Helping you understand amyloidosis

These proteins exist in a fibre‑like form (amyloid fibrils, amyloid deposits) that build up and interfere with the structure and function of affected organs throughout the body.

There are various types of amyloidosis. Different proteins are implicated in different types of amyloids. Treatment is now available for most types of amyloidosis, but accurate diagnosis and 'aggressive' intervention are essential.

Patient information leaflets

AA amyloidosis

AL amyloidosis

• myeloma.org.uk

Amyloidosis and the heart

Dry mouth

Hereditary ATTR amyloidosis

Hereditary ATTR Thr60Ala amyloidosis

Hereditary ATTR Val122Ile amyloidosis

Hereditary fibrinogen Aα-chain amyloidosis

Localised amyloidosis

Stem cell transplantation

Troubleshooting advice for patients taking drugs for AL amyloidosis

Wild type ATTR amyloidosis (formerly known as senile systemic amyloidosis)

How is amyloid made?

Most amyloid‑forming proteins are in the blood, with some in the bone marrow (AL amyloidosis) and others in the liver (e.g. in ATTR amyloidosis and in AA amyloidosis). 

In most cases, amyloids form when too many of these proteins are produced (e.g. in AA amyloidosis) or in abnormal forms (e.g. in AL amyloidosis and in hereditary amyloidosis, such as familial ATTR types of amyloidosis). In‑wild type ATTR amyloidosis, ATTR amyloid deposits are formed in older people from deposition of a normal blood protein, called transthyretin (TTR) produced in normal quantities.

The proteins that form amyloid gather and become lodged in the tissues. Once this begins, amyloid tends to build up faster than it can be broken down. Amyloidosis is usually a progressive disease unless the production of the amyloid-forming protein can be reduced.

How are amyloid-forming proteins produced?

This differs with the type of amyloid. 

The amyloid‑forming protein in AL amyloidosis is known as monoclonal immunoglobulin light chains, or light chains for short. The abnormal light chain protein is produced by an abnormal growth of plasma cells in the bone marrow, which do not usually cause symptoms themselves.

Hereditary types of amyloids occur when a gene is inherited from a parent that causes a blood protein to be made slightly abnormally. DNA tests usually support a diagnosis. Many with potential amyloid-causing genes never develop the disease. Among those who do, it can progress very slowly.

In non‑hereditary ATTR amyloidosis, a normal (‘wild‑type’) form of transthyretin (TTR) is converted into amyloid in the bodies of some older people. We are not sure why.

In AA amyloidosis, the amyloid‑forming protein is called serum amyloid A protein (SAA). The concentration of SAA in the blood is greatly elevated in many inflammatory diseases, such as rheumatoid arthritis. SAA is converted into AA amyloid in about 1‑5% of patients who have persistently high levels.

In the past, patients with kidney failure often developed dialysis‑related amyloidosis due to a blood protein called β2‑microglobulin which is normally cleared by the kidneys. Current dialysis systems are better at clearing β2‑microglobulin, so this amyloidosis type has become less common.

What types of amyloidosis are there?

There are over 30 types of amyloids in man. Many are very rare or do not cause major disease. Some types cause problems purely or mainly in just one part of the body. 

Among patients with systemic amyloidosis, where amyloid deposits are distributed throughout the body, AL is most common, followed by ATTR (both hereditary and wild‑type ATTR amyloidosis). 

AA amyloidosis has become far less common in recent years due to effective new treatments for many inflammatory conditions. It now accounts for only about 5% of cases seen at the NAC. Non‑ATTR hereditary amyloidosis is very rare.

How does amyloid affect the body and cause symptoms?

The build‑up of amyloid in various organs gradually interferes with their function.

• Kidneys: it may cause them to leak healthy blood proteins into the urine (proteinuria or nephrotic syndrome), or to lose their ability to purify the blood effectively (renal failure).
• Intestine: this can cause poor appetite, diarrhoea, or weight loss.
• Skin: can cause easy bruising.
• Heart muscle: causes it to become unusually stiff, leading to fatigue, shortness of breath and fluid retention.
• Nerves: can cause abnormal sensation and weakness or interfere with the body’s automatic functions such as bladder, bowel, and blood pressure control.
• Wrist joints: can cause carpal tunnel syndrome. There is often some amyloid in blood vessel walls which can increase the risk of bleeding or bruising.

What symptoms does amyloidosis cause?

Symptoms are often very non‑specific. They include:

• tiredness
• weight loss
• weakness
• loss of appetite.

Symptoms related to specific organs might include:

• swollen ankles (oedema) due to kidney or heart involvement
• tingling in the fingers or toes (paraesthesia) due to nerve involvement
• breathlessness due to amyloid in the heart.

How is amyloidosis diagnosed?

Diagnoses often come late because there may not be symptoms for many years, and then are often not specific and vary greatly by patient.

Diagnosis is usually by examining a biopsy (small tissue sample) under the microscope. These can be taken from almost any organ and are performed because an organ such as the kidney is not working properly, or because the possibility of amyloidosis has been considered. For the latter, a biopsy may be taken from the fat under the skin in the stomach area (abdominal fat biopsy).

