A Guide to Lymphedema

[lymphede...@gmail.com]

A Guide to Lymphedema

Posted 01/23/2008
Kristiana D Gordon; Peter S Mortimer
Author Information

Abstract

Lymphedema is a chronic debilitating condition that may lead to
significant physical and psychological morbidity. Swelling results in
discomfort, reduced mobility and impaired function. Recurrent
infections further complicate the management of this challenging
condition. Many patients currently receive inadequate care as
lymphedema fails to receive appropriate recognition by the medical
community. This article aims to provide dermatologists with a greater
understanding of the etiology of lymphedema and increased knowledge
for managing this condition.

Introduction

Lymphedema is a debilitating condition, manifesting in edematous
swelling due to excess accumulation of lymph fluid in tissues caused
by inadequate lymph drainage. Although other forms of edema cause limb
swelling, only lymphedema will produce brawny, hard and warty changes
of the skin and subcutis that limits the presence of pitting.
Lymphedema may be defined as an edema of greater than 3 months
duration that does not subside upon elevation of the affected site,[1]
or as the swelling of soft tissues resulting from the accumulation of
protein-rich interstitial fluid caused by a low output failure of
lymph flow.[2]

The terms 'lymphedema' and 'elephantiasis' are often used
interchangeably. Parasitologists and Tropical Disease physicians use
the term elephantiasis when referring to filariasis-induced
lymphedema. 'Elephantiasis' should be reserved as a descriptive term
relating to the skin changes observed in advanced lymphedema,
irrespective of cause.

Epidemiology

Physicians and surgeons diagnose lymphedema relatively infrequently.
[3] This may be due to uncertainty as to when to make the diagnosis,
especially during early stages of the disease. This undoubtedly
impacts upon patient care, as appropriate treatment becomes delayed
unnecessarily.
The literature relating to the prevalence of lymphedema is limited.
The prevalence of primary lymphedema within North America has been
estimated as 1.15 per 100,000 children, primarily affecting females
approaching the menarche.[4]

Secondary lymphedema (i.e., arm swelling following breast cancer
treatment) reportedly affects 15-20% of women receiving axillary
dissection and/or radiotherapy as part of their breast cancer therapy.
[5]

The total burden of lymphedema within the general population is
largely unknown. It is now known that, in the steady state,
interstitial fluid is removed from the tissues by the lymphatics and
not by venous reabsorption as was previously thought. This knowledge,
therefore, implicates lymphatic failure in all forms of chronic edema.
[6] Moffatt and colleagues attempted to gauge the prevalence of
chronic edema as a surrogate for lymphedema, within the population of
southwest London. Within the community of 619,000 adults, 823 were
found to have chronic edema. The estimated prevalence of chronic limb
edema was 1.33 out of 1000 people within the population, increasing to
5.4 out of 1000 in patients over 65 years of age. Fewer than 25% of
the cohort experienced chronic edema as a result of cancer therapy. A
total of 29% of patients had experienced recurrent cellulitis - acute
inflammatory episodes secondary to predominately streptococcal
bacterial infection.

Anatomy & Pathophysiology

The lymphatic system is primarily concerned with draining materials
from tissue spaces that cannot return directly to the bloodstream.
These materials include proteins and cells such as macrophages and
lymphocytes, as well as malignant cells.

Lymphatics are essentially of two types:

· Noncontractile initial lymphatics that absorb protein and fluid from
the interstitial space and transport them to the larger collecting
lymphatics;· Larger contractile collectors that are responsible for
pumping lymph to the regional lymph nodes.[7] Unidirectional flow is
maintained by a series of valves.

Lymph absorption and transport within the initial vessels are enhanced
by tissue deformation caused by skeletal muscle contractions,
pulsation of adjacent arteries and local massage. The supply of lymph
by initial lymphatics largely determines the force and frequency of
contractions within the collecting lymphatics. These physical effects
on pressure are probably influential on lymph transport in collecting
vessels when pumping or contractility fails, similar to how cardiac
massage maintains a circulation during cardiac arrest.

