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doi: [ 10.1111/j.1529-8019.2010.01366.x ]
Chronic Pruritus: a Paraneoplastic Sign
Chronic itch could be a presenting sign of malignancy. Pruritus of lymphoma is the common prototype of paraneoplastic itch and can precede other clinical signs by weeks and months. Paraneopalstic pruritus has also been associated with solid tumors and is an important clinical symptom in paraneoplastic skin diseases such as erythroderma, Grovers disease, malignant acanthosis nigricans, generalized granuloma annulare, Bazex syndrome and dermatomyositis. In any case with high index of suspicion a thorough work-up is required. This review highlights the association between itch and malignancy and presents new findings related to pathophysiological mechanisms and the treatment of itch associated with malignancy. Combinative therapies reducing itch sensitization and transmission using selective serotonin and neuroepinephrine reuptake inhibitors, Kappa opioids and Neuroleptics are of prime importance in reducing this bothersome symptom.
Chronic pruritus is defined as itch which last more than 6 weeks ( 1 ). It has been linked to internal malignancy and in particular lymphoproliferative disease( 2 ). Paraneoplastic itch is defined as : 1. itch that occurs early during the natural process or even precedes the clinical evidence of the malignancy. 2. It is not caused by the neoplastic mass invasion or compression and 3. subsides after the removal of the tumor. Pruritus of lymphoma is the common prototype of paraneoplastic itch and can precede other clinical signs by weeks and months( 2 ). Although generalized idiopathic pruritus has been often linked to internal malignancy( 3 ), there are few studies that examined the prevalence of itch in malignancies. Itch associated with malignancy could range from mild to intractable, which is defined as a chronic itch state in which the cause cannot be removed or treated, and no relief or cure has been found in the generally accepted course of medical practice ( 1 ).
The purpose of this review is to highlight the association between itch and malignancy and to present new findings related to the pathophysiological mechanisms and the treatment of itch associated with malignancy.
Prevalence of chronic itch has been reported decades ago as high as 30% in patients with Hodgkin’s disease( 4 ). A small-scale study showed that approximately 15% of patients with non-Hodgkin’s disease suffered from generalized pruritus( 5 ). According to a retrospective study recently conducted at MD Anderson ( 6 ), the incidence of itch is about 19% in patients with Hodgkin’s disease who were referred to dermatology.
Itch has been reported to be a preceding sign in patients with multiple myeloma ( 7 ), however there is no data on its prevalence.
Several small scale studies examined the underlying etiology of idiopathic generalized pruritus and found that malignancy is a cause in less than 10% of the patients. Lymphoma and leukemia were the most common malignancies ( 8 – 10 ).
Pruritus as a paraneoplastic sign in solid tumors of different types has been anecdotally reported ( 11 ). Pruritus was found in one out of the 9 patients with paraneoplastic syndromes among 68 patients who suffered with non-small cell lung carcinoma ( 12 ). In patients with extrahepatic cholestatic, itch may be caused by obstructive tumor in the pancreatic head and primary sclerosing cholangitis ( 2 ). Intractable pruritus has been reported as an initial presentation of insulinoma ( 13 ).
Although the pruritus may occasionally be present years before the tumor becomes detectable, a full investigation for a causative solid tumor is probably not warranted, unless other skin manifestations or clinical signs suggestive of malignancy exist.
Clinical characteristics of pruritus in malignancy
Itch can present with ichthyosiform skin changes on the extremities ( 2 ) or as a new-onset eczema lesions with Hodgkin’s disease ( 6 ). Severe intractable itch has been reported in lymphoma patients. Some of the most severe pruritic cases in our practice suffer from lymphoma. Nocturnal itch is common in all forms of chronic itch ( 14 ). Patients with paraneoplastic itch often suffer from severe intractable itch and present with secondary skin lesions as a result of the malicious itch-scratch cycle that include excoriations, hyperpigmentation or hypopigmentation, lichenification, prurigo nodules and scars.
Aquagenic pruritus is itch that develops minutes after contact with water of any temperature with no visible skin rash or urticaria. It is more commonly known to be associated with polycythemia vera, however several reports demonstrate an association with other lymphoproliferative diseases ( 15 – 16 ). Aquagenic pruritus can precede the development of T cell lymphoma or myelodysplasia by several years.
