Lymphangioleiomyomatosis

Author: Joel Moss MD PhD Deputy Chief, Translational Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health

Coauthor: John A Kelly MB BCh MD Assistant Professor of Medicine and Micro-Immunology, Dartmouth Medical School; Staff Pulmonologist, White River Junction Veterans Affairs Medical Center

Nov 19, 2008

Background

Lymphangioleiomyomatosis (LAM) is a rare disorder resulting from proliferation in the lung, kidney, and axial lymphatics of a neoplastic cell having a smooth muscle cell phenotype (LAM cell). Cystic destruction of the lung with progressive pulmonary dysfunction and the presence of abdominal tumors (eg angiomyolipomas [AML], lymphangioleiomyomas) characterize the disease. Because this condition typically occurs in premenopausal women, involvement of the female hormones in disease pathogenesis is a current hypothesis.

Pathophysiology

Lymphangioleiomyomatosis (LAM) cell proliferation may obstruct bronchioles, possibly leading to airflow obstruction, air trapping, formation of bullae, and pneumothoraces. Obstruction of lymphatics may result in chylothorax and chylous ascites. Obstruction of venules may result in hemosiderosis and hemoptysis. Excessive proteolytic activity, which relates to an imbalance of the elastase/alpha1-antitrypsin system or metalloprotease (MMPs) and their inhibitors (tissue inhibitors of metalloproteases [TIMPS]) may be important in lung destruction and formation of cystlike lesions.

Frequency in the USA

The frequency of Lymphangioleiomyomatosis (LAM) is unknown. To date, more than 500 cases exist in the United States. As the disease becomes better recognized because of increased awareness and better diagnostic techniques, the prevalence may increase.

Mortality/Morbidity

Earlier reports indicate a grim prognosis with progressive respiratory failure and death within 10 years of diagnosis. Recent reports are more favourable, with 78% of patients who are affected alive at 8.5 years. The statistics may improve further as patients are diagnosed earlier (lead time bias) or with more benign disease.

Race

No racial predilection for LAM exists.

Sex

LAM primarily is a disease of women; however, rare case reports of LAM in men exist, primarily in men with tuberous sclerosis complex, an inherited disorder having shared features with LAM.

Age

Although primarily a disease of women of childbearing age, LAM has been reported in patients aged 12 years to patients older than 70 years. Some of the latter patients have been on hormone replacement therapy.

Clinical

History

• Common lymphangioleiomyomatosis (LAM) symptoms
  • Dyspnea
  • Manifestations of pneumothorax
  • Cough
• Less common symptoms
  • Chest pain
  • Chylothorax
  • Chyluria
  • Pericardial effusion
  • Pneumoperitoneum
  • Lymphedema
• Exacerbations of LAM are described during pregnancy, menstruation, and estrogen (ER) use.

Physical

• Lymphangioleiomyomatosis (LAM) examination usually normal
• Less common findings
  • Crackles
  • Wheezes
  • Clubbing
  • Pleural effusion
  • Pneumothorax
  • Ascites
• Signs of tuberous sclerosis
  • Facial angiofibromas
  • Ungual fibromas
  • Hypomelanotic macules, ash-leaf spot
  • Shagreen patch, a cluster of hamartoma typically located on the lower back
  • Forehead plaque
  • Retinal hamartoma

Causes

• The etiology of lymphangioleiomyomatosis (LAM) is unknown; however, the fact that the condition occurs primarily in women who are premenopausal and is exacerbated by high ER states suggests a role for hormones in this condition.
• The link with tuberous sclerosis (TSC) suggests a genetic component.