What is amyloidosis?
What are the types of amyloidosis?
How is amyloidosis diagnosed?
What are the treatment options for amyloidosis?
What is the prognosis for people with amyloidosis?
What hospitals specialize in treating amyloidosis?
What is Amyloidosis? The amyloidoses are
rare diseases first described over 200 years ago. The disease manifests itself
when amyloid proteins deposit and accumulate in the body's organs and
tissue. This accumulation may happen systemically (throughout the body) or locally
(in one tissue).
Each year 3000 cases of amyloidosis are diagnosed in the United States. Amyloidosis
is generally a disease of middle-aged
people and older, although the disease has been seen in individuals in their
thirties. Men are more likely to be affected
than women by a ratio of about 1.5:1. Other diseases can increase the risk of
amyloidosis, and family history of the disease
may indicate a hereditary version. Ten to 15% of people with multiple myeloma
develop the amyloidosis. Long-term kidney
dialysis may increase the risk of dialysis-associated amyloidosis.
Symptoms of the disease could include the following:
- fatigue and weight loss
- a feeling of fullness
- tingling and numbness in the lower extremities
- shortness of breath and possibly an enlarged tongue.
Types of Amyloidosis:
Systemic Amyloidosis Systemic amyloidosis involves the deposition
of amyloid throughout various tissues; including muscles, connective tissues,
organs and peripheral nerves. There are a number of types of systemic amyloidosis.
They include AL amyloidosis, hereditary amyloidosis and AA amyloidosis.
Localized amyloidosis involves tumor-like nodules that can be found on the lung,
larynx, skin, bladder, small bowel and tongue. Localized amyloidosis may affect
people with type II diabetes, people with certain cancers of the thyroid or
endocrine system, and many people over the age of 80. The ratio of systemic
to localized amyloidosis is 9:1.
AL Amyloidosis (Primary)
AL amyloidosis is the most common form of the disease. AL amyloidosis is a plasma
cell disorder the cause of which is unknown. The bone marrow produces many cells,
red and white blood cells, platelets and antibodies that are proteins. In the
case of AL amyloidosis, the bone marrow plasma cells produce mis-folded proteins
(parts of antibodies called “light chains”) that travel through
the body and self-assemble and deposit in various organs, ultimately causing
organ failure if the deposition is not stopped.
AL amyloidosis can affect a single organ or multiple organs. Common combinations
of organ involvement include; heart/kidney, heart/GI tract and kidney/peripheral
nerves, but almost any combination may present. About one third of people with
AL have a high level of protein in the urine with few symptoms of organ involvement.
Another third have symptoms of protein accumulation in the heart and in one
quarter of AL patients the protein builds up in the liver and gastrointestinal
AA Amyloidosis (Secondary)
AA amyloidosis may occur in the course of a chronic inflammatory disease or
chronic infection such as rheumatoid arthritis, familial Mediterranean fever
(FMF), osteomyelitis, tuberculosis or inflammatory bowel disease. In the United
States, this form of amyloidosis is rarely seen. This is because the medical
treatment available for inflammatory diseases and chronic infection keeps them
in check thus not triggering the development of AA. AA is much more prevalent
in third world countries. The kidneys are the most common organ affected by
AA amyloidosis. Progression to dialysis and kidney failure is the common cause
of death for AA amyloidosis.
AF Amyloidosis (Familial)
As the name implies, this form of amyloidosis can be inherited, is the only
form that is hereditary and is not as rare as originally thought. Presence of
the disease is due to inheriting an abnormal gene (a mutation) which leads to
production of proteins that have the potential of forming amyloid. Symptoms
of this disease normally do not present themselves until middle age or later.
If a particular person has the mutated gene, each of their children has a 50%
chance of inheriting the mutation. Not all people with one of the mutations
will necessarily get sick. Some individuals only develop a small amount of amyloid
in their body and some people may not accumulate any amyloid at all.
How Amyloidosis is Diagnosed
The diagnosis starts with a thorough physical examination and establishment
of the patient's medical history. The symptoms presented will help to determine
tests that may be performed.
Monoclonal light chains found in the blood serum or urine by immunofixation
electrophoreses (IFE) or free light chain (FLC)
assay indicate the precursor protein to AL amyloid may be present. Free light
chain assays are only 80-90% sensitive and many facilities do not have them
or use them as an initial screening test. Additional testing including a bone
marrow biopsy may be required to confirm the presence and nature of the underlying
plasma cell disease.
BNP, a hormone produced when the heart is stressed, is measured via a blood
test. If elevated, it may indicate heart involvement with amyloid. An echocardiogram
may show the thickening of the heart walls, which could also indicate cardiac
involvement. If urinary protein levels are markedly elevated, it may indicate
kidney involvement with amyloid Elevated alkaline
phosphatase is an indicator of possible liver involvement with amyloid. As some
of these tests are indicators of several forms
of the disease it is important that the results be reviewed in conjunction with
all the other test results to assure a proper diagnosis and not be looked at
Any diagnosis of amyloidosis must be confirmed with a positive biopsy. Tissue
samples for the biopsy can be taken from abdominal fat or the rectum. Biopsy
of the suspected organ is not always necessary but can be useful.