Paraneoplastic pruritus could present as part of a primary epidermal and dermal skin diseases associated with malignancy. Recently, we reported 2 cases of generalized granuloma annulare with severe itch as the initial presentation of chronic myelomonocytic leukemia ( 17 ). Generalized granuloma annulare has been associated with lymphoma and leukemia ( 18 ). Pruritus is a common manifestation in dermatomyositis ( 19 ), an average of 18-32% of patients with dermatomyositis have or will develop malignancy ( 20 ).
Transient acantholytic dermatosis (Grovers Disease) is an extremely pruritic papulovesicular disease that occurs mainly on the trunk in adult men. It has been reported to be associated with hematological malignancies, although it is not clear whether the association is related to B symptoms of sweat and fever that induce this rash ( 21 – 24 ). Erythroderma is another paraneoplastic skin manifestation that is extremely itchy and is commonly associated with hematologic malignancies ( 25 ). Recently paraneopalstic pemphigus presented as severe erythrodermic pruritic rash ( 26 ).
Eruptive seborrheic keratosis with pruritus (Lesser Trelat sign) has been reported to be associated with adenocarcinoma of the gut and hematopoietic malignancies in more than a century, however the validity of this sign is debated ( 27 – 28 ).
Malignant acanthosis nigricans (MAN) is highly associated with adenocarcinoma of the gut and is frequently associated with generalized itch in 41% of the patients in a large survey of 90 patients with MAN ( 29 ).
Bazex syndrome (acrokeratosis paraneoplastica) is a rare acral papulosquamous eruption that has been reported to be pruritic. It occurs predominantly in males and is associated with squamous cell carcinomas of the head and neck and aerodigestive ways ( 30 ).
In any patients with suspected paraneoplastic pruritus, a thorough history and a complete physical examination including an exam for lymph nodes are central to the evaluation of pruritus. Diagnostic testing is directed by the clinical evaluation. Laboratory tests should include a complete blood cell count (CBC), LDH and liver function tests. Radiological tests including CT of chest and abdomen are recommended to rule out lymphoma. A detailed history and exam will be helpful to direct further investigation; for example, a patient with bone pain should undergo blood and urine tests to rule out myeloma. As mentioned above, aquagenic pruritus can precede the development of T cell lymphoma or myelodysplasia by several years. Therefore, it is our recommendation that in any patient who suffers from aquagenic pruritus, a complete blood cell count (CBC) as well as chest X ray to be performed followed by yearly blood tests and chest X rays.
The pathophysiological mechanisms of pruritus associated with malignancy remains poorly understood. Recently major advancements have been achieved in understanding the neurobiology of itch both peripherally and centrally. In the following section we will briefly review recent findings on itch neural pathway receptors and mediators and treatment strategies that could play a role in chronic itch associated to malignancy.
Itch-selective and specific neural pathway
It has been for long time suggested that nonhistaminergic pathway likely plays a role in the transmission of chronic itch( 31 – 32 ). In the last three years, several groups were able to identify a distinct group of nerve fibers that transmit non-histaminergic itch in the spinal cord of monkeys, as well as in humans( 33 – 35 ). These fibers were found to respond to Mucuna pruriens, a plant reported by Shelley decades ago to induce itch without flare, which contains a protease named mucunanin ( 36 – 37 ). Mucunanin induces itch by activation of C nerve fibers that do not respond to histamine, but respond to mechanical stimuli. ( 33 – 35 ). The role of this newly identified itch pathway in chronic itch and systemic diseases remains to be elucidated. Sun and Chen ( 38 – 39 ) have recently identified an itch specific gene, a G protein (GRPR) within the spinal cord of mice that mediates pruritus but does not respond to painful stimuli. GRPR gene is a member of the bombesin family, bombesin is an amphibian protein widely distributed in gastrointestinal tract and central nervous system. It is abundant in malignant gastric and lung tumors in humans ( 39 ). However, these cancers commonly are not associated with itch in humans. The role of GRPR in the pathogenesis of chronic itch in humans remains to be determined.
