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LAM

Home ▶ Patients ▶ Lung Disease Week at the ATS ▶ 2020 ▶ LAM ▶ General Information


General Information

lam

Lymphangioleiomyomatosis (LAM) is a rare disease that mostly afflicts young women. LAM is a multi-system disorder that commonly affects both the lungs and kidneys.  LAM can occur in two settings, either as part of tuberous sclerosis complex (TSC-LAM) or in a sporadic form in women who do not have TSC (sporadic LAM or S-LAM).  Both S-LAM and TSC-LAM are associated with mutations in the tuberous sclerosis genes (TSC1 or TSC2).  Deficiencies of the encoded proteins, hamartin or tuberin, result in loss of cell regulation ultimately leading to inappropriate cellular proliferation, migration and invasion.  Patients with TSC-LAM have a germline mutation in a TSC gene present in all cells of their body (i.e. “first hit”) and LAM develops when a “second hit” somatic TSC mutation occurs.  In patients with S-LAM, both the first hit and the second hit TSC mutations are confined to the lung, kidney and lymph nodes. 

LAM patients typically develop pulmonary cysts which can be associated with rather rapid lung function decline. Other manifestations of the disease include renal angiomyolipomas, chylous effusions, lymphangioleiomyomas and abdominal/retroperitoneal lymphadenopathy.  For some patients, the diagnosis is made after presenting with a pneumothorax which is a common complication due to the pulmonary cyst formation.  In the presence of compatible CT findings, other manifestations of the disease including angiomyolipomas, chylous effusions, lymphangioleomyomas, history of tuberous sclerosis complex and elevated serum vascular endothelial growth factor – D (VEGF-D) can increase certainty of the diagnosis.  In the absence of such confirmatory features, lung biopsy may be required to confirm the diagnosis.

Treatment strategies for LAM currently consist of mTOR (mechanistic target of rapamycin) pathway inhibitors such as sirolimus.  Sirolimus has documented efficacy in reducing the size of angiomyolipomas and slowing lung function decline.  In patients with severe disease, lung transplantation may be a viable option.  Research is ongoing to better understand the disease pathogenesis and develop additional pharmacotherapeutic options for patients.

Source:

Meilan Han, MD, MS
Professor of Medicine
Division of Pulmonary and Critical Care
University of Michigan

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 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. The discovery of a genetic link between LAM and tuberous sclerosis complex, another rare disease, leads scientists to estimate that more than 250,000 women worldwide are unaware they have LAM.