Amyloidosis is a rare disease in which amyloid proteins can build up in your blood and be deposited in various organs—interfering with normal organ function and even leading to organ failure.* The disease has no cure, but an early diagnosis can help prevent further organ damage. It’s important to know the signs, symptoms, and risk factors of amyloidosis so you know when to seek medical attention. 

What are the symptoms of amyloidosis?

Symptoms may not become noticeable until the condition is advanced. The symptoms that do manifest can depend on which organs are affected. 

Symptoms of amyloidosis can include:

• Swelling of legs and ankles
• Weakness and fatigue
• Shortness of breath (with little exertion)
• Numbness, tingling, or pain in hands, wrists, and/or feet
• Diarrhea (with or without blood) or constipation
• Unintentional weight loss of >10 pounds 
• Enlarged tongue, possibly rippled around the edge
• Skin changes (thickening, easy bruising, purple patches around eyes)
• Irregular heartbeat
• Difficulty swallowing

What causes amyloidosis?

There are many subtypes of amyloidosis, which include:

• AL amyloidosis (primary amyloidosis): The most common subtype, AL amyloidosis is caused by abnormal white blood cells, called plasma cells, in the bone marrow. It usually affects the heart, kidneys, liver, and nerves.
• AA amyloidosis (secondary amyloidosis): The AA subtype is caused by the inflammatory protein serum amyloid A. Usually triggered by an inflammatory disease, AA amyloidosis most commonly affects the kidneys, liver, and spleen.
• Hereditary amyloidosis (familial amyloidosis): This occurs when a particular protein (transthyretin, or TTR) produced by the liver is abnormal. It mostly affects the nerves, heart, and kidneys. 
• Wild-type amyloidosis (ATTRwt amyloidosis): This occurs when your TTR is normal but produces amyloid anyway. It mainly develops in men over age 70 and affects the heart. It can also lead to carpal tunnel syndrome.
• Localized amyloidosis: This subtype is not systemic and frequently has a better prognosis than those that affect multiple organ systems. It may affect the bladder, skin, throat/trachea, or lungs. 
• Dialysis-related amyloidosis (beta2-microglobulin amyloidosis or ABM2): This type occurs in patients who are near end-stage kidney disease (ESKD), usually after years of being on dialysis.

What are the risk factors for amyloidosis?

Your risk of amyloidosis may increase due to:

• Age: Most diagnoses occur between the ages of 60 and 70.
• Sex: Amyloidosis is more common in men.
• Other conditions: Chronic infections and inflammation raise the risk of AA amyloidosis.
• Family history: Some forms of the disease are hereditary.
• Dialysis: Even if you’re on dialysis, abnormal proteins can build up in your blood.
• Race: African ancestry seems to increase the risk of a genetic mutation linked to amyloidosis.

What are some complications of amyloidosis?

Amyloidosis can seriously damage your:

• Heart: Amyloid reduces your heart’s ability to fill with blood between heartbeats. Less blood is pumped with each beat. This can become life-threatening.
• Kidneys: Amyloid can harm the kidneys’ filtering system, causing protein to leak from your blood into your urine, which may eventually lead to kidney failure.
• Nervous system: Amyloidosis that affects your nervous system can affect multiple organ systems—compounding organ damage and reduced function.

How is amyloidosis diagnosed?

Treatments vary, depending on your amyloidosis subtype and the organ(s) affected, so a precise diagnosis is critical. 

• Blood and urine tests may be analyzed for abnormal protein. Thyroid and liver function tests may also be ordered. 
• A tissue sample (biopsy) may be taken from subcutaneous abdomen fat, bone marrow, or an affected organ (liver, kidney, etc.).
• Imaging tests may be ordered, such as an echocardiogram (to show how well your heart is functioning), an MRI (to assess the structure of your heart), and/or nuclear imaging (to reveal early heart damage and help determine the subtype).

How is amyloidosis treated?

Since there is currently no cure for this disease, treatments are intended to reduce amyloid production and control symptoms. The two primary treatments include medication and medical procedures.

Medications may include:

• Chemotherapy to halt the growth of abnormal protein-producing cells 
• Heart medications to thin your blood, control your heart rate, and/or increase urination
• Targeted therapies, such as patisiran (Onpattro) and inotersen (Tegsedi) to intercept faulty genes and tafamidis (Vyndamax, Vyndaqel) and diflunisal to stabilize the protein in your blood

Surgical and other procedures include:

• Autologous blood stem cell transplant, in which your stem cells are harvested to be reintroduced to your body following chemotherapy
• Dialysis if you have sustained severe kidney damage
• Organ transplant to replace your heart, kidneys, or liver, depending on the organ(s) affected, and the severity of the damage

It’s important to note that amyloidosis can be triggered by another medical condition, such as rheumatoid arthritis (RA) or tuberculosis, and your doctor will need to treat both the underlying condition and amyloidosis.

*Mayo Clinic. (2020, Mar. 14). Amyloidosis. https://www.mayoclinic.org/diseases-conditions/amyloidosis/