LYMPHEDEMA PATHOPHYSIOLOGY
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Understanding Lymphedema Pathophysiology and Treatment
By: Joachim E. Suther
Lymphedema,
a protein rich swelling which usually
affects the extremities, is a very common condition worldwide.
Complete
Decongestive Physiotherapy is done successfully in Europe for
decades in the
treatment of primary and secondary Lymphedema and is now becoming
widely
recognized in the U.S.
UNDERSTANDING LYMPHEDEMA
PATHOPHYSIOLOGY AND TREATMENT
Joachim E. Zuther
Chronic peripheral lymphedema, an accumulation of protein rich fluid in
the
superficial tissues, is a very common and serious condition with
significant
consequences for the patient.
One of the main reasons for the development of lymphedema are surgical
interventions in combination with lymph node dissections, such as
mastectomy or
lumpectomy due to breast cancer, which is the number one cause for this
disease
in the U.S.
Although reliable statistics on the overall incidence of lymphedema are
not
available, conservative numbers estimate the incidence of secondary
upper
extremity lymphedema to be around 2.5 million. In addition to that
there is a
large number of patients suffering from primary lymphedema, which
usually
affects the lower extremities and is caused by congenital malformations
of the
lymphatic system.
Anatomy and Physiology of
the Lymphatic System
Unlike the blood system the lymphatic system works according to the one
way
principle, its main purpose is to transport "waste materials" from the
interstitial tissues back into the blood system.
These materials, also called lymphatic loads, consist of protein,
water, cells
and fat, are drained by the various vascular structures of the
lymphatic system
and filtered by a large number of regional and central lymph nodes
before they
enter the venous system. Part of these waste materials are also cell
products
and cell residues including foreign materials.
Initial lymphatic system: Lymph vessels start in almost every tissue as
lymph
capillaries. These initial lymphatics are made up of endothelial cells
which
overlap each other. Capillaries do not have a continuous connection
like blood
capillary endothelial cells do. A surrounding fiber net, anchoring
filaments,
arranged around the lymph capillaries, enables these small vessels to
stay open,
even under high tissue pressure.
Lymph capillaries collect lymphatic loads from the interstitial areas
and
gradually join together into bigger lymph vessels, so-called
precollectors which
then drain into collectors.
Collectors: One segment of a lymph collector is called lymph angion.
Contractions of smooth muscles situated in each lymph angion, generate
the
propulsive force of the lymph flow.
The pumping is aided by a large number of valves located inside the
collectors
which allow the lymph flow in only one direction. After passing a large
number
of lymph nodes, where foreign substances like bacteria are filtered out
and
necessary immune reactions are activated, the lymph fluid empties into
the
venous system, mainly via the thoracic duct.
The thoracic duct is the largest lymph vessel of the body. Under
physiological
conditions approximately 1-2 liters of lymph fluid drain in 24 hours
via the
thoracic duct into the left venous angle, formed by the left internal
jugular
and the left subclavian vein.
Starling's equilibrium: The amount of water and protein transported via
the
lymphatic system is depending on forces being active in the area of the
blood
capillaries.
Starling's equilibrium describes the balance of capillary filtration
and
capillary reabsorption. The transport of fluid through the membrane of
blood
capillaries depends on four variables:
1. blood capillary pressure (BCP)
2. colloidosmotic pressure (COP) of the plasma proteins
3. colloidosmotic pressure (COP) of the proteins located in the
interstitial
tissue
4. tissue pressure (TP)
Ultrafiltration:
blood capillary
pressure > COP of plasma
proteins
Reabsorption:
blood capillary
pressure < COP of plasma
proteins
Under physiological conditions 10-15% of the ultrafiltrate remains in
the
interstitial tissues and is then drained by the lymphatic system.
Shifting of Starling's equilibrium towards an increase in
ultrafiltration, e.g.
increased blood capillary pressure (inflammation, venous hypertension)
or
decreased colloidosmotic pressure (hypoproteinemia), can cause an
increased
amount of water and proteins, thus creating a higher burden on the
lymphatic
system. A healthy lymphatic system is, for some time, able to prevent
the onset
of edema, under normal conditions the transport capacity (TC) of the
lymphatic
system is approximately 10 times higher than the physiological amount
of the
lymphatic loads (LL) of water and protein => functional reserve
(FR) of the
lymphatic system.
Pathophysiology of
Lymphedema:
As long as the lymphatic loads remains lower than the transport
capacity of the
lymphatic system, the lymphatic compensation is successful.
If the amount of water and protein exceeds the transport capacity,
edema will
occur. This condition is called dynamic insufficiency of the lymphatic
system,
the lymph vessels are intact but overwhelmed. The result is an
accumulation of
fluid in the tissue which is usually treated successfully with
elevation of the
affected limbs, compression and decongestive exercises.
Lymphedema is caused by a mechanical insufficiency, or low-volume
insufficiency
of the lymphatic system.
In this case the transport capacity of the lymphatic system drops below
the
physiological level of the lymphatic loads of water and protein, that
means the
lymphatic system is not able to manage its main purpose which is to
clear the
interstitial spaces from excess water, protein and other chemical,
organic and
inorganic cell products.
The reasons for mechanical insufficiencies are various and mainly
caused by
surgery, radiation, trauma or inflammation.
Accumulation of high protein fluid is the result which is then
recognized as
lymphedema or lymphostatic edema.