The lymphatic system forms a vital part of the immune response.
Bacteria, viruses, fungi and toxins that penetrate the skin are
absorbed preferentially by lymphatics.[8] Without initial lymphatics a
primary immune response cannot develop.[9]

Edema is an excess of interstitial fluid, which must be increased by
more than 100% before it is clinically detectable. Dermal edema
manifests as 'peau d'orange', owing to expansion of the
interfollicular dermis, whereas deeper subcutaneous edema will produce
pitting. Edema of any cause is due to capillary filtration
overwhelming the lymph drainage system, as interstitial fluid is
almost entirely reabsorbed by the lymphatics. Most edemas arise from
increased capillary filtration overwhelming lymph drainage for a
sufficient period of time and, therefore, represent relative lymphatic
failure. Lymphedema, however, is edema primarily due to the failure of
lymph drainage when lymph-transport capacity falls below normal.

The lymphatic system may fail for a number of reasons. Primary
lymphedema may arise from an intrinsic abnormality; for example,
genetically determined aplasia, hypoplasia or dysfunction of lymphatic
vessels.[10] Secondary lymphedema results from lymphatic damage due to
an extrinsic factor, such as surgical lymphadenectomy.

Primary Lymphedema

Primary lymphedema may be classified based upon the age of onset:
congenital (present at or soon after birth) or delayed onset (usually
postpubertal). Alternatively, lymphedema may be classified according
to whether it is familial or sporadic. In recent years a number of
genes have been implicated in primary lymphedema, most notably
Milroy's disease and lymphedema-distichiasis syndrome (see "Mechanisms
for Primary Lymphedema and Related Conditions").
Milroy's disease is a congenital form of primary lymphedema with
autosomal dominant inheritance. The typical phenotype is of bilateral
lymphedema below the knee and hydrocoeles are also present in males.
Brawny skin texture is a prominent feature and pitting is minimal.
Mutations in the VEGFR-3 gene on chromosome 5 are responsible.[11-15]

Lymphedema-distichiasis syndrome manifests with bilateral below-knee
lymphedema of postpubertal onset. It is associated with congenital
distichiasis, which is an accessory row of lower lid eyelashes. Other
features include congenital heart defects and varicose veins.[16] This
autosomal dominant condition is attributable to a mutation in FOXC2.
[17-20]

The most common form of primary lymphedema is the sporadic type.
Familial forms represent only 5-10% of primary lymphedema. Meige's
disease is considered the most common form of inherited lymphedema,
primarily affecting adolescent females. However, the underlying
genetic defect has yet to be identified.[21] The phenotype is of mild
bilateral lymphedema that rarely extends above the knee. There are no
other associated clinical features. Investigation with lymphography
demonstrates hypoplastic superficial collecting lymphatics as the
underlying abnormality, unlike:

· Milroy's disease, where there are dysfunctional initial lymphatics
and a failure of absorption of interstitial fluid;·

Lymphedema-distichiasis, where there is lymphatic valve failure giving
rise to lymph reflux.

Turner's (45 XO chromosomal abnormality), Noonan's and Proteus
syndrome (asymmetrical overgrowth of any body part associated with
macrodactyly and rugose palmoplantar tissue overgrowth)[22] are
examples of disorders due to genetic defects that include lymphedema
as part of their phenotype. Other examples include Aagenaes syndrome
(cholestasis and lymphedema), Hennekam's syndrome (lymphangiectasia
and lymphedema), hypotrichosis-lymphedema--telangiectasia syndrome
(attributable to mutations in SOX18) and microcephaly lymphedema-
chorioretinal dysplasia.

Klippel-Trenaunay syndrome (limb overgrowth, cutaneous angiomas and
venous disease) is an example of a sporadic condition with no
inherited pattern where lymphedema is a prominent feature.

Secondary Lymphedema

Secondary lymphedema develops from an acquired disruption of lymph
drainage routes (see "Causes of Secondary Lymphedema").[23] However,
few forms of lymphedema are mutually exclusive and a number of factors
are usually required to produce swelling.

Infection

A strong correlation between cellulitis and postcellulitic edema has
been reported.[24] However, it is most probable that patients with
lymphedema reportedly due to recurrent infection actually possess an
underlying subclinical lymphedema that has been unmasked by the
lymphatic damage from repeated episodes of cellulitis. It is difficult
to prove that infection actually causes lymphedema but recurrent
infection may lead to progressive lymphatic damage via lymphangitis
and lymphangiothrombosis.[25]

Lymphatic filariasis is the most common cause of lymphedema worldwide,
affecting an estimated 120 million people.[26] Mosquitoes are the
vectors for transmitting the larvae that migrate to the lymphatics and
hatch into adult worms, thus causing progressive disruption to
lymphatics resulting in lymphedema. The two major species of filariae
that cause lymphatic disease in humans are Wuchereria bancrofti and
Brugia malayi. Infection is concentrated in the tropics and does not
account for the majority of lymphedema seen in temperate zones.
Inflammation

A number of inflammatory conditions may predispose to the development
of lymphedema in a small number of patients. These include rheumatoid
arthritis, psoriasis and sarcoidosis.[27,28] Facial lymphedema with
involvement of the forehead and cheeks has been reported in patients
with rosacea and acne vulgaris. It has been proposed that chronic
inflammation leads to progressive interference with lymphatic
drainage.

