Hereditary lymphedema type I associated with VEGFR3 mutation: the first de novo case and atypical presentations.

Hereditary lymphedema type I associated with VEGFR3 mutation: the first de novo case and atypical presentations.

October 2006

Ghalamkarpour A,
Morlot S,
Raas-Rothschild A,
Utkus A,
Mulliken JB,
Boon LM,
Vikkula M.

Laboratory of Human Molecular Genetics, Christian de Duve Institute of Cellular Pathology, Universite catholique de Louvain, Brussels, Belgium.

Mutations in the vascular endothelial growth factor receptor 3 gene, VEGFR3/FLT4, have been identified in a subset of families with hereditary lymphedema type I or Milroy disease (MIM 153100). Individuals carrying a VEGFR3 mutation exhibit congenital edema of the lower limbs, usually bilaterally and below the knees, sometimes associated with cellulitis, prominent veins, papillomatosis, upturned toenails, and hydrocele.

In this study, we report the first de novo VEGFR3 mutation in a patient with sporadic congenital lymphedema. We also describe three other families with a VEGFR3 mutation. In each family, one individual had an atypical clinical presentation of hereditary lymphedema type I, whereas the others had the classical VEGFR3 mutation-caused phenotype. The atypical presentations included pre-natal pleural effusion, spontaneous resorption of lymphedema and elephantiasis. Three of the four identified mutations were novel. These data show that de novo VEGFR3 mutations may be present in patients without family history of congenital lymphedema. This has implications for follow-up care, as such individuals have nearly a 50% risk for occurrence of lymphedema in their children.

Our findings also indicate that although most patients with a VEGFR3 mutation have the well-defined phenotype for hereditary lymphedema type I, there are exceptions that should be considered in genetic counseling. Because VEGFR3 mutation can cause generalized lymphatic dysfunction and can thus result in hydrops fetalis, VEGFR3 screening should be added to the investigation of cases of hydrops fetalis of an unknown etiology.

PMID: 16965327 [PubMed - in process]

* * * *

Wide clinical spectrum in a family with hereditary lymphedema type I due to a novel missense mutation in VEGFR3.

August 2006

Spiegel R,
Ghalamkarpour A,
Daniel-Spiegel E,
Vikkula M,
A Shalev S.
Genetic Institute, Ha'Emek Medical Center, Afula, 18101, Israel.
Hereditary lymphedema type I (HL-I), also known as Milroy disease, is an autosomal dominant disorder characterized by typical phenotype of infantile onset lower-limb lymphedema accompanied by variable expression of recurrent episodes of cellulites, toenail changes, and papillomatosis. Mutations in the vascular endothelial growth factor receptor 3 (VEGFR3), also known as FLT4 gene, which encodes a lymphatic endothelial-specific tyrosine kinase receptor, have been identified as a genetic cause of HL-I. We report a large Muslim Arab family residing in northern Israel with 14 individuals presenting clinical features of HL-I. Genetic analysis revealed novel missense mutation E1106K in the tyrosine kinase domain II of VEGFR3 that cosegregates with the disorder in the family. Most affected individuals presented with bilateral congenital lower-limb lymphedema. Wide intrafamilial phenotypic variability included two asymptomatic individuals, a case of prenatal hydrothorax evolving to hydrops fetalis, and a late-onset complication, yet unreported, of chronic degenerative joint disease of the knees. This report broadens the known "classic" phenotype of HL-I.

PMID: 16924388 [PubMed - as supplied by publisher]

Exercise, Lymphedema, and the Limb at Risk

Exercise, Lymphedema, and the Limb at Risk

Bonnie B. Lasinski, MA, PT, CLT-LANA

How many clinicians are at a loss for words when they are asked about what kind of exercise is "good" for individuals with lymphedema? How many individuals living with lymphedema or a limb at risk for lymphedema have asked their healthcare professional for advice concerning exercise only to receive conflicting information? It is difficult to "recruit" presenters to provide workshops/discussions on exercise for both patients and professionals alike. Exercise and lymphedema - it is a controversial subject.

Twenty-four years ago, I was asked to do a presentation on exercise after mastectomy for a one day seminar sponsored by the American Cancer Society's Long Island Division, entitled "Living With Cancer". When I contacted the coordinator of the workshop, Diana Rulon, she informed me that she was not "interested in exercise after mastectomy - she was interested in exercise for lymphedema!"

You can imagine my shock and fear at that moment. I had no special training in lymphedema management, in fact, no one did. We were just beginning to hear strange tales of a treatment from Europe that seemed ridiculously mild for the severe swellings I had seen in my limited experience. But, I figured no problem. I'll just go to the medical library, research the articles, and develop my talk from there. Well, that was 1980 and there were no articles, except for a few abstracts of German and French studies. Now, I was really in trouble. Well, long story short, I was inspired by the dedication of Diana Rulon who tried to find help for other women like herself, who had long been ignored by their doctors and told to live with their problem. Thus began my journey in lymphedema management.

Trial by fire, you might say! We presented a very basic, common sense talk on lymphedema, trying to define it in simple terms (no small feat when the literature was so poor - the definition at that time was a 2 centimeter difference between forearms - as if that was the only place one could have lymphedema!). Next, Diana presented some practical suggestions for nutrition that she had found helpful to her and several other women she knew. Finally, I wrapped up the session with some very basic information on exercise progression and then opened the floor for questions. The response was overwhelming. The participants were so grateful that their problem was finally acknowledged, even on such a basic level.

Twenty-four years later, although the medical management of lymphedema has come a long way, thanks in great part by the advocacy of Saskia Thiadens and the NLN, there is still much work to do. Basic and advanced research on the effects of exercise as a lymphedema risk reduction modality must be explored. The basic criticism of the precautions about exercise contained in the 18 Steps to Prevention of Lymphedema and other risk reduction guidelines is that they are "anecdotal" at the present time, due to the lack of controlled double-blind studies to prove their efficacy. Some medical professionals have taken the position that the individual with a limb at risk (or with lymphedema) should go ahead and pursue whatever exercise/activity they wish and "see what happens". Unfortunately, lymphedema is a chronic condition, which, presently, has no cure. While it is true that not all individuals who have had lymph node disruption (surgical or radiological) will develop lymphedema, until physicians can better predict who is at greater risk for lymphedema, a prudent approach to exercise is advisable. In the case of individuals with primary lymphedema or established secondary lymphedema, working up to a level of exercise that promotes fitness while avoiding exacerbating the lymphedema is a good goal.

I'm sure that some of you may have been told in the past that you should not exercise if you have lymphedema, or that certain types of exercise are contraindicated if you have lymphedema. This is not the case. I would like to review some basic principles of anatomy and physiology and pathophysiology of lymphedema and how these relate to exercise and lymphedema. Lymphedema occurs when there is an imbalance between lymph transport capacity and lymph load. After any surgical disruption or radiation treatment to a lymph node region, a state of latent lymphedema occurs. That is to say that the lymph transport capacity is reduced but it is still greater or equal to the lymph load. Acute/chronic lymphedema develops when that balance is shifted and lymph load exceeds the impaired lymph transport capacity. In the case of Primary Lymphedema, where there is a malformation/malfunctioning of the lymphatic transport system that results in a reduced lymphatic transport capacity, lymph load often exceeds that transport capacity, and progressive lymphedema develops over time.