Classification of
Lymphedema:
Secondary
Primary
1.Caused by lymph node
dissections, 1.caused
by
malformations of the
e.g. axilla, groin, pelvis or
neck,
lymphatic system (hyperplasia,
radiation of lymph nodes, trauma
or
hypoplasia, aplasia or sclerosis
infection ofthe lymphatic
system.
of lymph nodes)
2.Affects extremities,
genitalia,
2.Can be present at birth (congenital
abdomen or the face
a
lymph-edema), develop around the
(lymphedema precox) or
after
age of puberty
the age of 35 (lymphedema tardum)
Any lymphedema left untreated gradually worsens and will have
significant
consequences.The first stage of lymphedema (reversible stage) is
characterized
by a smooth texture of the tissue, the lymphedema is "pitting" and may
vanish more or less over night. If protein rich edema persists, the
congested
protein molecules are replaced by fibrotic tissue, i.e. the lymphedema
becomes
harder (stage II) and in addition to that patients are prone to
developing
frequent infections which additionally worsen the condition. Typical
for the
third stage of lymphedema, lymphostatic elephantiasis, is an extreme
increase of
the swelling combined with skin changes, loss of function and other
complications.
Since lymphedema, primary or secondary, is a progressive condition,
treatment
should begin as early as possible. The goal of the treatment is to
remove the
excess lymphatic loads of water and protein and to restore the
disturbed
equilibrium in the interstitial tissues of the affected area.
Treatment of Lymphedema
with Complete Decongestive
Physiotherapy:
Complete Decongestive Physiotherapy (CDP), done successfully in Europe
for
decades, is a non-invasive therapy with long lasting results. CDP,
which now
becomes widely recognized in the U.S., is superior to all other
approaches to
treat lymphedema (pumps, medication, surgery) and designed to reduce
and to
maintain the reduction of the swollen extremity.
At the end of the last century Winiwarter, professor of surgery,
already
described the basic steps of this therapy. The technique was improved
in the
1930s by Vodder, a physical therapist from Denmark, who successfully
treated
lymphedema.
In the 1980s Foeldi considerably improved this therapy by developing a
technique
called Complete Decongestive Physiotherapy, which even in advanced
stages of
lymphedema shows remarkable results.
CDP is done in two phases. The first phase, intensive phase, lasts
between two
and four weeks (in extreme cases longer), treatments are done twice a
day, five
days a week. The goal of this phase is to decongest the swollen
extremity to a
normal or near normal size. Simultaneously the patient is instructed in
techniques designed to maintain and even improve the condition after
the
intensive phase of the therapy.
The first phase is immediately followed by phase two, the maintenance
and
improvement phase which the patients continues at home.
For the safety of the patients and to achieve good results it is
absolutely
mandatory that the therapist is thoroughly trained in all components of
CDP.
Only certified MLD/CDP therapists have a complete understanding of the
pathophysiology of lymphedema and its treatment.
CDP consists of four basic
steps :
1. Manual Lymph Drainage
2. Compression Therapy
3. Meticulous Skin and Nail Care
4. Remedial Exercises
Manual Lymph Drainage is a gentle manual treatment technique which
improves the
activity of intact lymph vessels by mild mechanical stimuli. The goal
of this
treatment is to move excess lymphatic loads of water and protein into
areas with
still sufficient lymphatics.
Since the elastic fibers of the skin are destroyed during the course of
lymphedema it is mandatory to apply sufficient compression to the
affected area
in order to prevent reaccumulation of fluid. Compression therapy in
phase one is
achieved by short-stretch bandages applied after each treatment. After
the
extremity is decongested the patient is fitted with a sufficient
compression
garment that needs to be worn during the daytime. At night the patient
applies
mild compression using bandages.
Before treatment can be started the skin has to be free of infections
or fungal
affections.
During the treatment it is mandatory to apply a low-pH lotion to
maintain the
moisture of the skin.
Remedial exercises performed by the patient wearing the compression
bandage or
garment aid the lymphokinetic effects of the joint and muscle pumps.
References:
1. Marvin Boris, et al.
Lymphedema Reduction By Noninvasive Complex Lymphedema Therapy
Cornell University School of Medicine and Lymphedema Therapy. Woodbury,
NY
2. M.Foeldi, S.Kubik
Lehrbuch der Lymphologie
Gustav Fischer Verlag, Germany 1992
3. L.Clodius, M.Foeldi
Therapy For Lymphedema Today
Inter. Angio., 3 1984
4. S.Kubik
The Lymphatic System
Springer, NY 1985
5. M.Foeldi, E.Foeldi
Das Lymphoedem
Gustav Fischer Verlag, Germany 1991
6. G.Bringezu, O.Schreiner
Die Therapieform Manuelle Lymphdrainage
Otto Haase Verlag, Germany 1987
7. R.Lerner, J.Petrek
Lymphedema
Diseases Of The Breast, Lippincott - Raven, 1996
8. J.R. Casley-Smith
Lymphedema, The Poor and Benzo-Pyrones: Proposed Amendments To The
Consensus
Document
Lymphology 29, 1996 137-140
9. E.Foeldi
Preventions of Dermatolymphangioadenitis By Combined Physiotherapy Of
The
Swollen Arm After Treatment For Breast Cancer
Lymphology 29, 1996 48-49
10. E.Foeldi, M.Foeldi, L.Clodius
The Lymphedema Chaos: A Lancet
Ann Plast Surg 22:505-515
http://www.naturalhealthweb.com/articles/Zuther.html
--------------------
Primary Lymphedema: A Review of Pathophysiology, Diagnosis & Management
Family Physicians are key to treating developmental disorders
By Clare A. Green, DO
Abstract
Lymphedema is the accumulation of lymph in the interstitial spaces
caused by a
fault in the lymphatic system. Failure of any part of the lymphatic
system
results in the accumulation of plasma proteins in the interstitial
fluid,an
increase in interstitial fluid colloid osmotic pressure and subsequent
edema.
