Lymphatic Obstruction (Lymphedema)

Definition/Description

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Lymphatic obstruction is a blockage of a lymph vessel that drains fluid and immune cells from tissue throughout the body[1].[2] An obstruction could cause an impaired contraction of the collecting lymphatics, causing lymphedema which is a build up of lymph fluid in the soft tissue.[3]

Lymphedema has been classified into grades of severity by the International Society of Lymphology:

  • Stage 0 (Latent lymphedema) - Lymph transport capacity is reduced, no clinical edema is present.
  • Stage1 - Reversible pitting edema with elevation; Increasing edema with increase in activity, heat, and humidity.
  • Stage 2 - Accumulation of protein-rich nonpitting edema with connective scar tissue. Irreversible ; does not resolve overnight; increasingly more difficult to pit.Clinical fibrosis is present.Skin changes present in severe stage 2.
  • Stage 3(Lymphostatic Elephantiasis) - Accumulation of protein-rich edema with significant increase in connective and in scar tissue. Severe non-pitting fibrosis edema.Strophic changes (hardening of dermal tissue, skin folds, skin papillomas, and hyperkeratosis) [3][4][1]

Types of Lymphoedema

Lymphedema can be divided into 2 categories primary/ idiopathic and secondary/ acquired. The primary cause of lymphedema happens due to a malformation of the lymph vessels. Secondary lymphedema is damage that has been done to normal healthy lymph vessels.[3]

Primary/Idiopathic Lymphoedema

Approximately 1 in 6000 people develop primary lymphoedema[5]. This form of lymphoedema isn’t inherited through family history and wouldn’t be passed onto future generations. However, people can develop primary lymphoedema in relation to other genetic and congenital abnormalities where the lymph nodes or lymph vessels don't develop properly[6]. Currently there is not a large body of evidence regarding the causes of primary lymphoedema. Future research is required to further investigate developmental causes to ensure effective treatments are provided[7].

Primary lymphoedema can be idiopathic, intrinsic or spontaneous. Idiopathic means there is no know cause, intrinsic results from an abnormal lymphatic system and spontaneous means the condition has developed on its own without any interference[7].

There are three classifications depending on the onset of symptoms[8]:
Primary lymphoedema pic.png

Secondary/Acquired Lymphoedema

Secondary lymphoedema is more common than the primary form. The lymphatic system is damaged due to an external cause compromising the function of the lymph nodes. Consequently, swelling accumulates in the affected part of the body. Causes of secondary lymphoedema include[9]:

Secondary causes pic.png
  • Malignant tumours - the presence of cancer tumours can block the flow of lymph fluid 
  • Surgery (cancer and non-cancer related) – increases the risk of disturbing the function of lymphatic pathways
  • Radiotherapy - destroys cancerous tissue but can also damage healthy lymph nodes
  • Infections – contributes to increased swelling in the affected area
  • Inflammation – contributes to excess fluid build up in the affected area
  • Obesity – increased the pressure on the lymphatic system that could ultimately damage lymph nodes
  • Disease - for example, venous, joint, diabetes
  • Trauma - lymphoedema can occur following severe trauma, for example, compound fractures

In more developed countries malignancy and the treatments associated with the condition are the main roots of cause for acquiring secondary lymphoedema[10]. Although the treatments have a number benefits, their outcomes can lead to disruption of the lymphatic system. If a patient receives radiation treatment in addition to cancer surgery, they are at a higher risk of acquiring lymphoedema.

In developing countries the most common cause of secondary lymphoedema is filiariasis, a parasitic infection with filarial worms[11]. It commonly occurs in areas of poverty where there is poor sanitation and diseased water[7]. An infected female mosquito bites the human and a parasite enters the lymph vessel causing lymph vessel paralysis. The condition occurs in approximately 120 million people worldwide[6]. The physical and psychological effects of filiariasis intensify poverty because those affected become socially isolated and unable to carry out daily activities.