Our lymphatic system, in addition to filtering out waste products, helps our bodies maintain fluid balance so that we are neither dehydrated nor edematous. 90% of the water component of our blood that perfuses the capillary network and nourishes our cells returns to the heart via the venous system. The 10% that is left behind in the tissues along with the extracellular protein that filters out of the capillaries, can only return to the heart via the lymphatics. That 10% can amount to up to 2 liters a day. While 2 liters may not seem like much, it adds up day after day, if there is impairment in lymph drainage. In addition, the extracellular proteins can only return to the central circulation via the lymphatic vessels. The diameter of these molecules is too large to fit into the openings in the vein walls - the openings in the lymphatic vessel walls are large enough for these protein molecules to enter easily.

So lymphedema is not only a problem of excess water remaining in the tissues, but of excess protein that remains in the tissues as well. Unfortunately, the body always moves for a state of balance so it actually tends to pour more water into the tissues to "dilute" this protein concentration - thus a vicious cycle develops. This problem is compounded by the fact that the white blood cells called macrophages, which are part of our immune response, do not work properly in the lymphedematous fluid. This is why anyone with lymphedema is at increased risk for infection in his or her affected limb.

What does all this have to do with exercise?

A review of the acute and chronic effects of exercise is helpful to understand how the limb at risk or a lymphedematous limb might respond to various types of exercise. The acute responses to exercise include increases in heart rate, stroke volume, cardiac output, blood flow to active muscles, systolic blood pressure, arteriovenous oxygen difference, ventilation, oxygen uptake, and a decrease in blood pH and plasma volume. Chronic adaptations to exercise include biochemical changes in skeletal muscles, decreased resting heart rate, decrease in total body fat, blood lipids, and the density and strength of bone and connective tissue. During exercise, blood is redirected to the muscles. At rest, only 21% of the cardiac output goes to the muscles, compared with as much as 88% during exhaustive exercise. As the body heats up, an increasing amount of blood is directed to the skin, to conduct heat away from the body core.1 Remember that lymph transport has to be equal to or greater than lymph load. When you exercise, your muscles need extra blood to supply the oxygen needed for your muscles to do the work of the exercise. Extra blood flow means that extra water will remain in the extracellular spaces needing transport via the lymphatic system.

The question is how much is too much? That is very individual. It is important that any exercise program be gradually progressed to avoid sprain/strain. More importantly, a slow progression allows the individual to monitor their affected limb or limb at risk for any sensation of aching or fullness that could indicate an overwhelming of the lymphatic system.

Exercise can increase the uptake of fluid by the initial lymphatics and enhance the pumping of the collecting lymphatics. In addition, exercise mobilizes the joints and strengthens the muscles of the involved limb/limbs/trunk quadrant, thus decreasing the risk of strain/sprain.2 Exercise is best done with compression on the affected limb either from compression bandages or compression garments. The bandages provide a new "tight" skin for the muscles to contract against, assisting in pumping the lymph out of the extremity into the central circulation.

When lymphedema exists, the remaining lymph vessels that are functioning are working double time to try to carry the load. These vessels become over dilated (stretched) and eventually, their walls can overstretch and fail, causing a worsening of the swelling. Wearing compression bandages/garments provides support to the skin and to the lymphatic vessels directly under the skin, called the superficial lymphatic network. It is these vessels that help to carry the load when the larger vessels have been cut away from the lymph nodes or have been damaged due to trauma or chronic venous disease, or in the case of primary lymphedema, when there are too few large lymph collectors in a region due to improper vessel/node development during fetal growth.

Of course, certain types of exercise are considered higher risk than others. For example, high speed activities like tennis, bowling and racquetball, place more stress on the upper limb while jogging, stair-climbing machines, downhill skiing, water skiing, football, soccer place more stress on the lower extremities or have higher injury risk than other activities such as swimming, brisk walking, and cycling. That is not to say that someone with lymphedema of the leg should not jog for exercise, or that the person with lymphedema of the arm and hand should not play tennis or golf. It is also important to know whether an individual was skilled at a sport/activity prior to their developing lymphedema. A sport-specific exercise program can be developed for the individual to build strength, flexibility and endurance in the muscle groups most used in that sport/activity. Ultimately, the decision to "play" should be an individual one, but an informed one.

Many men and women with lymhedema or a limb at risk want to work out with weights. A slow progression of light weights can be done safely and can allow an individual to develop good strength and power in any muscle group. The important thing to consider is whether you feel good after the exercise and how your affected limb reacts after you exercise. You must also consider your level of daily activity and modify accordingly - if you have had a particularly difficult day and your affected limb is more swollen, you may choose to do a different activity i.e. swim instead of walk, or you may realize that the best activity for that day is to rest with your limb elevated. The importance of deep abdominal breathing exercise should not be overlooked. Deep breathing enhances the pumping in the thoracic duct (the major lymphatic vessel draining the lower body and the left upper trunk/arm/hand).

A recent series of case reports published in the Journal of Surgical Oncology3 challenges the theory that vigorous upper body exercise is contraindicated for individuals who have had axillary dissection during surgery for breast cancer. The study followed a group of 24 women for 9 months. These women were recruited to participate in a training program to prepare for competition in the World Championship Dragon Boat Festival in Vancouver, British Columbia. Dragon Boat racing involves strenuous repetitive upper body exercise. 18-20 women paddle 40-60 foot boats for a distance of 500-650 meters. Circumferential measurements were collected on 20 of the 24 participants (limbs were measured at 4 places) pre training, at the start of the racing, and 7 months after the races. According to the authors, only two women, who had pre-existing mild lymphedema, had increases in their upper arms (5/8 inch) and none of the other participants developed lymphedema.

One of the authors of the study, herself a breast cancer survivor participated in the program. The authors conclude that strenuous upper body exercise may not cause lymphedema or worsen a pre-existing lymphedema.

It is important to note that the participants in this study completed a two-month training program of stretching, strengthening, and aerobic exercises prior to engaging in the actual strenuous activity of Dragon Boat racing. Many individuals who undergo breast surgery/axillary dissection/radiation are not enrolled in supervised progressive exercise programs like the participants of this study. Providing structured, individualized exercise programs should be a goal of all centers that perform cancer surgeries. While I do not discourage individuals from participating in sports and exercise, I do caution them that they should consider themselves "athletes" in the "game" of life. As such, each individual should engage in a stretching/strengthening program to prepare them for full participation in whatever activity they choose.

References:

1. Nieman, David C. Exercise Testing and Prescription: A Health Related Approach, 4th ed. Mountain View, California, Mayfield Publishing Co., 1999: P, 190-205. 2. Casley-Smith, Judith R, Casley Smith, John R. Modern Treatment for Lymphoedema, 5th ed. Adelaide, Australia, The Lymphology Association of Australia, 1997: p. 188-189. 3. Harris, Susan R, Niesen-Vertommen, Sherri. Challenging the Myth of Exercise-Induced Lymphedema Following Breast Cancer: A Series of Case Reports. Journal of Surgical Oncology 2000; 74:94-99.