Primary lymphedema is caused by pathology affecting the lymphatics directly, rather than the lymphatics failing secondary to pathology of another organ system. The diagnosis of primary lymphedema is a diagnosis of exclusion, and many differential diagnoses must first be considered.
Lymphedema is associated with other anomalies of development and is a feature of several developmental syndromes. Primary lymphedema has a significant genetic inheritance pattern. The frequency at birth of those who will develop primary lymphedema is estimated to be about 1 in 6,000 with a sex ratio of about one male to three females.4
Imaging studies used to evaluate the lymphatic system include venography, lymphangiography and radio-isotopic tracers (lymphangioscintigraphy). Disease management is multifactorial, primarily focused on prevention, or slowing the rate of progression.
Patients must take an active role in controlling their disease by wearing the compression hosiery, frequently elevating the affected extremity, and following through with therapies recommended by their primary care physician. Drug therapy has not shown much benefit, and surgery is saved for extreme cases.
The
Clinical Picture
Lymphedema is defined as a swelling in some part of the body owing to a
fault in
the lymphatic system. Primary lymphedema is due to pathology affecting
the
lymphatics directly. The vast majority of patients complain of swelling
of the
lower limbs.
The swelling may be present in one or both legs and be present at birth or develop at any age afterwards, with a peak onset between the ages of 10 and 25 years. Lymphedema has a variable clinical onset, progress, and picture - it has a high incidence in females with an increased onset in the ages associated with the menarche and child bearing.
Despite the advances in technology and our knowledge of anatomy and physiology, the lymphatic system is almost as mysterious now as it was in the 1800s, when Milroy first described a family with lymphedema passing through six generations.6 Much of the pathophysiology discussed later is speculative, based on animal studies and theory.
Although there are centers that specialize in the treatment of lymphedema, most often it is diagnosed and managed by the primary care physician, along with a team of health care professionals. Primary lymphedema is a lifetime condition with no known medical cure.
The key to management is aggressive maintenance to slow disease progression. The maintenance, or preventative medicine,” is monitored by the patient’s primary care physician.
To give a complete overview of primary lymphedema, this paper will review the pathophysiology of the disease, the association with several developmental disorders, the genetic inheritance, and the management and treatment in clinical practice today.
Pathophysiology
of Lymphedema
Anatomy of the Lymphatic System
The lymphatic system begins developing at approximately 20 weeks
gestation, and
continues to undergo changes until puberty. The three components of the
lymphatic system are:
the spleen, thymus, tonsils, liver, and visceral lymphoid tissues in the gastrointestinal and pulmonary systems.
perfusing all the tissues of the body, the channels are connected by lymph nodes. The channels begin as blind thinly walled tubes, lymphatic capillaries, which join to form capillary plexus that in turn form larger trunks. The trunks eventually drain into two main trunks that empty into the venous system in the cervicothoracic area, either the right lymphatic duct, or the thoracic duct.
the substance that leaks out of the arterial capillaries, into the interstitium, and into the single-cell lymphatic vessels. Lymph fluid contains proteins, salts, water soluble fats, and clotting factors. Bacteria and smaller viruses are found in the peripheral lymph before filtration through a lymph node or one of the organized lymphoid tissues. The primary cells of lymph are lymphocytes.
The primary function of the lymphatic system is to clear the interstitial spaces of excess water, large molecules and particles and to subsequently transport them from the tissues back to the intravascular circulation. Starling’s hypothesis states that the exchange of water and small molecules across the capillary membrane is largely governed by the transmural capillary hydrostatic and colloid osmotic pressures. The colloid osmotic pressure is dependent on the relative impermeability of the capillary membrane to plasma proteins.
It has been known since 1896 that a proportion of the plasma proteins pass through the capillary wall but not all of it returns directly to the circulation.2 The concept of the lymphatic system as absorbing vessels, whose main function is to return to the bloodstream those protein molecules that fail to return via the venular capillaries, was first elaborated by Drinker in 1931; a concept that has been confirmed repeatedly with experiments using radio-active labeled plasma proteins.2
Iodine labeled albumin studies in man indicate a daily exchange between the intra and extravascular pools of 140% of the total body albumin. Failure of any part of the lymphatic system will inevitably result in the accumulation of plasma proteins in the interstitial fluid and therefore lead to an increase in interstitial fluid colloid osmotic pressure and the movement of more water into the interstitial space, i.e., edema.
Lymphedema is the accumulation of lymph in the interstitial spaces, principally of the subcutaneous fat, caused by a fault in the lymphatic system. Although there are many descriptive classification of the causes of lymphedema there is no classification based on the disordered physiology because the etiology of primary lymphedema remains obscure.
Between 1950 and 1960 Kinmonth introduced x-ray lymphangiography and subsequently devised a radiological classification based on 100 lymphographs.2 He described three radiological appearances:
No vessels visualized—which he called aplasia. True aplasia—no lymphatics—does occur but is very rare and likely only to be associated with those lymphedemas that are present at birth.
A reduced number of vessels visible–hypoplasia.
An increased number of dilated vessels visible—hyperplasia.
The mechanisms controlling the collection and passage of lymph, from the interstitial spaces to the blood system, remain largely unknown, however from the available research the various stages of lymph collection and transport can be discussed under the following descriptive functions:2
System
Overload
The capillary wall becomes more permeable in severe pathological
conditions.
