Lymphangioleiomyomatosis

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Lymphangioleiomyomatosis
Classification and external resources
Lymphangioleiomyomatosis.jpg
Figure A shows the location of the lungs and airways in the body. The inset image shows a cross-section of a healthy lung. Figure B shows a view of the lungs with LAM and a collapsed lung (pneumothorax). The inset image shows a cross-section of a lung with LAM.
ICD-9 516.4
ICD-O: 9174/1
OMIM 606690
DiseasesDB 30755
eMedicine med/1348 radio/415
MeSH D018192

Lymphangioleiomyomatosis (LAM) is a rare lung disease that results in a proliferation of disorderly smooth muscle growth (leiomyoma) throughout the lungs, in the bronchioles, alveolar septa, perivascular spaces, and lymphatics, resulting in the obstruction of small airways (leading to pulmonary cyst formation and pneumothorax) and lymphatics (leading to chylous pleural effusion). LAM occurs in a sporadic form, which affects only females, usually of childbearing age; LAM also occurs in patients who have tuberous sclerosis.

Signs and symptoms[edit]

Symptoms of LAM may include:[1][2]

Symptoms are more likely in women, with average age at onset 34 years. Symptoms may precede radiographic abnormalities.[3]

Causes[edit]

The proliferating smooth muscle that occurs in the type of LAM seen in patients with tuberous sclerosis (TSC-LAM) has been shown to represent clones of the smooth muscle in those patients' renal angiomyolipomas. Thus it is believed to represent metastases of this "benign" tumor. There is a female preponderance to TSC-LAM.[2][4]

Investigations[edit]

Investigations may include:

  • Spirometry studies, which may include an increased FVC, with a decreased FEV1/FVC ratio.[3]
  • High-Resolution CT, which may demonstrate an interstitial pattern with cystic changes [5]
  • Vascular endothelial growth factor D, which is typically elevated.

Diagnosis[edit]

Micrograph of lymphangioleiomyomatosis. H&E stain.
CT scan of the lungs in a patient with lymphangioleiomyomatose showing numerous thin walled cysts within the lungs.

In patients with typical cystic changes on high resolution CT scanning serum levels of vascular endothelial growth factor-D greater than 800 pg/ml are considered to be diagnostic for LAM.[5]

A lung biopsy may also be necessary to make a diagnosis. Video-assisted thoracoscopic biopsy is the most definitive and widely used technique, but transbronchial biopsy can also be effective [6][7]

In some cases, the diagnosis of LAM can be made with confidence on clinical grounds (without biopsy) in patients with typical cystic changes on high resolution CT scanning of the lung and findings of tuberous sclerosis, angiomyolipoma or chylothorax[1]

Serum VEGF-D concentration has been shown to be a biologically plausible and useful biomarker in lymphangioleiomyomatosis that correlates with disease severity and treatment response. [8]

Treatment[edit]

LAM may be treated with a number of therapies.[9]

Anti-estrogen therapy. This may include use of tamoxifen or surgical removal of the ovaries. Other drugs may include progesterone or GnRH agonists. This therapy has been in use since the 1980s, and was developed in light of reports of LAM worsening during pregnancy.[1][2] None of these therapies has been shown to be clearly efficacious, and all have undesirable side-effects. There is some evidence which shows that tamoxifen may actually cause worsening of LAM in some patients.[9]

Sirolimus. Sirolimus is an antiproliferative and immunosuppressant interleukin-2 inhibitor that is used in some patients with LAM. Unlike anti-estrogen therapy, Sirolimus has statistically significant efficacy, improving quality of life in mild-to-moderately severe LAM patients.[10]

Lung transplantation may be considered when pulmonary function has sufficiently deteriorated. Following lung transplant, LAM patients have Kaplan-Meier estimators (survival curves) similar to other lung transplant patients. Although LAM has been reported to recur in the transplanted lung [1], there have been no reported cases of graft failure or death due to recurrence.[citation needed] LAM-specific complications may occur secondary to transplantation, include pneumothorax secondary to a ruptured cyst, chylothorax, LAM recurrence, and abdominal complications.[which?][1][11] General transplant-related may include bacterial, viral and fungal lung infections, and rejection of the lung, including graft-versus-host disease and host-versus-graft disease.[3]

A chylothorax should be managed conservatively. Surgical interventions may be pursued, including pleural abrasion, pleurodesis and pleurectomy, however these should be avoided in early stages of the disease, as intervention may impact on future lung transplantation.[2][9]

A single case report of an apparent response of LAM to Doxycycline has recently been reported.[12] However, this therapy has not been proven in a clinical trial.

Prognosis[edit]

10-year survival figures range from 49-79%,[3] with LAM believed to be progressive, ultimately leading to respiratory failure. High reported survival may stem from improvements in diagnosis, allowing for earlier diagnosis of LAM at a less severe stage. Thus survival differences may not reflect changes in treatment, but rather earlier diagnosis.[2] There are women who have survived LAM for more than 30 years, and continue to survive, according to The LAM Foundation.

