Widespread Itch Algorithm

Safety

Red Flags — Exclude Sinister Causes First

Done

Scope: assessment of generalised pruritus, particularly pruritus without a primary rash, in adults in primary care. Look for red flags of haematological malignancy, cholestasis, pregnancy-related cholestasis and advanced systemic disease, without over-investigating uncomplicated acute itch or implying that itch alone predicts malignancy.

Drenching night sweats + weight loss Generalised pruritus with unexplained lymphadenopathy, splenomegaly, persistent fever, drenching night sweats or significant unexplained weight loss → targeted investigation (FBC + film, LDH, ESR, calcium, LFTs) and consider a suspected cancer pathway referral (NICE NG12). Same-day referral if acutely unwell, severe cytopenia, hyperviscosity symptoms, rapidly progressive lymphadenopathy or clinical instability; suspected sepsis → assess risk per NICE NG253 (any high-risk criterion → call 999, immediate emergency transfer)

Palpable lymphadenopathy Unexplained lymphadenopathy or splenomegaly with associated pruritus, fever, night sweats or weight loss, or unexplained lymphadenopathy where lymphoma is suspected → consider a haematology suspected cancer pathway referral (NICE NG12). Not for pruritus alone. (Hodgkin's lymphoma can cause severe itch)

Jaundice Yellow sclera/skin + pruritus → Same-day LFTs + bilirubin (cholestatic liver disease, biliary obstruction, pancreatic cancer). Jaundice with fever or RUQ pain, or systemically unwell → same-day medical assessment. Aged 40 and over with jaundice → pancreatic suspected cancer pathway referral (NICE NG12)

Polycythaemia features Facial plethora, aquagenic itch (worse after hot shower — not specific for PV), headache, visual disturbance → repeat FBC; persistent erythrocytosis, thrombocytosis, leukocytosis, splenomegaly or hyperviscosity symptoms → discuss/refer to haematology. Interpret haematocrit with hydration, smoking, hypoxia, sleep apnoea and testosterone use — a raised haematocrit alone does not diagnose PV (JAK2/erythropoietin via haematology)

Uraemic features Advanced CKD + severe itch with uraemic symptoms (nausea, confusion), biochemical deterioration or treatment failure → same-day renal/medical review; assess renal control, calcium/phosphate/PTH, medicines, xerosis and sleep. eGFR <15 is not a standalone dialysis threshold

Cholestasis of pregnancy Otherwise unexplained generalised or palmoplantar itch in pregnancy, especially at night, with normal-appearing skin → contact the maternity service the same day for LFTs, random total bile acids and fetal/obstetric assessment. Reduced fetal movements → immediate maternity assessment

Significant unexplained weight loss + itch → assess significant or progressive unexplained weight loss according to age, associated symptoms, examination and the relevant NICE NG12 (updated April 2026) criteria. Do not investigate all patients with itch and minor weight fluctuation for occult malignancy; CT is not a blanket primary-care test

Generalised itch + iron deficiency → investigate according to the iron-deficiency pathway, not because itch itself predicts GI cancer. If iron-deficiency anaemia is present, follow NICE/BSG iron-deficiency anaemia guidance — in men and postmenopausal women, bidirectional endoscopy is commonly the first-line GI investigation. Non-anaemic iron deficiency needs individualised assessment and does not automatically meet a suspected cancer referral threshold or require FIT/endoscopy

Generalised pruritus without a visible primary skin lesion can occur in Hodgkin's lymphoma and may precede diagnosis by months, but most generalised itch is not due to malignancy — NG12 referral depends on lymphadenopathy, splenomegaly or systemic features, not itch alone. Aquagenic pruritus is associated with polycythaemia vera but is not specific for it. Suspected ICP is managed by maternity: normal initial results do not exclude it if itching persists, and repeat testing is arranged through maternity care. In intrahepatic cholestasis of pregnancy the stillbirth risk rises mainly when peak bile acids reach 100 µmol/L or more (RCOG Green-top 43, 2022) — early detection is critical. Missing these diagnoses in a 10-minute appointment has serious medico-legal consequences.

