Pruritus (generalised itch): a systematic workup guide for general practice

Itch in general practice — a frequently missed systemic signal

Itch (pruritus) is one of the most common dermatological complaints seen in general practice — and when it presents without a visible rash, it is one of the most likely to be underinvestigated. The “itch without rash” category, classified by the International Forum for the Study of Itch (IFSI) as Group II pruritus, can be the presenting feature of conditions ranging from iron deficiency and thyroid disease to lymphoma, CKD, and biliary obstruction.

The consultation challenge is that chronic itch is distressing and has a high psychological burden — it disrupts sleep, impairs concentration, and affects mood and relationships. Patients often arrive frustrated after multiple presentations where treatment has focused on symptom suppression rather than cause. eTG’s dermatology chapter and RACGP guidance in Australian Family Physician both emphasise a cause-first approach: identify the underlying mechanism, treat it where possible, and layer symptomatic relief on top.

This article covers the systematic approach to generalised pruritus in Australian general practice — from history and workup, through management by mechanism, to the important special circumstances of uraemic pruritus, cholestatic pruritus, and pregnancy-related itch.

A. Core clinical — the AU general-practice framework

IFSI classification

The IFSI classification provides a practical framework:

Group I — Pruritus on diseased or inflamed skin: Visible skin changes are present — eczema, urticaria, scabies, psoriasis, tinea, contact dermatitis, bullous pemphigoid, or cutaneous T-cell lymphoma. The workup is primarily dermatological.

Group II — Pruritus on non-inflamed skin: Normal skin appearance despite significant itch. Requires systematic investigation for systemic, metabolic, drug, neurological, or psychogenic causes. This is the group in which missing a diagnosis carries the greatest risk.

Group III — Chronic scratch lesions: Lichen simplex chronicus (localised lichenified plaque from habitual scratching) or prurigo nodularis (firm, excoriated nodules from chronic repeated scratching). These are the secondary consequences of prolonged itch from either Group I or Group II causes.

Causes by category

Dermatological (Group I): Atopic dermatitis, urticaria, scabies (look for burrows in web spaces, wrists, axillae, genitalia), head lice, dermatitis herpetiformis (associated with coeliac disease — biopsy shows IgA deposition), bullous pemphigoid (intense pruritus often preceding blisters in older adults), psoriasis, pityriasis rosea, tinea and candidiasis.

Systemic and metabolic (Group II — itch without rash):

• Chronic kidney disease — uraemic pruritus affects 40–80% of patients on haemodialysis and can also occur in pre-dialysis CKD
• Cholestatic liver disease — primary biliary cholangitis (PBC), biliary obstruction, primary sclerosing cholangitis, viral hepatitis, drug-induced cholestasis, cirrhosis of any cause
• Iron deficiency — even without anaemia; ferritin below 30 ng/mL is the relevant threshold
• Polycythaemia vera — aquagenic pruritus (water-triggered) is near-pathognomonic; check FBC and JAK2
• Thyroid disease — hyperthyroidism most commonly; hypothyroidism via dry skin and xerosis
• Lymphoma — Hodgkin lymphoma (alcohol-induced pruritus is a classic historical feature), non-Hodgkin lymphoma, cutaneous T-cell lymphoma
• Solid malignancy — paraneoplastic pruritus is less common but recognised, particularly with pancreatic, gastric, and CNS tumours
• HIV infection — direct or through opportunistic infections and associated medication
• Hepatitis C — pruritus can be a presenting feature before overt hepatic symptoms

Drug-induced: Always review the full medication list. Common offenders include opioids (direct mast cell degranulation and spinal mechanisms), ACE inhibitors, statins, allopurinol, antimalarials (hydroxychloroquine), beta-blockers, amiodarone, and hydroxyethyl starch. Drug withdrawal as a diagnostic test is appropriate when a medication is a plausible cause.

