What Is Amyloidosis?

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Amyloidosis is a rare condition that causes an abnormal buildup of a protein called amyloid throughout the body. This amyloid build-up is dangerous and can cause damage to organs and organ failure.

Amyloid can build up in one or more organs, or it can build up throughout the body. Most types of amyloidosis cannot be prevented, but symptoms can be managed with treatment. Here is what you need to know about amyloidosis, including types, symptoms, causes, diagnosis, and treatment.

Doctor and patient discuss amyloidosis
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Types of Amyloidosis

Some types of amyloidosis can be life-threatening, while others cause less harm. The type of amyloidosis depends on the type of protein that accumulates.

The most common types of amyloidosis are amyloid light chain amyloidosis, autoimmune amyloidosis, familial amyloidosis, wide-type (or senile) amyloidosis, dialysis-related, and cardiac amyloidosis.

Amyloid Light Chain Amyloidosis

Amyloid light-chain amyloidosis (AL amyloidosis)—also called primary amyloidosis—is the most common type of amyloidosis, accounting for 70% of people living with amyloidosis.

With AL amyloidosis, the body’s immune system produces abnormal antibodies (proteins) called light chains. Normally, bone marrow cells—called plasma cells—produce antibodies that fight infections. But sometimes, plasma cells can produce extra pieces of antibodies called light chains that misfold and bind together to form amyloid fibers.

Amyloid fibers will circulate into the bloodstream and deposit throughout the body leading to organ damage. Organs that might be affected include the heart, kidneys, nerves, skin, soft tissues, the tongue, and the gut. 

Autoimmune Amyloidosis

Autoimmune amyloidosis (AA)—also called secondary amyloidosis—occurs as a result of a reaction from a chronic inflammatory disease or a chronic infection. High levels of inflammation and infection can cause your liver to produce high levels of a protein call serum amyloid A protein (SAA).

Ongoing inflammation may cause a part of the SAA protein—the AA—to separate and deposit in tissues. Under normal circumstances, an inflammatory reaction breaks down the SAA proteins and it is recycled, as would happen with all proteins.

Researchers don’t know why SAA doesn’t completely break down for some people especially those with chronic, inflammatory diseases. For them, there will be AA amyloid deposits in many of the tissues throughout their bodies, with the kidneys most commonly affected.

People with AA amyloidosis may experience complications of other organs, including the heart, digestive tract, liver, spleen, and thyroid.

Any chronic inflammatory condition can lead to AA amyloidosis, but people with rheumatic conditions like rheumatoid arthritis and inflammatory bowel disease seem to have the highest risk.

AA amyloidosis is also associated with heredity diseases that disrupt inflammatory genes like familial Mediterranean fever (FMR). FMR causes frequent episodes of fever often accompanied by pain in the abdomen, chest, or joints.

Transthyretin Amyloidosis

Transthyretin (ATTR) amyloidosis is the second most common type of amyloidosis. There are two types of ATTR amyloidosis: heredity (familiar) ATTR amyloidosis and wild-type ATTR amyloidosis.

Transthyretin (TTR) is a protein produced in the liver that helps to move thyroid hormone and vitamin D into the bloodstream. With ATTR amyloidosis, TTR becomes unstable and breaks apart, depositing in the heart or nerves.

Hereditary ATTR (hATTR) Amyloidosis

This type of amyloidosis is caused by a gene mutation of TTR that has been inherited from one parent. That means hATTR runs in families although having a relative with the condition, or a gene mutation, doesn’t mean you will develop the condition.

Additionally, having the gene mutation cannot predict when you will be diagnosed or how severe your symptoms will be. Besides affecting the heart and nerves, heredity hATTR can affect the digestive system and kidneys, and cause swelling and other symptoms throughout the body.

Wild-Type ATTR Amyloidosis

With wild-type ATTR amyloidosis, the amyloid is caused by a normal wild type protein. This type of amyloidosis is not heredity. Rather, as a person ages, the normal TTR protein will become unstable, misfold, and form amyloid fibers.

These fibers usually find their way to the wrist into the narrow pathway called the carpal tunnel leading to carpal tunnel syndrome, a condition that causes hand and arm numbness and tingling. Fibers can also deposit in the spinal canal leading to spinal stenosis and in the heart leading to heart failure or irregular heart rhythm.

Dialysis-Related Amyloidosis

Dialysis-related amyloidosis (DRA) affects people who have been on dialysis for a long time. It is also common in older adults.

The type of amyloidosis is caused by the buildup of beta-2 microglobulin deposits in the blood. These can build up in many tissues—most commonly the bones, joints, and tendons.

Cardiac Amyloidosis

Amyloid deposits can also affect the muscle of the heart and make it stiff. The deposits weaken the heart and affect its electrical rhythm. Cardiac amyloidosis also reduces blood flow to the heart. Eventually, the heart is unable to pump normally.

Amyloidosis Symptoms

The symptoms of amyloidosis tend to be subtle and will vary depending on where the amyloid protein is collecting.

