What is amyloidosis?
Amyloidosis is a disease that leads to the buildup of protein in vital organs, which causes these organs to become damaged. Our bodies make several proteins that can cause amyloidosis. In order to treat a patient who has amyloidosis, it’s very important to know the exact protein that is causing the disease.
What are the types of protein that can cause amyloidosis?
These are the most common types of protein that can cause amyloidosis:
AL (light chain) amyloidosis: In amyloidosis of the light chain type, a cell in your bone marrow called the plasma cell makes too much of an abnormal part of your antibodies. Antibodies (also called immunoglobulins) are proteins that normally help you fight infections. However, in AL amyloidosis, the plasma cell is no longer under the normal control of the immune system. The plasma cell continues to make antibodies (not in response to infection), and the antibody protein that is made is abnormal. The abnormal light chain portion of the antibody is not able to leave your body as it normally does in the urine, and instead is deposited into your organs.
Our bodies make two light chain proteins, kappa and lambda. Either can cause amyloidosis, but you can only have one of these light chain types, not both. Organs that are commonly affected are the heart, kidney, skin, stomach, small and large intestines, nerves, and liver. Sometimes only one organ is affected, and other times many are involved.
There is a similar type of amyloidosis that is produced by the heavy chain portion of the antibody called AH amyloidosis. AL or AH amyloidosis can also occur due to a cancer of the plasma cell called multiple myeloma.
ATTR (transthyretin) amyloidosis: Transthyretin is a protein made by the liver to help carry thyroid hormones in your blood. Transthyretin amyloidosis has two forms, hereditary and senile:
- In the hereditary form, there is an error in the DNA that makes the transthyretin protein. This error is passed from one generation to the next and leads to too much of the transthyretin protein. Over time, the transthyretin protein builds up in the organs and causes organ failure. It can take several decades before organ damage is noticeable. This form of transthyretin amyloidosis can affect the heart, nerves, and kidneys.
- In the senile form, there is no DNA error in the transthyretin gene. Instead, the transthyretin protein itself becomes abnormal and begins to build up in the body over several years. This form of transthyretin amyloidosis usually affects the hearts of men around 80 years of age. Carpal tunnel syndrome can develop several years before cardiac failure and can be an important clue to making this diagnosis.
AA (apo serum amyloid A) amyloidosis: The protein apo serum amyloid A occurs in high levels where inflammation (irritation and swelling) is present in the body. It can cause amyloidosis when high levels of the protein occur for long periods of time. Worldwide, this is the most common type of amyloidosis due to its association with inherited periodic fever syndromes such as Familial Mediterranean Fever. Other chronic (long-term) inflammatory conditions that can cause AA amyloidosis are Crohn’s disease, ulcerative colitis, rheumatoid arthritis, and chronic infections. Organs commonly affected include the kidney and intestines.
What are the signs or symptoms of amyloidosis?
- swelling of the feet or legs
- shortness of breath
- abnormal heart rhythms
- swelling of the feet or legs
- excessive bubbles in the urine
- urinating less
- getting up at night to urinate
Stomach or intestine damage:
- bleeding from the rectum
- vomiting blood
- poor appetite
- bloating or excessive gas
- abnormal sensation in the fingers and toes, which can spread up the arms and legs (foot “falls asleep”)
- weakness in the arms or legs
- lightheadedness upon standing
- diarrhea or constipation
- bruising or bleeding easily
- weak fingernails and toenails
- rapid hair loss
- purple color on the eyelids or around the eyes and other areas of skin folds
Tongue enlargement is rare, but if it occurs, the person should be tested for amyloidosis.
How is amyloidosis diagnosed?
There are many tests that are used in making the diagnosis of amyloidosis. The most useful test is to obtain a biopsy of an affected organ. A biopsy is the removal of cells or tissue for examination.
To perform a biopsy for amyloidosis, a needle is used to gather the tissue from the kidney, liver, or bone marrow. To take a biopsy from the heart, a small catheter (a thin, hollow tube) is placed into a vein in your neck and then guided into the right side of your heart. A very small device takes a small piece of the heart muscle, which is removed through the same vein. While these biopsies may sound painful, there is actually very little pain.
The biopsy sample will be examined under a microscope by a pathologist, who will perform special tests to identify the exact protein causing the amyloidosis.
In addition to the biopsy, several other tests will be done to check for organ damage:
- Blood samples will be taken to check for kidney, heart, and liver damage.
- A separate blood sample will measure the light chains in your blood if you have the AL type of amyloidosis. All patients with this type will have a bone marrow biopsy.
- A 24-hour collection of urine can be done at home and returned to your doctor to check for kidney damage.
- Tests to check for heart damage include an electrocardiogram (EKG) and an echocardiogram (ultrasound of the heart).
How is amyloidosis treated?
The treatment of amyloidosis depends on the type of protein that is causing the amyloidosis.
- AL amyloidosis: This is the only type of amyloidosis that is treated with chemotherapy. Chemotherapy drugs commonly used to treat amyloidosis include melphalan, cyclophosphamide, bortezomib, and lenalidomide. For most patients, one or two of these drugs are combined with a steroid medication (dexamethasone or prednisone). These drugs work together to kill the plasma cell that produces the light chain protein. Some patients will be considered for high-dose chemotherapy with melphalan and an autologous stem cell transplant (bone marrow transplant).
It is important to know the blood levels of the kappa and lambda light chains before treatment. In order to determine how the patient is responding to treatment, these blood levels are tested after each month of treatment or after a stem cell transplant. The goal of treatment is to normalize the abnormal free light chain. The blood levels of the kappa and lambda light chains are also used to monitor the disease. Depending on the patient’s response to treatment, he or she can live many years.
- ATTR amyloidosis: There is no standard treatment for ATTR amyloidosis yet. Drugs that can be used include doxycycline and diflunisal. They are often used in combination. Several drugs are being tested for treatment of ATTR amyloidosis. Since the transthyretin protein is made in the liver, liver transplantation is a possible treatment for ATTR amyloidosis.
- AA amyloidosis: For AA amyloidosis due to Familial Mediterranean Fever, colchicine is very effective. This medicine decreases fever symptoms associated with Familial Mediterranean Fever and can eliminate AA amyloidosis caused by this disease. For other disorders, the treatment is aimed at the disease that is causing the amyloidosis. There are many good treatment options available for Crohn’s disease, ulcerative colitis, and rheumatoid arthritis that can also treat the AA amyloidosis.
- The National Kidney and Urologic Diseases Information Clearinghouse: Amyloidosis and Kidney Disease
- Amyloidosis Foundation: FAQs
- National Organization for Rare Disorders: Amyloidosis
- Amyloidosis Support Groups
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This information is provided by the Cleveland Clinic and is not intended to replace the medical advice of your doctor or health care provider. Please consult your health care provider for advice about a specific medical condition. This document was last reviewed on: 3/14/2015...#15718