Amyloidosis

About amyloidosis

Amyloidosis can be:

• acquired – occurs spontaneously
• hereditary – occurs due to a faulty gene.

It can also be:

• localised – amyloid protein produced and deposited only in one small area of the body
• systemic – amyloid protein circulates in the blood and deposits in one or several organs of the body.

Amyloidosis is not a cancer but it is equally as serious.

Amyloidosis is classified according to the main protein trigger that causes that particular type of amyloidosis. Each type is given an abbreviation where the first letter A stands for amyloid and the subsequent initials stand for the amyloid protein. For example, in AL amyloidosis the A stands for amyloid and L for the type of fibril protein, light chain.  More than 20 different types of amyloidosis have been identified at this time. Many of these are obscure and cause few problems. Each type of amyloidosis is different, requiring different treatments.

Over the past 10 years there has been a much greater understanding of these diseases. With earlier diagnosis, great improvements in assessment and treatment regimes, many patients are now experiencing long remissions and living full lives.

What are the types of amyloidosis?

AL amyloidosis

AL amyloidosis is a light chain amyloid caused by a bone marrow disorder. AL amyloidosis is caused by an abnormal protein (light chains) made by abnormal plasma cells found in the bone marrow. Plasma cells are part of the body’s immune system. They are responsible for making antibodies, also called immunoglobulins.

In AL amyloidosis a clone or single population of plasma cells grows excessively and produces an abnormal protein called an immunoglobulin light chain. They build up in the bloodstream and are progressively deposited as amyloid fibres (fibrils) in the tissues and organs of the body. AL amyloidosis can involve the kidney, heart, nervous system, liver and gastrointestinal soft tissues. AL amyloidosis is the most commonly diagnosed form of systemic amyloidosis in the western world. Learn more about AL amyloidosis here.

AA amyloidosis

AA amyloidosis occurs when the serum amyloid A (SAA) protein increases substantially in response to a long-term inflammatory disorder. AA amyloidosis used to be known as reactive or secondary amyloidosis, and occurs in patients who have a history of rheumatoid arthritis (children and adults), bronchiectasis, inflammatory bowel disease infections or familial Mediterranean fever, an inherited condition characterised by recurrent episodes of painful inflammation in the abdomen, chest, or joints. The number of people with this type of amyloidosis seems to be declining in the western world with better treatment and control of such inflammatory diseases. The kidney and liver can be affected by this type of amyloidosis.

ATTR and AFib

ATTR (transthyretin gene mutation) and AFib (fibrinogen alpha chain gene mutation) amyloidosis are known as the two main types of hereditary amyloidosis. These types of amyloidosis occur when a gene mutation is inherited leading to the life-long production of an abnormal protein. This amyloid protein deposits in the organs and tissues of the body in the form of an amyloid fibril. Because the protein is not easily broken down it gradually builds up in the organs and tissues of the body disrupting their function. Major organs involved with this type include the heart, nervous system and kidneys. This mutant gene can be passed from one generation to another. Hereditary amyloidosis is known as an autosomal dominant disease, meaning that someone with the mutant gene may have inherited it from their father or mother and they in turn are capable of passing the gene to their children, who each have a 50% chance of inheriting it.

ATTR also includes senile amyloidosis but this is not an inherited disease. It is caused by overproduction of the normal protein TTR. This condition, which mainly affects the heart, is becoming more common as the average age of the population increases. Senile amyloidosis of the heart often coexists with benign bone marrow disorders creating the false impression that AL amyloidosis is the diagnosis.

How common is amyloidosis?

Amyloidosis is known as a rare group of diseases. In Australia a diagnosis of amyloidosis is not required to be reported on a state or national register, so we have no accurate way of knowing how many people are diagnosed with the disease each year.

Who gets amyloidosis?

Amyloidosis can occur at any age but it is more common in adults over the age of 50. Amyloidosis occurs more frequently in men than in women.

Causes of amyloidosis

At this time it is not known what triggers the initial formation of the amyloid protein and why this happens in such a small proportion of the population. Amyloidosis can be acquired (occurs spontaneously) or hereditary (occurs due to a faulty gene).

