Management of LAM

Renal Angiomyolipoma

Kidney tumors called angiomyolipomas, unusual hamartomas containing fat, smooth muscle and blood vessels, are present in about 90% of patients with TSC and 30%-50% of sporadic LAM. Hemorrhage into an angiomyolipoma can produce symptoms from chronic intermittent flank pain to acute abdomen with hypovolemic shock.

In most patients, angiomyolipomas are clinically silent, however flank pain, hydronephrosis, hematuria and loss of renal function can all occur. In LAM patients without TSC, angiomyolipomas are usually unilateral, small, solitary, and restricted to the kidney while in LAM associated with TSC they are more often larger, bilateral, multiple, multi-organ involving the spleen or liver, and prone to hemorrhage. The risk of renal hemorrhage from angiomyolipomas is associated with large size and with profusion of aneurysms.

Click here to read article on Renal Angiomyolipomas by Drs. Bissler and Kingswood.

Pleural Complications in LAM

Pneumothoraces ultimately occur in approximately 60-70% of patients with LAM and the rate of recurrence is over 70%; the highest among all chronic lung diseases. The average number of subsequent pneumothoraces for those who have had a sentinel pneumothorax is 4.4. The average lifetime pneumothorax-related burden for LAM patients with a history of pneumothorax who responded to a LAM Foundation questionnaire was approximately 3.5 events, 5 interventions, one month in the hospital and $75,000 in estimated hospital costs. The recurrence rate following conservative therapy such as aspiration or chest tube drainage is about 66%, and following chemical or surgical pleurodesis are 27% and 32%, respectively. It is unclear why the recurrence rate following pleural fusion is so much higher for LAM than for other cystic lung diseases, such as Langerhan's cell histiocytosis, but it is possible that the remarkable profusion of cysts on the surface of the LAM lung prevents apposition and fusion of the lung and the parietal pleura. The LAM Foundation Pleural Disease Consensus Committee recommended ipsilateral pleurodesis with the initial pneumothorax in each hemithorax, although when surveyed patients often preferred a more conservative approach. Chylous pleural effusions occur in about one third of patients and may be unilateral or bilateral. Pleurodesis is generally an effective approach for chylothorax, but less invasive treatments such as thoracentesis or observation may suffice in some cases.

Explaining pleurodesis to your patients.

Lifestyle

Caring for Patients with Lymphangioleiomyomatosis (LAM)

As LAM is a very inconsistent disease with some patients remaining stable over many years and other declining more rapidly, may clinicians do not treat asymptomatic LAM patients with any specific therapy until it is clear that they have progressive disease.   Although patients with LAM have been managed empirically with anti-estrogen therapies, there is no proof that these strategies are effective and few physicians would now regularly start patients on hormonal treatment for LAM.  Progestins can cause fluid retention and mood swings, and the benefits of Gonadotropin-releasing hormone agonists are unproven. Induction of early menopause is distressing and morbid in young women. There is no proven role for corticosteroids, immunomodulatory cytoxic agents or ovarian irradiation in the treatment of LAM. Oophorectomy is no longer recommended because the benefits are unknown and the risk of bone and heart disease is increased. More recently evidence has been accumulating that drugs like sirolimus may prevent decline in lung function and possibly improve chylous complications in some patients.  At present, in the face of therapeutic uncertainty, the patient and physician should make all treatment decisions jointly, after thorough discussion of the risks and limited available data.

Role of Hormones in Women with LAM

Since LAM occurs almost exclusively in women of reproductive age, researchers believe the hormone, estrogen, might be involved in the abnormal muscle cell growth that characterizes the disease.  Although there is no direct evidence that there is a relationship between estrogen and LAM, the treatment of LAM has focused on reducing the production or effects of estrogen.  This could include progestins or other hormone suppressing drugs.  Additionally, doctors believe pregnancy may accelerate the progression of LAM.  The risk of pregnancy in LAM has not been rigorously studied. However, it is likely that pregnancy can increase the risk of pneumothorax occurring and these may be more difficult to treat.  Pregnancy may also be associated with the increased growth and bleeding in angiomyolipomas and possibly accelerated decline in lung function.  Although women with LAM may have successful pregnancies, pregnancy may be more of a risk for those with poor lung function.  The physician and patient should discuss the risks of pregnancy carefully and decisions should be made on an individual basis.

