Patient Care

LAM is a very heterogeneous disease with some patients remaining stable over many years and other declining more rapidly. Many clinicians do not treat asymptomatic LAM patients with any specific therapy until it is clear that they have progressive disease. In the face of the present therapeutic uncertainty, the patient and physician should make all treatment decisions jointly, after thorough discussion of the risks and limited available data.

Renal angiomyolipomaplus

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 patients with 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 LAMplus

Pneumothoraces occur in approximately 60-70% of patients with LAM and the rate of recurrence is over 70%. The average lifetime pneumothorax-related burden for LAM patients with a history of pneumothorax 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 pulmonary 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 recommends ipsilateral pleurodesis with the initial pneumothorax in each hemithorax. However, patients often prefer a more conservative approach towards pleural interventions aimed to prevent recurrence, thus a decision to pursue pleurodesis should be made jointly by the patient and treating clinician. It is important to note that prior pleurodesis is not a contraindication for future need for lung transplantation.

Chylous pleural effusions occur in about one third of patients and may be unilateral or bilateral. Small chylous effusions can usually be managed conservatively without requiring interventions. Shortness of breath may mandate drainage with a tube or catheter, and in some cases this may need to be repeated. Sirolimus is very effective at treating chylous pleural effusions and should be the first line of treatment for chylous effusions in patients with LAM. In refractory cases, imaging with heavy T2 weighted MRI sequences may help identify the site of chyle leakage.

Role of hormones and pregnancy in women with LAMplus

Since LAM occurs almost exclusively in women of reproductive age, researchers believe estrogen might be involved in the abnormal muscle cell growth that characterizes the disease. Based on this belief, various hormonal treatments such as progesterone, selective estrogen receptor modulators (SERMs), gonadotrophin release hormone (GnRH) agonists, oophorectomy, etc. have been tried for patients with LAM with varying results. At this time, there is not enough evidence to suggest a benefit from hormonal therapy in patients with LAM, and routine use of such therapies should be avoided.

It is clear, however, that excessive estrogen has a deleterious effect on disease progression and LAM, and thus exogenous estrogen supplementation should be avoided in patients with LAM. 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 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.

Other pulmonary management issuesplus

  • Patients with LAM should avoid exposure to tobacco smoke.
  • Patients should receive prophylactic vaccination against influenza (flu) and pneumococcus. Most other vaccinations are safe in patients with LAM, except the fact that patients on 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. In fact, in a recently conducted analysis in Brazil, pulmonary rehabilitation was found to be safe, and resulted in improved exercise capacity, dyspnea, daily physical activity, quality of life and muscle strength in patients with LAM.
  • A trial of bronchodilators should be considered in those patients with LAM who have airway obstruction, seen on lung function 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.
  • Lung function tests should be performed at regular intervals to monitor disease progression.

Bone disease managementplus

Bone densitometry should be considered in all patients who are immobilized and/or are on antiestrogen therapies. Calcium and bisphosphonate therapy should be considered in osteoporotic patients.

Cardiovascular healthplus

Proper attention should be paid to cardiovascular health in patients who are rendered menopausal by therapy.

LAM and air travelplus

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 to 20% of flights. Pneumothorax occurred in 10 flights, including eight episodes that were radiographically documented, but in five of these cases symptoms suggestive of pneumothorax were present prior to boarding. Based on data from two different studies, the pneumothorax risk for patients with LAM is 1-2% per flight. There have been no air travel-associated incidents requiring hospitalization among the over 500 LAM patients who have participated in the decade-long NHLBI protocol.

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 unexplained chest pain, shortness of breath, or symptoms suggestive of a new pneumothorax, appropriate radiologic testing should be performed prior to air travel.

Vaccinationsplus

Patients with LAM should remain up to date with appropriate vaccinations. Live vaccines should be avoided in patients taking immunosuppressive agents, so vaccination recommendations differ between LAM patients who are on mTOR inhibitors and those who are not, so we will consider these separately below.

