The National Institutes of Health has classified amyloidosis as a rare condition — one that affects fewer than 200,000 Americans. (1) While most experts who study the disease say it’s presumably much more common than those estimates, it’s a fact that most doctors aren’t well trained to spot the signs or symptoms of amyloidosis. This can make it difficult for individuals with amyloidosis to find a proper diagnosis and treatment.
“It’s very likely that many patients who have amyloidosis die without ever knowing they had it,” says Morie Gertz, MD, an amyloidosis expert and professor of medicine at Mayo Clinic in Rochester, Minnesota. Especially for people with diseases of the heart, liver, or kidneys, there’s a small but distinct possibility that amyloidosis either caused or (more likely) contributed in some way to the development of those problems.
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“Cardiologists are just now becoming more savvy,” meaning they’re more aware of the signs and symptoms of amyloidosis, says Raymond Comenzo, MD, a professor at the Tufts University School of Medicine in Boston and the director of the school’s John C. Davis Myeloma and Amyloid Program. But apart from heart specialists working at major medical centers, there’s a high likelihood that a doctor treating someone with amyloidosis won’t recognize the disease’s indicators, he says.
Dr. Comenzo points out that there are roughly 30 different amyloid-producing proteins that can malfunction, each producing different types of amyloidosis as a result — and each having potentially different symptoms. While some types and symptoms are more common than others, all this variability can make diagnosis a struggle.
Plus, most symptoms of amyloidosis are what doctors term “nonspecific,” meaning they are not specific to amyloidosis and are linked to a number of different and unrelated medical conditions.
Many individuals with amyloidosis will see multiple doctors to address their various symptoms, and it may take years before receiving an accurate diagnosis, according to Comenzo. Additionally, there are individuals with the condition who never manage to get diagnosed.
“It’s really hard for patients,” Dr. Gertz says.
Though Amyloidosis Symptoms Vary Widely, These Are Some of the Most Common Ones
While amyloidosis can cause a wide range of nonspecific symptoms — symptoms that are dictated by the organ or other part of the body that is most affected — some are much more common than others.
“I’d say the most common symptoms are swelling, weight loss, shortness of breath with exertion, and numbness or tingling in the feet,” Gertz says. These symptoms usually result from amyloid protein accumulations in a patient’s heart or kidneys. He’s quick to add that, in 100 people with these symptoms, only one (or even none) might turn out to have amyloidosis. But these are the kinds of things that may raise suspicion of amyloidosis.
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Comenzo agrees. “If someone has persistent shortness of breath and their doctor can’t figure out why, and they’re also swollen and have lost 40 pounds, then it’s legitimate to push forward and look for amyloidosis,” he says.
Specific Urine and Blood Tests Can Help Point to or Rule Out Amyloidosis
If an individual’s symptoms point to amyloidosis, the first step in confirming the presence of the disease would be either a urine test, a blood test, or both. High levels of protein in a person’s urine can be caused by the buildup of amyloid in that person’s kidneys. “Protein in urine is a very powerful indicator of amyloidosis,” Gertz says. “It’s not routine to do this kind of urine analysis, but it’s a simple test.”
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Along with checking a patient’s urine for protein, several types of blood testing can provide clues that point toward amyloidosis. These tests may be able to detect an elevated presence of certain antibodies, as well as some biomarkers of heart disease — either of which could help a doctor zero in on one or another form of amyloidosis. (2)
Tissue Biopsies Can Often Confirm Amyloidosis
If a doctor suspects amyloidosis, those early tests will usually be followed by some kind of tissue or bone marrow biopsy. Amyloidosis is a disease caused by the buildup of protein deposits, Comenzo says, so doctors can use biopsies to find evidence of these deposits.
Doctors may perform a biopsy on the affected organ — such as the kidneys or heart. But in some cases, they can also look at the tissues of a “surrogate site,” such as abdominal fat, he says.
What are they looking for? “If you look at tissue that has amyloid in it, you will see these little needles,” Comenzo explains. “These little needles vary in length, but they have a characteristic width that is diagnostic of amyloid.”
Some other types of tissue analysis may also help to confirm the presence of amyloid deposits. “There’s a particular type of dye called Congo red that puts itself between these strands of amyloid fibrils,” Comenzo explains. When this dye is added to amyloid-riddled tissue and looked at under polarized light, the tissue appears to be “apple green,” he says. (However, Congo red staining alone is not enough to diagnose amyloidosis, according to research from 2019.)
Diagnosing a Specific Subtype of Amyloidosis Can Be Tricky, Too
While the above tests can help doctors determine if a patient has amyloidosis, they do not reveal exactly which type of the disease is present. This step is critical because amyloidosis treatment differs from one type to the next.
To pin down the type of amyloidosis someone has, doctors may employ a few different categories of follow-up analysis. For example, “mass spectrometry” is a process that allows doctors to determine which specific type of protein is involved in an individual’s disease. Also, genetic testing can in some cases help doctors pin down specific types of amyloidosis (if there is a genetic component to the disease). (3)
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What’s important to know is that diagnosing amyloidosis is usually a complicated and multistage process, Comenzo says. It’s also one that can take weeks or even months to complete. But it’s worth it. A proper diagnosis ensures an amyloidosis patient will receive the type of care and treatment needed for the best possible outcome.