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Differential Diagnosis, Investigation, and Current
Treatment of Lower Limb Lymphedema
Alok Tiwari, MRCSEd; Koon-Sung Cheng, FRCS; Matthew Button, MRCS; Fiona Myint, FRCS; George Hamilton, FRCS
Hypothesis: The causes and management of lower limb
lymphedema in the Western population are different from
those in the developing world.
Objective: To look at the differential diagnosis, meth-
ods of investigation, and available treatments for lower
limb lymphedema in the West.
Data Source: A PubMed search was conducted for the
years 1980-2002 with the keyword “lymphedema.” En-
glish language and human subject abstracts only were ana-
lyzed, and only those articles dealing with lower limb
lymphedema were further reviewed. Other articles were
extracted from cross-referencing.
Results: Four hundred twenty-five review articles per-
taining to lymphedema were initially examined. This re-
view summarizes the findings of relevant articles along
with our own practice regarding the management of
lymphedema.
Conclusions: The common differential diagnosis in West-
ern patients with lower limb swelling is secondary lymphe-
dema, venous disease, lipedema, and adverse reaction to
ipsilateral limb surgery. Lymphedema can be confirmed
by a lymphoscintigram, computed tomography, mag-
netic resonance imaging, or ultrasound. The lymphatic
anatomy is demonstrated with lymphoscintigraphy, which
is particularly indicated if surgical intervention is being
considered. The treatment of choice for lymphedema is
multidisciplinary. In the first instance, combined physi-
cal therapy should be commenced (complete deconges-
tive therapy), with surgery reserved for a small number
of cases.
Arch Surg. 2003;138:152-161
L
YMPHEDEMA IS the swelling of
a body part due to an abnor-
mality in the locoregional
lymphatic drainage. This re-
sults in an increase in inter-
stitial volume secondary to the accumu-
lation of tissue (lymphatic) fluid. It is most
common in the lower limb (80% of cases)
but can also occur in the arms, face, trunk,
and external genitalia.
1
Lymphedema is an important differ-
ential diagnosis in lower limb swelling, with
various investigation and treatment op-
tions available. In this review, we look at
the common causes of lower limb swell-
ing and their clinical features, the investi-
gations used to exclude nonlymphedema-
tous causes, and the current treatment of
lymphedema in the Western population. Fi-
lariasis, the most common cause world-
wide, and the management of postmastec-
tomy lymphedema are not discussed
although the general principles apply to
both of these conditions.
METHODS
A PubMed search was conducted for the years
1980-2002, using the keyword “lymphe-
dema.” All abstracts were studied and only ar-
ticles dealing with lower limb lymphedema
were further scrutinized. Other articles were
extracted by cross-referencing.
RESULTS
DIFFERENTIAL DIAGNOSIS
A swollen leg may be due to local or sys-
temic causes. Systemic causes include con-
gestive cardiac failure, renal failure, hy-
poalbuminemia, and protein-losing
nephropathy. Local causes include pri-
mary and secondary lymphedema,
2-8
lipe-
dema,
2,4,5,9-12
deep vein thrombosis (DVT)
and chronic venous disease,
2-5,7,8
postop-
erative complications following ipsi-
lateral, surgery,
3,13-17
cellulitis,
4,8,18,
Baker
cyst
13,18
and cyclical
19
and idiopathic
edema.
5,7
In children, lower limb swell-
ing is seen in association with arthritis but
the underlying mechanism for this asso-
ciation is unknown.
20
Primary Lymphedema
This is caused by a congenital abnormal-
ity or dysfunction in the lymphatic sys-
SPECIAL ARTICLE
From the University
Department of Surgery, Royal
Free Hospital National Health
Service (NHS) Trust
(Drs Tiwari, Cheng, Button,
Myint, and Hamilton); and
North Middlesex University
Hospital NHS Trust
(Dr Myint), London, England.
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tem and can be further classified according to age at ini-
tial examination. The congenital form is detected at birth
or in the first year of life and may either be sporadic or
familial. The familial form is known as Milroy disease and
is rare.
21
It is thought to result from an autosomal inher-
itance of a single gene.
22
The onset of lymphedema prae-
cox is between the ages of 1 and 35 years.
6
The onset of
lymphedema tarda occurs after 35 years of age.
6
The most common of these is the praecox variety.
Primary lymphedema is more common in females, espe-
cially lymphedema praecox, where the onset is particu-
larly common around menarche.
