Amyloidosis

Overview

Amyloidosis is a condition in which the body is unable to deal with certain proteins that have folded into an abnormal shape. Normally, proteins in the body do their job and are then broken down and cleared away. In amyloidosis, some proteins misfold into a stiff, insoluble structure called amyloid and gradually accumulate in organs, disrupting the way those organs work.

Amyloid deposits can build up in almost any organ. The heart, kidneys, liver, nervous system, and digestive tract are the most commonly affected. Because different organs produce such different symptoms, amyloidosis can be difficult to recognize at first — and is sometimes mistaken for other conditions.

Amyloidosis is a rare disease, and it comes in several distinct types. Each type has a different cause, a different course, and a different treatment. So when a doctor tells you that you have amyloidosis, understanding which type you have is the first and most important step.

There is genuinely good news: treatment has advanced significantly in recent years. For several types of amyloidosis, medications now exist that can halt or substantially slow the progression of the disease. Early diagnosis makes a real difference to what is possible.

Types of Amyloidosis

Amyloidosis is not one disease but a group of related conditions. What distinguishes each type is which protein is misbehaving and accumulating.

• AL amyloidosis (light chain amyloidosis). The most common type. Certain immune cells in the bone marrow produce an abnormal protein in excessive amounts, and this protein builds up in the organs. The heart and kidneys are most often affected. AL amyloidosis can be associated with a bone marrow cancer called multiple myeloma, though in many cases myeloma is not present.
• ATTR amyloidosis (transthyretin amyloidosis). A protein made by the liver called transthyretin misfolds and accumulates. There are two subtypes. The hereditary form is caused by a gene change passed down through families and tends to start at a younger age. The wild-type form has no specific genetic cause and typically affects men over the age of 60. Both forms mainly affect the heart and nerves.
• AA amyloidosis (secondary amyloidosis). In people with long-standing inflammatory conditions such as rheumatoid arthritis, inflammatory bowel disease, or chronic infections, the body produces a particular protein in large amounts over many years. This protein can eventually accumulate, mainly in the kidneys. Bringing the underlying inflammatory disease under control can slow or stop AA amyloidosis from progressing.
• Dialysis-related amyloidosis. In people who have been on kidney dialysis for many years, a specific protein can build up in the joints and bones, causing joint pain and a condition called carpal tunnel syndrome.

Symptoms

The symptoms of amyloidosis depend on which organs are affected. This is why the condition sometimes goes unrecognized for a long time or gets confused with other diseases.

When the heart is affected, the following symptoms can occur:

• Shortness of breath. When amyloid deposits make the heart muscle stiff, the heart cannot pump blood efficiently. Breathlessness that first appears during exertion — climbing stairs or walking briskly — can gradually occur with lighter activity or even at rest.
• Swelling in the legs. When the heart is not pumping well, fluid accumulates in the body. Swelling in the ankles and legs that tends to worsen during the day is a common sign.
• Palpitations and fainting. Amyloid can affect the heart's electrical system, causing an irregular heartbeat, palpitations, or sudden fainting episodes.
• Severe fatigue. When the heart is struggling to circulate blood efficiently, the whole body feels the effect. A deep tiredness that makes even everyday tasks feel difficult is a common experience.

When the kidneys are affected, the following symptoms can occur:

• Foamy urine. When amyloid damages the kidneys, they begin to leak protein into the urine. Noticeable foaming or bubbling in the toilet bowl can be a sign of this.
• Swelling throughout the body. As protein leaks out of the blood, fluid seeps into surrounding tissues. Puffiness around the eyes, swelling in the legs, and sometimes fluid in the abdomen can develop.

When the nerves are affected, the following symptoms can occur:

• Numbness, tingling, or burning in the hands and feet. When nerves are damaged by amyloid deposits, the hands and feet begin to feel strange — numb, tingly, or burning. This sensation can gradually spread upward over time.
• Balance problems and falls. Nerve damage can also affect balance and walking, increasing the risk of falls.
• Dizziness when standing up. When the nervous system is involved, the body's ability to regulate blood pressure can be impaired. Standing up from a seated or lying position can bring on sudden dizziness or light-headedness.
• Diarrhea or constipation. Amyloid affecting the nerves that control the digestive tract can disrupt bowel habits in either direction.

Other symptoms include the following:

• Weight loss and loss of appetite. These become more noticeable when the digestive system is involved or as the disease progresses more broadly.
• An enlarged tongue. In AL amyloidosis, the tongue can become visibly larger than normal, causing difficulty swallowing and speaking.
• Bruising around the eyes. Spontaneous purple bruising around the eyes — often first noticed on waking — is one of the more distinctive signs of AL amyloidosis.
• Carpal tunnel syndrome. Numbness and pain in the hand spreading from the wrist. When this occurs in both hands simultaneously, it is worth investigating for amyloidosis.

When to See a Doctor

Because many symptoms of amyloidosis overlap with other common conditions, it can be easy to overlook in the early stages. But the following situations are worth bringing to a doctor's attention.

