LYMPHANGIOLEIOMYOMATOSIS: A REVIEW
Jisna K. Philip*, Tasnim Nazeer, Dr. Subash Chandran M. P, Dr. Karthika Lal B., Dr. Prashobh G. R.
Lymphangioleiomyomatosis (LAM) is a cystic lung disease. It is a multisystem disease of women. It is mainly reported in women of child bearing age, most commonly with dyspnea and pneumothorax. It is mainly characterized as proliferation of abnormal smooth muscle-like LAM cells, leading to the formation of lung cysts, fluid-filled cystic structures in the axial lymphatics (eg, lymphangioleiomyomas), and renal angiomyolipomas. The major cause of LAM mutations of the TSC1 or TSC2 genes, which encode for hamartin and tuberin, two proteins with a major role in control of the mammalian target of rapamycin (mTOR) signaling pathway. LAM may present with progressive dyspnea, recurrent pneumothorax, or chylothorax. It is extremely difficult to treat and has poor prognosis. Pulmonary function tests indicates reduced flow rates (forced expiratory volume in the first second) and diffusion capacity. Exercise testing shows gas exchange abnormalities, ventilatory limitation, and hypoxemia. Other test for finding out severity and progression of disease include lung histology scores, quantification of computed tomography, pulmonary function testing, 6-minute walk tests, cardiopulmonary exercise testing, and measurement of serum vascular endothelial growth factor D levels. Two mTOR inhibitors that are effective in stabilizing lung function and reducing the size of chylous effusions, lymphangioleiomyomas, and angiomyolipomas are Sirolimus and Everolimus. Combination of Sirolimus and hydroxychloroquine causes ihibition of autophagy and has been proposed as a possible treatment for LAM. Treatment with Simvastatin targets RhoA GTPases. It inhibits Rho GTPases and promotes apoptosis. This targets signaling pathways considered important in the pathogenesis of disease.
Keywords: lymphangioleiomyomatosis, dyspnoea, Sporadic LAM, TSC1 and TSC2 mutations, Sirolimus.
[Full Text Article]