflux into the skin, leak through the skin (especially between the toes), into the peritoneum as chyloperitoneum, into the thorax as chylothorax and into the urine as chyluria.
Acquired lymphoedema often affects only one limb, except when the obstructing lesion is due to an infective agent such as the filarial nematode Wuchereria bancrofti. This is a mosquito-borne parasite of tropical regions. The other infective agents that cause secondary lymphoedema are lymphogranuloma inguinale, tuberculosis and recurrent non-specific infection.
Tumour-induced secondary lymphoedema is most commonly associated with metastatic tumour of the breast causing upper limb lymphoedema and pelvic tumours of the cervix, ovary and uterus in the female, and of the prostate in males giving rise to lower limb lymphoedema.
Iatrogenic or trauma-induced lymphoedema occurs most frequently as a result of block dissections of either the axilla or groin, or in association with radiation of the same region.
The pathological complications of lymphoedema include recurrent infection such as cellulitis and chronic thickening of the skin with hyperkeratosis. In the very long term, lymphangiosarcoma may develop (see External genitalia in the male).
Primary or idiopathic lymphoedema can manifest clinically at various ages. Congenital lymphoedema is apparent at, or within a few weeks of, birth, often in association with some other congenital abnormality.
Lymphoedema praecox refers to lymphoedema not present at birth but which appears before the age of 35 years. It usually affects adolescent women.
Lymphoedema tarda becomes evident after the age of 35 years. This group of patients, usually females, may have uni- or bilateral limb swelling which can affect the upper or lower limbs. There may be a temporal relationship with a minor injury or surgery on the limb that preceeds the onset of the swelling. Initially the swelling is soft and pitting but with time the tissues become more indurated and fibrous. This change is hastened and accentuated by attacks of cellulitis.
Lymphoedema tends to affect the foot and the toes. In the later stages, the skin becomes thickened and hyperkeratotic with wart-like excrescences. In the severe and chronic stage, the limb has a tree trunk-like appearance and can be distinguished from venous oedema by the absence of prominent pigmentation and the chronic venous ulceration commonly seen in severe venous insufficiency oedema.
The swelling of secondary lymphoedema develops more rapidly, often in an older age group and may be associated with dragging discomfort. This form of lymphoedema is frequently secondary to an obstructing lesion; thus there may be changes at the site of obstruction such as scarring, swelling and local erythema. As with primary lymphoedema, these patients are prone to episodes of cellulitis and lymphangitis.
It is important to distinguish lymphoedema from venous oedema or if the swelling involves the lower limbs, or there is compression in the popliteal fossa. The clinical presentation, history and examination will usually suggest either of these conditions but each can be readily excluded by the use of duplex scanning of the lower limb venous system. If the scan does not demonstrate venous obstruction or venous valvular incompetence, the swelling is more likely to be lymphatic in origin. It is important to ensure that the iliac venous system has been sonographically interrogated before a venous cause is excluded.
Oedema associated with generalised problems, such as hypoproteinaemia, nephrotic syndrome or cardiac failure, will be excluded on clinical examination, biochemical tests (e.g. liver function tests, serum protein levels, urea, creatinine and electrolytes) and an examination of the urine for protein.
Specific investigations for lymphoedema are not usually employed as they rarely impact on management. They include lymphoscintography. Radioactive labelled colloids can be injected into the interdigital spaces and should appear within 30 minutes in the regional nodes if the lymphatic vessels are normal. Reduced uptake implies hypoplastic or obliterated lymphatic vessels. In obstructive secondary lymphoedema the radionucleotide uptake in the regional nodes is often normal. It may be slow in the more proximal nodes, indicating an obstruction at that level.
Computed tomography scanning of the regional node area will give an assessment of nodal enlargement if these are obstructive. In primary lymphoedema the number and size of nodes may be diminished.
Lymphangiography is now seldom used because it may accentuate the obliterative process of primary lymphoedema and give rise to infection or an inflammatory process that may relate to the contrast medium used. It will give information about the type and site of lymphatic obstruction and valvular incompetence in the lymph vessels in particular cases.
Hence the diagnosis of lymphoedema, particularly in primary lymphoedema, tends to be a diagnosis of exclusion.
The extent and severity of lymphoedema should be determined and recorded as baseline information to gauge subsequent treatment. The minimum is precise measurements of limb circumference with reference to defined bony points, for example 2 cmabove the medial malleolus.
The major aim of investigating a patient with lymphoedema is to determine whether or not underlying pathology exists.
The treatment of lymphoedema is essentially conservative.
Conservative treatment aims to preserve the quality of the skin, prevent lymphangitis and reduce limb size. Skin quality can be maintained by careful avoidance of trauma and regularly applying a water-based skin lotion. Non-skin drying soaps should be used to minimise the loss of oil from the skin.
Patients with lymphoedema are predisposed to cellulitis and spreading lymphangitis. The problem is that infection will further damage the lymphatic system. Patients should be warned to avoid trauma and to seek early and aggressive management of skin sepsis. Streptococci are the most common organisms causing cellulitis. Early treatment with systemically administered penicillin is indicated if any form of skin sepsis develops. The most common portal of entry is via associated interdigital fungal infection with tinea pedis. If a patient has recurrent attacks of cellulitis, long-term daily prophylaxis with 250 mg of pencillin twice daily is appropriate. For those allergic to penicillin, erythromycin may be given as treatment for acute infections. Any interdigital fungal infection should be treated regularly with an anti-fungal powder, and if there is an established infection, oral griseofulvin can be taken. If the infection fails to respond to standard treatment, alternative antibiotics can be considered.
Limb swelling is best managed with graded compression stockings. The patient should sleep with the foot of the bed elevated on the equivalent of two house bricks and graded compression stockings fitted before the patient gets out of bed. The stockings may range from 30 to 50 mm Hg in their compression depending on the tolerance of the patient. For those with whole limb swelling, the pantyhose or thigh stocking should be used. Similar stockings can be used for those with arm oedema.
Intermittent pneumatic compression may help to reduce limb swelling. The pneumatic compression is applied as a multi-cell unit arranged concentrically. The multi-cell unit inflates successively from peripheral to proximal and thus has a ‘milking’ action driving fluid from the periphery to the centre. The outcome for the use of compression stockings and the intermittent use of external pneumatic compression devices will achieve very satisfactory limb size control in the majority of patients.
Surgical treatment is rarely performed, being reserved for the few patients who cannot have their swelling controlled by compression, have repeated bouts of sepsis or in whom skin changes and the persisting swelling might suggest there is a risk of a neoplasm. Surgery may either involve excision of subcutaneous tissue (Charles operation) or attempts at lymphatic bypass - the latter being still experimental.
Prognosis and results of treatment
The majority of patients can control their leg swelling with compression stockings during the day and nocturnal elevation. The ability to achieve this goal is largely dependent upon the determination and compliance of the patient. This can be facilitated by putting the patient in touch with the local lymphoedema society (see ‘Further reading’).
Davies D, Rogers M. Morphology of lymphatic malformations: a pictorial review. Australas J Dermatol. 2000; 41: 1–5.
Gloviczki P. Principles of surgical treatment of chronic lymphoedema. Int Angiol. 1999;18:42–46.Szuba A, Rockson SG. Lymphoedema: Classification, diagnosis and therapy. Vasc Med. 1998;3:145–156. www.lymphoedema.org.au