Lymphangioleiomyomatosis: Frequency, Heritage Pattern, Diagnosis and Treatment

It is a condition that affects the lungs, kidneys and lymphatic system.

The lymphatic system consists of a network of vessels that carry lymphatic fluid and immune cells throughout the body.

The lymphatic fluid helps to exchange immune cells, proteins and other substances between the blood and tissues.

Lymphangioleiomyomatosis occurs almost exclusively in women. It often presents as a characteristic of a hereditary syndrome called tuberous sclerosis complex. When lymphangioleiomyomatosis occurs alone it is called isolated or sporadic.

The signs and symptoms of lymphangioleiomyomatosis appear more often during the thirties of a woman. The affected women have an excessive growth of abnormal smooth muscle cells (LAM cells) in the lungs, resulting in the formation of lung cysts and the destruction of normal lung tissue.

They may also have an accumulation of fluid in the cavity around the lungs (chylothorax).

Pulmonary abnormalities resulting from lymphangioleiomyomatosis can cause shortness of breath (dyspnea), chest pain, and cough, which can lead to blood (hemoptysis).

Many women with this disorder have recurrent episodes of collapsed lung (spontaneous pneumothorax).

Pulmonary problems can be progressive and, without lung transplantation, can eventually lead to limitations in activities of daily living, the need for oxygen therapy and respiratory failure.

Although LAM cells are not considered cancerous, they can spread between tissues (metastasis). As a result, the condition may reappear even after lung transplantation.

Women with lymphangioleiomyomatosis may develop cysts in the lymphatic vessels of the chest and abdomen. These cysts are called lymphangioleiomyomas.

Affected women can also develop tumors called angiomyolipomas composed of LAM cells, fat cells and blood vessels.

Angiomyolipomas usually develop in the kidneys. Internal hemorrhage is a common complication of angiomyolipomas.

Frequency

Lymphangioleiomyomatosis occurs in approximately 30 percent of women with tuberous sclerosis complex. It is estimated that sporadic lymphangioleiomyomatosis, which occurs without the tuberous sclerosis complex, affects 3.3 to 7.4 per million women worldwide.

This condition can be underdiagnosed because its symptoms are similar to those of other lung disorders such as asthma, bronchitis and chronic obstructive pulmonary disease.

Genetic changes

Mutations in the TSC1 gene or, more commonly, in the TSC2 gene, cause lymphangioleiomyomatosis. The TSC1 and TSC2 genes provide instructions for the manufacture of hamartin and tuberin proteins, respectively.

Within cells, these two proteins probably help regulate cell growth and size. Proteins act as tumor suppressors, which normally prevent cells from growing and dividing too quickly or uncontrollably.

When both copies of the TSC1 gene are mutated in a particular cell, that cell can not produce functional hamartin; Cells with two altered copies of the TSC2 gene are unable to produce any functional cells.

The loss of these proteins allows the cell to grow and divide in an uncontrolled manner, resulting in tumors and cysts associated with lymphangioleiomyomatosis.

It is not well understood why lymphangioleiomyomatosis occurs predominantly in women. Researchers believe that the female sex hormone estrogen may be involved in the development of the disorder.

Heritage pattern

Sporadic lymphangioleiomyomatosis is not inherited. Instead, the researchers suggest that it is caused by a random mutation in the TSC1 or TSC2 gene that occurs very early in development.

As a result, some of the cells in the body have a normal version of the gene, while others have the mutated version.

This situation is called mosaicism. When a mutation occurs in the other copy of the TSC1 or TSC2 gene in certain cells during a woman’s life (a somatic mutation), it can develop lymphangioleiomyomatosis.

These women usually do not have a history of this disorder in their family.

Diagnosis

Making a diagnosis of a genetic or rare disease can often be a challenge. Health professionals often look at a person’s medical history, symptoms, physical examination and the results of laboratory tests in order to make a diagnosis.

The following resources provide information related to diagnosis and testing for this condition. If you have questions about how to get a diagnosis, you should contact a health professional.

Test resources

The Genetic Testing Registry (RPG) provides information about genetic testing for this condition. The target audience of the RPG are health care providers and researchers.

Patients with specific questions about a genetic test should contact a health care provider or a genetics professional.

Treatment

Although there is currently no cure for lymphangioleiomyomatosis, the research has led to great progress in the treatment of symptoms, and diagnosis and understanding.

There are a number of treatments that can relieve symptoms or prevent complications of the disease. Treatments vary from one patient to another, depending on the severity of the disease.

Not all patients have the same response to treatment.

Medications (eg, diuretics, hormone therapy, bronchodilators that relax the muscles around the airways).

Oxygen therapy – as lung capacity decreases, supplemental or full-time oxygen therapy may be necessary.

Treatment with Sirolimus – Rapamycin (Sirolimus) blocks the affected pathway in cells with lymphangioleiomyomatosis, which helps stop its uncontrolled growth.

The use of treatment with Sirolimus can be considered in patients with moderate or severe lymphangioleiomyomatosis, or those with progressive disease.

Procedures to remove air or fluid from the chest or abdominal cavities and prevent it from accumulating again.

Procedures to remove angiomyolipoma, or benign renal tumors

Lung transplant – a procedure to replace one or both lungs, this should be considered as a last resort due to the risk of serious adverse reactions, including major bleeding, pneumonia, pulmonary edema, long-term infections and possibly painful scarring.

Since lymphangioleiomyomatosis occurs almost exclusively in women of reproductive age, researchers believe that the estrogen hormone may be involved in the abnormal growth of muscle cells that characterize the disease.

Although there is no direct evidence that there is a relationship between estrogen and lymphangioleiomyomatosis, treatment has focused on reducing the production or effects of estrogen.

This could include estrogen or other hormone-suppressing drugs.

In addition, doctors believe that pregnancy can accelerate the progression of lymphangioleiomyomatosis. Women with lymphangioleiomyomatosis are urged to talk to a health professional before they become pregnant.