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Review article

Sweating in advanced cancer

Robert Twycross

Sweating (perspiration, diaphoresis, hidrosis) is Paradoxically, sweating is sometimes cold-

the secretion of fluid, mainly water and sodium induced. Ingestion of spicy food may cause
chloride, from the eccrine (sweat) glands onto ‘gustatory sweating’ limited to the lips, nose
the skin. Sweating occurs only in humans and and forehead. After drinking alcohol,
apes, and is an important component of the vasodilation may result in sweating. It
thermoregulatory system. It aids cooling by the commonly occurs in response to
evaporation of sweat from the body surface embarrassment, anxiety, fear, and severe pain.
(Pittelkow and Loprinzi 2003). Other mammals Sweating also occurs at the menopause and
must pant, rest, splash with water, or move to after ovarian or testicular ablation in addition
a cooler place to lower body temperature. to the characteristic hot flushes (Hargrove and
Evaporation of secretions occurs constantly Eisenberg 1995).
from the skin and the mucous membranes of Hyperhidrosis, i.e. inappropriate high-volume
the mouth and respiratory tract. The basal level sweating, occurs in various disorders. In
of ‘insensible’ water loss is about 50ml/h, i.e. malignant disease, as with chronic infections,
about 1200ml/24h (Ganong 1979). The it may occur only at night (‘night sweats’), and
maximum possible secretion from 3–4 million tends to be paroxysmal whatever time it
glands in the skin is 2–3L/h (Ryan 1996). occurs. If there is associated pyrexia, there is
Sweating typically occurs during and after no fixed pattern (Boggs and Frei 1960). Thus
exercise, when there is a high ambient it may be continuous, intermittent, remittent,
temperature, or when there is a pyrexia. low-grade, hectic, or any combination of these
However, infants and sedentary old people types.
tend to sweat insufficiently, and may develop Anatomy
hyperthermia in these circumstances. Two types of gland secrete moisture onto the
surface of the body:
Correspondence
apocrine
Dr. Robert Twycross DM FRCP
l

WHO Collaborating Centre for Palliative Care, l eccrine.

Sir Michael Sobell House, Churchill Hospital,
Apocrine glands develop at puberty and their
Oxford, OX3 7LJ, UK
ducts empty into hair follicles. They occur in
Tel: 044 1865 225891
the scalp, axillae, around the nipples and in
Fax: 044 1865 225599

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the anogenital area. Secretions contain proteins Pathogenesis in advanced cancer

and complex carbohydrates, and are under Sweating is particularly associated with
adrenergic control (Kirby 1990). Hodgkin’s disease and several other types of
malignant disease, as well as with any type of
The eccrine glands secrete sweat, a watery fluid widely disseminated malignancy and/or liver
containing chloride, lactic acid, fatty acids, metastases. The prevalence in advanced
glycoproteins, mucopolysaccharides and urea, malignancy may be as high as 14-28% (Grond
directly onto the skin surface. There are two et al. 1994; Quigley and Baines 1997). Most
functionally separate sets of eccrine glands. cases are infective or paraneoplastic (Boggs
One set populates the entire skin except the and Frei 1960). Hormonal insufficiency and
palms and soles and is responsible for thermal drugs probably account for most of the rest
regulation; secretion is controlled by (Box A). Sweating also occurs as part of a
cholinergic (muscarinic) postganglionic withdrawal syndrome seen after the abrupt
sympathetic fibres. The other set is confined discontinuation of various psycho-active drugs,
to the palms, soles and axillae and is controlled including opioids. Sometimes there is more
by adrenergic fibres. Those on the palms and than one cause, e.g. both liver metastases and
soles respond mostly to emotion whereas those morphine.
in the axillae respond to both heat and
emotion.

Box A Causes of sweating in advanced malignant disease

Functional Pathological, generalized

Primary Infection
Gustatory (localised) Acute
Anxiety, fear Chronic, e.g. tuberculosis
Menopausal, post-castration Neoplastic
Drugs Hodgkin’s disease
Interferon Ewing’s sarcoma
Opioids Renal cell cancer
Pilocarpine Ovarian cancer
SSRIs Phaeochromocytoma
Tamoxifen Hepatoma
Tricyclic antidepressants (paradoxical) Hepatic metastases
Drug withdrawal syndromes Carcinoid syndrome

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Sweating in advanced cancer

Pathological, localized (neurogenic) Endocrine disorder

Sympathetic neuropathy, e.g. Diabetes insipidus
Pancoast’s tumour (see text) Diabetes mellitus
Intrathoracic tumour Hyperthyroidism
Retroperitoneal tumour Hypoglycaemia
Hypopituitarism

