The human circulatory system is made up of two interacting but closed systems:

the arterial-venous blood system and the lymphatic system. The lymphatic system is a network of vessels which carries away the lymph fluid that has "swept up" cells and cell debris such as proteins from within the tissues of the body. Thus proteins, fats, fluids,

cellular debris and other toxins as well as bacteria, and viruses are collected and eliminated from the body by a healthy lymphatic system. Unlike the circulatory system the lymphatic system relies on muscle movement to push the lymph fluid from

one lymph vessel into the next.

In this way, the role of the lymphatic system is to direct lymph fluid from distant tissues (skin, muscles, visceral organs, lung, and intestine) to the lymph nodes and then to drain that fluid into the large veins of the chest and neck. Major lymph node-bearing areas include the neck, chest, abdomen and, importantly, the axilla (underarm) and groin. When the lymphatic system is damaged, then swelling (edema) or lymphedema results from an accumulation of the protein- and particle-rich fluid within the body's tissues.

There are two types of lymphedema: primary and secondary. Primary lymphedema occurs in patients who have a congenital abnormality of their lymphatic system, and may be evident from birth. Secondary lymphedema is an acquired condition resulting from the disruption or obstruction of the normal lymphatic system due to disease, trauma, surgery and/or radiation.

Primary lymphedema

Primary lymphedema is an inherited condition due a genetic defect or congenital

abnormality, due to lymphatic damage which occurred either in utero or during birth.

Symptoms of lymphedema appear from puberty and commonly affect the legs.

Incidence

The incidence of primary lymphedema is considered neither common nor rare, although the availability of published figures for the incidence and prevalence is scanty. Prevalence estimates for this hereditary and lifelong condition are 1.15/100,000

(1 in 87,000) persons under the age of 20. Published observations suggest those with primary lymphedema (non-cancer-related disease) represent 28% of those chronic        outpatients requiring lymphedema care. The incidence of primary lymphedema is reported to be about one in every 6000 births, which equates to 26.5 new cases pa in Australia and 659 pa in the US.

(See Table 1).

a Reported incidence of primary lymphedema (hereditary and congenital) is one in every 6000 births (The National Breast and Ovarian Cancer Centre (NBOCC) review of research evidence on Secondary Lymphoedema)
b Australian population is 23m; number of new births pa: 159,100 (0.8%) year ended 31 March 2013 (Source www.abs.gov.au/ausstats/abs@.nsf/mf/3101.0)
c US population is 313.9m; number of new births pa: 3,953,590 (source www.cdc.gov/nchs/fastats/births.htm, accessed 19th Nov 2013)
d (Stats from HMRI). This is a population rate of 1.7%. Thought an underestimate, as not all cases of lymphedema are reported
e (Rockson) 2009, www.lymphnotes.com

Secondary lymphoedema

The most common cause of secondary or acquired lymphedema in developed countries is predominantly a direct consequence of surgery and radiotherapy to treat cancer. However, the extent to which lymphedema occurs as a result of recurrent infections, injuries including burns, vascular surgery, arterial disease, drug administration is significantly under-reported.

Cancer and cancer related treatments

The most common cause of secondary lymphedema in the western world is cancer and its subsequent treatment (surgery and radiation). The cancers reported as most likely to lead to lymphoedema include: breast, prostate, gynecological (vulvar, cervical and womb cancer), bladder, penile, lymphoma, melanoma and head and neck cancer.

Lymphoma can result from cancer or its treatment if:

  • Axillary lymph node removal is required to treat the cancer;

  • Malignancy or tumor is present in the lymphatic system, physically blocking lymph flow;

  • Scarring and adhesions develop during the treatment of cancer that decrease or block lymph flow lymph nodes; and/or

  • Radiation therapy over the lymph nodes which damages and scars the nodes, and so impairs lymph flow.

The relationship between lymph nodes and cancer treatment is demonstrated using breast cancer as the case study. Surgical removal of the breast (mastectomy) (breast cancer) is widely held to drive the incidence of lymphedema. Those at greatest risk of lymphedema are those women with breast cancer who have had axillary node dissection and clearance (Figure 1) at the time of their surgery, particularly with adjuvant radiation therapy. The rate of incidence of new cases is rapid in the first 3 years after cancer treatment, although lymphoedema may continue take up to 30 years to develop; consequently, the delayed onset of lymphedema in these patient groups suggests that the reported incidence is underestimated, as it is based on a clinical follow-up of only 2 to 5 years.

a)

b)

Figure 1:

 

(a) Lymphatic system of the healthy breast; (b) Axillary lymph node clearance: Once axillary nodes (a) are removed during surgical treatment for breast cancer, the lymphatic flow from the affected arm

(b) is unable to drain into the chest cavity and hence into the circulatory system. The fluid will then "back-up" all the way down to the hand causing considerable swelling, diagnosed as lymphoedema.

Other significant causes of lymphedema include:

  •  Radiotherapy: Controlled doses of radiation, used clinically to destroy cancer tissue, can also permanently damage healthy tissue such as lymph nodes or vessels, resulting in lymphedema.

  • Trauma: Secondary lymphedema also results from trauma, burns injuries, non-filariasis infection, and obesity. Trauma can destroy lymphatic structures contained in the skin, resulting in impaired lymph flow, as can occur in severe burns, in limb injuries such as a dislocated knee, or reconstructive surgery. The relative estimates of incidence and prevalence from these sources are under-reported.

  • Inflammation: Conditions that cause tissue inflammation, such as rheumatoid arthritis and eczema, may also permanently damage the lymphatic system.

  • Venous diseases: Venous and arterial disease which affect the flow of blood through blood vessels, may cause build-up of excess blood or fluid in tissues and subsequent tissue damage. This damage can affect the drainage of the lymphatic system and lead to lymphoedema. Candidate venous diseases include deep vein thrombosis (DVT) and varicose veins. Similarly, lymphedema may occur as a result of vascular surgery.