Freephone helpline 0808 808 5555 information@lymphomas.org.uk www.lymphomas.org.uk Peripheral neuropathy – a guide for people with lymphoma Peripheral neuropathy means damage to nerves of the peripheral nervous system. The peripheral nervous system consists of nerves that connect the central nervous system (the brain and the spinal cord) with the rest of the body. These nerves control the movements of our arms and legs and carry sensations from the body back to the brain. Peripheral neuropathy is a side effect of some of the drugs that are used to treat lymphoma. It can also occasionally occur as a symptom of the lymphoma itself. Most commonly, people first notice 'pins and needles' or numbness in their fingers or toes. For most people neuropathy will be a temporary problem, but it is important to recognise the symptoms and report them to your medical team. They can then adjust your treatment if necessary. In this article we are aiming to answer questions you might have about peripheral neuropathy: • What is peripheral neuropathy? (see below) • Why do people with lymphoma develop peripheral neuropathy? (page 2) • How likely am I to get peripheral neuropathy? (page 3) • What are the symptoms of peripheral neuropathy? (page 4) • How is peripheral neuropathy diagnosed? (page 5) • Will the neuropathy get better? (page 5) • Is there any treatment for peripheral neuropathy? (page 5) • Is there anything I can do myself? (page 6) What is peripheral neuropathy? The body’s nervous system is made up of several parts. The brain and the spinal cord make up the ‘central nervous system’ or CNS. The CNS communicates with the rest of the body through two types of nerves: •the cranial nerves, which supply the head, heart and some abdominal organs; these come directly from the brain •the nerves that run between the CNS and the rest of the body – the peripheral nervous system; these nerves detect sensations and control our muscles and they start in the spinal cord. Peripheral neuropathy LYM0058/PeriphNeur/2013v2 1/10 The peripheral nervous system can be divided into: • motor nerves that carry messages from the brain, down through the spinal cord to muscles, making them move • sensory nerves that carry information about sensations felt by the skin and joints back through the spinal cord to the brain – sensations of touch, pain, temperature, vibration and awareness of the position of our joints • autonomic nerves that transmit messages to and from the body’s internal organs – such as messages about blood pressure, heart rate, the need to pass water, the movement of food through the gut and messages that control sexual function. ‘Neuropathy’ means damage to nerves. ‘Peripheral neuropathy’ means damage to the nerves of the peripheral nervous system. Any of the three types of nerves might be damaged if you have peripheral neuropathy. Why do people with lymphoma get peripheral neuropathy? There are three main reasons why you might develop peripheral neuropathy if you have lymphoma: 1. The lymphoma itself can cause peripheral neuropathy – this is an unusual cause. 2.Some drugs used to treat lymphoma can cause peripheral neuropathy as a side effect – this is the most common cause. 3.You might have other conditions or illnesses that can also cause peripheral neuropathy or you might be taking drugs for other conditions that cause neuropathy as a side effect. Neuropathy caused by the lymphoma itself The lymphoma itself can cause peripheral neuropathy. This can happen when lymphoma cells grow into nerves or around the tiny blood vessels that supply the nerves – but this happens very rarely. Usually it happens because of chemicals that some lymphomas produce. These chemicals are abnormal proteins called paraproteins, which are antibodies that can stick onto nerves and damage them. In one type of lymphoma called Waldenström’s macroglobulinaemia (the most common type of lymphoplasmacytic lymphoma), peripheral neuropathy is particularly common. This lymphoma produces a paraprotein called 'immunoglobulin M' or IgM. This abnormal protein can attack nerve endings in the hands and feet. Up to half of people with Waldenström’s macroglobulinaemia develop peripheral neuropathy. Neuropathy caused by lymphoma treatments Some of the drugs used to treat lymphoma can cause nerve damage, especially certain chemotherapy drugs (see page 3). This is the most common reason for having peripheral neuropathy if you have lymphoma. Whether this problem develops depends on which drugs you are being treated with and on how much of them you receive altogether. Peripheral neuropathy LYM0058/PeriphNeur/2013v2 2/10 Other medical conditions that cause neuropathy You might already have another condition that can cause peripheral neuropathy, such as diabetes or low vitamin B12 levels. Alcoholism can cause peripheral neuropathy. Drugs that you might be taking for something else can also cause peripheral neuropathy as a side effect (though this is rare). If you already have a condition that can cause nerve damage, you are at higher risk of developing neuropathy or of it getting worse as a side effect of anti-lymphoma drugs. These other conditions are therefore taken into account when your medical team decides what dose of drug to give you. How likely am I to get peripheral neuropathy? Whether you develop neuropathy will depend on: • which drugs you are being treated with (see below) •whether you are being given more than one drug that can cause peripheral