Lymphangioleiomyomatosis

Lymphangioleiomyomatosis (LAM) is the result of disorderly smooth muscle proliferation throughout the bronchioles, alveolar septa, perivascular spaces, and lymphatics, resulting in the obstruction of small airways (leading to pulmonary cyst formation and pneumothorax) and lymphatics (leading to chylous pleural effusion). LAM occurs in a sporadic form, which only affects females, who are usually of childbearing age. LAM also occurs in patients who have tuberous sclerosis. more...

Cause

The cause of the sporadic form of LAM is unknown. This type only affects women.

The proliferating smooth muscle that occurs the type of LAM seen in patients with tuberous sclerosis (TSC-LAM) has been shown to represent clones of the smooth muscle in those patients' renal angiomyolipomas, and thus is believed to represent metastases of this "benign" tumor. There is a female properandence to TSC-LAM. (reference: Henske EP. Metastasis of benign tumor cells in tuberous sclerosis complex. Genes, Chromosomes & Cancer. Dec. 2003. 38(4):376-81)

Radiography

With LAM, there is diffuse replacement of the pulmonary parenchyma by thin-walled cysts measuring 2-20 mm in diameter, with equal involvement of upper and lower lung zones. On chest X-rays, superimposition of the cysts gives a reticulonodular pattern of interstitial lung disease. High-resolution CT of the chest is both more specific for the diagnosis, as well as better able to assess the degree of pulmonary involvement.

Prognosis

Without lung transplant, there is a 50-80% 5-year survival rate.

Complications

• Worsening pulmonary insuffiency
• Pneumothorax, secondary to rupture of a cyst into the pleural space
• Chylous pleural effusions

Treatment

The association of LAM with women of childbearing age suggests that hormonal stimulation plays a role in the disease process, and several approaches to treatment involve diminishing the effect of estrogen. At one time or another, therapeutic approaches have included

• progesterone
• oophorectomy
• tamoxifen
• gonadotropin-releasing hormone (GnRH) agnonists
• androgen therapy

No therapy is clearly efficacious, and all have undesirable side-effects.

When pulmonary function deteriorates to the point where oxygenation is inadequate, lung transplantation is usually performed. Following lung transplant (usually unilateral), LAM patients have survival curves similar to other lung transplant patients.

Research

The drug Sirolimus (also known as Rapamycin) is being investigated in clinical trials as a possible treatment. It has been shown to shrink angiomyolipomas in animals. For more information see this interview.

Support

LAM Action (UK)

The LAM Foundation (US)

Read more at Wikipedia.org