Diagnose

Characterise the Itch — History Tool

Done

Use a structured history to distinguish dermatological from systemic causes before examining. The history drives the investigation strategy.

Onset & duration

Acute (<6 weeks) vs chronic (>6 weeks). Sudden onset suggests drug reaction or contact allergen. Gradual onset suggests systemic cause.

Distribution

Generalised = likely systemic. Localised = likely dermatological. Palms/soles nocturnal = cholestasis of pregnancy. Perianal/genital = threadworm, lichen sclerosus.

Timing

Nocturnal: scabies, uraemia, cholestasis. Post-hot shower (aquagenic): polycythaemia vera. Seasonal: dry skin (winter itch), atopic flares.

Associated skin changes

Primary rash present → dermatological cause. No rash (pruritus sine materia) → absence of a primary lesion increases the importance of systemic, medication-related, neuropathic and psychogenic causes, but does not exclude dermatological disease (it can be subtle or obscured by scratching). Excoriations only = not diagnostic.

Drug history

Full drug review including OTC, herbal. Common culprits: opioids, ACE inhibitors, diuretics, statins, calcium channel blockers, allopurinol.

Systemic symptoms

Weight loss, fatigue, night sweats, thirst, polyuria, jaundice, dyspnoea — any positive → investigate for systemic disease.

Contact history

New soap, detergent, cosmetics, jewellery (nickel), occupation exposure, pet contact.

Family/household

Others affected → scabies (highly contagious), contact dermatitis from shared products.

The pattern of itch is highly diagnostic: aquagenic itch is not specific for polycythaemia vera but should prompt an FBC. Nocturnal itch affecting multiple household members is scabies until proven otherwise — prescribing without diagnosing leads to treatment failure and ongoing transmission. Drug-induced pruritus is often reversible on withdrawal.

Diagnose

Classify Cause — Dermatological vs Systemic vs Neuropathic vs Psychogenic

Done

The International Forum on the Study of Itch (IFSI) classifies chronic pruritus into categories that guide investigation and treatment.

Category 1
Dermatological

Primary skin lesion present. Eczema, psoriasis, urticaria, lichen planus, scabies, tinea. Manage the underlying skin condition. Most common category in GP.

Category 2
Systemic

No primary skin lesion. Causes: hepatic (cholestasis, PBC, PSC), renal (CKD, uraemia), haematological (polycythaemia vera, lymphoma, iron deficiency), endocrine (thyroid disease, diabetes), drug-induced.

Category 3
Neurological

Neuropathic itch: brachioradial pruritus (UV-induced, cervical spine), postherpetic itch, small fibre neuropathy. Often burning/stinging quality. Responds to gabapentinoids not antihistamines.

Category 4
Psychogenic

Diagnosis of exclusion. Associated with anxiety, depression, OCD (compulsive scratching), delusional parasitosis. Often accompanies other psychological symptoms.

Category 5
Mixed

Multiple simultaneous causes (e.g., eczema + CKD + drug). Common in elderly. Address each component.

Chronic pruritus

Duration >6 weeks. Requires assessment with a basic screen and targeted tests guided by findings. Do not attribute to dry skin alone without excluding systemic cause.

Classification prevents therapeutic nihilism — antihistamines are only modestly effective in IgE-mediated conditions (urticaria, atopic eczema) and are largely ineffective for systemic, neuropathic, or cholestatic pruritus. Misclassification leads to years of inadequate treatment. Elderly patients often have mixed-category itch with xerosis, polypharmacy, and CKD contributing simultaneously.

Diagnose

Targeted Examination

Done

Inspect exposed skin initially and arrange/repeat a complete skin examination if the diagnosis remains unclear or symptoms persist. Examine lymph nodes and abdomen; other systemic examination directed by history findings.

Full skin exam

Entire body surface including scalp, genitalia, interdigital spaces, axillae. Look for: primary lesions (papules, vesicles, urticaria), burrows (scabies — especially web spaces, wrists, belt line), excoriations, secondary changes (lichenification, prurigo nodularis). Check finger webs, wrists, genitalia, buttocks and waistline (scabies); scalp, nails and mucosa (psoriasis, lichen planus); subtle eczema, xerosis, urticaria and prurigo; patches or plaques suggesting cutaneous T-cell lymphoma.