Neuropathic:

• Brachioradial pruritus — localised to the outer forearms; burning or stinging quality; often worse in summer and on sun exposure; associated with cervical spine pathology — obtain cervical spine MRI or CT
• Notalgia paraesthetica — interscapular, medial to the scapula; associated with thoracic spine pathology
• Post-herpetic itch (after herpes zoster) — dermatomal distribution, often persistent after the rash has resolved
• Multiple sclerosis — paroxysmal pruritus

Psychogenic and functional: Anxiety and depression are bidirectionally related to chronic itch — each exacerbates the other. Delusional infestation (Ekbom syndrome) — belief of infestation with parasites despite no evidence — requires organic exclusion and careful psychiatric assessment.

History

A structured history guides the investigation:

• Duration and character — onset, whether generalised or localised, burning (neuropathic) vs crawling (psychogenic or drug) vs raw vs aching
• Temporal pattern — nocturnal worsening (scabies, cholestatic liver disease), post-bath (polycythaemia vera), seasonal (brachioradial pruritus)
• Triggering factors — heat, water, exercise, alcohol, specific foods
• Skin findings — any rash (even minor) changes the Group II assessment
• Systemic symptoms — weight loss, fever, night sweats, lymphadenopathy (B-symptoms for lymphoma)
• Comorbidities — kidney disease, liver disease, thyroid disease, diabetes
• Full medication list — current and recent
• Pregnancy status — in women of reproductive age; trimester if pregnant
• Sexual history and IDU — HIV and hepatitis risk
• Travel — parasitic infections
• Psychological history and sleep impact — pruritus severity scales and sleep disruption indicate need for mental health assessment

Examination

• Full skin examination — primary lesions vs secondary scratch lesions; distribution; dermoscopy for scabies burrows or lice
• Lymph node survey — cervical, axillary, inguinal
• Abdominal examination — hepatomegaly (liver disease), splenomegaly (lymphoma, PV, portal hypertension), jaundice (cholestasis)
• Thyroid palpation and eye signs (exophthalmos of Graves’ disease)
• Neurological examination in localised pruritus — dermatomal sensory changes (brachioradial, notalgia)

B. Evidence on investigation and targeted treatment

Systemic treatment — by mechanism

eTG and the European guideline on chronic pruritus (Weisshaar JEADV 2019) both emphasise mechanism-directed therapy:

Foundational skin care for all: Liberal emollient application at least twice daily is foundational — particularly for xerotic and uraemic pruritus in older adults and CKD patients. Preferred preparations in Australian practice include Cetaphil, QV Cream, Dermeze, and Dexeryl (thicker preparations are more effective than lotions for severe dryness). Tepid (not hot) showers, soap substitutes rather than soap, cotton clothing, cool bedroom environment, and trimmed fingernails are cornerstones that patients often overlook.

Antihistamines: Non-sedating antihistamines (cetirizine, loratadine, fexofenadine) have strong evidence for urticaria and histaminergic pruritus but limited evidence for most other forms of chronic pruritus. Sedating antihistamines (hydroxyzine 10–25 mg nocte, doxepin 10–25 mg nocte, chlorpheniramine) are useful at night for sleep disruption from pruritus — their H1-blocking and mild anxiolytic effects are clinically helpful, though falls risk in older adults limits daytime use.

Gabapentin and pregabalin — uraemic and neuropathic pruritus: Gabapentin (300–1800 mg/day in divided doses; dose reduce in CKD — typically post-dialysis dosing in haemodialysis patients) and pregabalin (75–300 mg/day; renally dose-adjusted) have RCT evidence for both uraemic pruritus and neuropathic forms including brachioradial pruritus. They are PBS Authority-listed for neuropathic pain; prescribing for pruritus is off-label but well-supported by evidence and specialist practice. Both are SafeScript/RTPM-monitored substances.

Cholestatic pruritus — naltrexone, rifampicin, cholestyramine: Naltrexone 25–50 mg/day (opioid antagonist) has RCT evidence for cholestatic pruritus — the mechanism involves disruption of central opioid-mediated itch signalling that is amplified in cholestasis. PBS Authority listing is for opioid and alcohol use disorder; use for cholestatic pruritus is off-label. Cholestyramine (a bile acid sequestrant) is first-line for biliary obstruction-related pruritus but compliance is challenging given its taste and texture. Rifampicin is a second-line specialist option for refractory cholestatic pruritus — monitor liver function tests given hepatotoxicity risk and be alert to its potent CYP induction effects on other medications. Sertraline 75–100 mg/day has emerging evidence as an alternative in cholestatic pruritus.

