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Amyloidosis

• Signs and Symptoms
• What Causes It?
• Who's Most At Risk?
• What to Expect at Your Provider's Office
• Treatment Options
• Prognosis/Possible Complications
• Following Up
• Supporting Research

Amyloidosis is a group of diseases in which a protein, called amyloid, builds up in the organs and tissues. 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, occurs when bone marrow produces too much of certain fragments of antibody proteins, which build up in the blood stream and may be deposited in body tissues.
• Familial (hereditary) amyloidosis is a genetic form passed down in families that often affects nerves and kidneys.
• Secondary amyloidosis (AA) develops 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. 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). Beta ₂ -microglobulin amyloidosis occurs in people with kidney failure who have been on dialysis for a long time (beta ₂ -microglobulin is a protein that can build up in the blood as a result of kidney failure).

Signs and Symptoms

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

Any tissue may be affected in primary amyloidosis. Signs and symptoms may be vague and can include the following:

• Heart disease and irregular heart beat
• Kidney disorders, including kidney failure
• Gastrointestinal (GI) disorders, such as perforation (hole), bleeding, slow movement of matter through the GI tract, and blockage
• Enlarged liver
• Diminished function of the spleen
• Diminished function of the adrenal and other endocrine glands
• Skin conditions, such as growths, color changes, purpura (bleeding into the skin) around the eyes, and easy bruising
• Enlarged tongue, sometimes with swelling under the jaw, breathing difficulties, and sleep apnea
• Lung problems
• Swelling of the shoulder joints (may look like shoulder pads under the skin)
• Bleeding problems

Signs and symptoms of hereditary amyloidosis may include the following:

• Nervous system disorders
• Gastrointestinal conditions, such as diarrhea and weight loss
• Heart problems
• Carpal tunnel syndrome
• Kidney disease, though this is less common than in primary amyloidosis

Signs and symptoms of secondary amyloidosis may include the following:

• Kidney disease, which may lead to kidney failure; this is the cause of death in 40 - 60% of cases.
• Enlarged liver
• Enlarged spleen
• Heart problems -- this is rare, and less severe than in other forms of amyloidosis.

Most people who are diagnosed with secondary amyloidosis have had their related inflammatory disease for a decade or more.

What Causes It?

No one knows what causes amyloidosis, and there may be more than one cause. Hereditary amyloidosis results from genetic changes that cause the body to make abnormal proteins. Age seems to play a role in amyloidosis -- researchers think the disease may be triggered by damage that builds up in the body as we get older. This kind of damage may come from the body's use of oxygen (oxidation) and from free radicals (harmful byproducts formed when cells use energy). Amyloid is also more likely to form in people who have immune system problems. Once amyloid deposits have started, they seem to continue building up in the same locations.

Who's Most At Risk?

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

• Men
• Being more than 50 years old. Even in people with hereditary forms, amyloid deposits severe enough to cause problems are usually detected later in life.
• 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 rheumatoid arthritis, inflammatory bowel disease, familial Mediterranean fever, or ankylosing spondylitis)
• Long-term dialysis
• Inherited genetic changes that affect proteins in the body

What to Expect at Your Provider's Office

Your health care provider may suspect amyloidosis based on your symptoms. They may perform blood or urine tests, but the only way to definitively diagnosis amyloidosis is by doing a biopsy, using a needle to remove a small amount of tissue to test for amyloid. With hereditary amyloidosis, DNA tests may reveal the genetic change that caused the condition. Special x-ray 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 find out more about your condition, such as which organs are affected and whether your condition is getting worse.

Treatment Options

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

Prevention

Those who have hereditary amyloidosis in their family 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. Chemotherapy is used to treat primary amyloidosis. Depending on the organs that are affected, your health care provider may 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). There is no treatment per se for secondary amyloidosis. The underlying condition must be treated. A liver transplant may be necessary for hereditary amyloidosis.

Drug Therapies

A combination of prednisone (a corticosteroid) and melphalan (Alkeran, also used to treat some kinds of cancer) is used to treat primary amyloidosis. Stem-cell transplants are also a treatment for primary systemic amyloidosis.

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

• Diuretics to relieve swelling caused by fluid retention
• Anti-arrhythmics to control heart rhythm
• Metoclopramide to help empty food from the stomach
• Antibiotics to control bacteria that may cause diarrhea or prevent the body from absorbing nutrients

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 for if the kidneys are failing
• Kidney, liver, heart, or bone marrow transplant
• Spleen removal
• Pacemaker implantation to control heart rhythm

Complementary and Alternative Therapies

Dietary choices, supplements, and herbs that aid in lessening inflammation in general may, theoretically, help to prevent amyloidosis. Damage from oxidation may play a role in development of amyloidosis (see section titled What Causes It? ), so you may want to add antioxidants to your diet -- they may help slow the disease. Amyloidosis should never be treated with complementary and alternative therapies alone. Be sure to talk to keep all of your health care providers informed about any medications, herbs, or supplements you are taking.

