Lymphangioleiomyomatosis (LAM)


  • Lymphangioleiomyomatosis, or LAM as it is usually called, is a rare lung condition that affects a certain type of muscle cell and only occurs in women.

    It affects around one woman in a million; around 60 people in the UK are known to have it. It appears to occur worldwide and is equally rare in other countries.

    The average age of onset of LAM in people in the United Kingdom is 34. It nearly always starts before the menopause. When, very rarely, it has been diagnosed after the menopause, it has usually been in women taking hormone replacement therapy (HRT).

    LAM mainly affects the lungs, where it causes an overgrowth of a certain type of cell (smooth muscle cell). This overgrowth occurs around the airways (breathing tubes), the blood vessels and the lymph vessels (a means of draining excess fluid from the lungs). The cells lead to cysts developing in the lung and these may be seen on a chest x-ray and are shown very clearly on a CT scan of the lung.

    The main effects of LAM are in the lung but quite a few people also have a tumour in the kidneys and sometimes more than one; they are not malignant but can cause bleeding. Fibroids may also be more common in people with LAM and lymph nodes may be enlarged in other parts of the body but they don't usually cause problems.

    The name lymphangioleiomyomatosis reflects the different components of the disease. 'Lymph' and 'angio' refer to the lymph and blood vessels that are involved and 'leiomyo' refers to the smooth muscle.

    What happens when you have LAM?

    LAM affects different people in different ways. The main problem usually is breathlessness, particularly when people exert themselves. This is due to the effect of the cells on the airways and also to the cysts, which take up space in the lungs. Some people are breathless due to the development of fluid around the lung (known as a pleural effusion). This occurs when the lymph vessels are blocked and this usually causes the fluid to be milky (chylous). Occasionally some lymph is coughed up as sticky whitish phlegm. Similarly because LAM can affect the blood vessels in the lung some people cough up blood from time to time.

    For many people with LAM the first sign is when they develop a collapsed lung, known as a pneumothorax. This occurs when one of the cysts bursts and air leaks into the space around the lung. Pneumothorax usually causes sudden onset of breathlessness, often with a sharp pain, and it requires treatment in hospital. If it recurs a small operation may be needed. The operation will prevent a further pneumothorax though some people continue to be aware of occasional gurgling in their chest after it.

    What causes LAM?

    The cause of LAM is at present unknown. We know it is not inherited and it is not passed on to children. It might be due to a change (mutation) in a chromosome, which controls the growth of smooth muscle cells in the lung. Why this should happen is not clear, however, but is the subject of research.

    Effect of hormone changes on LAM

    LAM usually progresses over time although the rate at which it does so varies considerably between individuals. Since LAM generally occurs before the menopause it is thought to be influenced by female hormones such as oestrogen and progesterone. Oestrogens may accelerate the disease and progesterone may slow it down. The effect of events such as pregnancy that cause hormones to change and the effect of hormones in the contraceptive pill and in hormone replacement therapy (HRT) are not well established but the best evidence to date suggests the following:

    Pregnancy

    
Some people with LAM have been pregnant without any worsening of the condition. In others, however, the disease has deteriorated. Complications such as pneumothorax and a pleural effusion appear to occur more often during pregnancy.

    Hormone replacement therapy (HRT)

    
HRT contains oestrogens and it may therefore make LAM worse.

    Menopause

    
The rate at which LAM progresses may slow down after the menopause, although this is not always the case.

    The contraceptive pill


    Most contraceptive pills contain oestrogen and progesterone and although there is no evidence that they make LAM worse, there is a progesterone-only contraceptive pill which may be safer. Alternative means of contraception which do not use hormones could also be used.

    Fertility treatment

    
If oestrogen makes LAM worse it is likely that fertility treatment will do the same. People who wish to consider becoming pregnant or who are taking or wish to take the contraceptive pill, HRT or fertility treatment should discuss this with their physician before making changes.

    How is LAM diagnosed?

    Many symptoms of LAM are similar to those of more common lung diseases such as asthma and for this reason people may have symptoms for a long period before LAM is diagnosed correctly. Symptoms, X-rays and breathing (lung function) tests may suggest LAM but the diagnosis is usually confirmed by a CT (detailed X-ray) scan of the lungs and sometimes a lung biopsy.

    In someone with LAM the CT scan usually shows typical cysts throughout the lungs. A biopsy may be performed where the doctor feels more information is needed to ensure that the diagnosis is correct. This is usually carried out through a fairly small incision in the chest under a general anaesthetic. In LAM the biopsy will show the typical cysts and smooth muscle cells. The kidney tumours are also seen best on a CT scan although they can also be seen with ultrasound.

    Is there any treatment for LAM?

