Forms of lymphedema
Lymphedema is swelling of a limb, less commonly the trunk, neck, or head, caused by the accumulation of lymph between the tissues. The disease can be congenital (primary) or acquired (secondary). Despite the different forms, the symptoms and treatment are the same.
The lymphatic system and its function
In your body, the blood (which is largely made up of water) is “rotated”, circulated by three systems.
- Heart and arteries. The heart is the most important engine of the (cardiovascular) sytem. The contraction of the heart pumps blood into the arteries. It flows through the ever-smaller diameter arteries then enters the capillaries and into the space between the cells (intercellular space).
- Veins. Its capillaries “collect” the blood in the intercellular space and bring it back towards the heart. The flow of blood in the veins is driven upwards by the contractions of the muscles.
- The veins do not collect all interstitial fluids (or tissue fluids), that is, what the arteries bring from the intercellular space, without residue. The “remainder” is the lymph, which contains proteins, water, fats, and “waste” produced by the cells. This is what lymphatic vessels (lymph collecting vessels) collect. It flows through the lymph nodes, which filter out waste and foreign matter (e.g., pathogens). The lymph that has passed through several groups of lymph nodes, eventually returns to the bloodstream.
Lymphedema is a circulatory problem in which part of the lymph is not collected, leaving it in the interstitial space and causing swelling.
Primary (congenital) lymphedema
Primary lymphedema results from developmental abnormalities leading to pathological lymphatics. It can affect the lymphatic vessels and their function, the lymph nodes, or even the entire lymphatic system.
The abnormalities can be, for example, the underdevelopment of the lymphatic system (hypoplasia) or, on the contrary, overgrowth (hyperplasia).
Hypoplasia is the most common disorder in which the number of the lymphatic vessels and / or lymph nodes are lower, or their sizes are smaller than normal.
In case of hyperplasia due to dilation of the lymphatic vessels (lymphangiectasia, dilatation) and / or increase in the size of the lymph nodes, the “ventils” in the lymphatic vessels – also known as valves- malfunction. These would be responsible for directing the lymphatic fluid towards the heart.
Imagine it as a flood-gate that you lower or raise if necessary. If the flood-gate “gets stuck”, the water flow cannot be controlled.
In the case of underdevelopment of the lymphatics (Lymphatic aplasia), less lymph can flow through the lymphatic vessels and / or lymph nodes, meaning that the transport capacity is too “low”.
Primary lymphedema is significantly less common than its secondary form. According to a publication (1), roughly one in every six thousand people have congenital lymphedema. Three times more women are affected than men. There is no explanation as to why primary lymphedema is more common in women.
The role of inheritance
Primary lymphedema is an autosomal dominant inherited disease in the development of which several genes may be involved (2). Consequently, congenital lymphedema can be passed onto offspring – fortunately, not all children will necessarily “get it”.
To put it simply, we get one half of our somatic genes from our mother and the other half from our father. If at least one gene from one of them carries the disease, then we can be sick, too. It may be that although both of our parents are lymphatic patients (have lymphedema), but we inherit the healthy gene from both of them, i.e., that do not carry the disease, so we won’t be sick.
In genetics, the strength of genes is characterized by penetrance; strong penetrance refers to the development of the disease in each and every offspring who has inherited an abnormal gene. If, despite the fact that the offspring inherits the defective gene, but the disease develops in only a subset of cases, the penetrance is inconsistent or varying.
This is also characteristic of the lymphedema gene; i.e., despite having the gene, symptoms of lymphedema do not appear in all cases. The disease can “skip” one or more generations.
The varying appearance results in the edema affecting the left leg in one family member, the right leg in the other, and both in a third.
When does primary lymphedema occur?
In some cases, and especially in boys, developmental disorders of the lymphatic system can be detected even at birth. In contrast, in girls, the onset of symptoms usually occurs only later, during puberty or pregnancy, in most cases between the ages of 10 and 25 years.
It is generally true that the symptoms of primary lymphedema do not appear as long as the lymphatic system functions efficiently enough to perform its function.
