Amyloidosis

Amyloidosis is a rare disease in which a protein called amyloid accumulates in various tissues and organs, impairing normal function.

Amyloidosis causes few or no symptoms in some people, while producing severe symptoms and fatal complications in other people. The severity of the disease depends on which organs are affected by amyloid deposits. Amyloidosis is twice as common in men as in women and is more common among older people.

Many forms of amyloidosis exist, and the disease can be classified into four groups: primary amyloidosis, secondary amyloidosis, hereditary amyloidosis, and amyloidosis associated with normal aging.

Primary amyloidosis (light chain amyloidosis) occurs with abnormalities of plasma cells, and some people with primary amyloidosis also have multiple myeloma (cancer of the plasma cells (see Section 14, Chapter 175)). Typical sites of amyloid buildup in primary amyloidosis are the heart, lungs, skin, tongue, thyroid gland, intestines, liver, kidneys, and blood vessels.

Secondary amyloidosis may develop in response to various diseases that cause persistent infection or inflammation, such as tuberculosis, rheumatoid arthritis, and familial Mediterranean fever. Typical sites of amyloid buildup in secondary amyloidosis are the spleen, liver, kidneys, adrenal glands, and lymph nodes.

Hereditary amyloidosis has been noted in some families, particularly those from Portugal, Sweden, and Japan. The amyloid-producing defect occurs because of mutations in specific proteins in the blood. Typical sites for amyloid buildup in hereditary amyloidosis are the nerves, heart, blood vessels, and kidneys.

Amyloidosis associated with normal aging usually affects the heart. What causes amyloid to build up in the heart, other than age, usually is not known. Amyloid also accumulates in the brain of people with Alzheimer's disease and is thought to play a role in causing Alzheimer's.

See the table Effects of Amyloid Buildup.

Symptoms and Diagnosis

The accumulation of large amounts of amyloid can disturb the normal functioning of many organs. Many people have few symptoms, whereas others develop severe, life-threatening disease. Common symptoms are fatigue and weight loss. Other symptoms of amyloidosis depend on where the amyloid builds up.

Amyloidosis is sometimes difficult for doctors to recognize because it produces so many different problems. However, a doctor may suspect amyloidosis when several organs fail; when fluid accumulates in the tissues, causing swelling (edema); or when unexplained bleeding occurs, especially in the skin. The hereditary form is suspected when an inherited peripheral nerve disorder is discovered in a family.

The diagnosis is generally made by testing a small amount of abdominal fat obtained through a needle inserted near the navel. Alternatively, the doctor can perform a biopsy by taking a sample of tissue from the skin, rectum, gums, kidney, or liver and examining it under a microscope with the use of special stains.

Prognosis and Treatment

There is no cure for amyloidosis. However, in secondary amyloidosis, treating the underlying disease usually slows or reverses the amyloidosis. Primary amyloidosis with or without multiple myeloma has a bleak prognosis; most people who have both diseases die within 1 to 2 years. People with amyloidosis who develop heart failure have a poor prognosis as well.

Treatment to decrease or control symptoms and complications of amyloidosis has been only modestly successful for most people. Chemotherapy (prednisone and melphalan, sometimes combined with colchicine) and stem cell transplantation offer relief to some people. Colchicine alone may help relieve amyloidosis that is triggered by familial Mediterranean fever. Accumulations of amyloid in a specific area of the body can sometimes be removed surgically.

Organ transplants (for example, of a kidney or the heart) have extended the lives of a small number of people with organ failure due to amyloidosis. The disease usually continues to progress, however, and eventually the transplanted organ accumulates amyloid. The exception is liver transplantation (see Section 16, Chapter 187), which usually stops the progression of amyloidosis in the hereditary form of the disease.