General symptoms of amyloidosis include:

  • Changes to the skin which may include a waxy thickening, easy bruising of the chest, face, and eyelids, or purple patches around the eyes
  • Severe fatigue that can make even the simplest tasks harder
  • Dizziness or near fainting when standing because the nerves that control blood pressure are affected
  • Numbness, tingling, weakness, or pain in the hands or feet—this is because amyloid proteins collect in the nerves of the fingers, toes, and soles of the feet
  • Urine changes when amyloidosis damages the kidneys causing proteins to leak from the blood into the urine. Urine may also appear foamy.
  • Swelling in the legs, feet, ankles, and/or calves
  • Diarrhea or constipation when amyloidosis affects the nerves controlling the bowels
  • An enlarged tongue if amyloidosis affects the muscles of the tongue
  • Muscle enlargement including in the shoulders
  • Unintentional and significant weight loss because of protein loss.
  • Loss of appetite
  • Digestive system problems that make it harder to digest food and absorb nutrients

Symptoms experienced by people with cardiac amyloidosis include:

  • An irregular heartbeat
  • Shortness of breath even with light activity
  • Signs of heart failure—swelling in the feet and ankles, extreme fatigue, weakness, etc.

Causes

Some types of amyloidosis are caused by outside factors like inflammatory diseases or long-term dialysis. Some types are heredity and caused by gene mutations. Many affect multiple organs while others may affect only one part of the body. 

Certain risk factors can predispose a person to amyloidosis. These may include: 

  • Age: Most people who are diagnosed with AL amyloidosis are between ages 50 and 65 although people as young as 20 can develop this condition.
  • Sex: AL amyloidosis affects more men than women.
  • Other diseases: People with chronic infections and inflammatory diseases have an increased risk for AA amyloidosis.
  • Family history: Some amyloidosis types are heredity.
  • Race: People of African descent have an increased for carrying a genetic mutation associated with cardiac amyloidosis.
  • Kidney dialysis: In people on dialysis, abnormal amyloid proteins can build up in the blood and become deposited into tissue.

Diagnosis

Diagnosing amyloidosis can be hard because symptoms can be vague and not specific. Therefore, it is important to share with your doctor as much information as you can to help them make a diagnosis.

Your doctor will start by performing a thorough physical exam and requesting a detailed medical history. They will also request a variety of tests to help in making a diagnosis.

Testing may include:

  • Blood and urine testing: Both bloodwork and urine testing can check amyloid protein levels. Blood tests can also check thyroid and liver function.
  • Echocardiogram: This is an imaging test using sound waves to take pictures of the heart.
  • Biopsy: With a biopsy, your doctor will remove a sample of tissue from the liver, kidneys, nerves, heart, or another organ to figure out what type of amyloid deposits you may have.
  • Bone marrow aspiration and biopsy: The bone marrow aspiration test uses a needle to remove a small amount of fluid from inside a bone. A bone marrow biopsy removes tissue from inside the bone. These samples are then sent to a lab to check for abnormal cells.

Once your doctor makes a diagnosis of amyloidosis, they will want to figure which type you have. This can be done using immunohistochemistry and protein electrophoresis.

Immunohistochemistry (IHC) is the most commonly used method to subtype amyloidosis. This test involves tissue collection to detect specific amyloid molecules on cells.

A protein electrophoresis test can identify and measure the presence of certain, abnormal proteins, the absence of normal proteins, and/or detect various electrophoresis patterns associated with certain diseases.

This test can be done using either a urine sample or blood sample. When used in combination with IHC testing, it can detect 90% of amyloidosis conditions.

Treatment

There is no cure for amyloidosis but treatment can manage the signs and symptoms of the condition and limit the production of amyloid proteins. When amyloidosis has been triggered by another condition, treating the underlying condition can also be helpful.

Medications used to treat amyloidosis include:

Chemotherapy drugs: Many of the same medications used to treat some types of cancer are used to treat amyloidosis. These drugs can help to stop the growth of abnormal cells responsible for amyloid proteins.

Heart medicines: If amyloidosis has affected your heart, your doctor might include blood thinners to reduce clot risk and medications to control your heart rate. They may also prescribe medications that work to reduce strain on the heart and kidneys. You may need to reduce your salt intake and take diuretics (to reduce water and salt from the body).

Targeted therapies: Targeted therapies, like Onpattro (patisiran) and Tegsedi (inotersen) can interfere with signals sent to genes that create amyloids. Other drugs like Vyndamax (tafamidis) can stabilize proteins in the bloodstream and prevent amyloid deposits.

Some people may need surgery or other procedures to treat amyloidosis:

  • Organ transplant: Some people may need a kidney, liver, or heart transplant if those organs have been severely damaged by amyloid deposits.
  • Dialysis: A person whose kidneys have been damaged by amyloidosis may need dialysis to filter wastes, salts, and other fluids from the blood regularly.
  • Autologous blood stem cell transplant: This procedure will harvest your own stem cells from your blood and after you have high-dose chemotherapy, they will be returned. 

A Word From Verywell

Amyloidosis cannot be cured or prevented. It can be deadly if it affects the heart or kidneys. But early diagnosis and treatment are vital to improving survival.

Talk to your doctor about your treatment options and how to work towards making sure your treatment is doing what it should. Your doctor can make adjustments as needed to reduce symptoms, prevent complications, and improve your quality of life.

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