eMedicine Specialties > Pulmonology > Idiopathic Lung Disorders

Lymphangioleiomyomatosis: Treatment & Medication

Author: Joel Moss, MD, PhD, Deputy Chief, Translational Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health
Coauthor(s): John A Kelly, MB, BCh, MD, Assistant Professor of Medicine and Micro-Immunology, Dartmouth Medical School; Staff Pulmonologist, White River Junction Veterans Affairs Medical Center
Contributor Information and Disclosures

Updated: Nov 19, 2008

Treatment

Medical Care

  • General care for lymphangioleiomyomatosis (LAM)
    • Pleural effusions - 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)
    • Pulmonary dysfunction - General pulmonary care (eg, vaccines), bronchodilators (+/- benefit), supplemental oxygen, pulmonary rehabilitation
    • Lung transplantation4
  • Hormonal manipulation
    • Medroxyprogesterone - Utility not known, recent case series does not support use
    • Gonadotropin-releasing hormone agonists - Utility not known, few case reports support use
    • Tamoxifen not recommended
    • Oophorectomy not thought to be effective based on recent case series
  • New experimental therapies
    • Rapamycin-initial trials in AML, now being investigated as a therapy in pulmonary LAM
    • Doxycycline-anti-angiogenic, antibiotic and matrix effects
    • Octreotide

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.
  • Consider lung transplantation for patients with end-stage pulmonary disease.
  • The Medscape Transplantation Specialty Center may be helpful.

Consultations

  • Pulmonologist
    • Pulmonologist helps establish the diagnosis and monitor pulmonary function.
    • A pulmonologist can address issues such as vaccinations, oxygen therapy, and pulmonary rehabilitation.
    • Depending on disease severity, referral to a transplant center may be beneficial. Consider patient referral to a center with an interest in LAM.
  • Endocrinologist and/or obstetrician-gynecologist
    • These specialists may help to address the hormonal issues involved, particularly when considering hormonal manipulation.
    • An endocrinologist can assist with prophylaxis and treatment of osteoporosis in patients in whom exogenous ER is contraindicated.
  • A urologist may assist with renal AML management.
  • A dietitian may help to consult patients on MCT diets for chylous ascites or pleural effusions.
  • Consider referral to specialist center.

Diet

  • Most patients with LAM do not have special dietary requirements; however, if a patient is on therapies to lower ER or is postmenopausal and not on ER replacement therapy, address other cardiac risk factors (eg, cholesterol levels).
  • Some patients with chylous effusions or ascites may try an MCT diet (see Medical Care).

Activity

  • Although the literature is sparse with regard to activities that can cause barotrauma in patients with LAM, theoretical concern exists regarding certain activities such as flying, particularly in patients with LAM and a history of prior pneumothorax.
  • Reports show pregnancy exacerbating the disease; therefore, specialists generally recommend that patients with LAM avoid becoming pregnant. However, some patients with mild disease have had a normal pregnancy with little deterioration in lung function.

Medication

The goals of pharmacotherapy for lymphangioleiomyomatosis (LAM) are to reduce morbidity and to prevent complications.

Rapamycin: The TSC genes are believed to regulate a protein, called mammalian target of rapamycin (mTOR), which is known to control cell growth and proliferation. Rapamycin inhibits the activity of mTOR. In a phase I/II clinical trial, use of rapamycin was associated with a reduction in size of renal AMLs. A second clinical trial is underway looking at the effect of rapamycin on pulmonary function.

Doxycycline: Doxycycline, a drug with antibiotic, anti-angiogenic, and anti-MMP activities is being tested for its ability to improve pulmonary function in LAM.

Progestins

Because LAM is predominantly a disease of premenopausal women, researchers hypothesize that hormones, especially ERs, play a pathogenic role. A recent retrospective review of LAM does not support the use of progestins in the disease.


