Introduction

Definition of lymphoedema

Skin and tissues swell and change as a result of the body accumulating more lymphatic fluid due to a chronic condition called lymphoedema. The lymphatic system is unable to transport the protein-rich fluid that gradually builds up in the interstitium and fibro-adipose tissue. Distal swelling in the extremities, such as the arms, hands, legs, and feet; proximal swelling in the breast, chest, shoulder, pelvis, groin, genitals, and face/intraoral tissues; limited joint range of motion due to swelling and tissue alterations; skin discolouration; pain and altered sensation; limb heaviness; and trouble dressing are all indications of lymphoedema.¹

Distinction between primary and secondary lymphoedema

There are two types of lymphoedema, i.e., primary and secondary lymphoedema. These are:

• Primary lymphoedema: Primary lymphoedema is a congenital or inherited condition that causes a malformation of the lymphatic system and is usually caused by a genetic mutation. Primary lymphoedema comes in three varieties:
  • Congenital lymphoedema, which appears at birth or within two years of birth
  • Lymphoedema praecox, which appears during puberty or the beginning of the third decade 
  • Lymphoedema tarda, which appears after the age of 35
• Secondary lymphoedema: Irritation, damage, or blockage of the lymphatic system can result in secondary lymphoedema. Although filariasis from Wuchereria bancrofti infection is the most common cause of lymphoedema worldwide, the majority of secondary lymphoedema cases in developed countries are caused by cancer or are related to cancer treatment. This includes medical treatment, local radiation therapy, and surgical excision of lymph nodes¹

Scope and aim of the article

The fundamental causes of secondary lymphoedema after cancer treatment are examined in this article. It emphasises how damage to the lymphatic system from surgery or radiation causes tissue changes, inflammation, and fluid accumulation. The aim is to highlight the clinical significance of pathophysiology in improving patient outcomes, diagnosis, and treatment.

Overview of the lymphatic system

Normal structure and function of lymphatic vessels and nodes

Immune function and the removal of surplus extracellular fluid depend on the lymphatic system, also referred to as the lymphoid system, a component of the circulatory system. Different lymphoid organs, lymph, lymphatic vessels and plexuses, lymph nodes, and lymphatic cells comprise the lymphatic system.

Transporting excess protein molecules and interstitial fluid into the venous circulation while preserving volume balance is the primary function of the lymphatic system. The lymphatic system is essential for immune surveillance because it shields the body from infections and foreign objects. Leukocytes and antigens are transported to lymph nodes, from which antigen-primed and targeted lymphocytes and other immune cells are transported into the lymphatic and blood vessels.²

Key components affected in secondary lymphoedema

The clinical condition known as lymphoedema is caused by lymphatic fluid stasis, which is caused by damage to lymphatic vessels and can be explained by three mechanisms: The main source of inflammation is CD4+ T cells, which also influence the VEGF-C/VEGFR axis and lead to abnormal lymphangiogenesis; adipocyte hypertrophy and adipose tissue deposition are regulated by the interaction between CCAAT/enhancer-binding protein α and peroxisome proliferator-activated receptor-γ; and tissue fibrosis is caused by Th2 cell overactivity, which releases profibrotic cytokines such as IL-4, IL-13, and the growth factor TGF-β1.³

Aetiology of secondary lymphoedema

Common causes of post-cancer treatment

Cancer and cancer treatments that disrupt the flow of lymphatic fluid can cause lymphoedema, also known as secondary lymphoedema. Lymphoedema may develop years after the end of cancer treatment or soon after. It usually develops gradually over several months or years. Lymph fluid may accumulate and result in lymphoedema if cancer or cancer treatment impairs lymph fluid flow or damages lymph nodes and vessels.⁴

Radiotherapy

The lymphatic system may suffer irreversible damage and lose its capacity to drain fluid if radiotherapy is required to kill cancerous cells in it. Your lymphatic system may suffer irreversible damage and lose its capacity to drain fluid if radiotherapy is required to kill cancerous cells in it.⁵

Infections

Lymphoedema can occasionally be brought on by an infection, such as cellulitis. The tissue surrounding the lymphatic system may sustain scarring from severe cellulitis.