Injury by trauma, heat, irradiation, and infections all cause edema
secondary to
increased capillary permeability. Venous congestion causes edema by
preventing
reabsorption in the venular capillaries. Provided the lymphatic
pathways are
normal this type of edema is eventually cleared, although this may take
longer
to resolve than the initial injury.
Inadequate
Collection
Like the venous system, the lymphatic vessels rely on unidirectional
valves and
exterior compressive forces to propel the fluid. The lymphatic terminal
buds are
in the tissues, the entry point for the extravascular fluid to enter
the
lymphatic system. It is hypothesized that when tissues are lax, the
pores of the
terminal buds are open to allow free flow inwards, and during tissue
compression
(caused by movement and exercise) the pores in the terminal segment are
closed.
Work done by Guyton and Casley-Smith suggests that in lymphedema the minor changes of tissue pressure that effect the opening and closing of the pores are absent because the interstitial pressure is both postitive and relatively constant.2 The pores may be kept permanently closed by the increased tension in the filaments attached to the endothelial cells caused by increased tissue pressure and tissue fibrosis, a situation which will prevent their alternate opening and closing and so make the collection system inadequate or incompetent.
Abnormal
Lymphatic Contractility
The walls of all lymphatics, except the terminal segments, contain
smooth muscle
cells and nerves. Studies by Olsewski and Engeset (1979), suggest that
there are
rhythmic contractions of the lymphatics at rest and that lymph flow
occurs
during the waves of lymphatic contraction. They also claim that
skeletal muscle
contractions per se do not increase lymph flow but that muscular
activity is
associated with an increased number of intrinsic contractions.2
Autonomic
Control
The sympathetic nervous system plays an important role in controlling
the rest
of the vascular tree. In 1968 Browse showed that limb lymphatics
contract in
response to sympathetic nerve stimulation, so raising the possibility
that
lymphatic contractility and lymph propulsion may be under nervous
control.2
Insufficient
Lymphatics
As confirmed by lymphangiography, the majority of patients with
lymphedema have
a reduced number of lymphatics. Whether the patient is born with this
reduced
number which manifests itself as lymphedema later in life or whether it
reflects
an acquired occlusion following some form of damage to the lymph
vessels is
often unclear. The reduced number of lymphatics are eventually
inadequate,
particularly following incidents which cause edema such as trauma or
inflammation.
LymphNode
Obstruction
The two most obvious and well known examples of lymphatic obstruction
are
lymphedema following block dissection of nodes (as in breast cancer
patients),
and lymphedema caused by filarial tropical elephantiasis. Other studies
have
correlated non-filarial primary lymphedema to the deposition of silica
particles
from the soil, as well as the presence of shrunken, fibrotic lymph
nodes.
Central
Vessel Defects
Congenital or acquired abnormalities of the central abdominal or
thoracic
collecting ducts may cause lymphedema. Congenital abnormalities may be
without
symptoms, however, usually they cause bilateral lymphedema with
moderate
dilatation of the vessels and nodes. Acquired obstruction of the
thoracic duct,
in children or adults, through trauma, mediastinitis, tumors, venous
thrombosis
or surgery is often symptomless. It may occasionally cause chylothorax
but
hardly ever causes peripheral edema.
Classification—Primary
vs. Secondary Lymphedema
Primary lymphedema is lymphedema caused by a primary abnormality or
disease of
the lymph conducting elements of the lymph vessels or lymph nodes.
Secondary lymphedema is edema caused by disease in the nodes or vessels that began elsewhere (neoplastic or filarial) or began in the cellular-nonconducting elements of the nodes (lymphocytic proliferative disorders). Secondary lymphedema may also occur following surgical removal of lymph nodes or vessels; such as in mastectomy for breast cancer.
Developmental
Disorders of the Lymphatic System
There are several different developmental disorders which are
associated with
lymphedema.5 Many of them present with lymphedema at birth, and should
be
considered when diagnosing a newborn with peripheral edema. As many of
the
syndromes are associated with other congenital anomalies, the presence
of
lymphedema may stimulate a more careful scrutiny of the other organ
systems
Turner
Syndrome
Turner syndrome is a collection of anomalies linked to the XO
karyotype. Among
multiple malformation syndromes, Turner sydrome is most often
associated with
congenital lymphatic disorders. The manifestations may include cystic
hygroma,
hydrops fetalis and peripheral edema. More well known features of
Turner
syndrome are the short stature, webbed neck, infertility, poor pubertal
development and shield chest.
Klinefelter
Ayndrome
Klinefelter Syndrome also occasionally is associated with lymphatic
blockage or
fetal hydrops. This syndrome is associated with a 47XXY karyotype and
occurs in
1/500 newborns. Other features of Klinefelter are tall stature, long
upper
extremities, poor pubertal development, microorchidism and sterility.
Trisomy
21
Cystic hygroma and lymphedema have been occasionally noted in children
with Down
Syndrome. Other features of Down Sydrome are characteristic facies,
short broad
hands, heart defects and mental retardation.
Klippel-Trenaunay-Weber-
Syndrome
Klippel-Trenaunay and Parkes Weber syndromes are panangiopathis
associated with
localized overgrowth of bone and soft tissue of a limb or portion of
the trunk.
A variety of blood and lymph vascular malformations may be seen,
including
hemangiomas, arteriovenous malformations, port-wine stains, varicose
veins,
lymphangiomas, and lymphedema.
Noonan
Syndrome
Noonan Syndrome has been suggested to have a “Turner-like” phenotype
with
similar manifestations that include peripheral lymphedema, hypoplastic
nails,
and shield chest. They often exhibit right sided cardiac abnormalities.