Etiology/Causes

Primary Cause

  • Unknown
  • Hereditary
  • Developmental abnormalities:
    • Aplasia
    • Hypoplasia (75% of cases)
    • Hyperplasia(15% of cases)

Secondary Cause

  • Filariasis (mosquito bite- parasitic infection)
  • Primary or Metastatic Neoplasm (benign or malignant)
  • Surgery (lymph node dissection or removal)
  • Radiation treatment
  • Chemotherapy
  • Severe infection
  • Other surgeries( multiple abdominal or pelvic surgeries
  • Lipedema
  • Chronic venous insufficiency
  • Liposuction
  • Crush injury
  • Compound fracture
  • Severe Laceration
  • Degloving skin injury
  • Burns
  • Obesity
  • Multiparity
  • Paralysis
  • Prolonged systemic cortisone (cortisone skin)
  • HIV/AIDS[3]

The most common cause for secondary lymphedema worldwide is filariasis a parasitic infection caused by mosquitoes.[3] The most common reason for lymphatic obstruction is the removal or enlargement of the lymph nodes in the US.[2]

Cancer

Lymphoedema following breast cancer surgery is the highest overlooked cause of secondary lymphoedema. Harmer[12] states approximately 28% of people will acquire lymphoedema after receiving this treatment. The procedure involves removing one or more lymph nodes located under the arm, leaving fewer lymph nodes to drain all the lymph. Continually working under high pressures eventually causes the remaining lymph nodes to become damaged and lymph leaks into the lymph vessels. Consequently excess fluid builds up in the affected area[13].

Cancer Research UK[14] discusses the vicious cycle between cancer and the body’s immune system. Cancerous cells are destroyed by the immune system and treatments for cancer. However, the condition can weaken the immune system if lymph nodes are blocked by cancerous tissue and unable to function properly.

A combination of surgery and radiotherapy treatment leads to a higher risk of acquiring secondary lymphoedema. Radiation therapy aims to stop cancer from coming back by using high-radiation energy to destroy cancerous cells[15]. It either occurs before surgery to reduce the size of a tumour, or after surgery to abolish the remainder of the tumour. Lymphoedema can occur as a result of this treatment when the function of the lymphatic system has been comprised and fluid isn’t drained away[16].

Infection

Infection is a key issue commonly related to lymphoedema. It either results from swelling or causes it to develop[17]. Lymph nodes help fight infections but when they are damaged infections can develop quicker. Infection usually develops following a break in the skin, for example a cut. It is important patients receive treatment quickly to prevent the infection becoming acute and spreading within the affected area. A common antibiotic used to treat cellulitis is penicilin[18]. The Lymphoedema Support Network[19] defines cellulitis as “acute spreading inflammation of the skin and subcutaneous tissue”. It causes the skin to become warm, red, swollen and painful with onset either sudden or progressing over a few hours. If the lymph tissue is damaged there is added strain on the lymphatic system. In an infected limb, the inflammatory process attracts fluid which results in an increase in swelling. Consequently, lymphoedema is exacerbated during this period inflammation[20].

75-90% of cellulitis occurs in the lower body and is caused by bacteria entering inflamed or broken skin. Al-Niaimi and Cox[21] state that cellulitis is responsible for 3% of UK hospital admissions. This common occurrence puts financial strain on the NHS; therefore, infection prevention is a large part of lymphoedema treatment. There is a strong link between leg cellulitis and lymphoedema, where progression of the condition can lead to ulceration and septicaemia. Each cellulitis episode exacerbates secondary lymphoedema, which in turn increases the risk for a further infection episode. A Cochrane review found that a quarter of lymphoedema patients would acquire cellulitis[21]. All of which discussed above emphasises the need for effective treatment and management of lymphoedema to prevent infection and hospital admissions

Upper Limb Lymphoedema

Causes of upper limb lymphoedema include[22]:

  • Trauma or injury – removal of lymph nodes during breast cancer surgery, upper body radiotherapy, burns, and scarring
  • Cancer that has spread to the upper body compromising the function of the lymph nodes
  • Following deep vein thrombosis (DVT) or high doses of intravenous (IV) drugs
  • Reduced upper limb mobility as a result of an illness, for example, multiple sclerosis or stroke

Epidemiology

Epidemiology focuses on why diseases or conditions develop in different societies and how common the occurence is. The prevalence is the volume of people who are 'at risk' of having the condition at the same time. Finally, the incidence is the portion of new people that have acquired the condition over a specific period of time[23].

The epidemiology regarding lymphoedema isn't widely reported because it isn't always a notifiable disease[24]. However, the condition is becoming more common and the cost of healthcare required can put financial strain on the NHS. Therefore, it is important to understand the prevalence to help improve current and future healthcare and disease management[25]. This will assist healthcare professionals cope with the increase strain of this condition on future service delivery.