Lymphedema Therapy

Lymphedema Exposition - Margate, Florida - Nov 9, 2006

Lymphedema Exposition - Margate, Florida - Nov 9, 2006

Free Community Event

THURSDAY, NOVEMBER 9, 2006

NORTHWEST MEDICAL PARK
2960 STATE ROAD 7, SUITE 104
MARGATE, FL 33063

8:30 am – 4 pm

SPEAKERS – VENDORS – RAFFLES – REFRESHMENTS

8:30 – 8:50 a.m. Exhibits

8:55 a.m. Opening Remarks

9-9:30 a.m. Stasis Dermatitis and Related Disorders of the Lower Extremities - Brad P. Glick, DO, MPH

9:35 – 10:05 Venous Ulcers - Robert J. Snyder, DPM

10:10 – 10:40 Breast Cancer and Lymphedema, Sentinel Lymph Node and Malignant Melanoma - David Porudominsky, MD

10:40 – 11 Break/Exhibits

11 – 11:30 Breast Cancer and the Environment Sandra Blank, Executive Director, Florida Breast Cancer Resource Network

11:35 – 12:05 Lebed Method – Therapeutic Exercise and Movement for Upper and Lower Extremity Lymphedema Sherry Lebed Davis, President

12:05-1:30 Lunch/Exhibits 1:30 – 2 Post Mastectomy Pain Syndrome - Andrew J. Goldberg, MD

2:05 – 2:35 “Life in the Flash Lane” – Menopause - Tara A. Solomon, MD

2:40 – 3:15 Treatment for Lymphedema and other edemas Cathy Kleinman-Barnett, MOTR/L, CLT-LANA, LMT, CLM

3:15 Closing Remarks/Raffles

3:30 – 4 Exhibits

RSVP: 954-978-4180

Make a Place for Your Illness and Put It in Its Place

Make a Place for Your Illness and Put It in Its Place

by Pauline A. Salvucci, MA, Self Care Connection

"A place for everything, and everything in its place." That may be a fine idea if you're eyeing the clutter on the living room floor, or a pile or two of old magazines and catalogues collecting dust in a corner. But what has it got to do with chronic illness? A lot.

Chronic illness is never a welcomed guest in anyone's life. However, when it becomes a visitor in yours, in many cases, it's there to stay. How you cope with your illness will determine, in great part, how well you live your life. Of the three primary factors which measure your ability to cope: your attitude, the social context of your life, and the quality of resources available to you, your attitude becomes the foundation upon which the others build. Making a place in your life for your illness may sound like a strange thing to do, but it's a crucial step in learning how to cope with illness and putting it in its place. Here are some suggestions:

Acceptance and denial are normal steps toward making a place for illness

When you begin to accept your illness, you open yourself up to see what's on your plate. Then you can begin to interact with it and make a place for it. When you deny your illness, you close yourself off to yourself, and you shut down. Feeling both acceptance and denial are normal responses to chronic illness. Being sick makes you different from healthy people. And, if your illness isn't visible, you may deny it more than if it were. Accepting illness is a process. It doesn't happen all at once. Don't be harsh on yourself when you fluctuate between accepting your illness and denying it. Acceptance isn't something you do once and for all. Acceptance lives in the present moment. Little by little as you accept your illness, you make room for it in your life.

Adapting to change takes time and patience

Like an onion, you peel off one layer of change at a time. The changes you often are faced with will stretch and challenge your ability to adapt. You may have to let go of, or even say goodbye to some parts of your life, either for a time, or perhaps permanently. Grieve this loss. Perhaps create a ritual to say goodbye, but don't deny those parts of your life which you enjoyed and which were important to you. They are a very real part of your history and deserve your respect. Your life is different than it was before you became ill, but don't treat your past and the things you enjoyed as if they never existed. As you make the changes your illness requires, you can become more flexible and creative in adapting to change. An idea that may help you is to keep a journal of the changes you've already made and how you made them. This can serve as a reminder of your accomplishments, and as a guide for making other changes. As you develop a greater degree of flexibility in adapting to change, the easier change becomes.

Befriend your illness as a part of your life

Chronic illness is your daily companion You already know how it affects your body. Now get to know what you feel and think about it, and especially how you treat it. If you consider your illness an enemy to be crushed, or an unwelcomed guest which you refuse to tolerate, or even an interloper you must annihilate, how will you allow your illness to be what it is, a part of your life which you can learn to befriend? Do you remember what Lincoln said about a house being divided against itself unable to stand? If you're divided against yourself by refusing to knowyour illness, or by waging war against it, how will you come to befriend it? Consider giving your illness a name and talking with it. Speak from your heart and your passion. Write down everything you think and feel about it. Don't keep your thoughts running around in your mind creating havoc. Then, listen to what your illness says to you in return. If you find this difficult to do, don't be discouraged. It is difficult, but there are rewards. An uneasy alliance is better than none at all.

Do you feel as if you're losing yourself?

Do you feel as if your blue moods are turning into dark depression? Is inertia increasingly becoming more a part of your life? Do you do less for yourself on the days when you could be doing more? Do you isolate yourself from your loved ones and friends? If over a period of time, you are regularly experiencing these feelings and can't shake them, don't hesitate to find professional help. Ask your doctor to refer you to a therapist whose specialty is working with people with chronic illness. These therapists can help you to make your way through difficult times. Yes, it's important to talk with your friends and family, but talking with a professional can be very freeing. They are available to help you sort out your experiences and the many feelings and thoughts you have about yourself and your illness. This isn't the time to "tough it out", or attempt to dismiss your feelings with a mind over matter mentality. Allow yourself to get whatever help you need. It can make a real difference in your life.

How often during the course of a day do you talk about your illness or refer to it?

Do you feel it's taking more of your time and energy than you would like it to? That can happen, especially when you are initially diagnosed and you're learning about your illness and trying to figure out your relationship with it. If it becomes a habit, and you feel as if you're losing perspective, here's a way to regain your balance. Create "talk space". Choose a comfortable place in a room in your home and make time to talk about your illness with your partner and your family. Let them know what you're experiencing and thinking. This is a time for honest sharing, for you and for your loved ones. Allow this "talk space" to be the place and time where you discuss your illness. Keep the rest of your home an "illness free talk zone". This will allow you and your family to enjoy one another's company and conversation without reverting to the topic of illness.

Seeing with new eyes doesn't mean looking through rose colored glasses

When it comes to putting your illness in its place, you might try seeing with new eyes. When it takes you more time to do just about everything, when simple tasks frustrate you because they're not so simple to do anymore, when the familiar becomes foreign, when you can not do the many things you once loved doing, maybe seeing with new eyes can help. If you were an artist and can no longer paint, you can still go to museums or art galleries. If you can't do that, you can enjoy art on the Internet since it offers you access to the world's best museums, galleries and art exhibits. If you worked with your hands and can no longer use tools to do a job or hobby, teach someone else to do what you know how to do so well. Share your knowledge and lend your expertise. If you loved nature and the outdoors, but can no longer hike, drive along some of the scenic roadways and enjoy the beauty and majesty of nature. Find a way to keep what you have been passionate about in your life. It takes time, work, patience, spirit and heart to make a place for illness in your life. Seeing with new eyes is both a tribute to courage and the ability to put illness in its place.

