Amyloidosis: Symptoms, Types & What to Know

Tingling, pain and numbness in the hands and wrists. Fatigue. Shortness of breath. Irregular heartbeat. Lower back pain. Weight loss. Constipation or diarrhea. Erectile dysfunction.

Though these symptoms can be attributed to a variety of health conditions, they are classic indications of amyloidosis — a disease often thought to be rare but likely more prevalent because it can often go underdiagnosed.

Amyloidosis can run in families — 1 in 25 Black Americans carry a gene that increases the risk of developing a subtype of amyloidosis — but other forms of the condition can develop due to chronic inflammation, or for no known reason at all.

We spoke with Dr. Mahwash Kassi, the director of cardiac amyloidosis clinic at the DeBakey Heart and Vascular Center, who treats heart failure and heart transplant patients that experience amyloidosis.

What is amyloidosis?

Amyloidosis is a rare disease that can affect several organs within the body, including the heart, kidneys, nerves and gastrointestinal tract. The condition develops when proteins in your body take on an abnormal shape and begin clumping together.

The proteins, called amyloid fibrils (depending on the type of amyloidosis), are produced in the bone marrow or liver, moving throughout the body and collecting in the organs or tissue. These proteins can stockpile in a single organ or in different organs in the body based on the type of amyloidosis. Over time, the buildup of the proteins causes organ damage and, ultimately, organ failure.

"This disease has been misconceived as a very rare disease," Dr. Kassi says. "Luckily, more awareness is emerging around disease. It presents very subtly. Symptoms at the beginning can be vague and attributed to other conditions, like aging or carpal tunnel, so it's commonly misdiagnosed and overlooked."

Types of amyloidosis

There are two main types of amyloidosis, including:

• AL amyloidosis: This type of amyloidosis occurs when the body makes too many misshapen amyloid light chain (AL) proteins that help create antibodies. These abnormal proteins gather in many organs, including the heart, kidneys, nerves and gastrointestinal tract. This is the most common form of amyloidosis, with the Amyloidosis Foundation estimating that there are 4,500 new cases of the condition every year in the U.S. The condition usually affects people over the age of 50.
• TTR amyloidosis: This amyloidosis type occurs when your liver creates an abnormal form of a protein called transthyretin. These abnormal proteins commonly build up in the heart and nerves. TTR can be inherited and run in families or be nonhereditary and simply develop in someone's lifetime, with diagnosis usually coming after age 70. The inherited form of TTR amyloidosis is caused by one of over 130 known genetic mutations, all of which have a 50-50 chance of being passed to a child.

You may have seen commercials highlighting the symptoms of amyloidosis. Those advertisements are for a particular subtype of TTR amyloidosis. Keep in mind: The name of TTR amyloidosis diagnoses can include different letters based on the type of proteins and organs affected.

Amyloidosis symptoms and warning signs

"Symptoms usually depend on the specific type of abnormal proteins and the organ or organs where they collect," Dr. Kassi says. "When the heart is affected, for example, people will often experience symptoms of heart failure. They'll faint easily, have leg swelling and fatigue, or have shortness of breath."

General amyloidosis symptoms can include:

• Bicep tendon rupture
• Carpal tunnel syndrome (especially when the condition is in both wrists)
• Constipation and/or diarrhea
• Dizziness and low blood pressure when standing (orthostatic hypotension)
• Enlarged tongue (particularly in AL amyloidosis)
• Irregular heartbeat (arrhythmia)
• Numbness/tingling or pain in the hands, wrists or feet
• Inability to feel the difference between warm or cold in hands and feet
• Pain or cramping in legs when standing or walking that dissipates when sitting down or bending forward (spinal stenosis)
• Purple patches around the eyes (commonly referred to as "raccoon eyes" — this appears more often in AL amyloidosis)
• Weight loss

"There are many conditions that share a variety of these symptoms, especially as we get older," Dr. Kassi says. "If you're being treated for your symptoms, and you don't see improvement, you may want to ask your physician for testing. The risk of organ failure increases as the condition goes untreated and the fibrils are allowed to accumulate unchecked."

