LAM

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General Information

LAM Week

What is Lymphangioleiomyomatosis (LAM)?

LAM is a progressive cystic lung disease typically manifesting in women of reproductive age.  LAM can be either sporadic or associated with tuberous sclerosis complex (TSC).  LAM involves smooth muscle proliferation that contributes to parenchymal cysts formation in the lungs.  While LAM is considered an interstitial lung disease, clinically, it is essentially a cystic lung disease and shares significant physiological features of emphysema including bilateral multiple cysts and airflow obstruction. Mutations in the TSC1 and TSC2 genes have been implicated in LAM, but TSC2 mutations are the predominant mutation in sporadic LAM.

Who is at risk?

LAM primarily occurs in women of childbearing age, the few case reports of LAM in men are likely to have TSC rather than true LAM.  Estrogen appears to play a role since the onset of disease is typically after menarche.  The average age of diagnosis is around 35 years old and it is unknown if there is a racial predilection.  The prevalence has been estimated around 3.4-7.8 cases per million women. 

What are the symptoms of LAM?

The presenting symptoms can be non-specific including fatigue, cough, hemoptysis and chest pain.  In some reports, nearly half the patients present with dyspnea and/or spontaneous pneumothorax.   Due to the non-specific nature of the symptoms, diagnosis is often delayed for approximately 5 years after symptom onset.  Chylous fluid accumulation is also commonly noted.  Extrapulmonary manifestations include angiomyolipomas of the kidney and meningiomas.  Pregnancy and the use of oral contraceptive pills have been implicated in the progression of LAM.

How is LAM diagnosed?

Diagnosis typically requires surgical lung biopsy for pathologic confirmation.  HMB-45 staining is highly specific for LAM.  However, in the setting of the appropriate clinical features (such as a young female who presents with recurrent pneumothoraxes), the diagnosis can be established based on the high resolution computed tomography (HRCT) images.  These characteristic HRCT findings include relatively uniform sized (~ 2cms) thin wall cysts lungs in both lungs.  Recently, serum vascular endothelial growth factor D (VEGF-D) levels have been studied as a possible screening test for LAM.  A level greater than 800 pg/ml achieved 100 percent specificity in one study.

What is the prognosis and management of LAM?

The management of LAM has typically centered around supportive care including avoidance of estrogen therapy and supplemental oxygen if needed.  Bronchodilator therapy may provide symptomatic benefit in patients with airflow obstruction. The mTOR inhibitor, sirolimus, has now been approved by the US Food and Drug Administration for treatment of moderate to severe pulmonary LAM.  Sirolimus has been shown to slow the rate of disease progression. 

LAM is a progressive disease and patients with advanced disease may benefit from lung transplantation.  However, the median transplant free survival time has been reported as 29 years from symptom onset.  There have been reports of several complications post lung-transplant including recurrent LAM in the transplanted allograft.

What are complications or special considerations for LAM?

Pregnancy has been reported to lead to exacerbations of LAM and decisions about family planning and pregnancies should be made on an individual basis.  While pneumothoraces have been associated with air travel, the literature suggests that air travel is well tolerated by most patients. Chylothorax may occur due to rupture of the lymphatics or obstruction of the thoracic duct.  Management of a chylothorax can be difficult and include dietary modifications, pleurodesis or thoracic duct ligation. 

References:

  1. McCormack FX. Lymphangioleiomyomatosis: a clinical update. Chest. 2008Feb;133(2):507-16. Review. PubMed PMID: 18252917.

  2. Henske EP, McCormack FX.  Lymphangioleiomyomatosis –a wolf in sheep's clothing.  J Clin Invest.  2012:122(11):3807-3816.


Four Facts About LAM

  1. Lymphangioleiomyomatosis (LAM) is a progressive disease that predominantly affects women, especially during the prime of their lives.  Symptoms may include shortness of breath, collapsed lung, chest pain, cough, fatigue and in 40% of patients one or more benign kidney tumors called angiomyolipomas.

  2. Women with LAM may be misdiagnosed with asthma, emphysema, or bronchitis. The diagnosis of LAM can most often be made without surgical lung biopsy using a combination of high resolution CT imaging of the lungs and abdomen, clinical signs and symptoms, serum VEGF-D levels and sometimes transbronchial biopsy.

  3. In May of 2015, the FDA approved Sirolimus as a proven therapy for LAM that can stabilize lung function and improve some measures of quality of life and functional performance. Lung transplant remains the option of last resort for patients with advanced disease.

  4. Median survival in patients with LAM has varied from 10 to 30 years. Most patients have dyspnea on exertion with daily activities by 10 years after symptom onset and many will require supplemental oxygen over that interval.

Last Reviewed: March 2016