    Unfortunately there is no cure for LAM as yet. Treatment may be given to deal with symptoms or complications (supportive treatment) or it may be given in the hope that it will reduce the rate at which LAM progresses.

    Supportive treatment

    Breathlessness. The treatment for breathlessness depends on the cause of the breathlessness. For example, if there is a pneumothorax or a pleural effusion, treating these should help the breathlessness. Some people benefit from the beta-agonist inhalers used by asthmatic people such as Ventolin and Bricanyl.

    Fluid on the chest (pleural effusion). If this is large it may be helpful to remove the fluid, though in the long term it is better to prevent it accumulating. This may be helped by a low fat diet or by progesterone treatment.

    Pneumothorax. This is usually treated initially by sucking the air out of the space round the lung with a needle or tube inserted under a local anaesthetic. If it recurs it is often treated with a small operation, which sticks the outside of the lung to the inside of the ribcage so that it can't collapse again. This is known as a pleurodesis and is carried out with a general anaesthetic.

    Lung transplant. Lung transplantation is a possibility for people with severe LAM. More than 82 people with LAM have had a lung transplant and the outcome appears to be similar to people who have had a transplant for other conditions. A lung transplant is a major undertaking, however, and the results for lung transplantation are not yet as good as those for a kidney transplant. It is only considered therefore when LAM has become severe.

    Flu jab. As with all people with a lung condition it is sensible to have a 'flu jab' each winter. It may also be worth having a pneumococcal vaccination to reduce the risk of pneumonia. This should be discussed with your doctor.

    Treatment to help prevent LAM progressing

    Various treatments have been tried for LAM, particularly hormone treatments. Because LAM is rare it has not been possible to study different treatments in the way that they would normally be studied in other diseases - by comparing treatment with a dummy treatment (placebo) in a controlled trial. The treatments outlined below appear to have been helpful to some people although it isn't clear whether they suit all people and they can have some side effects.

    The following treatments have been tried:

    Progesterone. This is the most common treatment used in the United Kingdom. It is usually given by an injection every 3 or 4 weeks. There is also a tablet form but whether this is effective is uncertain. There may be no side effects from progesterone but nausea, a bloated feeling, headache and swollen ankles can occur.

    Removing the ovaries (oopherectomy). Removing the ovaries reduces the levels of the female hormone oestrogen. It has been tried more in the United States than in the United Kingdom. How helpful it is is uncertain.

    Tamoxifen. Tamoxifen blocks the effects of oestrogen and is sometimes used by people with breast cancer. Experience with this is even more limited.

    Hormones to reduce the release of oestrogen. These drugs are usually given by injection or by nasal spray. Experience is, again, limited.

    Treatment for kidney tumours

    
Some people with LAM have a benign tumour in the kidney (called an angiomyolipoma). Most kidney tumours in LAM are small, do not cause symptoms and do not need treatment. Occasionally, larger tumours cause pain or bleeding and may need to be treated. This is done either by removing the tumour with an operation or blocking its blood supply (embolisation) which causes it to shrink. Embolisation is done through a catheter and does not normally need a general anaesthetic. People recover more quickly from embolisation. It is not possible to treat all tumours in this way however and the procedure is not performed in all hospitals.

    LAM and tuberous sclerosis

    
Both the lung condition and the kidney tumours seen in LAM can occur in a small number of people with another disease, tuberous sclerosis. Tuberous sclerosis is generally associated with unusual skin changes, tumours in other organs and sometimes epilepsy (fits), learning and behavioural problems. There is a very important difference between tuberous sclerosis and LAM which is that tuberous sclerosis is inherited whereas LAM occurring on its own is not inherited. Most women with LAM do not have tuberous sclerosis and when tuberous sclerosis is present it is usually obvious from childhood. Very occasionally people with tuberous sclerosis have a limited form of the disease and few problems and the diagnosis may be overlooked for a time. For these reasons some women with LAM may need tests to ensure they do not have a mild form of tuberous sclerosis and LAM.

    Air travel

    Because air travel is associated with a fall in air pressure it can lead to problems with a pneumothorax. If you fly with a small pneumothorax this will become larger as the cabin pressure falls and this could lead to worsening breathlessness. Because LAM is associated with cysts in the lung there will be an increased risk of a pneumothorax developing during a flight. In a survey in the US 1 in 20 people with LAM had had a problem when flying although we don't know the nature of them. The risk is probably small for most people and whether it is acceptable or not depends on various individual factors, including your lung function and whether you have had an operation to stick the lung down.

    Further Information

    People with LAM often feel isolated and are unlikely to know anyone who has heard of LAM or who has the condition. LAM Action was set up as a self-help group and keeps a list of people who are happy and willing to talk to other people. The other function of the trust is to raise money for research.


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