Research is going on all the time into possible causes of amyloidosis and certain factors have been identified that mayput some people at an increased risk. These include:

• patients who require kidney dialysis for a long period of time may be at increased risk of dialysis-associated amyloidosis, although this is rare with modern dialysis techniques.
• patients with myeloma may also develop AL amyloidosis (15-20% of myeloma patients)
• patients with a long-term chronic infectious or inflammatory disease are at risk of developing AA amyloidosis
• people who inherit a certain gene mutation may develop hereditary amyloidosis

Symptoms of amyloidosis

Symptoms of amyloidosis depend on which tissues and organs are affected and to what degree. Symptoms vary greatly from patient to patient and between the different types of amyloidosis.

Symptoms are often vague, mimicking other medical conditions. The most common symptoms are:

• fatigue/tiredness
• unexplained weight loss
• swelling of the ankles and legs due to fluid accumulation.

Other symptoms vary depending on the organ or tissues most affected and may include:

• shortness of breath
• loss of appetite
• enlarged tongue
• unexplained bruising around the eyes
• numbness or tingling in the hands and feet
• lumps in the soft tissue.

Due to the rarity of the disease and vagueness of symptoms, diagnosis may be difficult or delayed. Some of the symptoms described above may also be seen in other illnesses, including viral infections. So, most people with these symptoms don’t have amyloidosis. However, it is important to see your doctor if you have any unusual symptoms, or symptoms that persist much longer than expected so that you can be examined properly.

Diagnosis of amyloidosis

Amyloidosis can be difficult to diagnose. There is no specific blood test and results of investigations vary greatly from patient to patient. The diagnosis of amyloidosis starts when a doctor becomes suspicious of the patient’s symptoms. A definitive diagnosis of amyloidosis can only be made through a biopsy.

Once a diagnosis of amyloidosis has been made further tests will be undertaken in the laboratory to establish which type of amyloidosis you have. This is important as the treatment is radically different for the various types of amyloidosis. Sometimes the tests determining the type of amyloidosis are not conclusive and a DNA test may be suggested.

Bone marrow biopsy

When AL amyloidosis is suspected, a bone marrow biopsy may also be performed to establish the presence of abnormal plasma cells. A bone marrow biopsy involves taking a sample of bone marrow, usually from the back of the hip bone and sending it to the laboratory for examination under the microscope. Regardless of the organs predominately affected, amyloid deposits are often present throughout the body and therefore a less invasive biopsy of abdominal fat tissue, rectum or lip may be performed.

The bone marrow biopsy may be done in the haematologist’s rooms, clinic or day procedure centre and is usually performed under local anaesthesia with sedation given either by tablet or through a small drip in your arm. The sample of bone marrow is examined in the laboratory to determine the number and type of cells present and the amount of haemopoiesis (blood forming) activity taking place there.

Other tests

Further tests will then usually be arranged to establish whether the heart and kidneys or other organs of the body have been affected by the aggregation of the amyloid protein and by how much. These tests include blood and urine tests, ECGs, echo cardiograms and sometimes scans and nerve conduction tests. Not all of these will be necessary for every type of amyloidosis. These results will provide a baseline of your disease and general health which will be compared with later results to assess how well you are progressing and responding to treatment.

Treatment of amyloidosis

There is a range of treatments available for amyloidosis with much research being carried out around the world to find new treatments.

Once a firm diagnosis has been made and the subtype of amyloidosis is identified, your doctors will discuss their recommended treatment regime with you. Regardless of the type of amyloidosis you have the goals of treatment are:

• to stop or slow the production of the amyloid protein
• to preserve and support affected organs and tissues
• to improve your quality of life.

AA amyloidosis

AA amyloidosis is managed by controlling the underlying inflammatory disease and therefore reducing the production of the amyloid protein SAA. If the SAA level can be reduced to almost normal and remains there for a long time there is a chance that the existing amyloid will eventually regress, improving the organ function. New treatments that interfere with the process of amyloid deposition are also being studied in AA.

AL amyloidosis

Over the past 10 years an increasing range of therapies has been developed. Even though treatment for AL amyloidosis is still not thought to be curative, many patients are living long and active lives. In deciding on the best treatment for you, your medical team will take into account a number of factors including your age, general health and the extent to which your organs have been affected by the disease. They will also consider potential complications of therapy.