Epidemiology[edit]

LAM almost always affects women, with only a handful of cases reported in men.[citation needed] The first of these was in a man with tuberous sclerosis, reported in 2000 from the Mayo Clinic by a team led by Henry Tazelaar[13]

See also[edit]

References[edit]

  1. ^ a b c d Johnson, SR; Cordier, JF, Lazor, R, Cottin, V, Costabel, U, Harari, S, Reynaud-Gaubert, M, Boehler, A, Brauner, M, Popper, H, Bonetti, F, Kingswood, C, Review Panel of the ERS LAM Task, Force (January 2010). "European Respiratory Society guidelines for the diagnosis and management of lymphangioleiomyomatosis.". The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology 35 (1): 14–26. doi:10.1183/09031936.00076209. PMID 20044458. 
  2. ^ a b c d e Yu, J; Astrinidis, A; Howard, S; Henske, EP (April 2004). "Estradiol and tamoxifen stimulate LAM-associated angiomyolipoma cell growth and activate both genomic and nongenomic signaling pathways.". American journal of physiology. Lung cellular and molecular physiology 286 (4): L694–700. doi:10.1152/ajplung.00204.2003. PMID 12922981. 
  3. ^ a b c d Pallisa, E; Sanz, P; Roman, A; Majó, J; Andreu, J; Cáceres, J (October 2002). "Lymphangioleiomyomatosis: pulmonary and abdominal findings with pathologic correlation.". Radiographics : a review publication of the Radiological Society of North America, Inc. 22 Spec No: S185–98. doi:10.1148/radiographics.22.suppl_1.g02oc13s185. PMID 12376610. 
  4. ^ Clemm, C; Jehn, U; Wolf-Hornung, B; Siemon, G; Walter, G (Apr 15, 1987). "Lymphangiomyomatosis: a report of three cases treated with tamoxifen.". Klinische Wochenschrift 65 (8): 391–3. doi:10.1007/BF01745582. PMID 3586575. 
  5. ^ a b Young, LR; Vandyke, R; Gulleman, PM; Inoue, Y; Brown, KK; Schmidt, LS; Linehan, WM; Hajjar, F; Kinder, BW; Trapnell, BC; Bissler, JJ; Franz, DN; McCormack, FX (September 2010). "Serum vascular endothelial growth factor-D prospectively distinguishes lymphangioleiomyomatosis from other diseases.". Chest 138 (3): 674–81. doi:10.1378/chest.10-0573. PMC 2940071. PMID 20382711. 
  6. ^ Ye, L; Jin, M; Bai, C (October 2010). "Clinical analysis of patients with pulmonary lymphangioleiomyomatosis (PLAM) in mainland China.". Respiratory medicine 104 (10): 1521–6. doi:10.1016/j.rmed.2010.05.003. PMID 20627505. 
  7. ^ Torre, O; Harari, S (July 2010). "The diagnosis of cystic lung diseases: a role for bronchoalveolar lavage and transbronchial biopsy?". Respiratory medicine. 104 Suppl 1: S81–5. doi:10.1016/j.rmed.2010.03.021. PMID 20430602. 
  8. ^ Young, L; Lee HS, Inoue Y, Moss J, Singer LG, Strange C, Nakata K, Barker AF, Chapman JT, Brantly ML, Stocks JM, Brown KK, Lynch JP 3rd, Goldberg HJ, Downey GP, Swigris JJ, Taveira-DaSilva AM, Krischer JP, Trapnell BC, McCormack FX; MILES Trial Group. (Aug 2013). "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 6: 445–452. doi:10.1016/S2213-2600(13)70090-0. PMID 24159565. 
  9. ^ a b c Clemm C, Jehn U, Wolf-Hornung B, Siemon G, Walter G (Apr 1987). "Lymphangiomyomatosis: a report of three cases treated with tamoxifen". Klin Wochenschr 65 (8): 391–3. doi:10.1007/BF01745582. PMID 3586575. 
  10. ^ McCormack, FX; Inoue, Y; Moss, J; Singer, LG; Strange, C; Nakata, K; Barker, AF; Chapman, JT; Brantly, ML; Stocks, JM; Brown, KK; Lynch JP, 3rd; Goldberg, HJ; Young, LR; Kinder, BW; Downey, GP; Sullivan, EJ; Colby, TV; McKay, RT; Cohen, MM; Korbee, L; Taveira-DaSilva, AM; Lee, HS; Krischer, JP; Trapnell, BC; National Institutes of Health Rare Lung Diseases, Consortium; MILES Trial, Group (Apr 28, 2011). "Efficacy and safety of sirolimus in lymphangioleiomyomatosis.". The New England Journal of Medicine 364 (17): 1595–606. doi:10.1056/NEJMoa1100391. PMC 3118601. PMID 21410393. 
  11. ^ Boehler, A; Speich, R; Russi, EW; Weder, W (Oct 24, 1996). "Lung transplantation for lymphangioleiomyomatosis.". The New England Journal of Medicine 335 (17): 1275–80. doi:10.1056/NEJM199610243351704. PMID 8857007. 
  12. ^ Moses, MA; Harper, J; Folkman, J (2006-06-15). "Doxycycline treatment for lymphangioleiomyomatosis with urinary monitoring for MMPs.". The New England Journal of Medicine 354 (24): 2621–2. doi:10.1056/NEJMc053410. PMID 16775248. 
  13. ^ Aubry, MC; Myers, JL; Ryu, JH; Henske, EP; Logginidou, H; Jalal, SM; Tazelaar, HD (August 2000). "Pulmonary lymphangioleiomyomatosis in a man.". American Journal of Respiratory and Critical Care Medicine 162 (2 Pt 1): 749–52. doi:10.1164/ajrccm.162.2.9911006. PMID 10934115. 

External links[edit]