Amyloidosis

Amyloidosis is a rare group of disorders caused by the accumulation of amyloid, an abnormal protein produced by the bone marrowIs soft, spongy tissue found in bones that makes blood cells.. When amyloid accumulates in organs and tissues, it can disrupt normal function and can possibly lead to organ damage and/or failure. Amyloid deposits are most commonly found in the heart, brain, kidneys, spleen, nervous system, or gastrointestinal system, however it can also accumulate in other parts of the body.

While amyloidosis is not classified as a cancerA disease where abnormal cells split without control and spread to other nearby body tissue and/or organs. Cancer cells can also spread to other parts of the body through the bloodstream and lymph systems., it is equally severe and can be life-threatening. In many cases this disease presents in people with long-term health problems, such as certain types of bloodhello cancers (e.g., multiple myeloma), or severe kidneyBody organ or part that filters blood and gets rid of waste products making them into urine (wee). disease. However, it is possible to develop amyloidosis without evidence of another disease.

Amyloidosis is more common in males, and is often diagnosed in people between the ages of 60-70. However, anyone can develop this disease.

Types of Amyloidosis

There are several different types of amyloidosis, which can be categorised by the type of amyloid protein that has accumulated.

AL Amyloidosis

AL amyloidosis, also known as immunoglobulin light chain amyloidosis or primary amyloidosis, is the most common subtype of this disease. It is caused by abnormal changes to immunoglobulins (also known as antibodies), which are cells
• the smallest, living parts of the body. Cells work together to form or build the body
• a human is made up of millions of Cells
• Cells reproduce themselves to make sure a body stays working
• sometimes Cells can be abnormal or damaged and these can be cancer cells
in the immune system that help fight disease. These changes cause excess production of ‘light chains’, which are a component of immunoglobulins, and can deposit into organs and tissues. AL amyloidosis most commonly affects the kidneys, heart, nervous system, liver, and gastrointestinal system, and is often associated with conditions such as multiple myeloma, Waldenstorm macroglobulinemia, non-Hodgkin lymphomaKnown as a blood cancer, it is cancer of the white blood cells., or chronicA long-lasting disease that changes slowly. lymphocytic leukaemia.

AL amyloidosis is often aggressive, and may not have as good of a prognosisTo predict how a disease/condition may progress and what the outcome might be. as other types of amyloidosis.

AA Amyloidosis

AA amyloidosis, also known as secondary amyloidosis, is a common subtype of amyloidosis that is caused by the accumulation of fragments of serum amyloid A (SAA), a type of protein produced by the liver that has many vital functions in the immune system. It is most commonly found in the kidneys, spleen, and liver, and is associated with long-term inflammatory conditions, such as rheumatoid arthritis, bronchiectasis, inflammatory bowelThe intestines (like a tube) that run between the stomach and anus (bum) and is made up of the small bowel (small intestine) and the large bowel (colon and rectum). (see ‘small intestine’; and ‘colon’ for more information). disease, tuberculosis, or familial Mediterranean fever.

AA amyloidosis can be aggressive, but often has a better prognosis than AL amyloidosis.

ATTR Amyloidosis

ATTR amyloidosis, also known as transthyretin (TTR) amyloidosis, is the most common type of hereditary amyloidosis that is caused by a genetic mutation of the TTR gene. TTR is responsible for the transportation of vitamin A (a nutrient vital for vision, growth, cell division, reproduction and immunity) and thyroxine (a thyroid hormoneA chemical made in different body parts/organs that is sent out to other parts of the body through the bloodstream. Hormones watch over and help control how other cells or organs act. vital for heart and digestive function, metabolism, brain development, bone health and muscle control) throughout the body, so when a mutation causes a change in how much vitamin A and thyroxine is distributed, it can cause adverse effects on the body. This subtype has been linked to people of African descent, and often involves the heart, nervous system, and kidneys.

ATTR amyloidosis can be aggressive, but often has a better prognosis than AL amyloidosis.

