Pruritus and sweating

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Pruritus is an unpleasant sensation provoking the desire to scratch. Ask whether a rash preceded scratching: eczema, urticaria, scabies, fungal disease and contact reactions begin in skin, whereas cholestatic, uraemic and haematological itch often lacks a primary eruption. Excoriations, lichenification and infection may then obscure the original pattern. Localised neuropathic itch follows nerve or spinal disease and may include burning or altered sensation.

Systemic assessment should remain purposeful. Dark urine, pale stool and jaundice point to cholestasis; reduced renal function and restless sleep support uraemic itch; aquagenic symptoms, sweats, nodes or weight loss raise haematological disease. Check thyroid, glucose, iron and malignancy clues when clinically plausible. Review opioids, antibiotics, anticancer medicines and recent additions, but distinguish a stable adverse effect from an acute severe cutaneous drug reaction.

Skin care is the foundation. Keep the room cool, use lukewarm rather than hot bathing, wash with an emollient or soap substitute and apply a fragrance-free leave-on emollient soon afterwards and repeatedly. Reduce friction with loose cotton clothing, trim nails and use cool compresses. Treat scabies, fungal infection, eczema or urticaria specifically. Avoid indiscriminate topical antihistamines and fragranced products that sensitise skin.

Cholestatic itch reflects bile-related mediators and altered endogenous opioid signalling rather than histamine alone. Image potentially reversible extrahepatic obstruction when intervention fits goals. Cholestyramine binds bile acids in the gut and is usual first-line medicine, but causes constipation and binds many oral drugs; schedule other medicines at least one hour before or four to six hours after it. Rifampicin is an effective specialist second-line option but can cause hepatitis, renal injury and major enzyme-inducing interactions.

Uraemic itch needs optimisation of kidney care, phosphate and skin dryness and review of dialysis adequacy where relevant. Gabapentin or pregabalin can help some patients, but tiny renal-adjusted doses may be required, especially after dialysis, and opioid co-prescribing increases sedation and respiratory risk. Do not convert a renal symptom into medicine toxicity. Ultraviolet B or kidney-specialist options may suit selected patients.

Sweating assessment separates generalised fever or autonomic activation from local hyperhidrosis. Record temperature during episodes, rigors, nocturnal pattern, flushing, pain, anxiety, menopause, glucose symptoms and medicine or substance timing. Opioids, antidepressants, corticosteroids, hormonal therapies and withdrawal commonly contribute.

Key points

First-line assessment maps timing, triggers, rash before scratching, systemic clues, medicines and effects on skin and sleep.
Treat airway swelling, wheeze, shock or rapidly spreading urticaria as possible anaphylaxis; fever with rigors, hypotension or confusion requires urgent infection assessment.
First-line itch care uses a cool environment, soap substitute, regular fragrance-free emollient, short nails, loose cotton clothing and treatment of the primary skin disorder.
Antihistamines help urticaria and other histamine-mediated itch but usually have little direct benefit in cholestatic or uraemic pruritus; sedation is not the same as antipruritic efficacy.
For cholestatic pruritus, relieve a reversible biliary obstruction when appropriate; cholestyramine is usual first-line drug treatment and must be separated from other medicines.
Rifampicin, opioid-pathway medicines and treatments for uraemic itch require specialist selection, interaction checks and liver or renal monitoring.
First-line sweating care treats fever, pain, anxiety, withdrawal or endocrine cause and uses a fan, breathable layers, bedding changes, hydration and skin-fold protection.
Refractory sweating may justify specialist off-label treatment only after cause review and non-drug care.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Cutaneous and histamine causes

Eczema, urticaria, scabies, fungal infection, contact allergy, xerosis and wounds generate local inflammatory or histamine-mediated itch.

Systemic pruritus

Cholestasis, kidney failure, thyroid or iron disorders and haematological malignancy activate non-histamine neural and circulating itch pathways.

Medicine and neurological causes

Opioids, antibiotics, anticancer agents, nerve injury, spinal disease and central lesions can produce generalised or anatomically localised itch.

