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AMYLOIDOSIS

Definition Amyloid is a protein-polysaccharide complex substance having starch-like characteristics. Amyloidosis occurs when this substance is deposited into organs or tissues.

Cause Amyloidosis is thought to result from many factors. The cause is unknown.

PREVALENCE AND INCIDENCE OF AMYLOIDOSIS

Amyloidosis is a rare disease. About two-thirds of patients with amyloidosis have primary (where no specific cause or disease is related to the abnormal protein deposits), less than 5% have secondary (associated with another chronic disease, often in multiple myeloma), less than 5% familial (inherited) and less than 5% have senile (occurring secondary to old age) amyloidosis. In patients with primary amyloidosis, 95% are over the age of 40 and 66% are men.

SIGNS & SYMPTOMS

Weakness or fatigue

Weight loss

Heart damage (congestive heart failure)

    shortness of breath

    swelling of the feet and legs

    chest pains

    irregular heart rhythm

    lightheadedness (due to lowering of blood pressure during sudden position changes)

Abnormal sensations of the arms, feet, or legs

Symptoms related to autonomic neuropathy (e.g. gastrointestinal symptoms such as bloating, diarrhea, etc...) especially in the neuropathic hereditary familial amyloidosis.

Large Amyloid deposits may produce bone damage and cause bone fractures.

DIAGNOSIS

SUBJECTIVE CRITERIA

The clinical diagnosis is often delayed either because the initiating mechanism is unclear (as in primary amyloidosis) or the signs and symptoms of the primary disease mask or merge with those of the deposits of Amyloid itself.

Amyloidosis should be suspected with the slow onset of unexplained protein in the urine or kidney failure, enlarged liver or spleen, enlarged tongue, unexplained cardiac damage, malabsorption of food, nerve damage, and skin lesions (especially around the eyes).

OBJECTIVE CRITERIA

Physical examination. A sudden drop in blood pressure following changes in posture often develop during the course of the disease. This could be due to direct involvement of the blood vessels or infiltration or dysfunction of the nerves controlling the blood vessels. Vision disturbances secondary to Amyloid deposit behind the lens occurs in familial amyloidosis. Easy bruisability and flesh discoloration, as well as changes in the texture of the skin (i.e. waxy non-itchy rash), which could be widely distributed with a specific prevalence at the eyelids, ears and body folds. Tongue enlargement is present in only 10% of the patients. Generalized swelling of the lymph glands is infrequent, but may be the initial manifestation of primary amyloidosis. Signs of fluid overload or congestive heart failure may be noted by long and hard examination. Fluid in the belly could be noted and may be related to heart failure or liver failure. The occurrence of liver failure is rare. Nerve symptoms and signs (numbness involving the lower extremities and muscle wasting) are related to damage of the sensory and motor nerves. Skin involvement in systemic amyloidosis may manifest as bruises, raised skin lesions or nodules, hair loss, nail abnormalities or skin thickening.Physical examination. A sudden drop in blood pressure following changes in posture often develop during the course of the disease. This could be due to direct involvement of the blood vessels or infiltration or dysfunction of the nerves controlling the blood vessels. Vision disturbances secondary to Amyloid deposit behind the lens occurs in familial amyloidosis. Easy bruisability and flesh discoloration, as well as changes in the texture of the skin (i.e. waxy non-itchy rash), which could be widely distributed with a specific prevalence at the eyelids, ears and body folds. Tongue enlargement is present in only 10% of the patients. Generalized swelling of the lymph glands is infrequent, but may be the initial manifestation of primary amyloidosis. Signs of fluid overload or congestive heart failure may be noted by long and hard examination. Fluid in the belly could be noted and may be related to heart failure or liver failure. The occurrence of liver failure is rare. Nerve symptoms and signs (numbness involving the lower extremities and muscle wasting) are related to damage of the sensory and motor nerves. Skin involvement in systemic amyloidosis may manifest as bruises, raised skin lesions or nodules, hair loss, nail abnormalities or skin thickening.

ROUTINE LABORATORY ABNORMALITIES

Hematology. Anemia is not a prominent feature in primary amyloidosis. When present, it is usually due to kidney failure, multiple myeloma, or stomach bleed. High platelet count occurs in 5-10% of the patients and may be a clue to the diagnosis.Hematology. Anemia is not a prominent feature in primary amyloidosis. When present, it is usually due to kidney failure, multiple myeloma, or stomach bleed. High platelet count occurs in 5-10% of the patients and may be a clue to the diagnosis.

