What is multicompartment lymphatic failure?

The lymphatic system helps protect against illness and delivers important nutrients throughout the body. Acting like a sponge, the lymphatic system absorbs extra lymph fluid — watery fluid containing protein, electrolytes, cells and other substances — from the body’s organs, and then returns it to the bloodstream through lymphatic vessels and veins. When something disrupts or damages normal lymphatic flow, lymphatic fluid can leak into the chest, abdomen, pericardium or other body cavities. This can cause serious health conditions.

Multicompartment lymphatic failure is a rare condition in which lymphatic fluid leaks into multiple body cavities (or compartments) at the same time. These compartments may include the chest, the intestine, the peritoneum (smooth tissue that lines the inside of the abdomen and surrounds many organs inside of it) and the skin. When lymphatic fluid leaks into the chest compartment, it can cause chylothorax, plastic bronchitis and chylous pericardium. When lymphatic fluid leaks into the intestine, it can cause protein-losing enteropathy. Leaks into the peritoneal can lead to ascites, and lymphatic fluid seeping into the skin can cause swelling (or edema).

What causes multicompartment lymphatic failure?

Multicompartment lymphatic failure can happen because of problems a person is born with (primary), or because of problems that develop later in life (secondary). Our imaging has shown that leaks in the lymphatic system can be in one small area (localized) or spread out (diffuse), which can lead to multicompartment lymphatic failure.

Experts at the Jill and Mark Fishman Center for Lymphatic Disorders at Children’s Hospital of Philadelphia (CHOP) are global leaders in lymphatic research, diagnostics and treatment. Our team’s research is changing the way the scientific and medical communities think about multicompartment lymphatic failure. 

Primary causes

Lymphatic channel disorders (lymphatic malformation)

• RASopathies
• Central Conducting Lymphatic Anomaly (CCLA)
• Lymphangiomatosis/Generalized Lymphatic Anomaly (GLA)
• Kaposiform Lymphatic Anomaly (KLA)
• Gorham-Stout Disease (GSD)
• Syndromes (Trisomy 21, DiGeorge syndrome, Turner syndrome)

Secondary Causes

Disruptions to normal lymphatic flow (mechanical obstruction)

• Elevated central venous pressure (CVP)
• Elevated intrathoracic pressure (ITP)
• Obstructing tumors or masses
• Thoracic duct (TD) occlusion
• Congenital diaphragmatic hernia
• Prematurity with chronic lung disease
• Congenital heart disease

What are the signs and symptoms of multicompartment lymphatic failure?

The signs and symptoms of multicompartment lymphatic failure depend on the location of the leak.

Lymphatic leakage into the chest may cause:

• Difficulty breathing
• Coughing
• Chest pain
• Hypoxia (not enough oxygen to the body)
• Fast heart rate 

Lymphatic leakage into the peritoneum may cause:

• Ascites
• Swollen or enlarged abdomen (abdominal distention)
• Nausea
• Vomiting

Lymphatic leakage into the intestine may cause:

• Low levels of albumin (a type of protein found in the blood)
• Diarrhea
• Electrolyte imbalance

Lymphatic leakage into the skin may cause:

• Edema
• Increased risk of cellulitis (bacterial infection of the skin)

How is multicompartment lymphatic failure diagnosed?

The world-renowned experts in CHOP’s Jill and Mark Fishman Center for Lymphatic Disorders use dynamic contrast magnetic resonance lymphangiography (DCMRL), a specialized imaging technique developed to accurately locate lymphatic leaks.

During DCMRL, a safe dye called an MRI contrast agent is injected into the lymphatic system to make it visible on an MRI scan. By tracking the flow of the dye, doctors can examine the lymphatic system more clearly. The contrast agent is introduced in one of the following ways:

• Through the lymph nodes in the groin (inguinal lymph node access)
• Through the liver (intrahepatic access)
• Through the tissue that connects the intestines (mesenteric access)
• Through the lymph channels in the skin (peripheral access)

Each access point used in DCMRL gives a unique view of the lymphatic system, providing the most complete imaging possible. For individuals with multicompartment lymphatic failure, inguinal, intrahepatic and mesenteric access points are used. For individuals with lymphedema, peripheral access points are used. This allows doctors to clearly see the structure of the lymphatic system, how lymph flows, how fast it moves and where any leaks are coming from.

How is multicompartment lymphatic failure treated?

In the Jill and Mark Fishman Center for Lymphatic Disorders, children and adults with multicompartment lymphatic failure are treated by the world’s most experienced specialists in lymphatic imaging and intervention. 

Treatment for multicompartment lymphatic failure depends on the underlying cause and which parts of the lymphatic system are affected. One treatment involves a procedure called percutaneous selective lymphatic embolization, which targets the leaking lymphatic channels. There are also other procedures that help relieve pressure in the lymphatic system, such as:

• Transcatheter thoracic duct decompression: A minimally invasive procedure where a small tube (catheter) is used to place a small, tube-like device (covered stent) between the heart and the vein that the thoracic duct drains into. This helps reduce pressure and allows the lymphatic fluid to drain more easily.  
• Hraska procedure: A surgical procedure that uses a conduit to create a new pathway between the heart and the vein that the thoracic duct drains into. This lowers the pressure in the thoracic duct, helping lymphatic fluid flow more effectively.
• Lymphovenous anastomosis: A surgical procedure that connects a blocked lymphatic channel, such as the thoracic duct, to a nearby vein. This allows the lymphatic fluid to flow back into the venous system.
• Lymphocutaneous anastomosis: A surgical procedure where a large lymphatic channel is stitched to the skin, allowing lymphatic fluid to drain outside of the body. This is a temporary solution to improving lymphatic flow.
• Thoracic duct drain: A minimally invasive procedure where a catheter is inserted into the thoracic duct to allow lymphatic fluid to drain out of the body. This is a temporary solution to improving lymphatic flow. 

Medical management

Medical treatment can also be an important part of managing multicompartment lymphatic failure. Different medications may be used to control symptoms or treat underlying conditions that are causing lymphatic leaks. For example, targeted therapies like trametinib, a MEK inhibitor, have been effective in treating certain lymphatic problems, especially those linked to genetic conditions, such as RASopathies. Other medications, such as diuretics or drugs that help improve lymphatic function or reduce inflammation, can also be helpful. Along with medication, following a low-fat diet can reduce the amount of lymphatic fluid produced, which may improve the condition.

What is the long-term outlook for patients with multicompartment lymphatic failure?

The long-term outlook for patients with multicompartment lymphatic failure depends on the cause of their condition. The treatment options available are advanced and still evolving, with more to discover about their effectiveness. The team of experts at the Jill and Mark Fishman Center for Lymphatic Disorders is committed to ongoing research to better understand the long-term outlook for patients and how lymphatic imaging and treatments can improve care for this condition.