Schedule a medical evaluation if:

• You have unexplained fatigue, breathlessness, and leg swelling occurring together
• You have noticed obvious foaming in your urine
• Numbness, tingling, or burning is affecting both hands or both feet
• Spontaneous bruising around your eyes has appeared
• You have carpal tunnel symptoms in both hands at the same time
• You have rheumatoid arthritis or another chronic inflammatory condition and your kidney test results are worsening
• There is a family history of amyloidosis, or unexplained heart or nerve disease in close relatives

Causes

The cause of amyloidosis depends on the type, but the underlying problem is always the same: a protein in the body folds into the wrong shape and cannot be cleared away.

• In AL amyloidosis, certain bone marrow cells have gone out of control and are producing an abnormal protein in excessive amounts. Why this happens in some people and not others is not yet fully understood. These cells sometimes develop into a cancer called myeloma, but in many patients they do not.
• In hereditary ATTR amyloidosis, a gene change inherited from a parent causes the liver to produce a version of transthyretin protein that misfolds more easily. Not everyone who carries this gene change will develop the disease, but a significant proportion will as they age.
• In wild-type ATTR amyloidosis, there is no specific inherited gene change. The transthyretin protein simply becomes more prone to misfolding with advancing age. This form is particularly common in men in their 70s and 80s and can go undetected for years.
• In AA amyloidosis, long-standing inflammatory or infectious diseases — such as rheumatoid arthritis, Crohn's disease, or tuberculosis — cause the body to produce a particular protein continuously over many years. This protein is harmless in small amounts, but persistent overproduction can eventually lead to tissue accumulation.

Risk Factors

The known risk factors for amyloidosis include the following:

• Older age. Amyloidosis can develop at any age but becomes considerably more common after 60. Wild-type ATTR amyloidosis in particular is predominantly a disease of men in their 70s and 80s.
• Family history. In hereditary ATTR amyloidosis, a family history of the condition is an important risk factor. The gene change is passed from parent to child and is more common in certain families and ethnic groups.
• Multiple myeloma or similar blood disorders. AL amyloidosis is closely linked to bone marrow conditions. People diagnosed with myeloma are monitored for amyloidosis development.
• Chronic inflammatory diseases. Rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease, and chronic infections raise the risk of AA amyloidosis. How long you have had the inflammatory disease and how well it has been controlled are the most important factors determining this risk.
• Long-term kidney dialysis. Patients who have been on dialysis for many years can develop a buildup of certain proteins in their joints, leading to pain and mobility problems.
• Male sex. Some forms of amyloidosis — particularly wild-type ATTR — are considerably more common in men.

Diagnosis

Diagnosing amyloidosis can take time. Because the symptoms resemble so many other conditions, it is sometimes only identified after other possibilities have been ruled out. But with the right tests, a clear diagnosis is achievable.

Diagnostic methods include the following:

• Blood and urine tests. These look for abnormal proteins in the blood and urine. In AL amyloidosis, the abnormal protein produced by bone marrow cells can be detected this way. Tests that reflect kidney function and measure the strain on the heart also provide important early clues about which organs are being affected.
• Biopsy. A small tissue sample examined under a microscope is required to confirm the diagnosis. In many cases, a simple fat pad biopsy — in which a tiny amount of fat tissue is taken from just below the skin of the abdomen — is sufficient and is minimally uncomfortable. If needed, a sample can be taken from the heart, kidney, or liver. Amyloid deposits are identified in the sample using special stains that make them glow under the microscope.
• Heart ultrasound (echocardiogram). This checks whether the heart has been affected by amyloid deposits. A heart with significant amyloid has a characteristic thickened, sparkling appearance on ultrasound that an experienced doctor will recognize.
• Cardiac MRI. Provides more detailed images of amyloid in the heart. Helps both to confirm the diagnosis and to assess how far the disease has progressed.
• Nuclear scan (scintigraphy). A specialized scan that can detect ATTR amyloidosis in the heart without a biopsy. In the right clinical setting, a positive result on this scan strongly supports the diagnosis of ATTR amyloidosis.
• Genetic testing. When hereditary ATTR amyloidosis is suspected, a gene test is performed. This is particularly valuable when there is a family history of the condition or when the disease appears at a relatively young age.
• Bone marrow biopsy. In AL amyloidosis, this test assesses the number and characteristics of the abnormal bone marrow cells producing the protein. This information shapes the treatment plan.

Treatment

Treatment for amyloidosis varies considerably depending on the type. But the shared goal is always to stop or slow new amyloid from forming and to protect the organs that have already been affected.