Nutrition and Supplements

Some animal studies suggest that the following dietary choices may help prevent the disease for someone who is at high risk, or help slow the disease once amyloidosis has developed:

• Limit the amount of meat you consume. Researchers suspect that a substance called amyloid enhancing factor (AEF), sometimes found in diseased animal foods, may increase the risk of amyloidosis in people who eat these foods. AEF has been shown to hasten the growth of amyloid deposits in mice.
• Fish oil supplements (1,000 mg capsule one to two times per day), which are high in omega-3 fatty acids, appear to help prevent amyloidosis in mice and may help to reduce inflammation in chronic inflammatory conditions such as rheumatoid arthritis. Fish oil can have a blood-thinning effect, so make sure all your prescribing doctors are informed of what you are taking.
• Vitamin C (1 - 2 g per day). A well-designed animal study suggested that high doses of vitamin C may help the body break down amyloid and prevent amyloidosis from worsening, but there is no evidence this works in humans.

Additional supplements include:

• DMSO (dimethyl sulfoxide, 7 - 15 g per day orally, and 50 - 100% solution applied to skin topically 2 times per week), an organic liquid that is used as an industrial solvent, has shown mixed results in scientific studies. Never take DMSO without your doctor's supervision.
• Bromelain (250 - 500 mg three times per day), an enzyme derived from pineapple, fights inflammation and may help break down amyloid deposits in kidney tissue, though evidence is slight. Bromelain is often combined with turmeric, which strengthens its effects.
• Resveratrol, an antioxidant found in grape skins, grape juice, and wine (especially red wine), may help reduce free radicals that encourage amyloid production. There is no established dosage, so talk to your doctor. Resveratrol should not be taken if you take blood-thinning medication or have high blood pressure or heart failure.
• Glutathione is an antioxidant produced by the body. Low levels may be associated with higher levels of beta ₂ -microglobulin in people on dialysis with or without amyloidosis. This suggests there may be a link between glutathione levels in the blood and development or worsening of beta ₂ -microglobulin amyloidosis. Although studies have not been conducted to evaluate supplementation with glutathione for amyloidosis, some doctors may recommend 500 mg two or three times a day for people on dialysis to try to prevent the disease. Several glutathione supplements are available. Consult a trained, naturally oriented physician to make sure you get a high-quality supplement.
• Quercetin (500 mg two times per day) is an antioxidant with anti-inflammatory properties. It has not been studied for amyloidosis, however.

To help prevent inflammation in general:

• Avoid processed foods, caffeine, food additives, dairy products, and refined sugars.
• Eat more whole grains, fresh fruits and vegetables, nuts, seeds, and cold-water fish.

Herbs

Flavonoids are plant compounds that fight damage from oxidation and free radicals, as well as inflammation. They may be useful as a supportive therapy to standard medical care in treating amyloidosis:

• Pycnogenol ( Pinus pinaster , 200 mg per day), which comes from the bark of French maritime pine, is rich in flavonoids. One laboratory study suggested that pycnogenol protected cells of cattle from free radical damage due to amyloid deposits.
• Gingko (Gingko biloba) extract also contains flavonoids. It has been suggested as a treatment for Alzheimer's disease. Given the link between Alzheimer's and amyloid deposits, gingko may help treat amyloidosis as well, especially because it is also an antioxidant.

Prognosis/Possible Complications

Most people with primary amyloidosis die within 2 years of diagnosis, usually of heart failure, uremia (toxic buildup of wastes in the blood), or other complications. About 20% survive 5 years or longer. With secondary amyloidosis, most people survive 5 - 10 years after their condition surfaces. Survival depends on how well the underlying condition is treated. In hereditary amyloidosis, the outlook varies depending on the type of gene mutation and when the condition is diagnosed. Some people survive as long as 15 years after the disease develops.

Following Up

After diagnosis, tests may be performed 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.

Supporting Research

Adachi N, Koh CS, Tsukada N, Shoji S, Yanagisawa N. In vitro degradation of amyloid material by four proteases in tissue of a patient with familial amyloidotic polyneuropathy. J Neurol Sci. 1988;84(2-3):295-299.