Medroxyprogesterone acetate (Provera, Depo-Provera)

A derivative of progesterone. Reports describe stabilization or occasional improvement with progesterone therapy, especially in the presence of chylous effusions or ascites; however, data supporting its use in LAM are not strong.

Adult

400-1600 mg IM qmo
20-60 mg PO qd

Pediatric

Not established

Aminoglutethimide can depress serum levels of medroxyprogesterone acetate; the following laboratory tests can be affected: plasma and urine steroid levels, certain coagulation levels, protein-bound iodine, and certain thyroid function tests

Documented hypersensitivity; cerebral apoplexy; pregnancy; breast malignancy; undiagnosed vaginal bleeding; thrombophlebitis; liver dysfunction

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

Perform a pretreatment breast and pelvic examinations; weight gain and/or fluid retention can occur; caution in patients with history of depression or seizures; observe patients diagnosed with diabetes for deterioration in glucose tolerance; perform liver function tests and bone density determinations; caution in asthma, renal or cardiac dysfunction, or thromboembolic disorders
Avoid in patients with meningioma

More on Lymphangioleiomyomatosis

Overview: Lymphangioleiomyomatosis
Differential Diagnoses & Workup: Lymphangioleiomyomatosis
Treatment & Medication: Lymphangioleiomyomatosis
Follow-up: Lymphangioleiomyomatosis
References
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References

  1. Carsillo T, Astrinidis A, Henske EP. Mutations in the tuberous sclerosis complex gene TSC2 are a cause of sporadic pulmonary lymphangioleiomyomatosis. Proc Natl Acad Sci U S A. May 23 2000;97(11):6085-90. [Medline].

  2. 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. Apr 1998;62(4):810-5. [Medline].

  3. Bonetti F, Chiodera PL, Pea M, Martignoni G, Bosi F, Zamboni G, et al. Transbronchial biopsy in lymphangiomyomatosis of the lung. HMB45 for diagnosis. Am J Surg Pathol. Nov 1993;17(11):1092-102. [Medline].

  4. Boehler A, Speich R, Russi EW, Weder W. Lung transplantation for lymphangioleiomyomatosis. N Engl J Med. Oct 24 1996;335(17):1275-80. [Medline].

  5. Kitaichi M, Nishimura K, Itoh H, Izumi T. Pulmonary lymphangioleiomyomatosis: a report of 46 patients including a clinicopathologic study of prognostic factors. Am J Respir Crit Care Med. Feb 1995;151(2 Pt 1):527-33. [Medline].

  6. Adema GJ, de Boer AJ, Vogel AM, Loenen WA, Figdor CG. Molecular characterization of the melanocyte lineage-specific antigen gp100. J Biol Chem. Aug 5 1994;269(31):20126-33. [Medline].

  7. Bonetti F, Pea M, Martignoni G, Zamboni G, Iuzzolino P. Cellular heterogeneity in lymphangiomyomatosis of the lung. Hum Pathol. Jul 1991;22(7):727-8. [Medline].

  8. Corrin B, Liebow AA, Friedman PJ. Pulmonary lymphangiomyomatosis. A review. Am J Pathol. May 1975;79(2):348-82. [Medline].

  9. Eliasson AH, Phillips YY, Tenholder MF. Treatment of lymphangioleiomyomatosis. A meta-analysis. Chest. Dec 1989;96(6):1352-5. [Medline].

  10. Kalassian KG, Doyle R, Kao P, Ruoss S, Raffin TA. Lymphangioleiomyomatosis: new insights. Am J Respir Crit Care Med. Apr 1997;155(4):1183-6. [Medline].

  11. Moss J. LAM and Other Diseases Characterized by Smooth Muscle Proliferation. ed. New York, NY: Marcel Decker; 1999.

  12. Moss J, DeCastro R, Patronas NJ, Taveira-DaSilva A. Meningiomas in lymphangioleiomyomatosis. JAMA. Oct 17 2001;286(15):1879-81. [Medline].

