CHAPTER
58 Lymphatic disorders
LEARNING OBJECTIVES
To understand:
The main functions of the lymphatic system
The development of the lymphatic system
INTRODUCTION
The lymphatic system was first described by Erasistratus in
Alexandria more than 2000 years ago. William Hunter, in the
late eighteenth century, was the first to describe the function of
the lymphatic system. Starlings pioneering work on the hydro-
static and haemodynamic forces controlling the movement of
fluid across the capillary provided further insights into the func-
tion of the lymphatics. However, there is much about the lym-
phatic system that is not understood and debate continues over
the precise aetiology of the most common abnormality of the
system, namely lymphoedema.
ANATOMY AND PHYSIOLOGY OF THE
LYMPHATIC SYSTEM
Functions
The principal function of the lymphatics is the return of protein-
rich fluid to the circulation through the lymphaticovenous junc-
tions in the jugular area. Thus, water, electrolytes, low molecular
weight moieties (polypeptides, cytokines, growth factors) and
macromolecules (fibrinogen, albumin, globulins, coagulation
and fibrinolytic factors) from the interstitial fluid (ISF) return
to the circulation via the lymphatics. Intestinal lymph (chyle)
transports cholesterol, long-chain fatty acids, triglycerides and
the fat-soluble vitamins (A, D, E and K) directly to the circula-
tion, bypassing the liver. Lymphocytes and other immune cells
also circulate within the lymphatic system.
Development and macroanatomy
In the human embryo lymph sacs develop at 67 weeks gestation
as four cystic spaces, one on either side of the neck and one in
each groin. These cisterns enlarge and develop communications
that permit lymph from the lower limbs and abdomen to drain
William Hunter, 17181783, anatomist and obstetrician who became the first Professor
of Anatomy at the Royal Academy of Arts, London, UK. He was the elder brother of John
Hunter, the anatomist and surgeon.
Erasistratus of Chios, c.300250 BC, of the Medical School at Alexandria in Egypt is regarded by many as the first physiologist.
Ernest Henry Starling, 18661927, Professor of Physiology, University College, London, UK.
Josef Disse, 18521912, a German anatomist.
10-58-B&L_26th-Pt10_Ch58_cp.indd 923
The various causes of limb swelling
The aetiology, clinical features, investigations
and treatment of lymphoedema
via the cisterna chyli into the thoracic duct, which in turn drains
into the left internal jugular vein at its confluence with the left
subclavian vein. Lymph from the head and right arm drains via
a separate lymphatic trunk, the right lymphatic duct, into the
right internal jugular vein. Lymphatics accompany veins every-
where except in the cortical bony skeleton and central nervous
system, although the brain and retina possess cerebrospinal fluid
and aqueous humour, respectively.
The lymphatic system comprises lymphatic channels, lym-
phoid organs (lymph nodes, spleen, Peyers patches, thymus,
tonsils) and circulating elements (lymphocytes and other mono-
nuclear immune cells). Lymphatic endothelial cells are derived
from embryonic veins in the jugular and perimesonephric areas
from where they migrate to form the primary lymph sacs and
plexus. Both transcription (e.g. Prox1) and growth (e.g. VEGF-
C) factors are essential for these developmental events.
Microanatomy and physiology
Lymphatic capillaries
Lymphatics originate within the ISF space from specialised
endothelialised capillaries (initial lymphatics) or non-endothe-
lialised channels such as the spaces of Disse in the liver. Initial
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lymphatics are unlike arteriovenous capillaries in that:
they are blind-ended;
they are much larger (50 m);
they allow the entry of molecules of up to 1000 kDa in size
because the basement membrane is fenestrated, tenuous or
even absent and the endothelium itself possesses intra- and
intercellular pores;
they are anchored to interstitial matrix by filaments. In the
resting state, initial lymphatics are collapsed. When ISF
volume and pressure increases, initial lymphatics and their
pores are held open by these filaments to facilitate increased
drainage.
Terminal lymphatics
Initial lymphatics drain into terminal (collecting) lymphatics
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that possess bicuspid valves and endothelial cells rich in the
contractile protein actin. Larger collecting lymphatics are sur-
rounded by smooth muscle. Valves partition the lymphatics into
segments (lymphangions) that contract sequentially to propel
lymph into the lymph trunks.
Lymph trunks
Terminal lymphatics lead to lymph trunks, which have a struc-
ture similar to that of veins, namely a single layer of endothelial
cells, lying on a basement membrane overlying a media compris-
ing smooth muscle cells that are innervated with sympathetic,
parasympathetic and sensory nerve endings. About 10 per cent
of lymph arising from a limb is transported in deep lymphatic
trunks that accompany the main neurovascular bundles. The
majority, however, is conducted against venous flow from deep
to superficial in epifascial lymph trunks. Superficial trunks form
lymph bundles of various sizes, which are located within strips
of adipose tissue, and tend to follow the course of the major
superficial veins.
Starlings forces
The distribution of fluid and protein between the vascular system
and ISF depends on the balance of hydrostatic and oncotic pres-
sures between the two compartments (Starlings forces), together
with the relative impermeability of the blood capillary mem-
brane to molecules over 70 kDa. In health there is net capillary
filtration, which is removed by the lymphatic system.
Transport of particles
Particles enter the initial lymphatics through interendothelial
openings and vesicular transport through intraendothelial pores.
Large particles are actively phagocytosed by macrophages and
transported through the lymphatic system intracellularly.
Mechanisms of lymph transport
Resting ISF is negative (2 to 6 mmH2O), whereas lymphatic
pressures are positive, indicating that lymph flows against a small
pressure gradient. It is believed that prograde lymphatic flow
depends upon three mechanisms:
1 transient increases in interstitial pressure secondary to muscu-
lar contraction and external compression;
2 the sequential contraction and relaxation of lymphangions;
3 the prevention of reflux because of valves.
Lymphangions are believed to respond to increased lymph
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flow in much the same way as the heart responds to increased
venous return in that they increase their contractility and stroke
volume. Contractility is also enhanced by noradrenaline, sero-
tonin, certain prostaglandins and thromboxanes, and endothe-
lin-1. Pressures of up to 3050 mmHg have been recorded
in normal lymph trunks and up to 200 mmHg in severe lym-
phoedema. Lymphatics may also modulate their own contrac-
tility through the production of nitric oxide and other local
mediators. Transport in the thoracic and right lymph ducts also
depends upon intrathoracic (respiration) and central venous
(cardiac cycle) pressures. Therefore, cardiorespiratory disease
may have an adverse effect on lymphatic function.
In summary, in the healthy limb, lymph flow is largely due to
intrinsic lymphatic contractility, although this is augmented by
exercise, limb movement and external compression. However,
in lymphoedema, when the lymphatics are constantly distended
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with lymph, these external forces assume a much more impor-
tant functional role.
ACUTE INFLAMMATION OF THE
LYMPHATICS
Acute lymphangitis is an infection, often caused by Streptococcus
pyogenes or Staphylococcus aureus, which spreads to the draining
lymphatics and lymph nodes (lymphadenitis) where an abscess
may form. Eventually this may progress to bacteraemia or septi-
caemia. The normal signs of infection (rubor, calor, dolor) are
present and a red streak is seen in the skin along the line of the
inflamed lymphatic (Figure 58.1). The part should be rested to
reduce lymphatic drainage and elevated to reduce swelling, and
the patient should be treated with intravenous antibiotics based
upon actual or suspected sensitivities. Failure to improve within
48 hours suggests inappropriate antibiotic therapy, the presence
of undrained pus or the presence of an underlying systemic dis-
order (malignancy, immunodeficiency). The lymphatic damage
caused by acute lymphangitis may lead to recurrent attacks of
infection and lymphoedema; patients with lymphoedema are
prone to so-called acute inflammatory episodes (see below).
Figure 58.1 Acute lymphangitis of the arm. Erythematous streaks extend
from the site of primary infection on the volar aspect of the forearm to
epicondylar nodes at the elbow and from there to enlarged and tender
axillary lymph nodes.
LYMPHOEDEMA
Definition
Lymphoedema may be defined as abnormal limb swelling caused
by the accumulation of increased amounts of high protein ISF
secondary to defective lymphatic drainage in the presence of
(near) normal net capillary filtration.
The scope of the clinical problem
At birth, 1 in 6000 people will develop lymphoedema with an
overall prevalence of 0.132 per cent. The condition is not only
associated with significant physical symptoms and complications
but is also a frequent cause of emotional and psychological dis-
tress, which can lead to difficulties with relationships, education
and work (Summary box 58.1).
Despite this significant impact on quality of life, many suffer-
ers choose not to seek medical advice because of embarrassment
and a belief that nothing can be done. Patients who do come
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Summary box 58.1
Symptoms frequently experienced by patients
with lymphoedema
Swelling, clothing or jewellery becoming tighter
Constant dull ache, even severe pain
Burning and bursting sensations
General tiredness and debility
Sensitivity to heat
Pins and needles
Cramp
Skin problems, including flakiness, weeping, excoriation
and breakdown
Immobility, leading to obesity and muscle wasting
Backache and joint problems
Athletes foot
Acute infective episodes
forward for help, especially those with non-cancer-related lym-
phoedema, often find they have limited access to appropriate
expertise and treatment. Lymphoedema is often misdiagnosed
and mistreated by doctors, who frequently have a poor under-
standing of the importance of the condition, believing it to
be primarily a cosmetic problem in the early stages. However,
making an early diagnosis is important because relatively simple
measures can be highly effective at this stage and can prevent
the development of disabling late disease, which is often very
difficult to treat. It is also an opportunity for patients to make
contact with patient support groups (Summary box 58.2).
Summary box 58.2
What every patient with lymphoedema should
receive
An explanation of why the limb is swollen and the
underlying cause
Guidance on skin hygiene and care and the avoidance of
acute infective episodes
Antifungal prophylactic therapy to prevent athletes foot
Rapid access to antibiotic therapy if necessary, hospital
admission for acute infective episodes
Appropriate instructions regarding exercise therapy
Manual lymphatic drainage (MLD)
Multilayer lymphoedema bandaging (MLLB)
Compression garments and, if appropriate, specialised
footwear
Advice on diet
Access to support services and networks
The severity of unilateral limb lymphoedema can be classi-
fied as:
mild: <20 per cent excess limb volume;
moderate: 2040 per cent excess limb volume;
severe: >40 per cent excess limb volume.
Pathophysiology
The ISF compartment (1012 litres in a 70-kg man) constitutes
50 per cent of the wet weight of the skin and subcutaneous
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Lymphoedema 925
tissues and, in order for oedema to be clinically detectable, its
volume has to double. About 8 litres (protein concentration
approximately 2030 g/L, similar to ISF) of lymph is produced
each day and travels in afferent lymphatics to lymph nodes.
There, the volume is halved and the protein concentration
doubled, resulting in 4 litres of lymph re-entering the venous
circulation each day via efferent lymphatics. In one sense, all
oedema is lymphoedema in that it results from an inability of
the lymphatic system to clear the ISF compartment. However, in
most types of oedema this is because the capillary filtration rate is
pathologically high and overwhelms a normal lymphatic system,
resulting in the accumulation of low-protein oedema fluid. In
contrast, in true lymphoedema, when the primary problem is
in the lymphatics, capillary filtration is normal and the oedema
fluid is relatively high in protein. Of course, in a significant
number of patients with oedema there is both abnormal capillary
filtration and abnormal lymphatic drainage, as in chronic venous
insufficiency (CVI) for example.
Lymphoedema results from lymphatic aplasia, hypoplasia,
dysmotility (reduced contractility with or without valvular insuf-
ficiency), obliteration by inflammatory, infective or neoplastic
processes, or surgical extirpation. Whatever the primary abnor-
mality, the resultant physical and/or functional obstruction
leads to lymphatic hypertension and distension, with further
secondary impairment of contractility and valvular competence.
Lymphostasis and lymphotension lead to the accumulation
in the ISF of fluid, proteins, growth factors and other active
peptide moieties, glycosaminoglycans and particulate matter,
including bacteria. As a consequence, there is increased collagen
production by fibroblasts, an accumulation of inflammatory cells
(predominantly macrophages and lymphocytes) and activation
of keratinocytes. The end result is protein-rich oedema fluid,
increased deposition of ground substance, subdermal fibrosis
and dermal thickening and proliferation. Lymphoedema, unlike
all other types of oedema, is confined to the epifascial space.
Although muscle compartments may be hypertrophied because
of the increased work involved in limb movement, they are
characteristically free of oedema.
Classification
Two main types of lymphoedema are recognised:
1 Primary lymphoedema, in which the cause is unknown (or at
least uncertain and unproven); it is thought to be caused by
congenital lymphatic dysplasia.
2 Secondary or acquired lymphoedema, in which there is a
PART 10 | VASCULAR
clear underlying cause.
Primary lymphoedema is usually further subdivided on the basis
of the presence of family history, age of onset and lymphangi-
ographic findings (Tables 58.1 and 58.2) (see below).
Risk factors for lymphoedema
Although the true risk factor profile for lymphoedema is not cur-
rently known, a number of factors are thought to predispose an
individual to its development and predict progression, severity
and outcome of the condition (Table 58.3).
Symptoms and signs
In most cases, the diagnosis of primary or secondary lymphoe-
dema can be made and the condition can be differentiated from
other causes of a swollen limb on the basis of history and exami-
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Table 58.1 Aetiological classification of lymphoedema.