Endogenous opioids and chronic itch
Intense, generalized itch is known to be one of the most common side effects of analgesic therapy with exogenous mu-opioids such as morphine. Endogenous opioids are important players in the pathogenesis of itch per se, as well as itch related to systemic disease. It has been proposed that chronic systemic itch is related to an imbalance between mu and kappa opioids ( 31 , 40 )
The role of endogenous opioid system in the pathogenesis of pruritus in lymphoma has not been studied yet. However, the efficacy of butorphanol (a kappa-opioid agonist and mu-opioid antagonist) in the treatment of pruritus in a non-Hodgkin lymphoma patient indicated the possible involvement of opioids in the modulation of this type of pruritus ( 41 ).
Cytokines and itch
Cytokines such as IL-6 and IL-8, which have been reported to increase in chronic kidney disease associated itch and atopic dermatitis respectively ( 42 – 43 ) are closely related to pathophysiology of lymphoma ( 44 – 45 ). Their roles in pathogenesis of itch in lymphoma are worthy of further investigation. The recent discoveries of IL-31 (a TH2 cell-derived cytokine) capable of eliciting itch, and increased IL-31 level in atopic dermatitis and prurigo nodularis, indicated a potential role of this cytokine in the modulation of chronic itch ( 46 ). An IL-31 antibody could effectively reduce scratching behavior in an atopic dermatitis-like murine model during the onset of clinical skin manifestations, suggesting the potential therapeutic role of IL-31 antibody in treatment of chronic itch ( 47 ). A mutation in the in the OSMR gene, which encodes oncostatin M receptor beta (OSMRbeta), an interleukin (IL)-6 family cytokine receptor has been recently discovered in patients with familial lichen amyloidosis, a severe form of localized itch ( 48 ). Therefore assessing the role of IL31and interleukin 6 in itch associated to lymphoproliferative diseases is a timely topic.
New Treatment options
Recently nalfurafine (TRK-820), a kappa-receptor agonist, has been launched in Japan as the first oral non histaminergic oral anti pruritic in the treatment of severe ESRD-associated pruritus ( 49 ). It has also been shown to successfully relieve pruritus in an animal model with cholestasis ( 50 ). However, TRK-820 is not available commercially yet in the US. Butorphanol is a commercially available analgesic; it works as an antagonist of mu-receptors and an agonist kappa-receptor, which was showed to be efficient in the treatment of intractable pruritus associated with lymphoma and other systemic diseases ( 41 ).
Aprepitant is a neurokinin 1 receptor antagonist widely used as antiemetic agent in chemotherapy and has recently been reported to be an effective antipruritic agent in 3 cases of Sezary syndrome with severe itch ( 51 ). The recommended dose was 80 mg per day. Future controlled trials are required to clarify the role of this expensive drug as an anti-pruritic for lymphoma.
Current Treatment Strategies
The focuses of current strategies are to reduce the intensity of itch and to block afferent transmission via peripheral and central neural mechanisms. There are a limited number of studies examining the efficacy of these agents for the treatment of itch in malignancy and most of the data presented is based on case series or small-scale studies. The purpose of this section is to review the rational systemic therapeutic ladders for pruritus associated with malignancy and in particular with lymphoproliferative diseases (see figure 1 , table 2 ).
Therapeutic ladder of treatment of pruritus in lymphoma.
Recommended systemic treatment for paraneoplastic associated pruritus.
|Drug names||Antipruritic mechanisms||Suggested doses|
|Hydroxyzine||H1-antihistamine and sedating||50-100 mg/day|
|Doxepin||H1-antihistamine and tricyclic antidepressant||25-75 mg/day|
|Naltrexone||Mu-opioid antagonist||25-50 mg/day|
|Butorphanol||Mu-antagonist and kappa-agonist||1-4 mg/day intranasally|
|Gabapentin||Central and peripheral itch pathway inhibitor||300 mg up to 3200 mg/day|
|Pregabalin||Central and peripheral itch pathway inhibitor||150 mg/day to 300 mg/day|
|Mirtazapine||Selective α2 adrenergic receptor antagonist||15 mg at night|
|Paroxetine||Selective serotonin reuptake inhibitor|
|Thaldiomide||Central and peripheral itch pathway inhibitor Anti TNF, antiangiogenic||100mg/day up to 200mg|
|Aprepitant||Neurokinin 1 inhibitor||80 mg at day time|
Antidepressants for itch
Selective serotonin reuptake inhibitors (SSRIs)
SSRIs such as sertraline and paroxetine, act by selective inhibition of serotonin reuptake. Their beneficial effect is working presumably via alteration of neurotransmitters’ concentrations within the central nervous system. A randomized, controlled study addressing paraneoplastic pruritus has shown that paroxetine significantly reduces itch ( 52 ). A recent open-labeled study showed paroxetine and fluvoxamine to be efficient in the treatment of different types of chronic itch including itch associated to systemic lymphoma and solid carcinoma ( 53 ). The antipruritic effect takes 2-3 weeks from commencement of treatment to become effective.