23
Symptoms may be
linked to a minor trauma,
24
suggesting that the abnormal
lymphatics have coped under normal circumstances but
are unable to cope with an increase in tissue fluid.
Alternatively, primary lymphedema can be classi-
fied according to the abnormality found in the lymphat-
ics. Thus, it may be aplastic, hypoplastic, or hyperplas-
tic. These terms suggest an abnormality in the
development of the lymphatic system. While this is true
for congenital lymphedema, cases of later-onset pri-
mary lymphedema might be due to an acquired abnor-
mality. It is difficult to prove whether the abnormal lym-
phatics seen when these patients were investigated had
existed in the same state since birth. Browse and Stew-
art have made a case for a new classification system that
disposes of these terms.
25
Primary hypoplastic lymphedema can be further sub-
divided into proximal and distal hypoplasia. The most
common form of primary lymphedema is distal hypo-
plasia. It is milder, often bilateral, and symptoms are con-
fined to below the knee.
24
Not surprisingly, proximal dis-
ease causes more severe symptoms, with whole-limb
swelling. Patients with primary hyperplastic lymphe-
dema have an increased number and size of lymphatics.
It is unusual in that it has a male preponderance and is
more often familial.
26
An association with other congeni-
tal abnormalities is sometimes seen.
26
The thoracic duct
may be absent or abnormal in such patients.
26
Secondary Lymphedema
This is edema due to a reduction in lymph flow by an
acquired cause. The causes of secondary lymphedema in-
clude trauma,
4,5,7
recurrent infection,
4,5,7
and malig-
nancy, including metastatic disease.
5,27-29
In the devel-
oped world, the most common cause of secondary
lymphedema is malignancy (including that resulting from
cancer treatment). Lymphedema is common in the de-
veloping world secondary to infection with the parasitic
nematode Wuscheria bancrofti (otherwise known as fi-
lariasis), making this the most common cause of lymphe-
dema worldwide.
It is unusual for surgery alone to cause lymphe-
dema, as lymphatics have excellent regenerative capa-
bilities. Some series have shown significant lymphatic
damage in more than 60% of patients undergoing vari-
cose vein surgery.
30
Lymphedema is unusual after vari-
cose vein surgery but patients should be examined pre-
operatively, as vein stripping can significantly exacerbate
mild lymphedema. Patients with venous disease have been
shown to have impaired lymphatic drainage.
31
Even after radical lymph node excision for malig-
nancy, lymphedema does not always ensue. When it does
occur, it is often a late complication. The reasons for this
late development are uncertain, but gradual failure of dis-
tal lymphatics, which have to “pump” lymph at a greater
pressure through damaged proximal ducts, has been pos-
tulated. The transected lymphatics will regenerate after
node clearance procedures. If combined with radio-
therapy, however, the risk of lymphedema is higher, as
fibrous scarring reduces regrowth of ducts.
32
Recurrent cellulitis can complicate venous disease
of the lower limb, exacerbating swelling in venous hy-
pertension and making venous ulcers harder to treat be-
cause lymph exudes through ulcers. The common causes
of lymphedema are shown in
Figure 1.
CLINICAL FEATURES OF LIMB SWELLING
The clinical features of the common causes of lower limb
swelling are discussed to allow a differential diagnosis
and appropriate investigations.
Lymphedema
Lymphedema is found in both sexes, although women
are investigated for this disease more often than men.
5
It
can be seen at any age as already noted, and two thirds of
cases are unilateral.
5
The distal part of the leg is affected
initially, with proximal extension occuring later. The feet
are not spared. Patients with complete absence of lym-
phatics have a history of long-term swelling, while those
with impaired lymphatics have a shorter history.
18
The initial symptom is usually painless swelling. The
patient may also complain of a feeling of heaviness in the
limb, especially at the end of the day and in hot weather.
Symptoms may vary throughout the menstrual cycle.
33
On initial examination, the swelling is seen as pit-
ting edema, but with time, fibrosis in the subcutaneous
tissues causes the classical nonpitting signs.
34
The dis-
tribution is asymmetrical, and patients have a positive
Stemmer sign (the inability to pinch the skin of the dor-
sum of the second toe between the thumb and
forefinger).
12
Early in the disease process, the edema can
spread proximally (or distally) but this is uncommon af-
ter the first year. Radial enlargement, however, is usu-
ally progressive if treatment is not instituted.