If a hereditary form of amyloidosis is suspected genetic testing is required
to confirm the type. This is a simple blood test where the genes are analyzed
to determine which mutation is present.
If the initial diagnosis indicates AL amyloidosis, it is very important to
also investigate a potential for a hereditary form of the disease, especially
in the case of African Americans, patients who have dominant peripheral neuropathy
and those with kidney involvement without amyloid in the bone marrow. The genetic
testing is required as the course of treatment is completely different for these
two forms of the disease.
Treatment of Amyloidosis
The treatments for each type of amyloidosis differ. Extension of life and improved
quality of life are the major outcomes that are sought.
AL Amyloidosis - The treatment target for AL therapies is to eliminate
the precursor protein of the amyloid that is depositing in the body. The first
thing that needs to be done for these patients once diagnosed is to assess the
extent of organ involvement. This will steer the proper treatment option. In
most cases a patient with more than two major organs involved will not be a
candidate for a autologous stem cell transplant.
Autologous stem cell transplant involves utilizing the patients own stem cells.
The process begins with mobilizing the stem cells from the bone marrow into
the blood stream so that
they can be collected. The next step is to administer a predetermined
dose of IV melphalan (chemotherapy) to kill off all of
the cells in the bone marrow. At this point the collected stem
cells are re-infused into the blood stream to allow for them to
migrate back into the bone marrow where they generate the red
and white blood cells and platelets needed for normal blood
For patients who are not candidates for stem cell transplant
there area number of oral chemotherapy treatments that are
options. They include combinations of dexamethasone and
melphalan chemotherapy or immunomodulator drugs such as
Thalidomide or lenalidomide (Revlimid). Interferon and other
chemotherapy combinations have also been used. New agents
are being investigated in recently developed clinical trials that
could prove useful in the future.
Dexamethasone and prednisone are steroids. It has been
steroids reduces the serum free light chains and slows the
deposition of amyloid in the body. The other drugs mentioned
are various chemotherapy immunomodulator agents that have
shown to have some effect. Sometimes it may be necessary to
use a number of the different protocols in succession.
Throughout treatment, the serum free light chains and other
blood counts are monitored to determine the effectiveness of the
AF Amyloidosis - In hereditary amyloidosis, the amyloid
forming protein is usually produced in the liver. With this is mind, liver transplants
are sometimes performed in patients with the intention of preventing further
amyloid deposition. Recent research has found that there may be drug therapy
options for patients with the disease caused by the mutated transthyretin protein
and clinical trials are on-going.
AA Amyloidosis - Since AA amyloidosis is caused by an
underlying inflammatory or infectious disease treatment involves eliminating
the source of the inflammation and/or infection.
Supportive Care Supportive care is important to address specific problems and
symptoms that are caused by the amyloid deposits in the body. In the case of
cardiac or kidney involvement, edema (fluid buildup) can be a problem and a
diuretic can be prescribed to help minimize the problem. In some cases, compression
stockings can be of benefit and elevating the legs can help lesson the swelling.
Patients with congestive heart failure due to amyloid in their heart need special
diets and medication under the care of a cardiologist who understands the needs
related to amyloid heart disease. If the gastrointestinal tract is involved,
diet modifications and some medications can help with diarrhea and the feeling
of fullness. Some patients with macroglossia (enlarged tongue) have difficulty
swallowing and sometimes aspirate fluids into their lungs. Thickeners can be
obtained to mix into everyday fluids that will help to minimize aspiration into
Prognosis for an Amyloidosis Patient
With early diagnosis, the outlook for patients with amyloidosis has shifted
to hopeful in the last decade. The early diagnosis allows treatment to begin
before the amyloid protein build-up in the body becomes too great to overcome.
Without treatment, the outlook for patients with AL amyloidosis is not good,
many passing away within 18 - 24 months after diagnosis. Early diagnosis
is the key to managing the disease.
In familial amyloidosis, the outlook varies depending on the
type of gene mutation and when the condition is diagnosed.
Some patients may survive up to 15 years after the disease
Localized amyloid tumors can be surgically removed and
generally do not recur.
Major U.S. Amyloidosis Treatment Centers
Boston University Medical Center - Boston, MA AMyloid Treatment and Research
The Mayo Clinic - Rochester, MN www.mayoclinic.org/amyloidosis/index.html
Memorial Sloan-Kettering Cancer Center - New York, NY www.mskcc.org/prg/prg/bios/532.cfm
The CMCF would like to recognize the Amyloidosis Foundation for providing this
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