Selective Neuroepinephrine Re-Uptake Inhibitors (SNRI)
SNRIs relieve itch possibly by reducing central sensitization to itch due to their effects on both serotonin and noradrenergic α2 receptors, as they do in treatment of neuropathic pain ( 54 ). We found mirtazapine to be particularly effective in treatment of nocturnal pruritus ( 55 ). Mirtazapine has been reported to be effective in the treatment of itch associated with lymphoma ( 56 ). The new SNRIs such as venlafaxine and duloxetine do not seem to have significant antipruritic effects in our experience.
Gabapentin and pregabalin are structural analogues of the neurotransmitter gamma-aminobutyric acid (GABA). The exact mechanisms of their antipruritic effect are not clear. They probably inhibit central itch pathways, as they do in neuropathic pain ( 57 ).
Sedating antihistamines still have a role in treating itch, especially nocturnal itch ( 54 ). Sedating antihistamines such as hydroxyzine at high dose commonly are used to treat pruritus in patients with systemic itch probably by exerting a beneficial effect through their soporific properties. Doxepin, a tricyclic antidepressant, has a similar effect as SSRI and is also used to treat nocturnal itch, probably amid its potent antihistamine H1 receptor property.
Thalidomide has been used for more than decade as an antipruritic and may exert its effect by several mechanisms including suppression of excessive tumor necrosis factor alpha production, as well as a peripheral and central nerve depressant. Pruritus disappears in a period of 2-3 weeks. The major adverse effects are peripheral neuropathy and its high teratogenic effect that requires mandatory monitoring in women of reproductive potential in the US in the STEPS program. In the last 5 years, Thalidomide became an important part of chemotherapy of hematologic malignancies including myeloma, lymphoma and solid tumors. Interestingly, the less neurotoxic derivative of thalidomide Lenalidomide that has been recently approved has been reported to induce pruritus ( 58 ).
Ultraviolet (UV) therapy
UVB is well known to relieve pruritus in systemic diseases particularly in chronic renal disease. The role of UV therapy including both narrow band UV-B and Psoralen plus ultraviolet (UV) A (PUVA) is well established for cutaneous T cell lymphoma ( 59 ), but has not been reported to our knowledge for itch associated with systemic lymphoma and other malignancies.
Treatment of pruritus in lymphoma (see figure 1 )
A recent case series reported that the combination of low dose of mirtazapine (7.5 to 15 mg at evening) and gabapentin (300 mg at night up to 900-2400 mg per day) was effective in treatment of the itch of cutaneous of T-cell lymphoma ( 60 ). Butorphanol has been used to treat intractable itch in lymphoma with dose of 3-4 mg/day. Another option that we found helpful to alleviate intractable lymphoma itch is oral prednisone 40 mg tapering down gradually in 3 weeks( 2 ). Thalidomide the costly drug is a second line anti pruritic agent that could be considered and can also be part of the chemotherapeutic regimen.
Pruritus resolves rapidly after successful removal and treatment of the underlying malignancy.
Chronic itch could be a presenting sign of malignancy. In any case with high index of suspicion a thorough work-up is required. The underlying mechanisms responsible for this type of itch are still largely unclear. The recent advances in understanding specific itch pathways and mediators will hopefully lead to novel therapies. Combinative therapies reducing itch sensitization and transmission are of prime importance.
Skin paraneoplastic syndromes that itch.
|Paraneoplastic syndrome||Associated malignancies|
|Lesser Trelat||Adenocarcinoma of gut, hematologic malignancies|
|Generalized granuloma annulare||Lymphoma, leukemia,|
|Grovers Disease||Hematological malignancies|
|Dermatomyositis||carcinoma of colon in men breast ovaries|
cancer in women
Nasopharangyeal carcinoma in Asians
|Bazex syndrome||head and neck upper airway digestive tract carcinoma (pharynx, larynx, esophagous)|
|Malignant Acanthosis Nigricans||Adenocarcinoma of gut|
Dr Yosipovitch is supported by NIH Grant 1R01AR055902-01A1
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Common symptoms of lymphoma
Watch Dr Andrew Davies, Consultant in Medical Oncology, talk about the most common symptoms of lymphoma
There are over 60 types of lymphoma , broadly divided into Hodgkin lymphoma and non-Hodgkin lymphoma . These lymphomas can start almost anywhere in the body and can have many different symptoms. The exact symptoms they cause depend on the type of lymphoma and where it is in the body.
