Hereditary Lymphedema - Causes, Diagnosis, and Treatment

Introduction:

Lymphedema is a condition in which fluid collects in tissues, causing swelling. Lymphedema can be classified as primary and secondary lymphedema. Hereditary lymphedema is primary lymphedema that develops as a result of abnormalities in lymph nodes or vessels due to genetic changes or mutations. Secondary lymphedema is a condition that develops as a consequence of injury to the lymphatic system caused by factors such as surgery, radiation therapy, tumors, trauma, or infections, even in the absence of any structural abnormalities. The lymphatic system comprises a complex network of vessels, nodes, and ducts responsible for filtering and circulating lymph, a fluid rich in proteins and blood cells, throughout the body.

What Is Hereditary Lymphedema?

Hereditary lymphedema is characterized by chronic swelling or edema of certain parts of the body. It is a genetic condition, and it is inherited in an autosomal dominant manner. In this condition, the lymphatic fluid collects in the subcutaneous tissues under the epidermis (outermost layer of the skin) because of obstruction, underdevelopment, or malformation of various lymphatic vessels. This results in swelling (lymphedema), thickening, and hardening of the skin of the affected areas, usually the legs and feet. The degree of edema is generally progressive, though it was found to improve in the early years in some patients.

What Are the Types of Hereditary Lymphedema?

1. Type I - It is also known as Milroy disease, and it is a congenital condition that affects children of age up to two years.

2. Type II - It is also known as Meige disease or lymphedema praecox. It affects people aged from two to 35 years.

3. Lymphedema Tarda - It affects people after 35 years of age.

What Are the Signs and Symptoms of Hereditary Lymphedema?

• Swelling can occur in various areas of the body, including the legs, trunk, genitalia, face, and arms.

• Tightness and discomfort in affected areas.

• Tingling sensations (paresthesia).

• The skin of affected areas becomes dry, scaly, and thickened (hyperkeratosis) with a woody texture.

• Cellulitis refers to a bacterial infection that affects the skin and underlying soft tissues.

What Is the Cause of Hereditary Lymphedema?

The cause of type I hereditary lymphedema is mutations (changes) in the FLT4 (FMS-like tyrosine kinase 4) gene. Genes contain instructions for the synthesis of proteins, which are integral to numerous bodily functions. When changes or mutations happen in this gene, the protein product may be inefficient, faulty, overproduced, or absent. It can affect many organ systems of the body depending on the functions of the particular protein. FLT4 gene provides instructions to create a protein known as vascular endothelial growth factor receptor 3 (VEGFR-3) that is responsible for the development and maintenance of the lymphatic system. Some cases of type II hereditary lymphedema and lymphedema tarda are linked to mutations in the FOXC2 (forkhead box C2) gene, which has an essential role in regulating lymphatic valve development. Mutations in these genes result in abnormalities in the lymphatic system that does not allow fluids to drain properly, causing edema.

How to Diagnose Hereditary Lymphedema?

The diagnosis of hereditary lymphedema is made through clinical evaluation and some specialized imaging tests, such as:

• Lymphoscintigraphy - In this test, a tracer (radioactively labeled colloid substance)is injected intradermally (through the skin) into either hands or feet and monitored as it is transported through the body. The time taken by the tracer to reach the point of injection to the regional lymph node is recorded. In the case of type 1 hereditary lymphedema, the tracer moves sluggishly or not at all from the site of injection.

• Ultrasound - This diagnostic test employs echoes of sound waves to generate images of the specific body part under examination. It is used to evaluate venous conditions like venous blood clots and varicose veins. It is also helpful to identify an affected fetus during pregnancy if the swelling on the top of the feet is visible in the second or third trimester.

• MRI (Magnetic Imaging Resonance) Scan - By utilizing a combination of a magnetic field and radio waves, this imaging technique produces detailed cross-sectional images of the affected area of the body. It is capable of identifying distinctive features associated with hereditary lymphedema, such as edema, lymphocele (a sac-like structure filled with lymph fluid), and fibrosis (the development of fibrous tissue).

What Are the Treatment Options for Hereditary Lymphedema?

The main focus of the treatment of hereditary lymphedema is to manage symptoms, primarily reduce edema and prevent infection. For cases of lower leg edema, a lymphedema therapist is consulted. Treatment options may include fitting compression hosiery and /or bandaging, supportive shoes, massage, and good skin care.

Complete Decongestive Therapy (CDT)- Itis a treatment procedure that involves specialized manual techniques in combination with multi-layered compression bandaging, exercise, meticulous skin care, and the use of well-fitted compression garments. In cases where extreme lymphedema affects and impairs daily activities, rehabilitation therapy is recommended.

Surgery

• Microsurgical Anastomosis - This involves the joining of small lymphatic vessels to nearby small veins in order to create new pathways to rechannel lymphatic fluid flow into the venous system and hence reduce swelling. This surgery is reported to have limited effectiveness and is not usually recommended.

• Surgery for removing excess fibrous tissue is also an option for severe cases of lymphedema, but continued use of compression garments is necessary.

Medications

• Antibiotics - Used to treat infections like cellulitis and as a preventive measure for recurrent infections.

• Topical Antifungals - Used to treat athlete’s foot.

• Diuretics - Spironolactone, is given as a valuable adjunct to dietary control.

1. To prevent the progression of infection or edema, the patients should avoid long periods of immobility with their legs placed in downward positions at a level lower than the heart and decrease salt intake to reduce fluid retention. Due to decreased resistance to infection, it is crucial to exercise special attention and care in order to prevent wounds in the affected areas.

2. Genetic testing and counseling may benefit people with hereditary lymphedema.

Conclusion

Hereditary lymphedema is an inherited condition that results in the swelling of body parts. The diagnosis is usually made through clinical evaluation identifying swelling or lymphedema in lower limbs. Though there are many treatment approaches for this condition, currently, there is no gene therapy available for the treatment. Individuals with the disease face an elevated risk of developing malignancy at the affected site compared to the general population.