Blood chemistry. Levels of serum alkaline phosphatase (an enzyme involved in the integrity of the bone as well as one of the liver enzymes) could be increased in about 25% of the patients. Low blood protein levels are usually present when kidney dysfunction results in losing large amounts of protein in the urine. The latter usually results in significant elevation of the cholesterol and triglyceride levels.Blood chemistry. Levels of serum alkaline phosphatase (an enzyme involved in the integrity of the bone as well as one of the liver enzymes) could be increased in about 25% of the patients. Low blood protein levels are usually present when kidney dysfunction results in losing large amounts of protein in the urine. The latter usually results in significant elevation of the cholesterol and triglyceride levels.

Electrocardiogram (EKG) usually reveals low voltage and false signs of heart attacks. Electrocardiogram (EKG) usually reveals low voltage and false signs of heart attacks.

DEFINITIVE CRITERIA

The diagnosis is established by the demonstration of Amyloid material in tissue specimens. The substance has a homogeneous, amorphous appearance under the regular light microscope and stains pink with DHNE. Under polarized light, Amyloid stained with Congo red produces an apple-green reflection. Experience in the staining technique and interpretation are important before the technique can be used routinely.

The most common tissues demonstrating amyloidosis at biopsy include fat from the abdominal wall (80%), bone marrow biopsy (50%), and rectal biopsy (80%).

If the disease is suspected in the absence of an easily accessible specific organ, abdominal aspirate is recommended; as this aspirate is positive in more than 80% of the patients. A bone marrow sample should be obtained to determine the degree of the plasmacytosis to rule out multiple myeloma. With bone marrow specimens, stains for Amyloid are positive in slightly more than 50% of patients. If the abdominal fat and bone marrow samples are negative and clinical suspicion is high, a rectal biopsy should be taken and must include the submucosa. This biopsy is positive in approximately 80% of patients. If these sites are negative, tissue should be obtained from a suspected involved organ. Kidney biopsy results in a high incidence of positive findings in patients with protein losing syndrome or kidney failure. Liver biopsy frequently discloses Amyloid. Tissue obtained at carpal tunnel decompression should always be examined for Amyloid because it is positive in a large percentage of patients with primary amyloidosis. The sural nerve is an excellent source of biopsy material in patients with peripheral neuropathy (nerve damage).

It is important to differentiate between the different types of amyloidosis.

NATURAL HISTORY OF THE DISEASE

Primary amyloidosis. Currently, the median survival of patients with primary amyloidosis is almost two years. The survival Has improved due to several factors; earlier diagnosis, improved supportive care, and possible advances in medical management of the disease. Patients who demonstrate only peripheral neuropathy have a median survival of more than five years. Heart involvement accounts for death in almost 50% of the patients. The degree of cardiac involvement is an important prognostic factor. The presence of heart failure, abnormal urine protein and a large liver, as well as the extent of weight loss, have a significant influence on the survival during the first year.

Secondary amyloidosis. The natural history of secondary amyloidosis depend on the primary diagnosis.

Familial amyloidosis. In neuropathic familial amyloidosis, death usually occurs within ten years. In cardiopathic familial amyloidosis, progressive heart failure begins in the fourth or fifth decade of life and leads to death in 2-6 years.

Senile amyloidosis. Senile cardiac amyloidosis is commonly recognized post mortem. If diagnosed before death, it is usually discovered in the eighth decade of life and is characterized by heart failure with an average survival of 26 months. This is much longer than that seen with cardiac primary amyloidosis.

TREATMENT

Therapy of primary amyloidosis is not satisfactory. Because Amyloid fibrils consist of variable portions of a monoclonal immunoglobulin light chain and it is a plasma cell dyscrasia, treatment with chemotherapy that is known to be effective against multiple myeloma and other related disease has been attempted. More recently, therapy with high dose steroids and -Interferon appears to be showing promising results. Preliminary data relative to high dose chemotherapy followed by bone marrow transplantation might be a potential area for further investigation.

Questions related to Amyloidosis

 
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