The diagnosis of lymphatic disease is “is announced” when the swelling appears. In primary lymphatic disease, the lower extremities are affected in the vast majority of the cases.
Secondary (acquired) lymphedema
The cause of secondary lymphedema is a lesion “acquired” in life. In general, the event leading to damage to the lymphatic system is well identifiable. This causes a sudden or gradual malfunction or obstruction in the lymphatic vessels and / or lymph nodes.
It usually affects the limbs, but may also appear in extreme forms, on the trunk, abdomen, head and neck, and external genitalia.
Occurrence: two worlds
With regard to secondary lymphedema, the world can be divided into two parts. We could also say that it can be divided into poor and rich countries.
In poor areas, the lack of clean drinking water is the main cause of the disease. In Africa, India, Southeast Asia and South America, as well as in the Pacific Islands and the Caribbean, the most common cause of lymphedema is a filamentous worm, Wuchereria bancrofti. The worm enters the body with the contaminated drinking water and then its larvae travel in the lymphatic vessels and destroy them. This worm infection is called filariasis. According to the WHO, 1.3 billion people are at risk of the disease and more than 120 million people are still infected, 40 million of whom have severe lymphedema.
Worm-induced lymphedema is virtually non-existent in developed countries, where clean drinking water is widely available.
In rich countries, the most common causes of secondary lymphedema are accidental injury (trauma), surgery, or radiation for therapeutic purposes.
It is a very common companion to breast cancer surgery and radiation therapy. Breast cancer is one of the most common malignancies, with hundreds of thousands of new cases identified each year. That is, potentially this many new lymphedema patients “develop”.
Main causes of acquired lymphedema
No swelling develops as long as the (tissue) fluids brought by the arteries are collected by the joint action of the venous and lymphatic systems. In a healthy person, there is a balance between the amounts transported in and out.
Lymphatic injury and the destruction of the lymphatic vessels can be caused by several things.
It can also occur in the event of an accident, injury or bone fracture. Lymphatic injuries or cutting of the lymphatic vessels can also occur during curative surgeries. It is very common a few years after varicose vein removal surgeries. Liposuction for cosmetic purposes can also have late consequences.
With luck, the ruptured lymphatic vessels – being damaged in the course of an injury or surgery -, “fuse together”. Many times, however, the developing scar constricts, narrows the vessel and so the lymph cannot flow. The phenomenon is a bit similar to when you break a garden watering hose – so water can’t flow.
A “side effect” associated with therapy
During tumour removal surgeries, it is common to remove the regional lymph nodes and lymphatic vessels in addition to the diseased tissues. Thereafter, radiotherapy treatment is also given to the affected area. The radioactive rays cause inflammation of the treated lymph nodes and lymphatic vessels. It heals slowly and with scarring, thus lymphedema may develop even years after treatment.
The “normal” side effect of breast cancer treatment is the development of lymphedema. Obviously, only the treatment of the tumor can lead to saving the patient’s life. However, in my experience, a significant proportion of the patients are not informed of the expected consequences and therefore are not prepared for what to do about it.
How long does it take for lymphedema to develop?
If the lymphatic vessels or lymph nodes become occluded or are completely absent, then it is obvious that no lymph is removed from the affected area either.
In mild and lucky cases, lymphatic vessels remain in the area, which dilate and take over the extra load. When the lymph nodes, and the lymphatic vessels of a region are removed, then there is no “route” left for the lymph to leave. It accumulates in the tissues, causing swelling in the lower and upper limbs, but it may also affect other parts of the body.
Secondary lymphedema may develop immediately after surgery and/or radiation, however, the average time of appearance of this complication is between 14 and 24 months after surgery. Sometimes, it can take a few, or even 20 years after surgery / injury to develop. This is explained by the fact that other lymphatic vessels can take over the functions of the affected lymphatic vessel(s). With advancing age, other factors, for example, body weight gain, further surgeries, radiation, injury, infection, etc. may occur. However, further damages caused by these can no longer be compensated.
Nevertheless, in many cases, despite the accident, surgery or irradiation, the symptoms do not appear, but the risk of lymphedema onset lasts for a lifetime.