Spinal cord disease Auto-immune disease

Cerebrovascular (i.e. post-stroke) Shock

Hypotheses to explain paraneoplastic sweating o

35 C. On one occasion, he developed a chest
include: infection and his temperature increased to
o
37.5 C, but he was told that he could not have
l the release of pyrogens as a result of
an infection because his temperature was
leucocyte infiltration or necrosis of the
‘normal’. He had also noted that, just before
tumour
the onset of an episode of sweating, his
l a substance (cytokine?) released by the temperature would increase but, using the
o
tumour which acts either directly on the standard definition of pyrexia (above 38 C),
hypothalamus or indirectly via endogenous he was still technically apyrexial.
pyrogen (Hami and Trotman 1999; Thus, it seems reasonable to postulate that, in
Johnson 1996). some patients, a substance is released by the
The pyrogens then induce a prostaglandin tumour which lowers the thermal set-point in
cascade which results in pyrexia and the hypothalamus. Then, following a tumour-
consequential sweating (Tabibzadeh et al. related release of endogenous pyrogen,
1989; Tsavaris et al. 1990). However, some sweating occurs in an attempt to restore the
patients with paraneoplastic sweating do not body temperature to its malignancy-lowered
have an associated pyrexia. Indeed, in one thermal set-point – but in the absence of
small series, only one patient out of seven was pyrexia as normally defined.
pyrexial (Deaner 2000). A clue to explaining
Hypercapnia, plasma osmolality, intravascular
the apparent dissociation between sweating
volume changes, and dehydration can also
and pyrexia is contained in the following case
impact on the hypothalamic thermoregulatory
history.
centre, lowering the thermal set-point and
Case history resulting in an increased tendency to sweating
A man complained of troublesome sweating. (Pittelkow and Loprinzi 2003).
Some months earlier, after the diagnosis of
Abnormal localised sweating may be
mesothelioma, he noted that his normal
o associated with lesions of the nervous system
temperature had decreased from 37 C to about

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(Box A). For example, pressure on the l how long has it been troublesome?
sympathetic chain in the thorax by a lung l is there diurnal variation? (Some patients
cancer or mesothelioma may result in only experience night sweats)
ipsilateral hyperhidrosis. In contrast, with a l is there an associated pyrexia? (Consider
Pancoast tumour, the sympathetic chain checking every 4 hours for 48 hours)
subserving the ipsilateral upper quadrant may l is the sweating related to another event?
be damaged, causing regional anhidrosis and (For example, a recent change in drug
compensatory hyperhidrosis on the therapy or castration)
contralateral side (Pleet et al 1983, Middleton l are there any apparent precipitating factors?
1976) .
Consider checking the white blood cell count
and examining the urine for pus cells. Urine
Evaluation
and blood cultures, and a chest radiograph are
It is useful to have working definitions of mild,
sometimes also appropriate. At some centres,
moderate and severe sweating, such as:
‘blind’ antibiotic therapy is used as a diagnostic
l mild: symptom elicited only on direct test. Guidance about appropriate therapy
questioning should be obtained from a microbiologist.
l moderate: symptom reported, drying with
towel required, change of clothes
unnecessary Management
l severe: symptom reported as drenching Correct the correctable
sweats, need to change clothes/bed linen l tre at infection with the appropriate
(Quigley and Baines 1997) antibiotic
l hormone deficiency after castration: hormonal
Although there are several objective tests to or non-hormonal treatment (Box B)
determine the pattern and extent of l drug-induced: if possible, discontinue the
hyperhidrosis (Pittelkow and Loprinzi 2003), causal agent, e.g.
these are generally inappropriate in patients if a tricyclic antidepressant or an SSRI is
with advanced cancer. As with other the cause, switch to venlafaxine
symptoms, the diagnosis of the cause of the
if morphine is the cause, consider switching
sweating is based largely on probability and
to an alternative strong opioid, although
pattern recognition. Paraneoplastic sweating
this may not be beneficial (Mercadante
is a diagnosis of exclusion. Questions to ask
1998; Zylicz and Krajnik 2003).
include:

l is the sweating localised or generalised?

l how severe is it?

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Sweating in advanced cancer

Box B Drug treatment for menopausal and post-castration hot flushes and/or sweating

Hormonal

Megestrol acetate 40mg o.m., with a trial reduction to 20mg after 1 month if effective
(Quella S et al. 1998).

Medroxyprogesterone 5-20mg b.d.-q.d.s.

Diethylstilbestrol 1mg o.m. (Miller J and Ahmann F 1992)

A progestogen is the hormonal treatment of choice

Non-hormonal

Clonidine 100microgram o.n. (Pandya K et al. 2000) or 50microgram t.d.s., increasing

up to 1200microgram/day (Miller M 2003); 40% response rate, may cause nocturnal restlessness
(Twycross R et al. 2002a), and is ineffective in men.

Note: abrupt discontinuation may cause a hypertensive crisis.

Gabapentin (Guttuso T 2000); a promising open-label study, but no published controlled

studies.

Venlafaxine 37.5mg o.d., increasing to 75mg o.d. after 1 week; 60% response rate
(Loprinzi C et al. 2000)

Venlafaxine is the non-hormonal treatment of choice

Note that placebo reduces menopausal flushes However, at many centres, hormonal treatment
by a mean of 20-25%. In 20% of women, the is no longer the treatment of choice for hot
reduction will be >50% (Figure 1) (Loprinzi flushes in cancer patients (Figure 2).
et al. 2001). Hormonal treatment is equally
effective in breast and prostate cancer; the
maximum effect comes after 3-4 weeks.