Most of the symptoms of lymphoma can also be symptoms of many other illnesses. These are often mild illnesses such as infections but they can sometimes be more serious conditions.
Because the symptoms of lymphoma are very general, it can sometimes be difficult to diagnose.
The most common symptoms of lymphoma are:
Swollen lymph nodes
The most common sign of lymphoma is a lump or lumps, usually in the neck, armpit or groin. They are usually painless. These lumps are swollen lymph nodes . Lots of things that aren’t lymphoma can cause lumps – and not all lymphomas cause obvious lumps.
Fatigue means being exhausted for no obvious reason or feeling washed out after doing very little. It is not the same as normal tiredness; fatigue is overwhelming and doesn’t usually feel better after sleep or rest. Fatigue can be caused by many different things. Lymphoma is just one of them.
Unexplained weight loss
Unexplained weight loss means losing a lot of weight quite quickly when you’re not trying to. It can be a symptom of lymphoma – but it can be caused by other things, too.
Lymphoma can cause night sweats that make your nightclothes and bed sheets soaking wet. The night sweats are often described as ‘drenching’. They can happen with any type of lymphoma and can also happen during the day. Night sweats can also have causes other than lymphoma.
Itching (‘pruritus’) without a rash can be a symptom of lymphoma but it can have many other causes. It can be very troublesome, particularly in hot weather.
Lymphoma affects everybody differently. For example:
- You might have lots of symptoms, only a few symptoms, or no symptoms at all. (Sometimes lymphoma is discovered during tests for something else.)
- You might have symptoms in one area (local symptoms) or symptoms that affect your whole body (systemic symptoms).
- You might feel well or you might become very unwell quickly.
Local symptoms and systemic symptoms
Some symptoms of lymphoma affect the area in and around the lymphoma itself. These are called ‘local symptoms’. The most common local symptom is a swollen lymph node or nodes. Other local symptoms are caused by swollen nodes pressing on nearby tissues. The symptoms you experience depend on where the swollen lymph nodes are. You might have:
- chest symptoms , such as cough or breathlessness
- abdominal (tummy) symptoms , such as a sense of fullness
- skin symptoms , such as a rash or itching
- pain (although this is uncommon)
- brain and nerve symptoms (again, these are uncommon), such as fits (seizures), dizziness or weakness in an arm or leg
- swelling in your arms or legs
- anaemia (low numbers of red blood cells), which can make you feel tired.
Some symptoms of lymphoma affect your whole body. These are called ‘systemic symptoms’. They are caused by the chemicals produced by the lymphoma itself and your body’s reaction to the lymphoma. Systemic symptoms include:
- weight loss
- night sweats
- frequent infections .
Around 1 in 4 people with Hodgkin lymphoma and 1 in 3 people with high-grade non-Hodgkin lymphoma may have systemic symptoms. Systemic symptoms are less common in people with low-grade non-Hodgkin lymphoma .
What should I do if I have symptoms of lymphoma?
Most of the symptoms of lymphoma can occur in other, more common illnesses as well. Having one or more of these symptoms doesn’t necessarily mean you have lymphoma.
If you think you might have lymphoma, or you are worried about any aspect of your health, visit your GP.
You can also find helpful information and advice about your health on NHS Choices or Patient.Info .
If you have a diagnosis of lymphoma and you’re finding it difficult to manage your symptoms, we have some general guidance for coping with some of the common symptoms of lymphoma . Speak to your doctor for advice about managing your individual symptoms.
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You may hear the term ‘B symptoms’, especially when your lymphoma is being staged. Staging is the process of working out how many different parts of your body are affected by lymphoma. The following symptoms are referred to as B symptoms:
- unexplained weight loss
- night sweats
- fever .
Doctors will take into account whether you have any B symptoms when they plan your treatment .
