What is pruritus and when is it called chronic?
The European guideline uses the International Forum for the Study of Itch (IFSI) terminology: pruritus and itch are synonyms, defined since Hafenreffer (1660) as an unpleasant sensation that provokes the desire to scratch. Chronic pruritus (CP) is itch lasting 6 weeks or longer, whether continuous or intermittent. The 6-week cut-off is a practical rule that tells the clinician when to start a diagnostic work-up; in chronic itch, long-term changes in how the nervous system processes itch set in.
Itch may be the first sign of a disease. It can precede the diagnosis of an underlying illness by years (premonitory pruritus) or be the early sign of a neoplasm such as Hodgkin lymphoma (paraneoplastic itch). In some diseases scratching does not relieve itch (cholestatic pruritus); in others scratching worsens it (symptomatic dermographism).
How is chronic pruritus classified (IFSI groups)?
The IFSI classifies chronic pruritus by what the skin looks like at the time itch started. This is a bedside classification, and the first decision in the approach.
| Group | Skin findings | Examples |
|---|---|---|
| I — pruritus on primarily diseased (inflamed) skin | Primary lesions present since itch began: erythema, vesicles, papules, blisters, pustules, wheals | Atopic dermatitis, scabies, urticaria, lichen planus, dermatitis herpetiformis, bullous pemphigoid |
| II — pruritus on primarily non-diseased skin | Skin normal at onset (scratch marks may appear later) | Systemic disease, neurological or psychiatric disease, drugs |
| III — pruritus with chronic secondary scratch lesions | Extensive nodular, excoriated or lichenified scratch lesions persisting for months to years | Prurigo nodularis, lichen simplex; cause may be dermatologic, systemic, neurological, psychiatric or drug-related |
Primary lesions (macules, vesicles, blisters, pustules, wheals) are those the disease itself produces. Secondary lesions — excoriations, crusts, ulcers, lichenification, scars, pigment change — are the result of scratching. Many patients overlap groups; for example, a dialysis patient can have nummular eczema, CKD and chronic scratch lesions together.
How do dermatologic and systemic causes of itch compare?
The guideline groups causes into dermatological, systemic, neurological, psychiatric/psychosomatic, drug-induced and mixed. Systemic causes classically give itch without a primary rash, often generalised and constant.
| Feature | Dermatologic itch (group I) | Systemic itch (group II) |
|---|---|---|
| Skin at onset | Primary lesions present | Normal skin |
| Distribution | Follows the dermatosis (e.g. web spaces in scabies, extensors in dermatitis herpetiformis) | Usually generalised; may be localised (genital itch in diabetes) |
| Pattern | Intermittent or constant; may be worse at night (scabies) | Constant itch is typical of renal, cholestatic and lymphoma-related itch |
| Work-up | Skin biopsy, microbiology, scrapings, immunofluorescence | Blood and organ tests, imaging, drug history |
| Treatment | Treat the dermatosis | Treat the underlying disease plus symptomatic itch therapy |
| Cause | High-yield point (European S2k guideline) |
|---|---|
| Chronic kidney disease (CKD-aP) | Moderate to severe itch in up to 30% of dialysis patients; mechanism unknown (PTH, divalent ions, opioid receptors, xerosis and micro-inflammation suggested) |
| Cholestasis / hepatobiliary disease | Itch may precede the diagnosis of primary biliary cholangitis by years; jaundice is not required; raised serum autotaxin (lysophosphatidic acid pathway) is specific to cholestatic itch |
| Iron deficiency | Associated with chronic itch; mechanism unknown. Iron overload (haemochromatosis) can also cause itch |
| Thyroid disease and diabetes | Fewer than 10% of patients report itch; hypothyroid itch is probably from dry skin. Primary hyperparathyroidism often causes itch |
| Haematological malignancy | Itch in about 30% of Hodgkin lymphoma, 15–50% of non-Hodgkin lymphoma and 15–50% of polycythaemia vera; Hodgkin itch often starts on the legs and is worse at night |
| HIV and other infections | Itch can be the first presentation of HIV (prevalence up to 45% in one study); pruritic papular eruption is a major cause in African patients with HIV; up to 15% of chronic hepatitis C patients report itch |
| Connective tissue disease | Cutaneous lupus (76.8% had itch in one study) and dermatomyositis; Sjögren syndrome itch is linked to dry skin |
| Neurological | Small-fibre neuropathy usually begins on palms and soles; neuropathic itch comes with tingling, burning or numbness |
| Drugs | Drug itch without a rash is about 5% of adverse cutaneous reactions; ACE inhibitors, amiodarone, many antibiotics, antidepressants, beta-blockers, statins and hydroxyethyl starch are among those listed |
How do you approach a patient with chronic itch?