Dupilumab and JAK inhibitors — atopic dermatitis: Dupilumab (Dupixent) is a biologic anti-IL-4Rα antibody with transformative evidence for pruritus reduction in moderate-to-severe atopic dermatitis — the Liberty AD trials demonstrated very large pruritus score reductions sustained over time. It is PBS Authority-listed for severe atopic dermatitis meeting specific criteria. Oral JAK inhibitors (abrocitinib, upadacitinib) and topical JAK inhibitor (ruxolitinib) are PBS-listed for severe atopic dermatitis where dupilumab has failed or is inappropriate.

Difelikefalin — uraemic pruritus on dialysis: Difelikefalin (Korsuva), a peripheral kappa-opioid receptor agonist, demonstrated significant reduction in dialysis-associated pruritus in the KOMFORT trial (Fishbane NEJM 2020). It received FDA approval in 2021 for haemodialysis-associated pruritus. As of mid-2026, difelikefalin is not TGA-approved in Australia — Australian patients currently access gabapentin or pregabalin as first-line systemic therapy for uraemic pruritus.

Phototherapy: Narrowband UVB phototherapy is effective for refractory uraemic pruritus and atopic dermatitis-associated pruritus. Refer to a dermatologist for this option. MBS item 30187/30189 applies.

C. Intrahepatic cholestasis of pregnancy — do not miss

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver condition causing generalised pruritus — characteristically worst on the palms and soles — without a primary rash. It typically presents in the third trimester and resolves after delivery, but carries significant fetal risks that make recognition urgent.

Diagnosis: Serum bile acids ≥10 μmol/L confirms the diagnosis. Liver function tests may be mildly elevated; bilirubin can be elevated in severe cases.

Risk stratification:

• Bile acids 10–39 μmol/L — mild ICP; still requires obstetric involvement
• Bile acids ≥40 μmol/L — severe ICP; significantly elevated risk of intrauterine fetal death, preterm birth, and meconium-stained liquor
• Bile acids ≥100 μmol/L — very high risk; delivery decision requires urgent obstetric review

Management:

• Ursodeoxycholic acid 500–1000 mg twice daily — reduces pruritus severity and lowers bile acid levels; standard care per RANZCOG obstetric guidelines
• Vitamin K supplementation if prothrombin time is prolonged
• Delivery timing: 36–37 weeks for mild-to-moderate ICP; earlier delivery for severe or escalating bile acids
• Refer to obstetrics immediately when ICP is diagnosed or strongly suspected
• ICP recurs in subsequent pregnancies in up to 70% of cases — counsel women about screening in future pregnancies

D. Australian operations

MBS items

MBS Online items relevant to pruritus management:

• Items 23/36/44 — standard GP consultation levels
• Items 132/133 — consultant physician (dermatologist, nephrologist, gastroenterologist, haematologist, neurologist) initial and subsequent
• Item 30068 — punch biopsy of skin for histopathology
• Item 73807 — MBS pathology bundle applicable to initial blood workup
• Item 73881 — serum bile acids (for ICP diagnosis)
• Items 30187/30189 — phototherapy (dermatology-referral basis)
• Item 56401 — CT abdomen (targeted investigation for malignancy workup)
• Items 965/967 — GPCCMP for chronic complex pruritus with identified systemic cause
• Item 715 — ATSI Health Assessment (chronic conditions including CKD-related pruritus)

PBS prescribing highlights

• Emollients (Cetaphil, QV, Dermeze) — General Schedule or retail pharmacy
• Topical corticosteroids — General Schedule
• Topical calcineurin inhibitors (tacrolimus, pimecrolimus) — General Schedule for atopic dermatitis
• Cetirizine, loratadine, fexofenadine — General Schedule (also OTC)
• Hydroxyzine, doxepin — General Schedule
• Gabapentin/pregabalin — Authority Required (neuropathic pain indication); SafeScript monitored
• Naltrexone — Authority Required (opioid/alcohol use disorder); off-label for cholestatic pruritus
• Dupilumab — Authority Required (severe atopic dermatitis meeting PBS criteria)
• Ursodeoxycholic acid — Authority Required for PBC; off-label and often self-funded for ICP
• Cholestyramine — General Schedule