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Swollen lymph nodes
Lymph nodes help to fight infection. They can become swollen for lots of reasons, even when they’re working as they should.
A swollen lymph node or nodes is the most common symptom of lymphoma – but lymphoma is not the most common cause of swollen lymph nodes. Most people who have swollen lymph nodes do not have lymphoma. More common causes of swollen lymph nodes include:
- infections, such as coughs, colds, ear and throat infections
- illnesses that affect the immune system , such as rheumatoid arthritis
- severe skin diseases such as eczema or psoriasis
- some medicines.
Swollen lymph nodes caused by infections are usually sensitive or painful to the touch. The swelling normally goes down within 2 or 3 weeks.
Swollen lymph nodes caused by lymphoma:
- are most commonly found in the neck, armpit or groin
- are usually smooth and round
- tend to be mobile (they move out of the way when you press on them)
- have a ‘rubbery’ texture
- are usually painless – although they can sometimes ache or cause pain in nearby areas (for example, if they’re pressing on a nerve)
- rarely, can become painful a few minutes after drinking alcohol (this affects up to 5 in 100 people with Hodgkin lymphoma and is probably due to blood vessels in the lymph node widening in response to alcohol).
Having swollen lymph nodes does not necessarily mean you have lymphoma. If you notice a lump that doesn’t go away within 2 to 3 weeks, or you find that a lump is getting bigger, see your doctor.
Lymph nodes in the neck, armpit or groin are close to the surface of the skin and are easy to see and feel. Others, such as those deep inside the abdomen (stomach) or the chest, can’t be felt from the outside. If these swell, they might cause pain if they press on internal tissues, or they might only be found on a scan .
Around 2 in 3 people with lymphoma have swollen lymph nodes that they can feel. It might be the only sign that anything is wrong.
You might have swollen lymph nodes:
- in just one area of your body, which can happen with any type of lymphoma
- spread throughout your body (known as ‘generalised lymphadenopathy’), which is more common in non-Hodgkin lymphoma than Hodgkin lymphoma .
Swollen lymph nodes in lymphoma are caused by a build-up of cancerous cells in the lymph nodes. Sometimes the disease is active, making lots of cancerous cells, while at other times it quietens down and some of the cells die. This means the swollen lymph nodes can sometimes grow and shrink, especially in people with low-grade non-Hodgkin lymphoma .
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Fatigue is overwhelming physical, emotional or mental exhaustion for no obvious reason. It isn’t relieved by sleep or rest. People describe it as feeling drained of energy, or being so tired you can’t do your normal activities. Sometimes even simple daily tasks, such as getting dressed, can feel too much.
Many conditions can make you feel fatigued, including anaemia (low red blood cell count), underactive thyroid, depression and anxiety, chronic fatigue syndrome and glandular fever. If you feel fatigued, it does not necessarily mean that you have lymphoma.
Exactly why lymphoma causes fatigue is not known. It is likely that there are several reasons for it.
If you are experiencing fatigue, speak to your doctor. We also have some suggestions that may help you cope with fatigue .
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Unexplained weight loss
‘Unexplained’ weight loss means losing weight over a short period of time without trying to. The NHS advises that you see your GP if you lose more than 5% of your normal body weight over 6 to 12 months. For an average person, this means losing around half a stone (7lbs) or more. People with lymphoma might lose more than this: over 10% of their body weight within 6 months. For example, a person who usually weighs 11 stone (70kg) might lose 15lbs (7kg) or more.
Weight loss can happen in people with lymphoma because cancerous cells use up your energy resources. In addition, your body uses energy trying to get rid of the cancerous cells. Weight loss is more common with lymphomas that grow very quickly and put a sudden demand on your body.
As with many other symptoms, weight loss can happen for a lot of other reasons, such as stress, depression, diseases of the digestive tract, or overactive thyroid. Lymphoma is just one of the possible causes of unexplained weight loss.
Contact your doctor if you lose more than 5% of your body weight over 6 to 12 months without trying to.
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If you have night sweats, it does not necessarily mean you have lymphoma. Night sweats can also be caused by other conditions, such as a viral infection, anxiety, menopause or some medicines.
Doctors don’t know exactly why lymphoma causes night sweats. One possible reason is that they are your body’s natural reaction to your temperature rising above a normal level ( fever ). Night sweats may also be a response to some of the chemicals produced by the lymphoma cells.