neuropathy • how much of the drug(s) you receive altogether •whether or not you have any other condition (such as diabetes) or are taking any other medication that can cause peripheral neuropathy •your age – older people are more likely to develop this side effect than younger people. The chemotherapy drugs that most commonly cause neuropathy are the anti-cancer drugs called ‘vinca alkaloids’. The vinca alkaloids include the drugs vincristine, vinblastine and vindesine. Vincristine (Oncovin®) is the most likely of these to cause peripheral neuropathy. Many combination chemotherapy treatments for lymphoma, such as CHOP and CVP, contain vincristine. Vinblastine is part of ABVD, which is a chemotherapy regimen that is often used to treat Hodgkin lymphoma. Platinum-based drugs such as cisplatin, oxaliplatin and carboplatin can also cause peripheral neuropathy. These drugs are most likely to be used to treat lymphoma that has come back after treatment. Other anti-lymphoma drugs that can cause peripheral neuropathy are bortezomib, thalidomide and brentuximab vedotin. There are no exact figures available for how common peripheral neuropathy is in people on chemotherapy drugs. It is quite common for people who are receiving treatment with vincristine to experience some mild symptoms, such as tingling in their fingers and toes. It is not common for chemotherapy to cause severe neuropathy symptoms, however. Research has suggested that older people seem to be more vulnerable to developing peripheral neuropathy and many hospitals will decrease the dose of chemotherapy drugs in older people if that is possible. Peripheral neuropathy LYM0058/PeriphNeur/2013v2 3/10 What are the symptoms of peripheral neuropathy? Peripheral neuropathy does not usually show up right at the start of treatment. It usually comes on over a period of a few weeks, starting some weeks after the treatment begins. It often gets worse shortly after each course of chemotherapy. Neuropathy causes symptoms by leading to too much nerve activity or to loss of nerve activity. The symptoms will depend on which nerves are affected. Chemotherapy drugs tend to affect sensory nerves (the nerves of feeling) more commonly than motor nerves (the nerves of movement). Symptoms of sensory neuropathy The most common changes in sensation that occur are: • pins and needles • burning sensations • increased sensitivity to touch • increased sensitivity to cold (with oxaliplatin treatment) • unexplained sensations (eg feeling as if you have something in your shoe) • pain, especially stabbing pains •numbness • decreased awareness of extremely hot or cold temperatures •decreased awareness of exactly which position your joints are in when you aren’t looking directly at them. These symptoms are more common in the hands and feet than further up the body but they can move upwards over time. They often start in the toes. If your fingers are affected, the changes in sensation can mean that fiddly things such as doing up buttons can become difficult. People often say that they feel clumsy or unsteady on their feet. Neuropathy can also increase your risk of burning yourself when you are cooking or bathing. Symptoms of motor neuropathy If the nerves to the muscles (the motor nerves) are affected, you can experience muscle twitches or cramps and these can be painful. Some people describe having ‘restless legs’. Sometimes the muscles can become weak and it can become more difficult to do things like writing, carrying shopping and climbing stairs. Symptoms of autonomic neuropathy If the nerves to the internal organs (the autonomic nerves) are affected, you can experience light-headedness or dizziness when you get up after sitting or lying down. Autonomic neuropathy can also cause constipation and abdominal bloating or problems with passing water (such as not being able to wait). Men with neuropathy can experience impotence. Peripheral neuropathy LYM0058/PeriphNeur/2013v2 4/10 How is peripheral neuropathy diagnosed? Your symptoms are the most important clue if you have developed a peripheral neuropathy. It is important that you tell your medical team if you develop any of the nerve symptoms we have described here while you are on treatment for lymphoma. This is because the nerve damage can often be reversed if the drug is stopped or the dose is cut down. Your team will also be checking your nervous system when they examine you and they will be able to tell if the nerves are being affected. Doctors will sometimes do special nerve tests called ‘nerve conduction studies’ or muscle tests called 'electromyography' (EMG) if a peripheral neuropathy is suspected. Will the neuropathy get better? It is not essential to stop the drug straightaway but if the neuropathy gets worse this might be necessary. Most doctors will reduce the dose of vincristine as a first step, for example, if this drug is causing symptoms. Alternatively, they might switch you to another form of vinca alkaloid such as vinblastine or vindesine, which are less likely to cause problems. The symptoms usually stop getting worse and start to go away once the treatment stops, but it can take many weeks or even several months before you notice much improvement. Providing the nerve damage is not too severe, there are usually very few long-term effects. Some people will have more long-lasting numbness or tingling in their hands and feet, however. This might never go away completely. If your lymphoma comes back and