Lymphangioleiomyomatosis Treatment & Management
- Author: Joel Moss, MD, PhD; Chief Editor: Zab Mosenifar, MD, FACP, FCCP more...
General care for patients with lymphangioleiomyomatosis (LAM) addresses the following findings :
- 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 ; supplemental oxygen, pulmonary rehabilitation, smoking cessation
- Standard vaccination for respiratory infections
- Osteoporosis - Standard surveillance and treatment; avoid exogenous estrogens
- 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.[28, 29, 30, 31]
- 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.
Possible options for hormonal manipulation include the following:
- Medroxyprogesterone - Utility not known; recent case series does not support its use
- Gonadotropin-releasing hormone agonists - Utility not known; few case reports support their use
- Tamoxifen does not appear to be effective 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)
New experimental therapies include the following:
- Chloroquine - Inhibitor of autophagy
- Aromatase inhibitors - Antiestrogenic effects
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.
Consider lung transplantation for patients with end-stage pulmonary disease.
The Medscape Transplantation Specialty Center may be helpful.
Pulmonologists help 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 transplantation center may be beneficial.
Consider patient referral to a center with expertise in lymphangioleiomyomatosis (LAM).
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 MCT diets for chylous ascites or pleural effusions.
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 MCT diet (see Medical Care).
Despite the theoretical risk of pneumothorax in patients with lymphangioleiomyomatosis (LAM), studies show no increased risk, even in patients with a prior history.
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.
Ferrans VJ, Yu ZX, Nelson WK, Valencia JC, Tatsuguchi A, Avila NA, et al. Lymphangioleiomyomatosis (LAM): a review of clinical and morphological features. J Nihon Med Sch. 2000 Oct. 67(5):311-29. [Medline].
Moss J. LAM and Other Diseases Characterized by Smooth Muscle Proliferation. 1st ed. New York, NY: Marcel Decker; 1999.
Hayashi T, Fleming MV, Stetler-Stevenson WG, Liotta LA, Moss J, Ferrans VJ, et al. Immunohistochemical study of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in pulmonary lymphangioleiomyomatosis (LAM). Hum Pathol. 1997 Sep. 28(9):1071-8. [Medline].
Yu JJ, Robb VA, Morrison TA, Ariazi EA, Karbowniczek M, Astrinidis A, et al. Estrogen promotes the survival and pulmonary metastasis of tuberin-null cells. Proc Natl Acad Sci U S A. 2009 Feb 24. 106(8):2635-40. [Medline]. [Full Text].
Meraj R, Wikenheiser-Brokamp KA, Young LR, McCormack FX. Lymphangioleiomyomatosis: new concepts in pathogenesis, diagnosis, and treatment. Semin Respir Crit Care Med. 2012 Oct. 33(5):486-97. [Medline].
Harknett EC, Chang WY, Byrnes S, Johnson J, Lazor R, Cohen MM, et al. Use of variability in national and regional data to estimate the prevalence of lymphangioleiomyomatosis. QJM. 2011 Nov. 104(11):971-9. [Medline].
Matsui K, Beasley MB, Nelson WK, Barnes PM, Bechtle J, Falk R, et al. Prognostic significance of pulmonary lymphangioleiomyomatosis histologic score. Am J Surg Pathol. 2001 Apr. 25(4):479-84. [Medline].
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. 2006 Jan 1. 173(1):105-11. [Medline].
Oberstein EM, Fleming LE, Gomez-Marin O, Glassberg MK. Pulmonary lymphangioleiomyomatosis (LAM): examining oral contraceptive pills and the onset of disease. J Womens Health (Larchmt). 2003 Jan-Feb. 12(1):81-5. [Medline].
Crino PB, Nathanson KL, Henske EP. The tuberous sclerosis complex. N Engl J Med. 2006 Sep 28. 355(13):1345-56. [Medline].
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. 2000 May 23. 97(11):6085-90. [Medline].
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. [Medline].
Young LR, Vandyke R, Gulleman PM, Inoue Y, Brown KK, Schmidt LS, et al. Serum vascular endothelial growth factor-D prospectively distinguishes lymphangioleiomyomatosis from other diseases. Chest. 2010 Sep. 138(3):674-81. [Medline]. [Full Text].
Young L, Lee HS, Inoue Y, Moss J, Singer LG, et al. Serum VEGF-D a concentration as a biomarker of lymphangioleiomyomatosis severity and treatment response: a prospective analysis of the Multicenter International Lymphangioleiomyomatosis Efficacy of Sirolimus (MILES) trial. Lancet Respir Med. 2013 Aug. 1(6):445-52. [Medline]. [Full Text].
