Lymphangioleiomyomatosis (LAM)
Lymphangioleiomyomatosis (LAM) is a rare lung disease that almost exclusively affects women, causing abnormal cells to grow in the lungs, kidneys, and lymphatic system, leading to breathing difficulties and other serious complications.
Table of contents
- What is Lymphangioleiomyomatosis?
- Types of LAM
- Who is Affected by LAM?
- Symptoms and Warning Signs
- What Causes LAM?
- Possible Complications
- How LAM is Diagnosed
- Treatment Options
- Living with LAM
- Outlook and Prognosis
What is Lymphangioleiomyomatosis?
Lymphangioleiomyomatosis, commonly known as LAM, is a rare and progressive lung disease that primarily affects women. The disease is characterized by abnormal growth of smooth muscle-like cells, especially in the lungs, lymphatic system, and kidneys.[1] These abnormal cells, called LAM cells, grow out of control and create problems throughout the body.[2]
In the lungs, LAM obstructs the airways and damages lung tissue, leading to the formation of fluid-filled pockets called cysts. These cysts prevent air from moving freely in and out of the lungs, which can lower the amount of oxygen that reaches the rest of the body.[2] Over time, this damage causes breathing difficulties and can lead to respiratory failure, a condition where organs don’t receive enough oxygen to work properly.[2]
- Lungs
- Kidneys
- Lymphatic system
Types of LAM
There are two distinct forms of LAM that affect women.[1] Sporadic LAM occurs for unknown reasons when a genetic change happens spontaneously during a person’s life. This type cannot be passed on to children.[1][2]
The second type, called TSC-LAM, occurs in some people who have an inherited genetic disorder called tuberous sclerosis complex (TSC). This is a rare condition that causes tumors to grow in various organs including the brain, kidneys, heart, eyes, and lungs.[5] About three out of every ten women with tuberous sclerosis also have LAM, and this risk increases with age.[3][5]
Who is Affected by LAM?
LAM affects women almost exclusively, with very few cases ever reported in men. Only one known case of sporadic LAM has occurred in a man.[1] The disease typically appears during childbearing years, between puberty and menopause.[2] Most women are diagnosed between the ages of 20 and 40, with the average age at diagnosis being approximately 35 years old.[3]
Because of this pattern, experts believe the hormone estrogen or having a uterus may play a role in how the disease develops.[1] LAM often gets worse during pregnancy and while using medications that contain estrogen.[1]
It is estimated that for every million women, three to seven will have LAM, though a 2023 study of four European countries suggests the number may actually be higher, at least 21 cases per million women.[3] All races are affected, and women with LAM have been identified in more than sixty countries.[3]
Symptoms and Warning Signs
Some women with LAM have no symptoms or very mild symptoms at first, while others experience more significant problems from the beginning.[3] The most common symptoms include shortness of breath that can get worse over time, fatigue, chest pain, cough, and abdominal bloating.[1][3]
Many women may also cough up blood or a sticky, whitish substance called chyle, which is lymph fluid from the digestive system.[1] Other symptoms can include wheezing and breathlessness during physical activity.[8]
LAM can develop slowly, and many women have symptoms for several years before being diagnosed.[3] Diagnosis is typically delayed by 5 to 6 years because the symptoms are often similar to those of more common lung diseases such as asthma, bronchitis, or emphysema.[6][2]
For many women, the first sign of LAM is a collapsed lung, also called pneumothorax. This happens when a cyst bursts and air leaks into the space around the lung, causing sudden stabbing chest pain and difficulty breathing that requires immediate medical treatment.[2]
What Causes LAM?
LAM is caused by mutations or changes in two genes called TSC1 and TSC2. These are tumor suppressor genes, which normally keep certain cells from multiplying out of control.[1] When one of these genes has a mutation, smooth muscle cells multiply when they shouldn’t, creating cysts in the lungs, tumors in the kidneys called angiomyolipomas, and tumors in the lymphatic system.[1]
You can either inherit an abnormal copy of TSC1 or TSC2 from a biological parent who has one, or changes to the gene can happen spontaneously for unknown reasons.[1] Inherited changes in these genes cause tuberous sclerosis, and more than 30% of women with tuberous sclerosis develop LAM.[1] Changes to TSC2 that you didn’t inherit cause sporadic LAM, without additional symptoms of tuberous sclerosis.[1]
Possible Complications
A collapsed lung is the most common complication of LAM. About three-quarters of women with LAM will experience at least one collapsed lung during the course of the disease, and these often happen more than once.[3] Over half of all women with LAM will have a collapsed lung at least once, and many women are diagnosed with LAM after experiencing lung collapse.[1]
Another complication involves the kidneys. Angiomyolipomas are benign (non-cancerous) fatty tumors that occur in the kidneys of most patients with TSC-LAM and around 30 to 40% of those with sporadic LAM.[3] Most are small and don’t cause symptoms, but they can bleed, particularly those over 4 centimeters in diameter, requiring medical intervention.[3]
LAM cells can also block lymph flow, causing milky fluid called chyle to collect in the chest, pelvis, and abdomen. This is referred to as chylous pleural effusion (fluid around the lungs) when it occurs in the chest.[3] These lymphatic problems occur more frequently in patients with sporadic LAM, affecting approximately 30 to 40% compared to 10% for TSC-LAM.[3]
Other complications include fluid around the lungs called pleural effusion and blockage in the lymph system.[1]
How LAM is Diagnosed
