Lymphoedema Association of Australia

Founding Chairman J.R. Casley-Smith, D.Sc. (Oxon&Adel.), M.D. (h.c. multi), M.B.B.S. Prof. (h.c. multi)

Chairman: Dr. Judith R. Casley-Smith, Ph.D., M.A., M.D. (h.c.) Prof.(h.c. multi)

Home Page: http://www.lymphoedema.org.au

2000 Newsletter

Introduction

In this newsletter I am including a questionnaire for those people for whom lymphoedema is a problem and one for either a partner, friend or relative to fill out and return to the L.A.A.

This questionnaire was trialled by the S.A. Support Group and I thank those people who took the time to reply and so help to make the one now presented clearer and easier to answer. I presented some of the trends shown from the Pilot Study at the N.L.N. conference but it is too early to give you these results. It will also be of interest to see if there is a notable variation between different countries and between city and rural populations, as I hope all our members both in Australia and overseas will participate in this study. If you are a Healthcare professional, I would ask you to pass this on to one (or more preferably) of your patients to complete and return. To make this simple I have re-explained some of the various causes of lymphoedema, and the difference between lipoedema and lymphoedema.

DeCourcy Squire, P.T., has very kindly written a very good and clear article on Primary lymphoedema. I am also including a small section on fungal infection (tinnea or Athlete's foot) because it would seem that the dangers associated with this are not always recognised.

There is exciting news about topical benzo-pyrones (see P. 10.). Updated lists of therapists can be found on our website http://www.lymphoedema.org.au as can necessary changes of available material and prices . We expect therapists to notify us immediately of any change of contact details.

Because of the increasing costs of running the Association and the extra work and costs associated with our new Goods and Services Tax some prices have unfortunately had to be raised (including memberships). If you are able and willing to receive future newsletters via email, would you please fill out the appropriate part of the membership form and return with your subscriptions. This would be of great help to us. In future newsletters a publication list of new therapists and any change of contact numbers will be published, so please keep this list for future reference. Therapists will only be listed if their membership subscriptions are current. Your membership subscriptions for 2001 are due now.

The home page is constantly being updated. However we hope that in the near future it will be redesigned to make it easier to read and to find the sections in which you are interested. Watch for this event!

Fungal Infections

Fungal infection is a 'ringworm' and looks like red patches of skin, often with white flakey skin over this area, and if under nails, the condition of these is affected and they become hardened, distorted and often yellowed.

One of the points that did emerge from the pilot questionnaire was that fact that a significantly larger proportion of patients with lymphoedema of the arm reported the presence or occurrence of this, than did those with lymphoedema of the leg. I would have expected the opposite to be the case. The result had to make me wonder if this were a) that people with lymphoedema of the arm are sometimes more mobile and able to check between the toes for this than those with lymphoedematous legs or b) that those with lymphoedema of the legs are already aware of this risk and are, or have been, using an anti-fungal cream or powder prophylactically. The latter should ask someone, such as the family physician, to regularly check for this.

I would like to point out that this does not just occur between toes, where it is most common, and possibly under the nails (if it has been present long term), but can easily be transferred to other warm, moist areas e.g. groin (including the vulva or around the scrotum) and under the breasts. Consider how you dry yourself after bathing e.g. the top part of the body is usually dried first, then the lower trunk, the legs and finally between the toes. As this part of the towel is in your hands, you often finish up by redrying those areas that are harder to dry i.e. between the legs and under the breasts. This can immediately transfer any fungal infections that may be present between the toes.

People often think that smelly feet are just smelly feet, but it is usually a sign of infection and infection smells. Transmission of this problem occurs through wearing the same shoes, clothes or in some cases the same rubber gloves, walking barefooted or resting feet etc on the same surfaces e.g. carpets and shower floors. It can frequently be transmitted or contracted in public areas e.g. footbaths at swimming pools.

Tinnea can also be transferred from your partner, so if he or she has this problem, this too should be rectified.

Fungal infections, in themselves will exacerbate any lymphoedema already present by increasing inflammation and its sequelae. Quite apart from this they affect the integrity of the skin and thereby provide a site for easy entry of bacteria. This will then cause a further inflammatory response and again worsen the lymphoedema. Whereas for minor tinea, a topical application (powder or cream) is usually satisfactory, for long term infections where it is deep seated or for toes which are difficult to apply them between, an oral anti-fungal may be necessary. This must be obtained with a doctor’s prescription and needs to be taken for at least 6 months (or longer) depending on the drug prescribed. I cannot stress enough how important it is for you to avoid these infections if at all possible.

Causes of Lymphoedema

1. Primary Lymphoedema

This is a genetic abnormality causing an insufficiency in lymphatic drainage. It can be present at birth, or more commonly occur at puberty or later in life. Pregnancy can cause a later onset or worsen the lymphoedema (because of the extra pressure of the foetus on pelvic lymphatic drainage). Sometimes lymphoedema may be of primary origin but the onset can be triggered by e.g. an injection or drip put into a limb "at risk" e.g. in the case of lymphoedema originally of one leg only, onset in the other leg can be precipitated by this. Sometimes this lymphatic deficiency is almost minimal and limbs can remain 'normal', i.e. in size, for years, but the onset may be triggered later in life by a traumatic incident.