Lymphoedema is another symptom of filariasis. Microscopic, thread-like worms are the parasitic cause of lymphatic filariasis. The adult worms obstruct lymph drainage and only reside in the human lymphatic system. Though not usually a risk in the UK, it is a common cause of lymphoedema worldwide.⁵

Obesity

Another potential cause of secondary lymphoedema is obesity. Obese people are more likely to develop swollen body parts, especially those who are extremely obese. It has been suggested that the excess adipose tissue somehow obstructs the lymphatic channels, reducing the amount of fluid that flows through them, though the exact cause of this is unknown. In these cases, losing weight is an essential part of treatment, and even a modest weight reduction can have a big impact on swelling.⁵

Diagnosis and assessment

Clinical signs and patient history

The first stage of the diagnosis process is a thorough medical history, with special attention to any treatments related to cancer, such as radiotherapy or lymph node dissection. Patients may experience pain, tightness, or heaviness in their limbs even before there is visible swelling. Pitting oedema is one of the early physical examination symptoms that worsens with movement or heat. In more severe stages, the limb may appear larger due to thicker skin, decreased suppleness, and a positive Stemmer's sign, which is the inability to pinch the skin on the finger or toe.

Imaging methods

Imaging helps confirm the diagnosis, assess the extent of lymphatic dysfunction, and rule out other possible causes like venous insufficiency or deep vein thrombosis. Lymphatic drainage is either absent or delayed in the gold standard, lymphoscintigraphy. Ultrasound is useful to detect soft tissue thickening or fluid accumulation and to rule out vascular causes. MRI or MR lymphangiography provides high-resolution images of lymphatic structures, which are particularly useful in cases that are complex or unclear.

System of tagging

To assess severity and direct treatment, staging is crucial. The commonly used International Society of Lymphology (ISL) classification comprises:

Stage 0: Subclinical; no visible swelling is present, but there is lymphatic damage.

Stage I: Pitting reversible oedema that gets better with elevation.

Stage II: Non-pitting, irreversible oedema that does not go away with elevation.

Stage III: Severe skin changes, fibrosis, and swelling are signs of lymphostatic elephantiasis.

Management implications

The value of knowing pathophysiology for customised care

Effective treatment requires an understanding of the underlying pathophysiology. Clinicians can avoid using a one-size-fits-all approach by selecting interventions that target particular stages of lymphoedema by having a thorough understanding of the mechanisms underlying fluid accumulation, inflammation, and tissue fibrosis.

Overview of surgical, medical, and conservative choices

The mainstay of treatment is still conservative management, such as complete decongestive therapy (CDT), which incorporates skin care, exercise, compression therapy, and manual lymphatic drainage. Antibiotics for recurrent cellulitis or topical treatments for skin changes are examples of medical interventions. When conservative measures are not enough, surgical options like vascularised lymph node transfer or lymphovenous anastomosis may be considered.

Focus on long-term monitoring and early detection

Even in the latent stage, early detection of lymphoedema improves results by enabling prompt intervention before irreversible changes take place. Being a chronic condition that can worsen or recur, lymphoedema requires constant monitoring. In order to manage symptoms and avoid complications, long-term care entails routine evaluation, patient education, and support.

Summary

After cancer treatment, damage to the lymphatic system results in secondary lymphoedema, which shows up as decreased drainage, protein-rich fluid buildup, ongoing inflammation, and progressive tissue changes like fibrosis and skin thickening. For timely diagnosis and effective, stage-appropriate treatment, a full understanding of these processes is required. Since lymphoedema can significantly affect a patient's physical function, quality of life, and emotional well-being, it requires comprehensive management. A multidisciplinary approach ensures comprehensive care that addresses both medical and psychosocial needs by bringing together oncologists, physiotherapists, dermatologists, lymphoedema specialists, and mental health specialists. Patient education helps people manage their illness by recognising symptoms early and caring for their skin, applying compressions, and altering their lifestyles.