Lymphangioleiomyomatosis (LAM)

What causes LAM

LAM is caused by changes in the TSC1 or TSC2 genes, which normally act as brakes on cell growth through a pathway called mTOR. When these genes do not work, LAM cells grow and spread through the lungs and lymphatic system. They release enzymes that break down lung tissue, forming cysts.

There are two forms:

• Sporadic LAM: gene changes occur only in the LAM cells, not inherited. Affects an estimated 3 to 8 women per million.
• TSC-associated LAM: occurs in women with tuberous sclerosis complex, an inherited condition, many of whom have lung cysts on CT, often mild.

Estrogen appears to promote disease activity, which may explain why it mainly affects women of reproductive age and can worsen in pregnancy.

Symptoms

• shortness of breath, first with exertion, gradually progressing
• pneumothorax (collapsed lung): sudden chest pain and breathlessness; occurs in more than half of people with LAM and often recurs
• fatigue
• cough and wheezing, sometimes misdiagnosed as asthma
• coughing up blood
• chylothorax: milky lymphatic fluid around the lungs, causing breathlessness
• abdominal or pelvic lymph node masses (lymphangioleiomyomas)
• kidney angiomyolipomas: benign tumors that can bleed

Diagnosis

LAM is often diagnosed after years of misdiagnosis.

• High-resolution chest CT: shows many round, thin-walled cysts evenly spread through both lungs. This is essential.
• Serum VEGF-D test: a level of 800 pg/mL or higher in a woman with typical cysts confirms LAM without a biopsy.
• Other confirming features: tuberous sclerosis complex, kidney angiomyolipomas, chylous effusions or lymphangioleiomyomas.
• Biopsy: lung or lymph node biopsy if the diagnosis remains uncertain.
• Lung function tests: usually show airflow obstruction and reduced gas transfer; used to monitor progression.
• Abdominal imaging for angiomyolipomas and lymphatic masses.

Treatment

Sirolimus

Sirolimus, an mTOR inhibitor, is the main treatment. It stabilizes lung function in most people, reduces chylous fluid collections and shrinks angiomyolipomas and lymphatic masses. It is recommended for people with abnormal or declining lung function or problematic chylous effusions. Side effects include mouth ulcers, diarrhea, acne-like rash, swelling and raised cholesterol; blood levels are monitored. Everolimus is a related alternative in some cases.

Managing complications

• Pneumothorax: chest tube drainage; after the first episode, a procedure to make the lung stick to the chest wall (pleurodesis) is often recommended because recurrence is so common.
• Chylothorax: sirolimus, drainage and dietary changes.
• Angiomyolipomas: monitoring, mTOR inhibitors, or embolization for large or bleeding tumors.

Supportive care

• bronchodilator inhalers for those with reversible airflow obstruction
• supplemental oxygen when needed
• pulmonary rehabilitation
• vaccinations against flu, COVID-19 and pneumococcus
• avoiding estrogen-containing medicines
• counseling about pregnancy, which can worsen LAM and increase pneumothorax risk
• discussing air travel with your doctor, especially after a recent pneumothorax

Lung transplant

For advanced disease, lung transplantation is an option with outcomes similar to or better than other transplant indications. LAM can recur in the transplanted lung but rarely causes major problems.

Outlook

LAM progresses at different rates. Many people live for decades after diagnosis, and sirolimus has changed the outlook by slowing decline. Regular follow-up at a specialist center, such as a LAM Foundation clinic, helps tailor treatment.

Frequently asked questions

What is LAM lung disease?

LAM is a rare, progressive disease, almost only in women, in which abnormal cells grow in the lungs, lymph system and kidneys. They create many cysts that gradually damage the lungs, causing breathlessness and collapsed lungs.

What are the first symptoms of LAM?

Early symptoms are often shortness of breath on exertion, which may be mistaken for asthma, or a sudden collapsed lung with chest pain and breathlessness. Some women first learn they have LAM after a CT scan done for another reason.

How is LAM diagnosed?

A high-resolution chest CT shows the typical cysts. A blood test for VEGF-D above 800 pg/mL, or the presence of tuberous sclerosis complex, kidney angiomyolipomas or chylous fluid, can confirm the diagnosis without a biopsy.

What is the life expectancy with LAM?

It varies widely. Many women live for decades after diagnosis, especially with sirolimus, which slows lung function decline. Lung transplantation is an option if the disease becomes advanced.