Lymphatic & Venous Disorders

Lymphatic Diseases and Vascular Anomalies

Beyond lymphedema, there are a large number of human diseases that directly or indirectly impact the lymphatic system. Below are brief descriptions of a few of these numerous syndromes, including the symptoms, diagnosis and treatment, where applicable.

Lymphangioma

Lymphangiomas are lymphatic defects that typically develop during fetal growth. They are normally detected within the first two years of life but may also develop later in life following trauma. Ultrasounds and MRI are the most useful techniques for diagnosis. Lymphangiomas can present as small fluid-filled vesicles or large masses of soft tissue and can be encased within a fibrous capsule. They can be further classified by their size and depth of formation. Surgical excision is employed for the more superficial lesions while deeper lesions are typically treated with sclerotherapy, the injection of a chemical agent that causes the lesion to shrink, also used in the treatment of varicose veins.

Lymphangioleiomyomatosis (LAM)

Lymphangioleiomyomatosis is a syndrome that results in the spread of abnormal smooth muscle cells (or LAM cells) through lung tissue and lymphatics leading to obstruction of small airways in the lung and lymphatic wall thickening. It is characterized by the presence of pulmonary cysts and angiomyolipomas, tumors consisting of LAM cells, fat tissue, and underdeveloped blood vessels. It is an extremely rare disease, found in fewer than 1 in one million individuals and typically affects only women of child-bearing age. Diagnosis occurs through tissue biopsy of lungs or lymphatics. Treatment typically focuses on reducing pulmonary complications.

Lipedema

Lipedema is a condition that involves the accumulation of excessive fatty tissue in the lower half of the body. It occurs symmetrically on both sides and usually extends from the waist to just above the ankles. Lipedema occurs almost exclusively in women, typically triggered at puberty but can also occur following pregnancy or gynecological surgery. Patients frequently describe a family history of large legs and lipedema is often accompanied by a hormonal disorder. Unlike non-lipedemic fat, the fat component of lipedema cannot be significantly decreased by diet. Although lymphatic function is typically normal in lipedema, the excess fat can cause secondary lymphedema, in a condition called lipo-lymphedema. Treatment of lipedema includes correction of any hormonal imbalances if possible and liposuction of the legs.

Cystic angiomatosis

Cystic angiomatosis is a condition of unknown cause that is present at birth. It is defined by the presence of numerous skeletal cysts that are usually round or oval but vary widely in size. The cysts usually appear during the first few decades of life. Patients have soft tissue masses, bone pain and bone fractures caused by cyst growth. The cysts are easy to detect on x-rays because they represent areas of destroyed bone. Biopsies are performed to confirm diagnosis. Chemotherapy and radiotherapy have been attempted but have not been particularly effective.

Maffucci's syndrome

Maffucci's syndrome is rare; fewer than 200 cases have been reported since it was first described in 1881. It is characterized by the presence of hard cysts just beneath the skin and hemangiomas, abnormal lumps or tumors of blood vessels. These tumors commonly lead to pathological fractures of bones and although most of the tumors are benign, there is a 15-20% incidence of malignancy. Improper formation of bone in cartilage is also seen. Maffucci's syndrome often impairs lymphatic function, leading to secondary lymphedema. Patients are normal at birth and develop lesions during childhood and puberty.

Diffuse hemangiomatosis

Diffuse hemangiomatosis is an extremely rare syndrome with fewer than 70 reported cases. It is defined by the presence of non-malignant, internal hemangiomas, or tumors of blood vessels, that affect at least three organ systems. All described patients have lesions of the skin, liver, brain, lungs, and gastrointestinal tract. Treatment with corticosteroids and interferon-α has been attempted and has been moderately successful.

Gorham's disease

Gorham's disease is the uncontrolled growth of non-malignant vascular channels that cause destruction of the affected bone. It is associated with the presence of small knots of blood and lymphatic vessels. The shoulder and pelvis are the most frequently affected areas. Fluid accumulation in the lungs and area surrounding the heart are possible complications. Treatment involves surgical removal and reconstruction of affected areas and radiation therapy.

Proteus syndrome

Proteus syndrome causes an overgrowth of various tissues, including skin, bones, muscles, fatty tissues, and blood and lymphatic vessels. It is characterized by tumors just beneath the skin, excessive growth of the bone, overgrowth of connective tissue in palms of hands and soles of feet, pigmented birthmarks or moles, and partial gigantism of hands or feet. It is sporadic and mosaic, meaning that individuals have some cells with the mutation and some that are normal. Orthopedic complications, including scoliosis (curvature of the spine), are common. Treatment is generally surgery or physical therapy.

Klippel-Trenaunay syndrome

This birth defect occurs when blood and/or lymph vessels fail to form properly. Symptoms include port wine stains, varicose veins, and enlargement of bone and soft tissue. Usually the syndrome affects only a single extremity but it can be seen in multiple areas or the entire body. It is hypothesized that multiple gene mutations are involved. Complications of Klippel-Trenaunay syndrome include pain and lymphedema. Doppler ultrasounds, CT and MRI are important tools for diagnosis. Treatment is primarily aimed at management of lymphedema through use of compression therapy.

Blue rubber bleb nevus syndrome

This syndrome is named for the blue-ish colored nevi, or moles, which are rubbery and also soft and easy to compress. In addition to the nevi present on the skin, blue rubber nevus syndrome is characterized by hemangiomas, or abnormal lumps of blood vessels, in the gastrointestinal tract that can lead to bleeding or iron deficiency. Symptoms are either present at birth or develop within the first years of life and progress in size and number over time. Deformities of the surrounding bone may occur as a result of pressure from the hemangiomas. Treatments includes transfusions and iron supplementation for blood loss, and sclerotherapy, or injection of a chemical agent that decreases the size of the lesions.

Protein-Losing Enteropathy (PLE)

Protein-Losing Enteropathy is characterized by excessive protein loss into the gastrointestinal tract leading to abnormally low levels of protein in the blood. It is associated with numerous disorders, including inflammatory bowel disease, infection, celiac disease, and cardiac disease. PLE can lead to generalized edema due to increased pressure throughout the lymphatic system of the gastrointestinal tract and the loss of water soluble proteins. Diagnosis relies on laboratory analysis of cholesterol levels and protein levels in blood and feces. Intravenous administration of radioactive-labeled molecules allows for estimates of protein loss.  Treatment of PLE depends on the underlying cause of the syndrome and ranges from dietary changes to surgical intervention

Intestinal Lymphangiectasia

Symptoms of intestinal lymphangiectasia include severe edema or swelling, thickening of the wall of small intestine, Protein-Losing Enteropathy, accumulation of fluid in the abdomen, and collection of fluid surrounding the lungs. It can also result in enlarged lymph vessels supplying the small intestine. Intestinal lymphangiectasia can be primary, or present at birth, or secondary and caused by inflammatory involvement of the lymphatic system. The exact cause is unknown. It can also lead to a malabsorption of fat, especially long-chain fatty acids. CT scanning is very useful in diagnosis. Management includes the replacement of long chain fatty acids in the diet with medium chain triglycerides to reduce intestinal protein losses.

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