Despite
similarities, Noonan syndrome is distinct from Turner’s in that males
and
females are equally affected. Most cases of Noonan syndrome are likely
due to an
altered autosomal gene.
Noone-Milroy-Type
Hereditary Lymphedema
Also known as Lymphedema I, this disorder presents as brawny edema
usually of
the lower extremity. The diagnosis is usually made at birth. Tissue
swelling
occurs distally or proximally in the involved limbs, and either
hypoplasia or
hyperplasia of the lymphatics has been found.
Meige-Type
Lymphedema
Also known as Lymphedema II, this syndrome is similar to Lymphedema I
but the
onset of peripheral edema occurs during the second to the fifth
decades. The
legs are the most commonly involved, and lymphangiography reveals
hypoplasia of
peripheral lymphatics with dilation of lymphatic trunks.
Lymphedema-Hypoparathyroidism
Syndrome
The major diagnostic criteria for this syndrome include congenital
lymphedema—which
develops soon after birth, hypoparathyroidism, nephropathy, mitral
valve
prolapse, and brachytelephalangy.
Please refer toTable 1 and Table 2 for a comparison of the developmental disorders described.
The
Inheritance of Primary Lymphedema
The frequency at birth of those who will develop primary lymphedema is
estimated
to be about 1 in 6000 with a sex ratio of about one male to three
females.4
It is clear from the studies done by Dale, that lymphedema passes from generation to generation.4 True dominant inheritance, recessive and sex linked inheritance were excluded. In those patients with a genetic origin of their lymphedema, the form of inheritance is that of a modified dominant single autosomal gene.
On average, half the offspring of these subjects will carry the gene. The expression of this dominant gene approaches 50 percent and in those patients who develop lymphedema the majority will have done so by the age of 30 years. The expression of lymphedema is sex influenced and is much higher in females than males, 66 percent and 30 percent respectively.
In those patients who have no preceding family history probably only a small proportion have received a new mutation, thus creating a risk to children in this group which is higher than to siblings. In those patients with no preceding family history the risk to children in about 1 in 12.4
The
Diagnosis of Primary Lymphedema
Diagnosis of primary lymphedema, as in all diseases, relies primarily
on history
and physical exam. A patient presenting with lower extremity edema and
a family
history of hereditary lymphedema will be easier to diagnose than an
infant with
no family history. Primary lymphedema is usually differentiated from
secondary
lymphedema by history as well.
Most cases of lymphedema, both primary and secondary, affect limbs. Presumably this is because there are reduced options for collateral lymph drainage. Swelling results in discomfort, heaviness, reduced mobility, and impaired function. Moderate to severe pain is not a feature of lymphedema and, if present, should suggest alternative pathology. However the size and weight of some limbs soon produce secondary complications such as musculoskeletal problems.
Difficulty in the clinical diagnosis of lymphedema is likely to be encountered in the early stages before the characteristic skin and subcutaneous tissue changes ensue. It is not uncommon for lymphedema to present with swelling which comes and goes.
Differential
Diagnosis
If lymphedema presents in a newborn, developmental disorders of the
lymphatic
system, as described in the previous section, must be considered.
Cancer rarely presents in the first instance with lymphedema because lymph flow is maintained remarkably well through malignant nodes. Lymphoma does not produce lymphedema, and it is only in circumstances of advanced cancer (prostate carcinoma) where swelling can be a presenting feature.
Filiariasis, causing lymphedema by obstruction of the lymphatics, is a diagnosis which must be investigated in persons living in the tropics or with a history of traveling to the tropics.
A condition often confused with filarial elephantiasis is podoconiosis or non filarial elephantiasis. The clinical manifestations of swollen feet and legs are no different from that of any other cause, but the cause in this condition is uptake of microparticles of silica through the soles of the feet. It exists in non-filarial areas of tropical Africa, Central America, and India, and occurs only in barefoot walkers.
Heart failure
may cause
bilateral peripheral edema, and should be considered first in a patient
with
known hypertension or coronary artery disease. Associated symptoms are
dyspnea
on exertion, orthopnea, and paroxysmal nocturnal dyspnea. On physical
examination there may be pulmonary rales, distended neck veins,
tachycardia,
cardiomegaly, or gallop. Diagnostic studies to rule out heart failure
include a
chest radiograph and echocardiogram.
Cirrhosis is also a cause of bilateral peripheral edema. Associated
symptoms are
alcoholism, ascites, jaundice, and abdominal swelling. On physical exam
corresponding findings are hepatomegaly, jaundice, ascites, and
gynecomastia.
Diagnostic studies confirming cirrhosis include abnormal liver function
tests,
and liver biopsy.
Nephrotic syndrome is a cause of bilateral edema which is found primarily in children. Associated symptoms are polyuria and eyelid swelling. On physical exam there may also be edema of the eyelids and hypertension. Diagnostic studies in patients with nephrotic syndrome reveal albuminuria and hypercholesterolemia.
Hypoproteinemia will cause peripheral edema in malnourished individuals. Diagnostic studies for hypoproteinemia include serum protein and electrophoresis
Venous insufficiency can cause unilateral or bilateral peripheral edema, most often in female patients. The edema is usually alleviated with recumbency, and varicose veins are found on physical exam.
Thrombophlebitis is a cause of peripheral edema which usually presents with a sudden onset of swelling, redness and pain. Precipitating factors of thrombophlebitis are trauma, immobilization, childbirth, drugs, and birth control pills. On physical exam there is a tender cord, positive Homans’ sign, warmth, and low grade fever. Diagnostic studies are duplex/doppler ultrasonography, venogram, or computed tomography.