ATTRwt Amyloidosis

ATTRwt amyloidosis, also known as wild-type ATTR amyloidosis, age-related amyloidosis, or senile amyloidosis, occurs when the TTR gene has not been genetically mutated but is still deposited into tissues and organs. It is highly associated with aging, and is most commonly diagnosed in people over the age of 70. Unlike ATTR amyloidosis, this wild-type variant is not considered hereditary, is often less aggressive, and can have a better prognosis.

Dialysis-related amyloidosis, also known as Beta2-microglobulin amyloidosis or amyloid associated with the beta-2m protein (ABM2), occurs in patients with end-stage kidney disease who have experienced long-term dialysisRemoving waste and waste fluids from the body through a filter by filtering blood or tummy fluids. (a treatment used to remove of filter accumulated waste in the blood). It occurs when the beta2-microglobulin protein, which is normally filtered out by a healthy kidney, accumulates in an unhealthy kidney. Dialysis-related amyloidosis is a relatively new subtype of amyloidosis, so limited research has been done into the aggressiveness and prognosis of this disease.

Organ-specific Amyloidosis

Organ-specific amyloidosis occurs when amyloids have accumulated within a single organ, and is not circulating throughout the body. Common types of organ-specific amyloidosis include:

Cardiac amyloidosis (amyloidosis in the heart).
Alzheimer disease-associated amyloidosis (amyloidosis in cerebral vessels in the brain, associated with Alzheimer’s disease).
Cutaneous amyloidosis (amyloidosis of the skin).
BladderA small, elastic/muscle type sac/bag in the body, where urine (wee) is stored for urinating/weeing. Is found in the lower abdomen/belly area. amyloidosis (amyloidosis of the bladder).
Gastrointestinal amyloidosis (amyloidosis occurring in the gastrointestinal system).
Hepatic amyloidosis (amyloidosis of the liver).
Renal amyloidosis (amyloidosis of the kidneys).
Ocular amyloidosis (amyloidosis of the eye).
Laryngeal amyloidosis. (amyloidosis of the larynx/voice box).

The aggressiveness and prognosis of organ-specific amyloidosis often varies by subtype.

Leukocyte Cell-derived Chemotaxin-2 (LECT2) Amyloidosis

Leukocyte cell-derived chemotaxin-2 (LECT2) amyloidosis, also known as ALECT2, is a rare form of amyloidosis that most commonly affects the liver and kidney. Leukocyte cell-derived chemotaxin factor 2 is a protein associated with tissue growth and repair following cell damage. Because of how rare LECT2 amyloidosis is, there has been limited research done into the aggressiveness and prognosis of this disease.

Insulin Amyloidosis

Insulin amyloidosis, also known as insulin-derived amyloidosis, is a less common type of amyloidosis that generally occurs as a complication of insulin therapy, most commonly affecting patients with diabetes mellitus. This condition generally develops in the skin, often around the injection site due to an accumulation of insulin in these areas. This disease often interferes with insulin therapy and is not well understood due to its rarity.

Rare Forms of Amyloidosis

These forms of amyloidosis are considered very rare:

Apolipoprotein A-1 (APOA1) amyloidosis.
Apolipoprotein A-IV (APOA4) amyloidosis
Fibrinogen amyloidosis.
Gelsolin amyloidosis.
Lysozyme amyloidosis.

Treatment

When cancers are detected, they are staged and graded based on size, metastasisKnown as secondary cancer, it grows/spreads from the original/ primary cancer. (whether the cancer has spread to other parts of the body) and how the cancer cells look under the microscope. Staging and grading helps your doctors determine the best treatment for you. However, because amyloidosis is not a cancer, the disease is generally not staged or graded. Instead of staging and grading, your doctor will recommend a treatment plan based on the following factors:

Cancer location.
Whether or not the cancer has metastasised.
Your age.
General health.
Your treatment preferences.

