Approach Considerations

General care for patients with lymphangioleiomyomatosis (LAM) addresses the following findings^[13]:

Pleural effusions - Consider chemical pleurodesis; surgical obliteration of the pleural space; medium-chain triglyceride (MCT [not a component of chyle]), lipid-free diet to reduce chyle flow (utility unknown)
Ascites - Paracentesis, MCT diet (utility unknown)
Airways disease and hypoxemia - Bronchodilators may be of benefit^[16]; supplemental oxygen, pulmonary rehabilitation, smoking cessation
Standard vaccination for respiratory infections
Osteoporosis - Standard surveillance and treatment; avoid exogenous estrogens^[30]
Lung transplantation^[36]

Some reports suggest worsening of disease during pregnancy. Therefore, specialists generally recommend that caution be exercised when patients consider becoming pregnant. Despite the potential hazards, patients with mild disease have had uneventful pregnancies with little deterioration in lung function.

Sirolimus

In May 2015, sirolimus (Rapamune) was the first drug approved by the US FDA for LAM. It has demonstrated improvement in lung function in patients with LAM. Sirolimus also reduces the size of angiomyolipomas, lymphangioleiomyomas, and chylous effusions. The therapeutic response, however, is generally not sustained.^{[37, 38, 39, 40]}

A clinical trial of 89 patients over 12 months showed patients taking Rapamune had a slower decline in lung function than those taking a placebo. After the drug was stopped, the decline in lung function resumed at the same rate as the placebo group.^[37]

Hormone therapy

Possible options for hormonal manipulation include the following:

Medroxyprogesterone - Utility not known; recent case series does not support its use^[41]
Gonadotropin-releasing hormone agonists - Utility not known; few case reports support their use
Tamoxifen does not appear to be effective^[31]and is not recommended due to estrogen receptor agonist activity
Rate of decline in lung function trends to be less in postmenopausal women (eg, surgical oophorectomy, age)

Novel therapies

New experimental therapies include the following:

Chloroquine - Inhibitor of autophagy
Aromatase inhibitors - Antiestrogenic effects

Everolimus, an oral mTOR inhibitor, has been investigated as a treatment of renal angiomyolipoma associated with TSC or sporadic LAM.^[42]A 4-year double-blind, placebo-controlled, phase 3 follow-up trial showed reduction in angiomyolipoma volume in 54% of patients.^[19]During the extension phase of the study, 58% of patients achieved angiomyolipoma response. The most common adverse events reported were stomatitis (42%), hypercholesterolemia (30.4%), acne (25.9%), aphthous stomatitis and nasopharyngitis (each 21.4%).^[18]

Surgical Care

Management of recurrent pneumothoraces or pleural effusions may require surgical intervention; in addition, patients with AML can develop complications (eg, hemorrhage), requiring intervention. Arterial embolization is favored over surgical resection.^[43]

Consider lung transplantation for patients with end-stage pulmonary disease.

The Medscape Transplantation Specialty Center may be helpful.

Consultations

Pulmonologists can help establish the diagnosis and monitor pulmonary function. A pulmonologist can address issues such as vaccinations, oxygen therapy, and pulmonary rehabilitation. Consider patient referral to a center with expertise in lymphangioleiomyomatosis (LAM). Depending on disease severity, referral to a transplantation center may be beneficial.

AN endocrinologist and/or obstetrician-gynecologist may help address issues involved in hormonal manipulation therapy. An endocrinologist can assist with prophylaxis and treatment of osteoporosis in patients in whom exogenous estrogen is contraindicated. A urologist may assist with management of renal AML.

A dietitian may help to advise patients on medium chain triglyceride (MCT) diets for chylous ascites or pleural effusions.

Diet

Most patients with lymphangioleiomyomatosis (LAM) do not have special dietary requirements; however, if a patient is on antiestrogen therapies or is postmenopausal and not on estrogen replacement therapy, other cardiac risk factors relevant to diet (eg, cholesterol levels) should be addressed.

Although the use of rapamycin is favored, some patients with chylous effusions or ascites may try an medium chain triglyceride (MCT) diet (see Medical Care).

Activity

LAM is associated with reduced bone mineral density and osteoporosis. Weight-bearing exercise and strength training should be encouraged.^[13]

Guidelines

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Kalassian KG, Berry GJ, Raffin TA. Lymphangioleiomyomatosis: clinical aspects. Moss J, ed. LAM and Other Diseases Characterized by Smooth Muscle Proliferation. New York, NY: Marcel Dekker; 1999. 45-60.
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Smolarek TA, Wessner LL, McCormack FX, Mylet JC, Menon AG, Henske EP. Evidence that lymphangiomyomatosis is caused by TSC2 mutations: chromosome 16p13 loss of heterozygosity in angiomyolipomas and lymph nodes from women with lymphangiomyomatosis. Am J Hum Genet. 1998 Apr. 62(4):810-5. [QxMD MEDLINE Link]. [Full Text].
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Author

Joel Moss, MD, PhD Deputy Chief, Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health

Joel Moss, MD, PhD is a member of the following medical societies: Alpha Omega Alpha, American College of Chest Physicians, American Society for Clinical Investigation, American Society for Biochemistry and Molecular Biology, American Thoracic Society, Association of American Physicians, Phi Beta Kappa

Disclosure: Nothing to disclose.

Coauthor(s)

Arnold S Kristof, MDCM, FRCPC Associate Professor of Medicine, Department of Medicine, Respiratory and Critical Care Divisions, Associate Member, Department of Microbiology and Immunology, Research Director, Meakins-Christie Laboratories, McGill University Faculty of Medicine; Attending Physician, Respiratory and Critical Care Divisions, McGill University Health Centre, Royal Victoria Hospital, Canada

Arnold S Kristof, MDCM, FRCPC is a member of the following medical societies: American College of Chest Physicians, American Society for Biochemistry and Molecular Biology, American Thoracic Society, Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Harold L Manning, MD Professor, Departments of Medicine, Anesthesiology and Physiology, Section of Pulmonary and Critical Care Medicine, Dartmouth Medical School

Harold L Manning, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Thoracic Society

Disclosure: Nothing to disclose.

Chief Editor

Zab Mosenifar, MD, FACP, FCCP Geri and Richard Brawerman Chair in Pulmonary and Critical Care Medicine, Professor and Executive Vice Chairman, Department of Medicine, Medical Director, Women's Guild Lung Institute, Cedars Sinai Medical Center, University of California, Los Angeles, David Geffen School of Medicine

Zab Mosenifar, MD, FACP, FCCP is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, American Thoracic Society

Disclosure: Nothing to disclose.

Acknowledgements

John A Kelly, MB, BCh, MD † Assistant Professor of Medicine and Microbiology and Immunology, Dartmouth Medical School; Staff Pulmonologist, White River Junction Veterans Affairs Medical Center.

Acknowledgments

This work was supported in part by the Division of Intramural Research, National Institutes of Health, National Heart, Lung, and Blood Institute (J.M.) as well as National Institutes of Health R01-CA125436, Tuberous Sclerosis Alliance, LAM Foundation, LAM Canada (A.K.).