To diagnose LAM, a healthcare provider will examine you and ask about your symptoms. They will order or perform tests and imaging to better understand how well your lungs are working, the levels of oxygen in your blood, whether there are any changes in your lungs, and if you have higher levels of certain proteins in your blood.[1]
Because symptoms of LAM are similar to those of other, more common lung conditions, it can be hard for healthcare providers to diagnose the disease.[1][2]
Your doctor will first conduct a complete medical history and evaluate your lung function using a device called a spirometer, which measures the amount of oxygen in your blood.[5] If LAM is suspected, your physician will take a high-resolution CT scan to determine if you have any cysts, abnormal cell clusters, excess fluid, or enlarged lymph nodes.[5]
Additional tests may include pulmonary function tests, a six-minute walk test, blood tests, and exercise tests.[5] A blood test for a protein called VEGF-D can also be helpful in diagnosis.[7]
If these tests are inconclusive, your physician may take a biopsy of your lungs to look for LAM cells.[5] Because this condition is so rare and difficult to diagnose, it is important to see a team of specialists who have experience in diagnosing LAM.[5]
Treatment Options
LAM is a progressive disease, meaning it gets worse over time. There is no cure for LAM, but there are effective medicines that can help relieve symptoms and prevent complications.[10] Treating LAM focuses on preserving lung function, preventing complications, and minimizing the severity of symptoms.[5]
Medications
Sirolimus (also known as rapamycin, brand name Rapamune) was approved by the U.S. Food and Drug Administration in May 2015 as the first drug for treatment of LAM.[12][14] This medication is the first-line treatment option for managing symptoms and complications of LAM. It works by controlling the abnormal growth and movement of LAM cells and may help stabilize lung function, shrink kidney and lymph node growths, and reduce fluid in the lungs.[10][12]
Side effects of sirolimus can include diarrhea, nausea, acne, mouth ulcers, high blood cholesterol, swelling of the mouth and lips, and fluid buildup in the legs.[10][16] The medicine may also affect your ovaries, liver, and kidneys and raise your risk of infections.[10]
Everolimus (brand name Afinitor), a similar medication, is also sometimes used to treat LAM, particularly for kidney tumors, although it is not FDA-approved specifically for LAM.[10][12]
Your healthcare provider may also prescribe bronchodilators, medicines that help relax and open airways if you are wheezing or having trouble breathing.[5][10] Many women with LAM find that bronchodilator inhalers help to reduce breathlessness.[12]
Oxygen Therapy
If you do not have enough oxygen in your blood, you may need supplemental oxygen.[10] At first, you may only need oxygen therapy during high-energy activities or while sleeping. Eventually, you may need full-time oxygen therapy.[10] Many devices are available that deliver pure oxygen to your lungs, including small, portable tanks.[5]
Surgical Options
Your physician may suggest procedures to remove excess air or fluid from your chest or abdomen to alleviate shortness of breath, relieve discomfort, and prevent future buildup.[5] In severe cases of lung damage from advanced LAM, a lung transplant may be necessary.[5][10]
Living with LAM
Receiving a diagnosis of LAM can trigger a wide range of feelings including anger, denial, shock, grief, helplessness, confusion, despair, sadness, or fear. These feelings are common and are all part of the normal grieving process.[16] Some women actually feel relief knowing there is an explanation for their symptoms.[16]
It is important for you to take good care of your health by adopting a healthy lifestyle, including eating a healthy diet, being as physically active as you can, getting plenty of rest, and not smoking.[17] Be sure to get your flu shot every year, as well as other vaccines such as the pneumonia vaccine and the COVID-19 vaccine.[7][17]
Even though almost all women with LAM have difficulty breathing, it is important to continue exercising. The best way to get started with an appropriate training program is to attend pulmonary rehabilitation, where trained personnel monitor oxygen levels and heart rate to make sure that exercise is helping safely.[16]
You should avoid heavy lifting and discuss with your LAM specialist before considering getting pregnant.[7] Because the role of hormones in LAM is not well understood, if your lung function is normal, pregnancy may be an option, but it’s important to discuss pregnancy plans with specialists who understand LAM.[19]
You will work with a pulmonologist, a healthcare provider who specializes in the lungs, to determine the best way to monitor your condition. They will test your lung function periodically.[7] Contact your provider if you develop sudden or worsening shortness of breath, chest pain, or coughing up blood.[7]
To help manage stress, patients may consider complementary therapies such as exercise, acupuncture, massage therapy, yoga, and reflexology.[16] If the stresses accompanying a LAM diagnosis become overwhelming, it’s important to seek emotional support from friends, relatives, or professionals such as a psychologist or counselor.[16]
Outlook and Prognosis
The outlook for people who have LAM is much better today than it was in the past, as diagnosis and treatments have advanced.[17] Many people with LAM are living longer and with fewer complications.[17]
LAM’s progression is different for everyone. For some women, the disease progresses slowly, while for others, it advances rapidly. In all cases, lung function tends to decrease over time, with premenopausal women having a faster rate of lung decline than postmenopausal women.[3]
The median survival of patients with LAM is estimated at more than 20 years after diagnosis, with a transplant-free survival probability of 94% at 5 years, 85% at 10 years, 75% at 15 years, and 64% at 20 years.[3] Many people with LAM can live decades after their diagnosis before needing a lung transplant, though the progression depends on many factors including type of LAM, age, and response to treatment.[7]