Specialist referral pathways

• Dermatologist — refractory, uncertain diagnosis, suspected cutaneous T-cell lymphoma, phototherapy
• Gastroenterologist or hepatologist — cholestatic liver disease, ICP
• Nephrologist — uraemic pruritus in CKD
• Haematologist — polycythaemia vera, suspected lymphoma
• Neurologist — brachioradial pruritus, notalgia paraesthetica, MS-related pruritus
• Obstetrician — ICP in any severity
• Psychiatry or psychology — psychogenic pruritus, delusional infestation, severe depression or anxiety comorbidity

E. Special populations

Older adults: Xerosis (“winter itch”) from age-related reduction in skin lipids and sebaceous gland activity is the most common cause of pruritus in older adults and is under-recognised as treatable. Aggressive emollient use, soap substitute adoption, and tepid showering address the majority of cases. Bullous pemphigoid may present with intense pruritus weeks before blisters appear — consider biopsy in older adults with refractory pruritus and no other explanation.

People with CKD on dialysis: Uraemic pruritus is extremely prevalent and often undertreated. Optimise dialysis adequacy; ensure intact skin care regimen; use gabapentin post-dialysis (dosed after dialysis to avoid accumulation); consider referral to a nephrologist for management review and to assess whether difelikefalin access is available through a trial or compassionate access pathway.

People with HIV: Pruritus is common from both the direct effects of HIV and from medication side effects (particularly some antiretrovirals). Screen for CD4 count-related opportunistic skin conditions. In well-controlled HIV on effective ART, primary evaluation should still be directed at systemic causes as above.

Children: Atopic dermatitis is the dominant Group I cause in children. Scabies should always be considered in preschool-age children with itch, particularly if others in the household are affected. Group II workup in children follows similar principles but with age-appropriate reference ranges.

When to escalate

Escalate urgently when:

• Pruritus occurs in a pregnant woman in the third trimester — order bile acids immediately; if elevated ≥40 μmol/L, refer to obstetrics without delay
• Pruritus is accompanied by B-symptoms (fever, night sweats, weight loss) or lymphadenopathy — suspected lymphoma warrants prompt haematology referral and imaging
• Pruritus with new jaundice, pale stools, or dark urine — cholestatic obstruction; urgent gastroenterology or hepatology referral
• Pruritus with new neurological symptoms — brachioradial pruritus with arm weakness or cervicogenic headache needs neurological imaging
• Refractory pruritus despite initial treatment and cause-directed therapy — refer to dermatologist

What this article is and is not

This is general health information drawn from eTG, AMH, RACGP guidance, the European guideline on chronic pruritus (Weisshaar JEADV 2019), Kidney Health Australia resources, and Australasian College of Dermatologists guidance. It is not personal medical advice and does not create a doctor–patient relationship. Decisions about investigation pathways, medication choice, and specialist referral are made with a treating clinician based on individual clinical circumstances.

For consumer information: HealthDirect — Itchy skin, Better Health Channel — Itching, DermNet NZ — Pruritus.

---

Sources cited

1. Therapeutic Guidelines (eTG) — Dermatology: pruritus
2. Australian Medicines Handbook
3. RACGP AFP — Pruritus evaluation in general practice
4. Australasian College of Dermatologists — Chronic pruritus
5. Kidney Health Australia — CKD symptom management
6. NPS MedicineWise — Skin treatments
7. Weisshaar E et al — European guideline on chronic pruritus (JEADV 2019)
8. Fishbane S et al — Difelikefalin for haemodialysis pruritus (NEJM 2020)
9. RANZCOG — Intrahepatic cholestasis of pregnancy
10. DermNet NZ — Pruritus
11. HealthDirect — Itchy skin
12. Better Health Channel — Itching
13. MBS Online
14. PBS Online