Widespread Itch Algorithm

Safety

Red Flags — Exclude Sinister Causes First

Done

Screen immediately for haematological malignancy, solid organ cancer, and advanced systemic disease before attributing itch to benign causes.

Drenching night sweats + weight loss Pruritus + B-symptoms → Same-day bloods + urgent haematology (lymphoma, leukaemia)

Palpable lymphadenopathy Cervical/axillary/inguinal nodes + itch → 2WW haematology referral (Hodgkin's lymphoma classically causes severe itch)

Jaundice Yellow sclera/skin + pruritus → Same-day LFTs + bilirubin (cholestatic liver disease, biliary obstruction, pancreatic cancer)

Polycythaemia features Facial plethora, aquagenic itch (worse after hot shower), headache, visual disturbance → FBC same-day (polycythaemia vera)

Uraemic features Known CKD + severe itch, nausea, confusion → eGFR, U&Es same-day (uraemic pruritus — dialysis threshold)

Cholestasis of pregnancy Pruritus in 2nd/3rd trimester, especially palms/soles at night → Same-day LFTs + bile acids (risk of stillbirth)

Unexplained weight loss >5% + itch → 2WW CT chest/abdomen/pelvis (occult malignancy)

Generalised itch + iron deficiency without anaemia or obvious source → 2WW upper GI endoscopy (GI malignancy)

Generalised pruritus without visible primary skin lesion (pruritus sine materia) is a paraneoplastic phenomenon in up to 30% of Hodgkin's lymphoma cases — the itch may precede lymphoma diagnosis by months. Aquagenic pruritus is pathognomonic for polycythaemia vera in 40–50% of cases. Intrahepatic cholestasis of pregnancy carries a 1–2% stillbirth risk if bile acids exceed 40 µmol/L — 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) → systemic cause more likely. 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 90% specific for polycythaemia vera when combined with erythrocytosis. Nocturnal itch affecting multiple household members is scabies until proven otherwise — prescribing without diagnosing leads to treatment failure and ongoing transmission. Drug-induced pruritus accounts for up to 5% of chronic itch referrals and is fully 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 systematic investigation. 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

Full skin examination is mandatory. 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).

Dermographism

Stroke skin firmly — immediate whealing = symptomatic dermographism (commonest cause of physical urticaria). Positive in 5% population

Lymph nodes

Cervical, axillary, inguinal, epitrochlear. Firm, non-tender, rubbery nodes → 2WW 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: ice pack test (cooling relieves neuropathic itch), dermatomal distribution, check cervical spine range of movement.

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 pruritus without primary skin lesion (>6 weeks), investigate systematically. Do not skip the screen even if a skin cause seems likely in an elderly patient.

First-line bloods
All patients

FBC (polycythaemia, eosinophilia, anaemia, lymphocytosis) · LFTs (cholestasis, hepatitis) · Renal function/eGFR · TFTs · Fasting glucose/HbA1c · Ferritin (iron deficiency without anaemia causes itch) · ESR/CRP · Calcium

Directed second-line

ANA/ANCA (autoimmune) · SPEP (myeloma) · HIV test · Coeliac serology (IgA tTG) · Hepatitis B and C serology · Bile acids (if pregnant or cholestasis suspected) · AMA/ANA (PBC if alkaline phosphatase elevated)

Pregnancy

LFTs + serum bile acids if 2nd/3rd trimester — bile acids >40 µmol/L = high risk → same-day obstetric referral

Imaging

CXR: mediastinal lymphadenopathy (lymphoma). Abdominal USS: hepatic/biliary pathology, splenomegaly. CT chest/abdomen/pelvis: if B-symptoms, weight loss, or lymphadenopathy.

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. In one study, 6% of patients with unexplained pruritus had undiagnosed lymphoma. Eosinophilia >1.5 × 10⁹/L warrants urgent haematology referral (hypereosinophilic syndrome). A structured investigation screen has a diagnostic yield of approximately 25% in chronic idiopathic pruritus.

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

Cholestasis of pregnancy with bile acids >40 µmol/L → obstetrics · Uraemic crisis (eGFR <15, symptoms of uraemia) → nephrology · B-symptoms + lymphadenopathy → haematology

2WW

Suspected lymphoma (lymphadenopathy + pruritus + B-symptoms) → haematology · Unexplained weight loss + pruritus → CT-guided 2WW · Polycythaemia vera (Hb >185 M/>165 F + aquagenic itch) → haematology · NICE NG12: pruritus with splenomegaly/lymphadenopathy → suspected haematological cancer referral

Urgent routine (2–4 weeks)

Abnormal LFTs with cholestatic pattern → hepatology/gastroenterology · 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 (for dialysis optimisation or naltrexone) · Psychological itch, delusional parasitosis → liaison psychiatry · CKD-associated itch with eGFR 15–45 → nephrology for difelikefalin consideration

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) was approved in 2022 for haemodialysis-associated pruritus with 70% response rate — 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 neck downwards, including under nails, leave 8–12 hours, wash off. Repeat after 7 days. Treat ALL household contacts simultaneously. Wash clothing/bedding at 60°C.

