Amyloidosis is a group of diseases in which an abnormal protein called amyloid builds up in the organs and tissues. This protein is soluble in its normal form, but it becomes insoluble and starts to build up when it is misfolded (misshaped).The buildup may happen in a single organ (localized) or throughout the body (systemically). Amyloid deposits can affect any organ or tissue.

There are three major types of systemic amyloidosis:

• Primary amyloidosis (AL), the most common form in adults, occurs when bone marrow produces too much of certain abnormal fragments of antibody proteins, which build up in the bloodstream and can deposit in body tissues.
• Familial (hereditary) amyloidosis is a genetic form passed down in families that often affects the heart, nerves, and kidneys.
• Secondary amyloidosis (AA) develops in children or adults along with a chronic infectious or inflammatory disease, such as tuberculosis or rheumatoid arthritis.

Localized amyloidosis is associated with aging, as the body seems to naturally make amyloid as it ages. Different abnormal proteins or protein fragments may be involved. Two common conditions associated with localized amyloidosis are type 2 diabetes (where protein builds up in the pancreas) and Alzheimer's disease (where protein builds up in the brain). Beta2-microglobulin amyloidosis occurs in people with kidney failure who have been on dialysis for a long time (beta2 -microglobulin is a protein that can build up in the blood and joints as a result of kidney failure).

The signs and symptoms of amyloidosis depend on the location and size of the amyloid deposits.

Amyloidosis may affect any tissue and give rise to:

• Heart disease and irregular heart beat
• Nervous system disorders, including stroke
• Kidney disorders, including kidney failure
• Gastrointestinal (GI) disorders
• Enlarged liver
• Spleen problems
• Diminished function of the adrenal and other endocrine glands
• Skin conditions, commonly including purpura (bleeding into the skin) around the eyes, easy bruising, and nail abnormalities
• Enlarged tongue is a common sign, sometimes with swelling under the jaw, breathing difficulties, and sleep apnea
• Lung problems
• Swelling of joints
• Carpal tunnel syndrome
• Bleeding problems

Symptoms may be vague and can include the following:

• Fatigue
• Weight loss
• Breathing problems
• Numbness or tingling sensations (paresthesia)

There is no certain cause for amyloidosis. The disease arises due to protein misfolding. Hereditary amyloidosis results from genetic changes that cause the body to make abnormal proteins. Abnormal or misfolded proteins deposition affects the function of organs. Once amyloid deposits start, they seem to continue building up in the same locations. The heart, kidneys, nervous system, and GI tract are the most commonly affected.

People with the following profile are at increased risk for developing amyloidosis:

• Men - two thirds of people with AL are men.
• People over age 60
• Disease affecting the antibody-producing plasma cells in the blood (such as multiple myeloma, malignant lymphoma, benign monoclonal gammopathy, or Waldenström's macroglobulinemia)
• Chronic infectious or inflammatory disease (such as tuberculosis, rheumatoid arthritis, familial Mediterranean fever, or ankylosing spondylitis)
• Long-term dialysis
• Inherited genetic changes that affect proteins in the body

Your health care provider may suspect amyloidosis based on your symptoms, and will perform a physical exam, including blood or urine tests. Other conditions must be excluded. The only way your doctor can definitively diagnose amyloidosis is using a needle to remove a small amount of tissue to test for amyloid (called a biopsy). With hereditary amyloidosis, DNA tests may reveal the genetic change that caused the condition. Special studies of tissue samples may show the structure of amyloid deposits. Depending on the signs and symptoms, your health care provider may use other tests to learn more about your condition, such as which organs are affected and whether your condition is getting worse.

There is no cure for amyloidosis. Treatment focuses on lessening symptoms and reducing production of amyloid.

Prevention

Those who have hereditary amyloidosis should consider going to genetic counseling to learn about the risks of passing the condition to their children.

Treatment Plan

Treatment involves decreasing the proteins that can make up amyloid. Doctors may use chemotherapy or stem cell transplantation to treat AL. For AA (secondary amyloidosis), the underlying condition must be treated. A liver transplant may be necessary for hereditary amyloidosis.

Depending on which organs are affected, your health care provider may also ask you to follow a special diet (a low-sodium diet, for example, may help control fluid retention if your heart or kidneys are affected).