Trauma

Trauma to the lymphatic system may occur during surgery, for example,
during vein harvesting or varicose vein surgery. Radiotherapy or
lymphadenectomy as part of cancer treatment may also damage lymph
drainage. However, the advent of sentinel node biopsy as an
alternative to axillary node clearance has been associated with a
reduction in the rate of lymphedema formation in breast cancer
patients.[29] Severe accidental trauma may also result in permanent
lymphatic dysfunction.

Venous Disease

Edema frequently complicates venous insufficiency due to increased
capillary filtration arising from venous hypertension. The resulting
edema is due to the inability of the lymphatic system to compensate
for this overload. Venous disease is often associated with lymphedema
and may give rise to gross swelling and skin changes. Increased
capillary filtration will, at first, increase lymph flow but over time
lymph drainage will fail in a manner analogous to high-output cardiac
failure.

Malignancy

Cancer-related lymphedema may be due to the underlying cancer or its
treatment. Recurrent malignancy should always be suspected in a cancer
survivor presenting with lymphedema.

Immobility & Dependency

Lymphedema may arise from immobility as the lymphatic system requires
movement and exercise to generate initial lymphatic transport via
changes in tissue pressures. One scenario is that of 'armchair legs',
a term coined by Sneddon and Church,[30] referring to patients who
spend day and night in armchairs with dependent lower limbs. This
condition is otherwise known as elephantiasis verrucosis nostras,
because of the gross skin changes that result. Despite no premorbid
lymphatic abnormality, immobility results in minimal lymph drainage
and a functional lymphedema. Over time, the failing lymphatics will
develop irreversible damage and a permanent lymphedema will ensue.

Clinical Features of Lymphedema

Lymphedema typically affects the extremities, mostly due to limited
opportunities for lymph drainage at the root of the limb. However,
detailed examination will often reveal lymphedema of the associated
quadrant of the trunk owing to shared lymph drainage routes; for
example, edema of the breast or posterior axillary fold as well as the
arm.

The clinical signs of lymphedema occur in the skin and subcutis.
Protein-rich materials, lipids and debris accumulate in addition to
water. This results in solid and fluid components to the swelling,
giving rise to the brawny nature of edema that resists pitting.[31]
Patients may present with varying degrees of severity, from mild
swelling to grotesque enlargement. Lymphedema of the leg may be
perceived by the patient as an asymmetry or increased circumference of
the limb that often develops overnight. The swelling does not usually
improve with elevation, except in the very early stages of the
disease, or when compounded by coexistent venous disease. Patients may
complain of pain or discomfort in the initial phase, prompting a
preliminary diagnosis of deep vein thrombosis.

Clinical examination reveals a number of skin changes in addition to
the aforementioned brawny fibrotic skin. Kaposi-Stemmer's sign is
pathognomonic of lymphedema,[32] and represents the inability to pinch
or pick up a fold of skin at the base of the second toe because of its
thickness.
Dilatation of the upper dermal lymphatics and subsequent fibrosis
heralds the onset of papillomatosis. Skin creases become pronounced
and hyperkeratosis develops. As lymph stasis progresses within the
dermis, these skin changes become more pronounced and may be referred
to as elephantiasis.

When engorged lymphatic vessels become visually apparent, like a
blister on the skin surface, they are termed lymphangiectasia.
Clinically, these appear as clusters of translucent, thick-walled,
fluid-filled vesicles. Lymph fluid may leak as a result of minimal
trauma and is termed lymphorrhea.

The severity of the lymphedema may be classified according to the
clinical features and limb volume ( Table 1 ).[33] Severity scoring
may be useful for monitoring response to therapy over a prolonged
period. Alternatively, patients may be staged upon the physical and
psychosocial impact of the disease.

