Understanding Amyloidosis: Diagnosis, Treatment, and the Critical Need for Timely Intervention

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• What is Amyloidosis?
• Why Amyloidosis Diagnosis is Challenging
• Consequences of Delayed Diagnosis
• The Role of Specialized Amyloidosis Centers
• Advanced Diagnostic Imaging for Amyloidosis
• Full Transcript

What is Amyloidosis?

Amyloidosis is a serious disease caused by the deposition of abnormal, insoluble protein fibers in the extracellular space of tissues and organs. As explained by Professor Sir Dr. Mark Pepys, MD, these protein fibrils, which can be formed from different precursor proteins, share a similar structure. Their accumulation distorts the architecture of organs, leading to a progressive and severe compromise of function.

There are many different forms of amyloidosis, each classified by the specific protein that forms the fibrils. Despite this variety, the end result is organ damage. Amyloidosis is classified as a rare disease, yet it is responsible for approximately one in a thousand deaths in developed countries. Dr. Anton Titov, MD, notes that untreated amyloidosis is invariably fatal, making its recognition and management a critical clinical priority.

Why Amyloidosis Diagnosis is Challenging

The diagnosis of amyloidosis presents significant challenges for clinicians. Its rarity means many physicians may see only a handful of cases throughout their entire careers. This lack of exposure contributes to a low index of suspicion for the disease.

Furthermore, as Professor Sir Dr. Mark Pepys, MD, emphasizes, systemic amyloidosis can affect virtually any organ in the body, with the exception of the brain parenchyma. This leads to an incredibly diverse range of potential symptoms. A patient can present with heart failure, kidney failure, neuropathy, or issues with the liver, skin, or spleen. Because the clinical picture mimics so many more common conditions, doctors often do not consider amyloidosis and therefore do not order the specific diagnostic tests required to identify it.

Consequences of Delayed Diagnosis

The delay in achieving a correct amyloidosis diagnosis has devastating consequences for patients. Dr. Pepys describes a common scenario where patients spend years undergoing investigations, often at multiple different hospitals, before a diagnosis is finally made, sometimes by accident. This prolonged diagnostic odyssey means that by the time patients are referred to specialists, they often have advanced, irreversible organ damage.

This late-stage presentation directly impacts survival. Dr. Anton Titov, MD, discusses the sobering statistic that about a quarter of patients with AL amyloidosis, the most common systemic form, still die within the first six months after diagnosis. This short survival is not primarily due to a lack of effective treatments but is a direct result of the extensive and irreversible damage—particularly to the heart—that has already occurred before therapy can begin.

The Role of Specialized Amyloidosis Centers

Given the complexity and rarity of amyloidosis, expert care is essential. Professor Sir Dr. Mark Pepys, MD, explains that successful treatment requires clinicians who have extensive experience managing a high volume of diverse amyloidosis cases. To address this need, the UK National Health Service established the National Amyloidosis Centre in 1999, directly funded by the Department of Health.

This center concentrates expertise and serves the entire national caseload. It is a unique, world-leading institution with over 60 staff members, including senior clinicians, nurses, radiographers, and scientists. The center sees over 4,000 patient visits annually, including about 1,000 new referrals, allowing for an unparalleled depth of experience in diagnosing and advising on treatment for all forms of this complex disease.

Advanced Diagnostic Imaging for Amyloidosis

A major breakthrough in amyloidosis management came from a diagnostic technique invented by Professor Sir Dr. Mark Pepys, MD, in the 1980s. While tissue biopsy remains the diagnostic gold standard, it only samples a tiny area and cannot quantify the total body amyloid burden. Dr. Pepys developed a method using a radioactive tracer that specifically localizes to amyloid deposits anywhere in the body.

This imaging technique allows physicians to see the full distribution of amyloid and monitor whether deposits are increasing or decreasing in response to treatment. Although the original tracer does not image the heart, this gap has been filled by the advent of cardiac magnetic resonance imaging (MRI). Dr. Anton Titov, MD, highlights that cardiac MRI is now an immensely powerful tool for diagnosing, quantifying, and monitoring cardiac amyloidosis in great detail, representing a major advance in patient care.

Full Transcript

Dr. Anton Titov, MD: Professor Sir Mark Pepys is a world leader in amyloidosis research and drug development. He discusses his lifetime’s work on amyloidosis diagnosis and treatment discovery.

Dr. Anton Titov, MD: Professor Mark Pepys, you are a world leader in amyloidosis research and treatment. What is amyloidosis?

Dr. Mark Pepys, MD: Amyloidosis is a disease caused by the deposition of abnormal insoluble protein fibers. They are deposited in the extracellular space in various tissues and organs. There are many different forms of amyloidosis.

Dr. Mark Pepys, MD: Amyloidosis is characterized by different proteins that form these fibrils. The protein type that makes the fibrils eventually does not matter. The fibrils look very similar histologically, morphologically, and by various imaging techniques. Fibrils have similar effects. They distort the structure and, therefore, the function of whatever tissue is involved.

Dr. Mark Pepys, MD: Amyloidosis is a rare disease. It is probably responsible for the deaths of about one in a thousand people in developed countries. So it is rare but not vanishingly rare.

Dr. Mark Pepys, MD: Amyloidosis is clinically very important because untreated amyloidosis is always fatal. Even with the best treatment currently available, amyloidosis is still fatal in nearly everybody who is ill with it. Although survival is now much better than it was in the past.

Dr. Anton Titov, MD: A major problem in the clinical recognition of amyloidosis and in its diagnosis is this. Amyloidosis is sufficiently rare that many doctors haven't seen probably any cases. Perhaps doctors saw maybe only a few cases of amyloidosis in their whole clinical career.