The aim of treatment is to rapidly reduce the free light chains that are causing the production of amyloid. Targeting the plasma cells within the bone marrow, which are producing the free light chains, achieves this. Once the production of the amyloid protein is slowed or stopped, the amyloid fibrils already deposited in the organs may slowly move out of the affected organs. The function of the affected organs may then slowly improve. Sometimes, however, the organs may be damaged to the point where the organ function does not improve greatly. At this time there are no specific treatments that can directly clear amyloid deposits from the organs and tissues of the body.

Hereditary amyloidosis

Liver transplantation may be considered to remove the source of the amyloid-forming TTR variant. However, transplantation can be limited by the presence of amyloid in the heart, especially in an older patient. Liver transplant is only suitable for a minority of patients with ATTR. Drugs are being trialled at this time to stop the formation of the amyloid protein.

Senile systemic amyloidosis

Treatment is generally aimed at treating the symptoms of the disease. Because the heart is the most commonly affected organ, this disease will be monitored and treated by a cardiologist. As chemotherapy may actually disadvantage these patients, careful review is required to clarify the diagnosis particularly if the amyloid is found only in the heart.

Tests will be performed throughout your treatment to see whether there is evidence of your amyloid responding to treatment. Treatment regimes may be changed or started at any time if the required results are not achieved or if you are experiencing severe side effects or toxicities with the treatment. Your medical team will continually check any affected organs to see how they are standing up to the treatment and whether there has been an improvement in performance status.

Side effects of amyloidosis treatment

All treatments can cause side effects. However, the type and severity will vary between individuals, depending on the type of treatment used and how an individual responds to it. In general, more intensive treatment is associated with more severe side effects. It is important to report any symptoms you are having to your doctor or nurse. In most cases they can be treated and are reversible.

When to contact your doctor or hospital

As a general rule, while you are having treatment you will need to contact your doctor or hospital immediately if you have any of the following:

• a temperature of 38^oC or over (even if it returns to normal) and/or an episode of uncontrolled shivering (a rigor)
• bleeding or bruising, for example blood in your urine, faeces, sputum, bleeding gums or a persistent nose bleed
• nausea or vomiting that prevents you from eating or drinking or taking your normal medications
• severe diarrhoea, stomach cramps or constipation
• coughing or shortness of breath
• a new rash, reddening of the skin, itching
• a persistent headache
• a new pain or soreness anywhere
• if you cut or otherwise injure yourself
• if you notice pain, swelling, redness or pus anywhere on your body.

Medicines

Cortico-steroids

Cortico-steroids are hormones that are produced naturally by the body in the adrenal glands. Man-made cortico-steroids such as prednisone, dexamethasone and methylprednisolone are very important in the treatment of amyloidosis and are commonly used alone or in combination with chemotherapy in the treatment of amyloidosis.  The types of side effects seen with cortico-steroids depend largely on how long they are used for, and the dose given. If you are using them for a short time you may notice that your appetite increases or you may feel more restless than usual. Some people find it more difficult to get to sleep at night and sleeping tablets or natural therapies are sometimes recommended. Cortico-steroids can cause a rise in the blood sugar. Diabetics may find they need more of their diabetes medication while they are taking these drugs. Some people who are not normally diabetic may require treatment to keep their blood sugar at acceptable levels. It is important to keep a check on the blood sugar and keep a diary of the levels and the amount of diabetic medication being taken. Diabetics will already know how to do this. People whose blood sugar only goes up when they are on cortico-steroids will be given information on diet and taught how to measure their blood sugar and adjust their medication. Many of the side effects of cortico-steroids are temporary and should pass once you finish taking them. Long-term use may cause some other effects such as fluid retention and an increased susceptibility to infections. Aching joints such as the knees and hips have also been reported. Remember to tell your doctor and nurses about any side effects you are having as they can usually suggest ways to help you.

Thalidomide

Thalidomide, although strictly speaking is not a chemotherapy drug, does have side effects which have to be carefully monitored. It can cause several side effects including drowsiness, lack of concentration, dizziness, constipation, skin rash and, in some cases, heart problems and nerve damage (peripheral neuropathy). Due to its sedative effects it is recommended that you take thalidomide in the evening. Regular laxatives and a high fibre diet can help prevent the risk of constipation. Nerve damage is usually felt as a tingling and loss of sensation in the hands and feet. It is important that you tell your doctor if you experience symptoms of nerve damage, as the dose of thalidomide may need to be reduced or stopped. Thalidomide can increase the risk of developing a clot in the veins (thrombosis). Your doctor may prescribe a blood-thinning medication while you are taking this drug. Thalidomide is harmful to babies developing in the womb and should never be taken by pregnant women. It is important to avoid becoming pregnant and to use a suitable form of contraception, if necessary, while taking thalidomide and for some time afterwards. There are special government regulations relating to the prescribing and dispensing of thalidomide, which you and your doctor have to abide by. Your doctor will explain these regulations to you.