Primary Congenital (onset <2 years old): sporadic;

lymphoedema familial (NonneMilroys disease)
Praecox (onset 235 years old): sporadic;
familial (LetessierMeiges disease)
Tarda (onset after 35 years old)
Secondary Parasitic infection (filariasis)
lymphoedema Fungal infection (tinea pedis)
Exposure to foreign body material (silica
particles)
Primary lymphatic malignancy
Metastatic spread to lymph nodes
Radiotherapy to lymph nodes
Surgical excision of lymph nodes
Trauma (particularly degloving injuries)
Superficial thrombophlebitis
Deep venous thrombosis

Table 58.2 Clinical classification of lymphoedema.

Grade (Brunner) Clinical features

Subclinical (latent) There is excess interstitial fluid and histological
abnormalities in lymphatics and lymph nodes,
but no clinically apparent lymphoedema
Figure 58.2 The foot of a patient with typical lymphoedema.
I Oedema pits on pressure and swelling largely
or completely disappears on elevation and bed
rest
II Oedema does not pit and does not
significantly reduce upon elevation, positive
Stemmers sign
III Oedema is associated with irreversible skin
changes, i.e. fibrosis, papillae

nation without recourse to complex investigation (Table 58.4).

Unlike other types of oedema, lymphoedema characteristically
involves the foot (Figure 58.2). The contour of the ankle is
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lost through infilling of the submalleolar depressions, a buffalo

hump forms on the dorsum of the foot, the toes appear square
because of confinement of footwear and the skin on the dorsum
of the toes cannot be pinched because of subcutaneous fibrosis
(Stemmers sign). Lymphoedema usually spreads proximally to
knee level and less commonly affects the whole leg (Figure 58.3).
In the early stages, lymphoedema will pit and the patient will
report that the swelling is down in the morning. This represents
a reversible component to the swelling, which can be controlled.
Failure to do so allows fibrosis, dermal thickening and hyperkera-
tosis to occur. In general, primary lymphoedema progresses more
slowly than secondary lymphoedema. Chronic eczema fungal
infection of the skin (dermatophytosis) and nails (onychomyco-
sis), fissuring, verrucae and papillae (warts) are frequently seen
in advanced disease. Ulceration is unusual, except in the pres-
ence of chronic venous insufficiency. Figure 58.3 The lower leg of a patient with typical lymphoedema.

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 Lymphoedema 927

Table 58.3 Risk factors for lymphoedema.

