What is the management of Lymphangioleiomyomatosis (LAM)?

Management of Lymphangioleiomyomatosis (LAM)

For patients with LAM and abnormal or declining lung function, treat with sirolimus rather than observation; this is a strong recommendation that can stabilize lung function and prevent progressive respiratory decline. 1

Pharmacological Treatment

Sirolimus (mTOR Inhibitor) - Primary Therapy

• Sirolimus is the only evidence-based pharmacological treatment for LAM and should be initiated in patients with abnormal or declining lung function. 1
• The drug works by inhibiting the constitutively activated mTOR pathway that drives LAM cell proliferation. 2
• Sirolimus has been shown to slow the rate of lung function decline in clinical trials. 3
• For patients with problematic chylous effusions (chylothorax or chylous ascites), sirolimus should be tried before proceeding to invasive management. 1
• Sirolimus can also regress renal angiomyolipomas, which occur in 30-50% of LAM patients. 2, 3

Therapies to AVOID

• Do NOT use hormonal therapies including progestins, GnRH agonists, tamoxifen, or oophorectomy—these lack evidence of effectiveness. 1, 2
• Do NOT use doxycycline as treatment for LAM. 1

Management of Pneumothorax

• Pneumothorax occurs in approximately 70% of LAM patients and has a high recurrence risk. 3
• Offer pleurodesis after the first pneumothorax rather than waiting for recurrence. 4
• This aggressive approach is justified given the high recurrence rate in LAM. 4
• Pleurodesis should NOT be used as a reason to exclude patients from lung transplantation eligibility. 4

Supportive Care Measures

Respiratory Management

• Use bronchodilators for airflow obstruction. 2
• Provide supplemental oxygen therapy for hypoxemia. 2
• Monitor lung function regularly to detect decline that would warrant sirolimus initiation. 2

Management of Renal Angiomyolipomas

• Screen for renal angiomyolipomas, which occur in 30-50% of patients. 2
• Interventional treatment may be needed for symptomatic or enlarging lesions. 2
• Sirolimus can cause regression of angiomyolipomas. 2, 3

Lymphatic Complications

• Manage chylothorax and chylous ascites with sirolimus before considering invasive procedures. 1
• These complications result from lymphatic obstruction by LAM cells. 2

Monitoring and Follow-up

• Disease progression varies significantly between individuals—some experience rapid decline while others remain stable for years. 2
• Regular pulmonary function testing is essential to detect declining lung function that would trigger sirolimus therapy. 2
• Monitor for development of pneumothorax, chylous effusions, and progression of angiomyolipomas. 2
• Screen patients with tuberous sclerosis complex (TSC), as 30-40% of adult females with TSC develop LAM. 2

Lung Transplantation

• Consider lung transplantation for patients with end-stage respiratory failure despite medical management. 5
• Mean transplant-free survival exceeds 20 years from diagnosis, indicating generally favorable prognosis. 3
• Prior pleurodesis should not disqualify patients from transplant consideration. 4

Key Clinical Pitfalls to Avoid

• Do not delay sirolimus in patients with documented lung function decline—early intervention can stabilize disease. 1
• Do not use hormonal manipulation strategies—despite the disease predominantly affecting women and worsening during high estrogen states, hormonal therapies are ineffective. 1, 2
• Do not wait for recurrent pneumothorax before offering pleurodesis—the first pneumothorax warrants definitive management. 4
• Do not assume all cystic lung diseases are LAM—confirm diagnosis with VEGF-D testing, characteristic imaging, or tissue biopsy when clinical features are incomplete. 1