Such procedures are quick and safe. Biopsies are usually retained by hospitals in a preserved state for many years; we often find it valuable to re‑examine them in our own laboratory and to perform additional specialised tests to try to determine the precise type of amyloid.

What is an amyloid scan (SAP scan)?

In 1987, Professor Mark Pepys invented a new diagnostic approach for amyloidosis. Together with Professor Philip Hawkins, he developed the whole-body scan (known as the SAP scan, SAP scintigraphy or amyloid scan) to diagnose most cases of amyloidosis.

SAP is 'serum amyloid P', a normal blood protein that binds to amyloids. We tag this with a trace of radioactive iodine, so SAP can be imaged throughout the body by a gamma camera scanner. An SAP scan shows the location and quantity of amyloid deposits in organs throughout the body.

Most patients with systemic amyloidosis have some amyloid in sites other than the biopsied sites, even when those organs appear to be working normally. 

SAP scans are whole-body and can monitor changes in the amount of amyloid and response to treatment over months and years.

Unfortunately, hollow or moving organs such as the stomach or heart cannot be assessed reliably by SAP scans. However, SAP scans have dramatically reduced the need for biopsies and help us to tailor individual treatment.

How is an amyloid scan performed? Are there side effects?

This test should not have side effects, and none have occurred in over 35,000 patient studies.

The dose of radioactivity is very small and is comparable with an X‑ray of the back. We administer potassium iodide before the procedure, a natural mineral that reduces absorption of radiation. The SAP protein is purified from healthy blood donors then treated and tested to minimise risk. 

Once radiolabelled SAP is given by intravenous injection, we gather images from the whole-body gamma scanner 6‑24 hours later.

The scanner is an open device on which patients lie fully clothed for about 40 minutes. A technician, and if desired, a carer, stay in the room whilst the scan is performed. It is not necessary to fast before the procedure.

What other tests can help diagnose amyloidosis?

DPD scans

SAP scanning does not show amyloid deposits in the heart. We use a different radioactive marker, called 99mTc‑DPD, that does work. DPD scans provide very useful information. ATTR deposits can be detected in the heart by DPD scans at an early stage when other heart tests appear normal.

We perform DPD scans in patients with suspected or diagnosed ATTR amyloidosis in the amyloid clinic. By combining a 3D image of the radioactivity, Single Positron Emission Computerised Tomography (SPECT), with a routine CT scan, we see the structure of the heart and the amyloid in it.

The DPD tracer is injected into the vein and a scan is performed 5 minutes after the injection and then 3 hours later. For each scan, patients lie on the open scanner while a “whole body sweep” is performed. The scanning camera is then rotated to provide the SPECT‑CT of the heart.

Cardiac MRI scans

Cardiac magnetic resonance (CMR) is a huge advance in amyloidosis. The technique pioneered by Dr Marianna Fontana uses a magnetic field and radio waves to obtain detailed pictures of the heart. It is safe, painless and does not involve any exposure to radiation.

During the scan, contrast material may be injected into the patient’s vein. Patients lie still inside a closed tunnel scanner for up to one hour. Doctors can then examine the pictures and data. CMR data is superior to that provided by echocardiography.

CMR can accurately measure the size of the amyloid deposits within the heart wall. Repeated measurements determine the build‑up of amyloid deposits and their regression with treatment. NAC has lately confirmed that cardiac amyloid can regress in many treated patients.

What treatments are available?

Amyloidosis was widely considered untreatable 30 years ago, but there are now effective treatments for most types of the disease.

Treatment varies for each type of amyloidosis, but our aim is to reduce the amount of amyloid forming protein in your bloodstream. When this is slowed or halted, the existing deposits often gradually go away. (Compare to a sink with a small plughole. If the tap is on full, water will build up. When the tap is turned down or off, the water will drain away.)

There is no diet or lifestyle that affects amyloidosis, but affected mice given vitamin C supplements seem to stay in better health. If patients wish to pursue this, we recommend 250mg daily. Very large doses of vitamin C may be harmful. Dietary, salt or fluid restrictions may be necessary due to heart or kidney problems in some patients.

The other important part of treatment is to protect and support the organs affected by amyloid. Organs that contain amyloid - particularly the kidneys - are more vulnerable to stress from high blood pressure, dehydration, serious infections, general anaesthetics, and surgery. We must be attentive to these, even when things are going well.

Is treatment effective?

Where affected organs are not too badly damaged, their function can stabilise and even improve. If amyloid build ups are stopped, up to 50% of the existing deposits can disperse each year. The rate is slower in some patients and in certain organs.

Amyloid regression is usually linked with improvement in general well‑being as well as stabilisation or recovery of organ function. Unfortunately, organs that are severely damaged before treatment may continue to deteriorate.

Wild‑type ATTR amyloidosis usually progresses slowly. Although there are currently no treatments that suppress production of the amyloid forming protein, we can use supportive measures to manage symptoms for many years.