2. Secondary Lymphoedema

This is due to an outside factor which reduces the drainage of the once normal lymphatics. Some causes are listed below to lymphatic drainage through the nodes.

a. Cancer: This in itself can cause blockage. If a limb, or neck and face suddenly swells, this should be the first thing checked for especially after the age of 30 years. Patients should never be treated without a thorough investigation and diagnosis.

b. Secondary metastases: As for cancer.

3. Trauma

1. Accidents: including bad fractures, where vessels may be severed or crushed.
2. Surgery: particularly surgery for carcinomas, (including melanomas) where nodes are removed. Other forms of surgery that can cause lymphoedema are; liposuction, the stripping of varicose veins, knee reconstructions and other operations that may inadvertently damage the lymphatic system, or overload a somewhat reduced system that up to that point was functional.
3. Radiotherapy: This is used to kill the cancer cells nodes, and thereby blocks them and can lead to lymphoedema. It may also cause burn and scarring leading to constriction of and damage to the lymphatics. In rare cases chemotherapy may also cause blockage of nodes.
4. Paralysis:-especially if the patient spends much of the time in a wheel chair with their legs in a downward position
5. Allergic reactions: These can include spiderbites, (especially white tailed or red-back spiders), cat scratch allergy, tampon shock, coral abrasions, and adverse drug reactions (only rarely), and occasionally by severe infections.
6. Self - mutilation: drainage may be impeded and result in lymphoedema if a person applies a tourniquet to a limb.

4. Filariasis Lymphatic vessels and valves are damaged and at a later stage may be blocked by the parasite (transmitted by mosquitoes). Lymphoedema will not be apparent until a number of years after the original infestation.
5. Chronic Venous Insufficiency (CVI): Lymphoedema can occur in the later stages on top of the original venous oedema
6. Lipoedema: Lymphoedema can occur in the more severe stage of this disease but does not always happen.
7. AIDS: Lymphoedema can occur in the later stages.
8. Benign growths: these can affect drainage e.g. lymphadenomas.
9. Some other causes are: Leaking breast implants, (where silica lodges in the nodes) and podoconiosis (through entry via the feet), after deep vein thrombosis, and after severe mastitis where infection was not adequately treated.

Where can lymphoedema occur?

Whereas lymphoedema is usually diagnosed in limbs, it is often neglected or thought of as unimportant in other areas of the body. This may not seem of great importance to the treating physician or surgeon, but can make a great difference in the comfort, general well-being (including healing) and self-image of everyone who has to cope with this.

Lymphoedema can occur in any limb, the face, neck and trunk, in one or both breasts, or in deep organs or the abdominal cavity. i.e. anywhere in the body. It is more easily recognisable if it appears in a limb but, because these drain to particular sets of nodes e.g. arms to axillary (under the arm) nodes and the legs drain to the superficial inguinal (in the groin - crease of the leg between the leg and the trunk) and then on to the deep pelvic nodes, the adjacent superficial regions of the trunk may also be involved. These also drain to the same nodal areas i.e. thoracic (chest) area both anterior and posterior (front and back) drains to the left axillary nodes from the midline to the left side and from the midline to the right axillary nodes on the right side. These include the breasts. Similarly with the superficial abdominal (again anterior and posterior i.e. front and back) which on the left hand side drain to the nodes in the left groin (sup. inguinal) and on the right to the right groin (sup. inguinal). This drainage divides superficial drainage of the trunk into 4 lymphatic quadrants (or lymphotomes i.e. drainage areas to the same outlet or set of nodes).

Frequently this swelling is overlooked and sometimes not treated adequately and yet it is often this that causes as much of a problem as the limb swelling, and sometimes this is the only major problem.

The "division" lines between these are called watersheds. However when an overload of one area occurs there are small collateral (just under the skin) lymphatic vessels that naturally cross these lines and extra lymph will flow to the adjacent areas (quadrants) thereby compensating for the extra load in one particular area. This may mean that these areas also can become overloaded and start to swell e.g. an opposite side of the chest and a normal breast, and/or the abdominal area below this area on the same side after a post-mastectomy operation.

This can usually be easily rectified by improving the deep as well as the surface drainage that these adjacent areas drain to with correct massage. The affected area (lymphotome) can then have a free pathway for redirecting and improving drainage. Swollen or "lumpy" breasts can be quickly reduced especially if treated early before too much fibrosis occurs. This also applies e.g. to a lump or bulge under a scar under the arm on the side of the chest. Other scars (e.g. from completely different and previous operations) may limit where or how this drainage can be achieved.

The genital areas also drain to the inguinal (or groin) nodes and if these are affected, swelling of this area may be a problem. Certainly this area is "at risk".

Lymphoedema can also manifest as hydroceles i.e. a contained swelling in a particular area. These frequently occur in the genital region but can also be located in other areas.

How does the body react to compensate for overload?