For LAM patients who are NOT taking mTOR inhibitors, we recommend:

  1. 1. Annual influenza vaccination with the inactivated vaccine. Flumist (live attenuated influenza vaccine) is not recommended in LAM patients, because diffuse lung disease is a relative contraindication.
  2. Vaccination against pneumococcus:
    • All patients should receive Prevnar, one dose in lifetime; ideally given before Pneumovax, but at least 1 year after Pneumovax.
    • All patients should receive Pneumovax, one dose every 5 years; given at least 2 months after Prevnar.
  3. Shingles (H. Zoster) vaccination:
    • For those over age 60.
    • For those over age 50 who are about to begin mTOR inhibitor therapy, optimally at least 4 weeks prior to starting.
    • Since immunity only lasts 5 years, revaccination may be necessary (although not if on mTOR inhibitor therapy by that time).
  4. Hepatitis (A and B) vaccines: recommended for all patients
  5. Tetanus vaccine: recommended for all patients

In specials circumstances such as travel to areas of endemicity; other vaccines may be considered where applicable.

For LAM patients who ARE taking mTOR inhibitors, we recommend:

  1. Annual influenza vaccination with the inactivated vaccine. Flumist (live attenuated influenza vaccine) is not recommended in patients with LAM.
  2. Vaccination against pneumococcus:
    • All patients should receive Prevnar, one dose in lifetime; ideally given before Pneumovax, but at least 1 year after Pneumovax.
    • All patients should receive Pneumovax, one dose every 5 years; given at least 2 months after Prevnar.
  3. Shingles (H.Zoster) vaccination should NOT be given while on mTOR inhibitors:
    • Patients over age 50 who are about to begin mTOR inhibitor therapy should be vaccinated, optimally at least 4 weeks prior to starting.
    • Patients could be vaccinated during a hiatus in therapy with mTOR inhibitors, such as when they are held for upcoming surgery.
    • A new zoster subunit vaccine that would be appropriate for use in patients on mTOR inhibitors is under development (Cunningham, A.L. NEJM 2016) and may be available soon.
  4. Hepatitis (A and B) vaccines: recommended for all patients.
  5. Tetanus vaccine: recommended for all patients.
  6. Avoid other live virus vaccines:
    • Measles, mumps, rubella
    • Oral polio
    • Smallpox
    • Rotavirus
    • Yellow fever
    • Rabies

Table 2 summarizing recommendations for patient on mTOR inhibitors

In specials circumstances such as travel to areas of endemicity; other vaccines may be considered where applicable.

General Comments:

Inactivated or recombinant flu vaccines (i.e. the injectable types of flu vaccine that your physician will offer to you) should not be used in anyone with prior severe allergy without consulting an allergist, and should be used with caution in: patients with moderate or severe acute illness with or without fever, history of Guillain-Barré syndrome within 6 weeks of previous influenza vaccination, people with egg allergy (hives only allergy can be mitigated with additional safety measures).

Minor illnesses (such as diarrhea, mild upper respiratory infection with or without low-grade fever, other low-grade febrile illness) are not contraindications to vaccination. Adults with egg allergy of any severity can receive inactivated vaccines with the same indications as those without egg allergy, since the new preparations contain much smaller quantities of egg products.

Contraindications to Pneumovax and Prevnar include severe prior allergic reaction, and moderate or severe acute illness. Patients with a documented true allergic reaction (rather than a history of egg allergy) to Prevnar or Pneumovax should seek the advice of an allergist.

Although inactivated and recombinant flu and pneumococcal vaccinations can result in soreness and low grade fever and muscle aches, they cannot produce flu or pneumonia.

There is a growing literature suggesting that patients on low dose immunosuppression (such as low dose sirolimus) can take shingles vaccine safely, but further studies are needed before this recommendation can be made.

Information provided by:
Frank McCormack, MD
Scientific Director, The LAM Foundation

Senu Apewokin, MD
Infectious Disease, University of Cincinnati Medical Center