Related Conditions
Your doctor should investigate any symptoms you report, regardless of your blood test results. Your symptoms might indicate a condition associated with Waldenstrom's macroglobulinaemia, which may need treatment. WM can affect all parts of your body, causing other conditions to develop. These include:
Hyperviscosity Syndrome (HVS)
What is it?
If you have Waldenstrom's macroglobulinaemia, your body produces too many abnormal white blood cells, which in turn produce too much of a protein called IgM. If the levels of IgM in your body become too high, they can cause your blood to be thicker and become slow moving – this is called hyperviscosity (HVS). HVS can be serious, and is one factor that might prompt your doctor to decide you need to start WM treatment.
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What are the symptoms?
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Headaches
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Dizziness
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Confusion
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Nosebleeds
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Changes in vision (blurred vision, double-vision or blind spots)
How is it diagnosed?
Your doctor will be able to tell if you have HVS by doing a blood test called a plasma viscosity test. This measures the thickness of your blood. If your blood or plasma viscosity levels are very high, you may have already developed some of the symptoms of HVS, so it is important to mention these when talking with your healthcare team.
The levels of IgM in people with HVS differ so if your blood tests show a relatively high level of IgM in your blood, it doesn’t necessarily mean that you have developed – or will develop – HVS.
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How can it be treated?
Plasma exchange (also called plasmapheresis) is used to treat HVS. This treatment involves your blood being drawn into a machine which removes the plasma from your blood and swaps it with a harmless replacement fluid. It usually takes between 1-3 procedures for your symptoms to reduce and your plasma viscosity to return to a normal level.
Being diagnosed with HVS will prompt your doctor to look into putting you on treatment for your WM, as it indicates that your WM has progressed. Your doctor will discuss your treatment options with you.
Cold agglutinin disease (CAD)
What is it?
People with Waldenstrom's macroglobulinaemia produce abnormal levels of a protein called IgM. IgM can cause the red blood cells to stick together in the coolest parts of the body, like the hands and feet, tip of the nose or the ear lobes. These cause ‘clumps’ of red blood cells, which break down. This can cause anaemia, because your body doesn’t have enough red blood cells.
The antibodies that clump the red blood cells are triggered when your body temperature drops below normal, hence ‘cold’ agglutinin disease.
What are the symptoms?
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Fatigue
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Painful fingers and toes when exposed to the cold
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Shortness of breath
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Dizziness
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Dark urine
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Pale/yellow skin (jaundice)
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Chest pains or irregular heartbeat
How is it diagnosed?
CAD is diagnosed through a blood test. Your doctor will look for a lower number of red blood cells that will indicate you have anaemia, as well as seeing if your red blood cells are sticking together. If the tests show signs of CAD and you’re describing CAD symptoms, your doctor can do another blood test called a direct antiglobulin test – or Coombs test – that will show if the abnormal antibodies are sticking onto your red blood cells.
How can it be treated?
Your doctor will recommend you do things to keep your body temperature up to stop the antibodies attacking your red blood cells. This could include:
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Wearing more clothes, both in summer and winter
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Avoiding air conditioning where possible
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Staying away from cold food or drink
If you doctors decides that you need treatment, this may include blood transfusions and treatment such as rituximab or combination of drugs that treat WM. Alternatively, you may be eligible for treatment on clinical trials.
The decision to use drugs to treat CAD depends on your individual circumstances, like the severity of your CAD, any previous treatment you’ve had for your WM and your general health.
Bing Neel Syndrome (BNS)
What is it?
BNS is a rare complication of Waldenstrom's macroglobulinaemia, where the abnormal cells your body is producing enter your spinal cord or brain. This causes problems in the central nervous system, that may progressively get worse as time goes by.
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BNS can develop at any time during someone’s WM journey: before they receive a diagnosis, at the same time as their diagnosis or when they are in remission following treatment. You may not have WM symptoms alongside your BNS ones, as sometimes BNS can develop even when your WM is in remission.
What are the symptoms?
Most symptoms felt by people with BNS are related to their central nervous system. This means that symptoms are highly varied. They can include:
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Headaches
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Tingling or numbness in hands or feet
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Problems with vision
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Seizures
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Difficulties with walking
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Balance problems
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Loss of movement in limbs
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New memory problems
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Nausea
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Problems with the nerves in the face
How is it diagnosed?