24
With time,
skin changes are seen over the affected area; the skin be-
Lymphedema
Primary
Congenital Praecox Tarda
Age <1 y Age 1-35 y Age >35 y
Secondary
Lymphatic
Obstruction
Lymphatic
Interruption
Malignancy
Infection
Radiotherapy
Groin Surgery
Lymph Node
Excision
Figure 1. Causes of lymphedema.
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comes thicker (hyperkeratosis) and rougher (papilloma-
tosis) and skin turgor is increased
34,35
(Figure 2). In se-
vere cases, the skin can break down, with lymph exuding
through any skin breaks. This compromises healing and
leads to an increased risk of infection. Recurrent infec-
tions, cellulitis, and lymphangitis are common. This un-
fortunately can lead to further deterioration in lym-
phatic drainage, ending in a vicious cycle of infection and
worsening edema.
Lymphangiosarcoma is a rare late complication of
lymphedema.
34
This was originally described in the
lymphedematous arms of patients following radical mas-
tectomy (Stewart Treves syndrome
36
) but has also been
described in patients with Milroy disease.
37
It appears to
be an earlier complication following radical mastec-
tomy than in those with congenital lymphedema (aver-
age, 10 vs 38 years postdiagnosis).
38
Treatment is pri-
mary radiotherapy, with surgery reserved for patients with
discrete, nonmetastatic disease.
Lipedema
The clinical features of lipedema (also known as lipoma-
tosis of the leg) include early age of onset, female exclu-
sivity, and positive family history in some patients.
11,12
The clinical signs include elastic symmetrical enlarge-
ment of both legs with sparing of the feet,
11,12
so called
“riding breech thighs” and “stove pipe legs,”
39
hypo-
thermia of the skin, a negative Stemmer sign, and plan-
tar positioning alterations.
10,12
Weight loss does not af-
fect leg appearance.
12
DVT and Chronic Venous Disease
Deep vein thrombosis results in obstruction to venous
flow, occurring mainly in the soleal plexus. The clinical
picture is thus one of a swollen, warm, tender calf. The
resulting edema is pitting in nature and is usually much
softer than in established lymphedema. Often, there are
underlying risk factors, such as recent surgery or immo-
bility, malignancy, a preceding long flight, or thrombo-
philia. The diagnosis is confirmed with duplex scan-
ning or venography. Treatment is with anticoagulation.
40
One of the long-term sequelae of DVT is postphle-
bitic syndrome. Here, there is reflux in the deep venous
system, or deep venous insufficiency, resulting in chronic
swelling of the limb, lipodermatosclerosis, and varicose
veins, and in severe cases, venous ulceration. On clini-
cal grounds alone, this may be more difficult to differ-
entiate from lymphedema, and further investigation, as
outlined later in this article, may be required.
40
Postoperative Swelling (Predominantly
After Arterial Reconstruction)
The incidence of peripheral edema following arterial re-
construction is high, especially if the procedure is a femo-
ropopliteal bypass.
41
If the swelling is significant (⬎4.5-cm
increase in diameter), it is more likely to be due to throm-
bosis of the tibial or popliteal veins.
42
Following arterial
reconstruction, there may be impairment of lymphatic
drainage or lymphatic disruption secondary to the sur-
gical dissection in the thigh and popliteal region.
14,15,17,41
The swelling may persist for up to 3 months.
INVESTIGATION OF LIMB SWELLING
The main reason for investigating is not only to confirm
the diagnosis but to exclude a potentially lethal condi-
tion, such as DVT. General examination is necessary to
exclude medical causes, such as cardiac failure. Simple
serum biochemical analysis should exclude hepatic or re-
nal impairment, and analysis of the urine should ex-
clude any protein-losing nephropathy.
Clinical Examination
The contralateral leg may be used to assess whether the
affected leg is actually swollen. However, the disease may
itself affect both sides, or the unaffected leg may previ-
ously have been larger than the diseased leg. The Leg-O-
Meter (Franc¸ois Zuccarelli, MD, Hoˆpital St-Michel, Ser-
vice de Chirurgie Vasculaire, De´partment de Phle´bologie
et d’Angeiologie, Paris, France) is designed to measure the
circumference of the ankle or calf.
43
This has high inter-
observer reliability and is easy to use. It has been mainly
used in assessing leg swelling related to venous disease and
has so far not been validated in lymphedema. A normal
tape measure will assess the swelling relative to the con-
tralateral leg but this is not a reliable technique.