Dermographism

Stroke skin firmly — immediate whealing supports symptomatic dermographism (inducible urticaria) but does not establish the cause of generalised itch.

Lymph nodes

Cervical, axillary, inguinal, epitrochlear. Unexplained lymphadenopathy (e.g. firm, non-tender, rubbery or persistent nodes) → assess against NG12 lymphoma criteria → Suspected cancer: haematology Lymphoma/CLL

Abdomen

Hepatomegaly, splenomegaly (haematological malignancy, portal hypertension), ascites (chronic liver disease).

Jaundice assessment

Scleral icterus, skin colour, spider naevi, palmar erythema, leukonychia → liver disease.

Thyroid

Goitre, thyroid eye disease signs → thyroid dysfunction (both hypo- and hyperthyroidism can cause pruritus).

Nails

Leukonychia (hypoalbuminaemia), koilonychia (iron deficiency), nail changes in psoriasis, lichen planus.

Neurological screen

If brachioradial pruritus suspected (often dorsolateral forearms): dermatomal distribution, cervical spine range of movement; the ice-pack sign (cooling relieves itch) is a supportive manoeuvre only, not a validated routine test.

Scabies burrows in web spaces are pathognomonic but easily missed — misdiagnosis as eczema leads to years of inappropriate treatment and ongoing community transmission. Splenomegaly in the context of pruritus has a high positive predictive value for haematological malignancy or polycythaemia vera and mandates urgent investigation. Prurigo nodularis (hyperkeratotic nodules on extensor surfaces from chronic scratching) is a clinical diagnosis that signals long-standing undertreated itch requiring specialist input.

Diagnose

Investigations — Systematic Screen

Done

For persistent generalised itch without a clear primary skin disorder, use a basic screen and add targeted tests based on clinical findings (PCDS; BAD 2018) rather than blanket advanced investigation.

Initial screen
Persistent itch, no primary rash

FBC (haematocrit, eosinophilia, anaemia, lymphocytosis) · Ferritin and iron studies where indicated · Renal function/eGFR · LFTs including bilirubin and alkaline phosphatase · Bone profile/calcium · TFTs · CRP or ESR where systemic inflammation is suspected · Urinalysis where clinically indicated · HbA1c if diabetes suspected

Directed second-line

Blood film and LDH if haematological disease is suspected · AMA if alkaline phosphatase is persistently raised or cholestatic liver disease is suspected · Hepatitis B/C and HIV according to risk and clinical context · SPEP only if features suggest plasma-cell or systemic disease · JAK2 (with haematology) if PV suspected · Coeliac serology (IgA tTG) if clinically indicated · Bile acids (if pregnant or cholestasis suspected). Do not make LDH, SPEP, ANA/ANCA, HIV, hepatitis serology or CT routine for every patient with itch.

Pregnancy

LFTs + random total bile acids (fasting not generally required), arranged with maternity; normal initial results do not exclude ICP if itching persists — repeat via maternity care — bile acids ≥100 µmol/L = higher stillbirth risk (RCOG Green-top 43, 2022) → suspected cholestasis of pregnancy needs same-day maternity referral

Imaging

CXR: consider in persistent unexplained generalised pruritus without a primary rash, particularly with respiratory symptoms, lymphadenopathy, weight loss or concern about mediastinal disease — not automatically for every patient. Abdominal USS: hepatic/biliary pathology, splenomegaly. CT chest/abdomen/pelvis: not a blanket primary-care test — consider for severe persistent unexplained pruritus with normal initial investigations only after clinical review and discussion with dermatology/medicine.

Skin scraping

If scabies suspected: dermoscopy (visualise burrows/mites) or skin scraping sent for microscopy. Clinical diagnosis usually sufficient for treatment

When NOT to investigate

Do NOT order full screen for acute itch (<6 weeks) with clear dermatological cause (e.g., acute urticaria, contact dermatitis). Treat and review.