Lymphoma can cause night sweats that are severe enough to make your nightclothes and bed linen soaking wet. They are often described as ‘drenching’. They can happen with any type of lymphoma. Although they are usually called night sweats, they can also sometimes happen during the day.
There are things you can do that might help you to cope with night sweats , but do also speak to your medical team for advice.
Contact your doctor if you have night sweats that regularly wake you up or if you also have other symptoms, such as fever or unexplained weight loss.
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Itching (also known as ‘pruritus’) can be caused by many different conditions, including allergies, skin conditions such as eczema, skin infections or menopause. It is not usually serious. Although itching is common in people with lymphoma, having itchy skin does not necessarily mean you have lymphoma.
Itching affects around 1 in 3 people with Hodgkin lymphoma and 1 in 10 people with non-Hodgkin lymphoma . It can affect:
- areas of skin near lymph nodes that are affected by lymphoma
- patches of skin lymphoma
- the lower legs
- the whole body.
Itching in lymphoma is thought to be due to chemicals released by your immune system, as part of its reaction against the lymphoma cells. These chemicals irritate the nerves in your skin and make it itch.
Itching due to lymphoma can be severe. It may also cause a burning sensation. It is not usually associated with an obvious rash unless you have skin lymphoma.
Itching can be very difficult to tolerate, especially in hot weather. It is usually worse at night in bed. If you have a diagnosis of lymphoma and you are struggling to cope with itching, there are some things you could try that might help . Also speak to your medical team for advice.
Contact your GP if you have itching that affects your whole body or lasts for more than 2 weeks.
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Fever is a rise in your body temperature above the normal level. It is almost always caused by an infection , but there are a few other much less common causes, including lymphoma.
Lymphoma causes fevers because the lymphoma cells produce chemicals that raise your body temperature. Lymphoma usually causes mild fevers – a body temperature over 38°C or 100.4°F. These are described as ‘low-grade’ fevers. They usually come and go.
Contact your doctor if you have a fever without an obvious infection that lasts for 2 weeks or more.
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Difficulty getting over infections
Having lymphoma can mean that your immune system doesn’t work as well as it should .
Normally, white blood cells fight infections. If you have lymphoma, cancerous white blood cells (that make up the lymphoma) are produced instead of the healthy, ‘good’ white blood cells. This can make you pick up infections more easily. The infections could be more severe or last for longer than they would normally.
Infections often cause a high temperature and make you feel hot and shivery. Other symptoms depend on where in your body you have the infection – for example, you might have an earache, a cough, a sore throat, pain when you have a wee, or sickness and diarrhoea.
See your GP if you’re worried that you’re not getting better after a minor infection.
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Any type of lymphoma can cause swollen lymph nodes in the chest but they are especially common in Hodgkin lymphoma and some types of high-grade non-Hodgkin lymphoma (where the cells appear to be dividing quickly). Around 1 in 2 people with Hodgkin lymphoma have swollen lymph nodes in their chest.
Swollen lymph nodes in the chest can press on your airways, lungs, or blood vessels. They can also make fluid collect around your lungs. This can cause:
- a dry cough
- shortness of breath
- noisy breathing
- pain behind the breastbone
- a feeling of pressure in the chest.
These symptoms may be worse when you lie down.
It is important to remember that all these symptoms can happen with many other illnesses, especially lung diseases. Having these symptoms doesn’t necessarily mean you have lymphoma.
Visit your GP if you’ve had a cough lasting more than 3 weeks or shortness of breath lasting more than 4 weeks.
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Abdominal (tummy) symptoms
Lymphoma can develop in lymph nodes in the abdomen (tummy) or lymphatic tissue in your liver or spleen . It can also develop outside your lymphatic system (‘extranodal’ lymphoma). The gut is the most common place for extranodal lymphoma to develop.
Symptoms of lymphoma in the tummy depend on what part of the tummy is involved. For example:
- If your spleen is very swollen, you might have pain behind your ribs on the left side, or you might feel bloated or full after eating only small amounts of food. You or your doctor might be able to feel the swollen spleen as a lump in the top left hand side of your tummy.
- If you have lymphoma affecting your liver, your tummy might become swollen, the whites of your eyes and your skin might develop a yellow tinge (jaundice), or you might notice a build-up of fluid in your abdomen. This can make you feel bloated.