Water displacement volumetry, although not com-
monly used, measures leg volume
44
and is more accu-
rate than calculating the leg volume from circumferen-
tial measurements with a tape measure.
45
In lymphedema,
Figure 2. Anterior view of bilateral lymphedema showing the typical skin
changes associated with lymphedema.
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the tissue tonicity (degree of tissue resistance to me-
chanical compression) is either higher or lower com-
pared with the nonedematous leg.
46
Measurement of tis-
sue tonometry is more useful in assessing the response
to treatment than in the intitial assessment of disease. Bio-
electrical impedance has been used successfully for the
evaluation of swelling in patients with postmastectomy
lymphedema but has not yet been evaluated for leg
edema.
47
Finally, Cesarone and coworkers
48
developed the
edema tester. This involves applying a plastic plate with
either protrusions or holes over the swollen area, apply-
ing pressure, and measuring the marks made. It may al-
low the differentiation between primary and secondary
lymphedema, although it is only recommended at present
as a screening tool.
Radiologic Investigation
Lymphangiogram. Before lymphoscintigraphy became the
gold standard, this was the main technique used for vi-
sualizing the lymphatics. It involves direct cannulation
of the lymphatics through a skin incision and may lead
to infection, local inflammation, and fibrosis. It is tech-
nically demanding, painful, and time-consuming, with
an increased risk of hypersensitivity reactions and em-
boli.
49
As a diagnostic tool, the technique has largely been
abandoned. However, it is still useful if operative inter-
vention (ie, bypass procedure) is to be undertaken.
50
Lymphoscintigram. This technique was first intro-
duced in 1953 and is now the gold standard for assess-
ing the lymphatics. The radiolabeled protein used is usu-
ally technetium Tc 99m–labeled colloid, including
antimony sulphur
4,5,7,10,51
and albumin.
15,18,52,53
It allows
measurement of lymphatic function, lymph movement,
lymph drainage, and response to treatment
51,54
To aid in the measurement of lymph flow, the pa-
tient should take an oral dose of heptaminol adenosine
phosphate to increase lymphatic flow.
55
The sensitivity
of the lymphoscintigram is 73% to 97% and the speci-
ficity is 100%.
4,56,57
A lymphoscintigram may be suffi-
cient if any bypass procedure is intended but some pa-
tients may also require a contrast lymphangiogram to fully
elucidate the lymphatic anatomy.
50,58
The amount of time that the lymphatics are visual-
ized is equally important. If lymphatics are not imaged
within the first hour after isotope injection, the diagno-
sis may be missed.
4
In some patients, the 1-hour image
may show normal lymphatics, while only delayed films
(2-24 hours postinjection) may show the true abnormal-
ity.
8,9
In one series, 32% of patients would have had nor-
mal lymphoscintigram results if only the 1-hour film had
been considered. Other techniques that improve detec-
tion of lymphatic abnormality include condensed image
processing using a modified Kleinhans score and time ac-
tivity curves.
5,59,60
Lymphoscintigraphy alone can exclude lymph-
edema as a cause of limb swelling in approximately one
third of patients.
5,52
A lymphoscintigram will also differ-
entiate between lymphedema and edema of venous ori-
gin.
8
In patients with venous leg ulcers, lymphscintigra-
phy reveals significantly reduced lymph drainage in both
the affected and the nonulcerated leg compared with con-
trols.
51
It is also lower in patients with varicose veins, es-
pecially if deep vein incompetence is present.
51
This sug-
gests that chronic venous insufficiency is also associated
with lymphatic insufficiency.
In postthrombotic disease, there is reduction in the
subfascial lymphatic flow whereas the epifascial flow re-
mains normal.
53
In lymphedema, both epifascial and sub-
fascial lymphatics are abnormal.
53
Therefore, both epi-
fascial and subfascial compartments must be evaluated
to differentiate between postthrombotic disease and
lymphedema.
19,53
In patients with lipedema, lymphscintigraphy will
confirm that peripheral lymphatics are essentially nor-
mal, although there may be slowness of the lymphatics
in these patients compared with normal subjects.
10,12,61
The lymphoscintigram pictures are often asymmetrical
in lipedema even though the disease is bilateral.
10
This
could be explained by the dynamic nature of the lym-
phoscintigram or the necessity to have the patient walk
about. The disease process primarily affects the lower third
of the leg.