Recommended Books:

Self-Care Now! 30 Tips to Help You Take Care of Yourself When Chronic Illness Turns Your Life Upside Down by Pauline Salvucci

Self-Care Now! 30 Ways to Overcome Obstacles That Prevent You From Taking Care of Yourself by Pauline Salvucci

Self-Care Now! 30 Tips to Help You Take Care of Yourself & Minimize Caregiver Burnout by Pauline Salvucci

9th State of Georgia Lymphedema Education & Awareness Day

9th State of Georgia Lymphedema Education & Awareness Day

MARK YOUR CALENDERS!

Our conferences here in Georiga are absolutely fantastic and there is no charge. The only expenses you might have would be the lunch and/or lodging if you come from out of town.

Last year we had Dr. Kathleen Francis updating us on research. She was great...totally cool person too!!!! Here's the scoop on this years conference: 9th State Of Georgia Lymphedema Education & Awareness Day

Sponsored by

Lighthouse Lymphedema Network

Luncheon & Program

Saturday, October 28, 2006 9:00 a.m. - 3:00 p.m. at the Renaissance Waverly Hotel 2450 Galleria Parkway, NW - Atlanta, GA

Speaker: David N. Finegold, M.D.

Some topics to be discussed:

· The genetics of primary lymphedema
· Post-mastectomy secondary lymphedema
· The future of lymphatic research

Our sincere thanks to the following businesses for their financial support of this educational seminar.

Please stop by the tables and see the services and products provided by our supporters for the treatment of lymphedema and related conditions.

· A Woman's Place - Northside Hospital
· BSN-Jobst
· CircAid Medical Products
· Compass Healthcare, Inc.
· Compression Design
· Drapers Fitness & Rehab Consulting
· Gwinnett Medical Center
· Juzo · Medi, USA
· Peninsula Medical (The Reid Sleeve People)
· Sigvaris, Inc.
· Solaris, Inc. (Tribute/Swell Spots)

Be there or be square

Treatment of Pediatric Lymphedema

The Treatment of Pediatric Lymphedema

by Steve

Any discussion of pediatric lymphedema must include information about our most current scientific understanding of the underlying causes. Pediatric lymphedema may be uncomplicated in its presentation, akin to a benign adult primary lymphedema, or may indeed be very medically complex. One must assume in any pediatric form of lymphedema that there is either a defect in the normal development of lymphatic tissue, or that the visible swelling may be one of the first signs and symptoms of malignant disease. For this reason no condition involving edema should be casually viewed or dismissed by the medical professional and immediate clarification as to the presence or absence of cancer must be investigated.

Classification

The two main classifications of lymphedema are primary and secondary and are labeled as such according to the cause of the lymphatic impairment. Primary lymphedema can be described as an inherent defect within the lymphatic tissue itself. This malformation may involve either the absence of tissue or a malformation of tissue, (usually lymph vessels) which results in the presence of abnormally high levels of proteins and tissue fluids within the tissue spaces (interstitium). Secondary lymphedema is always associated with a traumatic event or series of events. Causes include multiple infections of the skin or soft tissues, surgical removal of lymph nodes, as in cancer treatment, radiation therapy, acute thrombo-phlebitis (DVT) or other traumas. Again the consequence is similar (lymphedema) and results in a disturbance of normal lymphatic drainage.

Following astute investigation and differential diagnosis, benign primary lymphedema (not associated with cancer) occurring in an infant at birth or within the first year of life is classified as Type 1 Nonne-Milroy Syndrome ( Milroy's Disease). This ''congenital hereditary'' (present at birth, sometimes inherited) form of lymphedema is described as usually involving the lower extremities but sometimes the arms, hands and face and may also be associated with malformations of the intestinal lymphatics (hyperplasia or other dysplasia). The additional intestinal involvement may result in poor absorption of proteins into the blood stream. This is due to congestion created by large fatty molecules that also rely upon lymphatic vessels for absorption. Symptoms may include bloating of the abdomen (ascites), low blood albumin levels (hypo-proteinemia), high protein levels in the stool (protein losing enteropathy) and in advanced cases, a malnourished appearance. Some Milroy's patients may require special dietary guidelines involving less complex fatty acids, which are often times successful in alleviating the congested intestinal lymphatic system.

Additional classifications of primary lymphedema occurring in children include Type 2 Meige Syndrome. This non-congenital familial (not present at birth, sometimes inherited) form is associated with the changes of puberty and mainly occurs in females. As in Milroy's disease this form is associated with lower extremity lymphedema, is chronic and progressive if left untreated, but does not involve intestinal lymphatic malformations. Both Type 1 and Type 2 primary lymphedema can further be classified as lymphedema praecox, which is an umbrella label used to describe any primary lymphedema occurring before the age of 35. Of the two types, type 1 (Milroy's Disease) accounts for 6-7% of all lymphedema praecox cases. (1)

Differentiation

Other diseases associated with pediatric lymphedema, which are beyond the scope of this article include Klipple Trenaunay Weber Syndrome (KTWS, otherwise termed Angio-Osteohypertrophy Syndrome), Noonan's Syndrome, Turner's Syndrome, Amniotic Band Syndrome (3 chromosomal disorders) and others. Of the aforementioned syndromes, KTWS is not uncommonly encountered in a busy lymphedema clinic and is a serious medical disorder involving overgrowth of veins, arteries, bones and lymphatic tissues. Practicing lymphedema therapists and diagnosing physicians must be able to identify this condition and make treatment adjustments to accommodate the complications of this disease. It is recommended that those pediatric patients with KTWS and associated lymphedema seek expert physician supervision, preferably from a vascular surgeon with additional training in lymphology.

Diagnosis

As previously mentioned, pediatric lymphedema may be ''pure'' (uncomplicated) or complicated by other associated disorders of the vascular system or may involve physical obstruction, as in the case of malignancy. For this reason it is imperative to seek expert physician assessment in all cases. The correct diagnosis is nearly always gained clinically however, and relies in large part upon skilled observation, palpation and historical analysis. One safe and minimally invasive imaging procedure currently used to diagnose primary lymphedema is called Lymphangioscintigraphy (LAS). This procedure involves subcutaneous (within the dermis) injections of radioisotope tracers, which are photographed at set intervals to show the amount and speed of uptake and transport within the individuals' lymphatic system. However, when primary lymphedema is accurately diagnosed clinically, LAS may be omitted, as it will not change the course of treatment. Clearly, LAS is of great academic value and more importantly, may contribute to supporting the accuracy of the clinical diagnosis. Many times, as in the case of pediatric lymphedema, a clear image of the insufficient lymphatic drainage may put to rest parental concerns that lymphedema is not the only disease process at work.