you developed peripheral neuropathy on your first course of treatment, the doctors will take this into account when they plan what treatment to give you next. They will be aiming to avoid giving you any drugs that would cause neuropathy again or make your neuropathy worse. Is there any treatment for peripheral neuropathy? It is difficult to treat neuropathy once it has developed, but it usually improves by itself with time. The best course of action is to prevent any further damage to the nerves. This is why it is important to tell your medical team straightaway if you develop symptoms. Don’t keep your symptoms to yourself for fear that your treatment will have to be stopped. The doctors can reduce the amount of the drug you are having or change it to another drug so that your recovery from the lymphoma won’t be compromised. If you develop pain as a symptom of peripheral neuropathy there are a number of painkillers and other drugs that can help. Drugs that are also used to treat depression or seizures have been found to be helpful. These include amitriptyline, duloxetine (Cymbalta®, Yentreve®), carbamazepine (Tegretol®), pregabalin (Lyrica®) and gabapentin (Neurontin®). You might need to try more than one treatment before finding the best one for you. Peripheral neuropathy LYM0058/PeriphNeur/2013v2 5/10 Treatments that can be applied directly onto the skin include lidocaine plasters (Versatis®) and capsaicin cream. There are several treatments that your doctor can prescribe if you are having problems with symptoms of autonomic neuropathy, such as light-headedness, bladder or bowel problems or sexual difficulties. In people with Waldenström’s macroglobulinaemia the neuropathy often improves when the lymphoma is treated. Some people whose neuropathy is getting worse very rapidly might need to be treated with a procedure called 'plasmapheresis' (sometimes called 'plasma exchange'). This is done to remove the IgM protein from the blood. Intravenous immunoglobulin is occasionally used to treat the neuropathy of this lymphoma. We have separate information on Waldenström’s macroglobulinaemia. If you would like this, ring our helpline (0808 808 5555) or download it from our website (www.lympomas.org.uk). Is there anything I can do myself? There are one or two things you can do before you start your treatment for lymphoma to cut down your risk of developing peripheral neuropathy. There are also some things you can do to relieve symptoms and some precautions you should take to avoid injuring yourself. Cutting down the risk of developing peripheral neuropathy If you are going to have chemotherapy it is important to tell your doctor if you already have any of the symptoms described on page 4. If you already have symptoms or signs of peripheral neuropathy your team will then be able take this into account when they plan your treatment. It is also important to mention if your diet might be lacking in vitamins or if you drink quite a lot of alcohol. This is because it might be helpful for you to be prescribed vitamin supplements to cut down your risk of developing peripheral neuropathy while you are on chemotherapy. You might be advised to avoid alcohol while you are on treatment for lymphoma. Ask your medical team about this. If you are diabetic, it will help if you can control your blood sugar as well as possible. Researchers are trying to find ways of preventing nerve damage from occurring. One possible way of doing this is to give a 'neuroprotective' treatment at the same time as the chemotherapy, though this should still be regarded as experimental. Amifostine, which can be given with platinum-containing chemotherapy drugs like cisplatin, is one example of this approach. You could ask your medical team if they would recommend this type of drug for you. Peripheral neuropathy LYM0058/PeriphNeur/2013v2 6/10 Coping with the symptoms •Some people find that gentle exercise of the fingers and toes by flexing and stretching the muscles for a few minutes four times a day can help. • Gently massaging your fingers and toes can be helpful. •If possible, avoid things that make your symptoms worse, such as cold or alcohol – wear warm gloves and socks in cold weather for example. •Burning feet can be helped by cooling them down with cooling gels. Alternatively, standing barefoot on a cold floor or putting your feet in cold water for a few minutes can relieve the burning. •If your legs are very sensitive you might find it helps to lift the bedclothes off them at night using a bed cradle. •If you are constipated, ask your doctor for advice about using laxatives, drink plenty of fluids and eat a diet rich in fruit, vegetables and wholegrains. Some people with neuropathy have found relaxation techniques and acupuncture have helped them cope with their symptoms. Keeping safe • Wear gloves when gardening or washing up. •Take care when you are making hot drinks or cooking and always use oven gloves – it is easy to burn your fingers when you can’t detect extreme temperatures. •Test bathwater temperature using your elbow or a thermometer, or get someone else to check it before you get in. You can also use a thermometer to check the temperature of washing-up water. •Wear sensible footwear that fits well, avoid high heels, and check your feet every day for places that might be rubbing or reddened. If you have any concerns about your feet you should consult a chiropodist rather than try to treat them yourself. •Cut down your