A ruptured gastrocnemius muscle will cause peripheral edema, usually with a sudden onset in runners. On physical exam the extremity will be painful, and have ecchymoses of the ankle. Computed tomography is used for diagnosis.
A Baker’s cyst may cause peripheral edema in the patient with rheumatoid arthritis, and is diagnosed by arthrogram.
Dependency of the lower extremity is a common cause of peripheral edema in post stroke patients. This type of edema is exacerbated by venous insufficiency, and improved by muscle activity of the legs.
Lipedema causes bilateral peripheral edema in the obese female. It is exacerbated by weight gain, and improved by weight loss. On physical exam it differs from the other types of lymphedema noted in that it spares the foot.
Salt retaining
drugs are
also a cause of bilateral peripheral edema. These include: estrogens,
oral
contraceptives, NSAIDs, lithium and vasodilators.
Making the Diagnosis
Once the other etiologies in the differential for peripheral edema have
been
ruled out, primary lymphedema should be considered in any chronically
swollen
limb without pain or inflammation. Traditionally, lymphedema is
described as a
brawny edema that does not readily pit. This is not a reliable sign.
Although
most of the swelling occurs in the subcutaneous layer, it is the skin
that
exhibits the most changes. It becomes thicker as demonstrated by the
Kaposi-Stemmer sign, a failure to pick up or pinch a fold of skin at
the base of
the second toe.
Skin creases become enhanced and hyperkeratosis develops. Skin changes occur most frequently in the lower limb, owing to the compounding effects of gravity. The term mossy foot is used when the skin changes are advanced, and secondary bacterial and fungal infections are common.7
Imaging studies used to evaluate the lymphatic system include venography, lymphangiography and radio-isotopic tracers (lymphangioscintigraphy). When evaluating someone with primary lymphedema, the risks of the imaging studies must also be considered.
Commonly, in uncomplicated cases, the invasive studies are not performed secondary to the risk of damaging the delicate lymphatic system. Usually, a venous doppler is performed to exclude venous obstruction. MRI is another nonanvasine imaging study which may be used to determine area of lymphatic blockage.
There is no laboratory study used to diagnose primary lymphedema. Genetic studies may be done if a physician suspects an associated developmental disorder.
Treatment
Elastic
Hosiery
The cornerstone of limb lymphedema treatment is elastic hosiery. The
hosiery is
designed to limit capillary filtration by opposing capillary pressure
and act as
a counterforce to striated muscle contractions. Exercise, breathing and
posture
are important for clearance of central dilated and obstructed
lymphatics in the
thorax and abdomen, which will improve peripheral edema.
Massage
Massage is controversial, despite being an accepted treatment for
lymphedema in
continental Europe. The problem is that most types of massage are used
to
increase blood flow to the tissue—therefore increasing the amount of
fluid to
be transported by the defective lymphatic system.
However, gentle tissue movement is a stimulus to lymph flow without increasing blood flow (and, therefore, capillary filtration). Manual lymphatic drainage (MLD) therapy is a specific form of manual massage that is directed primarily at normally draining lymph node regions via extremely gentle tissue manipulation. MLD is the only effective treatment for midline lymphedema where external compression is impractical.
Osteopathic
Manipulative Therapy
Osteopathic Manipulative Therapy is a therapy used by Osteopathic
physicians to
maximize the functions of all organ systems by working to improve the
structure
of the body through the musculoskeletal system. Improving lymphatic
function is
one of the cornerstone principles of Osteopathic Manipulative Therapy.
There are
several treatment modalities, all of which have shown to be extremely
beneficial
in improving lymphedema.9
Skin
Care
Prevention of infection is crucial to control of lymphedema, as
cellulitis can
lead to deteriorating, irreversible swelling. Patients with advanced
lympedema
and recurrent cellulitis are recommended to be put on prophylactic
penicillin.
Care of the skin, good hygiene, control of tinea pedis, chronic
dermatitis, and
other inflammatory dermatoses, as well as good antisepsis following
abrasions
and minor wounds, are as important as in diabetes.
Compression
Pumps
Pneumatic compression therapy or intermittent/sequential pneumatic
compression
is another treatment of extremity lymphedema. It consists of an
inflatable
sleeve or boot connected to a motor driven pump. Immediately following
the
therapy a compressive stocking is fitted to prevent limb reswelling.
Bandaging
Multilayer bandaging involves application of layers of strong
nonelastic
bandages to generate a high pressure during muscular contractions but
low
pressure at rest.
Drug
therapy
Diuretics alone have very little benefit in lymphedema because their
main action
is to limit capillary filtration by reducing circulating blood volume.
Improvement from diuretics suggests that the predominant cause of the
edema is
not lymphatic.
The Rutoside group of drugs, Paroven, has been advocated for use in lymphedema and a recent controlled trial of benzopyrones showed benefit in a variety of forms of lymphedema. Currently these drugs have only been used in Europe, and present data shows that clinical effect is mimimal.7
There are several other alternative therapies that have not been reviewed by medical literature. Many herbal preparations, such as grape seed extract, have reported beneficial effect in lymphedema. Microwave heat therapy has been used in China, with mixed results. It is theorized that the heat helps to break down the chronic fibrosis.7
Surgery
Surgery for lymphedema is usually used as a last resort, and used more
commonly
in countries in which the other therapies are not available.
Unfortunately,
since it cannot correct the problem, lymphedema will recur, and
sometimes worsen
following surgery. Surgery for lymphedema can be of two types:
reconstructive
and debulking. Associated risks of surgery include infection and
inflammation,
which greatly accelerate the progression of the disease and
obliteration of the
lymphatic vessels.