Iron deficiency without anaemia is an under-recognised cause of itch — ferritin <15 µg/L causes pruritus via effects on epidermal nerve fibre density. Eosinophilia >1.5 × 10⁹/L warrants urgent haematology referral (hypereosinophilic syndrome). A basic screen with selective additional tests is preferred to blanket advanced investigation (PCDS; BAD 2018).

Refer

Referral Criteria — When Specialist Input Is Needed

Done

Most dermatological causes can be managed in primary care. Systemic causes and treatment-refractory cases need specialist input.

Same-day

Reduced fetal movements → immediate maternity assessment (any suspected ICP: same-day maternity contact) · Severe pruritus in advanced CKD with uraemic symptoms, biochemical deterioration or treatment failure → same-day renal/medical review (eGFR <15 is not a standalone dialysis threshold) · Lymphadenopathy with acute illness, severe cytopenia, hyperviscosity symptoms, rapidly progressive nodes or clinical instability → same-day haematology/medical assessment · Suspected sepsis → assess risk per NICE NG253 (any high-risk criterion → call 999, immediate emergency transfer) · Severe drug eruption or systemic illness → same-day assessment; blistering or peeling skin with mouth, eye or genital involvement (possible Stevens–Johnson syndrome/TEN) → call 999 or A&E · New jaundice → same-day LFTs + bilirubin; jaundice with fever or RUQ pain, or systemically unwell → same-day medical assessment

Suspected cancer

Unexplained lymphadenopathy or splenomegaly with associated pruritus, fever, night sweats or weight loss → consider a haematology suspected cancer pathway referral (not pruritus alone) · Aged 40 and over with jaundice → pancreatic suspected cancer pathway referral (NICE NG12) · Significant or progressive unexplained weight loss → assess against NG12 criteria by age and associated features · Aquagenic pruritus with persistent erythrocytosis, thrombocytosis, leukocytosis, splenomegaly or hyperviscosity symptoms → repeat FBC and discuss/refer to haematology (do not use international diagnostic thresholds as automatic referral triggers without local haematology interpretation) · NICE NG12 (updated April 2026): pruritus with unexplained splenomegaly/lymphadenopathy → consider a suspected haematological cancer pathway referral

Specialist (non-urgent)

Abnormal LFTs with cholestatic pattern → hepatology/gastroenterology (coordinate itch treatment with hepatology if cholestasis is unexplained) · Suspected PBC (raised ALP + AMA positive) → hepatology · Prurigo nodularis (secondary to chronic itch) → dermatology

Routine dermatology

Itch failing 3 months of primary care treatment · Diagnostic uncertainty · Suspected cutaneous T-cell lymphoma (mycosis fungoides — present as pruritic patches/plaques) · Suspected brachioradial pruritus

Routine other

Refractory uraemic pruritus → nephrology (renal control, calcium/phosphate/PTH, medicines, xerosis and sleep review) · Psychological itch, delusional parasitosis → liaison psychiatry · CKD-associated itch → nephrology; difelikefalin is recommended only for moderate to severe pruritus in adults having in-centre haemodialysis (NICE TA890, 2023)

Mycosis fungoides (cutaneous T-cell lymphoma) can masquerade as eczema or psoriasis for years — the clue is itch out of proportion to skin findings and poor response to standard treatments. Early dermatology referral is critical. Difelikefalin (a kappa-opioid receptor agonist) is recommended by NICE TA890 (2023) for pruritus in people having haemodialysis — a significant advance requiring nephrology prescribing.

Treat

Treatment Pathway — Stepwise Approach by Cause

Done

Treat the underlying cause first. Symptomatic antipruritic therapy alongside, not instead of, cause-directed treatment.

Scabies

Permethrin 5% cream First-line

Apply to the whole body per age-specific product instructions — adults usually from the neck down, including under nails; infants, young children and some older/immunocompromised patients may need scalp and face treatment per specialist/local guidance. Leave 8–12 hours, wash off. Repeat after 7 days. Treat ALL household and close physical contacts simultaneously. Wash clothing/bedding hot where possible; seal unwashable items for an appropriate period. Itch can persist for several weeks after successful treatment.

