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lymphangioleiomyomatosis

Monday 4 March 2013

Pulmonary lymphangioleiomyomatosis

WP

Definition: Lymphangioleiomyomatosis (LAM) is a rare lung disease that results in a proliferation of disorderly smooth muscle growth (leiomyoma) throughout the lungs, in the bronchioles, alveolar septa, perivascular spaces, and lymphatics, resulting in the obstruction of small airways (leading to pulmonary cyst formation and pneumothorax) and lymphatics (leading to chylous pleural effusion).

LAM occurs in a sporadic form, which affects only females, usually of childbearing age; LAM also occurs in patients who have tuberous sclerosis.

Sporadic LAM almost always affects women. Only a handful of cases have occurred in men. The first of these was in a man with tuberous sclerosis, reported in 2000.

TSC-associated LAM

The proliferating smooth muscle that occurs in the type of LAM seen in patients with tuberous sclerosis (TSC-associated LAM) has been shown to represent clones of the smooth muscle in those patients’ renal angiomyolipomas. Thus it is believed to represent metastases of this "benign" tumor.

There is a female preponderance to TSC-LAM. LAM occurs almost exclusively in women.

Clinical synopsis

The average age at onset of symptoms is approximately 34 years. The first symptoms of the disease can occur before an abnormality is detectable with chest plain radiographs or pulmonary function tests; even when such abnormalities exist, the disease may be initially misdiagnosed. There is often a delay between the onset of symptoms and correct diagnosis.

LAM commonly manifests as exertional dyspnea and recurrent pneumothorax. During the course of the illness, there may be nonproductive cough, hemoptysis, chylous pleural effusion, or chylous ascites.

Obstruction of pulmonary venules causes vascular congestion and hemoptysis, and lymphatic obstruction leads to chylothorax and chylous ascites.

Prognosis

The clinical course of patients with LAM shows considerable variation. The disease is believed to be slowly progressive, leading to respiratory failure and death. The 10-year survival from the start of symptoms in a study was 49%, although reported figures range from an 8.5-year survival probability of 38% to a 10-year survival of 79%.

Differences in survival rates may be due to improvements in diagnosis, particularly regarding the contribution of high-resolution CT, and do not mean that the progression of the disease has changed substantially. Diagnosis of mild asymptomatic forms may also have contributed to the longer survival rates.

Treatment and management

In light of the reports of clinical worsening of the disease during pregnancy and with use of exogenous estrogens, many clinicians have applied therapeutic hormone manipulation.

Antiestrogen therapy, first used in the early 1980s, consists of surgical castration by oophorectomy or administration of tamoxifen, progesterone, and gonadotropin-releasing hormone agonist or luteinizing hormone–releasing hormone.

Several studies have reported beneficial effects of antiestrogen hormone therapies for LAM, but careful scrutiny of some of these studies reveals that the treatment improved the chylothorax or chylous ascites, whereas pulmonary involvement seemed to remain stationary or to progress.

Since lung transplantation has become available for patients with poor response to therapies, certain treatments must be used with caution.

In fact, castration does not clearly demonstrate a beneficial effect on the course of the disease, and the long-term effects of castration, particularly in the postoperative period of lung transplantation, can increase bone complications.

In most cases, chylothorax should be managed conservatively. Chylothorax usually appears early in the course of the disease, when the patient’s functional status is good.

Early application of surgical techniques such as pleural abrasion, pleurodesis, or pleurectomy must be avoided because these treatments might limit future lung transplantation. Medical treatment includes tamoxifen, progesterone, and, in some cases, a low-fat diet.

When the patient’s functional status declines, bilateral lung transplantation is the best therapeutic option.

The guidelines indicating transplantation include progression despite medical treatment, forced expiratory volume in 1 second (FEV1)/forced vital capacity ratio of less than 50%, total lung capacity of greater than 130%, and FEV1 of less than 30%. In the largest published series of lung transplantations in LAM patients, the average FEV1 at the time of evaluation for the procedure was 24%.

Common postoperative complications of lung transplantation are bacterial, viral, and fungal infections; acute rejection episodes; and chronic rejection.

Complications specific to LAM are pneumothorax of the native lung after single-lung transplantation, chylothorax, recurrence of LAM, and abdominal complications