Many things work to prevent lymphoedema from occurring. These are called 'safety-factors'. The superficial drainage across 'watersheds' which has been discussed above is one of these. At the interstitial level (between the muscles and the skin), both in acute injury and inflammation, or where a person is at risk of lymphoedema a number of factors come into play to try and prevent the onset of lymphoedema. In an inflammatory (or traumatic) situation, there is excessive leakage of water, protein and cells etc. from the blood vessels. The changes in tissue pressure cause an increased uptake by the lymphatic system. Tissues cells (macrophages) become more active and lyse (breakdown) excess protein. Protein is a stimulus for the formation of fibrotic (scar) tissue, so that anything that reduces this acute phase helps to prevent this occurring and thereby blocking the channels between the blood vessels and the lymphatics as well as the transport of oxygen which promotes general tissue health and healing. This is aided by the increased contractions of the collecting lymphatics, which have muscle in their walls, and thereby increase clearance. It is only when these mechanisms become overloaded and the lymphatic drainage cannot cope with the lymphatic load from the tissues that lypmhoedema occurs. Contrary to the theory held for the last 100 years, it would seem that much of the return of water (75-80%) to the blood system occurs at the nodes rather than back via the venous capillaries. If the nodes are either few in number e.g. a) as they may be in primary lymphoedema or b) have been removed by surgery (and the lymphatics thereby severed), then this will greatly affect removal of the excess tissue fluid and cause further and long-lasting pathological changes.

Recognition, Diagnosis and Treatment of Lipodema Vs. Lymphoedema

Lipodema is a chronic disease of complex causes, many of which we understand little about. These include hormonal imbalance, an inability to metabolise exudate from blood vessels so that those proteins and cells that would normally be metabolised and returned to the circulation are deposited as adipose tissue in the subcutaneous tissue. The blood vessels themselves are affected, venous stasis and vasoconstriction occur and return is diminished especially at the subcutaneous level. This causes arterial constriction which accounts for the cold and often pale skin and leads to an increased lymphatic load(1). The condition worsens over years as tissue channels become progressively narrowed until the condition of a secondary lymphoedema, overlying the original lipodema, may lead to a situation where the patient may be either wheel-chair bound or bedridden. Weight gains can be up to or greater than 250 kgs. At this stage infections and intractable ulcers (or ones that necessitate skin grafts when lack of oxygenation to the skin causes problems with healing) which can be due to the simplest injury e.g. careless donning of a compression garment or other minor trauma, occur with an even higher frequency.

This condition occurs predominantly in women, and can in some cases be familial; the rare cases of men with lipodema always seem to include a hormonal imbalance which should be treated if possible. The macrophages themselves become overloaded and cease to play an active role in protein proteolysis and look like fat cells.

Lipodema is often misdiagnosed as obesity in its earlier stages but the symptoms are clear and distinctly recognisable clinically from this. In its later stages it may be more difficult to distinguish from lymphoedema, although the case history and distribution of excessive tissue should provide an indication. The overlying condition of lymphoedema may occur in the later stages. Lipodema can occur in the legs, buttocks and also, but not necessarily, in the arms. It does not involve either the feet or hands until the onset of lymphoedema. The mean age of diagnosis is approximately 35-36 years but it usually starts at puberty. Symptoms of onset, however, can start in childhood, and may be clinically detectable in adolescence. Cellulite, which is a very mild form of lipodema, usually occurs towards or after menopause. It has been suggested that a mixture of primary lymphoedema as well as lipodema can occur in some cases.

Differential Diagnosis

Lipodema

1. There is symmetrical bilateral enlargement of limbs, both in legs (with buttocks involved) or in both legs and arms, but with the obvious enlargement excluding the feet and hands, until the later stages. Enlargement is a gradual but continuous process.
2. There is no pitting with pressure. The tissue feels more like "rubber", and is not as hard and fibrotic as in a grade II lymphoedema. It does not, in the early stages, reduce with elevation.
3. There is pain on pressure, especially in the medial aspect of the thigh and the base of the spine. As the disease progresses, pain is often caused by the lightest of touches to the skin, particularly later in the day. Pain is also caused by "self pressure" e.g. crossing the legs or sitting with pressure on the spine. The abdomen may also be painful to pressure.
4. Stemmer's sign is negative; i.e. a skin fold test done on the second toe. If it comes up as a thin fold test when "pinched", no lymphoedema is present. If it is a "lump" this indicates lymphoedema.
5. Superficial capillaries are easily damaged i.e. the limb bruises easily.
6. Skin temperature is lowered. Hands may feel clammy (damp), but limbs are cold. General nourishment of the skin is also affected and may cause "patchy" skin, dry in one place, oily in others in the early stages. Skin elasticity is reduced and it usually has an "orange peel" appearance.
7. "Pins and needles" are common and movement seems to alleviate these to a large extent. A feeling of dizziness may be present. There seems to be a reduction of venous return in the legs when standing which can lead to fainting; this may be prevented by walking.
8. There is little or no loss of weight with rigorous diet. Many of these patients have eaten low calorie diets for many years. In some cases their stomachs have been stapled because of misdiagnosis. In some of these cases, this seems to have lead to the onset of stomach cancer. It is not the answer to the problem! Obesity, caused by overeating, does respond to a proper dietary regime; lipodema does not.
9. Joint pains (especially in knees) are common.
10. Infection of the limb, either bacterial or mycotic is not normally a problem.
11. Plantar support is reduced i.e. people have fallen arches.
12. The shape of lipodema may vary, from a inverted "pear" shape (like a classical Greek column) to a more bulbous shape from the ankles upward. (Figs. 1-2.) This also usually involves the buttocks.
13. Lymphoscintigraphy i.e. time of clearance of a radio-tracer injected into the feet to the inguinal nodes, is normal.