Treatments for amyloidosis

In the past, Dr. Kassi says that an amyloidosis diagnosis was considered a death sentence.

"Even at the time I was a fellow, we would send people home on hospice or palliative care," Dr. Kassi says. "But we live in a different age. Targeted therapies now exist depending on the type of amyloidosis. This is especially true for TTR amyloidosis, where we have drugs that can halt the protein production and stabilize the condition."

Dr. Kassi adds that ongoing studies of therapies are investigating the removal of the protein from the heart or affected organs. In addition, he notes, there is a gene therapy trial ongoing showing promise for TTR amyloid patients.

For individuals with AL amyloidosis, Dr. Kassi says there are newer chemotherapy options that are better tolerated and have fewer side effects.

Treatments can slow the progression of the disease, but Dr. Kassi emphasizes that organ damage remains difficult to reverse.

"Once the proteins have collected in an organ, especially in the heart, we don't have therapies to release or remove them," Dr. Kassi says. "That makes early diagnosis critical."

Treatment options will depend on the type of amyloidosis. Treatments can include:

• Chemotherapy: Certain types of cancer drugs can be used to help stop the growth of misshapen AL proteins to treat AL amyloidosis.
• Dialysis: Dialysis, a procedure to filter waste from the blood, may be required if the kidneys have experienced enough damage that their function is limited.
• Heart medications: If the heart is affected, medicines that increase urination (diuretics) help to prevent fluid buildup and can help lower the strain on your heart and kidneys. Blood thinners may also be prescribed to lower the risk of blood clots. Other medicines may be used to control the heart rate.
• Organ transplant(s): Amyloidosis can damage organs beyond repair and an organ transplant is needed. Transplants can help restore organ function and help the condition from returning. The types of transplants that may be necessary include:
  • Bone marrow transplant
  • Heart transplant
  • Kidney transplant
  • Liver transplant
  • Multi-organ transplant (Individuals may need a heart and liver transplant or heart and kidney transplant depending on various factors.)

• Targeted therapies: There are drugs for certain types of amyloidosis that target the signals sent from the genes that cause the condition. Other medicines can prevent the proteins from taking on the abnormal shape, which can slow the buildup.

"The newer treatment options for TTR amyloidosis improve symptoms, and patients have better outcomes," Dr. Kassi says. "We have several ongoing clinical trials including silencers, gene therapy and depletory agents that not only halt production but also remove the amyloid from the heart."

Who is at risk for amyloidosis?

Dr. Kassi says that everyone should know the signs of the condition since it's crucial for people to get treated as soon as possible when it can be most effective and to prevent significant organ damage.

"There is a lot we do not understand about amyloidosis, but in general, the patient profile is male, over 60 years of age," Dr. Kassi says. "However, women can get the condition and may be more at risk for types caused by inflammation. The wild-type TTR amyloidosis is considered an age-related phenomenon, while younger patients are often affected when they have a genetic variant or mutation."

Amyloidosis does have a genetic component, and the hereditary form of the condition is more likely to strike in younger individuals. Black Americans and people of Irish descent are more at risk of carrying the genes for TTR amyloidosis — which can do significant damage to the heart. However, there are other populations, including Latinos, where the disease can go underrecognized.

"We definitely see patients in Houston with a specific gene mutation that impact this population," Dr. Kassi says.

If your family health history includes a lot of heart failure, heart transplants or kidney transplants, Dr. Kassi recommends talking to your primary care provider to understand your risk.

"Genetic testing is available and can help your care team monitor you for any signs the condition is developing and complete diagnostic testing as needed," Dr. Kassi says.

Concerned about symptoms? Ask your doctor

Certain types of amyloidosis can be diagnosed with noninvasive tests, such as blood tests and imaging. A bone marrow aspiration or biopsy of the affected organ may also be ordered to aid in diagnosis.

"We want to intervene as soon as possible," Dr. Kassi says. "Those being treated for heart failure and still experiencing shortness of breath, as well as pain in the wrists or lower back pain, should talk to their cardiologist about amyloidosis."