Amyloidosis is a rare group of disorders caused by the accumulation of amyloid, an abnormal protein produced by the bone marrowsoft, 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, 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 bloodthe red bodily fluid that transports oxygen and other nutrients around the body cancers (e.g., multiple myeloma), or severe kidneya pair of bean-shaped organs in the abdomen that are responsible for filtering excess water and waste products from the blood and converting them into urine to be removed from the body 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 cellsthe basic structural and functional unit of all living things 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 lymphomacancers of the lymphatic system, or chronica long-lasting disease that changes slowly over time lymphocytic leukaemiacancer of blood and/or blood forming tissues.
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 bowelportion of the digestive system that digests food (small bowel) and absorbs salts and water (large bowel); also called intestines 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 substance produced by glands in the endocrine system that regulates various functions in the body 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
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 dialysisa procedure that removes excess fluid and/or waste from the blood in people whose kidneys aren't functioning properly. 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 hollow, muscular sac in the pelvis that stores urine 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 tissuea group of cells that work together to perform a function 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, metastasiswhen the cancer has spread to other parts of the body, also known as mets, and how the cancer cells look under the microscope. Stagingthe process of determining how big the cancer is, where it started and if it has spread to other areas 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 testinga procedure that analyses DNA to identify changes in genes, chromosomes and proteins, which can be used to analyse tumour DNA to help determine which treatment has the greatest chance of success, which analyses your tumoura tissue mass that forms from groups of unhealthy cells 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:
- Surgerytreatment involving removal of cancerous tissue and/or tumours and a margin of healthy tissue around it to reduce recurrence to remove as much of the amyloid deposits as possible.
- Organ transplanta surgical procedure that involves removing a failing or damaged organ and replacing it with a healthy one from a donor (in extreme cases).
- Chemotherapya cancer treatment that uses drugs to kill or slow the growth of cancer cells, while minimising damage to healthy cells.
- Bone marrow transplanta procedure that involves replacing unhealthy bone marrow with healthy bone marrow.
- Stem cell transplanta procedure that involves replacing unhealthy blood-forming cells (stem cells) with healthy stem cells.
- Targeted therapymedication that targets specific molecular features of cancer cells.
- Dialysis (if amyloid deposits are affecting the kidneys – not for people with dialysis-related amyloidosis).
- Clinical trialsresearch studies performed to test new treatments, tests or procedures and evaluate their effectiveness on various diseases.
- Palliative carea variety of practices and exercises used to provide pain relief and improve quality of life without curing the disease.
Risk factors
While the cause of amyloidosis remains unknown, the following factors may increase the riskthe possibility that something bad will happen 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.
- Hepatomegalyenlargement of the liver.
- Haematuriathe presence of blood in urine.
- Fatiguea state of extreme tiredness or exhaustion, can be physical or mental.
- Unexplained weight loss/loss of appetite.
- Swelling in the abdomenstomach, stomach area, belly or lower extremities.
- Purpuraa rash of small, red dots due to small superficial capillary bleeds; generally larger than petichiae on the skin, often around the eyes.
- Excess bleeding after an injury/impaired blood clotting.
- Dyspneadifficulty breathing, shortness of breath.
- Numbness, tingling and/or pain in the hands and feet.
- Diarrhoeafrequent discharge of watery or loose stools from the body.
- Constipationa condition where a person has difficulty passing faeces/stools.
- Macroglossiaa condition characterised by an abnormally large or oversized tongue.
- Splenomegalyenlargement of the spleen.
Not everyone with the symptoms above will have cancer, but see your general practitioner (GP) if you are concerned.
Diagnosis
If your doctor suspects you have amyloidosis, they may order the following tests to confirm the diagnosisthe process of identifying a disease based on signs and symptoms, patient history and medical test results and refer you to a specialist for treatment:
- Physical examinationan examination of your current symptoms, affected area(s) and overall medical history.
- Imagingtests that create detailed images of areas inside the body tests, potentially including:
- Echocardiograma type of ultrasound that uses sound waves to create detailed images of the heart to assess heart structure, function and blood flow.
- MRI (magnetic resonance imaging)a type of medical imaging that uses radiowaves, a strong magnet and computer technology to create detailed images of the body.
- CT (computed tomography) scana type of medical imaging that uses x-rays and computer technology to create detailed images of the body.
- Blood teststesting done to measure the levels of certain substances in the blood.
- Biopsyremoval of a section of tissue to analyse for cancer cells.