10
Lymphoscintigraphy also shows impair-
ment of lymphatic drainage or lymphatic disruption fol-
lowing arterial reconstruction.
14,15,17
Ultrasound. The ultrasound features of lymphedema are
volumetric changes (a minimal increase in the thick-
ness of the dermis,
62
an increase in the subcutaneous
layer,
62,63
and an increase, decrease, or no change in the
muscle mass
62
) and structural changes (hyperechogenic
dermis and hypoechogenic subcutaneous layer).
62
It al-
lows an assessment of soft tissue changes but does not
give information about the truncal anatomy of the lym-
phatics.
62
Duplex Ultrasound. In patients with lymphedema, there
is gradual impedance of venous return, which then ag-
gravates the edema. The duplex ultrasound may be a use-
ful investigation in patients with lower limb swelling.
63
In one series, a combination of a duplex scan and lym-
phoscintigram was able to diagnose the cause of the un-
explained limb edema in 82% of patients.
18
Some au-
thors, however, have not found any association between
chronic edema and increased venous reflux.
64
Computed Tomography. Computed tomography (CT)
scanning can be used not only to confirm the diagnosis
but also to monitor the effect of treatment.
65
The com-
mon CT findings in lymphedema include calf skin thick-
ening, thickening of the subcutaneous compartment, in-
creased fat density, and thickened perimuscular
aponeurosis.
2,13,65
A typical honeycomb appearance is seen
in most patients
2
(Figure 3).
In patients with chronic venous disease, there is en-
largement of the subcutaneous compartment and skin
thickening but no honeycomb appearance.
2
In lipe-
dema, there is enlargement of the subcutaneous com-
partment, normal skin thickness, and normal subfascial
compartment.
2
Computed tomographic scans of pa-
tients with DVT show an increase in the subcutaneous
layer, with signs of lymphedema, as well as an increase
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in the cross-sectional muscle area and enlarged superfi-
cial veins.
13
However, if calf swelling is not present fol-
lowing DVT, there will be no change in the muscle and
so CT becomes an unreliable investigation.
Magnetic Resonance Imaging (MRI). Magnetic reso-
nance imaging can differentiate among lymphedema, li-
pedema, and phlebedema.
66
Features of lymphedema on
MRI include circumferential edema, increased volume of
subcutaneous tissue, and a honeycomb pattern above the
fascia between the muscle and subcutis, with marked
thickening of the dermis.
3,66,67
It is, however, generally
difficult to differentiate primary from secondary lymphe-
dema using MRI.
68
Magnetic resonance imaging will also
show the typical features of angiosarcoma
69
while evalu-
ating the swollen limb.
Following reconstructive surgery, MRI shows the
edema to be located around the entire circumference of
the limb but restricted to the subcutaneous tissue, in-
creasing the leg volume by a mean of 26% (range,
8%-45%).
3
In DVT, there is edema of the leg muscles, par-
ticularly in the posterior compartments, with an in-
crease in the leg volume of 23% (range, 15%-90%).
3
In
chronic lymphedema, there is an increase in leg volume
of 40% (range, 27%-120%). Magnetic resonance imag-
ing in lipedema will confirm that peripheral lymphatics
are normal, soft tissue swelling consists solely of fat, and
subcutaneous edema is absent.
67
TREATMENT
The main aims of treating patients with lymphedema are
to prevent the progression of disease, to achieve me-
chanical reduction and maintenance of limb size, to al-
leviate the symptoms arising from lymphedema, and to
prevent skin infection. Hence, treatment depends on the
symptoms and the severity of the condition. The treat-
ment can be divided into conservative, pharmacologic,
and surgical.
Conservative
For the very mild cases, elevation of the affected limb
coupled with skin care may be sufficient. The latter is
particularly important to reduce the increased risk of cel-
lulitis and lymphangitis.
Physical Treatment
This modality consists of compression, special exercise,
massage, or a combination of the three to enhance lym-
phatic drainage. Compression with a custom-made elas-
tic stocking (minimum pressure, 40 mm Hg) is an effec-
tive method, particularly in secondary lymphedema.
70
In
a study of 40 patients with primary and secondary lymphe-
dema, only 1 limb from the secondary lymphedema group
deteriorated after compression with elastic stocking
therapy.
70
Multilayer bandaging is another form of compres-
sion and has been shown to be effective in both upper and
lower limb lymphedema.