Sweating drivers

Infection, malignancy, endocrine change, pain, panic, autonomic dysfunction, menopause, opioids, antidepressants and substance withdrawal increase sweat production.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Peripheral itch signalling
Cutaneous C fibres respond to histamine, proteases, cytokines and other pruritogens and relay signals through spinal pathways to sensory and affective centres.
2
Cholestatic signalling
Accumulated pruritogens and altered bile, lysophosphatidic and endogenous opioid pathways sensitise itch networks without producing a typical primary rash.
3
Uraemic sensitisation
Xerosis, inflammation, metabolic retention, neural change and altered opioid balance combine; symptom severity does not track one toxin concentration.
4
Itch-scratch cycle
Scratching briefly inhibits itch but damages barrier, releases inflammatory mediators and causes excoriation, infection and further itch.
5
Thermoregulatory sweating
Hypothalamic and sympathetic cholinergic pathways activate eccrine glands during heat, fever, emotion, endocrine change and medicine effects.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Primary dermatosis

A rash with diagnostic morphology and distribution precedes scratching and directs treatment toward eczema, urticaria, infestation, fungal disease or contact exposure.

Systemic itch

Generalised symptoms without a primary rash, especially with jaundice, renal impairment, aquagenic trigger or constitutional features, suggests an internal cause.

Neuropathic itch

Localised burning, tingling, sensory change or itch in a dermatome without inflammation suggests peripheral nerve, spinal or central pathway injury.

Infective sweating

Measured fever, rigors, hypotension, focal symptoms or new confusion makes infection a priority over symptomatic antiperspirant treatment.

Medicine-linked sweating

Onset after opioid, antidepressant, corticosteroid, hormone treatment or withdrawal and improvement with adjustment supports a pharmacological driver.

Anaphylaxis or severe drug reactionRed flag

Airway swelling, wheeze, shock, mucosal erosion, blistering, skin pain or systemic illness requires emergency treatment and immediate culprit-drug review.

Red flags requiring action

Tongue or throat swelling, stridor, wheeze, hypoxia, hypotension or collapse with itch is anaphylaxis until proven otherwise.
Fever, rigors, hypotension, tachypnoea, confusion or reduced urine output with sweating requires urgent sepsis assessment.
Skin pain, mucosal involvement, blistering, purpura or detachment after a new medicine suggests a severe cutaneous drug reaction.
Jaundice with fever and right-upper-quadrant pain suggests ascending cholangitis and requires urgent biliary and infection management.
Drenching sweats with persistent fever, nodes, splenomegaly or weight loss raises infection or haematological malignancy.
New drowsiness, falls, myoclonus or slow breathing after gabapentin in renal impairment suggests accumulation and toxicity.
Naltrexone or another opioid antagonist can precipitate severe withdrawal and loss of analgesia in a patient receiving opioids.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
First-line skin and systemic historyFirst stepFirst line
Why
Determine rash timing, distribution, water or heat triggers, contacts, jaundice, renal disease, fever, weight loss, medicines and effect on sleep.
Interpretation and limitations
A primary rash directs dermatological treatment; no rash plus systemic clues directs cause-focused blood and imaging assessment.
02
Complete skin and node examination
Why
Inspect scalp, finger webs, nails, flexures, genital region and skin folds for morphology, burrows, excoriation, infection, jaundice and nodes.
Interpretation and limitations
Secondary scratch marks are not a diagnosis; identifying the lesion before scratching prevents indiscriminate antipruritic prescribing.
03
Targeted first-line blood panelFirst line
Why
Use full blood count, ferritin, renal, liver, calcium, glucose, thyroid and inflammatory testing when systemic disease is plausible and actionable.
Interpretation and limitations
Results can identify cholestasis, advanced kidney disease, iron or endocrine abnormalities and infection but there is no single gold-standard pruritus blood test.
04
Cholestasis imaging
Why
Use ultrasound first for jaundice or cholestatic liver tests, followed by CT, MRCP or ERCP according to the suspected level and intervention plan.
Interpretation and limitations
An obstructed extrahepatic system may be relieved by drainage or stenting; intrahepatic cholestasis follows a medical pathway.
05
Kidney and dialysis review
Why
Assess estimated filtration, calcium-phosphate balance, dialysis adequacy, access and drug clearance with the renal team.
Interpretation and limitations
Optimising kidney care precedes or accompanies a very low renal-adjusted gabapentinoid trial; usual neuropathic doses may be unsafe.
06
Sweating episode assessment
Why
Measure temperature and glucose during symptoms and review infection focus, thyroid, menopause, pain, anxiety, withdrawal, medicines and bedding environment.
Interpretation and limitations
Objective fever or hypoglycaemia changes management; isolated medication-associated sweating may justify a goal-based adjustment rather than broad testing.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Urticaria and anaphylaxis

Transient raised wheals, angioedema, airway symptoms, wheeze or circulatory compromise indicate histamine-driven disease, with anaphylaxis requiring immediate treatment.