Investigations

Most cases of lymphedema are diagnosed on the history and clinical
findings. The use of imaging techniques is dependent on availability
and expertise. Color Doppler duplex ultrasound is useful in evaluating
venous abnormalities.[34]

X-ray-contrast lymphography remains the gold standard mode of
demonstrating lymphatic collectors and lymph nodes, but the technique
is invasive as it involves direct cannulation of the lymphatics.[35]
It is rarely used since the advent of lymphoscintigraphy (isotope
lymphography), which is now the investigation of choice for
determining if chronic edema is attributable to lymphatic failure.

Lymphoscintigraphy involves the simple process of injecting a radio-
labeled protein, exclusively cleared by lymphatics, into the dermis/
subcutis. Measurement of uptake and transit through the lymphatics
permits the qualitative and quantitative analyses of lymph drainage
and can discriminate lymphedema from lipedema and nonlymphatic edema.
[36,37] Lymphoscintigraphy can distinguish between different
mechanisms for lymphatic failure, that is initial lymphatic
dysfunction (e.g., Milroy's disease), lymph collector reflux
(Lymphedema-distichiasis syndrome) but cannot necessarily identify a
cause for lymphatic obstruction (Figure 1).

Figure 1. (click image to zoom) Lymphoscintigraphy imaging. (A)
Normal uptake of radiolabeled tracer within patent lymphatics from the
feet to ilio-inguinal nodes. (B) Milroy's disease with bilateral
aplasia of distal lymphatics. (C) Lymphedema-distichiasis syndrome
with distal lymph reflux as evidenced by increased number of lower
limb lymph vessels. (D) Proximal obstruction of lymphatics affecting
the lower left limb.

Computed tomography (CT) or MRI may prove useful in detecting the
cause of any lymphatic obstruction, such as from a tumor. Specific
features, such as a subcutaneous honeycomb pattern, can distinguish
lymphedema from lipedema.

If filariasis is suspected, a blood test looking for filarial
antibodies should be undertaken. Referral to a tropical medicine
center should be considered.

Clinical Features of Lymphedema

Lymphedema typically affects the extremities, mostly due to limited
opportunities for lymph drainage at the root of the limb. However,
detailed examination will often reveal lymphedema of the associated
quadrant of the trunk owing to shared lymph drainage routes; for
example, edema of the breast or posterior axillary fold as well as the
arm.

The clinical signs of lymphedema occur in the skin and subcutis.
Protein-rich materials, lipids and debris accumulate in addition to
water. This results in solid and fluid components to the swelling,
giving rise to the brawny nature of edema that resists pitting.[31]
Patients may present with varying degrees of severity, from mild
swelling to grotesque enlargement. Lymphedema of the leg may be
perceived by the patient as an asymmetry or increased circumference of
the limb that often develops overnight. The swelling does not usually
improve with elevation, except in the very early stages of the
disease, or when compounded by coexistent venous disease. Patients may
complain of pain or discomfort in the initial phase, prompting a
preliminary diagnosis of deep vein thrombosis.

Clinical examination reveals a number of skin changes in addition to
the aforementioned brawny fibrotic skin. Kaposi-Stemmer's sign is
pathognomonic of lymphedema,[32] and represents the inability to pinch
or pick up a fold of skin at the base of the second toe because of its
thickness.
Dilatation of the upper dermal lymphatics and subsequent fibrosis
heralds the onset of papillomatosis. Skin creases become pronounced
and hyperkeratosis develops. As lymph stasis progresses within the
dermis, these skin changes become more pronounced and may be referred
to as elephantiasis.

When engorged lymphatic vessels become visually apparent, like a
blister on the skin surface, they are termed lymphangiectasia.
Clinically, these appear as clusters of translucent, thick-walled,
fluid-filled vesicles. Lymph fluid may leak as a result of minimal
trauma and is termed lymphorrhea.

The severity of the lymphedema may be classified according to the
clinical features and limb volume ( Table 1 ).[33] Severity scoring
may be useful for monitoring response to therapy over a prolonged
period. Alternatively, patients may be staged upon the physical and
psychosocial impact of the disease.

Investigations

Most cases of lymphedema are diagnosed on the history and clinical
findings. The use of imaging techniques is dependent on availability
and expertise. Color Doppler duplex ultrasound is useful in evaluating
venous abnormalities.[34]

X-ray-contrast lymphography remains the gold standard mode of
demonstrating lymphatic collectors and lymph nodes, but the technique
is invasive as it involves direct cannulation of the lymphatics.[35]
It is rarely used since the advent of lymphoscintigraphy (isotope
lymphography), which is now the investigation of choice for
determining if chronic edema is attributable to lymphatic failure.