Other testing procedures such venography and lymphography, which involve injections of dye are both painful and potentially damaging to vessel structures and have also been associated with deadly allergic reactions (anaphylaxis). In more complicated cases involving combination forms of lymphedema, Magnetic Resonance Imaging (MRI), Computer Tomography (CT scan) and Venous Doppler studies may be required to assist in designing a successful treatment plan. In uncomplicated cases, they are not necessary and only incur additional expense.

Treatment

At present there is no cure for lymphedema. It is unfortunate that surgical interventions are still sometimes undertaken as a form as treatment for all types of lymphedema. Although many brilliant and well-intentioned surgeons have attempted a myriad of ingenious techniques, it remains a fact that no reliable benefits have come from these procedures. More often surgery results in significant additional cosmetic disfigurement or lymphatic impairment. The most common type of surgery can be categorized as a ''debulking procedure.'' It is not logical to believe that the removal of substantial amounts of subcutaneous tissue, containing functional lymphatic vessels, will result in an improvement of the overall condition. Surgery is therefore not indicated for extremity lymphedema.

Another common treatment for lymphedema is the pneumatic compression pump. Although pumps provide some relief and may temporarily halt the advancement of swelling, the benefits are nearly always temporary and may result in abnormally large accumulations of lymph at the root of the limbs and within the trunk. Significant numbers of patients with lower extremity lymphedema who have been treated by pumps report genital lymphedema following daily use (2). This consequence is nearly always avoided by comprehensive treatment with Complete Decongestive Therapy (CDT).

Complete Decongestive Therapy (CDT)

When the condition is present during infancy parents can benefit their child greatly by implementing a course of conservative treatment as early as possible. By initiating a sensible treatment strategy early on, it is hoped that the chronic and progressive consequences of the disease can be significantly lessened. The treatment method universally accepted as the gold standard of care for lymphedema is called Complete Decongestive Therapy (3). This program of treatment relies upon four interdependent components and is successful in halting the progression of the swelling, the chronic inflammatory changes within the skin (lymphostatic fibrosis) and promotes healthier immune response in the affected areas (4).

Additionally, CDT liberates the patient from encumbrances such as pneumatic compression pumps or limb elevation, and requires healthful activity levels and proactive patient involvement. The four components of CDT are: Manual Lymph Drainage (MLD), compression bandaging, remedial exercise and infection prevention (meticulous skin and nail care). Self-care training involving any of these components with the goal of optimizing the clinical treatment results in homecare should be seen as an important additional component.

CDT Guidelines for Pediatric Patients It has been the authors' experience that typical approaches to treatment must be significantly modified for the pediatric patient, especially in the case of infantile lymphedema. The following suggestions are the result of clinical experiences gathered through treatments involving dozens of children.

All parents of children with lymphedema must be educated about the condition so that a realistic picture of this chronic condition can be gained. No surgical cure or pharmaceutical medication is available. It is unfortunate that lymphedema is presently an incurable condition, however, with early competent guidance the secondary tissue changes associated with lymphedema can be greatly reduced. Overall limb size can be maintained at nearly normal girth and immune function can be enhanced with ongoing Manual Lymph Drainage treatments. These benefits cannot be underestimated, because the long-term impact is quite positive and rewarding. Normal limb function and socialization can be expected in most cases. Children with lymphedema can live very normal lives.

Be patient with the process

Overly aggressive care is never productive for the adult or child with lymphedema. Especially in pediatric cases where all tissues are delicate, great care must be taken to avoid creating injury or discomfort. One must remember that a comfortable and happy patient will be a compliant patient. This special child must not be mishandled. Parents can be ''consumed with worry'' and approach compression bandaging overzealously, with the mistaken impression that ''more pressure is better''. It is more likely however to produce discomfort, pain or skin infections which can actually cause a worsening in the condition. Pediatric patients cannot tell us what is bothering them early on, and without this feedback the caregiver must adopt a relaxed and careful approach to compression therapy.

Similarly, the Manual Lymph Drainage (MLD) treatments delivered by the parent may be counterproductive if they are heavy handed or rough. Lymphatic vessels are delicate, threadlike structures, which may spasm or become otherwise injured by inappropriate treatment. In the clinic, parents must invest time into learning the appropriate skills. This investment cannot be underestimated in its importance and also allows for question and answer sessions between parent and therapist. The better educated the parent the more likely they will be to provide high quality care for their child.

Depending upon the age of the child, most will initially need to adjust to this ''strange new routine'' as well as to the intervening therapist. Time must be budgeted for this necessary process to take place and may require ''play sessions'' at first to create a feeling of comfort and safety. Suggestions include setting up a television and video player in the treatment room as a distraction; bring favorite toys, music and foods. Place a soft clean quilt on the floor and attempt treatment and bandaging from this vantage point. Allow the parent to hold the child on his/ her lap while the therapist works. All the while verbal education can take place between therapist and patient, which is usually of great value. At first this format may seem unproductive and can be a source of further anxiety for the parent, however, should this step be omitted, the young child will not comply with any of the components of the program and will ultimately create an even less productive outcome. This approach may also allow for a more ''semi-intensive'' approach, in that the total treatment duration is reduced to 2 weeks versus 4+ weeks as in the case of an adult. Treatments can therefore be budgeted for future use involving frequent follow up visits where parent, patient and therapist can review home care techniques and remain current concerning the overall condition of the child.

Start with MLD and self-care suggestions

For the very young child of less than one year of age, therapists may be quite productive in administering MLD. This ''massage like'' treatment involving gentle, soothing skin manipulation is usually well received by the infant. Parents can observe and repeat the agreed upon treatment sequences at home and may find that the best time to administer treatment is during nap times or at night while the child is sound asleep. Older children of age 18 months to 3 years who are considerably more active and less agreeable to this routine may also benefit from similar timing. The quality of touch required for proper MLD treatment is so gentle that children will become positively conditioned, and in time will view it as another form of loving touch from the parent and therapist. They will also be able to develop skills for their self- care and can be engaged in practice as they mature.

The goals of MLD are to create more efficient drainage within the affected area and systemically offset the chronic skin changes associated with lymphedema. In children the early intervention of MLD is extremely valuable in slowing or reversing these effects especially on the dorsum of the hand and fingers and similarly on the dorsum of the foot and toes. In some cases the genital area is also chronically involved, MLD application is essential and may again, offset chronic skin changes.

Compression Therapy Considerations

As previously mentioned, pediatric tissues are far more delicate than those found in an adult. Compression therapy can be counterproductive if it is not administered with great care and skill. This becomes an additional burden to parents and must only be undertaken by responsible and cautious caregivers.

It has been the authors experience that some patients are simply too young to intervene with compression therapy. However, the skilled therapist may provide a modified bandage in the clinic to gain a clearer picture of the potential for improvement. This bandage may not be practical for parental application until a later date. A very young infant (1-4 months old) will benefit from the stimulation of MLD alone and, as the child begins to stand, gravity becomes an exacerbating factor, necessitating external support in the form of compression bandaging and/ or medically correct compression garments. The only situation where intensive compression bandaging would be provided before this time is in the case of massive swelling (elephantiasis), a situation rarely encountered in infants.