  • A study surveyed 308 centres (2743 people) in Spain and found that 36.8% suffered from primary lymphoedema. Of the 36.8%, 2% had acquired it at birth, 30% during adolescence and 68% were older adults[26] (see pie chart 1).
  • Approximately 90% of people with lymphoedema are affected in their lower body, 9% are affected in the upper body and the remaining 1% are affected in the genital region[27] (see pie chart 2).
    Pie chart 2b.png
    Pie chart 1.png
  • Lymphoedema occurs in approximately 240,000 people in the UK, older adults are more susceptible than the younger population[28].
  • Rockson and Rivera[29] mention that 1.15 in 100,000 people under the age of 20 will acquire primary lymphoedema.
  • Undergoing surgery as part of breast cancer treatment is one of the most frequent causes of developing secondary lymphoedema. 1 in 5 patients will develop this type of lymphoedema 6 months after receiving the surgery.[30].
  • Hampton[31] studied a population of 600,000 people over the age of 65 and concluded 1 in 200 people had chronic lymphoedema. 50% of these people had a reduced quality of life and hospital care cost the NHS £2300.
  • Ridner[32] discussed the incidence rates of cancer survivors developing lymphoedema. They reported the findings of a study focused on a population of 287 breast cancer survivors. The study concluded 6 years after receiving treatment 48% of the survivors had upper limb swelling at least once and 34% had clinical symptoms of chronic lymphoedema.
  • One third of females with damaged axillary nodes combined with radiation will develop lymphoedema[27]. This is supported by a study that assessed 744 patients who were treated for breast cancer in British Columbia. 5% of those who had axillary surgery developed lymphoedema, when radiotherapy was provided in addition to this the percentage increased to 30%[23]
  • Cellulitis is a one of the leading causes in developing lymphoedema. In 2003-2004 there were 45,522 cellulitis admissions reported by the NHS Institue for Innovation and Improvement[33], this again places a large strain and financial cost on the health service.

Prevalence

The incidence of lymphedema is unknown because it goes unreported. When looking at the primary cause 15% of lymphedema cases are reported at birth, 75% during adolescence with a ratio of 4:1 females to males, 10-20% after the age of 35, with 2 % in other syndromes. Secondary causes are just an approximation of the incidences of filariasis, an infection caused by mosquitoes, because it spans across the globe. There was an estimate of 420 million people were exposed to filariasis in Africa in the year 2000 and the WHO estimated 700,000 incidences in the Americas. There are around 3 million cases in the US with 30% of those secondary to breast cancer[3]. One study looked at 300 patients with breast cancer a year later the prevalence of clinically significant lymphedema was 33.5 % and 17.2 % had severe lymphedema. The prevalence of lymphedema was 13.4 % in patients treated with surgery only where as the prevalence was 42.4% in patients treated with surgery and radiotherapy. Post treatment lymphedema continues to be a significant problem following breast cancer therapy. Presence of co-morbid conditions and axillary radiation significantly increases the risk of lymphedema. A combination of axillary dissection and axillary radiation should be avoided whenever feasible to avoid lymphedema. [34]

Characteristics/Clinical Presentation

There are both physical and psychological effects of the chronic condition[35][36]. Early diagnosis is vital to ensure the correct treatment is chosen.

Physical Changes

  • Swelling in an arm or a leg. It may be the entire limb or only parts . Most likely unilateral, but can be bilateral
  • In the early stages pitting oedema occurs where the skin is pressed leaving an indent in the swelling. Elevating the arm creates a draining effect to reduce swelling
  • Can be fibrosis, pitting edema
  • Limbs can feel heavy and achy
  • There is altered sensation, for example, pins and needles, burning
  • Reduced mobility and range of movement of the affected limb/s
  • Pain and joint discomfort
  • Skin changes, for example redness and increased temperature
  • Nail discoloration[37]
  • Hyperkeratosis (thickening of the skin) and lymphangiectasia (dilated superficial lymph vessels)[38] 
  • Reoccurring infections in the involved limb
  • Hardening, thickening, or tightness of the skin[39][3]
  • Loss of hair
  • Loss of sleep[40]
  • Symptoms can increase during warm weather, menstruation, and if the limb has been left in its depended position.[1]
  • If primary and affecting the intestine signs and symptom include; abdominal bloating, diarrhea, and intolerance of fatty foods.[3]

When the condition affects the lower extremities, over time the affected person’s gait pattern is altered, leading to a higher risk of disability. The pictures below show how lymphodema can appear in the lower limbs. 