Bortezomib (Velcade)

The main side effects of bortezomib are peripheral neuropathy, autonomic neuropathy and thrombocytopenia. It also lowers immunity to certain viruses especially herpes zoster which increases the risk of shingles. Antiviral preventative therapy is often used with bortezomib. 

Lenalidomide (Revlimid)

Lenalidomide’s main side effect is depression of blood counts (causing anaemia and risk of infection) and an increased risk of blood clots. Therapy with a blood-thinning agent may be used to help reduce the risk. Lenalidomide may be harmful to babies developing in the womb and should never be taken by pregnant women. It is important to avoid becoming pregnant and to use a suitable form of contraception, if necessary, while taking lenalidomide, and for some time afterwards. There are special government regulations relating to the prescribing and dispensing of lenalidomide which you and your doctor have to abide by. The doctor will explain this to you.

Other side effects

Chemotherapy

Chemotherapy kills cells that multiply quickly, such as amyloid cells. It also causes damage to fast-growing normal cells, including hair cells and cells that make up the tissues in your mouth, gut and bone marrow. The side effects of chemotherapy occur as a result of this damage. These include:

Effects on the bone marrow

Chemotherapy affects the bone marrow’s ability to produce adequate numbers of blood cells. As a result, your blood count (the number of white cells, platelets and red cells circulating in your blood) will generally fall within a week of treatment. The length of time it takes for your bone marrow and blood counts to recover mainly depends on the type of chemotherapy given. When your platelet count is very low (thrombocytopenic) you can bruise and bleed more easily. During this time it is helpful to avoid sharp objects in your mouth such as chop bones or potato chips as these can cut your gums. Using a soft toothbrush also helps to protect your gums. In many cases a transfusion of platelets is given to reduce the risk of bleeding until the platelet count recovers. If your red blood cell count and haemoglobin levels drop you will probably become anaemic. When you are anaemic you feel more tired and lethargic than usual. If your haemoglobin level is very low, your doctor may prescribe a blood transfusion.

Risk of Infection

The point at which your white blood cell count is at its lowest is called the nadir. This is usually expected 10 to 14 days after having your chemotherapy. During this time you will be at a higher risk of developing an infection. At this stage you will also be neutropenic, which means that your neutrophil count is low. Neutrophils are important white blood cells that help us to fight infection. While your white blood cell count is low you should take sensible precautions to help prevent infection. These include avoiding crowds, avoiding close contact with people with infections that are contagious (for example colds, flu, chicken pox) and only eating food that has been properly prepared and cooked. If you do develop an infection you may experience a fever, which may or may not be accompanied by an episode of shivering where you shake uncontrollably. Infections while you are neutropenic can be quite serious and need to be treated with antibiotics as soon as possible. Sometimes your doctor may decide to use a drug to help the recovery of your neutrophil count. This drug works by stimulating the bone marrow to increase the production of neutrophils and is usually given as an injection under the skin (subcutaneous).

Nausea and vomiting

Nausea and vomiting are often associated with chemotherapy and some forms of radiotherapy. These days however, thanks to significant improvements in anti-sickness (anti-emetic) drugs, nausea and vomiting are generally very well-controlled. You will be given anti-sickness drugs before and for a few days after your chemotherapy treatment. Be sure to tell the nurses and doctors if the anti-emetics are not working for you and you still feel sick. Some people find that eating smaller meals more frequently during the day, rather than a few large meals, helps to reduce nausea and vomiting. Many find that eating cool or cold food is more palatable, for example jelly or custard. Drinking ginger ale or soda water and eating dry toast may also help if you are feeling sick.

Changes in taste and smell

Both chemotherapy and radiation therapy can cause changes to your sense of taste and smell. This is usually temporary but in some cases it lasts up to several months.