Your doctor may also recommend genetic testing, which analyses your tumour DNA and can help determine which treatment has the greatest chance of success. They will then discuss the most appropriate treatment option for you.

Treatment options for amyloidosis may include:

Surgery to remove as much of the amyloid deposits as possible.
Organ transplant (in extreme cases).
Chemotherapy
• a chemical drug treatment to kill or slow-growing cancer Cells
• these drugs are called cytotoxic drugs
.
Bone marrow/stem cell transplant.
Targeted therapies.
Dialysis (if amyloid deposits are affecting the kidneys – not for people with dialysis-related amyloidosis).
Clinical trials.
Palliative careLessening pain without curing the disease..

For more information on the treatment options, please refer to the Rare Cancers Australia treatment options page.

Risk factors

While the cause of amyloidosis remains unknown, the following factors may increase the risk of developing the disease:

Having long-term chronic infections of inflammatory diseases, such as:
- Multiple myeloma.
- Waldenstorm macroglobulinemia.
- Non-Hodgkin lymphoma, potentially including:
- Chronic lymphocytic leukaemia.
- Rheumatoid arthritis.
- Bronchiectasis.
- Inflammatory bowel disease.
- Tuberculosis.
- Familial Mediterranean fever.
Having certain genetic mutations.
Family history of amyloidosis.
People who have had long-term kidney dialysis treatment.
People who have had insulin therapy.

Not everyone with these risk factors will develop the disease, and some people who have the disease may have none of these risk factors. See your general practitioner (GP) if you are concerned.

Symptoms

The symptoms of amyloidosis often vary based on the location of the amyloid deposits.

The general symptoms of amyloidosis include:

Waxy skin.
Easy bruising.
Heart failure/cardiac abnormalities.
Enlarged liver (hepatomegaly).
Blood in urine.
Feeling weak or tired.
Unexplained weight loss/loss of appetite.
Swelling in the abdomenstomach, stomach area, belly, tummy or lower extremities.
Purple spots (purpura) on the skin, often around the eyes.
Excess bleeding after an injury/impaired blood clotting.
Shortness of breath.
Numbness, tingling and/or pain in the hands and feet.
DiarrhoeaWhere watery or loose faeces (stools; poo) is frequently/often released discharged from the body. Also called ‘the runs’..
Constipation.
Enlarged tongue.
Enlarged spleen (splenomegaly).

Not everyone with the symptoms above will have cancer, but see your general practitioner (GP) if you are concerned.

Diagnosis/diagnosing

If your doctor suspects you have amyloidosis, they may order the following tests to confirm the diagnosisUsing medical test results, identify and name a disease and/or condition. and refer you to a specialist for treatment.

Physical examination

Your doctor will collect your overall medical history, as well as your current symptoms. Following this, they may examine your body to check for any abnormalities.

Imaging & blood tests

The doctor will take images of your body using magnetic resonance imagingTaking images/photos of inside body parts using magnet rather than x-ray. (MRITaking images/photos of inside body parts using magnet rather than x-ray.), a computed tomography scan (CT scanA 3-D (three dimensional) x-ray pictures that gives more information than a normal x-ray.), x-rays, echocardiogram, bone scan and/or positron emission tomography (PET scanA test that uses a radioactive drug to show a picture of how your tissues and organs are working. Also known as a positron emission tomography scan.), depending on where it is suspected the disease is. The doctor may also look at other parts of the body and looks for signs of additional disease. Additionally, a blood test may be taken to assessTo measure, look at and learn from. your overall health and help guide treatment decisions.

Biopsy

Once the location of the cancer has been identified, the doctor will perform a biopsyTo take a small piece of body tissue and test it in a laboratory. to remove a section of tissue using a needle. In most cases, this will be done by a core-needle biopsy, which involves a larger, hollow needle being inserted into a small incision above the area to be biopsied. Once a sample has been removed, it will be sent to a lab and analysed for amyloid deposits.