Lymphangioleiomyomatosis (LAM): Symptoms, Diagnosis and Treatment

What is LAM?

Lymphangioleiomyomatosis, usually called LAM, is an ultra-rare, slowly progressive disease that occurs almost exclusively in women, typically starting in the childbearing years. Abnormal smooth-muscle-like cells, known as LAM cells, grow in the lungs, the lymphatic vessels and the kidneys. In the lungs they gradually replace normal tissue with many thin-walled air-filled cysts, which reduce the lungs' ability to move air and transfer oxygen.

LAM occurs in two forms. Sporadic LAM arises on its own, and is estimated to affect a few women per million. TSC-LAM occurs in women with tuberous sclerosis complex, a genetic condition, in whom lung cysts are common, although many have mild disease.

LAM is now classed as a low-grade, destructive, metastasising neoplasm. That description reflects how LAM cells behave biologically. In practice, LAM is a chronic lung disease that is managed with tablets and monitoring, and the outlook has improved considerably since the introduction of sirolimus.

Symptoms of LAM

• Breathlessness on exertion: slowly progressive over years, and often initially attributed to asthma or lack of fitness.
• Collapsed lung (pneumothorax): often the first sign, and frequently recurrent. Most women with LAM have at least one pneumothorax.
• Chylous effusions: milky fluid from the lymphatic system collecting around the lung or in the abdomen.
• Cough, wheeze and occasionally coughing up blood or chyle.
• Kidney angiomyolipomas: benign tumours of fat, muscle and blood vessels, which can bleed and cause flank pain.
• Lymphangioleiomyomas: fluid-filled swellings of lymph nodes in the abdomen or pelvis, sometimes causing bloating that is worse in the evening.

Causes and risk factors

LAM is caused by changes in the TSC1 or TSC2 genes, which normally control a cell growth pathway called mTOR. When these genes do not work, the mTOR pathway is constantly switched on and LAM cells grow and spread. In TSC-LAM, the gene change is inherited or present from birth. In sporadic LAM, the changes occur only in the LAM cells and are not passed on to children.

Oestrogen appears to promote LAM, which explains why it affects women, why symptoms can worsen in pregnancy, and why progression often slows after the menopause. LAM is not caused by smoking, although smoking damages the lungs further.

How LAM is diagnosed

LAM should be considered in any woman with a pneumothorax, a chylous effusion or emphysema-like changes at a young age. Current ATS/JRS guidance recommends a stepwise approach that often avoids lung biopsy.

Other cystic lung diseases that can look similar include pulmonary Langerhans cell histiocytosis, Birt-Hogg-Dube syndrome, lymphocytic interstitial pneumonia and emphysema.

Treatment

Sirolimus

Sirolimus, an mTOR inhibitor, is the main treatment for LAM. It stabilises lung function in most patients, shrinks chylous effusions, lymphangioleiomyomas and angiomyolipomas, and is recommended for women with abnormal or declining lung function or troublesome chylous collections. It does not cure LAM and is usually continued long-term, with blood level monitoring and attention to side effects such as mouth ulcers, raised cholesterol and swelling. Everolimus is an alternative in some situations.

Pneumothorax

Because collapse is likely to recur, guidelines advise pleurodesis after the first pneumothorax rather than waiting for a second. This is planned with a thoracic surgeon, ideally in a way that does not rule out future transplantation. See pleural disease for more on these procedures.

Other measures

• Avoiding oestrogen-containing medicines, including combined contraceptive pills and oestrogen hormone replacement.
• Bronchodilator inhalers for those with airflow obstruction.
• Influenza and pneumococcal vaccination, pulmonary rehabilitation and bone health assessment.
• Oxygen when levels are low, and referral for lung transplantation in advanced disease.
• Embolisation or kidney-sparing surgery for large angiomyolipomas, coordinated with urology.

Living with LAM

LAM progresses at very different rates in different women, and many live for decades after diagnosis. Regular lung function tests guide treatment decisions. Pregnancy can worsen LAM and increases the risk of pneumothorax, so it should be discussed with the team beforehand. Most women with stable LAM can fly, but should not fly with an untreated pneumothorax and should seek advice if they have large cysts or low oxygen levels. Women with TSC-LAM are also followed by specialists in genetics, neurology and nephrology as needed.

When to seek urgent care

Seek emergency care for sudden chest pain or breathlessness, which may indicate a pneumothorax, for sudden severe flank or abdominal pain, which may indicate bleeding from an angiomyolipoma, and for coughing up blood, breathlessness at rest or blue lips.

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