Lymphoscintigraphy involves the simple process of injecting a radio-
labeled protein, exclusively cleared by lymphatics, into the dermis/
subcutis. Measurement of uptake and transit through the lymphatics
permits the qualitative and quantitative analyses of lymph drainage
and can discriminate lymphedema from lipedema and nonlymphatic edema.
[36,37] Lymphoscintigraphy can distinguish between different
mechanisms for lymphatic failure, that is initial lymphatic
dysfunction (e.g., Milroy's disease), lymph collector reflux
(Lymphedema-distichiasis syndrome) but cannot necessarily identify a
cause for lymphatic obstruction (Figure 1).

Figure 1. (click image to zoom) Lymphoscintigraphy imaging. (A)
Normal uptake of radiolabeled tracer within patent lymphatics from the
feet to ilio-inguinal nodes. (B) Milroy's disease with bilateral
aplasia of distal lymphatics. (C) Lymphedema-distichiasis syndrome
with distal lymph reflux as evidenced by increased number of lower
limb lymph vessels. (D) Proximal obstruction of lymphatics affecting
the lower left limb.

Computed tomography (CT) or MRI may prove useful in detecting the
cause of any lymphatic obstruction, such as from a tumor. Specific
features, such as a subcutaneous honeycomb pattern, can distinguish
lymphedema from lipedema.

If filariasis is suspected, a blood test looking for filarial
antibodies should be undertaken. Referral to a tropical medicine
center should be considered.

Complications of Lymphedema

Patients with lymphedema encounter a number of problems. The major
complications are attributable to swelling and infection.

Limb swelling, of the lower limb in particular, may cause discomfort
and aching. Limb heaviness and reduced mobility result in a functional
impairment. Secondary musculoskeletal problems, such as back and joint
pain, may ensue. Perceived disfigurement is rarely discussed in
journals but is of prime concern to most patients. A combination of
these factors may significantly impact upon the patient's quality of
life.[45,46]

Infections with bacteria and fungi are common occurrences in patients
with lymphedema. This is almost certainly due to reduced immune
surveillance secondary to lymphatic dysfunction. Recurrent cellulitis
or lymphangitis is a particular problem. Constitutional symptoms such
as fever, severe vomiting or headache may occur suddenly without
heralding skin signs of cellulitis. The erythema and pain may fail to
develop within the lymphedematous limb for up to 24 h following the
onset of systemic symptoms. Repeated episodes of infection will
exacerbate lymphedema and predispose to further infections, thus
creating a vicious cycle of events. Repeated episodes of cellulitis
may impact upon patients' quality of life and affect their ability to
work. Up to 10% of patients may be forced to change or lose employment
as a result of their chronic edema.[1]

It is imperative that patients receive oral antibiotics at the
earliest possible opportunity. Prophylactic antibiotics are indicated
for attacks occurring more than once a year.

Phenoxymethyl penicillin 500 mg once daily is the recommended
antibiotic of choice as it is as effective as any broad-spectrum
antibiotic. Long-term prophylaxis may be necessary.[47]
Tinea pedis affects the majority of patients with severe lymphedema
since maceration between the toes creates an opportunistic
environment. Unfortunately, long-term use of topical antifungal creams
may create further skin maceration. Prophylactic application of half-
strength Whitfield's ointment or alcohol (providing that the skin is
not broken) at night is, therefore, advisable.

Lymphedema & Risk of Malignancy

In rare cases, lymphedema may be complicated by the development of
cutaneous malignancy. The most documented association is with
lymphangiosarcoma.[48] Stewart-Treves syndrome refers to the
development of lymphangiosarcoma in a patient with chronic
postmastectomy lymphedema. However, it is now accepted that
lymphangiosarcoma may occur in longstanding lymphedema of any
primary[49-51] or secondary[52-55] cause.

A number of other tumors have been reported in association with
lymphedema. These include basal cell carcinoma,[56] squamous cell
carcinoma,[57] lymphoma,[58] malignant melanoma[59] and Kaposi's
sarcoma.[60] The proposed theory for the association with malignancy
is that of altered immune surveillance in the lymphedematous region.
[61]

Management

Lymphedema is essentially irreversible end-stage lymphatic failure.
Unfortunately, a number of misguided clinicians will inform patients
with lymphedema that they 'need to learn to live with it' and that
treatment is unavailable. Although lymphedema remains incurable,
treatment is possible and can significantly improve symptoms and
quality of life.[62] The principle of treatment is to improve, through
stimulating interventions, lymph flow within existing or collateral
drainage routes.
Management of lymphedema varies across the globe, reflecting
differences in resources,
including healthcare funding. For example, physical/medical treatment
plays a pivotal therapeutic role in developed countries. In poorer
countries appropriate compression hosiery may be deemed too costly and
surgery plays a more prominent role.

