For many diseases, a slew of symptoms often points to a specific diagnosis. But for amyloidosis, the path to diagnosis can be trickier.
Amyloidosis can affect people of any age, but it is more common in older men. It occurs when abnormal proteins build up in the tissues and organs and form amyloid, which can impair organ function. Amyloidosis can affect one area of the body or multiple areas at once, depending on which type of amyloidosis is present.
“The protein in blood is not the issue; it’s the small, stiff protein fibers being deposited into organs where they don’t belong,” says UNC Health Care cardiologist Mirnela Byku, MD, PhD. “They stick to those tissues, and they create problems.”
For example, if the protein fibers deposit into the heart, they can cause inflammation and the buildup of scar tissue, which can lead to the stiffening of the heart muscle and heart failure.
Amyloidosis is considered a rare disease—about 4,500 new cases of the most common type are diagnosed each year in the U.S.—but recent research suggests it might be more prevalent than recently thought.
“Amyloidosis is thought to be way more common than what we know. For a long time, it’s been underdiagnosed due to the fact that a lot of its key symptoms are generic,” Dr. Byku says. “Autopsy and biopsy tissue data have shown that these abnormal protein deposits are much higher than the rate of clinical diagnosis.”
At UNC, a multidisciplinary team of specialists works to care for patients with amyloidosis, meeting regularly to collaborate on treatment plans and running clinical trials to study new drugs. The physician teams include cardiologists, oncologists, hematologists, nephrologists, neurologists and others.
“This type of multidisciplinary team is unique to amyloid specialty centers like UNC, and it’s critical to successfully managing patients. If I need to give someone chemotherapy for amyloidosis and that patient’s amyloid has damaged their heart and kidneys, for example, you can imagine that my treatment is far more effective if I have help from heart and kidney amyloid experts to manage those systems,” says Sascha Tuchman, MD, who directs the UNC Multiple Myeloma and Amyloidosis Program. “Patients do much better when we work as a team.”
Types of Amyloidosis
AL amyloidosis, also referred to as light chain amyloidosis, is historically thought to be the most common type in the U.S. It is caused when bone marrow produces abnormal “light chain” protein particles that form amyloid in different areas of the body. It can affect the heart, kidneys, skin, nerves, liver or other organs. It is often treated with chemotherapy and sometimes stem cell (bone marrow) transplantation.
AA amyloidosis happens as a reaction to other chronic infectious or inflammatory diseases, such as rheumatoid arthritis or Crohn’s disease. This type most commonly harms the kidneys, but patients might experience complications with the liver, spleen, thyroid, digestive tract or heart. It’s often treated with medication to address the underlying condition, such as anti-inflammatory drugs for rheumatoid arthritis.
TTR (transthyretin) amyloidosis is probably the most underdiagnosed type of amyloidosis. TTR proteins are produced in the liver; once in the bloodstream, they separate into smaller, misshaped units that eventually form the harmful amyloid fibers. These amyloid fibers most commonly deposit in the nerves and heart. However, the gastrointestinal tract can also be involved. Spinal stenosis and carpal tunnel syndrome are also common in this condition because of deposits in the spine and tendons. TTR amyloidosis can be genetically inherited.
- Hereditary (familial) TTR amyloidosis is an inherited condition that often affects the nerves and heart and runs in families. Many genetic mutations can increase a person’s risk of amyloidosis. The age when symptoms appear and how the disease progresses vary depending on the mutation.
- Wild-type (senile) TTR amyloidosis does not run in families. It is mostly a disease of older men and manifests with carpal tunnel syndrome, spinal stenosis and heart failure.
For TTR amyloidosis, new treatments are available that involve suppressing TTR protein production in the liver and stabilizing the TTR protein in the blood. Studies are ongoing to look at new medications that help the body to clear amyloid that’s deposited in organs already.
Symptoms of Amyloidosis
It may be hard to tell if you’re experiencing amyloidosis because the warning signs can be subtle. The symptoms a person experiences also largely depend on where the amyloid protein fibers are collecting in the body. Symptoms can include one or more of the following:
- Shortness of breath
- Swelling in the extremities
- Skin changes, such as easy bruising or purple patches around the eyes
- Thickened tongue
- Numbness and tingling in the hands and feet
- Carpal tunnel syndrome
- Back pain
- Unexplained weight loss
- Alternating and persistent constipation and diarrhea
Because many of these symptoms are common in other conditions, such as heart disease or diabetes, Dr. Byku says diagnosing amyloidosis is often challenging. If one or more of these symptoms is present without other explanation, it may indicate that amyloidosis is the underlying problem.
“For example, a thickened heart muscle is usually caused by longstanding high blood pressure,” she says. “But if you have someone who comes in with a thickened heart muscle, shortness of breath and normal to low blood pressure, that’s inconsistent with that condition.”
At that point, a doctor will go through a person’s medical history and perform a physical exam to look for other symptoms that could be related to amyloidosis.
The Importance of a Diagnosis and Treatment for Amyloidosis
Early diagnosis and starting treatment as soon as possible are key for people with amyloidosis. Amyloidosis is an incurable, chronic condition, but treatment can help manage disease progression and symptoms for a long time, even years. A person’s exact care plan will depend on the type of amyloidosis he or she is experiencing and factors unique to the patient. Left untreated, amyloidosis can lead to organ failure and death.
“Understanding which type of amyloidosis a person has is very important, so first you’ll have to do the right testing to diagnose the subtype,” Dr. Byku says. Blood tests, tissue biopsies and imaging tests might be performed.
The workup is complicated, so knowing what testing to do, interpreting results and arriving at a correct diagnosis of amyloidosis can be a challenge for physicians who don’t see a lot of this disorder, Dr. Tuchman adds.
“Patients can often be extremely ill. An incorrect diagnosis can lead to incorrect treatment, such as chemotherapy for a type of amyloid that doesn’t respond to chemotherapy, which just makes things worse,” he says. “I see diagnostic and therapeutic errors of that type at least once or twice a year. Referral to a specialty center to get the diagnosis and treatment plan right the first time around is so important for helping people to do well with amyloidosis.”
Learn more about treatment for amyloidosis at UNC Lineberger Comprehensive Cancer Center. If you’re experiencing symptoms that concern you, talk to your doctor or find one near you.