Extremity
elevation
Once started, treatment needs to be maintained; otherwise the edema
will
progress and become more and more difficult to reverse. Lymphedema of
the lower
limbs usually progresses even with treatment, however the rate and
degree of
progression is greatly reduced with treatment. Posture and limb
positioning are
important. Any dependent limb will swell as a result of increased
intravascular
hydrostatic pressure. Elevation of the affected limbs just above heart
level is
the most effective.
Weight
Management
There is some evidence that obesity exacerbates lymphedema,
particularly in the
lower leg, as it makes compression more difficult. A weight reduction
diet may
be indicated.
Coexsisting
Depression
Psychologically, many patients are affected by the disfigurement of
lymphedema,
and appropriate counseling may be a necessary part of
management.Physical
Handicap
Physical handicap is another aspect. Even those patients with mild lymphedema cannot tolerate prolonged standing, long distance running, or areas of high heat and humidity, as these situations increase capillary permeability and lymphatic load. Patients should be counseled on supportive footwear, and the need to elevate the affected extremity as frequently as possible during the day.
Disease
Progression
Air travel can also exacerbate lymphedema, some patients may want to
have the
affected extremity bandaged before travel to prevent increased
disability.
Lymphedema invariably requires the highest compression strength (>40mmHg) hosiery, and double hosiery may need to be worn on occasions to maintain control. Most garments last no more than 6 months, less in an active young patient.
Conclusion
The patient presented in the case report is an example of the typical
presentation of primary lymphedema. Her diagnosis had already been
made, but it
is evident that she could benefit from continued management and
education.
During her subsequent visits, she was educated in the importance of preventing the progression of her disease, by frequent foot elevation, wearing the compression stockings and supportive footwear, and by avoiding prolonged standing. She was treated monthly with Osteopathic Manipulative Therapy to improve lymphatic drainage. Her tinea pedis was treated and she was counseled about skin care. She went to genetic counseling regarding the inheritance of the disease, and was told that the chance of her child developing the disease was 20 percent.
Her pregnancy was uncomplicated, with the edema being most significantly affected in the last four weeks of gestation. She delivered vaginally, and her son had no congenital abnormalities.
The exacerbation of the peripheral edema, which occurred during the last month of her pregnancy, slowly reversed to her pre-pregnancy state over the period of three months.
Summary
The diagnosis of primary lymphedema, a disorder of the lymphatic
system, is made
primarily by family history and physical exam. The disease presentation
is
extremely variable, both in age of presentation, and severity of
disease. Many
times it is associated with other anomalies of development and is a
feature of
several developmental syndromes.
Primary lymphedema has a significant genetic inheritance pattern, although it can appear sporadically. Disease management is multifactorial, primarily focused on prevention, or slowing the rate of progression. Lymphedema is always progressive, but the discomfort and disability can be minimized by therapies which reduce the superfluous fluid as much as possible.
Patients must take an active role in controlling their disease by wearing the compression hosiery, frequently elevating the affected extremity, using supportive footwear, and having diligent skin care. Drug therapy has not shown much benefit, and surgery is saved for extreme cases.
The
pathophysiology of
lymphatic system disorders is not well understood. Hopefully further
investigations will better elucidate the nature of the disease, so that
treatment can be more directed at the cause of the disorder, rather
than the
symptom—peripheral edema.
Dr. Green recently completed a fellowship in OMM at Michigan State
University
College of Osteopathic Medicine, following a family practice residency
in
Muskegon, Michigan. She will practice family medicine in Oregon
--------------------
Lymphedema
Pathophysiology
http://www.nci.nih.gov/cancerinfo/pdq/supportivecare/lymphedema/healthprofessional/#Section_4
--------------------
Pathogenesis & lymphedema pathophysiology
http://www.emedicine.com/med/topic2722.htm
===========================Join us as we work for lymphedema patients everywehere:
Advocates for Lymphedema
Dedicated to be an advocacy group for lymphedema patients. Working towards education, legal reform, changing insurance practices, promoting research, reaching for a cure.
http://health.groups.yahoo.com/group/AdvocatesforLymphedema/
Subscribe: | AdvocatesforLymphedema-subscribe@yahoogroups.com |
Pat O'Connor
Lymphedema People / Advocates for Lymphedema
===========================
For information about Lymphedema
http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema\
For Information about Lymphedema Complications
http://www.lymphedemapeople.com/wiki/doku.php?id=complications_of_lymphedema
For Lymphedema Personal Stories
http://www.lymphedemapeople.com/phpBB2/viewforum.php?f=3
For information about How to Treat a Lymphedema Wound
http://www.lymphedemapeople.com/wiki/doku.php?id=how_to_treat_a_lymphedema_wound
For information about Lymphedema Treatment
http://www.lymphedemapeople.com/wiki/doku.php?id=treatment
For information about Exercises for Lymphedema
http://www.lymphedemapeople.com/wiki/doku.php?id=exercises_for_lymphedema
For information on Infections Associated with Lymphedema
http://www.lymphedemapeople.com/wiki/doku.php?id=infections_associated_with_lymphedema
For information on Lymphedema in Children
http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema_in_children
Lymphedema Glossary
http://www.lymphedemapeople.com/wiki/doku.php?id=glossary:listing
===========================
Lymphedema People - Support Groups
-----------------------------------------------
Children
with Lymphedema
The time has come
for families, parents,
caregivers to have a support group of their own. Support group for
parents,
families and caregivers of chilren with lymphedema. Sharing information
on
coping, diagnosis, treatment and prognosis. Sponsored by Lymphedema
People.
http://health.groups.yahoo.com/group/childrenwithlymphedema/
Subscribe: childrenwithlymphedema-subscribe@yahoogroups.com
......................