Upper limb/trunk lymphoedema Lower limb lymphoedema

Surgery with axillary lymph node dissection, particularly if extensive Surgery with inguinal lymph node dissection
breast or lymph node surgery Postoperative pelvic radiotherapy
Scar formation, fibrosis and radiodermatitis from postoperative Recurrent soft tissue infection at the same site
axillary radiotherapy Obesity
Radiotherapy to the breast or to the axillary, internal mammary or Varicose vein stripping and vein harvesting
subclavicular lymph nodes
Genetic predisposition/family history of chronic oedema
Drain/wound complications or infection
Advanced cancer
Cording (axillary web syndrome)
Intrapelvic or intra-abdominal tumours that involve or directly compress
Seroma formation lymphatic vessels
Advanced cancer Orthopaedic surgery
Obesity Poor nutritional status
Congenital predisposition Thrombophlebitis and chronic venous insufficiency, particularly post-
Trauma in an at-risk arm (venepuncture, blood pressure thrombotic syndrome
measurement, injection) Any unresolved asymmetrical oedema
Chronic skin disorders and inflammation Chronic skin disorders and inflammation
Hypertension Concurrent illnesses such as phlebitis, hyperthyroidism, kidney or
Taxane chemotherapy cardiac disease
Insertion of pacemaker Immobilisation and prolonged limb dependency
Arteriovenous shunt for dialysis Air travel
Air travel Living in or visiting an area for endemic lymphatic filariasis
Living in or visiting an area for endemic lymphatic filariasis
Reproduced with permission from: Lymphoedema Framework. Best practice management of lymphoedema. International Consensus. London: MEP Ltd, 2006. MEP Ltd 2006.

Lymphangiomas are dilated dermal lymphatics that blister
onto the skin surface. The fluid is usually clear but may be
blood-stained. In the long term, lymphangiomas thrombose
and fibrose, forming hard nodules that may raise concerns
about malignancy. If lymphangiomas are <5 cm across, they
are termed lymphangioma circumscriptum, and if they are
more widespread, they are termed lymphangioma diffusum. If
they form a reticulate pattern of ridges then it has been termed
lymphoedema ab igne. Lymphangiomas frequently weep (lym-
phorrhoea, chylorrhoea), causing skin maceration, and they
act as a portal for infection. Protein-losing diarrhoea, chylous
ascites, chylothorax, chyluria and discharge from lymphangi-
manifest (20 years). It presents as single or multiple bluish/red
skin and subcutaneous nodules that spread to form satellite
lesions, which may then become confluent. The diagnosis is usu-
ally made late and confirmed by skin biopsy. Amputation offers
the best chance of survival but, even then, most patients live for
less than three years. It has been suggested that lymphoedema
leads to an impairment of immune surveillance and so predis-
poses to other malignancies, although the causal association is
not as definite as it is for lymphangiosarcoma (Summary box
58.3).

PART 10 | VASCULAR
omas suggest lymphangectasia (megalymphatics) and chylous Summary box 58.3
reflux.
Ulceration, non-healing bruises and raised purple-red nodules Malignancies associated with lymphoedema
should lead to suspicion of malignancy. Lymphangiosarcoma was Lymphangiosarcoma (StewartTreves syndrome)
originally described in postmastectomy oedema (StewartTreves Kaposis sarcoma (HIV)
syndrome) and affects around 0.5 per cent of patients at a mean Squamous cell carcinoma
onset of ten years. However, lymphangiosarcoma can develop in Liposarcoma
any long-standing lymphoedema, but usually takes longer to Malignant melanoma
Malignant fibrous histiocytoma
Fred Waldorf Stewart, 18941991, Chairman of Pathology, Memorial Sloan-Kettering
Basal cell carcinoma
Hospital, New York, NY, USA. An annual award was instituted in his name by the Lymphoma
Department of Pathology called the Fred Waldorf Stewart Award.

Ab igne is Latin for from fire.

William Morrant Baker, 18391896, surgeon, St Bartholomews Hospital, London, UK, described these cysts in 1877.
Norman Treves, 18941964, an American surgeon. He had a special interest in male breast cancer.
Stewart and Treves reported this condition in a joint paper in 1948.

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 928 LY M P H AT I C D I S O R D E R S

Table 58.4 Differential diagnosis of the swollen limb.

Non-vascular General disease states Cardiac failure from any cause

or lymphatic
Local disease processes
Retroperitoneal fibrosis
Gigantism
Drugs
Trauma
Obesity
Venous Deep venous thrombosis
Post-thrombotic syndrome
Varicose veins
KlippelTrenaunays syndrome
and other malformations
External venous compression
Ischaemiareperfusion
Arterial Arteriovenous malformation
Aneurysm
PART 10 | VASCULAR
Liver failure
Hypoproteinaemia due to nephrotic syndrome, malabsorption, protein-losing enteropathy
Hypothyroidism (myxoedema)
Allergic disorders, including angioedema and idiopathic cyclic oedema
Prolonged immobility and lower limb dependency
Ruptured Bakers cyst
Myositis ossificans
Bony or soft-tissue tumours
Arthritis
Haemarthrosis
Calf muscle haematoma
Achilles tendon rupture
May lead to arterial, venous and lymphatic abnormalities
Rare
All tissues are uniformly enlarged
Corticosteroids, oestrogens, progestagens
Monoamine oxidase inhibitors, phenylbutazone, methyldopa, hydralazine, nifedipine
Painful swelling due to reflex sympathetic dystrophy
Lipodystrophy
Lipoidosis
There may be an obvious predisposing factor, such as recent surgery
The classical signs of pain and redness may be absent
Swelling, usually of the whole leg, due to iliofemoral venous obstruction
Venous skin changes, secondary varicose veins on the leg and collateral veins on the
lower abdominal wall
Venous claudication may be present
Simple primary varicose veins are rarely the cause of significant leg swelling
Rare
Present at birth or develops in early childhood
Comprises an abnormal lateral venous complex, capillary naevus, bony abnormalities,
hypo(a)plasia of deep veins and limb lengthening
Lymphatic abnormalities often coexist
Pelvic or abdominal tumour including the gravid uterus
Retroperitoneal fibrosis
Following lower limb revascularisation for chronic and particularly chronic ischaemia
May be associated with local or generalised swelling
Popliteal

Femoral
False aneurysm following (iatrogenic) trauma

PRIMARY LYMPHOEDEMA
Aetiology
It has been proposed that all cases of primary lymphoedema
are due to an inherited abnormality of the lymphatic system,
sometimes termed congenital lymphatic dysplasia. However,
it is possible that many sporadic cases of primary lymphoedema
occur in the presence of a (near-)normal lymphatic system and
are actually examples of secondary lymphoedema for which
the triggering events have gone unrecognised. These might
include seemingly trivial (but repeated) bacterial and/or fungal
infections, insect bites, barefoot walking (silica), deep venous
thrombosis (DVT) or episodes of superficial thrombophlebitis.
In animal models, simple excision of lymph nodes and/or trunks
leads to acute lymphoedema, which resolves within a few weeks,
presumably because of the development of collaterals. The
human condition can only be mimicked by inducing extensive
lymphatic obliteration and fibrosis. Even then, there may be
considerable delay between the injury and the onset of oedema.
Primary lymphoedema is much more common in the legs than
the arms. This may be because of gravity and a bipedal posture,

