Lymphangioleiomyomatosis

Abstract

Lymphangioleiomyomatosis (LAM) is a progressive lung disease of unknown cause which affects women. The disease occurs in isolation (sporadic LAM) with a prevalence of 1-2 per million and in approximately 40% of adult women with tuberous sclerosis complex (TSC). LAM is characterised by invasion of the lungs and axial lymphatics by smooth muscle like cells termed LAM cells which have mutations in TSC1 or more commonly TSC2 resulting in activation of mTOR, abnormal cellular growth and migration. LAM commonly presents with dyspnoea and pneumothorax. Diagnosis is generally made by the finding of thin walled cysts on CT scanning or
-smooth muscle actin and HMB45 positive cells on lung biopsy. LAM is characterised by progressive airflow obstruction and impaired gas transfer. Patients develop progressive dyspnoea,most have recurrent pneumothorax and some chylous effusions: survival is 76-90% at 10 years. Forty percent of patients have renal angiomyolipomas, benign tumours which should be screened for. LAM patients should receive influenza and pneumococcal vaccination, pulmonary rehabilitation and avoid oestrogen containing medications. Treatment is predominantly supportive with oxygen, bronchodilators and sometimes lung transplantation. Pleural complications are frequently recurrent and may need surgical treatment at an early stage. Although antioestrogen therapies are commonly used, there is no evidence base to support their efficacy. Progesterone therapy should only be considered in patients with poor or rapidly declining lung function. Currently, inhibitors of mTOR show promise in laboratory models and are in clinical trials.