risk of tripping by making sure your rooms, passageways and stairs are well lit and free of clutter. If you are finding it difficult to manage day-to-day tasks or to get about your home or outside because of neuropathy, ask to be referred to a physiotherapist or an occupational therapist. A physiotherapist might be able to organise aids such as sticks, braces or splints and can advise on exercises that might help. An occupational therapist might be able to advise you on adaptations to help you around the home if you have muscle weakness or balance problems. Peripheral neuropathy might not affect you very much or for very long. For some people, however, it can be more severe or long-lasting. If your symptoms are severe, you may feel very anxious, frustrated or depressed. Don’t hesitate to ask your medical team for help and advice if you find your symptoms difficult to cope with. Peripheral neuropathy LYM0058/PeriphNeur/2013v2 7/10 Conclusion • P eripheral neuropathy is quite a common side effect of some chemotherapy drugs, especially vincristine. •Tell your medical team if you have any symptoms of peripheral neuropathy before your treatment starts, if your diet is poor or if you drink a lot of alcohol. •Tell your medical team straightaway if you develop any of the symptoms of peripheral neuropathy, such as pins and needles, numbness, clumsiness or unsteadiness. • You can have your treatment adjusted if peripheral neuropathy develops. •Your lymphoma can still be successfully treated even if you develop peripheral neuropathy and have to have your treatment changed. •Peripheral neuropathy is often reversible if caught early, though symptoms can take weeks or even months to go away. • Take precautions to prevent injuring yourself while you have peripheral neuropathy. •There are things you can do yourself to help with the symptoms and there are treatments that the doctor can prescribe if you need additional help. Acknowledgement We would like to thank Dr Rob Hadden, Consultant Neurologist at King's College Hospital NHS Foundation Trust, London, for reviewing this article. Useful organisations The Neuropathy Trust Provides information and supports people affected by peripheral neuropathy and neuropathic pain. PO Box 26 Nantwich Cheshire CW5 5FP www.neurocentre.com British Red Cross Has a medical equipment lending service – get in touch with your local office (contact details available online). www.redcross.org.uk Disabled Living Foundation Provides information and advice on equipment that increases independence in activities of daily living. Helpline: 0300 999 0004 (10am–4pm, Monday to Friday) helpline@dlf.org.uk www.dlf.org.uk Peripheral neuropathy LYM0058/PeriphNeur/2013v2 8/10 References The full list of references is available on request. Please contact us via email (publications@lymphomas.org.uk) or telephone 01296 619409 if you would like a copy. Coyle N, et al. Understanding peripheral neuropathy (CancerCare booklet). 2008 Elsevier Oncology, New York, USA. Available at: http://media.cancercare.org/publications/ original/10-ccc_neuropathy.pdf (accessed 18 July 2013). Maloney KW. Nursing management of chemotherapy-induced peripheral neuropathy (CIPN). OncoLink, 2012. Available at: http://www.oncolink.org/resources/article1. cfm?c=424&id=1010 (accessed 18 July 2013). Perry MC (editor). The Chemotherapy Source Book. 4th edition. 2007. Lippincott Williams & Wilkins, Philadelphia, USA. Kaley TJ, DeAngelis LM. Therapy of chemotherapy-induced peripheral neuropathy. British Journal of Haematology, 2009. 145: 3–14. Baehring JM, et al. Neurological manifestations of Waldenström macroglobulinemia. Nature Clinical Practice. Neurology, 2008. 4: 547–556. Wickham R. Chemotherapy-induced peripheral neuropathy: a review and implications for oncology nursing practice. Clinical Journal of Oncology Nursing, 2007. 11: 361–376. Peripheral neuropathy LYM0058/PeriphNeur/2013v2 9/10 How we can help you We provide: a freephone helpline providing information and emotional support  0808 808 5555 (9am–6pm Mondays–Thursdays; 9am–5pm Fridays) or  information@lymphomas.org.uk ● ● information sheets and booklets about lymphoma (free of charge) ● a website with forums – www.lymphomas.org.uk ● ● the opportunity to be put in touch with others affected by lymphoma through our buddy scheme a nationwide network of lymphoma support groups. How you can help us We continually strive to improve our information resources for people affected by lymphoma and we would be interested in any feedback you might have on this article. Please visit www.lymphomas.org.uk/feedback or email publications@lymphomas.org.uk if you have any comments. Alternatively please phone our helpline on 0808 808 5555. We make every effort to ensure that the information we provide is accurate but it should not be relied upon to reflect the current state of medical research, which is constantly changing. If you are concerned about your health, you should consult your doctor. The Lymphoma Association cannot accept liability for any loss or damage resulting from any inaccuracy in this information or third party information such as information on websites which we link to. Please see our website (www.lymphomas.org.uk) for more information about how we produce our information. © Lymphoma Association PO Box 386, Aylesbury, Bucks, HP20 2GA Registered charity no. 1068395 Updated: August 2013 Next planned review: 2015 Peripheral neuropathy LYM0058/PeriphNeur/2013v2 10/10