Secondary Lymphoedema Accompanying by Lipodema in the later stages.

1. Stemmer's sign becomes positive.
2. Pressure will cause pitting, and there may be a small reduction with elevation.
3. Folds of skin will further enlarge and feet will swell (Fig. 4.). If arms are affected hands also will swell. If the top of the body is affected the shoulders, thoracic and neck area may be affected as well.
4. Infection may become a problem.

Diagnosis can normally be achieved by the taking of a careful case history and clinical observation (see above). In the later stages lymphoscintigraphy may clarify this, but the picture is so different from primary lymphoedema that this should seldom be necessary.

Psychological Problems

All of these patients present with a variety of these problems ranging from lack of self-confidence to lack of confidence in their medical or health workers, often because of misdiagnosis and lack of sympathy, and then to real depression and anxiety and because of their appearance and the lack of understanding of the condition, particularly as their mobility decreases. The whole problem, of course, becomes worse if the onset of lymphoedema further exacerbates the condition.

They are "blamed" for being overweight, told they eat too much or are "cheating" on their prescribed diets. If they are hospitalised for a weight loss program when the situation becomes very serious and they don't lose weight, they are often met by the comment "I am surprised" by their health care professionals and are summarily dismissed as "patients for whom nothing can be done" or "we don't know what is wrong with you" or "you'll just have to live with it". This is not helpful to the patient who should be made aware that the condition is a genetic abnormality and that their obesity is not their fault. Of course, up to a point dieting can help but it will never cure this condition. They obviously, and for good reason, become discouraged and dismayed by their problems, which seem not even to be recognised. When lymphoedema occurs on top of the lipoedema this is a situation which is almost a problem that is so great for them (and again often undiagnosed as such) that they need to be very strong people to cope with it. Sadly, many are not able to do this. Psychological counselling can be helpful; for this poorly understood condition it is seldom offered. Invalid Pensions are not the answer for those that have, until they could not, lead an active and productive life. In many centres in Australia and I am sure worldwide, these patients are turned away from treatment centres (for lymphoedema) as untreatable cases. In some cases they resort to surgery in a final effort to improve their condition. The result of some of these operations (including liposuction and limb reduction) are so appalling that they have to be seen to be believed.

Treatment

Lipodema can be treated and reduced with careful massage to the normal nodal groups after the truncal areas have been precleared i.e. the superficial inguinal and axillary nodes, then gentle superficial drainage towards these. and compression applied to the legs in the form of bandaging as garments. Although not as easy to treat as is lymphoedema, considerable reduction, easing of pain and improvement in mobility, can be of huge physical and psychological benefit to the patient. Compression bandaging is tolerable, especially after a few days of massage. The overlying lymphoedema, if present, can be greatly reduced. The improved mobility will increase the ability to exercise which will help the calf muscles pump and increase venous and lymphatic return. After the initial decongestion by manual drainage permanent compression causes a significant reduction in adipose tissue and also has a positive influence on the disturbed veno-arterial response.

Benzo-pyrones seem to help this condition considerably, presumably by their stimulation of macrophage numbers and activity. Many patients have reported a considerable weight gain when coumarin became unavailable in Australia. Interestingly, the Italian product CellaseneÔ which is recommended for cellulite, contains benzo-pyrones and other plant extracts that work in a similar way to benzo-pyrones, so despite medical scepticism, this may help in these conditions. Unfortunately the cost of these and other available benzo-pyrones are too high for many people who would benefit from them.

The only diet which may help is a very low protein only diet (250 mg per day) (and nothing else, except, of course, water), which will put the body into a state of ketosis where some of the excess fat may be metabolised. However this usually results in weight loss in already lean areas e.g. the waist and often the upper body. Operative procedures do not attack the cause of the problem. Careful liposuction may produce immediate reduction but considering the destruction of tissue it causes, long term results have not been clinically proven. Other reduction operations are contraindicated. Pumps are normally intolerable because of the pain they cause, and there is no published evidence of them ever being successful in this condition.

Lymphoedema.

Causes of secondary lymphoedema are frequently obvious from case histories and have been discussed already. However primary lymphoedema varies from lipodema in the following aspects.

1. Swelling is a-symmetrical. Indeed, often only one limb is affected, and the swelling clinically apparent (Fig. 5.). If a leg is lymphoedematous the foot is involved. The hand is usually involved with primary lymphoedema of the arm. Lymphoedema all over may present as more symmetrical but the feet are involved from onset.

2. In the early stages pitting may be present and it may reduce with elevation.

3. It is not painful on pressure. The only time pain is experienced is during an episode of infection. If swelling is rapid in the early stages of secondary lymphoedema this is frequently painful.

4. Stemmer's sign is positive.

5. The limb does not bruise easily, as it does in lipodema.

6. Skin temperature is higher in the lymphoedematous limb/s.

7. "Pins and Needles" are rare in primary lymphoedema, (although both these and paraesthesia may occur in secondary lymphoedema). Venous return is usually normal.

8. Dieting will not reduce primary lymphoedema.

9. Knee joints may be affected by both lymphoedema and extra leg weight and may cause pain such as arthritis. The condition is often diagnosed as this and under investigation is pathologically similar.