Glasgow CG, Avila NA, Lin JP, Stylianou MP, Moss J. Serum vascular endothelial growth factor-D levels in patients with lymphangioleiomyomatosis reflect lymphatic involvement. Chest. 2009 May. 135(5):1293-300. [Medline]. [Full Text].
Moss J, DeCastro R, Patronas NJ, Taveira-DaSilva A. Meningiomas in lymphangioleiomyomatosis. JAMA. 2001 Oct 17. 286(15):1879-81. [Medline].
Taveira-Dasilva AM, Stylianou MP, Hedin CJ, Hathaway O, Moss J. Bone mineral density in lymphangioleiomyomatosis. Am J Respir Crit Care Med. 2005 Jan 1. 171(1):61-7. [Medline].
Taylor JR, Ryu J, Colby TV, Raffin TA. Lymphangioleiomyomatosis. Clinical course in 32 patients. N Engl J Med. 1990 Nov 1. 323(18):1254-60. [Medline].
Taveira-DaSilva AM, Stylianou MP, Hedin CJ, Kristof AS, Avila NA, Rabel A, et al. Maximal oxygen uptake and severity of disease in lymphangioleiomyomatosis. Am J Respir Crit Care Med. 2003 Dec 15. 168(12):1427-31. [Medline].
Harari S, Torre O, Cassandro R, Taveira-DaSilva AM, Moss J. Bronchoscopic diagnosis of Langerhans cell histiocytosis and lymphangioleiomyomatosis. Respir Med. 2012 Sep. 106(9):1286-92. [Medline]. [Full Text].
Adema GJ, de Boer AJ, Vogel AM, Loenen WA, Figdor CG. Molecular characterization of the melanocyte lineage-specific antigen gp100. J Biol Chem. 1994 Aug 5. 269(31):20126-33. [Medline].
[Guideline] Johnson, S.R.; Cordier, J.F.; Lazor, R.; Cottin, V.; Costabel, U.; Harari, et al. European Respiratory Society guidelines for the diagnosis and management of lymphangioleiomyomatosis. Eur.Respir J. 01/2010. 35:14-26. [Medline].
Bonetti F, Pea M, Martignoni G, Zamboni G, Iuzzolino P. Cellular heterogeneity in lymphangiomyomatosis of the lung. Hum Pathol. 1991 Jul. 22(7):727-8. [Medline].
Taveira-DaSilva AM, Hedin C, Stylianou MP, Travis WD, Matsui K, Ferrans VJ, et al. Reversible airflow obstruction, proliferation of abnormal smooth muscle cells, and impairment of gas exchange as predictors of outcome in lymphangioleiomyomatosis. Am J Respir Crit Care Med. 2001 Sep 15. 164(6):1072-6. [Medline].
Boehler A, Speich R, Russi EW, Weder W. Lung transplantation for lymphangioleiomyomatosis. N Engl J Med. 1996 Oct 24. 335(17):1275-80. [Medline].
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. 2004 Dec. 126(6):1867-74. [Medline].
McCormack FX, Inoue Y, Moss J, Singer LG, Strange C, Nakata K, et al. Efficacy and safety of sirolimus in lymphangioleiomyomatosis. N Engl J Med. 2011 Apr 28. 364(17):1595-606. [Medline]. [Full Text].
Bissler JJ, McCormack FX, Young LR, Elwing JM, Chuck G, Leonard JM, et al. Sirolimus for angiomyolipoma in tuberous sclerosis complex or lymphangioleiomyomatosis. N Engl J Med. 2008 Jan 10. 358(2):140-51. [Medline].
Taveira-DaSilva AM, Hathaway O, Stylianou M, Moss J. Changes in lung function and chylous effusions in patients with lymphangioleiomyomatosis treated with sirolimus. Ann Intern Med. 2011 Jun 21. 154(12):797-805, W-292-3. [Medline]. [Full Text].
Davies DM, de Vries PJ, Johnson SR, McCartney DL, Cox JA, Serra AL, et al. Sirolimus therapy for angiomyolipoma in tuberous sclerosis and sporadic lymphangioleiomyomatosis: a phase 2 trial. Clin Cancer Res. 2011 Jun 15. 17(12):4071-81. [Medline].
Williams JM, Racadio JM, Johnson ND, Donnelly LF, Bissler JJ. Embolization of renal angiomyolipomata in patients with tuberous sclerosis complex. Am J Kidney Dis. 2006 Jan. 47(1):95-102. [Medline].
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. 1995 Feb. 151(2 Pt 1):527-33. [Medline].