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Lymphangioleiomyomatosis

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Orphan Lung Diseases

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Abstract

Lymphangioleiomyomatosis (LAM) is a rare multisystem disease which predominantly affects women. The disease occurs both sporadically and is common in women with tuberous sclerosis complex (TSC). The molecular pathogenesis of LAM is the consequence of constitutive activation of the mechanistic target of rapamycin (mTOR) signalling node in a clone of cells. Termed LAM cells, they arise from an unknown source and accumulate in the lungs, lymphatics, and form angiomyolipomas. Women with LAM develop lung cysts which lead to pneumothorax, impaired gas transfer and airway obstruction. Lymphatic involvement leads to lymph node enlargement, cystic lymphatic masses and chylous collections. Clinical manifestations and presentation are variable between individuals ranging from dyspnoea or pneumothorax due to advanced lung disease to the incidental discovery of asymptomatic lung cysts or lymphatic disease. Rate of loss of lung function is also highly variable although tends to be more rapid in premenopausal women. The diagnosis is made by the presence of characteristic lung cysts on CT with the coexistence of angiomyolipoma, lymphatic disease, elevated serum vascular endothelial growth factor-D or TSC. If these features are not present, a lung biopsy may be necessary. Treatment includes management of pneumothorax, bronchodilators for airway obstruction, pulmonary rehabilitation and oxygen. For those with abnormal or falling lung function, chylous collections and other TSC-related problems mTOR inhibitors are effective and generally well tolerated. For some lung transplantation may be appropriate.

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Authors and Affiliations

  1. Translational Medical Sciences, Nottingham NIHR Biomedical Research Centre and Biodiscovery Institute, National Centre for Lymphangioleiomyomatosis, University of Nottingham, Nottingham, UK

    Simon R. Johnson

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  1. Simon R. Johnson
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Correspondence to Simon R. Johnson .

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Editors and Affiliations

  1. Department of Respiratory Medicine, National Coordinating Reference Centre for Rare Pulmonary Diseases (OrphaLung), Louis Pradel Hospital, University of Lyon, Lyon, France

    Vincent Cottin

  2. Fondazione Policlinico A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, Italy

    Luca Richeldi

  3. National Jewish Health, Denver, CO, USA

    Kevin Brown

  4. Division of Pulmonary, Critical Care, and Sleep Medicine Department of Internal Medicine, University of Cincinnati, Cincinnati, OH, USA

    Francis X. McCormack

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Johnson, S.R. (2023). Lymphangioleiomyomatosis. In: Cottin, V., Richeldi, L., Brown, K., McCormack, F.X. (eds) Orphan Lung Diseases. Springer, Cham. https://doi.org/10.1007/978-3-031-12950-6_19

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  • DOI: https://doi.org/10.1007/978-3-031-12950-6_19

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