Presented by: Stanley Rockson, MD
Director, Center for Lymphatic and Venous Disorders
Stanford University Medical Center
April 24, 2014
The lymph system acts like an access road to the highway for blood flow. It carries fluid from every region of the body, collecting bacteria, viruses, and waste products, and carrying them through a system of segmented valves to the lymph nodes, where it is then filtered back into the blood. The lymph system acts as a sort of one-way street, picking up this fluid and returning it back to the heart. About 1 percent of the volume of fluid in the blood makes its way back to the heart through the lymph system.
“The lymph nodes are like the factory of the immune system,” said Stanley Rockson, MD, a professor of cardiovascular medicine and a noted expert on lymphatic disease, at a presentation sponsored by the Stanford Hospital Health Library. “They are a point of contact between the circulatory system and the immune system.”
The lymph system plays a central role in a number of disease mechanisms and their treatment, including inflammation, autoimmune disorders, heart disease, and obesity. It is involved in circulating HDL cholesterol (the “good” cholesterol), and a better understanding of its mechanisms may provide the mechanism to improve a major risk factor in heart disease. Cancer cells use the lymph system to metastasize and induce the growth of blood vessels that help them grow and spread.
A System Gone Awry
The immune system protects the body from diseases, infection, and other outside threats through any point of contact—mostly the skin, lungs, or gastrointestinal system. When it senses an invader, it activates the immune system to create a defense response. In the presence of lymphedema, this response mechanism becomes inefficient.
Lymphedema begins with an accumulation of tissue fluids in and just under the skin, most often in the arms or legs. The fluid drains slowly: As the fluid builds up, the swelling increases. Over time, the swelling can become painful and restrict movement. Lymphedema has no cure and is difficult to control.
Primary lymphedema involves a genetic predisposition to develop the disease, triggered at certain stages of life. Secondary lymphedema is caused when some external factor injures the lymph system, such as a trauma or infection. Many cancer patients—particularly women with breast cancer—develop lymphedema as a consequence of their treatment. Surgery (the removal of lymph nodes for staging) and radiation, or can cause a strain on the lymphatic system and a build-up of fluid.
It is estimated that 6-10 million people in the United States have lymphedema, yet the condition is poorly understood and often misdiagnosed. Dr. Rockson cited a study that found less than one hour was spent on teaching about lymphedema in more than half of the four-year medical curriculums in the U.S. About 25 percent of medical schools spent a total of less than 15 minutes on the disease. At the Stanford Center for Lymphatic and Venous Disorders, Dr. Rockson said he sees about 300 new patients every year.
An infectious variant of lymphedema affects 90 million people in underdeveloped countries in Africa and Asia, as well as in Haiti and Brazil. A primary lymphedema called lymphedema distichiasis that engorges the lower legs is characterized by the presence of double rows of eyelashes. An overgrowth of lymph vessels in the head and neck, called lymphangioma, affects mostly young children; lymphangioma can often be surgically removed but can recur.
Diagnosis and Treatment
Over time, the body can respond with complex physiological changes. The skin thickens like the rind of grapefruit, and the increased limb volume evolves into scarring and cellular overgrowth that will no longer respond to treatment.
“The limb becomes an immobile structure, with layers of fat, that no amount of massage can reduce. The muscles atrophy,” Dr. Rockson said. “The consequences are reduced physical ability, reduced productivity, and social isolation.”
One of the first steps in diagnosis and treatment is to identify the people most at risk to try to limit undue stress on the lymphatic system. A bioimpedance test uses a low-frequency current that moves quickly through water and slowly through tissue: The more fluid, the faster the current passes. The reading can determine a build-up before any edema is clinically detectable; it is used to screen individuals at high risk.
A physical maneuver at the bedside is used to determine if the edema is pitting, indicating the presence of excess tissue fluid. . Lymphoscintigraphy is an imaging technology that uses contrast material to objectively detect lymphatic malfunction.
“Our emphasis is on early intervention and reducing risk to minimize the swelling,” said Dr. Rockson. “It’s difficult to treat, but if we can limit the edema accumulation, we can slow the progression. Caught early, it may be more manageable, or even reversible.”
Therapy is designed to reduce swelling, restore function, and prevent the development of infection. Because lymphatic fluid is rich in bacteria, the immune system is compromised, which can lead to soft-tissue infection.
The first-line treatment for lymphedema is called Complex Decongestive Physiotherapy (CDPT), an integrated protocol of physical therapy, professional massage, multilayer bandaging, and exercise. Treatments by trained specialists are required over the long term, but studies report a 50 percent average reduction in excess limb size. Pneumatic compression devices should never be used as a substitute for CDPT but are sometimes useful in conjunction with physiotherapy.
Dr. Rockson conducts a number of studies to identify new and better targets for treating lymphedema. Genetic insights have already led to identifying some of the molecular pathways that lead to heredity lymphedema, and gene therapy in animal models for a form of congenital lymphedema, called Milroy’s Disease, has been shown reverse lymphedema. Other animal studies have identified disease pathways that point to targets for blood testing to detect early disease and stratify risk.
He also is working on complex algorithms to evaluate patients and determine which tests are relevant for their diagnosis. And Stanford will be the site of clinical trials in 2015 that will assess the benefits of applying gene therapy or bioengineering modifications at the time of surgery for autologous lymph node transfer.
Collaborative research is key, Dr. Rockson said, and he encourages patients to take part in the national lymphatic registry and tissue bank, to help investigations progress further. Stanford is a major partner in this collaboration with the Lymphatic Education and Research Network and the Feinstein Institute.
“These studies are all designed to improve our understanding of how the body orchestrates the development and repair of the lymphatic system,” he said. “Our mouse models are showing promising results that we hope to develop into human clinical trials in the near future.”
About the Speaker
Stanley Rockson, MD, is the Allan and Tina Neill Professor of Lymphatic Research and Medicine, director of the Stanford Center for Lymphatic and Venous Disorders, and professor of cardiovascular medicine. A renowned specialist in lymphatic and venous disorders, he cares for adult and pediatric patients and conducts basic research to develop insights in lymphatic health and disease that may lead to improved treatments. Dr. Rockson received his MD from Duke and did his residency at Brigham and Women’s Hospital in Boston and his fellowship at Massachusetts General Hospital in Boston. He is Board Certified in Internal Medicine and in Cardiovascular Medicine.
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