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 Secondar y lymphoedema 929

the fact that the lymphatic system of the leg is less well devel-
oped, or the increased susceptibility of the leg to trauma and/or
infection. Furthermore, loss of the venoarteriolar reflex (VAR),
which protects lower limb capillaries from excessive hydrostatic
forces in the erect posture, with age and disease (CVI, diabetes),
may be important.
Classification
Primary lymphoedema is usually classified on the basis of appar-
ent genetic susceptibility, age of onset or lymphangiographic
findings. None of these is ideal and the various classification sys-
tems in existence can appear confusing and conflicting as various
terms and eponyms are used loosely and interchangeably. This
has hampered research and efforts to gain a better understand-
ing of underlying mechanisms, the effectiveness of therapy and
prognosis.
Genetic susceptibility
Primary lymphoedema is often subdivided into those cases in
which there appears to be a genetic susceptibility or element to
the disease, and those in which there is not. The former may be
further divided into those cases that are familial (hereditary),
when typically the only abnormality is lymphoedema and there
is a family history, and those cases that are syndromic, when the
lymphoedema is only one of several congenital abnormalities
and is either inherited or sporadic. Syndromic lymphoedema
may be sporadic and chromosomal (Turners (XO karyotype),
Klinefelters (XXY), Downs (trisomy 21) syndrome) or clearly
inherited and related to an identified or presumed single-gene
defect (lymphoedemadistichiasis (autosomal dominant defect
in FOXC2 gene)), or of uncertain genetic aetiology (yellow-nail
and KlippelTrenaunayWebers syndromes). Familial (heredi-
tary) lymphoedema can be difficult to distinguish from non-
familial lymphoedema because a reliable family history may
be unobtainable, the nature of the genetic predisposition is
unknown and the genetic susceptibility may only translate into
clinical disease in the presence of certain environmental factors.
Although the distinction may not directly affect treatment, the
patients are often concerned lest they be passing on the disease
to their children.
Two main forms of familial (hereditary) lymphoedema are
recognised NonneMilroy (type I) and LetessierMeige (type
II) although it is likely that both eponymous diseases overlap
and represent more than a single disease entity and genetic
abnormality. Milroys disease is estimated to be present in 1 in
Age of onset
Lymphoedema congenita (onset at or within two years of birth)
is more common in males and is more likely to be bilateral
and involve the whole leg. Lymphoedema praecox (onset from
2 to 35 years) is three times more common in females, has a
peak incidence shortly after menarche, is three times more
likely to be unilateral than bilateral and usually only extends
to the knee. Lymphoedema tarda develops, by definition, after
the age of 35 years and is often associated with obesity, with
lymph nodes being replaced with fibrofatty tissue. The cause is
unknown. Lymphoedema developing for the first time after 50
years should prompt a thorough search for underlying (pelvic,
genitalia) malignancy. It is worth noting that, in such patients,
lymphoedema often commences proximally in the thigh rather
than distally (Figure 58.4).
Lymphangiographic classification
Browse has classified primary lymphoedema on the basis of lym-
phangiographic findings (Table 58.5 and Figures 58.5 and 58.6).
These findings may be related to the clinical presentations
described above. Some patients with lymphatic hyperplasia pos-
sess megalymphatics in which lymph or chyle refluxes freely
under the effects of gravity against the physiological direction of
flow. The megalymphatics usually end in thin-walled vesicles on
the skin, serous surfaces (chylous ascites, chylothorax), intestine
(protein-losing enteropathy), kidney or bladder (chyluria)
(Figure 58.7).
SECONDARY LYMPHOEDEMA
This is the most common form of lymphoedema. There are sev-
eral well-recognised causes including infection, inflammation,
neoplasia and trauma (Table 58.6).

PART 10 | VASCULAR
6000 live births and is probably inherited in an autosomal domi-
nant manner with incomplete (about 50 per cent) penetrance. In
some families, the condition may be related to abnormalities in
the gene coding for a vascular endothelial growth factor receptor
3 (VEGFR3) on chromosome 5. The disease is characterised by
brawny lymphoedema of both legs (and sometimes the genitalia,
arms and face), which develops from birth or before puberty. Figure 58.4 This patient, in her sixth decade, presented with rapid onset
The disease has been associated with a wide range of lymphatic of lymphoedema of the right leg. On further investigation she was found
abnormalities on lymphangiography. Meiges disease is similar to to have locally advanced bladder carcinoma. Note that unlike most
Milroys disease, except that the lymphoedema generally devel- cases of lymphoedema the swelling is greater proximally than distally.
ops between puberty and middle age (50 years). It usually affects
one or both legs but may involve the arms. Some, but not all, Sir Norman Leslie Browse, formerly Professor of Surgery, the United Medical and Dental
cases appear to be inherited in an autosomal dominant manner. Schools of Guys and St Thomass Hospitals, London, UK; former President of the Royal
College of Surgeons of England.
Lymphangiography generally shows aplasia or hypoplasia.

Henry Hubert Turner, 18921970, Professor of Medicine, The University of Oklahoma, OK, USA.
Harry Fitch Klinefelter, Jr, born 1912, Associate Professor of Medicine, The Johns Hopkins University Medical School, Baltimore MD, USA, described this syndrome in 1942.
John Langdon Haydon Down (sometimes given as Langdon-Down), 18281896, physician, The London Hospital, London, UK.
Max Nonne, 18611959, a neurologist of Hamburg, Germany, described this disease in 1891.
William Forsyth Milroy, 18551942, Professor of Clinical Medicine, Columbia University, New York, NY, USA, described the condition in 1892.
Henri Meige, 18661940, physician, La Salptrire, Paris, France, gave his description of the disease in 1899.

10-58-B&L_26th-Pt10_Ch58_cp.indd 929 10/09/2012 11:42

 930 LY M P H AT I C D I S O R D E R S

Table 58.5 Lymphangiographic classification of primary lymphoedema.

Congenital hyperplasia (10%) Distal obliteration (80%) Proximal obliteration (10%)

Age of onset Congenital Puberty (praecox) Any age
Sex distribution Male > female Female > male Male = female
Extent Whole leg Ankle, calf Whole leg, thigh only
Laterality Unilateral = bilateral Often bilateral Usually unilateral
Family history Often positive Often positive No
Progression Progressive Slow Rapid
Response to compression therapy Variable Good Poor
Comments Lymphatics are increased in Absent or reduced distal There is obstruction at the level
number; although functionally superficial lymphatics. Also of the aortoiliac or inguinal
defective, there is usually an termed aplasia or hypoplasia nodes. If associated with distal
increased number of lymph dilatation, the patient may benefit
nodes. May have chylous from lymphatic bypass operation.
ascites, chylothorax and protein- Other patients have distal
losing enteropathy obliteration as well

Filariasis oedema is often massive, in which case it is termed elephantiasis

This is the most common cause of lymphoedema worldwide,
affecting up to 100 million individuals. It is particularly preva-
lent in Africa, India and South America where 510 per cent
of the population may be affected. The viviparous nematode
Wucheria bancrofti, whose only host is man, is responsible for
90 per cent of cases and is spread by the mosquito. The disease
is associated with poor sanitation. The parasite enters lymphat-
ics from the blood and lodges in lymph nodes, where it causes
fibrosis and obstruction, due partly to direct physical damage and
partly to the immune response of the host. Proximal lymphat-
ics become grossly dilated with adult parasites. The degree of
PART 10 | VASCULAR
(Figure 58.8). Immature parasites (microfilariae) enter the blood
at night and can be identified on a blood smear, in a centrifuged
specimen of urine or in lymph itself. A complement fixation
test is also available and is positive in present or past infection.
Eosinophilia is usually present. Diethylcarbamazine destroys the
parasites but does not reverse the lymphatic changes, although
there may be some regression over time. Once the infection has
been cleared, treatment is as for primary lymphoedema. Public
health measures to reduce mosquito breeding, protective cloth-
ing and mosquito netting may be usefully employed to combat
the condition (Summary box 58.4).

Figure 58.6 This patient presented with lymphoedema of the right leg. A
bipedal lymphangiogram demonstrated normal lymphatics in the right
Figure 58.5 This patient presented with congenital lymphoedema of the leg up to the inguinal nodes, but no progression of contrast above the
right leg. The lymphangiogram shows lymphatic hypoplasia. inguinal ligament a case of proximal obstruction.

10-58-B&L_26th-Pt10_Ch58_cp.indd 930 10/09/2012 11:42

 Secondar y lymphoedema 931

Table 58.6 Classification of causes of secondary lymphoedema.

Classification Example(s)
Trauma and tissue damage Lymph node excision
Radiotherapy
Burns
Variscose vein surgery/harvesting
Large/circumferential wounds
Scarring
Malignant disease Lymph node metastases
Infiltrative carcinoma
Lymphoma
Pressure from large tumours
Venous disease Chronic venous insufficiency
Venous ulceration
Post-thrombotic syndrome
Intravenous drug use
Infection Cellulitis/erysipelas
Lymphadenitis
Tuberculosis
Filariasis
Inflammation Rheumatoid arthritis
Dermatitis
Psoriasis
Sarcoidosis
Figure 58.7 Lymphangiogram demonstrating reflux from dilated para- Dermatosis with epidermal involvement
aortic vessels into the left kidney in a patient with filariasis who pre- Endocrine disease Pretibial myxoedema
sented with chyluria. Immobility and dependency Dependency oedema
Paralysis
Factitious Self-harm
Reproduced with permission from: Lymphoedema Framework. Best practice
Summary box 58.4 management of lymphoedema. International Consensus. London: MEP Ltd, 2006.
MEP Ltd 2006.
Features of filariasis
Acute childhood and rapidly spreads proximally. The condition is
Fever prevented and its progression is slowed by the wearing of shoes.
Headache
Malaise Bacterial infection
Inguinal and axillary lymphadenitis Lymphangitis and lymphadenitis can cause lymphatic destruc-
Lymphangitis tion that predisposes to lymphoedema complicated by further
Cellulitis, abscess formation and ulceration
acute inflammatory episodes. Interestingly, in such patients,