Mucositis

Mucositis, or inflammation of the lining of the mouth, throat or gut is a common and uncomfortable side effect of chemotherapy and some forms of radiotherapy. It usually starts about a week after the treatment has finished and goes away once your blood count recovers, usually a couple of weeks later. During this time your mouth and throat could get quite sore. Soluble pain medication and other topical drugs (ones which can be applied to the sore area) can help. If the pain becomes more severe, stronger pain killers might be needed. It is important to keep your mouth as clean as possible while you are having treatment to help prevent infection. Avoid commercial mouthwashes, these are often too strong, or they may contain alcohol, which will hurt your mouth.

Bowel changes

Chemotherapy can cause some damage to the lining of your bowel wall. This can lead to cramping, wind, abdominal swelling and diarrhoea. Be sure to tell the nurses and doctors if you experience any of these symptoms. If you develop diarrhoea, a specimen will be required from you to ensure that the diarrhoea is not the result of an infection. After this you will be given some medication to help stop the diarrhoea and/or the discomfort you may be feeling. It is also important to tell the nurse or doctor if you are constipated or if you are feeling any discomfort or tenderness around your anus when you are trying to move your bowels. You may need a gentle laxative to help soften your bowel motion.

Parotitis

Associated with radiotherapy, parotitis is an inflammation of the saliva-producing glands in the mouth, which can occur if these glands are within the treatment field used. These include the parotid or submandibular glands, which are situated at the top of the jaw line, in front of the ears. Parotitis causes dryness of the mouth and jaw pain, which usually settles down within a few days, once the inflammation subsides.

Hair loss

Hair loss is unfortunately a very common side effect of chemotherapy and some forms of radiotherapy. It is, however, usually only temporary. The hair starts to fall out within a couple of weeks of treatment and tends to grow back three to six months later. Avoiding the use of heat or chemicals and only using a soft hairbrush and a mild baby shampoo can help reduce the itchiness and scalp tenderness which can occur while you are losing your hair. You need to avoid direct sunlight on your exposed head (wear a hat) because chemotherapy (and radiotherapy) makes your skin even more vulnerable to the damaging effects of the sun (i.e. sunburn and skin cancers). Remember that without your hair your head can get quite cold so a beanie might be useful. Hair can also be lost from your eyebrows, eyelashes, arms and legs.

Fatigue

Most people experience some degree of tiredness in the days and weeks following chemotherapy and radiotherapy. Having plenty of rest and a little light exercise each day may help to make you feel better during this time. It is important to listen to your body and rest when you are tired.

Fertility

Some types of chemotherapy and radiotherapy may cause a temporary or permanent reduction in your fertility. It is very important that you discuss any questions or concerns you might have regarding your future fertility with your doctor if possible before you commence treatment. In women, some types of chemotherapy and radiotherapy can cause varying degrees of damage to the normal functioning of the ovaries. In men, sperm production can be impaired for a while but the production of new sperm may become normal again in the future. There are some options for preserving your fertility, if necessary, while you are having treatment for amyloidosis.

Early menopause

Some cancer treatments can affect the normal functioning of the ovaries. This can sometimes lead to infertility and an earlier than expected onset of menopause, even at a young age. The onset of menopause in these circumstances can be sudden and, understandably, very distressing. Hormone changes can lead to many of the classic symptoms of Menopause. Some women experience decreased sexual drive, anxiety and even depressive symptoms during this time. It is important that you discuss any changes to your periods with your doctor or nurse.

Body image, sexuality and sexual activity

Hair loss, skin changes and fatigue can all interfere with how you feel about yourself as a man or a woman and as a “sexual being”. During treatment you may experience a decrease in libido and it may take some time for things to return to “normal”. It is perfectly reasonable and safe to have sex while you are on treatment or shortly afterwards, but there are some precautions you need to take. It is usually recommended that you or your partner do not become pregnant as some of the treatments given might harm the developing baby. As such, you need to ensure that you or your partner use a suitable form of contraception. Partners are sometimes afraid that sex might in some way harm the patient. This is not likely as long as the partner is free from any infections and the sex is relatively gentle. Finally, if you are experiencing vaginal dryness, a lubricant can be helpful.

Caring for someone with amyloidosis

We have a range of information and resources that may help when you are caring for someone with amyloidosis.