Previous treatments for LAM have been based on antagonism of estrogen action and are empiric, unproven and less used now. The most commonly employed treatment has been IM progesterone, which became the standard of care following a dramatic case report in 1987. Enthusiasm for the use of progestins has waned over time. In a recent retrospective analysis, Dr. Taveira-DaSilva et al found that progesterone treatment did not slow the decline in FEV1, and in fact, appeared to accelerate the rate of decline in diffusing capacity compared to untreated patients. Use of oral progestins or GnRh agonists has also been reported in case studies and small series, but neither has been assessed in clinical trials. There is no evidence that bilateral oophorectomy slows the rate of progression in LAM, and this therapy is much less commonly recommended than in the past. A trial of bronchodilator therapy should be considered as it may provide symptomatic benefit. Although abnormal bone density is common in women with LAM, progesterone therapy does not appear to accelerate the development of osteoporosis, and bisphosphonates are effective for this population.

Other Pulmonary Management Issues

Patients with LAM should avoid exposure to tobacco smoke.
Physicians also recommend that in LAM,like in other chronic lung diseases, patients may benefit from prophylactic vaccination against influenza (flu) and pneumococcus (a bacteria which causes pneumonia).  Most other vaccinations are safe in patients with LAM although those taking sirolimus should avoid ‘live’ vaccines.  
Based on data extrapolated from patients with COPD, it is likely that pulmonary rehabilitation, an exercise and education program tailored  to an individual patient’s needs, may improve exercise tolerance and feelings of breathlessness in patients with LAM.  Most pulmonary rehabilitation programs include graded aerobic and strength training and also educational sessions.  Although often aimed at those with COPD, pulmonary rehabilitation is likely to have similar benefits for patients with LAM.  

A trial of bronchodilators should be considered in those patients with LAM who have airway narrowing, seen in basic lung functioning tests. Based on extrapolation from the COPD populations, the use of oxygen may prolong life in hypoxic patients with LAM. Oxygen should be administered to maintain oxyhemoglobin saturations of greater than 90% with rest, exercise and sleep.

Bone Disease Management

Bone densitometry should be considered in all patients who are immobilized and/or on antiestrogen therapies. Calcium and bisphosphonate therapy should be considered in osteoporotic patients. Proper attention should be paid to cardiovascular health in patients who are rendered menopausal by therapy.

LAM and Airtravel

Many LAM patients have been advised to avoid air travel because of the theoretical risk of lung cyst rupture associated with atmospheric pressure changes during flight. In a questionnaire study of 276 patients who had taken 454 flights, Pollock-Bar Ziv et al found that air travel is generally well tolerated by most patients with LAM. Symptoms of anxiety, chest pain, shortness of breath, cyanosis or hemoptysis occurred in 10-20% of flights. Pneumothorax occurred in 10 flights, including eight episodes that were radiographically documented, but in five cases symptoms suggestive of pneumothorax were present prior to boarding. There have been no airtravel-associated incidents requiring hospitalization among the over 500 LAM patients who have participated in the decade-long NHLBI protocol, which has encouraged visits every six months. Airtravel, however, was not recommended to all patients.  If patients have a newly diagnosed pneumothorax, complete resolution for at least two weeks prior to flying is recommended based on expert opinion and limited available data.  In any patient with symptoms suggestive of a new pneumothorax, appropriate radiologic testing should be performed prior to air travel which based on available data may require a CT scan of the thorax as pneumothoraces may not always be seen on a chest Xray.