Lymphoedema red leg.png                Lymphoedema leg no. 2.png                  Lymphoedema leg no. 3.png

Figure 2[41]

Figure 3 [42]

Figure 4 [43]

Psychological Effects

There are psychological effects associated with the condition as a result of changes to body image.

  • Swelling and weight gain impact physical appearance that can affect one’s perception of how they look, consequently decreasing their self-confidence [44][36]
  • People commonly detach themselves from social events with family and friends leading to social isolation[45]
  • Disturbed sleeping pattern
  • Some people may feel they have a lack of support
  • Financial concerns as a consequence of treatment cost and potential job loss/change[45]
  • Some cancer survivors that have acquired secondary lymphoedema feel that it can be a constant reminder of previously having cancer[46]
  • For those that experience unilateral lymphoedema, commonly different sizes of garmets have to be worn on each side of the body and oversized clothes have to be worn because items such as jeans dont fit the limbs[46]. Psychologically this can largely impact the person because they may not feel comfortable with the way they look and therefore exclude themselves from public situations

Mason et al.[47]conducted a systematic review of literature that looked at the psychosocial aspects related to lymphoedema. It was found that people with the condition experience anger, depression, anxiety and relationship issues. People can feel embarrassed having to wear different clothes due to compression bandaging, swelling and weight gain. Ultimately, there is an overall decrease in quality of life (QoL) from reduced social and leisure activities. The study concluded more research is required that focuses on improving specific psychosocial issues rather targeting QoL to resolve issues such as anger and depression.

Another study[45] looked at the incidence, cost of treatment and complications of lymphoedema following breast cancer treatment. It concluded that 10% of the 1877 participant showed signs of lymphoedema 2 years after breast cancer treatment. A complication of the condition was the high medical costs for treatment. This lead to increased length of stay in hospital and ultimately reduced the patient’s QoL[45].

It is important for health professionals to recognise and fully understand the psychological and psychosocial implications for each individual patient to ensure person-centred care is provided. Communication and appropriate referrals to other health professionals is important in overall management of the condition, for example social workers and psychologists.

Stages of Lymphoedema

There are 4 stages which are discussed in the table below[48]. Lymphoedema is a chronic and incurable condition so treatment strategies focus on reducing disease progression through the stages. For example, management may focus of swelling reduction and infection prevention.

Stages table pic.png

The picture below shows how each of the above stages appear in the lower limb. 

Stages picture.png

Associated Co-morbidities

Risk factors for lymphedema include:

  • Removal or radiation of the lymph nodes
  • Tumors blocking the flow of lymph fluids
  • Overweight or obesity[40]
  • Diabetes
  • Infection
  • Scar tissues of lymph vessels by radiation
  • Post surgery inflammation
  • Increased Age
  • Poor nutrition
  • Cancer[49]

In addition, Presence of Lymhedema leads to significant morbidity, activity and participation restriction, reduced quality of life and economic hardship.[50]

Diagnostic Test

A thorough history must be taken. Palpation of the lymph nodes must be done to see if they are swollen or there are any abnormal changes. Measurements for the swelling limbs should also be taken.[40] In diagnosing the diagnostic tool used is the isotope lymphograph also called lymphoscintigraphy or lymphangioscintigraphy(LAS) is used to determine abnormal lymph nodes and lymphatics. Other imaging tools are MRI, MR Lymphography techniques, computed tomography (CT), Perometry, Bioimpedance analysis, Patient-Reported symptom assessments, ultrasonography(US), and DEXA,etc.[4][50]Progress can be measured by limb circumference and water displacement.[1] Clinicians must be reminded that none of the diagnostic tool is perfect in terms of accuracy.[50]

Systemic Involvement

Lymphedema can cause thickening of the dermis and can create ulcerations of the skin. Increased problems healing due to decreased oxygen supply to the tissue. The skin will stretch and cause folds in the skin. It can increase the risk of bacterial or fungal infections underneath the skin folds.
The increased swelling and weight of the limb can create problems in gait, ROM, functions, decreased sensation, balance, strength, increased fatigue and joint contracture due to inactivity.
If primary lymphedema is at birth then it could affect internal organs, including genitals and intestines.
If lymphedema is in the neck, jaw, or shoulders it could involve problems with speech, respiratory function, and swallowing.[3]

