Introduction

Imagine a connection of pipes like the one connecting your kitchen sink to the drainage systems outside. As you wash the dishes that morning, you realise that the water is not flowing out and just remains in the sink. When you call the plumber, he tells you that the pipes are blocked for some reason and cannot be drained. This concept is almost similar to what we're about to discuss below. 

Lymphedema is a medical condition where lymphatic fluid, a sort of protein-rich fluid that is supposed to be drained by your body's lymphatic system, accumulates in the tissues, causing swelling.

This swelling is most commonly seen in the arms or legs and is most often a result of a disruption in the lymphatic system, which is responsible for draining the excess fluid and maintaining immune function.

The causes of lymphedema can include

Congenital or hereditary malformations of the lymphatic vessels.Damage to the lymphatic system due to:

• Cancer
• Cancer treatments (like surgery or radiation)
• Trauma
• Surgery 

Parasite infections like filariasis, which are common in tropical regions 

The accurate classification and staging of lymphedema are essential to the effective diagnosis, treatment, and monitoring of the disease progression, while also improving long-term outcomes. 

Pathophysiology overview

The lymphatic system is a part of your immune system, consisting of vessels that carry lymphatic fluid, which is rich in protein, throughout the body. The lymphatic system is not just made up of these vessels but also of lymph nodes that serve as filters and contain cells that fight infection and cancer.¹

The lymphatic system is made up of vessels through which the lymphatic fluid is pushed by muscle contractions as you carry out daily tasks. Lymphedema occurs when the lymph vessels are unable to properly drain lymph fluid, leading to the accumulation of fluid in soft tissues. 

Without proper management, lymphedema can worsen, leading to

•  Limited mobility of the affected limb 
•  Chronic infections
•  Skin changes like thickening or darkening
• Sepsis 

Clinical classification of lymphedema 

The clinical classification can be based on the cause of the lymphedema, which would broadly categorise it into primary and secondary types.

• Primary lymphedema is a rare condition that arises due to abnormalities in the development of the lymphatic system, resulting they are not being enough vessels to handle the lymph fluid produced.

While in children the swelling is not as glaring, but as the individual grows older, the signs are more obvious.⁸

Primary lymphedema can also be classified into the following:⁹

• Congenital lymphedema, which appears in infants before 2 years, is caused by lymphatic aplasia or hypoplasia
• Lymphedema praecox appears in individuals between the ages of 2 and 35 years. It's commonly noted in females at the beginning of their menstrual cycle or during pregnancy
• Lymphedema tarda is commonly present after  35 years

Secondary lymphedema develops due to the obstruction of the lymphatic pathways by either surgery or other diseases that damage the lymphatic system, such as;

• Cancer treatment (surgery/radiation)
• Infection (e.g., filariasis)
• Trauma or injury
• Chronic venous insufficiency

Secondary lymphedema is much more common and may include:⁸

• Iatrogenic lymphedema

This is caused by medical treatments such as surgery or radiation therapy that end up destroying the lymphatic pathways—often as part of cancer treatment.

• Traumatic lymphedema

Injury to the lymphatic vessels will lead to obstruction of those vessels and the development of lymphedema.

Classification based on the severity 

The severity of lymphedema is categorised based on the increase in extremity volume. 

• Mild: There is an increase in extremity volume of <20%. Swelling is subtle and often temporary, with no functional limitation
• Moderate: Swelling is noticeable, with some skin changes and functional impairment. The rate of increase is between 20% and 40%
• Severe: In severe lymphedema, the extremity volume is >40%. There is persistent swelling, skin fibrosis, thickening, and risk of secondary infection³

Staging systems for lymphedema severity

While classifying lymphedema is a good way of diagnosing and tackling the disease, staging is also an important method in the management of lymphedema. 

There are several ways in which we can stage lymphedema, and we will discuss them below. 

International society of lymphology staging system

The ISL staging is one of the most well-known systems for staging lymphedema.

The staging is based on physical signs and progression:

• Stage 0 (Latency): There is no visible swelling, and it cannot be detected even by using a measuring tape, but there are early stages of lymphatic dysfunction
• It could be years before you notice swelling
• Stage I: Swelling is reversible, and you may notice that with some elevation, it does disappear. They may have the appearance of pitting oedema
• Stage II: Swelling becomes persistent and is no longer fully reversible. It may form fibrotic tissue and become harder to touch
• Stage III (Elephantiasis): There is severe swelling with skin thickening, fat deposition, and hyperpigmentation. Tissue in the area is now fibrotic²

Campisi's clinical staging

This system builds its data by using clinical findings, the physical state of the patient, and imaging results. It is used mainly in planning surgical procedures and evaluating the following; 

•  The size of the swelling
•  Skin alterations
•  Response to conservative management.

As such, lymphedema can be staged as follows:

• Stage IA, or latent lymphedema

This is lymphedema without clinical evidence of oedema, but there is the presence of impaired lymphatic transport capacity based on lymphoscintigraphy reports and with visible signs of initial immunohistochemical alterations of lymph nodes, lymph vessels, and extracellular matrix. 

• Stage I B, or initial lymphedema

This is lymphedema that can be reversed totally or partially, at least for a period, by elevation and a draining position. 

While there is still impairment in the capacity of lymph transport, it is worsened by the alterations of lymph vessels and the nodes that filter this fluid. 

• Stage II A or increasing lymphedema

The ability of the lymphatic system to transport fluid away from tissues becomes reduced, thus leading to recurrent episodes of inflammation in lymphatic vessels.

The skin and tissues thicken and harden due to the previously mentioned inflammation and fluid buildup. It also leads to the development of disability.

• Stage II B

Due to the previous hardening and thickening of skin and tissues, the limbs become cylindrical, column-shaped limbs, with lymphostatic skin changes still present and worsening disability.

• Stage IIIA

It is properly referred to as elephantiasis, with skin changes that include the hardening and thickening of skin and underlying tissues due to fibrosis, as well as the development of wart-like growths on the skin due to lymphatic blockage. There is life-threatening disability and no lymph transport capacity.⁴

• Stage III B

Presents as extreme elephantiasis with total disability.

CTCAE 

The Common Terminology Criteria for Adverse Events is a system that is commonly used in oncology. CTCAE grades lymphedema in relation to the adverse effects of cancer treatment:

 Grade 1: Asymptomatic or mild swelling

 Grade 2: Moderate symptoms, limits activities involved with the use of instruments 

 Grade 3-4: Severe swelling, significant functional disability, potentially life-threatening⁷

Limitations and considerations

While current staging systems are helpful for diagnosis, they also have certain limitations:

• Variations in Assessment:  Several doctors may examine the same patient and end up with different clinical reports
• Lack of standardisation: There is no single system being used worldwide
• Subjective symptoms, like pain, heaviness, and quality of life, are not always included in staging, and many systems do not account for these psychosocial factors

Conclusion

Lymphedema is a chronic condition that has no cure but can be sufficiently managed. Understanding and applying appropriate classification and staging systems helps us ensure that healthcare providers make informed decisions about their patients' health by making accurate diagnoses, guiding treatment, and improving patients' overall health. 

Staging systems like ISL, Campisi, and CTCAE offer insight into the severity and progression of the disease.

Looking ahead, the future lies in personalised staging, combining clinical symptoms, imaging, patient experience, and technology to improve outcomes and quality of life.

In the near future, combining a patient-centred approach that takes into consideration staging and quality of life will enhance the standard of care for individuals living with lymphedema.