71
This form of compression con-
sists of an inner layer of tubular stockinette followed by
foam and padding to protect the joint flexures and to even
out the contours of the limb so that the pressure is evenly
distributed. Compression is provided by an outer layer of
at least 2 short-stretch extensible bandages. Treatment us-
ing this technique in 90 female patients with either upper
or lower limb lymphedema was significantly more effec-
tive than hosiery alone.
71
In lipedema, no difference was
made by compressive stockings.
11
Another form of compression and massage comes
from pneumatic pumps.
72-74
These pumps allow the de-
velopment of high pressure up to 150 mm Hg. These pumps
can reduce the limb girth measurements by 37% to
68.6%.
74,75
Following treatment, however, patients should
continue to wear a compression stocking because there is
a high risk of recurrence. In a study using external pump
compression, a significant number of patients developed
genital edema.
76
The pumps may not be suitable for use
in patients with coexisting renal failure or congestive heart
failure. Patients should ideally also be free of metastasis
in the limb to prevent the risk of spreading the malig-
nancy.
73
One study reported that the use of a pneumatic
pump showed a greater effect in women, although why
this should be so is difficult to explain.
73
Usually a combination of these methods is em-
ployed to achieve optimal benefit.
77-79
Some authors have
called this approach either combined or complex physi-
cal therapy (CPT), while others have called it complete
decongestive therapy. They have been demonstrated to
significantly reduce the amount of edema and microlym-
phatic hypertension, paralleled with a considerable de-
crease in the mean circumference of the ankle and fore-
foot.
45,75,77-79,80
Following the initial stages of CPT, it is
important for these patients to continue to wear their com-
pression garments to prevent any relapse. The effect of
physical treatment is to produce focal lymphatic dam-
age to the endothelial lining of the lymphatics as well as
that of lymphatic pools. This leads to translocation of fluid
from the interstitium into the lymphatic lumen.
81
Some
patients with leg edema may benefit from raised leg ex-
ercise but this has not been shown to be of any benefit
when the cause of leg swelling is due to lymphedema.
82
Heat Therapy
Heat therapy has produced some benefits, which can be
achieved by hot water immersion, microwave, and elec-
tromagnetic irradiation. Microwave heat therapy has been
Figure 3. Typical computed tomographic findings in lymphedema showing
the honeycomb appearance.
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combined with compression hosiery,
83
hot water immer-
sion,
84
and benzopyrones
85
to reduce leg volume and im-
prove skin tonometry. This method of treatment has not
led to complications, to our knowledge, during or after
treatment.
The mechanism of action of thermal treatment is
not fully known. One group suggested that heat by
means of electromagnetic radiation produced its effect
by increasing the venous return rather than by improv-
ing lymphatic flow.
86
However, one criticism of this
study is that the subjects were normal rather than
patients with lymphedema, and heat may produce dif-
ferent effects in the 2 groups. Histologically, the skin
after heat treatment for lymphedema shows a near reso-
lution of perivascular cellular infiltration, disappearance
of the so-called lymph lakes, and dilatation of blood
capillaries.
84
This decrease in the dermal inflammatory
process associated with alteration of extracellular
matrix may explain the reduction of lymphedema seen
after heat treatment.
Pharmacologic Treatment
Micronized Purified Flavonoid Fraction. This is an ef-
fective drug in decreasing venous stasis and has also been
shown to be beneficial in idiopathic cyclic edema, chronic
venous insufficiency, and postmastectomy lymphe-
dema.
87
It exerts its action by reducing the capillary per-
meability and the inflammatory component typical of this
condition. Trials of this drug are awaited for lower limb
lymphedema.
Benzopyrones. This group of drugs has also been shown
to be effective in the treatment of lymphedema by re-
ducing edema fluid, increasing softness of the limbs, and
decreasing elevated skin temperature.
88
More impor-
tantly, there were markedly fewer instances of secon-
dary infection, and there was improvement in the symp-
toms, such as reduction in the bursting pain and feeling
of hardness, tightness, heaviness, swelling, and an in-
crease in mobility. Adverse effects, such as nausea and
diarrhea, were uncommon and had disappeared by 1
month of treatment. These findings were supported by
other groups using a combination of benzopyrones in ad-
dition to microwave heat therapy and compression treat-
ment.
85
Benzopyrones alone can provide adequate reduc-
tion in the symptoms and signs as well as a decrease in
instances of secondary infection.
