Amyloidosis (redirected from AA amyloidosis)

Amyloidosis 

Definition

Amyloidosis is a progressive, incurable, metabolic disease characterized by abnormal deposits of protein in one or more organs or body systems.

Description

Amyloid proteins are manufactured by malfunctioning bone marrow. Amyloidosis, which occurs when accumulated amyloid deposits impair normal body function, can cause organ failure or death. It is a rare disease, occurring in about eight of every 1,000,000 people. It affects males and females equally and usually develops after the age of 40. At least 15 types of amyloidosis have been identified. Each one is associated with deposits of a different kind of protein.

Types of amyloidosis

The major forms of this disease are primary systemic, secondary, and familial or hereditary amyloidosis. There is also another form of amyloidosis associated with Alzheimer's disease.

Primary systemic amyloidosis usually develops between the ages of 50 and 60. With about 2,000 new cases diagnosed annually, primary systemic amyloidosis is the most common form of this disease in the United States. Also known as light-chain-related amyloidosis, it may also occur in association with multiple myeloma (bone marrow cancer).

Secondary amyloidosis is a result of chronic infection or inflammatory disease. It is often associated with:

Familial or hereditary amyloidosis is the only inherited form of the disease. It occurs in members of most ethnic groups, and each family has a distinctive pattern of symptoms and organ involvement. Hereditary amyloidosis is though to be autosomal dominant, which means that only one copy of the defective gene is necessary to cause the disease. A child of a parent with familial amyloidosis has a 50-50 chance of developing the disease.

Amyloidosis can involve any organ or system in the body. The heart, kidneys, gastrointestinal system, and nervous system are affected most often. Other common sites of amyloid accumulation include the brain, joints, liver, spleen, pancreas, respiratory system, and skin.

Causes and symptoms

The cause of amyloidosis is unknown. Most patients have gastrointestinal abnormalities, but other symptoms vary according to the organ(s) or system(s) affected by the disease. Usually the affected organs are rubbery, firm, and enlarged.

Heart

Because amyloid protein deposits can limit the heart's ability to fill with blood between beats, even the slightest exertion can cause shortness of breath. If the heart's electrical system is affected, the heart's rhythm may become erratic. The heart may also be enlarged and heart murmurs may be present. Congestive heart failure may result.

Kidneys

The feet, ankles, and calves swell when amyloidosis damages the kidneys. The kidneys become small and hard, and kidney failure may result. It is not unusual for a patient to lose 20-25 pounds and develop a distaste for meat, eggs, and other protein-rich foods. Cholesterol elevations that don't respond to medication and protein in the urine (proteinuria) are common.

Nervous system

Nervous system symptoms often appear in patients with familial amyloidosis. Inflammation and degeneration of the peripheral nerves (peripheral neuropathy) may be present. One of four patients with amyloidosis has carpal tunnel syndrome, a painful disorder that causes numbness or tingling in response to pressure on nerves around the wrist. Amyloidosis that affects nerves to the feet can cause burning or numbness in the toes and soles and eventually weaken the legs. If nerves controlling bowel function are involved, bouts of diarrhea alternate with periods of constipation. If the disease affects nerves that regulate blood pressure, patients may feel dizzy or faint when they stand up suddenly.

Liver and spleen

The most common symptoms are enlargement of these organs. Liver function is not usually affected until quite late in the course of the disease. Protein accumulation in the spleen can increase the risk of rupture of this organ due to trauma.

Gastrointestinal system

The tongue may be inflammed, enlarged, and stiff. Intestinal movement (motility) may be reduced. Absorption of food and other nutrients may be impaired (and may lead to malnutrition), and there may also be bleeding, abdominal pain, constipation, and diarrhea.

Skin

Skin symptoms occur in about half of all cases of primary and secondary amyloidosis and in all cases where there is inflammation or degeneration of the peripheral nerves. Waxy-looking raised bumps (papules) may appear on the face and neck, in the groin, armpits, or anal area, and on the tongue or in the ear canals. Swelling, hemorrhage beneath the skin (purpura), hair loss, and dry mouth may also occur.