Dry skin / xerosis

Emollient therapy First-line

Apply emollient liberally and frequently, usually at least twice daily and after washing, and use as a soap substitute (e.g., Doublebase, Epaderm); prescribe sufficient quantity for the body area and severity. Crotamiton is not a preferred routine treatment (may irritate eczematous skin).

Urticaria

Non-sedating antihistamine First-line

Second-generation non-sedating antihistamine first-line (e.g. cetirizine or loratadine at standard dose). If inadequate, after confirming the diagnosis, increasing up to four times the standard dose is an off-label guideline strategy — document it and consider age, comorbidity and local protocol. Refractory urticaria → dermatology/allergy referral for specialist treatments (e.g. omalizumab). Avoid identified triggers.

Cholestatic pruritus

Colestyramine Specialist-directed

Coordinate with hepatology, particularly if cholestasis is unexplained. Dose and separation from other medicines per current product information and local formulary. Rifampicin (specialist supervision, interaction review, LFT monitoring) and naltrexone (contraindicated with opioids — may precipitate withdrawal) are specialist options, not routine primary-care steps.

Iron deficiency

Oral iron per local pathway Treat deficiency

Treat according to the current local anaemia/iron-deficiency pathway — once daily or alternate-day dosing depending on tolerability. Investigate the cause of iron deficiency. Resolution of itch is not guaranteed and should not be the expected endpoint.

Neuropathic itch

Gabapentinoid (with caution) Consider

Gabapentin is not universally first-line: renal-dose adjust, start low and titrate; caution in older adults, falls risk, respiratory disease and with opioids; review for sedation, dependence and misuse. Gabapentin and pregabalin are not interchangeable without dose adjustment (check SPC/local formulary). Capsaicin 0.025–0.075% cream for localised neuropathic itch. Antihistamines ineffective.

Symptomatic relief (all causes):

Step 1Emollients + cooling — Cool compresses, menthol 0.5–2% in aqueous cream. Keep nails short. Cotton clothing. Avoid hot baths.

Step 2Sedating antihistamine at night — Use cautiously and short-term: avoid or minimise in older adults (anticholinergic effects, falls, cognitive impairment). Hydroxyzine has QT-prolongation cautions and interactions. Often ineffective for non-histaminergic systemic or neuropathic itch. Dose per BNF/local formulary.

Step 3Topical corticosteroid — Only if inflammatory skin component present. Hydrocortisone 1% for mild/face. Betamethasone 0.1% for lichenified areas. Do NOT use on normal skin.

Step 4Specialist-directed options (off-label where applicable) — not a routine primary-care step; require indication, monitoring and interaction review: naltrexone (opioid antagonist — contraindicated with opioids) · mirtazapine (e.g. malignancy-related itch) · aprepitant (NK1 antagonist) · dupilumab (refractory atopic eczema)

Next steps: see Scabies · Urticaria · Atopic eczema · Iron deficiency anaemia · Haematological cancers

Sedating antihistamines have poor evidence for non-histaminergic pruritus (the majority of systemic causes) — their benefit is sedation, not antipruritic action. Hydroxyzine has evidence as a true antipruritic (H1 + 5-HT antagonism). Mirtazapine is a specialist-directed, off-label option in some cancer-related pruritus. Naltrexone blocks endogenous opioid-mediated itch signalling and is used by specialists in cholestatic, uraemic and malignancy-related pruritus — it is contraindicated in patients taking opioids. In scabies, failing to treat all household members simultaneously commonly leads to treatment failure and re-infestation.

Lifestyle

Non-Pharmacological Interventions — Essential Alongside Drug Treatment

Done

Use lukewarm rather than hot water, soap substitutes, regular emollients, cool clothing, short nails and avoidance of overheating. Address sleep disturbance and psychological distress. Prescribe these measures explicitly.

Skin hydration Apply emollient soon after bathing. Use soap substitute. Helps restore the skin barrier.

