Lymphangioleiomyomatosis: what is this disease, symptoms, treatment, prognosis

What is lymphangioleiomyomatosis?

Lymphangioleiomyomatosis (LAM) Is a rare progressive multisystem disorder that predominantly affects women of childbearing age. Occurs in women with tuberous sclerosisas well as in women who do not have this hereditary genetic disorder. LAM is characterized by the proliferation and uncontrolled growth (proliferation) of specialized cells (LAM cells, like smooth muscle) in certain organs of the body, especially the lungs, kidneys, and lymphatics nodes.

Common symptoms associated with lymphangioleiomyomatosis include coughing and / or shortness of breath (shortness of breath), especially after periods of physical exertion. People may also experience complications, including collapsed lung or fluid accumulation around the lungs (pleural effusion). The disorder is progressive and, in some cases, can lead to chronic respiratory failure.

Signs and symptoms

Symptoms of lymphangioleiomyomatosis vary from case to case. The specific symptoms depend on which organs are affected by the LAM cells. In most cases, the initial symptoms are mild and include shortness of breath, especially with exertion. Sufferers may also experience episodes of chest pain, coughing, wheezing, and coughing up a little blood (hemoptysis).

Some people may experience a buildup of fluid (such as chyle) in the chest cavity around the lungs (pleural effusion). Chyle is a cloudy liquid saturated with fat that is absorbed during digestion by the lymphatic vessels located around the intestines. Chyle usually flows through the lymphatic vessels into the upper chest (thoracic duct) and then is deposited in the veins where it mixes with blood. In some people with LAM, the lymphatic vessels may rupture or become blocked (clogged), resulting in a build-up of chyle in the chest cavity (chylothorax). In some cases, chyle can build up in the abdomen, causing bloating, a condition called chyle ascites. Axial lymph node involvement can also lead to the formation of lymphangioleiomas, chyle-filled lymphatic structures inside the chest and abdomen.

Some people with LAM may experience non-trauma-related lung collapse (spontaneous pneumothorax). Symptoms of a collapsed lung may include:

• sudden, sharp chest pain;
• shortness of breath (tachypnea);
• cardiopalmus (tachycardia);
• low blood pressure (hypotension);
• profuse sweating;
• dizziness.

In some patients, the collapse of the lung may recur.

Approximately 50 percent of people with lymphangioleiomyomatosis develop angiomyolipomas, which are benign tumors composed of fat, blood vessels, and cells similar to smooth muscles. These tumors affect the kidneys or abdomen and often cause no symptoms (asymptomatic). In some cases, they can cause flank pain, blood in urine (hematuria) or bleeding into the abdomen (bleeding into the abdomen).

Symptoms of lymphangioleiomyomatosis can progressively worsen as LAM cells continue to proliferate, eventually leading to chronic life-threatening respiratory failure. LAM symptoms often get worse during pregnancy. Many LAM cases are associated with osteoporosis, a condition characterized by progressive thinning of the bones.

Causes and risk factors

The exact cause of lymphangioleiomyomatosis is not known. Since the disease occurs almost exclusively in women of reproductive age, there may be a link between female hormones (i.e. e. estrogen and progesterone) and LAM.

Some scientists are studying the link between a rare genetic disorder known as tuberous sclerosis complex (TSC) and LAM. Approximately 30 percent of women with CTS have evidence of pulmonary lymphangioleiomyomatosis, suggesting that these disorders may have a common cause or origin. The tuberous sclerosis complex is caused by mutations in one of two genes known as the TSC1 gene or the TSC2 gene.

Recently, research has shown that some people with LAM who do not have CTS have somatic mutations (for example, mutations that occur in peripheral tissues after conception) in the TSC2 gene. These mutations were not found in blood, normal lung cells, or normal kidney cells in affected individuals. These data suggest that mutations in the TSC genes are the cause of LAM even in women who do not have the inherited TSC disorder.

Symptoms associated with lymphangioleiomyomatosis occur due to the spread and accumulation (proliferation) of LAM cells in various organs of the body, especially in the lungs. This abnormal spread leads to the formation of cysts as well as obstruction of the affected airways, blood vessels, and lymph vessels. Infiltration of the lungs with LAM cells can lead to progressive breathing difficulties, collapse of the lungs, and interference with the lungs' ability to deliver oxygen to the rest of the body.

Obstruction of blood vessels can lead to bleeding in the lungs (pulmonary hemorrhage) and coughing up blood (hemoptysis). Obstruction of the lymphatic vessels can lead to chylous effusions and ascites. Lymphatic vessels are part of the lymphatic system, blood vessels, ducts and nodes that filter and distribute lymphatic and blood cells throughout the body. Lymph is a fluid that circulates through the body to cleanse and strengthen tissues. After fulfilling its functions, lymph is drained through the lymphatic system.

Affected populations

LAM is a rare disease that predominantly affects women of childbearing age. The average age of those affected at the time of symptom onset is 33 years. More than 400 cases have been reported in the medical literature in the United States since Dr. von Stossel first described the disorder in 1937. It is estimated that over 1,000 women in the United States alone may have LAM. Many researchers believe that the disorder is underdiagnosed, making it difficult to determine its true frequency in the general population. The Tuberculosis Sclerosis Association recommends screening women with tuberculous sclerosis at least once upon reaching maturity.

