In amyloidosis, early diagnosis can be key to better outcomes and improved quality of life. Unfortunately, this condition can be difficult to diagnose, and delayed diagnosis is common. Amyloidosis is also thought to be underdiagnosed.

Amyloidosis is a rare condition in which the body makes an abnormally folded protein called amyloid. This protein builds up in tissues and organs and can affect many parts of the body. Amyloidosis can cause a wide variety of symptoms, including very general ones, making it difficult to distinguish from other diseases. For this reason, a range of tests may be used to diagnose amyloidosis. Various tests may serve to confirm a diagnosis, determine the specific type of amyloidosis, or help rule out other conditions.

Physical Exam

Your doctor may perform an examination to look for some of the common signs of amyloidosis. This exam may include:

• Asking you about your personal and family health history
• Checking your joints for stiffness or swelling
• Examining your muscles for unexpected weakness
• Looking at your skin to see if you have any rashes
• Assessing your tongue to see if it’s swollen

Your doctor may also collect blood or urine samples to run laboratory tests. If you have a form of amyloidosis that is systemic — it affects your entire body — amyloid proteins may be present in the blood or urine.

Biopsy

Although many other tests can help indicate whether amyloidosis is a possibility, a biopsy is necessary to confirm a diagnosis. During a biopsy, your doctor will remove a small piece of tissue to be examined for amyloid proteins. If your doctor thinks you may have a form of systemic amyloidosis, they may take a tissue sample from your bone marrow (spongy tissue inside certain bones), abdominal fat (sometimes called your “fat pad”), inner lip, or skin. However, if you have localized disease, which affects just one organ, the doctor may take a sample directly from that organ.

The biopsy sample will be sent to a laboratory and mixed with a dye called Congo red stain. A specialist called a pathologist will examine the sample under a special microscope. If amyloid proteins are present, the Congo red stain will make the sample appear green.

Bone Marrow Biopsy

The most common type of amyloidosis — known as AL amyloidosis, amyloid light-chain amyloidosis, or primary amyloidosis — is a disease of the bone marrow, which makes new blood cells. AL amyloidosis develops due to dyscrasia, or abnormality, of the plasma cells found in bone marrow. Plasma cells are white blood cells that protect the body from germs. When there are problems with these cells, they can make too much of a protein called immunoglobulin light chain, which is normally used to make infection-fighting antibodies. That’s why this type of amyloidosis is also called immunoglobulin light-chain amyloidosis.

If there’s a chance you have AL amyloidosis, your doctor may want to look closer at your bone marrow to see if you have abnormal plasma cells or amyloid deposits. A bone marrow test usually involves two parts:

• Aspiration — Removal of some of the bone marrow fluid
• Biopsy — Removal of a very small core of the solid bone marrow tissue

Other types of amyloidosis may start in different organs but can later spread to the bone marrow. You also may need a bone marrow aspiration or biopsy if your doctor suspects you have another form of amyloidosis.

Biopsies of Other Organs

If there’s a chance that some of your other organs are affected by amyloid deposits, your doctor may want to biopsy tissue at those locations too. For example, a type of amyloidosis known as AA amyloidosis can lead to kidney damage. If your doctor suspects you may have AA amyloidosis, they may want to take a biopsy of the kidney. Other areas that may need to be biopsied include the liver, heart, nerves, and organs of the digestive system.

Some people with amyloidosis also have skin symptoms. These can include purpura (small red or purple spots), blood blisters, brittle nails, and hair loss. Diagnosing these problems often requires a skin biopsy.

Imaging Tests

Your health care team can use imaging tests to visualize any abnormalities and get a closer look at how your organs are working. One test your doctor may use is an ultrasound, which takes pictures of organs using sound waves. Another possible imaging test is MRI, in which radio waves and magnetic fields create a precise picture of your internal organs. MRI can help your doctor evaluate organ health.

Nuclear imaging tests can also provide pictures of organs. Nuclear imaging uses a small amount of radioactive material to highlight different tissues. Doctors can use this information to get an idea of the type of amyloidosis and determine which amyloidosis treatment options may be most likely to help.

Some people with amyloidosis also get X-rays or CT scans. These imaging tests can help your doctor see if there are amyloid proteins in your joints, ligaments, tendons, or bones. This information can be helpful for diagnosing dialysis-related amyloidosis and other types of the condition that affect the joints.

Organ Tests

If your doctor finds amyloid fibrils (clumps) in certain organs, they may perform further tests to see if the organs are working correctly. Basic blood and urine tests can provide a clues to whether amyloidosis is causing damage in these organs:

• Kidneys — A lot of protein in urine may be a sign of kidney damage
• Liver — High levels of alkaline phosphatase in blood may indicate liver problems
• Heart — Blood tests that measure markers like troponin or brain natriuretic peptide can provide information about heart health

If you have wild-type ATTR or hereditary ATTR amyloidosis, your doctor may also test your cardiac function in more depth. Heart tests may include an electrocardiogram or an echocardiogram. These tests can check the structure and function of the heart and identify problems like cardiomyopathy, in which your heart has problems pumping blood correctly. Some people with heart-related amyloidosis end up having heart failure, so it’s important to regularly test the function of your heart.

People with gastrointestinal or digestive symptoms may also need other tests. One possible diagnostic test is an endoscopy, in which a tube with a camera is inserted down the throat and into the esophagus, stomach, and small intestines.

In another test, called a colonoscopy, a tube and camera go into the rectum and large intestine. These tests can help doctors visualize possible digestive system damage, take biopsy samples, and treat symptoms such as bleeding.

Determining the Type of Amyloidosis

After you have a diagnosis of amyloidosis, you’ll need to know which type of amyloidosis you have. If your health care team identifies amyloid fibrils during a biopsy of the bone marrow, kidney, or another organ, a pathologist may also test that same biopsy sample to determine exactly which abnormal proteins are causing the amyloid deposits.

If your doctor thinks you have AL amyloidosis, further testing can help your health care team determine if there are problems with your plasma cells or abnormal light-chain proteins. These tests may include:

• Bone marrow biopsy to look more closely at plasma cells
• Serum free light-chain assay to analyze levels of light-chain proteins in the blood
• Immunofixation electrophoresis to measure light-chain proteins in the blood or urine

AA amyloidosis occurs along with an underlying disease, such as rheumatoid arthritis or an inflammatory bowel disease like Crohn’s disease or ulcerative colitis. If you know you have one of these conditions, your doctor may want you to undergo diagnostic tests if you develop a symptom of amyloidosis. This often includes looking at protein levels in the urine or taking a kidney biopsy. Some people are diagnosed with AA amyloidosis without realizing that they have an underlying condition. If this is the case for you, you may also have diagnostic tests to figure out which other inflammatory disease you have.

Hereditary amyloidosis is caused by genetic mutations. However, hundreds of genetic changes may be responsible for this disease. To figure out which one you have, your doctor can take a blood sample and use genetic testing to read the sequence of genes like transthyretin (TTR).

Some people with kidney disease develop dialysis-related amyloidosis. This subtype often causes amyloid deposits to collect in the bones or joints, leading to bone cysts, joint pain, and swelling. Diagnosis often includes imaging tests, such as X-rays, to look for these signs.

You Are Not Alone With Amyloidosis

On MyAmyloidosisTeam, the social network for those living with amyloidosis, more than 2,000 members come together to discuss life with amyloidosis and share their experiences.

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