Infestation or infection

Nocturnal household itch, burrows, fungal margins, fever or crusted and exudative lesions suggests scabies, fungal disease or secondary bacterial infection.

Cholestatic disease

Generalised itch, often palms and soles, with dark urine, pale stool or jaundice requires liver tests and biliary assessment.

Uraemic or haematological disease

Advanced kidney impairment, aquagenic itch, nodes, splenomegaly, anaemia, fevers or weight loss redirects testing away from simple dry skin.

Drug reaction or withdrawal

A temporal relation to a new drug, dose change, opioid rotation, antidepressant or alcohol cessation can explain itch, sweating or both.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01Immediate safetySeparate allergy, infection and severe drug reactionFirst stepItch or sweating is acute with airway, breathing, circulatory, fever, mucosal or blistering features.

1Use ABCDE assessment, remove likely exposure, check observations and glucose and identify anaphylaxis, sepsis, cholangitis or severe cutaneous reaction.
2Give emergency treatment under the relevant pathway, stop suspect medicines when safe and obtain acute specialist help without delaying symptom relief.
3Document the reaction, suspected trigger, timing, treatment and future avoidance or allergy referral and reconcile the medicine record.

02General itchRestore the barrier and identify mechanismPruritus is persistent, sleep disturbing or damaging skin without emergency features.

1Decide whether rash preceded scratching, examine all skin and review systemic clues, renal and liver function, medicines, contacts and treatment goals.
2Use cool care, soap substitute, regular emollient, nail and fabric measures and treat a diagnosed eczema, urticaria, infection or infestation specifically.
3If no primary rash, select a cholestatic, uraemic, haematological, neuropathic or medicine pathway and review sleep, skin healing and adverse effects.

03Cholestatic itchRelieve obstruction or escalate sequentiallyEscalationCholestasis is supported clinically, biochemically or anatomically and itch remains burdensome.

1Assess for urgent cholangitis and potentially reversible extrahepatic obstruction, involving hepatobiliary or endoscopy teams when drainage fits goals.
2Begin cholestyramine under formulary guidance with explicit spacing from other medicines and proactive constipation and tolerability review.
3For persistent itch, seek hepatology or palliative advice for rifampicin or another sequential option, checking liver, renal, interaction and opioid status before each step.

04Uraemic itchOptimise kidney care before renal-dose treatmentAdvanced kidney disease or dialysis is present and no primary dermatosis explains the symptom.

1Review xerosis, phosphate, dialysis adequacy, medicines and sleep with renal and palliative teams and intensify fragrance-free emollient care.
2AlternativeWhen symptoms remain severe, consider a low post-dialysis or renal-adjusted gabapentinoid regimen or a kidney-service alternative under local protocol.
3Review within days for itch and sleep benefit, sedation, falls, myoclonus and breathing and stop or reduce promptly if toxicity appears.

05SweatingTreat the driver and protect comfortSweating is recurrent, drenching or distressing without an immediate emergency.

1Check temperature and glucose during an episode and review infection, malignancy, endocrine, menopause, pain, panic, opioids, antidepressants and withdrawal.
2Treat the driver when beneficial and use fan, breathable layers, spare bedding, safe hydration and meticulous fold and pressure-area skin care.
3If still severe, consider a time-limited specialist antimuscarinic trial only after cognition, bowel, bladder, glaucoma, mouth and heat-risk assessment, with a clear stop rule.

Key medicines and prescribing safety5 treatments · regimens, roles and cautions

Blocks H1 signalling in wheals and other histamine-driven itch; it is not a universal treatment for cholestatic or uraemic pruritus.

Non-sedating antihistamine for urticaria

For histamine-mediated urticaria, cetirizine 10 mg orally once daily is a common adult regimen; adjust for renal function and follow urticaria guidance if specialist up-dosing is considered.

Drowsiness can still occur and renal dose reduction may be needed; do not let antihistamine delay intramuscular adrenaline in anaphylaxis.

Binds bile acids in the gut and is the usual first-line drug for persistent cholestatic itch after obstruction has been considered.

Cholestyramine for cholestatic pruritus

Begin with 4 g orally once or twice daily and titrate under hepatology or palliative guidance; take other oral medicines at least 1 hour before or 4 to 6 hours after each dose.

Constipation, bloating, poor palatability, reduced absorption of medicines and fat-soluble vitamin deficiency limit treatment; avoid in complete biliary obstruction without specialist review.

Provides effective second-line relief for some patients whose cholestatic itch persists despite first-line treatment.

Specialist rifampicin trial after first-line failure

A specialist regimen commonly begins at 150 mg orally once daily and may increase to 300 mg daily or twice daily according to response, body size, interactions and local hepatology protocol.