PART 10 | VASCULAR
Funiculo-epididymo-orchitis
lymphangiography has revealed abnormalities in the contralat-
Chronic
Lymphoedema of legs (arm, breast)
eral, unaffected limb, suggesting an underlying, possibly inher-
Hydrocoele ited, susceptibility. Lymphatic and lymph node destruction by
Abdominal lymphatic varices tuberculosis is also a well-recognised cause of lymphoedema,
Chyluria especially in developing countries.
Lymphuria
Malignancy and its treatment
Treatment (surgery, radiotherapy) for breast carcinoma is the
most common cause of lymphoedema in developed countries,
but is decreasing in incidence as surgery becomes more con-
Endemic elephantiasis (podoconiosis) servative (see Chapter 53). Lymphoma may present with lym-
This is common in the tropics and affects more than 500 000 phoedema, as may malignancy of the pelvic organs and external
people in Africa. The barefoot cultivation of soil composed of genitalia. Kaposis sarcoma developing in the course of human
alkaline volcanic rocks leads to destruction of the peripheral immunodeficiency virus (HIV)-related illness may cause lym-
lymphatics by particles of silica, which can be seen in macro- phatic obstruction and is a growing cause of lymphoedema in
phages in draining lymph nodes. Plantar oedema develops in certain parts of the world.

10-58-B&L_26th-Pt10_Ch58_cp.indd 931 10/09/2012 11:42

 932 LY M P H AT I C D I S O R D E R S
Figure 58.8 Elephantiasis due to filariasis.
Trauma
It is not unusual for patients to develop chronic localised or gen-
eralised swelling following trauma. The aetiology is often multi-
factorial and includes disuse, venous thrombosis and lymphatic
injury or destruction. Degloving injuries and burns are particu-
larly likely to disrupt dermal lymphatics. Tenosynovitis can also
be associated with localised subcutaneous lymphoedema, which
can be a cause of troublesome persistent swelling following ankle
and wrist sprains and repetitive strain injury.
PART 10 | VASCULAR
Lymphoedema and chronic venous
insufficiency
It is important to appreciate the relationship between lym-
phoedema and CVI as both conditions are relatively common
and so often coexist in the same patient, and it can be difficult
to unravel which components of the patients symptom complex
are caused by each. There is no doubt that superficial venous
thrombophlebitis (SVT) and DVT can both lead to lymphatic
destruction and secondary lymphoedema, especially if recurrent.
Lymphoedema is an important contributor to the swelling of
the postphlebitic syndrome. It has also been suggested that lym-
phoedema can predispose to DVT, and possible SVT, through
immobility and acute inflammatory episodes. Certainly, tests of
venous function (duplex ultrasonography, plethysmography) are
frequently abnormal in patients with lymphoedema.
10-58-B&L_26th-Pt10_Ch58_cp.indd 932
It is not uncommon to see patients (usually women) with
lymphoedema in whom a duplex ultrasound scan has revealed
superficial reflux (such reflux is present subclinically in up to
one-third of the adult population). Although isolated, superficial
venous reflux rarely, if ever, leads to limb swelling; such patients
are frequently misdiagnosed as having venous disease rather
than lymphoedema, and are subjected mistakenly to varicose
vein surgery. Not only will such surgery invariably fail to relieve
the swelling, it will usually make it worse as saphenofemoral and
saphenopopliteal ligation, together with saphenous stripping,
will compromise still further drainage through the subcutaneous
lymph bundles (which follow the major superficial veins) and
draining inguinal and popliteal lymph nodes.
Miscellaneous conditions
Rheumatoid and psoriatic arthritis (chronic inflammation and
lymph node fibrosis), contact dermatitis, snake and insect bites,
and retroperitoneal fibrosis are all rare but well-documented
causes of lymphoedema. Pretibial myxoedema is due to the oblit-
eration of initial lymphatics by mucin.
Conditions mimicking lymphoedema
Factitious lymphoedema
This is caused by application of a tourniquet (a rut and sharp
cut-off is seen on examination) or hysterical disuse in patients
with psychological and psychiatric problems.
Immobility
Generalised or localised immobility of any cause leads to chronic
limb swelling that can be misdiagnosed as lymphoedema, for
example the elderly person who spends all day (and sometimes
all night) sitting in a chair (armchair legs), the hemiplegic stroke
patient and the young patient with multiple sclerosis.
Lipoedema
This presents almost exclusively in women and comprises bilat-
eral, usually symmetrical, enlargement of the legs and, some-
times, the lower half of the body because of the abnormal depo-
sition of fat. It may or may not be associated with generalised
obesity. There are a number of features that help to differentiate
the condition from lymphoedema but, of course, lipoedema may
coexist with other causes of limb swelling. It has been proposed
that lipoedema results from, or at least is associated with, fatty
obliteration of lymphatics and lymph nodes (Summary box
58.5).
INVESTIGATION OF LYMPHOEDEMA
Are investigations necessary?
It is usually possible to diagnose and manage lymphoedema
purely on the basis of history and examination, especially when
the swelling is mild and there are no apparent complicating
features. In patients with severe, atypical and multifactorial
swelling, investigations may help confirm the diagnosis, inform
management and provide prognostic information.
Routine tests
These include a full blood count, urea and electrolytes, creati-
10/09/2012 11:43

