What Is It?
Amyloidosis is a disease in which an abnormal protein called amyloid accumulates in body tissues and organs. The protein deposits can be in a single organ or dispersed throughout the body. The disease causes serious problems in the affected areas. As a result, people with amyloidosis in different body parts may experience different physical problems:
- Brain - Dementia
- Heart - Heart failure, an irregular or unstable heart rhythm, enlarged heart
- Kidneys - Kidney failure, protein in the urine
- Nervous system - Numbness, tingling or weakness from nerve disease
- Digestive system - Intestinal bleeding, intestinal obstruction, poor nutrient absorption
- Blood - Low blood counts, easy bruising or bleeding
- Pancreas - Diabetes
- Musculoskeletal system - Joint pain or swelling, weakness
- Skin - Lumps or purple discoloration
No one knows what causes amyloidosis though in some cases it develops due to chronic inflammation or a genetic mutation. To make matters more complex, amyloidosis is not a single disease, and there are many different types of amyloid proteins that can be involved. For example, Alzheimer's disease and Creutzfeldt-Jakob disease (a rare cause of dementia linked to viruses living in livestock) are two distinct conditions characterized by different types of amyloid deposits in the brain.
One of the methods physicians use to categorize the type of amyloidosis is to classify it as either primary or secondary. When there is no other underlying disease, and the main problem stems from amyloidosis, the disorder is considered primary. When another disease, usually a chronic inflammatory condition such as tuberculosis or a rheumatic disease (such as rheumatoid arthritis), leads to amyloidosis, the disorder is considered secondary.
A newer classification system divides amyloidosis into 4 categories, depending on the type of abnormal protein and the clinical situations in which the condition develops.
• AL amyloid – this is caused by white blood cells, called plasma cells, producing excessive protein
• ATTR amyloid – genetic mutations or the aging process can lead to excess production of amyloid protein called transthyretin and most often causes heart failure or nerve damage
• AA amyloidosis – this type is caused by chronic inflammation as with chronic infection or an autoimmune disease
• Other – this last group includes amyloidosis that may develop in people undergoing dialysis, have a type of amyloid that runs in their family, or amyloidosis limited to one organ (such as the skin, eye or gastrointestinal tract).
The symptoms caused by amyloidosis depend on the extent of the damage done by the protein deposits, and which body organs are affected. Symptoms can include:
- Difficulty breathing
- Chronic diarrhea, constipation or excessive gas
- Blood in the stool, which may look red or black like coffee grounds
- Weight loss
- Muscle weakness
- Joint pain
- An enlarged tongue
- Difficulty chewing or swallowing
- Memory problems
- Nerve pain or numbness
Amyloid proteins can build up for a long time before causing any symptoms, so the disease usually is not diagnosed until it is well established. Because the symptoms associated with amyloidosis are common to several different diseases, your doctor may run many different tests to check for other diseases first.
He or she will begin with a general examination to look for signs of disease that might be caused by amyloidosis. The examination might include:
- Examining joints for signs of joint swelling
- Examining the skin for rashes or discoloration
- A test checking for blood in the stool or an endoscopic procedure (in which a flexible, lighted tube with a tiny camera on the end is inserted into the rectum to the colon, or into the stomach through the mouth) to detect gastrointestinal bleeding
- Testing the heart for evidence of heart failure or enlargement
- Testing muscles for signs of weakness
- Examining hands, feet, arms and legs for signs of fluid swelling or poor sensation
- Checking mental status to assess possible dementia
Urine will be collected to test for excess protein, which is often a first sign of systemic amyloidosis that has infiltrated the whole body. Blood will be drawn and tested to look for evidence of abnormal blood counts, kidney or liver disease, or abnormal protein.
The only definitive test for amyloidosis is a biopsy, in which a small sample of affected tissue is removed surgically and examined. The amyloid protein can be identified when the biopsy specimen is stained and viewed under a microscope. Increasingly, DNA and protein analysis are used to identify different types of amyloidosis.
When the entire body is affected (a condition called systemic amyloidosis), biopsies of the rectum or from abdominal fat often reveal the diagnosis. If the amyloid has accumulated in a single organ, such as the brain, the biopsy needs to come directly from that organ. For this reason, many types of amyloidosis are difficult to diagnose. For example, in Alzheimer's disease, a biopsy of brain tissue rarely is done. The biopsy could injure the brain and while the results might provide a diagnosis, it would be unlikely to change treatment (because there is no effective treatment for amyloid in the brain). When amyloidosis is diagnosed or highly suspected, additional blood and urine tests will be done to look for diseases that could cause the protein accumulation.
Amyloidosis is usually a lifelong condition that cannot be reversed or cured. If amyloidosis is related to another disease, treatment will focus on treating that disease to stop further amyloid damage.
Because no one knows what causes amyloidosis, there is no way to prevent primary amyloidosis.
Secondary amyloidosis can be prevented only by preventing or promptly treating the inflammatory disease that can trigger amyloidosis. For example, if rheumatoid arthritis is kept under control with medications, the chance of developing amyloidosis is small.
For secondary amyloidosis, the goal is to treat the underlying disease. For example, treating tuberculosis should stop secondary amyloidosis from getting worse. Similarly, controlling the inflammation of rheumatoid arthritis with medications has made amyloidosis due to rheumatoid arthritis a rarity. A change in the type of dialysis membrane can be effective for amyloidosis related to dialysis.
There is no cure for most cases of primary amyloidosis. Treatment is directed at alleviating symptoms and trying to slow the progression of the disorder. Some medications, such as corticosteroids, chemotherapy agents and colchicine, may decrease inflammation and treat some cases of amyloidosis, but they are not very effective if the disease is severe or highly advanced. In recent years, several drugs have been approved to treat certain types of amyloid (called transthyretin, or TTR), including tafamidis, patisiran and inotersen. These drugs reduce the ability of TTR amyloid to deposit in tissues or impair the liver’s production of TTR amyloid.
Chemotherapy and/or bone marrow transplant may be highly effective for patients with primary amyloidosis that accompanies a form of bone marrow cancer called multiple myeloma. A bone marrow transplant is a procedure in which a patient's own bone marrow, which is often the source of amyloid protein, is destroyed and replaced with a donor's marrow. Certain forms of amyloidosis may respond to liver, heart and/or kidney transplant. New treatments are being investigated.
If patients develop severe complications from amyloidosis, those conditions will need to be treated. For example, dialysis may be necessary if kidney failure develops, and cardiac medications may improve heart function and reduce retained fluid if cardiac disease becomes a problem.
When To Call a Professional
Contact a doctor if you have any of the symptoms of amyloidosis, especially extreme fatigue, breathing problems, or black or bloody stools.
The outlook depends on the type of amyloidosis and how severe it is at the time of diagnosis. The progression of secondary amyloidosis caused by a chronic inflammatory condition, such as an infection or rheumatoid arthritis, can be controlled by treating the underlying condition. For many cases of amyloidosis, however, there is no effective therapy and the disease will get worse over months or years. The more areas of the body that are affected and the more impaired the body organs are, the lower the chances of a good outcome. Even so, increased recognition of amyloidosis and improved therapies over the last decade have led to improved survival.
National Institute of Arthritis and Musculoskeletal and Skin Diseases
National Institute of Diabetes and Digestive and Kidney Disorders
National Cancer Institute (NCI)
American Autoimmune Related Diseases Association (AARDA)