89
However, the effect
was slower when compared with that of physical therapy.
The reported advantages of benzopyrones included low
toxicity, oral or topical application, and the lack of need
for compression therapy, which is particularly helpful for
patients who do not tolerate high-pressure treatment.
90
The combination of benzopyrones, whether in a topical
or oral preparation, and CPT is significantly better than
CPT alone.
80
Benzopyrones work by increasing the number of
macrophages, thus enhancing proteolysis and resulting
in removal of protein and thereby edema.
91
In addition,
the stimulus that excess protein provides for inflamma-
tory and fibrotic process is removed and its presence as
a good culture medium for bacterial growth is also elimi-
nated. Benzopyrones, however, are not licensed for use
in the United Kingdom, Australia, or France due to re-
ports of hepatotoxicity
92
Surgical Treatment
The importance of accurate preoperative evaluation
cannot be overemphasized. Before any surgery,
patients should be admitted for a few days to allow leg
elevation and compression to optimize the leg for sur-
gery.
93
Following surgery, it is important for the
patient to wear some form of stocking to prevent
recurrence. This is especially true of patients undergo-
ing debulking procedures. The treatment can be
divided into debulking operations, bypass procedures,
and prophylactic surgery.
94
Debulking Procedures. One method, which has been de-
scribed but is not widely popular and is not a debulking
procedure according to the widely accepted definition,
is the subcutaneous drainage of lymphedema fluid by
means of multiperforated silicon tubes linked to a cham-
ber by a 1-way valve.
95
This chamber is in turn con-
nected to the venous system via the long saphenous vein
in much the same way as a peritoneovenous shunt. In a
study of 10 patients with moderate to severe lymphe-
dema, there was a mean reduction of 70% in peripheral
edema. One problem with such a device is limited long-
term patency because it is liable to block owing to the
high protein content of edema fluid. This may explain
the lack of popularity of this method.
A well-tested method, the Charles procedure, is the
radical excision of subcutaneous tissue together with pri-
mary or staged skin grafting. This involves removal of
the skin, subcutaneous tissue, and deep fascia en-bloc.
Some surgeons prefer primary skin grafting with either
the skin from the excised tissue or from a nonaffected
area. Others favor a delayed approach to skin grafting.
Both the 1-stage
96
and the 2-stage
97,98
procedures re-
ported good results in terms of function, contour, and
reduction in the incidence of secondary cellulitis. There
was no difference in results between congenital and ac-
quired lymphedema but men were shown to have less
improvement than women.
97
Skin and subcutaneous ex-
cision alone or in combination with liposuction im-
proves symptoms but leads to foot edema.
11
Servelle
99
de-
scribed a technique where the entire affected limb
undergoes a 2-stage reduction (first, the medial aspect
and later, the lateral aspect of the limb). This has been
termed total superficial lymphangiectomy and is prob-
ably a modification of the Homan procedure. This is in
contrast to the Charles procedure, where only the af-
fected part of the limb is treated and the cosmetic out-
come is mediocre.
The main complication of the above debulking pro-
cedure is infection and necrosis of the skin graft, which
can lead to poor cosmetic and functional results. A suc-
cessful surgical outcome is shown in
Figure 4 and a com-
plication is shown in
Figure 5. Liposuction has been
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used in a limited number of patients, with up to a 23%
reduction in volume
100
and with cellulitis as the main com-
plication.
Bypass Procedures. Bypass procedures are only per-
formed in selected cases; this is reflected in the litera-
ture by small patient numbers in the series reported. These
microsurgical procedures are reserved for patients in
whom intensive combined medical therapy has not pro-
duced clinical improvement. Lymphatic-venous anasto-
mosis can only be performed in the presence of a com-
petent venous system and intact lymphatic structures,
such as patent regional lymphatics and lymph nodes.
101
Nielubowicz and Olszewski
102
first attempted lym-
phovenous anastomosis in the treatment of lymphe-
dema. Unfortunately, this early technique was noted to
occlude owing to venous thrombosis at the anastomotic
site or to reendothelialization over the cut anastomotic
surface of the lymph node.
103
With refinement in the tech-
nique, direct end-to-side lymphatic-venous anastomo-
sis can be performed.
103
This technique avoids venous re-
flux into the lymphatics, seen with the end-to-end
technique, and thus decreases the risk of venous throm-
bosis. Also, by using a secondary tributary of the main
vein as the site of anastomosis, the risk of anastomotic
stricture is avoided. For the smaller pediatric patients,
lymphatic capsule-venous anastomosis is possible.