Summary box 58.5
Features of lipoedema that help differentiate it
from lymphoedema
Occurs almost exclusively in women
Onset nearly always coincides with puberty
Nearly always bilateral and symmetrical
Involvement of trunk
The feet are not involved, leading to an inverse shouldering
effect at the malleoli
No pitting
No response to elevation or compression
No skin changes of lymphoedema (negative Stemmers sign)
MRI shows subcutanteous fat but no fluid accumulation
nine, liver function tests, thyroid function tests, plasma total
protein and albumin, fasting glucose, C-reactive protein, urine
dipstick including observation for chyluria, blood smear for
microfilariae, chest radiograph and ultrasound.
Lymphangiography
Direct lymphangiography involves the injection of contrast
medium into a peripheral lymphatic vessel and subsequent
radiographic visualisation of the vessels and nodes. It remains
the gold standard for showing structural abnormalities of larger
lymphatics and nodes (Figure 58.9). However, it can be tech-
nically difficult, it is unpleasant for the patient, it may cause
further lymphatic injury and, largely, it has become obsolete as
a routine method of investigation. Few centres now perform this
technique and those that do generally reserve it for preoperative
evaluation of the rare patient with megalymphatics who is being
considered for bypass or fistula ligation. Indirect lymphangiog-
raphy involves the intradermal injection of water-soluble, non-
Normal Congenital
hyperplasia
Thoracic duct
nodes
Para-aortic
Iliac
Femoral
Figure 58.9 Lymphangiographic patterns of primary lymphoedema.
10-58-B&L_26th-Pt10_Ch58_cp.indd 933
Investigation of lymphoedema 933
ionic contrast into a web space, from where it is taken up by lym-
phatics and then followed radiographically. It will show distal
lymphatics but not normally proximal lymphatics and nodes.
Isotope lymphoscintigraphy
This has largely replaced lymphangiography as the primary diag-
nostic technique in cases of clinical uncertainty. Radioactive
technetium-labelled protein or colloid particles are injected into
an interdigital web space and specifically taken up by lymphat-
ics, and serial radiographs are taken with a gamma camera. The
technique provides a qualitative measure of lymphatic func-
tion rather than quantitative function or anatomical detail.
Quantitative lymphoscintigraphy is performed using a dynamic
(exercise) component in addition to the static test and provides
information on lymphatic transport.
Computed tomography
A single, axial computed tomography (CT) slice through the
midcalf has been proposed as a useful diagnostic test for lym-
phoedema (coarse, non-enhancing, reticular honeycomb pat-
tern in an enlarged subcutaneous compartment), venous oedema
(increased volume of the muscular compartment) and lipoedema
(increased subcutaneous fat). CT can also be used to exclude
pelvic or abdominal mass lesions.
Magnetic resonance imaging
Magnetic resonance imaging (MRI) can provide clear images of
lymphatic channels and lymph nodes, and can be useful in the
assessment of patients with lymphatic hyperplasia. MRI can also
distinguish venous and lymphatic causes of a swollen limb, and
detect tumours that may be causing lymphatic obstruction.
Ultrasound
Ultrasound can provide useful information about venous func-
tion including DVT and venous abnormalities.
Distal obliteration Proximal Proximal
(hypo/aplasia) obliteration obliteration
(hypo/aplasia) (hypo/aplasia)
with distal with distal
hyperplasia obliteration
PART 10 | VASCULAR
10/09/2012 11:43
 934 LY M P H AT I C D I S O R D E R S
Pathological examination
In cases in which malignancy is suspected, samples of lymph
nodes may be obtained by fine-needle aspiration, needle core
biopsy or surgical excision. Skin biopsy will confirm the diagno-
sis of lymphangiosarcoma.
Limb volume measurement
While not helpful in the diagnosis of lymphoedema, limb
volume measurement is a useful tool to determine severity of
lymphoedema, guide management and assess response to treat-
ment. Limb volume is typically measured at diagnosis, following
intensive treatment and at follow up. In unilateral limb swelling
the affected side can be compared to the contralateral unaf-
fected limb. In bilateral swelling the volume of both limbs is
tracked with time. Measurements are recorded in millilitres or
expressed as a percentage of the normal limb. Water plethysmog-
raphy (water displacement) is the gold standard method but
is limited by practicalities of measurement and hygiene issues.
Other options include circumferential limb measurements and
perometry (infrared light beams measure the outline of the limb
to calculate volume).
MANAGEMENT OF LYMPHOEDEMA
Overview
The evaluation of the lymphoedema patient needs to be holis-
tic and their care delivered by a multiprofessional team compris-
ing physical therapists, nurses, orthotists, physicians (dermatolo-
gists, oncologists, palliative care specialists), surgeons and social
service professionals. Although surgery itself has a very small
role, surgeons (especially those with breast and vascular inter-
ests) are frequently asked to oversee the management of these
patients. Early diagnosis and institution of management are
essential because at that stage relatively simple measures can be
highly effective and will prevent the development of disabling
late-stage disease, which is extremely difficult to treat. There is
often a latent period of several years between the precipitating
event and the onset of lymphoedema. The identification, edu-
cation and treatment of such at-risk patients can slow down,
even prevent, the onset of disease. In patients with established
lymphoedema, the three goals of treatment are to relieve pain,
reduce swelling and prevent the development of complications
(Summary box 58.6).
PART 10 | VASCULAR
Relief of pain
On initial presentation, 50 per cent of patients with lym-
phoedema complain of significant pain. The pain is usually
multifactorial and its severity and underlying cause(s) will vary
depending on the aetiology of the lymphoedema. For example,
following treatment for breast cancer, pain may arise from the
swelling itself (radiation and surgery induced); nerve (brachial
plexus and intercostobrachial nerve), bone (secondary deposits,
radiation necrosis) and joint (arthritis, bursitis, capsulitis) dis-
ease; and recurrent disease. Treatment involves the considered
use of non-opioid and opioid analgesics, corticosteroids, tricyclic
antidepressants, muscle relaxants, anti-epileptics, nerve blocks,
physiotherapy and adjuvant anticancer therapies (chemo-, radio-
and hormonal therapy), as well as measures to reduce swelling if
possible. In patients with non-cancer-related lymphoedema, the
best way to reduce pain is to control swelling and prevent the
10-58-B&L_26th-Pt10_Ch58_cp.indd 934
Summary box 58.6
Initial evaluation of the patient with
lymphoedema
History (age of onset, location, progression, exacerbating
and relieving features)
Past medical history including cancer history
Family history
Obesity (diet, height and weight, body mass index)
Complications (venous, arterial, skin, joint, neurological,
malignant)
Assessment of physical, emotional and psychosocial
symptoms
Social circumstances (mobility, housing, education, work)
Special needs (footwear, clothing, compression garments,
pneumatic devices, mobility aids)
Previous and current treatment
Pain control
Compliance with therapy and ability to self-care
development of complications. Whatever the cause, pain is a
somatopsychic experience that is affected by mood and morale.
These issues are important in patients with both cancer-related
lymphoedema, who are concerned about recurrent disease, and
non-cancer-related disease, who often have poor self-esteem and
problems with body image and perception.
Control of swelling
Physical therapy for lymphoedema comprising bed rest, elevation,
bandaging, compression garments, massage and exercises was
first described at the end of the nineteenth century, and through
the twentieth century various eponymous schools developed.
Although there is little doubt that physical therapy can be highly
effective in reducing swelling, its general acceptance and practice
has been hampered by a lack of proper research and confusing
terminology. The current preferred term is decongestive lym-
phoedema therapy (DLT), which comprises two phases. The first
is a short intensive period of therapist-led care and the second is a
maintenance phase in which the patient uses a self-care regimen
with occasional professional intervention. The intensive phase
comprises skin care, manual lymphatic drainage (MLD) and
multi-layer lymphoedema bandaging (MLLB), and exercises. The
length of intensive treatment will depend upon the disease sever-
ity, the degree of patient compliance and the willingness and abil-
ity of the patient to take more responsibility for the maintenance
phase. However, weeks rather than months should be the goal.
Skin care
The patient must be carefully educated in the principles and
practice of skin care. The patient should inspect the affected skin
daily, with special attention paid to skinfolds, where maceration
may occur. The limb should be washed daily; the use of bath oil,
e.g. Balneum, is recommended as a moisturiser and the limb must
be carefully dried afterwards. A hair drier on low heat is more
effective and hygienic, and less traumatic, than a towel. If the
skin is in good condition daily application of a bland emollient,
e.g. aqueous cream, is recommended to keep the skin hydrated.
If the skin is dry and flaky then a bland ointment, e.g. 50:50
white soft paraffin/liquid paraffin (WSP/LP), should be used
twice daily and, if there is marked hyperkeratosis, a keratolytic
agent, such as 5 per cent salicylic acid, should be added. Many
10/09/2012 11:43