Drug Therapies

To treat secondary (AA) amyloidosis, specific treatments for the underlying infectious or inflammatory condition are used.

To treat primary (AL) amyloidosis, doctors use combinations of prednisone (a corticosteroid) and melphalan (Alkeran, also used to treat some kinds of cancer). Other chemotherapy drugs may be used. Stem cell transplants are also a treatment for AL.

To help manage symptoms, your health care provider may suggest:

• Diuretics to relieve swelling caused by fluid retention
• Anti-arrhythmics to control heart rhythm
• Anti-inflammatory/immune suppressive therapy to reduce amyloid precursor load

Surgical and Other Procedures

Depending on which parts of the body are affected, if you have amyloidosis you may need one of the following procedures:

• Dialysis, if the kidneys are failing
• Kidney, liver, heart, or bone marrow transplant
• Spleen removal
• Pacemaker implantation to control heart rhythm
• Removal of localized amyloid deposits
• Carpal tunnel decompression

Complementary and Alternative Therapies

Dietary choices, supplements, and herbs that reduce inflammation may help prevent worsening amyloidosis. Amyloidosis should never be treated with complementary and alternative therapies alone. Work with a knowledgeable provider and inform all of your health care providers about any medications, herbs, or supplements you are taking.

Nutrition and Supplements

Reducing salt intake can slow disease progression if the heart or kidneys are affected.

No diet plan or supplements prevent or treat amyloidosis. The following supplements are sometimes used by people with amyloidosis:

• Fish oil supplements, which are high in omega-3 fatty acids, appear to attenuate a type of amyloidosis in mice. They may also help reduce inflammation in chronic inflammatory conditions, such as rheumatoid arthritis. No human studies support fish oil supplements as prevention or treatment for amyloidosis. Eating fish and seafood may be more beneficial than taking fish oil supplements. Fish oil can have a blood-thinning effect. If you are taking blood-thinning medications, such as warfarin (Coumadin) and aspirin, speak to your doctor before taking fish oil.
• Vitamin C has antioxidant effects and is found in citrus fruits, dark leafy greens, berries, and other foods. One animal study suggested that high doses of vitamin C may help the body break down amyloid and prevent amyloidosis from worsening. There is no evidence this vitamin C supplements would works to treat or prevent amyloidosis in humans.
• Quercetin is a flavonoid compound found in some plants (such as onions, berries, tea, broccoli, apples) and in St. John's Wort and Ginkgo biloba extracts (see below). Quercetin has been studied as anti-inflammatory or antioxidant in in vitro studies. A few studies showed quercetin improved brain function in a mouse model of Alzheimer disease. However, currently there are no human studies supporting any beneficial effects of quercetin in amyloidosis or any other disease. Quercetin can interact with certain medications and at high doses, there have been isolated reports of kidney damage. Speak with your physician before taking quercetin.

Herbs

Flavonoids are compounds found in some plants that may help fight damage from stress, oxidation, and inflammation. Herbs rich in flavonoids are sometimes used by people with Alzheimer disease and other types of amyloidosis:

• Ginkgo (Ginkgo biloba) extract contains flavonoids like quercetin and others and has been suggested as a treatment for Alzheimer's disease. Gingko may not be appropriate for people with certain conditions, such as diabetes, seizures, bleeding disorders, or those actively trying to get pregnant. Gingko can have a blood-thinning effect, and may increase the effect of blood-thinning medications, such as warfarin (Coumadin) and aspirin.
• St. John's Wort is a plant containing flavonoids. Its extract was showed to decrease amyloid accumulation in the brain of a transgenic mouse model of Alzheimer disease. There are no human studies supporting any therapeutic effect of St. John's Wort in any type of amyloidosis. St. John's Wort may interact with several medicines, including antidepressants, birth control pills, digoxin, as well as anticoagulants like warfarin. There are several side effects associated with use of St. John's Wort, including fatigue, dizziness, increased sensitivity to sunlight, and anxiety. Consult your health care provider before taking St. John's Wort.

Previously, AL was thought to be untreatable and deadly. With current therapy, most patients survive between 2 and 10 years after diagnosis. Survival depends on the extent of heart and kidney involvement.

After diagnosis, your doctor may perform tests on a regular basis to check levels of protein-related substances, the size and placement of amyloid deposits, the development of the disease, and the effects of treatment.

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