Medical Management

  • Primary lymphedema can be treated with sclerotherapy to seal a leaky lymph vessels and prevent reflux into the abdomen. Radiation therapy and surgical dissections[3]
  • Removal of abnormal lymph vessels[2]
  • Microsurgeries performed on lymph vessels to amastomose to a vein or another functional lymph vessel. It has an increased mortality and morbidity rate and are unsuccessful. [3]

Medications

There is not a specific lymphedema drug available. Different drugs such as benzopyrones ( Coumarin, Venalot, Daflon, natural ingredients such as rutin, horse chestnut, and rapeseed extract) can affect an increase in proteolysis, which can act to decrease protein concentration and decrease lymphedema. There is a chance for drug toxicity with these drugs. Diuretics that are used for sodium retention edema, are also being prescribed, even though they don’t affect lymphedema. Diuretics can cause an increase risk for electrolyte imbalance. Medications that could cause edema in the legs include NSAIDs, Norvasc for hypertension, Avandia for diabetes, and Lyrica[1] for diabetic neuropathy and shingles. Some chemotherapy medicines may cause a disturbance in behavior that could cause a lack of compliance with treatment.[3]

Physical Therapy Management

If treatment for cancer is necessary that should be completed first.[3] Practice pattern H in the Guide to Physical Therapy can help guide your interventions with lymphedema and the complications.[51] Physiotherapy can play a major role in the management of Lymphoedema, for a more indepth guide to physical therapy interventions visit here.

Interventions include:

  • Manual lymph drainage (to help improve the flow of lymph from the affected arm or leg from proximal to distal).
  • Short/low stretch Compression garment wear following lymphatic drainage.
  • Skin Hygiene and care (such as cleaning the skin of the arm or leg daily and moisten with lotion).
  • Exercise to improve cardiovascular health and help decrease swelling in some cases.
  • Patient education (instruction in proper diet to decrease fluid retention and how to avoid injury and infection, anatomy, and self bandaging).
  • Compression pumps
  • Psychological and emotional support
  • Garment fitting.[49][3][4]

Complex Decongestive Therapy:

  • Phase 1:
    • Skin care
    • Light manual massage (manual lymph drainage)
    • ROM
    • Compression (multi-layered bandage wrapping, highest level tolerated 20-60 mm Hg)
  • Phase 2:Image:Lymphedema_02_Base_175.jpg vascularweb.orgImage:Lymphdema_legs_pump.jpg infraredtherapy.com
    • Compression by low-stretch elastic stocking or sleeve
    • Skin care
    • Exercise
    • Light massage as needed

Contraindications for compression includes arterial disease, painful postphlebitic syndrome, and occult visceral neoplasia.[4]

Differential Diagnosis

Evidence

Courneya K, Mackey J, Bell G.Randomized Controlled Trial of Exercise Training in Postmenopausal Breast Cancer Survivors: Cardiopulmonary and Quality of Life Outcomes. Journal of Clinical Oncology, Vol 21, Issue 9 (May), 2003: 1660-1668. http://171.66.121.246/content/21/9/1660.full Accessed on 4/5/2011.

Badger C, Peacock J, Mortimer P. A Randomized, Controlled, Parallel-Group Clinical Trial Comparing Multilayer Bandaging Followed by Hosiery versus Hosiery Alone in the Treatment of Patients with Lymphedema of the Limb. Cancer 2000;88:2832–7.© 2000 American Cancer Society.https://www.cebp.nl/media/m1159.pdf  Accessed on 4/5/2011.
McNeely M, Magee D, Lees A, Bagnall K. The Addition of Manual Lymph Drainage to Compression Therapy For Breast Cancer Related Lymphedema: a Randomized Controlled Trial. Volume 86, Number 2, 95-106. http://resources.metapress.com/pdf-preview.axd?code=pm25575l0765836l&size=largest Accessed on 4/5/2011.

Resources

National Cancer Institute  http://www.cancer.gov/cancertopics/pdq/supportivecare/lymphedema/Patient/Page2#Section_69

Northwest Medical Center http://northwestmed.com/our-services/lymphedema-management.dot

http://www.vascularweb.org/vascularhealth/Pages/lymphedema.aspx

http://www.medicinenet.com/breast_cancer_and_lymphedema/louisville-ky_city.htm

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