commercially available soaps, creams and lotions contain sensi-
tisers, e.g. lanolin in E45 cream, and are best avoided as patients
with lymphoedema are highly susceptible to contact dermatitis
(eczema). Apart from causing intense discomfort, eczema acts as
an entry point for infection. Management comprises avoidance
of the allergen (patch testing may be required) and topical cor-
ticosteroids. Fungal infections are common, difficult to eradicate
and predispose to acute inflammatory episodes. Chronic applica-
tion of antifungal creams leads to maceration and it is better
to use powders in shoes and socks. Ointment containing 3 per
cent benzoic acid helps prevent athletes foot and can be used
safely over long periods. Painting at-risk areas with an antiseptic
agent such as eosin may be helpful. Lymphorrhoea is uncommon
but extremely troublesome. Management comprises emollients,
elevation, compression and sometimes cautery under anaesthetic
(Summary box 58.7).
Summary box 58.7
Skin care
Protect hands when washing up or gardening; wear a
thimble when sewing
Never walk barefoot and wear protective footwear outside
Use an electric razor to depilate
Never let the skin become macerated
Treat cuts and grazes promptly (wash, dry, apply antiseptic
and a plaster)
Use insect repellent sprays and treat bites promptly with
antiseptics and antihistamines
Seek medical attention as soon as the limb becomes hot,
painful or more swollen
Do not allow blood to be taken from, or injections to be
given into, an affected arm (and avoid blood pressure
measurement)
Protect the affected skin from sun (shade, high-factor sun
block)
Consider taking antibiotics if going on holiday
Apart from lymphangiosarcoma, acute inflammatory episodes
are probably the most serious complications of lymphoedema
and frequently lead to emergency hospital admission. About 25
per cent of primary and 5 per cent of secondary lymphoedema
patients are affected. Acute inflammatory episodes start rapidly,
often without warning or a precipitating event, with tingling,
pain and redness of the limb. Patients feel viral and severe
attacks can lead to the rapid onset of fever, rigors, headache,
vomiting and delirium. Patients who have suffered previous
attacks can usually predict the onset and many learn to carry
antibiotics with them and self-medicate at the first hint of
trouble. This may stave off a full-blown attack and prevent
the further lymphatic injury that each acute inflammatory
episode causes. It is rarely possible to isolate a responsible bac-
terium but the majority are presumed to be caused by group A
b-haemolytic streptococci and/or staphylococci. The diagnosis
is usually obvious but dermatitis, thrombophlebitis and DVT are
in the differential diagnosis. Oral amoxycillin is the treatment
of choice with erythromycin or clarithromycin in those with
penicillin allergy. Flucloxacillin should be added for those with
evidence of S. aureus infection (folliculitis, crusted dermatitis).
Oral clindamycin is a second line agent for those with failure
to respond to initial therapy. Hospital admission is required for
10-58-B&L_26th-Pt10_Ch58_cp.indd 935
Management of lymphoedema 935
patients with: signs of septicaemia; continuing or deteriorating
systemic signs after 48 hours of antibiotic treament; unresolving
or deteriorating local signs despite trials of first- and second-line
antibiotics. Intravenous amoxycillin or benzyl penicillin with
clindamycin in penicillin-allergic patients or as second-line
therapy is most commonly recommended. Bed rest will reduce
lymphatic drainage and the spread of infection, elevation will
reduce the oedema and heparin prophylaxis will reduce the
risk of DVT. Analgesia is often required but non-steroidal anti-
inflammatories (NSAIDs) should be avoided as they have been
associated with increased complications including necrotising
fasciitis. Any lymphatic massage should be ceased in the pres-
ence of active infection. Amoxycillin can be taken by patients
who self-medicate. The use of long-term prophylactic antibiotics
is not evidence based, but penicillin V 500 mg daily is probably
reasonable in patients who suffer two or more attacks per year.
However, the benefits of scrupulous compliance with physical
therapy and skin care cannot be underestimated.
Manual lymphatic drainage
Several different techniques of MLD have been described and
the details are beyond the scope of this chapter. However, they
all aim to evacuate fluid and protein from the interstitial space
and stimulate lymphangion contraction with decongestion of
impaired lymphatic pathways and development of collateral
routes. The therapist should perform MLD daily; they should
also train the patient (and/or carer) to perform a simpler, modi-
fied form of massage termed simple lymphatic drainage (SLD). In
the intensive phase, SLD supplements MLD and, once the main-
tenance phase is entered, SLD will carry on as daily massage.
Multilayer lymphoedema bandaging and
compression garments
Elastic bandages provide compression, produce a sustained high
resting pressure and follow in as limb swelling reduces. However,
the sub-bandage pressure does not alter greatly in response to
changes in limb circumference consequent upon muscular activ-
ity and posture. By contrast, short-stretch bandages exert support
through the production of a semi-rigid casing where the resting
pressure is low but changes quite markedly in response to move-
ment and posture. This pressure variation produces a massaging
effect within the limb and stimulates lymph flow. Whether the
aim is to provide support or compression, the pressure exerted
must be graduated (100 per cent ankle/foot, 70 per cent knee,
50 per cent mid-thigh, 40 per cent groin).
PART 10 | VASCULAR
Non-invasive assessment of the anklebrachial pressure
index (ABPI) using a hand-held Doppler ultrasound device is
usually necessary prior to commencing any form of compression
therapy, as it is rarely possible to feel pulses in the lymphoedema-
tous limb. Standard MLLB and compression is used in patients
with ABPI 0.8 and modified techniques with lower pressures
in those with moderate arterial disease (ABPI 0.50.8). MLLB
is contraindicated in severe arterial insufficiency (ABPI <0.5),
uncontrolled heart failure and severe peripheral neuropathy.
It is generally believed that non-elastic MLLB is preferable
(and arguably safer) in patients with severe swelling during the
intensive phase of DLT (Summary box 58.8), whereas compres-
sion (hosiery, sleeves) is preferable in milder cases and during the
maintenance phase. MLLB is highly skilled and to be effective
and safe it needs to be applied by a specially trained therapist. It
is also extremely labour intensive, needing to be changed daily.
10/09/2012 11:43
 936 LY M P H AT I C D I S O R D E R S

Enthusiasm for pneumatic compression devices has waxed

Summary box 58.8
Effects of MLLB
Reduces oedema
Restores shape to the affected area
Reduces skin changes (hyperkeratosis, papillomatosis)
Eliminates lymphorrhoea
Supports inelastic skin
Softens subcutaneous tissues
Compression garments form the mainstay of manage-
ment in most clinics. The control of lymphoedema requires
higher pressures (3040 mmHg arm, 4060 mmHg leg) than
are typically used to treat CVI. These may be reduced to
1525 mmHg in those with moderate arterial insufficiency
(Figure 58.10). Confusingly, the British (classes I: 1417 mmHg;
II: 1824 mmHg; III: 2535 mmHg) and international (USA)
(classes I: 2030 mmHg; II: 3040 mmHg; III: 4050 mmHg; IV:
5060 mmHg) standards are different. The patient should put
the stocking on first thing in the morning before rising. It can be
difficult to persuade patients to comply. Putting lymphoedema-
grade stockings on and off is difficult and many patients find
them intolerably uncomfortable, especially in warm climates.
Furthermore, although intellectually they understand the ben-
efits, emotionally they may find wearing them presents a greater
body image problem than the swelling itself.
and waned. Unless the device being used allows the sequential
inflation of multiple chambers up to >50 mmHg, it will probably
be ineffective for lymphoedema. The benefits to the patient are
maximised and complications are minimised if these devices
are used under the direction of a physical therapist as part of an
overall package of care.
Exercise
Lymph formation is directly proportional to arterial inflow
and 40 per cent of lymph is formed within skeletal muscle.
Vigorous exercise, especially if it is anaerobic and isometric,
will tend to exacerbate lymphoedema and patients should be
advised to avoid prolonged static activities, for example car-
rying heavy shopping bags or prolonged standing. In contrast,
slow, rhythmic isotonic movements (e.g. swimming) and mas-
sage will increase venous and lymphatic return through the
production of movement between skin and underlying tissues
(essential to the filling of initial lymphatics) and augmentation
of the muscle pumps. Exercise also helps to maintain joint
mobility. Patients who are unable to move their limbs benefit
from passive exercises. When at rest, the lymphoedematous
limb should be positioned with the foot/hand above the level
of the heart. A pillow under the mattress or blocks under the
bottom of the bed will encourage the swelling to go down
overnight.

Lower limb lymphoedema Peripheral arterial assessment

suitable for compression hosiery (ABPI)

NO COMPRESSION Severe arterial disease Moderate arterial disease ABPI >0.8

Refer to vascular specialist ABPI <0.5 ABPI 0.50.8

Prophylaxis Moderate/severe Severe lymphoedema Severe complex

Early/mild lymphoedema lymphoedema ISL stage III lymphoedema
ISL stages 011 ISL late stage IIIII Shape distortion* ISL stage III
No or minimal shape Some shape distortion* Active patients and those Shape distortion*
distortion Phlebolymphoedema at risk of oedema Pressure resistant
Maintenance (healed ulcer) returning (i.e. medium or high
Palliation Lipoedema Phlebolymphoedema pressure garments do
Elderly/arthritic Elderly/arthritic (active ulcer) not contain swelling)
Pressure sensitive Maintenance Gross forefoot oedema
Lipoedema Retromalleolar swelling
Controlled cardiac oedema
Dependency oedema
Neurological deficit
PART 10 | VASCULAR

Low: 1421 mmHg Medium: 2332 mmHg High: 3446 mmHg Very high: 4970 mmHg
Circular or flat knit Circular or flat knit or Flat or circular knit or Flat or circular knit or
Ready to wear combination combination combination
All styles Ready to wear or custom Custom made (or ready to Custom made (or ready to
made wear) wear)
All styles All styles All styles
MLLB

Successful outcome
No increase in swelling
No deterioration of skin, tissue density or shape
Improvement in patient/carer involvement and self-management skills

*For patients with shape distortion, flat knit hosiery is often preferable.
Including inelastic adjustable compression device.

Figure 58.10 Compression garments for lower limb oedema and lymphovenous oedema. Reproduced with permission from: Lymphoedema
Framework. Best Practice Management of Lymphoedema. International Consensus. London: MEP Ltd, 2006. MEP Ltd 2006.