10. Infection (both bacterial and mycotic), especially in the later grades of lymphoedema may be a considerable and ongoing problem, and cause an exacerbation of the lymphoedema.

As lymphoedema progresses from Grade I, there is excess fibrotic tissue (collagen), adipose tissue, (especially in primary lymphoedema), and a proliferation of other cellular and interstitial tissue elements. The limb ceases to pit with pressure, feels hard to the touch and much less "rubbery" than pure lipodema. As with lipodema, diagnosis can be clarified both with case histories and lymphoscintigraphy.

Psychological Problems

Lymphoedema can cause psychological problems as well as lipodema. These range again from concern and depression about appearance, to anxiety about the worsening of the condition and of infection, to depression, break-up of relationships with partners, especially if genital lymphoedema is involved etc. etc. This is balanced by the fact that many patients are now aware that some forms of treatment can be obtained, especially if they can afford it, or have Health Cover to assist them. In many areas the public patient is very poorly catered for. Despite these problems lymphoedema patients are usually less "psychologically fragile" than those with lipodema, partly due to the psychological abuse and mockery that many of the latter have suffered.

Treatment

Complex decongestive therapy (skin care, lymphatic drainage by massage, compression and exercises) are accepted as the best treatment for lymphoedema. Because of the inadequate lymphatic drainage and lack of nodes and with abnormal and fewer lymphatic vessels, drainage needs to be taken to truncal quadrants where lymphatic drainage is more normal. This of course depends on the individuals situation. What drainage that does exist in a limb should also be enhanced by massage. Pumps should never be used in primary lymphoedema. Surgery, unless in very skilled hands, is seldom beneficial in the long term.

The following figures illustrate a few of the typical differences between lipodema in its various stages (Fig. 1-3.), and primary lymphoedema of one leg (Fig. 4.). Arm illustrations are not included but for lipodema show bilateral symmetrical swelling as against a uni or bilateral a-symmetrical condition in primary lymphoedema.

New Advances In Understanding Primary Lymphoedema

DeCourcy Squire, P.T.

Lymphedema Therapy Centre, Inc U.S.A.

A child falls and develops swelling which does not go away. A teenager thinks he has a sprain–but gradually his whole leg becomes swollen and the other ankle starts to swell too. A mother notices that during each pregnancy her legs swell–but after the third pregnancy, the swelling remains, and after tests to rule out a blood clot, the swelling worsens significantly.

Primary lymphoedema–sometimes called "idiopathic" (of unknown origin)–has for many years been the least understood and most often undiagnosed or misdiagnosed form of lymphoedema. Now, exciting breakthroughs in medical research are helping us to identify and understand some of the underlying genetic causes of certain types of primary lymphoedema.

What is Primary Lymphoedema?

Primary lymphoedema differs from the more common secondary lymphoedema. Secondary lymphoedema is acquired: the cause is an injury to the lymphatic system (from cancer treatment where lymph nodes are removed or radiated; from filariasis, where parasitic worms get into the lymph vessels; from severe traumatic injuries; from longstanding venous problems, etc.)

In primary lymphoedema, the problem is one that is present from birth: an undeveloped or malformed lymphatic system.

*An estimated 1 person out of 6000 is born with primary lymphoedema.

*Swelling may be obvious at birth, but for about 75-80% of the people with primary lymphoedema, it does not develop until later. When it develops in childhood, adolescence, or early adulthood, it is termed "lymphoedema praecox." After the age of 35, it is known as "lymphoedema tarda."

*Sometimes the onset is gradual and sometimes it is sudden, triggered by a seemingly minor injury or infection.

*It can run in families ("Oh, you just have Aunt Mildred’s legs,") but more often (an estimated 80% of the time) it can appear out of the blue, with no traceable family history.

*It affects twice as many women as men

*It appears in legs four times more often than arms

*In about 70% of the cases, it affects only one leg, usually starting in the foot, ankle, and then calf. However, it can affect both legs, including the thighs, as well as the trunk, genitals, arms, and face.

A study (Casley-Smith and Casley-Smith, 1995) found that primary lymphoedema of the leg and secondary lymphoedema of the leg tended to get larger at about the same rate (which was slower than the progression of swelling of the arm). However a leg with primary lymphoedema often did not become fibrotic as quickly as a limb (arm or leg) with secondary lymphoedema. It’s possible a limb with primary lymphoedema may have more fatty tissue.

What Causes the Swelling in Primary Lymphoedema?

The lymphatic system varies a little in everyone: the number and size of lymph nodes, the number, exact location and specific direction of lymph vessels, and so on. When these variations become more extreme, a person can be at risk for lymphoedema. Some of the problems found in primary lymphoedema (whether hereditary or not) are as follows:

1. Too few initial lymphatics. The initial lymphatics are the start of the lymphatic system. They are tiny finger like projections in the dermis. They have flap-like valves that open and close to allow tissue fluid, proteins, and other large molecules, cells, germs, and debris to enter. The initial lymphatics are arranged in a mesh in the skin all over the body. They lead to a network of pre-collectors which connect the initial lymphatics to the collecting vessels (collectors).

When there are too few initial lymphatics in a particular area of the body, the tissue fluid and its components, including protein, is not able to enter the lymphatic system. It stagnates in the tissues causing a high-protein oedema.