Recent advances in the provision of care within the UK have seen the
establishment of dedicated lymphedema clinics, often within tertiary
referral hospitals or hospices. These specialist centers allow
treatment regimens to be tailored to an individual's needs. The most
important element of lymphedema management is ensuring patients obtain
an understanding of their condition and what they can do to help
themselves. Patient motivation and compliance is central to a
successful treatment regimen, especially when employing physical
treatment modalities. Treatment centers allow regular reassessment and
monitoring of progress that ensure good results. However, more centers
are required to meet the unmet need for the many patients with
lymphedema now identified in the community.[1]

Physical Therapy

A number of key issues need to be addressed for each patient:
reduction in limb swelling, prevention of skin changes (such as brawny
texture, prominent skin creases, hyperkeratosis, papillomatosis),
prevention of infection and treatment of specific problems like
lymphorrhea. These can be addressed through the four cornerstones of
physical therapy (see "The Four Cornerstones of Physical Therapy in
Lymphedema").[63] Treatment regimes should be considered as twofold:
an initial intensive treatment phase aiming for limb-volume reduction,
often combining external compression, exercise and massage therapies;
followed by the long-term maintenance phase of utilizing compression
hosiery to sustain a manageable limb volume.[64]

External Compression

External compression is not intended to 'squeeze' the edema from the
tissues but to complement the exercise regimen by enhancing the muscle-
pump effect. Compression also opposes excessive capillary filtration.
External compression can be achieved by multilayer lymphedema
bandaging (MLLB) or elastic hosiery garments. Multilayer bandaging
systems followed by the use of compression garments have been
demonstrated to be more useful than using compression garments alone.
[65]

Multilayer Lymphedema Bandaging

MLLB uses a system of strong nonelastic bandages providing a rigid
casing for the muscles to work against ( Table 2 ). They also provide
low-grade pressure at rest and so allow refilling of initial
lymphatics. Although technically more complex, it is possible to
bandage truncal and genital lymphedema. MLLB is a skill that takes
time and patience to learn. It should not be attempted without
appropriate training. Contraindications to MLLB include severe
peripheral arterial occlusive disease or severe peripheral
neuropathy.

MLLB is used to reduce limb size and restore shape, allowing
compression hosiery to be fitted to maintain the improvement.[65] MLLB
may improve the hyperkeratosis and papillomatosis associated with
chronic lymphedema. The use of MLLB may be reserved for patients with
moderate-to-severe lymphedema. Bandaging may be the only effective
treatment for extremely large limbs and for the management of
lymphorrhea.

MLLB of the limb should include the initial application of an
emollient to the affected area. This is followed by a single
protective layer of cotton tubular bandage next to the skin. A soft
synthetic wool or foam underpadding is then applied, bandaging
distally and moving proximally. Inelastic bandages are then applied
with the limb held in full extension. Several inelastic layers may be
required to achieve the desired pressure. These can be applied in
either a 'figure-of-eight' or spiral pattern - the former results in
higher sub-bandage pressures. It may be necessary to bandage the
entire limb to reduce the chance of bandage slippage, or when dealing
with inverted-champagne-bottle legs. If only part of the limb is to be
bandaged, ensure the MLLB extends beyond the affected area.[38]

As yet, no firm guidelines exist to indicate the frequency of MLLB
system changes. The authors' experience is that MLLB systems should be
changed daily for the first 7 days, in order to reduce slippage and
aid compliance. It may be possible to reduce the frequency to two or
three times per week based upon individual results.

Compression Garments

Elastic compression hosiery garments are used for patients with mild-
to-moderate lymphedema and following MLLB in those with severe
lymphedema. Compression garments are suited to motivated patients with
good dexterity, intact skin, minimal pitting edema or limb distortion.
They are contraindicated in patients suffering from arterial
insufficiency, severe peripheral neuropathy, lymphorrhea or extensive
ulceration.