Check baseline and early repeat liver and renal tests; hepatitis, haemolysis and renal injury occur and strong enzyme induction affects anticoagulants, steroids, anticonvulsants and many other medicines.

Can reduce severe uraemic itch and improve sleep when skin care and kidney optimisation are insufficient.

Gabapentin for uraemic pruritus

Use only a renal-service or palliative protocol; haemodialysis regimens may use a very low dose after dialysis rather than daily standard neuropathic dosing, with titration to benefit.

Renal accumulation causes dizziness, falls, somnolence, myoclonus and respiratory depression, especially with opioids; verify the exact regimen with renal pharmacy.

Reduces eccrine sweat-gland stimulation when cause treatment and environmental measures have failed and sweating remains severely distressing.

Oxybutynin for refractory sweating

An off-label specialist trial may begin at 2.5 mg orally once or twice daily and increase cautiously only if a meaningful benefit outweighs anticholinergic burden.

Dry mouth, blurred vision, constipation, urinary retention, tachycardia, delirium and impaired heat dissipation are important; avoid in uncontrolled narrow-angle glaucoma and high anticholinergic burden.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Skin breakdown

Repeated excoriation produces bleeding, lichenification, ulceration, cellulitis and pain, especially in oedematous, jaundiced or immunocompromised fragile skin.

Sleep and psychological injury

Night-time itch or drenching sweats cause persistent insomnia, irritability, impaired coping, hopelessness and substantial patient and caregiver exhaustion.

Fluid and thermal stress

Heavy sweating can worsen dehydration, postural symptoms and electrolyte disturbance, while antimuscarinics can prevent safe heat dissipation.

Medicine interactions

Cholestyramine reduces absorption, rifampicin induces metabolism and opioid antagonists can precipitate withdrawal or abolish essential analgesia.

Sedation and anticholinergic harm

Sedating antihistamines, gabapentinoids and antimuscarinics increase falls, delirium, urinary retention, constipation, dry mouth, heat intolerance and respiratory risk.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Use a patient-centred itch measure including sleep, skin injury and a chosen activity, not just visible rash severity.
Inspect excoriations, pressure areas and skin folds for bleeding, infection, maceration and response to emollient or barrier care.
During cholestyramine review stool frequency, bloating, adherence and timing of every important oral medicine.
During rifampicin follow the local baseline and early liver, renal and blood-count schedule and actively check induced medicine interactions.
During renal gabapentinoid treatment monitor alertness, gait, myoclonus, breathing and itch within days and after any kidney or dialysis change.
For sweating record measured fever, episode timing, bedding changes, hydration, skin integrity and the specific comfort benefit.
During oxybutynin monitor cognition, mouth, vision, bowel, bladder, pulse and heat intolerance and stop promptly when burden exceeds relief.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

A scratch rash can mislead

Excoriations are secondary evidence of itch; finding whether a primary lesion appeared first is the key diagnostic distinction.

Sedation is not itch control

A sedating antihistamine may aid sleep while leaving non-histaminergic itch unchanged and increasing delirium or falls.

Cholestyramine changes the whole chart

Its binding effect makes dose spacing for analgesics, anticoagulants, steroids and other essential oral medicines part of the prescription.

Opioid status changes cholestatic options

An opioid antagonist can remove analgesia and precipitate withdrawal, so it is never a casual next step in palliative care.

Dialysis timing matters

A small post-dialysis gabapentin dose may be safer than standard daily dosing because clearance changes dramatically across the treatment cycle.

Sweating treatment can impair cooling

Antimuscarinic suppression may relieve wetness but increases heat illness risk, especially during fever, hot weather or impaired cognition.

11Common pitfallsFrequent interpretation and management errors.

01
Calling excoriations a primary rash and missing systemic pruritus.
02
Using antihistamines for every itch and interpreting sedation as mechanism-specific benefit.
03
Missing anaphylaxis because itch is the most obvious initial symptom.
04
Treating feverish sweating symptomatically without checking infection and glucose.
05
Starting cholestyramine without separating essential oral medicines or preventing constipation.
06
Using rifampicin without baseline monitoring and a full interaction review.
07
Giving an opioid antagonist to a patient who depends on opioids for analgesia.
08
Using standard gabapentin doses in dialysis or severe renal impairment.
09
Adding oxybutynin despite delirium, retention, constipation and severe dry mouth.
10
Ignoring skin-fold maceration, pressure damage and fluid loss while focusing only on symptom scores.