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 bloodstream and can deposit 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). 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 as a result of kidney failure).

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

AL may affect any tissue. Signs and symptoms may be vague and can include the following:

• Heart disease and irregular heart beat -- The heart is involved in about 50% of patients with AL.
• Stroke
• 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
• Fatigue
• Weight loss

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 AL

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 AA have had their related inflammatory disease for a decade or more.

No one knows what causes amyloidosis.  There may be more than one cause. Hereditary amyloidosis results from genetic changes that cause the body to make abnormal proteins. Researchers think that as we get older, damage builds up in the body and triggers the disease. 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 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 50 -- 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

Your health care provider may suspect amyloidosis based on your symptoms, and will perform a physical exam, including blood or urine tests. The only way your doctor can definitively diagnose 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.

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 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 can make up amyloid. Doctors may use chemotherapy to treat AL. 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 cure for AA, but medication can improve survival. The underlying condition must be treated. A liver transplant may be necessary for hereditary amyloidosis.

Drug Therapies

Doctors use combination of prednisone (a corticosteroid) and melphalan (Alkeran, also used to treat some kinds of cancer) to treat AL. 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
• Metoclopramide to help empty food from the stomach
• Antibiotics to control bacteria that may cause diarrhea or prevent the body from absorbing nutrients
• 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

Complementary and Alternative Therapies

Dietary choices, supplements, and herbs that reduce inflammation may help prevent amyloidosis. Damage from oxidation may play a role in the development of amyloidosis (see What Causes It? section), so you may want to add antioxidants to your diet to help slow the disease. Not all antioxidants are compatible with certain medications. 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

Studies suggest that the following dietary choices may help prevent amyloidosis in people who are at high risk, or help slow the disease once it 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 accelerate the growth of amyloid deposits in mice.
• Fish oil supplements (1,000 mg capsule 1 - 2 times per day), which are high in omega-3 fatty acids, appear to help prevent amyloidosis in mice and may help reduce inflammation in chronic inflammatory conditions, such as rheumatoid arthritis. Fish oil can have a blood-thinning effect. Make sure to inform your prescribing doctors of what you are taking, particularly blood-thinning medications, such as warfarin (Coumadin) and aspirin.
• Vitamin C (1 - 2 g per day). One 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 may 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 3 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. Bromelain can interact with certain medications including some antibiotics. Bromelain has a blood-thinning effect and may increase the effect of blood-thinning medications, such as warfarin (Coumadin) and aspirin.
• 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. There is some concern that resveratrol may have estrogen-like effects, so people with a history of hormone-related conditions should consult their doctors. Don't take resveratrol 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 beta2 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 beta2 microglobulin amyloidosis. Studies have not evaluated supplementation with glutathione for amyloidosis. Some doctors may recommend 500 mg 2 - 3 times a day for people on dialysis to prevent the disease. Several glutathione supplements are available, but some are of questionable quality. Consult a trained, naturally oriented doctor to make sure you get a high-quality supplement.
• Quercetin (500 mg 2 times per day) is an antioxidant with anti-inflammatory properties. It has not been studied for amyloidosis. Quercetin can interact with certain medications; speak with your physician.

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 stress, oxidation, and 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. 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.

Previously, AL was thought to be untreatable and deadly.  With current therapy, many patients survive for more than 5 years. About 20% survive 5 years or longer. With AA, 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.

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.

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.

Buxbaum J. Treatment and prevention of the amyloidoses: can the lessons learned by applied to sporadic inclusion-body myositis? Neurology. 2006;66(2 Suppl 1):S110-3.

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

Ferri: Ferri's Clinical Advisor 2013, 1st ed. Philadelphia, PA. Mosby; 2012.

Firestein: Kelley's Textbook of Rheumatology, 8th ed. Philadelphia, PA: Saunders Elsevier; 2008.

Goldman. Goldman's Cecil Medicine, 24th ed. Philadelphia, PA. Saunders, An Imprint of Elsevier; 2011.

Goldman L. Inherited and metabolic hepatic disorders. Cecil Textbook of Medicine. 23rd ed. Philadelphia, Pa: Saunders Elsevier; 2008:1436-7;2083-7.

Hoffman: Hematology: Basic Principles and Practice, 5th ed. Philadelphia, PA. Elsevier Inc.; 2008.

Kholova I, Kautzner J. Current treatment in cardiac amyloidosis. Curr Treat Options Cardiovasc Med. 2006;8(6):468-73.

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.

Maneti L, Tansinda P, Vaglio A. Eprodisate in amyloid A amyloidosis: a novel therapeutic approach? Expert Opin Pharmacother. 2008;9(12):2175-80.

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.

Okuda Y, Yamada T, Matsuura M, Takasugi K, Goto M. Ageing: a risk factor for amyloid A amyloidosis in rheumatoid arthritis. Amyloid. 2011:18(3):108-11.

Pettersson T, Konttinen YT, Maury CP. Treatment strategies for amyloid A amyloidosis. Expert Opin Pharmacother. 2008;9(12):2117-28.

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

Sideras K, Gertz MA. Amyloidosis. Adv Clin Chem. 2009;47:1-44.

Stankovic K, Grateau G. Amyloidosis AA. Nephrol Ther. 2008;4(4):281-7.

Taal. Brenner and Rector's The Kidney, 9th ed. Philadelphia, PA. Saunders, An Imprint of Elsevier; 2011.

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

Vasala M, Immonen K, Kautiainen  H, Hakala M. More evidence of declining incidence of amyloidosis associated with inflammatory rheumatic diseases. Scan J Rheumatol. 2010: 39(6):461-5.

Zubkov A, Rabinstein A, Dispenzieri A, Wijdicks E. Primary systemic amyloidosis with ischemic stroke as presenting complication. Neurology. 2007;69(11):1136-41.