Once the child begins to stand, lymphedema of the legs and feet may begin to worsen. This is the point in time where some compression strategies should be explored and employed. Therapist and parent must consider the benefits and tradeoffs carefully however, as bulky, multi-layered bandaging may impact the child's ability to safely ''toddle''. Bending the knees to crawl is made more difficult, and in the case of arm lymphedema, tactile skills and simple grasping tasks may be largely compromised. For these reasons and including the child's tolerance level, an intensive phase of 2 weeks (10+ treatments) is usually adequate to deliver quality care, and homecare education to astute parents. Within this time frame the therapists goals should include: Achieving a fair amount of reduction (without force), learning the unique compression gradient for optimal long-term improvement, effectively educating one or more caregivers in basic tailored MLD techniques, applying compression bandages safely, and measuring for any necessary compression garments.

Special Compression Guidelines

Most bandaging materials are sized for the adult frame and are too large for most young children and especially the infant patient. Select 4cm compressions bandaging materials such as DemaBand® in these cases and graduate to 6cm Comprilan/Rosidal®, or at the maximum, 8cm materials for most children. Another special product that is kind to pediatric skin is Velfoam®. This fleece-lined foam padding material is quite kind to delicate tissues and should be incorporated or substituted for other forms of padding. Artiflex®, and Cellona® synthetic cotton padding products can also be used in combination with foam but should not be exclusively applied otherwise shifting will occur. Toes are usually too tiny to affectively wrap. A tourniquet effect is more likely on small circumferences and great caution should be used if an attempt is made. It is the authors' opinion that gentles MLD and manual manipulation can affectively treat toes. Fingers may be wrapped with traditional materials such as Transelast® or Elastomull® of an appropriate width. Take care to double the bandage into two-ply as it will concentrate the bandage on a smaller skin area

.Compression garments are usually fitted to age appropriate patients (12+ months). The benefit of these elastic sleeves is that they provide medically correct gradient pressure. By wearing a sleeve and glove or leg stocking daily, pediatric patients will experience liberation from cumbersome bandages. Normal developmental milestones can be reached without delay such as coordinated walking. Furthermore, since bandaging is practiced at night, parents can rest assured that less than expert-bandaging technique can be corrected by daytime gradient compression.

Activity and Lifestyle

Due to the chronic and lifelong nature of lymphedema, parents are encouraged to permit their child to engage in normal activities such as sports, arts and crafts, and outdoor play. With lymphedema comes an increased risk of acute infection (cellulites) especially when the skin is injured. However, to disallow normal play may have significant and more troubling side effects that may be mental or emotional in nature. Furthermore, many lymphedema patients have no history of infection following numerous traumas and are therefore capable of normal activity. If infections are an occurrence, some activities should be modified accordingly but with an awareness of these larger concerns. Lymphedema in the majority of cases is not a disabling condition, however children who have been raised to feel as though they have a disability are truly at a disadvantage and may not experience the joy and freedom of childhood that is their birthright.

See Also:

Children with Lymphedema - Yahoo Support Group

Children's and Pediatric Lymphedema

National Lymphedema Network - Parents' Lymphedema Action Network

Putting the Squeeze on Lymphedema

Putting the Squeeze on Lymphedema

Nursing Made Incredibly Easy!March/April 2006 Volume 4 Number 2Pages26 - 342006 Lippincott Williams & Wilkins, Inc. Volume 4(2), March/April2006, p 26-34

HOLCOMB, SUSAN SIMMONS ARNP, BC, PhD

Nurse Practitioner, Olathe Health System, Inc., Olathe,Kan.Consultant, Continuing Nursing Education, Kansas City, KansasCommunity College, Kansas City, Kan.

The author has disclosed that she has no significantrelationships with or financial interest in any commercial companiesthat pertain to this educational activity.

Abstract

When a portion of the lymphatic circulation develops abnormally orisinjured by trauma, surgery, or radiation therapy, fluid balance isthrown off kilter and the patient can experience severe swelling inanextremity. In this article, we'll help you learn about the differenttypes and stages of lymphedema and the treatment options for thisdifficult condition. We'll also offer you advice on preventionstrategies and patient teaching.

MOST OF US are familiar with lymphedema following breast cancertherapy, especially when axillary dissection and axillary radiationtherapy are used. Slightly more than a quarter of patients whoreceive treatment for breast cancer are affected by lymphedema, andit can cause substantial functional and psychological impairment.

Of course, cancer treatment isn't the only cause of lymphedema. Inthis article, I'll help you understand the types of lymphedema, itscauses, possible complications, and preventive and treatmentstrategies.

Let's start off with the causes and a description of the varioustypes of lymphedema.

A blockage in the flow

Lymphedema is the result of excess proteins, fluid, inflammation, and fibrosis in the lymphatic system. It's divided into two types: primary and secondary, based on the underlying cause.

Primary lymphedema affects anywhere from 1 to 2 million individuals in the United States. It's twice as common in women as in men, and it affects the lower extremities three times more often than the upper extremities. It's bilateral in two-thirds of cases. Primary lymphedema isn't a progressive disease.

Congenital lymphedema

Congenital lymphedema is typically characterized by absence or abnormality of the lymphatic tissue; it's clinically evident at birth. Milroy disease, a kind of congenital lymphedema, accounts for about 2% of all primary lymphedema cases.

Lymphedema praecox , which expresses itself between birth and 35 years of age, is the most common type of inherited primary lymphedema, accounting for 65% to 80% of all cases of primary lymphedema.
Lymphedema tarda , also known as Meige disease, has a late onset; it usually doesn't appear until after age 35. It's the rarest form of primary lymphedema.lymphedema praecox , and lymphedema tarda are forms of primary disease distinguished by the age of onset.

Secondary lymphedema , the kind most of us are familiar with, is an acquired condition. It's usually caused by an obstruction or trauma to the lymphatic system that interferes with lymphatic flow. In the United States, it's most commonly caused by injury to or removal of regional lymph nodes during surgery or radiation therapy, infection, or tumor growth. Secondary lymphedema affects between 2 and 3 million individuals in the United States. Worldwide, the most common cause of secondary lymphedema is filariasis, an infestation of the lymph nodes by the parasite Wuchereria bancrofti ; it's this organism that gives rise to elephantiasis.

No Way Out

The lymphatic system is made up of lymph vessels, tissue, and organs. Lymphocytes, a specialized type of white blood cell, circulate throughout the lymphatic system to help the body fight off disease and infection. Lymph vessels collect a fluid that's made up of protein, water, fats, and wastes from the cells of the body and then carry the fluid to the lymph nodes. Lymph nodes filter out potentially harmful waste and foreign materials. Lymph vessel walls are thinner than those of venous and arterial blood vessels, allowing larger proteins to permeate the vessel walls.

If excessive amounts of protein and fluid overload the lymphatic system, they begin to accumulate in the interstitial spaces. Lymphedema is distinct from other forms of edema in that material trapped in the interstitial spaces has a higher concentration of protein.