Bastianetto S, Ramassamy C, Doré S, Christen Y, Poirier J, Quirion R. The Ginkgo biloba extract (EGb 761) protects hippocampal neurons against cell death induced by beta-amyloid. Eur J Neurosci. 2000;12(6):1882-1890.

Beers MH, Porter R, eds. The Merck Manual of Diagnosis and Therapy . 18th ed. Whitehouse Station, NJ: Merck Research Laboratories; 2006:1310-12.

Cathcart ES, Elliott-Bryant R. Diet, amyloid enhancing factor (AEF) and amyloidogenesis: an hypothesis. Amyloid . 1999;6(2):107-113.

Cathcart ES, Leslie CA, Meydani SN, Hayes KC. A fish oil diet retards experimental amyloidosis, modulates lymphocyte function, and decreases macrophage arachidonate metabolism in mice. J Immunol . 1987;139(6):1850-1854.

Cohen AS. Clinical aspects of amyloidosis, including related proteins and central nervous system amyloid. Curr Opin Rheumatol . 1994;6(1):68-77.

Elliott-Bryant R, Cathcart ES. Amyloid enhancing factor and dietary transmission in accelerated amyloid A amyloidosis. Clin Immunol Immunopathol. 1998;88(1):65-69.

Falk RH, Skinner M. The systemic amyloidoses: an overview. Adv Intern Med . 2000;45:107-137.

Friedman S, Janowitz HD. Systemic amyloidosis and the gastrointestinal tract. Gastroenterol Clin North Am . 1998;27(3):595-614.

Gertz MA, Lacy MQ, Dispenzieri A. Amyloidosis. Hematol Oncol Clin North Am. 1999;13(6):1211-1233.

Gillmore JD, Hawkins PN, Pepys MB. Amyloidosis: a review of recent diagnostic and therapeutic developments. Br J Haematol . 1997;99(2):245-256.

Harman D. Nutritional implications of the free-radical theory of aging. J Am Coll Nutr. 1982;1(1):27-34.

Isobe T. AA amyloidosis and AL amyloidosis. Intern Med . 1993;32(12):919-920.

Jacobson DR, Buxbaum JN. Genetic aspects of amyloidosis. Adv Hum Genet. 1991;20:69-123, 309-311.

Lebrazi H, Hachulla E, Saile R. Treatments for amyloidosis beyond symptomatic care [in French]. Rev Med Interne. 2000;21(3):247-255.

Lim GP, Calon F, Morihara T, Yang F, Teter B, Ubeda O, Salem N Jr, Frautschy SA, Cole GM. A diet enriched with the omega-3 fatty acid docosahexaenoic acid reduces amyloid burden in an aged Alzheimer mouse model. J Neurosci . 2005 Mar 23;25(12):3032-40.

Liu F, Lau BH, Peng Q, Shah V. Pycnogenol protects vascular endothelial cells from beta-amyloid-induced injury. Biol Pharm Bull. 2000;23(6):735-737.

Merlini G. Treatment of primary amyloidosis. Semin Hematol . 1995;32:60-79.

Miyata T, Inagi R, Kurokawa K. Diagnosis, pathogenesis, and treatment of dialysis-related amyloidosis. Miner Electrolyte Metab . 1999;25(1-2):114-117.

Morena M, Cristol J, Canaud B. Why hemodialysis patients are in a prooxidant state? What could be done to correct the pro/antioxidant imbalance. Blood Purif. 2000;18(3):191-199.

Ravid M, Chen B, Bernheim J, Kedar I. Ascorbic acid-induced regression of amyloidosis in experimental animals. Br J Exp Pathol . 1985;66(2):137-141.

Sezer O, Eucker J, Schmid P, Possinger K. New therapeutic approaches in primary systemic AL amyloidosis. Ann Hematol. 2000;79(1):1-6.

Tan SY, Pepys MB, Hawkins PN. Treatment of amyloidosis. Am J Kidney Dis. 1995; 26(2):267-285.

Taussig SJ, Batkin S. Bromelain, the enzyme complex of pineapple (Ananas comosus) and its clinical application. An update. J Ethnopharmacol. 1988;22(2):191-203.

Wettstein A. Cholinesterase inhibitors and ginkgo extracts -- are they comparable in the treatment of dementia? Phytomedicine . 2000;6(6):393-401.

Woo P. Amyloidosis in children. Baillieres Clin Rheumatol. 1994;8(3):691-697.

• Review Date: 12/2/2006
• Reviewed By: Steven D. Ehrlich, N.M.D., private practice specializing in complementary and alternative medicine, Phoenix, AZ. Review provided by VeriMed Healthcare Network.

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