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Figure 1. Hot flushes in breast cancer survivors; percentage reduction in median weekly scores
(from Loprinzi, et al 2001, with permission)

Figure 2. Treatment ladder for hot flushes

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Sweating in advanced cancer

Non-drug treatment l paracetamol 500-1000mg q.d.s. or p.r.n.

l reduce ambient temperature l a non-steroidal anti-inflammatory drug
l encourage air-flow, e.g. draught, fan (NSAID), e.g. ibuprofen 200-400mg t.d.s.
l diet: avoid very hot drinks, spicy food or p.r.n., or the locally preferred alternative.
less bed-covers
Some people complain of a transient increase
l

l avoid plastic covers on pillows and mattress

in sweating after taking an antipyretic;
l cotton clothes; high ‘wicking’ property,
however, this is part of the process of cooling
resulting in enhanced evaporation.
down.
Although local treatment with aluminium
chloride hexahydrate (axillae) and formalin or It has been claimed that naproxen is the
gluteraldehyde (feet) are of value in emotional NSAID of choice for paraneoplastic pyrexia
sweating (Simpson N 1988), they are and sweating (Chang 1988). However, a
generally irrelevant in advanced cancer. Such comparison of 250mg b.d. with diclofenac
treatments work by blocking or destroying 25mg t.d.s. and indomethacin 25mg t.d.s. in
sweat glands. Iontophoresis (Murphy and 3 randomly allocated groups of 16 patients
Harrington 2000), botulinum toxin and demonstrated no significant difference
surgical approaches such as undercutting the between the three drugs (Figure 3), although
axillary skin, excision and sympathectomy, are the mean time to response was about 8 hours
also irrelevant (Atkins and Butler 2000; Collin for naproxen but over 20 hours for the other
and Whatling 2000). two drugs (Tsavaris et al. 1990). However, this
could reflect the relatively low doses of
Symptomatic drug treatment
diclofenac and indomethacin used.
Begin by prescribing an antipyretic:

Figure 3. NSAIDs and paraneoplastic pyrexia; three groups of 16 randomly allocated subjects.
Key: DS = diclofenac sodium 25 mg t.d.s., I = indomethacin 25 mg t.d.s., N = naproxen 250 mg b.d.
(from Tsavavis et al, 1990, with permission)

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What was surprising was the relatively poor agents has never been done. Similarly surprising
response to corticosteroids in dose equivalent was the observation that, although the
to at least 100mg of hydrocortisone/day antipyretic effect of an NSAID tends to wear
(Chang 1988). A complete response to off after 1-5 months, further benefit is obtained
naproxen 250-375mg b.d. was seen in 36/39 by switching to an alternative NSAID. However,
patients, but in only 6/12 given a corticosteroid the duration of benefit with the second- and
(Figure 4). It is difficult to explain this. third-line drugs is generally shorter.
However, a formal controlled trial of the two
If the sweating does not respond to an NSAID,

Figure 4. Effect of naproxen and corticosteroids on paraneoplastic pyrexia in a patient with Hodgkin’s
disease stage 4b (from Chang 1988, with permission)

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Sweating in advanced cancer

prescribe an antimuscarinic drug: l propranolol 10-20mg b.d.-t.d.s.

cimetidine 400-800mg b.d. (Pittelkow and
propantheline 15-30mg b.d.-t.d.s.; a safe l
l

Loprinzi 2003)
non-sedative drug (Miller M 2003)
l thioridazine 10-30mg o.n.; tends to cause l olanzapine 5mg b.d. (Zylicz and Krajnik
2003)
sedation in doses above 10mg; some
patients also need a daytime dose; said to l thalidomide 100mg o.n. (Deaner 2000;
be effective in 50-90% of patients; now Calder and Bruera 2000).
discouraged in the UK because of a danger Thalidomide should be the last resort even
of cardiac arrhythmias (Regnard 1996; though the response rate appears to be high
Cowap and Hardy 1998). (Deaner 2000). This is because of the likelihood
of an irreversible painful peripheral neuropathy;
amitriptyline 25-50mg o.n.; but may cause
it also has a tendency to cause somnolence
l

sedation, dry mouth and other (Twycross et al. 2002b). Figure 5 offers a
antimuscarinic effects possible 4-step treatment ladder.
l transdermal hyoscine hydrobromide Acknowledgement
500microgram over 3days or hyoscine The author thanks Dr Mary Miller for supplying
butylbromide 40mg/24h by continuous the case history, and for her helpful comments
subcutaneous infusion (Mercadante 1998). on the article.
If an antimuscarinic fails, other options include: R Twycross Clinical Reader Emeritus in Palliative
Medicine, Oxford University

Figure 5. Treatment ladder for paraneoplastic sweating

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