Respiratory system

Airways may be obstructed by amyloid deposits in the nasal sinus, larynx and traches (windpipe).

Diagnosis

Blood and urine tests can reveal the presence of amyloid protein, but tissue or bone-marrow biopsy is necessary to positively diagnose amyloidosis. Once the diagnosis has been confirmed, additional laboratory tests and imaging procedures are performed to determine:

Key terms

Amyloid — A waxy, starch-like protein.

Peripheral nerves — Nerves that carry information to and from the spinal cord.

Stem cells — Parent cells from which other cells are made.

Treatment

The goal of treatment is to slow down or stop production of amyloid protein, eliminate existing amyloid deposits, alleviate underlying disorders (that give rise to secondary amyloidosis), and relieve symptoms caused by heart or kidney damage. Specialists in cardiology, hematology (the study of blood and the tissues that form it), nephrology (the study of kidney function and abnormalities), neurology (the study of the nervous system), and rheumatology (the study of disorders characterized by inflammation or degeneration of connective tissue) work together to assess a patient's medical status and evaluate the effects of amyloidosis on every part of the body.

Colchicine (Colebenemid, Probeneaid), prednisone, (Prodium), and other anti-inflammatory drugs can slow or stop disease progression. Bone-marrow and stem-cell transplants can enable patients to tolerate higher and more effective doses of melphalan (Alkeran) and other chemotherapy drugs prescribed to combat this non-malignant disease. Surgery can relieve nerve pressure and may be performed to correct other symptom-producing conditions. Localized amyloid deposits can also be removed surgically. Dialysis or kidney transplantation can lengthen and improve the quality of life for patients whose amyloidosis results in kidney failure. Heart transplants are rarely performed.

Supportive measures

Although no link has been established between diet and development of amyloid proteins, a patient whose heart or kidneys have been affected by the disease may be advised to use a diuretic or follow a low-salt diet.

Prognosis

Most cases of amyloidosis are diagnosed after the disease has reached an advanced stage. The course of each patient's illness is unique but death, usually a result of heart disease or kidney failure, generally occurs within a few years. Amyloidosis associated by multiple myeloma usually has a poor prognosis. Most patients with both diseases die within one to two years.

Prevention

Genetic couseling may be helpful for patients with hereditary amyloidosis and their families. Use of Cholchicine in patients with familial Mediterranean fever has successfully prevented amyloidosis.

Resources

Organizations

Amyloidosis Network International. 7118 Cole Creek Drive, Houston, TX 77092-1421. (888) 1AMYLOID. 〈http://www.health.gov/nhic/Scripts/Entry.cfm?HRCode=HR2397〉.

National Organization for Rare Disorders. P.O. Box 8923, New Fairfield, CT 06812-8923. (800) 999-6673. http://www.rarediseases.org.

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amyloidosis /am·y·loi·do·sis/ (am?i-loi-do´sis) a group of conditions characterized by the accumulation of insoluble fibrillar proteins (amyloid) in various organs and tissues such that vital function is compromised. The associated disease states may be inflammatory, hereditary, or neoplastic, and deposition can be local, generalized, or systemic. The most widely used classification is based on the chemistry of the amyloid fibrils and includes primary (AL), secondary (AA), and familial forms.

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AA amyloidosis  secondary a.

AL amyloidosis  primary a.

ATTR amyloidosis  the most common form of familial amyloidosis (q.v.), associated with mutations of the gene encoding transthyretin.

familial amyloidosis  any inherited form of amyloidosis; usually used to denote any of various systemic autosomal dominant disorders of amyloid deposition that involve the nervous system. The most common form, ATTR amyloidosis, is associated with mutations of the transthyretin protein, but rare mutations of other proteins can also be a cause. The term can also, less commonly, be said to include several types of secondary amyloidosis in which the deposition is associated with an inherited disease (e.g., familial Mediterranean fever). Subclassifications are based on clinical presentation and biochemical composition of the fibrils deposited; originally they were distinguished on the basis of kinship. See also familial amyloid polyneuropathy, under polyneuropathy.