  13. Ryu JH, Moss J, Beck GJ, Lee JC, Brown KK, Chapman JT, et al. The NHLBI lymphangioleiomyomatosis registry: characteristics of 230 patients at enrollment. Am J Respir Crit Care Med. Jan 1 2006;173(1):105-11. [Medline].

  14. Steagall WK, Glasgow CG, Hathaway OM, Avila NA, Taveira-Dasilva AM, Rabel A, et al. Genetic and Morphologic Determinants of Pneumothorax in Lymphangioleiomyomatosis. Am J Physiol Lung Cell Mol Physiol. Jul 6 2007;[Medline].

  15. Steagall WK, Taveira-DaSilva AM, Moss J. Clinical and molecular insights into lymphangioleiomyomatosis. Sarcoidosis Vasc Diffuse Lung Dis. Dec 2005;22 Suppl 1:S49-66. [Medline].

  16. Taveira-DaSilva AM, Stylianou MP, Hedin CJ, Hathaway O, Moss J. Decline in lung function in patients with lymphangioleiomyomatosis treated with or without progesterone. Chest. Dec 2004;126(6):1867-74. [Medline].

  17. Taylor JR, Ryu J, Colby TV, Raffin TA. Lymphangioleiomyomatosis. Clinical course in 32 patients. N Engl J Med. Nov 1 1990;323(18):1254-60. [Medline].

  18. Urban T, Kuttenn F, Gompel A, Marsac J, Lacronique J. Pulmonary lymphangiomyomatosis. Follow-up and long-term outcome with antiestrogen therapy; a report of eight cases. Chest. Aug 1992;102(2):472-6. [Medline].

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Further Reading

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Keywords

LAM, progressive pulmonary dysfunction, abdominal tumors, angiomyolipomas, AML, abdominal mass, tuberous sclerosis, TSC, pulmonary disease, pneumothorax, lung disease, lung transplantation, lymphangioleiomyomatosis, LAM cell, lung cysts

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Contributor Information and Disclosures

Author

Joel Moss, MD, PhD, Deputy Chief, Translational Medicine 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 Society for Biochemistry and Molecular Biology, American Society for Clinical Investigation, American Thoracic Society, Association of American Physicians, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Coauthor(s)

John A Kelly, MB, BCh, MD, Assistant Professor of Medicine and Micro-Immunology, Dartmouth Medical School; Staff Pulmonologist, White River Junction Veterans Affairs Medical Center
John A Kelly, MB, BCh, MD is a member of the following medical societies: American Association of Immunologists, American College of Chest Physicians, and American Thoracic Society
Disclosure: Nothing to disclose.

Medical Editor

Ryland P Byrd Jr, MD, Professor, Department of Internal Medicine, Division of Pulmonary Medicine and Critical Care Medicine, James H Quillen College of Medicine, East Tennessee State University; Chief of Pulmonary Medicine, Medical Director of Respiratory Therapy, Intensive Care Unit, Program Director of Pulmonary Diseases and Critical Care Medicine Fellowship, James H Quillen Veterans Affairs Medical Center
Ryland P Byrd Jr, MD is a member of the following medical societies: American College of Chest Physicians, American Thoracic Society, and Southern Medical Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Harold L Manning, MD, Associate 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, and American Thoracic Society
Disclosure: Nothing to disclose.

CME Editor

Timothy D Rice, MD, Associate Professor, Departments of Internal Medicine and Pediatrics and Adolescent Medicine, Saint Louis University School of Medicine
Timothy D Rice, MD is a member of the following medical societies: American Academy of Pediatrics and American College of Physicians
Disclosure: Nothing to disclose.

Chief Editor

Zab Mosenifar, MD, Director, Division of Pulmonary and Critical Care Medicine, Director, Women's Guild Pulmonary Disease Institute, Executive Vice Chair, Department of Medicine, Cedars Sinai Medical Center; Professor of Medicine, David Geffen School of Medicine at UCLA
Zab Mosenifar, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, and American Thoracic Society
Disclosure: Nothing to disclose.

 
 
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