Purpose of review: Lymphangioleiomyomatosis (LAM) is a rare but devastating disease, leading to chronic respiratory failure. Considerable progress for comprehension of the disease has been made when mutations of the tuberous sclerosis genes TSC1 and TSC2, were discovered in LAM cells. Therapeutic consequences of these studies are important, leading to clinical trials with sirolimus for LAM.
Recent findings: In two studies, angiomyolipoma size decreased by 26-50% after 12 months of sirolimus treatment. In a recent 12 months controlled trial involving 89 patients with pulmonary LAM, sirolimus stopped lung function decline and improved quality of life and performance score. The protective effect of sirolimus was lost after treatment discontinuation, with a parallel lung function decline in both groups, similar to the increase in angiomyolipoma size. Sirolimus is associated with an excess of adverse events.
Summary: Sirolimus represents an important drug for LAM that should be proposed to patients with a rapid alteration of lung function or with a significant clinical impairment, after individual evaluation of the risk/benefit ratio. Sirolimus seems to have a sharper effect on the reduction of abdominal masses than on lung cysts. Tolerance and safety concerns are serious limits to the long-term treatment of patients with sirolimus.