hemodialysis-associated amyloidosis  that occurring in patients on long-term hemodialysis, caused by the deposition of beta2-microglobulin, which cannot be removed from the blood by hemodialysis, in the joints, synovial membranes, and tendon sheaths. Manifestations include carpal tunnel syndrome and arthritis.

hereditary amyloidosis  familial a.

primary amyloidosis  a systemic form in which the deposited fibrillar material is AL amyloid; it may be due to either aberrant synthesis or processing of immunoglobulin light chains. It is associated with tumors or dyscrasias of immunoglobulin-producing plasma cells and involves some combination of the skin and subcutaneous tissue, nerves, liver, spleen, heart, kidney, intestine, and tongue. Called also AL a..

reactive systemic amyloidosis  secondary a.

renal amyloidosis  amyloid deposits in the kidneys; in the primary type the fibrils are mainly AL amyloid, and in secondary types they are AA amyloid. Secondary types may accompany inflammatory disorders, chronic infectious diseases, or neoplastic diseases.

secondary amyloidosis  that in which AA amyloid is deposited, and which occurs secondary to a chronic inflammatory condition, either infectious or noninfectious. It usually involves the liver, spleen, and kidneys.

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am·y·loid·o·sis (m-loi-dss)

n.

A disorder marked by the deposition of amyloid in various organs and tissues of the body that may be associated with a chronic disease such as rheumatoid arthritis, tuberculosis, or multiple myeloma.

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amyloidosis (aˈ·m·loiˈ·dōˑ·sis),

n disease of unknown origin in which a waxlike, sticky, glycoprotein (amyloid) collects in organs and tissues, thus inhibiting normal function.

Amyloidosis.

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amyloidosis (am´iloidō´sis),

n a condition in which amyloid, a glycoprotein, is deposited intercellularly in tissues and organs. Four types of amyloidosis are recognized, two of which, primary amyloidosis and amyloid tumor, frequently produce nodules in the tongue and gingiva.

Amyloidosis.

amyloidosis, primary,

n a type occurring without a known predisposing cause. Amyloid deposits are found in the tongue, lips, skeletal muscles, and other mesodermal structures. The disease may be manifested by polyneuropathy, purpura, hepatosplenomegaly, heart failure, and the nephrotic syndrome.

amyloidosis, secondary,

n a type occurring secondary to chronic diseases such as tuberculosis, leprosy, rheumatoid arthritis, multiple myeloma, and prolonged bacterial infections. Amyloid deposits are found in parenchymal organs. The disease is usually manifested by proteinuria and hepatosplenomegaly.

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amyloidosis

the deposition in various tissues of amyloid. This protein is almost insoluble and once it infiltrates the tissues they become waxy and nonfunctioning. Systemic amyloidosis may be immunocytic or reactive (see below).

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cutaneous amyloidosis

multiple cutaneous, hard, painless, chronic plaques occur over the head, neck and shoulders of horses. There may be involvement of the nasal mucosa and resulting dyspnea.

familial renal amyloidosis of Shar pei dogs

manifested by episodic fever and swelling of one or both hocks which may resolve spontaneously, but is recurring. The condition is resistant to treatment and eventually there is renal and/or hepatic failure.

immunocytic amyloidosis, immunogenic amyloidosis, primary amyloidosis

amyloid produced from light chains of immunoglobulins as in plasma-cell dyscrasias. See also al protein.

reactive amyloidosis

is derived from excess serum protein SAA produced as a result of chronic antigenic stimulation. The kidney is most often affected and the amyloid is most often deposited in glomeruli but medullary deposits are seen in cats and cattle. Idiopathic amyloidosis is common in the dog and less common in cats. It is associated with chronic suppurative disease processes in cattle, antiserum production in horses, and it occurs rarely in pigs. Called also secondary alopecia.

renal amyloidosis

characterized by severe proteinuria and uremia. There is chronic diarrhea, polydipsia and anasarca. Seen particularly in dogs and cats.

secondary amyloidosis

reactive amyloidosis (above).