Treatment options include the following:

• Treatment for AL amyloidosis. The aim is to suppress the bone marrow cells that are producing the abnormal protein. Chemotherapy and newer targeted drugs reduce the number of these cells, cutting off the supply of amyloid. In suitable patients, high-dose chemotherapy followed by a stem cell transplant can produce long-lasting remission. Daratumumab is a newer treatment that has shown impressive results in AL amyloidosis in recent years. When treatment works well, the existing amyloid deposits in the organs can gradually decrease, and organ function can partially recover.
• Treatment for ATTR amyloidosis. The key approaches either prevent the transthyretin protein from misfolding in the first place or dramatically reduce how much of it the liver produces. Tafamidis is a tablet taken once daily that stabilizes the protein and has been shown to meaningfully slow the progression of heart disease in ATTR amyloidosis. Patisiran and inotersen are treatments that reduce the liver's production of this protein by a large amount; they are used for both heart and nerve involvement. Liver transplantation can be an option in some forms of hereditary ATTR amyloidosis, as it removes the source of the abnormal protein.
• Treatment for AA amyloidosis. Bringing the underlying inflammatory or infectious disease under control is the primary approach. Effective treatment of conditions like rheumatoid arthritis can stop AA amyloidosis in its tracks and, in some cases, even allow the deposits to partially resolve over time.
• Supporting the affected organs. Regardless of the type, managing the symptoms in the organs that have been damaged is an important part of care. This includes heart failure medication, dialysis or kidney transplantation for kidney failure, pain management and physiotherapy for nerve symptoms, and dietary adjustments when the digestive system is involved.

Complications

If amyloidosis is not treated or is caught late, it can cause serious and lasting damage. The complications depend largely on which organs have been affected.

• Heart failure. Amyloid deposits make the heart muscle stiff and impair its ability to fill and pump effectively. This type of heart failure can sometimes respond less well to standard heart medications — which is why treatments targeting amyloidosis directly are so important.
• Kidney failure. Progressive kidney damage can eventually mean the kidneys can no longer filter the blood adequately. In advanced cases, dialysis or a kidney transplant may be needed.
• Nerve damage. Numbness in the hands and feet can progress to weakness over time. Loss of balance increases the risk of falls. When the nerves controlling the bladder and digestive system are affected, daily life can be significantly disrupted.
• Dangerous heart rhythm problems. When amyloid affects the electrical system of the heart, serious rhythm disturbances can develop. An implantable defibrillator device may be recommended in some patients to reduce the risk of a life-threatening episode.

Living with Amyloidosis

Being diagnosed with amyloidosis can feel overwhelming. "How will this progress?" and "How will my life change?" are completely natural questions to ask. The honest answer is that it depends significantly on which type you have and how early it was caught — but for many people, a meaningful and manageable life is very much possible.

Staying on Top of Treatment

Taking your medication consistently makes a direct difference to how the disease progresses. For ATTR amyloidosis in particular, daily medication like tafamidis has been shown to measurably slow heart damage. Never stop your medication on your own; if you experience side effects, talk to your doctor — there are usually options to address this without stopping treatment.

Heart and Kidney Monitoring

Regular check-ups are essential for tracking how the disease is behaving and whether treatment is working. Your doctor will likely arrange blood tests, urine tests, heart ultrasounds, and other assessments at regular intervals. Missing these appointments can mean that important changes go unnoticed until they become harder to manage.

Eating Well and Managing Daily Life

If your kidneys are affected, your doctor or dietitian may advise you to limit salt, protein, or fluid intake. For the heart, reducing salt and avoiding excess fluid helps ease the workload. If your digestive system is involved, eating small, frequent meals of easily digested foods tends to work better than large meals. A dietitian who understands your situation can be enormously helpful in making these adjustments practical and sustainable.

Psychological Support

Being diagnosed with a rare and complex condition can feel isolating. Talking to a psychologist or counselor, and connecting with others through amyloidosis patient support groups, can both lighten the emotional burden and help you develop effective ways to cope. Keeping those close to you informed about the disease makes it easier for them to provide the kind of support that genuinely helps.

Talking to Your Family

If you have hereditary ATTR amyloidosis, this information matters for your family too. First-degree relatives can be tested to find out whether they carry the same gene change. For any family member who tests positive, this is an opportunity to begin monitoring and, if needed, treatment at the earliest possible stage — when it is most effective.

Preparing for Your Appointment

Coming prepared to your appointment helps you get the most out of the time with your doctor and makes it easier to have the conversation you need to have.

What you can do:

• Note when symptoms began and how they have changed over time
• Observe when symptoms like leg swelling, breathlessness, or numbness tend to be at their worst during the day
• Bring any recent blood or urine test results if you have them
• Mention any family history of heart disease, kidney disease, or nerve problems — especially if it occurred in multiple relatives or at a younger age
• Mention any diagnosis of rheumatoid arthritis or other chronic inflammatory condition
• List all current medications
• Write your questions down in advance so you don't forget them during the appointment

Questions you may wish to ask your doctor:

• Which type of amyloidosis do I have?
• Which of my organs are affected?
• How quickly is it progressing?
• Do I need treatment and which treatment is right for me?
• Is the goal to stop the disease or to slow it down?
• Could my family members be at risk? Should they be tested?
• Are there any dietary changes I should make?
• How often do I need to come in for check-ups?

Questions your doctor may ask:

• When did the first symptom appear and how did it start?
• Do you have swelling in your legs or around your eyes?
• Are you experiencing shortness of breath, and when does it feel worse?
• Do you have any numbness or tingling in your hands or feet?
• Do you have rheumatoid arthritis or any other chronic condition?
• Is there a family history of similar symptoms or unexplained heart disease?
• Have you noticed foaming in your urine?
• Have you lost weight recently without trying to?