Compression garments are categorized according to the type of fabric
they are manufactured from (e.g. circular knit or flat knit garments).
[66] Circular knit garments are fashioned from seam-free material
continuously knitted upon a cylinder. These garments may be thinner
and more cosmetically acceptable compared with flat knit hosiery. The
latter garments are thicker and made from pieces of material that are
sewn together to create custom-made compression hosiery. These
garments may be more suitable for patients with limb distortion or
those requiring the addition of zippers to the garment to aid
application.

The severity of lymphedema will determine the grade/class of
compression required from the garment ( Table 3 ). The reported
pressures (in mmHg) for each garment refer to the pressure applied to
the ankle at the smallest circumference.[66]

Specialist lymphedema centers offer regular appointments for limb
measuring and supply appropriately sized hosiery. Garments should be
fitted when the extremity is as close to a normal shape or size as
possible. They should be comfortable and should deliver a graduated
compression, highest distally. Patients are advised to wear the
compression garments continuously during the day and remove at night
when the extremity is elevated in bed and the muscles resting. Hosiery
should be replaced promptly each morning. To encourage compliance, the
elastic compression garments must fit correctly. Full-length or below-
knee hosiery can be supplied, depending on the patient's needs.

Two garments (or pairs) should be provided every 6 months, one to wear
each 24 h while the other is being washed. Frequent washing is
necessary to maintain the elastic properties of the garment. These
high-compression garments can now be prescribed by general
practitioners, providing the correct measurements and details (e.g.,
compression class) are known.

It is important to assess the patient's risk of arterial disease and
cutaneous sensation before considering external compression therapy.
Patients with a reduced Ankle Brachial Pressure Index (ABPI) of
0.5-0.8 mmHg should not receive sustained compression exceeding 25
mmHg.[67] Patients with an ABPI of less than 0.5 mmHg should not
receive compression hosiery at all. If arterial disease is suspected,
referral to a vascular surgeon should be made before introducing
compression.

Pneumatic compression therapy is another widely used treatment. It
involves connecting an inflatable boot or sleeve to a motor-driven
pump with the aim of displacing lymph towards the root of the limb
through cyclical inflations. However, swelling will rapidly return if
hosiery is not fitted immediately after the procedure. Few studies
report the beneficial use of pneumatic compression in lymphedema.[68]

Exercise

A program of exercise and movement should be instigated to maximize
lymph drainage.[69] Isotonic exercises involve muscle contractions
that encourage the passive and active phases of lymph drainage within
lymphatic vessels. Overexertion and static exercise should be avoided,
as these cause the swelling to worsen through increased blood flow.
Preferred exercise regimens include walking, swimming, cycling and low-
impact aerobics for lower-limb swelling.

Skin care

Meticulous hygiene is necessary to remove excess keratin and reduce
the bacterial load on the skin's surface. Patients must be encouraged
to cleanse the skin regularly and subsequently dry the area
thoroughly. Regular inspection by the patient is necessary to identify
fissuring or developing cellulitis. Even with excellent skin care,
bacterial or fungal infection may develop. At the earliest signs of
infection, topical or systemic antifungal or antimicrobial therapy
should be commenced, to prevent sepsis or a deterioration of the
lymphedema.

Massage

Manual lymphatic drainage (MLD) and simple lymphatic drainage (SLD)
are specific massage techniques designed to relocate lymph fluid from
the lymphedematous region to unaffected areas that may drain freely.
Tissue movement must be gentle if it is to stimulate lymph flow
without increasing blood flow.[70]

The principle behind MLD is to stimulate downstream lymph flow in
truncal/central collateral routes in order to 'clear the way ahead'
for the increased flow generated from the congested upstream regions
by exercise and compression. MLD forms the main treatment for midline
lymphedema of head and neck, breast and genitalia. A number of MLD
techniques are available but no single method appears to be superior.
A number of features are common to all methods, including the
positioning of the patient in the supine position (unless for head and
neck lymphedema) and undergoing daily treatments lasting approximately
1 h. Practitioners employ gentle pressure and slow movements to move
fluid towards functioning lymphatics. Massage starts distally and
moves proximally to drain the affected areas. Unaffected regions are
treated before the lymphedematous limb or region. Deep diaphragmatic
breathing is employed by the patient throughout the session.

MLD is a technique that is carried out by trained therapists, whereas
SLD is a 'best copy' carried out by the patient or carer for use in
the community setting. SLD should be taught to the patient by a
trained practitioner. Patients are encouraged to massage their swollen
limb for 15-20 min daily.