The protein and fluid in the interstitial spaces prompt an inflammatory response. Fibroblasts migrate to the area and deposit collagen. This changes the initial pitting edema into the brawny (orange), nonpitting edema characteristic of lymphedema. Pitting refers to the indentation that persists when a finger is pressed into an edematous area. See It's the pits for the International Society of Lymphology's staging system.

We'll look next at the clinical presentation of secondary lymphedema.

Secondary Lymphedema - keep it up

Secondary lymphedema can occur acutely, or it may have a more insidious, gradual onset. Four patterns of acute lymphedema are recognized:

Mild acute lymphedema lasts for only a few days. It usually occurs following surgery to remove a lymph node or after an injury to lymphatic vessels that occurs during surgery. This form of acute lymphedema may be recognized by a warm, erythematous, and nonpainful limb associated with the lymphatic chain near the area.Treatment includes elevating the affected extremity and contracting the muscles of the extremity to enhance blood flow and, consequently, lymphatic flow back to the heart.

The second type of acute lymphedema occurs 6 to 8 weeks after surgery or radiation to the affected area. It's noted by a warm to hot, erythematous, very tender limb.To treat it, the affected limb is elevated and anti-inflammatory medications are given to reduce inflammation of the lymphatic vessels and/or veins.

The third type of acute lymphedema affects the superficial lymphatic vessels and nodes following an insect bite or other minor injury in the area. The affected area's signs and symptoms are very similar to the second type of acute lymphedema in that the area is painful, warm to hot, and erythematous. Edema may also be apparent. The affected limb is elevated, and because the risk of infection is increased, antibiotic prophylaxis is given.

*** Editor's note - clinical studies actually indicate that secondary lymphedema may lie latent for years until it is "triggered" by an event that overwhelms the lymph system. ***

The fourth and most common type of acute lymphedema develops 18 to 24 months following cancer surgery, although in some cases, it may take years to develop. Pain is the hallmark symptom of the fourth type of acute lymphedema. It's typically felt in the neck, shoulders, back, and hips.This type of acute lymphedema is more complicated to treat because the painful affected areas tend not to be in an extremity, making elevation tricky. Pain medications and/or anti-inflammatory agents may help.Acute lymphedema generally resolves within 6 months. Factors that could cause acute lymphedema to become chronic include a surgical drain leaking protein into the surgical site, inflammation, paralysis of the affected limb, loss of lymphatic function in the area, and/or blockage of a vein by a blood clot or inflammation.In chronic lymphedema, the lymphatic flow can't meet the demands made on it. Many of the problems that cause acute lymphedema also contribute to chronic lymphedema. Unlike acute lymphedema, however, chronic lymphedema isn't reversible. Treatment is palliative, not curative. Pain, heat, edema, and erythema are also characteristic of chronic lymphedema. Elevation of the affected extremity doesn't help edema in chronic lymphedema, and the skin eventually becomes hardened or fibrotic.

Let's move on next to diagnosis and treatment of secondary lymphedema.

Nailing the diagnosis

Unlike patients with arterial or venous disease, most patients with lymphedema don't report symptoms other than those related to the weight and size of the limb. Oozing fluids may cause pruritus.

Your patient assessment must include a history and physical exam. Make sure you ask about past surgery, postoperative complications, radiation treatment, and how long it was between the time of surgery or radiation and the onset of lymphedema. You should assess the quality and behavior of the edema: Does it change with position? Has it progressed over time? Find out if there's a history of trauma or infection, and be sure you get the whole scoop on current medications.

No specific tests are used to diagnose lymphedema. Diagnosis is generally made on clinical presentation and history. Edema usually isn't detectable clinically until the interstitial volume is about 30% above normal.

Occasionally, imaging studies may be helpful to assess lymphatic flow or to identify tumors. The most commonly used noninvasive techniques are lymphoscintigraphy, computed tomography scans, and Doppler ultrasonography. In lymphoscintigraphy, a water-based radionuclide is injected into the lymphatic tissues, allowing the dynamics of the flow to be traced, any reversal of flow to be identified, and the severity of the obstruction to be determined.

If there are any lingering doubts over a diagnosis of lymphedema, a chemical evaluation of the protein content of the edema fluid should put them to rest. A tissue fluid analysis with a protein content between 1 and 5.5 g/dl usually indicates lymphedema; 0.1 to 0.9 g/dl is more indicative of venous or cardiac edema.

Better sooner than later

The main focus of treatment for secondary lymphedema lies in prevention. Lifestyle plays an important role, and patients should be encouraged to consume a healthy diet, maintain a normal body weight, and participate in regular exercise. Patients with lymphedema need to take particular care not to do anything that could lead to infection. Even a minor scratch to the skin near the area may become infected. The National Lymphedema Network, a nonprofit organization, offers an excellent guideline for risk reduction. See also Educating patients about lymphedema for more information.

The good news is that tissue loss or ulceration related to lymphatic obstruction with subsequent lymphedema is unusual. Tissue loss occurs because of a concurrent secondary pathology. As already noted, patients with lymphatic obstruction are prone to infections in the affected extremity caused by bacteria or, more commonly, fungus. As part of your assessment, you should examine intertriginous folds for ulcers and areas of infection. Explain to your patients that this is important to do at home too. It may be helpful to show them how to use a mirror to visually examine those hard-to-see nooks and crannies.

To be effective, lymphedema treatment must improve lymph flow and drainage. The best outcomes are obtained when therapy begins before irreversible sclerotic changes occur in the interstitium. Strict adherence to therapy is essential and lifelong.

Let's take a closer look at the types of lymphedema treatments.

Complete decongestive therapy (CDT) has four stages

Manual lymph drainage (MLD) is a gentle manual treatment administered by a trained therapist. MLD reroutes lymph flow around the blocked area into more centrally situated, healthy lymph vessels. From there, the flow can drain into the venous system. Special massage techniques help to break down fibrotic tissue to restore flow.

With compression bandaging , slightly elastic cotton bandages are wrapped around the affected extremity to increase tissue pressure, helping to push the excess fluid and protein out of the area. Compression bandaging also helps keep more fluid and protein from flowing in and breaks down areas of scarring and fibrosis. Note that compression-bandage therapy for lymphedema requires the application of more pressure than compression-bandage therapy for venous disease: about 30 to 40 mm Hg for venous disease versus about 50 to 60 mm Hg for lymphedema.

Remedial exercises are performed with compression bandages or compression garments in place. Breathing exercises help to increase the volume of lymph fluid carried through the thoracic duct (the body's largest lymph vessel).

Remedial exercises increase lymph vessel activity and improve lymph circulation.
Meticulous skin and nail care reduces bacterial and fungal growth, which decreases the risk of infection.

Contraindications for CDT and MLD include acute infection, cardiac edema, malignant disease, and pulmonary edema from chronic obstructive pulmonary disease.

*** Editor's note - new studies indicate that infact complete decongestive therapy does NOT cause cancer to spread and that it may be totally safe for cancer patients to continue this treatment. More research is being done to confirm this. ***

Get out and stay out

Once the excess protein and fluid are reduced and the extremity is at its smallest possible size, the goal is to keep the edema from coming back. Many patients find that daily wrapping and unwrapping of bandages is awkward and time-consuming, so carefully explain to them why the bandaging is necessary. Various commercially available binding garments can be helpful alternatives to bandaging. One note of caution, however: Whether a bandage or garment is used, it must be applied correctly; improper application can compress nerves or blood vessels, which can cause complications.