Dr. Mark Pepys, MD: The other problem is that amyloidosis can present with almost any symptom at all. This is because systemic amyloidosis can affect any tissue throughout the body. The exception is the brain substance itself.

Dr. Mark Pepys, MD: Amyloidosis can present clinically with manifestations in any tissue or any organ. Therefore people don't think of amyloidosis. Patients with amyloidosis can present with heart failure or kidney failure. Patients with amyloidosis can have problems with their nerves, or their skin, or their liver, or their spleen.

Dr. Mark Pepys, MD: Any part of the body can be involved in amyloidosis. Any organ can be the main part that is involved. Clinicians who are unfamiliar with amyloidosis don't think of it. Therefore physicians don't perform the correct diagnostic tests. They cannot diagnose amyloidosis. Doctors often don't recognize it.

Dr. Mark Pepys, MD: Sadly, it is a very common experience that we have. Patients are diagnosed with amyloidosis relatively late in the course of disease.

Dr. Anton Titov, MD: Correct diagnosis of amyloidosis is made often after several years of being ill. Patient is investigated by doctors sometimes in many different hospitals. Only then before somebody thinks of amyloidosis. Or the diagnosis is made by accident.

Dr. Mark Pepys, MD: Sadly that means that by the time patients come to us, it might be too late. We are experts in recognizing and treating amyloidosis. Even now, it happens. About a quarter of the patients have the commonest form of systemic amyloidosis. This is called AL amyloidosis. Patients still die within the first six months after being diagnosed. It is regardless of all the advances in treatment of amyloidosis. Amyloidosis is still a very major and serious unmet medical need.

Dr. Mark Pepys, MD: This is a reason why there is just 6 months survival after diagnosis of amyloidosis. It is the time lag before the correct diagnosis and initiation of therapy. Patients go around and around to various doctors. Patients live for such a short time after the diagnosis is made. It is because patients already have irreversible damage to the organs.

Dr. Anton Titov, MD: Amyloidosis particularly damages the heart. Amyloidosis also sometimes damages the kidneys and other organs. It may be difficult or impossible to salvage those failed organs. That is a major problem.

Dr. Mark Pepys, MD: The other problem in dealing with this relatively rare disease is this. Amyloidosis is so diverse. It is so complicated. The treatment requires really expert specialized clinicians. Experts must have seen a lot of amyloidosis. Experts manage the problems all the time.

Dr. Mark Pepys, MD: This is a reason why the UK National Health Service funded us in 1999 as the National Amyloidosis Centre for the whole UK. We are funded directly by the Department of Health in the UK. We provide diagnostic and treatment advisory services for the whole national caseload of amyloidosis. That means we have a concentration of expertise here.

Dr. Mark Pepys, MD: This is certainly unique in this country. We are world-leading in amyloidosis. We see more patients and a greater variety of different types of amyloidosis than most other medical centers around the world. We have over 60 people in the National Amyloidosis Centre. We have senior and less senior clinicians, nurses, radiographers, scientists in the laboratory, administrative people.

Dr. Mark Pepys, MD: We see over 4,000 patients per year with amyloidosis. About 1,000 patients are new cases of amyloidosis. Other patients are follow-ups.

Dr. Mark Pepys, MD: This center was based on my invention in the 1980s. I invented a new technique for diagnosing and monitoring systemic amyloidosis.

Dr. Anton Titov, MD: Until then the only method to diagnose amyloidosis was to have a tissue biopsy. You had to look at it under the microscope with appropriate special stains. That still is the gold standard for diagnosis of amyloidosis. But unfortunately these biopsies are very tiny.

Dr. Mark Pepys, MD: You can take a biopsy from the liver or the heart. But you have got an infinitesimally small sample of the whole organ. You cannot tell from that how much amyloid there is. You see amyloid only in your tiny biopsy. You don’t know where amyloidosis is in that organ or in other organs in the body.

Dr. Mark Pepys, MD: The only method of looking at the entire organ is to assess the function of the affected organs. I developed a diagnostic technique for amyloidosis. A radioactive tracer is given to the patient. This tracer specifically localizes to amyloid deposits. It doesn't go anywhere else.

Dr. Mark Pepys, MD: You can then image the patients after administering this tracer into a vein. You can see where the amyloid is located. You can identify whether amyloid is getting more or less. It is a quantitative diagnostic test. It is a very safe monitoring procedure. It is very informative about how much amyloid is present. We will know what is distribution of amyloid throughout the body.

Dr. Mark Pepys, MD: In its present form this diagnostic technique doesn't show up amyloid in the heart. This is for various technical reasons.

Dr. Anton Titov, MD: These problems are not possible to overcome. But fortunately we now have cardiac magnetic resonance imaging. This is an immensely powerful technique. Cardiac MRI enables a physician to diagnose, monitor, quantify and study in great detail and depth amyloidosis in the heart. MRI of the heart has been a very major recent advance.

Dr. Mark Pepys, MD: It was the development of that original tracer technique in the 1980s. Now we developed our clinical specialization. We were referred many patients. Because we were able to do more treatments for patients with amyloidosis. We helped patients more than other places.

Dr. Mark Pepys, MD: We are now funded by the UK Medical Research Council as a purely research endeavor. Then we became the de facto national referral center for amyloidosis over many years. Then in 1998-1999 the government set up this new scheme for specialist medical centers. They were dealing with relatively rare diseases. They wanted to focus on amyloidosis in just one or a few medical centers. We became the one National Amyloidosis Center.