There isn’t one test that can give a certain diagnosis of BNS. Instead, if you doctor suspects that you may have BNS, they will order a series of tests to determine the cause. You doctor should consider referring you to a centre that has expertise in treating BNS as it’s helpful to have input from haematologists and neurologists who are familiar with this rare condition and treat it regularly.
Your healthcare team will decide which tests you need, depending on your individual circumstances. The following may be performed:
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A lumbar puncture, where a small sample of fluid is taken from your spinal cord through a thin needle to check if WM cells are there. This is done under local anaesthetic and shouldn’t be painful, although you may have backache or headache for a few days afterwards
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Less common is a brain biopsy. This is where a sample of tissue from your brain is taken to see if WM cells are in your central nervous system. This is performed under general anaesthetic by a neurosurgeon
The following tests are also often necessary to support the diagnosis:
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An MRI scan of the head and spinal cord may help doctors see if there is any sign of BNS in your body
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Blood tests can help doctors understand more about your Waldenstrom's macroglobulinaemia.​
How can it be treated?
BNS is a rare condition, affecting around 1% of people living with Waldenstrom's macroglobulinaemia. Therefore, it is important that if diagnosed you are treated in a hospital where healthcare professionals regularly treat people with the disease. If in doubt, speak to your doctor about getting a second opinion.
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There is no standard treatment for BNS, and any decision about treatment will depend on your individual circumstances, like your symptoms, fitness and any previous treatment.
Some of the treatments for BNS may be familiar to you, as they are similar to those used to treat WM. Other treatments are similar to those used to treat other diseases of the central nervous system. These include:
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Steroids – hormones used to kill WM cells. However this treatment has been shown to only work in the short term and your BNS could come back quickly after finishing the treatment
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Chemotherapy including methotrexate, cytarabine and rituximab. The chemotherapy combination MATRix (methotrexate, cytarabine, rituximab and thiotepa) has been used to treat high grade central nervous system lymphoma
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Ibrutinib – a drug known as a BTK inhibitor, which has shown to be effective in treating people with BNS. This drug is available for people living in Scotland, but it no longer available for new patients in England and Wales.
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Stem cell transplant – an intense therapy that isn’t suitable for everyone and is only considered in patients who are fit
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Radiotherapy – which targets your brain with radiation to kill cells. This is only recommended in special circumstances, usually if other treatment is not suitable
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Rituximab and bendamustine – a chemo-immunotherapy often used as a first line treatment for WM. Rituximab alone is not advised for the treatment of BNS
Peripheral Neuropathy (PN)
What is it?
Peripheral neuropathy can be caused by any number of conditions – not just Waldenstrom's macroglobulinaemia – or even some treatments.
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The peripheral nervous system carries messages to and from your brain to various parts of your body – things like sensations (e.g. touch), muscle movement and organ function (e.g. your bladder telling you it is full).
With Waldenstrom's macroglobulinaemia, your body produces too many abnormal white blood cells, which in turn produce too much of a protein called IgM. In some people, the abnormal IgM targets nerves in the peripheral nervous system, damaging it.
The damage causes them to send too many or two few signals to other parts of your body – like a damaged electrical wire short-circuiting – which causes the symptoms people with PN describe.
Around half of people living with WM experience PN. It’s important to tell your healthcare team as soon as you can about any symptoms of PN, to prevent any further nerve damage.
Your doctor may also refer to PN as anti-MAG neuropathy. Myelin-associated glycoprotein (MAG) covers your nerve endings (like insulation on an electrical wire) and it is this that is damaged by IgM.
How is it diagnosed?
If you have PN symptoms, it’s recommended that your doctor refers you to a neurologist, who has the specialist knowledge to diagnose and treat you.
Your specialist will assess you, taking into account things like your symptoms, how fast your symptoms have developed and changed, and any treatment you’ve had. They’ll check your power, balance, co-ordination, reflexes and sense of touch.
They may also carry out tests called a nerve conduction study and an electromyography (EMG). These tests both use electric pulses to check how well your nerves and muscles are working. The nerve conduction test measures how fast your nerves send messages to your brain, whilst the EMG records the electrical activity in your muscles. Neither test is painful, although some people report discomfort.
On top of these tests, your neurologist will also take blood samples and, depending on the results of your other tests, in some circumstances they may ask for a biopsy.