2. Too few collectors (or too small). The collectors are in the tissue just below the skin. They travel up the limb to the lymph nodes, which are located throughout the body. When there are not enough collectors, the lymph fluid gets backed up in the pre-collectors and can reflux out the initial lymphatics and into the tissues again.

3. Too many collectors (or too large). Although it doesn’t seem as if this could be a problem, it is when the collectors become a tangled winding mass, not really leading anywhere.

The collectors are made up of units called lymphangions. At the beginning and end of each lymphangion is pair of valves which open to allow lymph fluid to pass from one lymphangion to the next and which prevents backflow of lymph fluid.

With an enlarged collector, these valves may not be able to meet and close. If the valves can’t work, then instead of lymph fluid moving to the nodes, it can also move backwards and reflux into the tissues.

4. Too few lymph nodes, or malformed nodes. The purpose of the nodes is to filter the lymph fluid, removing and destroying anything that is harmful, before the lymph fluid is returned to the blood stream. A blockage here will back fluid up through the collectors which become distended and incompetent. This eventually leads to reflux into the tissues which results in swelling.

An examination of 46 people with primary lymphoedema of the leg (Fox et al) found that 41/46 had problems in the lymph nodes located behind the knee. These were found to be hardened and malformed. This would seriously affect lymph flow from the calf and lateral ankle.

A lack of functional nodes would also affect the effectiveness of the immune system, leaving the person more prone to infections. A vicious cycle can begin. Persistent local infections of a limb can damage or destroy lymph collectors and eventually the lymph nodes. It can make the tissue in the area of the infection hard and fibrotic. This leads to less fluid being carried to the nodes and fewer nodes to filter it, thus hastening the onset of lymphoedema or worsening it.

5. A problem with abdominal lymphatics or a constriction/blockage at the thoracic duct. There are also initial lymphatics (called lacteals) and collectors in the intestinal tract and the other organs. The collectors mostly go to the largest lymph trunk in the body, the thoracic duct.         The thoracic duct passes through the diaphragm, up the body to the supraclavicular nodes. There the lymph is returned to the bloodstream through a connection with the subclavian vein.

Along the way from the abdomen, the lymph is filtered by numerous nodes. The thoracic duct carries not only the lymph from the various organs but also lymph from both legs, the lower trunk of the body, and the upper left half of the body, including left arm and left side of the head.

A problem with the abdominal lymphatics or with the thoracic duct can have much more serious consequences than lymphoedema of the limb. It can lead to conditions of chylous reflux (the backflow of lymphatic fluid from the intestines to other areas of the body) and protein-losing enteropathy (PLE). In PLE instead of plasma proteins being returned to the blood stream, they are lost in the intestinal tract and excreted. This leads to a lymphoedema of the intestinal wall and a generalized swelling of the body. It is a critical condition which requires medical intervention and a special diet.

What Are the Different Kinds of Primary Lymphoedema?

There are many different kinds of primary lymphoedema. Some are hereditary, but most are not. The list is far from complete. There are many syndromes which include lymphoedema, but they are rare syndromes. Listed below are a few of the identified syndromes.

Idiopathic Lymphoedema -Not Running in Families

This is the most common form of primary lymphoedema. As the name implies, this is primary lymphoedema of an unknown origin, and is not a part of a syndrome of other symptoms. It appears at birth or later on in an individual (more often female). Although it most commonly affects one lower extremity, it can affect any part of the body. It is not found in other family members because it is not hereditary and cannot be passed on to children. Lymphoscintigram findings will not show an obstruction as it would in acquired/secondary lymphoedema. Instead usually it will indicate a hypoplasia (underdevelopment of lymphatic vessels).   

Primary Hereditary Lymphoedemas: Lymphoedemas Which Run in Families

Milroy’s Syndrome [also called Nonne-Milroy Syndrome]: Lymphoedema present at birth. Often the problem is a lack of initial lymphatics. [Autosomal Dominant,* chromosome 5]

Meige’s Syndrome : Like Milroy’s, but the lymphoedema does not appear until later: lymphoedema praecox (before 35) or lymphoedema tarda (after 35). [Autosomal Dominant]

Primary Hereditary Lymphoedemas with other symptoms

Yellow Nail Syndrome [Samman-White Syndrome]: Syndrome which includes discoloured thickened nails, pulmonary problems,

and lymphoedema. Onset is usually childhood or early adulthood. [Autosomal Dominant]

Sharp-Aagenaes Syndrome: Distinguished by neonatal cholestasis (stoppage of bile excretion) with jaundice. The lymphoedema develops in early childhood and is equally seen in males and females. [Autosomal Recessive,* chromosome 15]

Lymphoedema with Distichiasis [Falls-Kertesz Syndrome]: As well as lymphoedema, there is an extra row of eyelashes (distichiasis); problems also include a widened spinal canal and other related problems. Onset is usually adolescence. [Autosomal Dominant, chromosome 16]

Avasthey-Roy Syndrome: As well as lymphoedema, there are arteriovenous malformations and pulmonary hypertension. Onset is usually adolescence. [Autosomal Dominant]

Hennekam’s Syndrome: Lymphoedema of face, genitals, and limbs; the face and nose are flat, the mouth narrow, the chin large, the ear malformed, the eyes protruding, the fingers can be webbed, the thumb large. There can be mild mental retardation. [Autosomal Recessive]