Additional Treatments

Drug Therapy

There is little use for drug therapy in the management of lymphedema.
Diuretics alone show minimal improvement in lymphedema, as their
primary action is to limit capillary filtration through a reduction of
circulating blood volume.

Benzopyrones are a peculiar and complex group of drugs. They are a
concoction of plant-based chemicals and all of them - Daflon500®,
Coumarin and Paroven® (the only one licensed for use in UK) - are
essentially the same group of drugs. Paroven may create a marginal
improvement in limb volume.[71] However, this has been demonstrated to
be of little clinical benefit to the patient. Similar disappointing
results have been reported with other drugs from this group, including
Coumarin.[72]

Surgery

Surgery must be considered as a palliative rather than curative
treatment for lymphedema. However, it may be indicated in those
patients for whom physical therapy has failed, or if the
lymphedematous region hinders daily functions and interferes with
primary physical therapy. Surgery typically involves the removal of
excessive tissue (de-bulking procedures) or the bypassing of a local
lymphatic defect. Plastic surgery may also be indicated to remove
redundant skin after highly successful medical therapy.

Traditional de-bulking operations are reserved for severe cases of
lymphedema when all else has failed, except in certain situations such
as eyelid or genital lymphedema where it may be considered at an early
stage. Limb-reduction surgery generally involves the elliptical
excision of skin and underlying subcutaneous tissue to the deep
fascia, orientated along the length of the limb, called the Sistrunk's
operation.[73] It is not an asthetically pleasing operation but may
deliver some symptomatic relief to the patient. This procedure may be
preferable to circumferential excisions and skin grafting, namely the
Charles' operation.[74,75]

Lymphatic bypass surgery aims to restore lymphatic function through
bypass of a localized block. For example lymphatic to lymphatic
grafting may attempt to bridge a block with normal lymphatic vessels
transplanted from a nonlymphedematous region.[48] Other procedures
utilize pedicles of tissue possessing healthy lymphatics (e.g.
omentum, mesentery or isolated small intestine) in attempts to provide
alternative pathways for lymph fluid to drain away from affected areas.
[76-79]

Surgery must be performed by surgeons possessing lymphedema
experience. Patients must receive additional lifelong postoperative
nonsurgical therapy, such as daily use of compression hosiery.
Summary & Conclusions

Lymphedema is a chronic debilitating condition that affects a
considerable number of patients. It may lead to significant physical
and psychological morbidity unless appropriately managed. Swelling
results in pain, impaired function and reduced quality of life.
Recurrent infections exacerbate lymphedema and lead to further
episodes of cellulitis, creating an inevitable spiral of decline.
Specialist lymphedema clinics provide advice and physical treatments
that significantly improve patient outcome and quality of life.
However, patient motivation and compliance remain central to
successful treatment.

Expert Commentary

In our opinion, lymphedema is under-reported and often poorly managed
by the medical community. Patients require support from a multitude of
disciplines but often achieve most help from lymphedema therapists and
nurses working in dedicated units. Although the responsibility of
carrying out treatment should rest with the individual, most patients
require long-term support in order to maintain the improvement in
swelling. Patient and physician education is key to the long-term
success in managing patients with lymphedema. Information resources
include the Lymphedema Support Network for patients and the British
Lymphology Society for healthcare professionals.

Five-year View

The field of lymphedema has recently experienced a number of exciting
advances. These include the identification of disease-causing
mutations responsible for specific forms of primary lymphedema (i.e.
Milroy's disease and lymphedema-distichiasis syndrome). It is likely
that further genes implicated in the development of primary lymphedema
will be identified. The upsurge in knowledge borne out of the
discovery of the genes and proteins controlling lymphangiogenesis is
likely to lead to new treatments targeted on molecular signaling known
to affect lymphatic function.

Information Resources

·Lymphedema Support Network's UK website offering support to patients
with lymphedema www.lymphoedema.org/lsn/index.html·
British Lymphology Society is a UK organization for healthcare
professionals dealing with lymphedema www.lymphoedema.org/bls/index.htm·
Australian Lymphedema website www.lymphoedema.org.au·
American National Lymphedema Network www.lymphnet.org

Reprint Address
Peter S Mortimer, St George's Hospital, Department of Dermatology,
Blackshaw Road, London, SW17 0QT, UK. E-mail: mort...@sgul.ac.uk

http://www.medscape.com/viewarticle/568789_1


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Pat O'Connor
Lymphedema People
http://www.lymphedemapeople.com