Lymphedema

Key takeaways:
~ Lymphedema is caused by interstitial fluid building up under your skin, often in the legs or arms.
~ Impairments to the lymphatic vessels prevent the fluid from being moved out of the tissue.
~ Genetic variants can increase the risk of lymphedema — and can point you towards natural solutions that may be more likely to work for you.

Members will see their genotype report below, plus additional solutions in the Lifehacks section. Consider joining today. 

What is lymphedema?

Lymphedema is the build-up of lymph fluid under your skin. For example, if one leg is swollen. Lymphedema affects about 3 million people in the US and 200 million worldwide. [ref]

Lymphedema can be mild – minor swelling, minor discomfort. Or it can cause a lot of swelling and pain.

The buildup of interstitial fluid is due to impaired lymphatic vasculature. Lymph moves through lymph vessels, and lymphedema occurs when the lymphatic system isn’t able to move fluid out of areas that are downstream of the disrupted or impaired areas.

Types of Lymphedema:

Primary lymphedema is caused by rare genetic mutations. It can start in infancy (Milroy’s disease), in the teen to young adult years (called Meige’s disease), or in middle age or beyond (lymphedema tarda).

Secondary lymphedema is the disruption of lymph drainage. It is most often caused by trauma or cancer treatment that damages a lymph node. Venous insufficiency or kidney disease can also be a cause of secondary lymphedema. In certain areas of the world, exposure to a nematode parasite can cause lymphedema. This is the most common type of lymphedema.

Quick note – not all edema (fluid) is lymphedema. There can also be swelling and fluid buildup from problems with your veins.

What is going on in lymphedema?

Before we get into the details, let’s take a quick tour through the lymphatic system.

The lymphatic system moves a fluid called lymph throughout the body. Similar to the circulatory system for blood, the lymphatic system moves fluid from tissues back into central circulation.

Lymph fluid originates in interstitial fluid – the fluid between cells. The lymph fluid is similar to blood plasma. It moves into small lymph capilaries and then into larger vessels and through the lymph nodes.

In the lymph nodes, lymphocytes (a type of white blood cell) filter out any foreign particles — viruses, bacteria, cancer cells.

Another job that the lymphatic system does it to transport fats absorbed in the digestive system.[ref]

Circling back to lymph forming from interstitial fluid… This fluid comes from the circulatory system. At the end of capillaries that bring in blood from the heart is an area where the lymph fluid is formed. Most of the blood in this area is going to return to the heart in the venous capilaries, but about 10% of the fluid is going to enter the lymphatic system.

 

There is no pump for the lymphatic system, like the heart pumps blood in the circulatory system. In the lymphatic system, the flow is slow and due to peristalsis, various lymph valves, and movement of adjacent muscles.

If excess pressure develops within the lymph system, fluid can leak back into the interstitial space. This causes the buildup seen in lymphedema. 

When the fluid accumulates, it can impact cell behavior within that specific tissue. One thing that can happen is that immune cells can be activated in the area or fibrosis can occur. [ref]

Secondary Lymphedema: Diving Deeper

Secondary lymphedema is the most common type of lymphedema. It is caused by disruption or obstruction in the lymph vessels, resulting in interstitial fluid build up.

For example, arm and chest lymphedema are a common problem for women who have had breast cancer treatment that damages the lymphatic vessels. A recent study on breast cancer survivors with lymphedema found that inflammatory biomarkers were elevated for several months after surgery.

Interestingly, women with lymphedema after cancer treatement were more likely to have had higher baseline (pre-surgery) levels of inflammatory biomarkers such as IL1A and IL6. Additionally, higher pre-surgery VEGF levels were also linked to an increased susceptibility to secondary lymphedema.[ref]

Another common cause of lymphedema is infiltration of the lymphatic vessels by a parasite called Wuchereria bancrofti. This is mainly a problem in tropical developing countries or for people who have traveled to those areas.

So… what initiates the lymphedema?

Leukotrienes: Inflammatory mediators driving lymphedema

Leukotreines are inflammatory mediators derived from lipids. For example immune system cells, such as neutrophils, macrophages, and mast cells, can for leukotriens from arachidonic acid (omega-6 fat).

LTB4 (leukotreine B4) is a leukotriene that is involved in lymphedema. LTB4 is produced in response to inflammatory cytokines, and it increases the ability of leukocytes (white blood cells) to cross through the endothelium (cells lining blood vessels and lymph vessels).

Animal studies show that LTB4 plays a central role in secondary lymphedema. Leukotrienes are produced in response to inflammation, thus making tissue inflammation central to the development of lymphedema.[ref]

Leukotriene B4 (LTB4) is an inflammatory lipid mediator which is synthesized from arachidonic acid using the enzyme 5-LO (ALOX5 gene, below in the genotype section). The final step in the production of LTB4 involves the LTAH4 enzyme (also below).

Once synthesized, LTB4 can increase vascular permeability. This is important during an active infection in order for immune system cells to respond to the site of the inflammation. However, vascular permeability after the infection needs to be halted.

LTB4 binds mainly to the BLT1 receptor. Neutrophils (a type of white blood cell) react by increasing the inflammatory response.

The increased inflammatory response initiated by leukotriene B4 interacts with lymphedema in a couple of ways.

FOXC2 (in the genotype report) is important for maintaining the integrity of the lymphatic system, especially in the areas around the lymphatic valves that keep lymph flowing in the right direction. FOXC2 also interacts with activated T cells in inflammation.[ref]

Increased fluid accumulation along with the leukotriene B4 molecule activates more of an inflammatory response to the area. It builds on itself. As the lymphedema persists for a longer time, the pro-inflammatory cytokines can cause fibrosis – thickening or scarring – in the area.[ref]

Genetics and Lymphedema:

Lymphedema due to physically damaged lymph vessels can happen to anyone, especially after surgery or cancer treatment.[ref] However, some people are more susceptible to secondary lymphedema than others. The genetic variants listed below in the genotype report are linked to leukotriene B4 formation, inflammatory cytokines, and the development of the lymphatic system.

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Lifehacks: Natural solutions for lymphedema

Talk with your doctor about your options for lymphedema. Common treatments include compression garments and manual lymph drainage.

Research shows that the accumulated fluid in lymphadema exacerbates the problems and causes more immune cells to infiltrate the tissue. Early intervention may be key, so don’t put off talking to your doctor about your options.[ref]

Physical therapy plus manual lymphatic drainage therapy:

Clinical trials show that both physical therapy and manual lymphatic drainage are important in reducing lymphedema in cancer patients.[ref]

Aquatic Training:

A study found that moderate intensity aquatic training exercise (water bikes, aqua-jogging, trampoline) for 6 weeks significantly decreased limb circumference and decreased lymphatic fluid.

The rest of this article is for Genetic Lifehacks members only. Consider joining today to see the rest of this article.

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