Lymphangioleiomyomatosis: a clinical review

Abstract

Lymphangioleiomyomatosis (LAM) is a diffuse cystic lung disease. There are two main types of LAM: sporadic, and LAM associated with the tuberous sclerosis complex (TSC), which is caused by mutations in the TSC1 and TSC2 genes. LAM is characterised by cystic lung disease resulting in progressive dyspnoea, renal angiomyolipomas and lymphatic complications. Pneumothorax occurs frequently (70%) and definitive management with pleurodesis is recommended as the risk of recurrence is high. Characteristic thin-walled cysts are seen on computed tomography and the presence of elevated serum levels of a vascular endothelial growth factor-D has good diagnostic specificity. Currently, no single clinical or serological factor has been shown to predict prognosis. However, over the past decade, significant advances in our understanding of the pathophysiology of LAM has led to improved recognition of this rare disease and identification of treatment options. Mechanistic target of rapamycin inhibitors slow the rate of lung function decline and can resolve chylous effusion and regress angiomyolipomas. Life expectancy in patients with LAM is favourable, with a mean transplant-free survival >20 years from the time of diagnosis. Continued advances in understanding the molecular basis of LAM will lead to improved therapeutic targets and the development of more robust prognostic indicators.Educational aimsTo illustrate the clinical features, common presentations and radiological features of LAMTo outline the diagnostic approach to LAM, including the role of VEGF-DTo review the current prognostic indicators in LAM, and outline the impact of lung function, hormonal status, VEGF-D and clinical presentation on outcomeTo inform clinicians on the management options for LAM both pharmacological and nonpharmacological

Long-term clinical course and progression of lymphangioleiomyomatosis in a single lung transplant referral centre in Korea

“…The efficacy of sirolimus has been demonstrated in patients with predicted FEV 1 value of 70% or less 8 , and with symptomatic chylothorax 11 . Other studies have suggested that patients with rapidly declining FEV 1 , reduced DL CO , exercise-induced or resting hypoxemia, angiomyolipomas or lymphangioleiomyomas might benefit from sirolimus 21 , 22 .…”

“…These patients, comprising nearly one-third of the study population, were associated with good baseline lung function, menopause at diagnosis, and absence of abdominal lymphadenopathy (Supplementary Table S3 ). Clinical manifestations of LAM are highly heterogeneous 21 . As seen in our study population (Supplementary Fig.…”

Lung cancer is also a hereditary disease

“…Lymphangioleiomyomatosis (LAM) is a diffuse cystic lung disease predominantly affecting females of reproductive age [65]. It is sometimes associated with the tuberous sclerosis complex (TSC), which is caused by germline pathogenic variants in the TSC1 and TSC2 genes [65].…”

“…Lymphangioleiomyomatosis (LAM) is a diffuse cystic lung disease predominantly affecting females of reproductive age [65]. It is sometimes associated with the tuberous sclerosis complex (TSC), which is caused by germline pathogenic variants in the TSC1 and TSC2 genes [65]. LAM is characterised by small thin-walled cysts throughout the lungs resulting in progressive dyspnoea and renal angiomyolipomas [64,65].…”

“…It is sometimes associated with the tuberous sclerosis complex (TSC), which is caused by germline pathogenic variants in the TSC1 and TSC2 genes [65]. LAM is characterised by small thin-walled cysts throughout the lungs resulting in progressive dyspnoea and renal angiomyolipomas [64,65]. Pneumothorax occurs frequently.…”