- Lymphoma in the stomach can cause inflammation of the stomach lining (gastritis), which may cause pain, nausea (feeling sick) and vomiting.
- Lymphoma in the bowel can cause abdominal pain, diarrhoea or constipation.
See your GP if you have blood in your poo, diarrhoea for more than 7 days, green or yellow vomit, vomiting lasting more than 2 days, or if you are dehydrated and you are unable to keep liquids down.
See your GP urgently if your skin or the whites of your eyes look yellow.
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Swollen lymph nodes themselves are not usually painful but lymphoma can press on the tissues around the nodes and cause pain. Where you feel the pain depends on where the lymphoma is.
Lymphoma in the bone itself is rare but when it does happen, it can cause pain in the affected bone. It is more common to have lymphoma in the bone marrow (the spongy part in the middle of some of our larger bones), but this doesn’t usually cause pain.
If you are worried about any aspect of your health, visit your GP.
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If you have skin lymphoma , you might get symptoms on your skin such as:
- flat red patches
- raised plaques with a scaly surface
Lymphoma in the skin can look a lot like other skin conditions, such as eczema or psoriasis. Skin lymphomas are usually low-grade lymphomas. Sometimes other parts of the body are also affected but for most people with skin lymphoma, it stays in the skin.
If you have a diagnosis of skin lymphoma and you are finding it hard to cope with your symptoms, there are some things you could try that might help . Also speak to your medical team for advice.
Contact your GP urgently if you have a rash that starts suddenly and spreads quickly, a rash that is all over your body, or a rash with other symptoms such as pain, fever or breathlessness.
Visit your GP if you have a rash that doesn’t go away within a few days or that is interfering with your normal life.
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Brain and nerve symptoms
Lymphoma that starts in or spreads to the brain or nervous system is very uncommon but can cause symptoms such as headaches, fits (seizures), memory problems, dizziness, sight problems, numbness, tingling or weakness in a limb. Many other conditions can also cause these symptoms, such as epilepsy, migraine or stroke.
Contact your GP if you have any of these symptoms.
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Swelling in the arms or legs
Swollen lymph nodes can sometimes block the lymphatic vessels that run through the body. This stops fluid called lymph draining properly from the body’s tissues. This fluid can build up, causing swelling and feelings of tightness, heaviness or soreness. This is called ‘lymphoedema’. It usually affects an arm or a leg, although other areas of the body can be affected depending on where your lymphoma is. Other conditions, such as infection, injury, or some types of surgery, can also cause lymphoedema.
It is important to know that lymphoedema is very uncommon and usually gets better once treatment is started. If you are finding it hard to cope with, there are some things you can do that might help .
See your GP if you have any symptoms of lymphoedema.
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Around 1 in 3 people with lymphoma have anaemia (low number of red blood cells). This can make you feel tired and breathless because your body has to work harder than usual to get enough oxygen. You might look pale and you may have heart palpitations.
Anaemia may be caused by lymphoma in the bone marrow or by bleeding due to lymphoma in the gut . If you have a swollen spleen, anaemia can also be caused by red blood cells collecting in the spleen or being destroyed in the spleen. Lots of other, less serious, conditions can also cause anaemia, such as heavy periods, pregnancy or stomach ulcers.
Contact your GP if you think you might be anaemic.
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- What is lymphoma?
- Symptoms of lymphoma
- Coping with symptoms of lymphoma
- Tests, diagnosis and staging
- Treatment for lymphoma
- Side effects of treatment
- Living with lymphoma
- Relationships and caring
- Useful organisations
- Our printed information
- Last reviewed
- Next planned review
Living with lymphoma booklet
Introduction to lymphoma
Symptoms of lymphoma information sheet
- Dr Graham Collins, Consultant Haematologist, Oxford University Hospitals NHS Foundation Trust.
- Laura Croan, Lymphoma Clinical Nurse Specialist, Belfast Health and Social Care Trust
- Dr Vince Ryan, General Practitioner, Hanham Health, Bristol
- Mairéad Mulhall, Macmillan Lymphoma Clinical Nurse Specialist, University Hospital Southampton NHS Foundation Trust
- We would like to thank the members of our Reader Panel who gave their time to review this information
Coping with symptoms of lymphoma
Tests, diagnosis and staging of lymphoma
Types of lymphoma
Treatment for lymphoma