Related disorders

Symptoms of the following disorders may be similar to those of LAM. Comparisons can be useful for differential diagnosis:

There are several obstructive lung diseases, which can cause symptoms similar to LAM. However, these diseases such as emphysema, asthma and chronic obstructive bronchitiscan be excluded by laboratory tests and X-ray studies.

• Tuberous sclerosis is a rare genetic multisystem disorder that usually manifests itself shortly after birth, but can occur in adulthood. The disorder may be characterized by episodes of uncontrolled electrical activity in the brain (epilepsy); mental retardation; distinctive skin disorders; and benign (noncancerous) tumor-like nodules (hamartomas) in the brain, specific areas of the eyes (eg, the retina), heart, kidneys, lungs, or other tissues or organs. In addition, many affected people may have cyst-like formations in certain skeletal areas, especially in the bones of the fingers and toes (phalanges). Characteristic skin lesions include sharply delineated areas of reduced skin coloration (hypopigmentation) that can develop into infancy, and relatively small, reddish nodules that may appear on the cheeks and nose, starting at about four years. These reddish lesions eventually enlarge, mix (coalesce) and form a warty appearance (sebaceous adenomas). Additional skin lesions may also develop, including flat, coffee-colored areas of increased skin pigmentation; Benign, fibrous nodules (fibroids) that occur around or under your nails or rough, raised, "uneven" lesions (shagreens) on the lower back. About 30 percent of people with tuberous sclerosis develop pulmonary lymphangioleiomyomatosis. Tuberous sclerosis results from changes (mutations) in a gene or genes that can occur spontaneously (sporadically) for unknown reasons or be inherited as autosomal dominant sign. Most cases present new (sporadic) gene mutations with no family history of the disease.
• Langerhans cell histiocytosis (GCR) is a rare spectrum of disorders characterized by overproduction (proliferation) and accumulation of a specific type of leukocytes (histiocytes) in various tissues and organs of the body. The appearance of GCL in the lungs may be similar to LAM on computed tomography.

Diagnostics

The diagnosis of lymphangioleiomyomatosis can be confirmed by careful clinical evaluation, which includes a detailed medical history and various specialized tests, including x-rays, pulmonary function tests and / or surgical removal and microscopic examination of the affected tissue (biopsy). In about 80 percent of people with LAM, CT scans will find cysts in the lungs or around one or both lungs (pleural effusion). CT scans of the abdomen may reveal angiomyolipomas or lymphangioleiomyomas, which confirm the diagnosis of LAM.

Surgical biopsy of an open lung is one of the definitive ways to confirm the diagnosis of LAM. These biopsy tissue samples confirm the presence of LAM cells.

Standard treatments

Treatment for lymphangioleiomyomatosis focuses on the specific symptoms that each person experiences. Accumulation fluid in the lungs (pleural effusion) can be drained with a surgically implanted shunt or tube. Surgical administration of a sterile irritant (such as oxycycline antibiotics) into the space surrounding the lungs, can help bring the lungs to the chest wall and reduce fluid buildup around lungs. Medications that temporarily dilate the bronchi (bronchodilators) can help relieve breathing problems (asthma-like symptoms) in some cases. Supplemental oxygen should be administered as needed.

Rapamycin (Sirolimus) has been approved for the treatment of lymphangioleiomyomatosis (LAM), a rare progressive lung disease that mainly affects women of childbearing age. Rapamycin is manufactured by Wyeth Pharmaceuticals, Inc., a subsidiary of Pfizer, Inc.

Since LAM is most common in young women of childbearing age, researchers suggest that female hormones such as estrogens play a role in the development of the disorder. The link between LAM and female hormones has not been proven. However, many doctors have investigated the use of agents that decrease the production or exposure of estrogen in the body. The results varied greatly among people. Such agents may include medroxyprogesterone acetate. Some patients have experienced symptomatic improvement while taking this medication, especially those with which chylothorax has recurred, but regular use is not recommended due to significant side effects effects. Estrogen drugs and dietary supplements should be discontinued in patients with LAM.

Diet replacement may or may not be beneficial for some women with chylothorax associated with LAM. Surgical removal of abdominal angiomyolipomas may be necessary if these growths are causing bleeding and pain. The initial recommendation is to embolize the angiomyolipoma, which can lead to necrosis of the lesion.

In people with severe cases of lymphangioleiomyomatosis, lung transplantation may be considered a last resort. Other treatments are symptomatic and supportive.

Because of the frequent association of LAM with osteoporosis, victims must undergo a bone mineral density test. Any loss of bone mineral density should be treated vitamin D, calcium supplements and bisphosphonates.

Forecast

Earlier reports indicated a dismal prognosis for lymphangioleiomyomatosis with progressive respiratory failure and death within 10 years of diagnosis. Recent reports, however, are more favorable: 71% of affected patients have been alive for more than 10 years. The statistics may improve as patients are diagnosed earlier or with more benign disease.