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 Management of lymphoedema 937

Drugs of compression hosiery for at least one year. While liposuction

There are considerable, and scientifically inexplicable, differ-
ences in the use of specific drugs for venous disease and lym-
phoedema between different countries. The benzpyrones are
a group of several thousand naturally occurring substances,
of which the flavonoids have received the most attention.
Enthusiasts will argue that a number of clinical trials have shown
benefit from these compounds, which are purported to reduce
capillary permeability, improve microcirculatory perfusion, stim-
ulate interstitial macrophage proteolysis, reduce erythrocyte
and platelet aggregation, scavenge free radicals and exert an
anti-inflammatory effect. Detractors will argue that the trials
are small and poorly controlled with short follow up and soft
end points, and that any benefits observed can be explained by
a placebo effect. In the UK, oxerutins (Paroven) are the only
such drugs licensed for venous disease and none has a license for
lymphoedema. Diuretics are of no value in pure lymphoedema.
Their chronic use is associated with side effects, including elec-
trolyte disturbance, and should be avoided.
With increasing understanding of lymphangiogenesis path-
ways there is hope that specific pharmacological targets or gene
therapy may become available in the future but this remains in
the very early stages at present.
Surgery
Only a small minority of patients with lymphoedema benefit
from surgery. Operations fall into three categories: bypass proce-
dures, liposuction and reduction procedures.
appears to be safe, results of long-term efficacy and effects on the
incidence of future lymphoedema complications (e.g. infection)
are awaited.
Limb reduction procedures
These are indicated when a limb is so swollen that it interferes
with mobility and livelihood. These operations are not cos-
metic in the sense that they do not create a normally shaped leg
and are usually associated with significant scarring. Four opera-
tions have been described.
Sistrunk
A wedge of skin and subcutaneous tissue is excised and the
wound closed primarily. This is most commonly carried out to
reduce the girth of the thigh.
Homans
First, skin flaps are elevated, and then subcutaneous tissue is
excised from beneath the flaps, which are then trimmed to size
to accommodate the reduced girth of the limb and closed prima-
rily. This is the most satisfactory operation for the calf (Figure
58.11). The main complication is skin flap necrosis. There must
be at least six months between operations on the medial and
lateral sides of the limb and the flaps must not pass the midline.
This procedure has also been used on the upper limb, but is
contraindicated in the presence of venous obstruction or active
malignancy.

Bypass procedures
The rare patient with proximal ilioinguinal lymphatic obstruc-
tion and normal distal lymphatic channels might benefit, at least
in theory, from lymphatic bypass. A number of methods have
been described including the omental pedicle, the skin bridge
(Gillies), anastomosing lymph nodes to veins (Neibulowitz) and
the ileal mucosal patch (Kinmonth). More recently, direct lym-
phaticovenular anastomosis (LVA) has been carried out on ves-
sels of 0.30.8 mm diameter using supermicrosurgical tech-
niques. The procedures are technically demanding and not
without morbidity. They are more ofen attempted in the upper
limb following lymph node resection or radiotherapy for breast
cancer. The outcomes are best in patients with earlier stages of
lymphoedema for whom the majority can be controlled with best
medical therapy alone. In those with later stage disease who
have failed conservative management, the outcomes of LVA

PART 10 | VASCULAR
have generally been disappointing.

Liposuction
Liposuction has been used in the treament of chronic lym-
phoedema. It is usually reserved for patients who have progressed
to non-pitting oedema. Case series reported thus far have shown
promising results with more than 100 per cent reduction in
limb oedema volume which can be maintained by ongoing use

Sir Harold Delf Gilles, 18821960, plastic surgeon, St Bartholomews Hospital, London,
UK. Born in New Zealand, widely considered the Father of Plastic Surgery, started his
craft to better the lives of the victims of the First World War. Later he became a pioneer
in gender reassignment (sex-change) surgery. He was joined in private practice by his
cousin, the other world famous plastic surgeon, Sir Archibald McIndoe. He excelled in
most sports cricket, rowing, golf, and was an accomplished painter.
Figure 58.11 Homans procedure involves raising skin flaps to allow the
excision of a wedge of skin and a larger volume of subcutaneous tissue
down to the deep fascia. Surgery to the medial and lateral aspects
of the leg must be separated by at least six months to avoid skin flap
necrosis.

John Bernard Kinmonth, 19161982, surgeon, St Thomass Hospital, London, UK.

Walter Ellis Sistrunk, 18801933, Professor of Clinical Surgery, Baylor University College of Medicine, Dalls, TX, USA.
Frederick Thompson, 19101975, plastic surgeon, The Middlesex Hospital, London, UK.
Major-General Sir Richard Havelock Charles, 18871934, a surgeon in The Indian Medical Service.

10-58-B&L_26th-Pt10_Ch58_cp.indd 937 10/09/2012 11:43

 938 LY M P H AT I C D I S O R D E R S

Thompson
This is a modification of the Homans procedure aimed to create
new lymphatic connections between the superficial and deep
systems. One skin flap is denuded (shaved of epidermis), sutured
to the deep fascia and buried beneath the second skin flap (the
so-called buried dermal flap) (Figure 58.12). This procedure
has become less popular as pilonidal sinus formation is common.
The cosmetic result is no better than that obtained with the
Homans procedure and there is no evidence that the buried flap
establishes any new lymphatic connections.

1 Subcutaneous 2
fat
Skin

Deep fascia
Bone Figure 58.13 The Charles procedure involves circumferential excision
of lymphoedematous tissue down to and including the deep fascia fol-
lowed by split-skin grafting. This procedure gives a very poor cosmetic
result but does allow the surgeon to remove very large amounts of tissue
3 4 and is particularly useful in patients with severe skin changes.

too diffuse to be corrected surgically, a peritoneal venous shunt

may be inserted, although occlusion and infection are important
complications. Medical treatment comprising the avoidance of
fat in the diet and the prescription of medium-chain triglycerides
(which are absorbed directly into the blood rather than via the
Figure 58.12 A cross-sectional representation of Thompsons reduction
lymphatics) may reduce swelling. Chylothorax is best treated by
operation; red arrows illustrate the buried dermal flap sutured to deep
pleurodesis, but this may lead to death from lymph-logged lungs
fascia.
as the excess lymph has nowhere to drain.

Chyluria
Charles Filariasis is the most common cause, with chyluria occurring in
This operation was initially designed for filariasis and involved 12 per cent of cases 1020 years after initial infestation. It usu-
excision of all of the skin and subcutaneous tissues down to the ally presents as painless passage of milky white urine, particularly
deep fascia, with coverage using split-skin grafts (Figure 58.13). after a fatty meal. The chyle may clot, leading to renal colic,
This leaves a very unsatisfactory cosmetic result and graft failure and hypoproteinaemia may result. Chyluria may also be caused
is not uncommon. However, it does enable the surgeon to reduce by ascariasis, malaria, tumour and tuberculosis. Intravenous
greatly the girth of a massively swollen limb. urography and/or lymphangiography will often demonstrate the
lymphourinary fistula. Treatment includes a low-fat and high-
Chylous ascites and chylothorax Title: Bailey & Loves Short Practice ofprotein diet,Edincreased oral
Surgery, 26th ISBN:fluids to prevent clot colic, and
9781444121278 Proof Stage: 1
laparotomy and ligation of the dilated lymphatics. Attempts
PART 10 | VASCULAR

These are associated with megalymphatics. The diagnosis may

and lymphangi- have also been made to sclerose the lymphatics either directly
www.cactusdesign.co.uk
be obvious if accompanied by lymphoedema
oma. However, some patients develop chylous ascites and/or or via instrumentation of the bladder, ureter and renal pelvis.
chylothorax in isolation, in which case the diagnosis can be
confirmed by aspiration and the identification of chylomicrons FURTHER READING
in the aspirate. Cytology for malignant cells should also be car-
ried out. A CT scan may show enlarged lymph nodes and CT Lee B-B, Bergan J, Rockson SG. Lymphedema: a concise compendium of
theory and practice. New York: Springer, 2011.
with guided biopsy, laparoscopy or even laparotomy and biopsy
Lymphoedema Framework. Best practice for the management of
may be necessary to exclude lymphoma or other malignancy. lymphoedema. International consensus. London: MEP Ltd, 2006.
Lymphangiography may indicate the site of a lymphatic fistula Szuba A, Rockson SG. Lymphedema: anatomy, physiology and
that can be surgically ligated. Even if no localised lesion is pathogenesis. Vasc Med 1997; 2: 3216.
identified, it may be possible to control leakage at laparotomy Twycross R, Jenns K, Todd J. Lymphoedema. Oxford: Radcliffe Medical
or even remove a segment of affected bowel. If the problem is Press, 2000.

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