Noonan’s Syndrome: Includes webbed neck, protruding upper chest, receding lower chest, cardiomyopathy, short stature. Appears very similar to Turner’s Syndrome, below, except is not sex-linked.. [Autosomal dominant, chromosome 12]

Jeken’s Syndrome: Includes mental retardation, abnormal fat distribution at buttocks, and ataxia. Lymphoedema onset is during infancy. [Autosomal recessive, chromosome 16]

Figueroa Syndrome: Cleft palate; lymphoedema starts during childhood or adolescence. [Autosomal dominant]

Primary Lymphoedemas Associated with other Syndromes- Do Not Run In Families

Klippel-Trenaunay-[Weber] Syndrome: Venous and arterial alterations are present; when the lymph vessels are involved, they are frequently varicose. In Weber’s Syndrome, the bones of a limb are also hypertrophied (larger).[not hereditary]

Turner Syndrome: Affects only females because it is sex-linked.* Frequently the lymphatic system, (specifically the valves), is underdeveloped, resulting in childhood lymphoedema. This sometimes resolves by adolescence. Other features of Turner’s Syndrome include short stature, infertility, and sometimes problems with the heart, kidney, or thyroid.(XO instead of XX chromosome; not hereditary]

*Some Basic Genetics Terms:

Autosomal: a gene that is not on the sex-linked chromosome(x and y are the sex-linked chromosomes)

Dominant: only one of these genes must be present for the trait to exhibit itself

Recessive: the gene must be present from both parents for the trait to exhibit itself; a person with only one of the genes is said to be a carrier.

Incomplete penetrance: the situation when the dominant gene or two recessive genes are present, so the person should exhibit the trait, but in a certain percentage of cases, this does not happen.

What is the Treatment for Primary Lymphoedema?

Currently, the best treatment for primary lymphoedema is the same as for secondary lymphoedema. While problems such as chylous reflux and protein-losing enteropathy (see #5 above, Causes of Lymphoedema) may require surgical and other medical intervention, problems 1-4 can be effectively treated using Complex Lymphatic Therapy (also called Complete Decongestive Therapy and a number of other phrases).

CLT consists of the following components:

1. Meticulous skin care and precautions to prevent infections and further damage to the lymphatic system;

2. MLD (manual lymph drainage), a gentle massage-like manual technique to move fluid out of swollen areas into regions with working lymph nodes;

3. Gradient compression wrapping with low stretch bandages and padding, to help soften tissue and to keep fluid from refilling, after it has been moved out with MLD;

4. The Lymphoedema Association of Australia exercises, which help stimulate lymph circulation;

5. The use of benzo-pyrones, where allowable;

6. Instruction in a home program. The home program includes similar elements to CLT:

a. A continuation of skin care and precautions;

b. Self- or carer-MLD;

c. Compression around the clock, but now a compression sleeve or stocking can be worn during the day instead of the bulky compression wrapping;

d. The LAA exercises;

e. The use of benzo-pyrones, where allowed;

f. Follow-up visits with the therapist to monitor progress

The main difference from treatment for secondary lymphoedema is during MLD. If there are functional regional lymph nodes, these can be used, in addition to using MLD to move some of the excess fluid to lymph nodes in other areas of the body. When many different parts of the body are affected ("lymphoedema-all-over") the emphasis will usually be to use the normal pathways to clear the trunk extensively.

What is New in Research on Primary Lymphoedema?

In the last few years, more information about primary hereditary lymphoedema has been emerging which may have hopeful implications for the treatment of all lymphoedemas. Now advances in DNA technology have enabled researchers to make much more detailed findings than was possible before.

What the researchers do first is to register and gather data on families with lymphoedema. A family tree of as many generations and members as possible is composed, with information about whether there was no swelling, mild swelling, or marked swelling (which tends to be variable within families), age of onset of the lymphoedema (which tends to be similar within families), site of swelling, associated medical problems and physical anomalies, etc.

In the past, research has been made more complicated because the primary hereditary lymphoedemas express themselves in many different ways. Even in the same family, one member may have only one foot swollen, another may have both legs involved, and still others may not exhibit any symptoms, even though some of them carry the genes. From family to family with primary lymphoedema the causative gene may differ and the other symptoms associated with the lymphoedema may be different. [See above for a list of some of the identified syndromes of primary lymphoedema.]

Now researchers are able to use DNA to check for linkages. By comparing the DNA samples of members with and without lymphoedema, they are able to trace which chromosome is involved, and the location of the specific gene on the chromosome. Thus, researchers have been able to pinpoint the gene for Milroy’s Syndrome (primary hereditary lymphoedema, with swelling present at birth) to a specific location on Chromosome 5 and to identify the mutation that caused lymphoedema to the Vascular Endothelial Growth Factor Receptor 3 (VEGFR-3.) The chromosomes and genes for other syndromes are slowly being uncovered as well.

What this opens the way for is the possibility in the future of a genetic test for lymphoedema. This could help identify which family members are at risk for developing lymphoedema or for passing it on. This could greatly help those at risk for it take precautions before developing it, and those definitely not at risk would not have to worry about such things as overheating, air travel, and over-exertion.