103
In another series of 15 patients who underwent lym-
phovenous bypass, there was a reduction of more than 5
cm in leg diameter in 9 (70%) of 13 patients followed up
for an average of 6 months,
104
while Struick and cowork-
ers
105
reported that 5 of 8 patients operated on demon-
strated significant improvement. There was also a signifi-
cant reduction in the postoperative incidence of cellulitis
in both studies. In a larger study (91 patients), Huang and
coworkers
106
showed that after a mean follow-up of 2 years,
this procedure led to a reduction in limb diameter of more
than 3 cm in 79.1% of patients. Only 4 patients were un-
able to undergo the bypass procedure because of fibrosis
and thus lack of a suitable lymphatic vessel.
Ipsen and coworkers
107
found that lymphovenous
bypass reduced limb circumference by 0.8 to 4.1 cm if
the bypass was performed for secondary lymphedema,
but there was no real difference seen if the procedure was
performed for primary lymphedema.
In the presence of coexisting venous disease, seg-
mental lymphatic autotransplantation has been per-
formed with successful results
108,109
but is rather tedious
and is associated with secondary lymphedema at the op-
erative site.
Another shunting procedure for use in the presence
of coexisting venous disease is autologous interposition
vein grafting.
110
This involves direct lymphatic-venous-
lymphatic anastomosis. However, like lymphatic-venous
bypass, severe hypoplasia, aplasia of lymphatics or lymph
nodes, or extensive damage to the superficial and deep
lymphatics are contraindications to the procedure. The
only surgical alternative for these patients with exten-
sive lymphatic damage and coexisting venous disease is
a debulking procedure.
Tanaka and coworkers
111
attempted adipolymphati-
covenous transfer, which uses the long saphenous vein
along with its lymphatics. This was shown to be success-
ful in the 3 patients on whom it was performed. Free au-
Figure 4. Successful debulking surgery of the right leg, and left leg
lymphedema.
Figure 5. A complication of debulking surgery for lymphedema.
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tografts of the greater omentum have been used in 21 pa-
tients by Egorov and coworkers.
112
Of the 19 patients
followed up, there was satisfactory to good reduction in
all of the patients. Complications included partial ne-
crosis of the omental transplant in 2 patients.
Prophylactic Surgery. In patients who undergo exten-
sive lymph node removal in the pelvic region, there is a
greater risk of lymphedema and lymphocysts. In these
patients, an omentoplasty may be useful. This was evalu-
ated by Logmans and coworkers
113
in 12 patients and 10
controls undergoing pelvic surgery. Magnetic reso-
nance imaging revealed postprocedure lymphedema in
5 (50%) of 10 patients in the control group and 2 (16.7%)
of 12 in the omentoplasty group.
Orefice and coworkers
114
have undertaken prophy-
lactic lymphovenous anastomoses in patients after ilio-
inguinal dissection mainly for malignant melanoma. The
patients with prophylactic bypass had significantly less
lymphoceles and reduced hospital stay. There was no re-
duction in the frequency of infection. Seven (30.4%) of
23 patients developed lymphedema after the prophylac-
tic treatment, while 39 (75%) of 52 in the nontreated
group developed lymphedema.
COMMENT
We have reviewed the literature on the diagnosis and
management of lower limb lymphedema in the Western
world during the last 20 years. We have summarized
the available modes of investigation, with indicators to
the differential diagnosis. The mainstay of treatment is
nonoperative, with CPT being the treatment of choice.
Pharmacologic therapy in the form of benzopyrones
seems to have been successful but is not available on li-
cense in many countries. Many surgical procedures are
available, but clinical trial numbers are still small and
further evaluation is required. Surgical intervention
should be reserved for the highly refractory cases only
(
Figure 6).
Accepted for publication September 15, 2002.
Corresponding author and reprints: George Hamilton,
FRCS, University Department of Surgery, Royal Free Hos-
pital and University College Medical School, Pond Street,
London, NW3 2QG England (e-mail: g.hamilton@rfc.ucl
.ac.uk).
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Exclude Medical Causes
Investigation Including US, Duplex,
CT, MRI, Lymphoscintigram
Lymphedema
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Lymphedema
Confirmed
General Advice
∗
Mild Severe
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Stockings Improvement
No Significant
Improvement
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