Lipedema
Lipodema Lipoedema
No matter how you spell it, this is another very little understood and
totally
frustrating conditions out there. This will be a support group for
those
suffering with lipedema/lipodema. A place for information, sharing
experiences,
exploring treatment options and coping.
Come join, be a part of the family!
http://health.groups.yahoo.com/group/lipedema_lipodema_lipoedema/?yguid=209645515
Subscribe: lipedema_lipodema_lipoedema-subscribe@yahoogroups.com
......................
MEN WITH LYMPHEDEMA
If you are a man with
lymphedema; a man with a loved one with lymphedema who you are trying
to help
and understand come join us and discover what it is to be the master
instead of
the sufferer of lymphedema.
http://health.groups.yahoo.com/group/menwithlymphedema/
Subscribe: menwithlymphedema-subscribe@yahoogroups.com
......................
All
About Lymphangiectasia
Support group for parents, patients, children who suffer from all forms
of
lymphangiectasia. This condition is caused by dilation of the
lymphatics. It can
affect the intestinal tract, lungs and other critical body areas.
http://health.groups.yahoo.com/group/allaboutlymphangiectasia/
Subscribe: allaboutlymphangiectasia-subscribe@yahoogroups.com
......................
Lymphatic
Disorders Support Group @ Yahoo Groups
While we have a number of support groups for lymphedema... there is
nothing out
there for other lymphatic disorders. Because we have one of the most
comprehensive information sites on all lymphatic disorders, I thought
perhaps,
it is time that one be offered.
DISCRIPTION
Information and support for rare and unusual disorders affecting the
lymph
system. Includes lymphangiomas, lymphatic malformations,
telangiectasia,
hennekam's syndrome, distichiasis, Figueroa
syndrome, ptosis syndrome, plus many more. Extensive database of
information
available through sister site Lymphedema People.
http://health.groups.yahoo.com/group/lymphaticdisorders/
Subscribe: lymphaticdisorders-subscribe@yahoogroups.com
===========================
Lymphedema People New Wiki Pages
Have
you seen our new
“Wiki” pages yet? Listed
below
are just a sample of the more than 140 pages now listed in our Wiki
section. We
are also working on hundred more.
Come
and take a stroll!
Lymphedema
Glossary
http://www.lymphedemapeople.com/wiki/doku.php?id=glossary:listing
Lymphedema
http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema
Arm
Lymphedema
http://www.lymphedemapeople.com/wiki/doku.php?id=arm_lymphedema
Leg
Lymphedema
http://www.lymphedemapeople.com/wiki/doku.php?id=leg_lymphedema
Acute
Lymphedema
http://www.lymphedemapeople.com/wiki/doku.php?id=acute_lymphedema
The
Lymphedema Diet
http://www.lymphedemapeople.com/wiki/doku.php?id=the_lymphedema_diet
Exercises
for Lymphedema
http://www.lymphedemapeople.com/wiki/doku.php?id=exercises_for_lymphedema
Diuretics
are not for
Lymphedema
http://www.lymphedemapeople.com/wiki/doku.php?id=diuretics_are_not_for_lymphedema
Lymphedema
People Online
Support Groups
http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema_people_online_support_groups
Lipedema
http://www.lymphedemapeople.com/wiki/doku.php?id=lipedema
Treatment
http://www.lymphedemapeople.com/wiki/doku.php?id=treatment
Lymphedema
and Pain
Management
http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema_and_pain_management
Manual
Lymphatic Drainage (MLD) and Complex Decongestive Therapy (CDT)
Infections
Associated with
Lymphedema
http://www.lymphedemapeople.com/wiki/doku.php?id=infections_associated_with_lymphedema
How
to Treat a Lymphedema
Wound
http://www.lymphedemapeople.com/wiki/doku.php?id=how_to_treat_a_lymphedema_wound
Fungal
Infections Associated
with Lymphedema
http://www.lymphedemapeople.com/wiki/doku.php?id=fungal_infections_associated_with_lymphedema
Lymphedema
in Children
http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema_in_children
Lymphoscintigraphy
http://www.lymphedemapeople.com/wiki/doku.php?id=lymphoscintigraphy
Magnetic
Resonance Imaging
http://www.lymphedemapeople.com/wiki/doku.php?id=magnetic_resonance_imaging
Extraperitoneal
para-aortic lymph node dissection (EPLND)
Axillary
node biopsy
http://www.lymphedemapeople.com/wiki/doku.php?id=axillary_node_biopsy
Sentinel
Node Biopsy
http://www.lymphedemapeople.com/wiki/doku.php?id=sentinel_node_biopsy
Small
Needle Biopsy - Fine Needle Aspiration
http://www.lymphedemapeople.com/wiki/doku.php?id=small_needle_biopsy
Magnetic
Resonance Imaging
http://www.lymphedemapeople.com/wiki/doku.php?id=magnetic_resonance_imaging
Lymphedema
Gene FOXC2
http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema_gene_foxc2
Lymphedema Gene VEGFC
http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema_gene_vegfc
Lymphedema Gene SOX18
http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema_gene_sox18
Lymphedema
and
Pregnancy
http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema_and_pregnancy
Home page: Lymphedema People
http://www.lymphedemapeople.com
Page Updated: Dec. 29, 2011