Arterial disease is a contraindication for the use of compression bandages or garments. Caution should also be used in patients with hypertension, paralysis, diabetes, asthma, and heart failure.

Specialized lymphatic drainage pumps, called gradient pneumatic lymphedema pumps or intermittent pneumatic compression pumps, are also available. The extremity or part of the extremity, such as the foot, is wrapped, and the pump applies gradient pressure with more pressure on the distal end than on the proximal end. The pump also provides sequential pressure, a technique like milking that pushes the fluid from the distal end of the extremity toward the trunk and central body cavity.

*** Editor's note - compression pumps have clinically been proven safe and effective for arm lymphedema. For lower limb lymphedema (leg lymphedema) there remains too great of a risk of genital lymphedema and damage to the cutaneous lymphatics to be a recommended treatment. See also: Why Compression Pumps Cause Complications with Lymphedema *** .

Water pills don't work

There's not much available in the way of effective medical therapy for lymphedema. Diuretics have little or no value. They draw off the excess water in the interstitial spaces, but not the excess protein. As soon as the diuretic is stopped, the concentrated proteins pull more water back into the affected area.

The dietary supplement coumarin, a benzopyrone, isn't approved in the United States and may produce serious adverse effects, in particular, liver toxicity. Selenium therapy for secondary lymphedema of the arm caused by breast cancer surgery is currently under investigation in a clinical trial. The theory behind the selenium trial is that the damage to the lymphatic system is linked to excessive generation of oxygen radicals; the researchers hypothesize that selenium, an antioxidant that gobbles up oxygen radicals, might decrease the damage to the lymph system.

Also under investigation in a clinical trial is the use of hyperbaric (high-pressure) oxygen therapy for the treatment of secondary lymphedema caused by breast cancer treatment. According to the National Institutes of Health ), the researchers think that hyperbaric oxygen may stimulate the growth of new lymphatic channels as well as lead to a reduction in scar tissues surrounding existing lymphatic channels in the armpit.

***Editor's note: see Complications of Lymphedema Debulking Surgeries***

Occasionally, surgery is used as a palliative treatment to relieve pressure and edema. It's usually considered the treatment of last resort to relieve otherwise intractable pain.

Complications associated with lymphedema are, in general, associated with an infection in the affected limb. If the pelvic lymphatic system is affected, problems of elimination may occur.

A rare and lethal complication is lymphangiosarcoma, cancer of the lymphatic vessels; it can develop after the patient has had chronic lymphedema for 10 years or more. The incidence is estimated to be 0.45% in patients who survive at least 5 years after radical mastectomy; a lower incidence of 0.07% is seen in patients after simple mastectomy. Death from lymphangiosarcoma generally occurs within 18 months, with the 5-year survival rate at around 10%.

Physical findings of lymphangiosarcoma are bluish-red or purplish bumps on the affected extremity that resemble slightly raised ecchymosis. The tumors are very aggressive and characteristically metastasize early to multiple sites, most often to the lungs. Treatment may involve amputation of the affected extremity or wide local excision of the lesions. Lymphangiosarcoma that arises following mastectomy is called Stewart-Treves syndrome.

Let's finish up with a discussion of some ways to keep your patient with lymphedema from getting worse or running into complications.

At home

Stress to all patients with lymphedema the importance of reporting any signs and symptoms of infection in the affected extremity to the primary care provider.

Patients should also be given nutritional guidance to help them maintain adequate protein balance to help fight off infection. In general, the diet should provide 30 to 35 calories/kg/day, including 1.25 to 2 g protein/kg/day. Most patients can benefit from taking a daily multivitamin with minerals.

Lymphedema is disfiguring, sometimes painful, disabling, and often leads to big changes in a patient's lifestyle. These factors can all lead to depression. Support groups, counseling, and antidepressant medications may be useful for treating emotional disorders associated with a diagnosis of lymphedema (see Thanks for your support ).

Keep in mind that early recognition and appropriate treatment can help minimize progression and complications of lymphedema. It's your responsibility to help patients recognize lymphedema, avail themselves of appropriate interventions, and help them maintain a good quality of life.

It's the pits

The International Society of Lymphology has set the following staging system:

* Stage 0 -Subclinical condition where swelling isn't evident despite impaired lymph transport. It may exist for months or years before edema occurs.

* Stage I - Pitting may occur and is reversible. It may take up to a few hours of rest and elevation to reverse.

* Stage II -Pitting occurs, and the edema isn't appreciably reduced with elevation of the affected limb. In late Stage II, the tissue hardens and becomes fibrotic, and pitting no longer occurs.

* Stage III -This stage is also referred to as elephantiasis. Pitting is absent. Skin changes like acanthosis, fat deposits, and warty overgrowths may develop. Fluid may ooze from the skin due to high pressure in the lymphatic and venous vessels. It most commonly occurs in the legs and results from long-standing, inadequately treated or untreated lymphedema.

Did you know

The following conditions can mimic signs and symptoms of lymphedema:* allergic disorders* heart failure * hepatic cirrhosis* hereditary angioedema* hypoproteinemia* idiopathic cyclic edema* kidney failure* lipidemia* postphlebitic syndrome* total body excess of free water* venous disease.

Educating patients about Lymphedema

General measures* Elevate the affected arm or leg above your heart as much as possible.* Avoid having blood drawn or injections given in the affected arm, and avoid injections into the hip on the side of the affected leg.* Don't have your blood pressure measured on the affected arm.* If your legs are affected, don't sit for more than 30 minutes before getting up for a break. Also, don't cross your legs when sitting.* Avoid tight clothing and jewelry.* Don't hold or wear a purse on the affected arm.* Don't use ice packs or heating pads on the arm or leg that has lymphedema.* Don't use the affected limb to test the temperature of water. Feelings of touch, temperature, and pain may be reduced in the affected leg or arm.* Follow the diet and exercise plan developed by your health care team.* Keep your medical appointments.Prevent infection* Keep the affected arm or leg clean and dry; apply moisturizer often.* Use gloves and wear shoes when gardening.* Cut nails straight across, and don't cut your cuticles. Do not bite your nails or fingers. See a podiatrist or primary care provider if a nail infection or an ingrown nail occurs.* Use an electric razor for shaving.* Use an antibacterial ointment on cuts and scrapes.* Use gauze, not tape bandages, to cover cuts or scrapes.Prevent inflammation* Avoid injury to the affected arm or leg.* Avoid physical exercise or activities that might lead to cuts or bruises.* Always wear socks and shoes, especially outdoors.* Use extreme care and use protective devices on hands when using needles, knives, scissors, or other sharp objects if you have an affected arm.* Avoid getting sunburned; use sunscreen with an SPF of 30 or greater.When to call your primary care provider* You have signs and symptoms of infection like redness, pain, heat, swelling, and fever.* You notice a rash.* Your affected limb suddenly gets larger.

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