Dry skin / xerosis

Emollient therapy First-line

Emollient 500g/week as soap substitute + moisturiser (e.g., Doublebase, Epaderm) twice daily minimum. Add topical crotamiton 10% cream if symptomatic relief needed.

Urticaria

Non-sedating antihistamine First-line

Cetirizine 10 mg OD or loratadine 10 mg OD. If inadequate: up to 4× licensed dose (off-label). Add montelukast 10 mg OD if refractory. Avoid triggers.

Cholestatic pruritus

Colestyramine 4–8g/day First-line

4g sachet before breakfast. Separate other medications by 1–4 hours. Second-line: rifampicin 150–300mg BD (monitor LFTs). Third-line: naltrexone 12.5–50mg OD.

Iron deficiency

Ferrous sulfate 200mg BD Treat deficiency

Continue for 3 months after ferritin normalises. Pruritus typically resolves within 4–6 weeks of treatment.

Neuropathic itch

Gabapentin 300mg OD–TDS First-line neuropathic

Start 300mg nocte, titrate up. Alternative: pregabalin 75mg BD. 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 — Chlorphenamine 4mg nocte (short-term, avoid in elderly). Hydroxyzine 25mg nocte — better evidence for pruritus than other antihistamines.

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 options — Naltrexone 12.5–50mg OD (opioid antagonist — effective across multiple pruritus types) · Mirtazapine 7.5–15mg nocte (H1 + 5-HT2 antagonism — useful for malignancy-related itch) · Aprepitant (NK1 antagonist) · Dupilumab (if atopic eczema refractory)

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 7.5–15mg nocte is particularly effective in cancer-related pruritus with NNT approximately 3.5. Naltrexone works by blocking endogenous opioid-mediated itch signalling — effective in cholestatic, uraemic, and malignancy-related pruritus. In scabies, failing to treat all household members simultaneously guarantees treatment failure and re-infestation within 6 weeks.

Lifestyle

Non-Pharmacological Interventions — Essential Alongside Drug Treatment

Done

Lifestyle modifications reduce itch intensity significantly and are often as effective as antihistamines. Prescribe them explicitly.

Skin hydration Apply emollient within 3 minutes of bathing. Use soap substitute. Reduces transepidermal water loss by 40–50%, directly reducing itch stimulus.

Cool bathing Lukewarm water (not hot). Hot water causes mast cell degranulation and histamine release — dramatically worsens all itch types. Reduces itch by 30–40%.

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 Cool bedroom (<18°C). Avoid overheating. Sweating exacerbates most itch conditions. Ceiling fans reduce nocturnal itch.

Stress management Psychological stress activates itch pathways via CRH/NK1 receptor activation. CBT reduces itch intensity scores by 30–40%. Refer to psychological therapies if appropriate.

Alcohol avoidance Alcohol causes vasodilation and pruritus flares in urticaria, eczema, psoriasis, and rosacea. Abstinence during flares recommended.

Diet review Identify and avoid triggers (pseudoallergens, food additives in chronic urticaria). Elimination diet supervised by dietitian if food triggers suspected.

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 — this is why cooling relieves itch of all causes. Emollient therapy alone reduces itch intensity by a mean of 35% in xerotic pruritus in the elderly.

Safety

Follow-Up, Monitoring & Safety-Netting

Done

Chronic pruritus requires systematic review. Many systemic causes evolve — a normal initial screen does not preclude future malignancy or organ disease.

2 weeks

Scabies treatment review: confirm household contacts treated, check for treatment failure (new burrows after 2nd application → consider oral ivermectin 200 mcg/kg single dose — off-label in UK, specialist prescription).

4–6 weeks

Symptomatic response to treatment: if iron deficiency treated, check itch resolution. If drug cause identified and stopped, confirm resolution. Adjust antihistamine dose if needed.

3 months

Chronic pruritus review: repeat FBC, LFTs, eGFR if initial screen was borderline. Check for new systemic symptoms. If no improvement → reassess diagnosis, consider referral.

6 months

If no cause found despite full investigation: repeat screen at 6 months. Malignancy and haematological disease can present with isolated pruritus months before other features emerge.

Safety-net — same day

New lymphadenopathy · Jaundice · Significant weight loss · Fever + night sweats · Aquagenic itch + headache/visual disturbance (polycythaemia)

Safety-net — 999

Anaphylaxis (urticaria + angio-oedema + dysphagia/dyspnoea/hypotension) → IM adrenaline 0.5mg, 999

Pregnancy special

Review bile acids every 1–2 weeks if cholestasis of pregnancy diagnosed. Bile acids >100 µmol/L → consider early delivery with obstetrics.

In a longitudinal study of chronic pruritus, 10% of patients with initial negative investigations were diagnosed with a systemic condition within 5 years. The most common late diagnoses were haematological malignancy, autoimmune liver disease, and occult carcinoma. The 6-month repeat screen is therefore not optional. Oral ivermectin (unlicensed) has 95% efficacy for crusted/Norwegian scabies and permethrin-resistant scabies — a single specialist-directed course resolves what years of permethrin failed to treat.