In the long run, there is the exciting potential to develop drugs that would stimulate the specific receptors and growth factors responsible for the lymphatic system. This could lead to a regrowth of underdeveloped or damaged lymphatic vessels. Separate research is currently underway looking at the potential for lymphangiogenesis: the stimulating of the (re) growth of lymph vessels. Advances in these areas could be helpful not only for hereditary lymphoedema, or even just primary lymphoedema, but for all lymphoedemas. Although it is still many years away, for the first time there is the real hope in the future for a cure for lymphoedema!

Resource List:

Casley-Smith, J.R., and Casley-Smith, J.R. Modern Treatment for Lymphoedema 5^th Ed., Lymphoedema Association of Australia, 1997, pp. 46-50, 74-75, 94, 147, 148-149

Evans,, A, Brice, G, Sotirova, V, Mortimer, P, Bennison, J, Burnand, KL, Rosbotham, J, Child, A, Sarfarazi, M, "Mapping of primary congenital lymphedema to the 5q35.3 region." American Journal of Human Genetics, Vol.64, pp. 547-555, 1999.

Finegold, D. "New Developments in Genetic Research in Lymphedema", presented at the NLN Conference, Orlando, 2000.

Foldi, M., and Casley-Smith, J.R., eds. Lymphangiology, Schattauer, 1983, pp. 235-239;263-267;772;777-782

Hennekam, R. "Syndromic Lymphatic Maldevelopment", presented at the NLN Conference, Orlando, 2000.

Levinson, K, "Recent Advances in the Genetics of Lymphedema," Lymph Link, Vol. 12 #4, Oct.-Dec. 2000

Olszewski, W., Ed. Lymph Stasis: Pathophysiology, Diagnosis, and Treatment, CRC Press, 1991, pp.379-386

Papendieck, C.M., "Angiodysplasia of etheLymphatic System in Pediatrics: Classificaiton, Signs and Syndromes", Presented at NLN conference, Orlando, 2000.

Weissleder, H. and Schuchhardt, C., eds. Lymphedema: Diagnosis and Therapy 2^nd Ed., Kagerer Kommunikation, 1997 pp. 75-79, 222-234

BENZO-PYRONES

The benzo-pyrones comprise a large group of organic compounds (Vitamin P). They all work the same way in the reduction of oedema by reactivating the macrophages and increasing the number of these cells that migrate to the site and lyse protein. The different compounds in this group are metabolised through different liver pathways; some have other effects as well. Dicoumarol, for example, is used as an anticoagulant agent (and although it has been proven to reduce oedema) clearly should never be used for this.

An update was done on the availability of these in the 1999 Newsletter. Since then we are delighted that topical coumarin (i.e. applied to the skin) has become available on the Australian and Italian markets. No serious side effects have ever been reported with topical application. (In all the time it was previously available, only 2 patients reported a skin reaction to the product). The metabolism is different from the oral form. A topical product was withdrawn, not because of any contraindications, but because, as a prescription item, the government wanted more efficacy trials done and this was impossible for us to organise at the time.

In Australia it is now available without prescription as Lymphoedema cream 75 ml. and Lymphoedema powder 50 gm. from:

Poppy Lane Skin Care and Lymphoedema Clinic, Phone (02) 9723 5402 Fax: (02) 9726 3322, email okino@rivernet.com.au

The web purchase site for powder & creams is http://member.rivernet.com.au/okino/products.html

From Italy, the powder only "Linfovenodren" (Coumarin) 50gr powder is available with prescription from SMA s.a., Via Tre Settembre, 11-Dogana (Rep. San Marino); tel: 00378-909532; fax 00378-909547

The new change of email for Pharm Products who supply 'Lypedim' ä (200 mg. coumarin tablets) is ppplm@md4.vsnl.net.in and pharm@tr.dot.net.in

Bandage Winders (made of stainless steel) are available from:

Ken Retallick Engineering

Mobile Australia, 0417 218 906

redlinek@hotmail.com

NEW PRODUCTS

Garments are available in India from:

Norma D.N.D. Products, 1111, Vikas Kunj, Vikas Puri, New Delhi - 110 018 Ph 559 5287, 554 5324, 552 1239, 554 6708 Fax: 011-552 1239. email: normadnd@vsnl.com

Sutherland Medical make a full range of bandages suitable for lymphoedema at very competitive prices. They will export to New Zealand and Asia.

PO Box 1194 Huntingdale, Vic 3166. Freecall 1800 677 054, Freefax 1800 356 338, email suthmed@ocean.com.au, Http://www.suthmed.com.au

Custom made shoes are available if needed in Australia from Doug and Joan Newlyn, 23 Brenda Tce, Largs North SA 5016 ph/fax (08) 8248 4028 and from Custom Fit Australia P/L 864 Nepean Hwy., Moorabbin, Vic. 3189 ph (03) 9532 2611, fax (03) 9532 1289.

Tracey Goodrich makes a very soft sheepskin car seat belt cover that is wonderful for people with either chest and arm or abdominal problems. She originally made them for comfort during pregnancy, but they are a bonus for many people, especially the elderly and are a safety factor in preventing injury to older children under accident condition. She has offered a donation on sale to the L.A.A. if you mention this when ordering.

The names and packaging of Hamilton Laboratories (Australia) Skin care range of products have changed. Contact your local pharmacies for updated information.