These tests will help your neurologist not only diagnose you, but help rule out other underlying conditions that might have caused the PN, like diabetes.
What are the symptoms?
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Tingling or ‘pins and needles’ in your feet or hands
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Tremors
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Numbness in your feet or hands
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Problems with walking, balance or co-ordination
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Muscle weakness
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Pain in your feet or hands, this may feel like a burning pain, or stabbing, shooting pains
How can it be treated?
Because there are so many different causes of PN, treatment varies from patient to patient. From the results of your tests, your healthcare team will be able to advise you on treatment.
Your doctors will assess your symptoms and history and discuss whether it is time for you to go on treatment – this is usually down to the severity of your symptoms and blood test results. If, for example, your PN and WM are not getting worse, then you might feel that it’s best to hold off on treatment and continue to be on active monitoring.
Treatment focusses on the root cause of the PN, which in this case means treating your WM. You can find out more about treatment for WM here. Although the goal is to ensure your symptoms don’t get worse, many WMers find their symptoms improve after treatment.
If you are in pain with your PN, speak to your neurologist who may be able to prescribe some painkillers to help. There are lots of different options when it comes to painkillers, depending on where you are experiencing the pain and any other symptoms you might have.
Sometimes, the damage to your nerves cannot be fixed by treatment. If you have on-going problems with movement and balance, speak to your healthcare team who can refer you to a physiotherapist with expertise in helping people with conditions like PN. They’ll be able to give you exercises to strengthen muscles and help you adapt.
Cryoglobulinaemia
What is it?
Some people with Waldenstrom's macroglobulinaemia may have higher levels of an antibody that is sensitive to cold temperatures. These antibodies are called cryoglobulins. When your body temperature drops below normal, cryoglobulins will clump together and block blood flow, usually in your hands, feet, ears and nose.​
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What are the symptoms?
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Pain in your hands or feet when you’re cold
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Blue tinge to your hands and feet when you’re cold
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Skin lesions that are purple or red-brown
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Skin ulcers
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Gangrene
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Swollen ankles and legs
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Joint pain
How is it diagnosed?
It’s important to raise these symptoms with your doctor, as it could be a sign that your Waldenstrom's macroglobulinaemia is progressing and you might need to start treatment. Your doctor will take blood tests to diagnose the condition, and to check for any other underlying causes for it.
How can it be treated?
In most cases, your doctor will take a conservative approach to treating your cryoglobulinaemia. This means that they will advise you take steps to keep your body temperature up to avoid the symptoms, instead of immediately going on treatment. For example, you could wear more layers and avoid cold food and drink.
If your symptoms are severe or getting worse, or your blood tests suggest that your WM is progressing, your doctor may decide that it’s time to consider treatment for your WM.
You can read more about starting treatment and the types of treatment for WM below.
Amyloidosis
What is it?
Amyloidosis occurs when abnormal proteins don’t develop correctly, or ‘misfold’, and build up in your organs, meaning they can’t work properly. In rare cases, Waldenstrom's macroglobulinaemia can a cause amyloidosis because the body is making abnormal B-cells. These cells can produce the abnormal proteins that misfold and cause amyloidosis.
What are the symptoms?
Symptoms can vary depending on what organs are affected by the amyloid protein, so you may only be affected by one or two of these.
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Fatigue and weakness
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Shortness of breath
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Swollen tongue
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Difficulty swallowing
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Tingling or numbness in legs and feet
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Sudden weight loss
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Frothy urine
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Diarrhoea
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Changes in skin colour
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Joint pain
How is it diagnosed?
Amyloidosis is rare. Therefore, you should be under the care of a specialist. In the UK, there is the National Amyloidosis Centre and doctors should refer any patient they suspect of having amyloidosis to the centre for further evaluation. You don’t need a definite diagnosis of amyloidosis to get referred.
Your doctor will take a small biopsy of the part of the body they suspect is affected by the amyloidosis. The biopsy will be studied under a microscope to see any build-up of amyloid proteins.
You may also have other tests, including scans of the organs affected to check how they’re functioning, as well as blood tests.
How can it be treated?
Like many WM related conditions or complications, your doctor will look at treating the root cause – in this case your WM. They’ll discuss different treatment options with you. You can read more about this here.
You may also need different treatments to help your affected organ(s) function properly.
You can read more about amyloidosis on the National Amyloidosis Centre’s patient website.