Cool bathing Lukewarm water (not hot). Hot water causes mast cell degranulation and histamine release — can worsen itch.

Nail care Keep fingernails cut short and clean. Reduces skin damage from scratching and secondary bacterial infection risk.

Clothing choice Loose, cotton clothing against skin. Avoid wool, synthetic fabrics. Cotton mittens at night if nocturnal scratching. Reduces mechanical itch triggers.

Temperature control Keep the bedroom cool. Avoid overheating. Sweating exacerbates most itch conditions. Ceiling fans reduce nocturnal itch.

Stress management Psychological stress activates itch pathways via CRH/NK1 receptor activation. Address sleep disturbance and psychological distress; refer to psychological therapies (e.g. CBT) if appropriate.

Alcohol avoidance Advise alcohol reduction where it worsens the underlying condition (e.g. flushing in urticaria or rosacea, liver disease).

Diet review Do not recommend broad elimination diets for chronic urticaria without a clear history. If food triggers are suspected, use a supervised, time-limited approach (dietitian) rather than prolonged restriction.

The scratch-itch cycle is self-perpetuating: scratching causes keratinocyte damage, releasing cytokines (IL-31, IL-33, TSLP) that amplify itch signalling. Physical barriers (mittens, nail cutting) break this cycle. Cool water activates TRPM8 (cold receptor) channels in sensory neurons, directly inhibiting TRPV1-mediated itch signals — which is why cooling often relieves itch. Regular emollient therapy is the mainstay for xerotic pruritus in older adults.

Safety

Follow-Up, Monitoring & Safety-Netting

Done

Review response and any new systemic symptoms within 4–8 weeks, sooner if severe. Repeat investigations only if symptoms persist, the examination changes, initial results were borderline/abnormal or new clinical features emerge. Refer if persistent severe itch remains unexplained despite appropriate assessment and treatment.

2 weeks

Scabies treatment review: itch can persist for several weeks after successful treatment. New burrows or new lesions suggest treatment failure or reinfestation — check all contacts were treated simultaneously and application technique, and seek specialist/local advice (oral ivermectin requires specialist/local prescribing advice and is not suitable in pregnancy or certain weight/age groups).

4–8 weeks

Symptomatic response to treatment: if iron deficiency treated, review response (itch resolution is not guaranteed). If drug cause identified and stopped, confirm resolution. Adjust antihistamine dose if needed.

Persistent symptoms

Repeat tests only if symptoms persist, the examination changes, initial results were borderline/abnormal or new features emerge. Check for new systemic symptoms. If no improvement → reassess diagnosis; refer to dermatology, haematology or general medicine if persistent, severe, progressive, associated with systemic findings or refractory to appropriate treatment.

Safety-net — same day

New lymphadenopathy · Jaundice · Significant weight loss · Fever + night sweats · Aquagenic itch + headache/visual disturbance (polycythaemia) · Itch in pregnancy, especially palms/soles or worse at night (contact maternity the same day) · Advanced CKD with nausea or confusion

Safety-net — 999

Anaphylaxis (urticaria + angio-oedema + dysphagia/dyspnoea/hypotension) → call 999; IM adrenaline 500 micrograms for adults using 1 mg/mL (1:1000), repeated after 5 minutes if no improvement; lie flat with legs elevated unless breathing is difficult (then position of comfort); do not allow the patient to stand or walk · Blistering or peeling rash with sore mouth, eyes or genitals, or feeling very unwell (possible Stevens–Johnson syndrome) → call 999 or go to A&E

Pregnancy special

Monitoring and timing of birth are maternity-led — no fixed GP bile-acid schedule. Bile acids ≥100 µmol/L are associated with increased fetal risk, but delivery timing depends on gestation, bile acids, comorbidities and obstetric assessment. Reduced fetal movements → immediate maternity assessment.

Some systemic causes declare themselves later, so re-assess when symptoms persist or new features emerge — but there is no general evidence for an automatic repeat full screen. Oral ivermectin (unlicensed) is a specialist/local-guidance option for crusted scabies or treatment failure.