- History. Onset and duration (6-week rule), whether skin lesions were present when itch began, distribution, day/night and seasonal pattern, triggers, drugs, family or contacts with itch, systemic symptoms.
- Look at the whole skin. Include scalp, nails, mouth and anogenital region. Separate primary from secondary lesions and place the patient in an IFSI group. Look for subtle primary disease: xerosis, 'well-groomed' scabies and pre-bullous pemphigoid.
- Biopsy (with direct immunofluorescence if autoimmune blistering disease, lupus or vasculitis is possible) when lesions are present or an 'invisible' dermatosis is suspected.
- First-step laboratory screen for itch with no obvious dermatosis (see table).
- If normal and itch persists: repeat the history, widen laboratory and imaging tests by suspected organ, and review drugs, neurological and psychiatric causes.
| Test | Looks for |
|---|---|
| Blood count with differential, ESR | Haematological disease, polycythaemia, infection or inflammation |
| Creatinine, urea | Kidney disease |
| AST, ALT, alkaline phosphatase, gamma-GT, bilirubin | Hepatobiliary disease and cholestasis |
| LDH | Lymphoma and other malignancy |
| TSH | Thyroid disease |
| HbA1c, fasting glucose | Diabetes |
| Ferritin, CRP | Iron deficiency; inflammation |
Constant itching suggests an internal disease such as renal or cholestatic itch or lymphoma. Nocturnal generalised itch with chills, fatigue, weight loss, fever and night sweats (B symptoms) suggests Hodgkin lymphoma. Winter itch is typical of dry skin (xerosis) in the elderly and of atopic dermatitis or psoriasis. Itch during exercise suggests cholinergic pruritus or cholinergic urticaria.
Which dermatoses are classically itchy?
These are the dermatoses where itch is the dominant symptom and where the exam asks you to identify the pattern.
| Disease | Itch and distribution | Key diagnostic point | Treatment note |
|---|---|---|---|
| Scabies (Sarcoptes scabiei var. hominis) | Intense itch, worse at night; symmetrical lesions on hands, wrists, axillae, thighs, buttocks, waist, soles, areola and genitals; neck and above usually spared | Burrows; the rash is a delayed Th1-mediated hypersensitivity to mite antigens. Female burrows 0.5–5 mm/day and lays 2–3 eggs/day | See scabies and pediculosis |
| Dermatitis herpetiformis | Intense itch with symmetrical grouped vesicles of 3–5 mm, usually excoriated; scalp, shoulders, buttocks, elbows, knees | Granular IgA deposits in dermal papillae on direct immunofluorescence; more than 90% have gluten-sensitive enteropathy | Dapsone relieves itch within about 3 days; gluten-free diet; NHL risk raised six- to tenfold in the first 5 years |
| Lichen planus | Itch from none to intense; shiny, flat-topped, polygonal violaceous papules with Wickham striae | Koebner phenomenon; band-like lymphocytic infiltrate at the dermo-epidermal junction, wedge-shaped hypergranulosis, saw-tooth rete ridges | See papulosquamous disorders |
| Lichen simplex chronicus | Chronic itch–scratch cycle; thickened leathery well-demarcated plaques with accentuated skin markings in a criss-cross pattern | Can follow atopic dermatitis, psoriasis, scabies, xerosis or neural itch (brachioradial pruritus, radiculopathy) | Break the itch–scratch cycle; treat the trigger |
| Prurigo nodularis | Extensive nodular, excoriated scratch lesions (IFSI group III) | Cause may be dermatologic, systemic, neurological, psychiatric or drug-related; investigate for these | Treat cause; symptomatic therapy |
How are uraemic and cholestatic pruritus treated?
Conventional-dose antihistamines are widely used but have not proven effective for itch in internal diseases such as renal failure and cholestasis. Non-sedating H1 blockers work mainly where mast cells drive the itch (urticaria, mastocytosis). Treatment of systemic itch therefore leans on drugs that act on opioid, neural and bile-acid pathways.
| Condition | Options listed in the guideline |
|---|---|
| CKD-associated pruritus | Difelikefalin (kappa-opioid agonist), 0.5 µg/kg IV after dialysis — recommended; gabapentin (300 mg three times a week after dialysis) or pregabalin (50 mg alternate days); naltrexone 50 mg/day (mu-opioid antagonist); moisturisers for dry skin |
| Cholestatic pruritus | Cholestyramine 4–16 g/day; rifampicin 300–600 mg/day (lowers autotaxin activity); naltrexone 25–50 mg/day; odevixibat (ileal bile acid transporter inhibitor) in children |
| Neuropathic itch | Gabapentin or pregabalin recommended |
For all patients the first step is general measures: keep room temperature low, wear breathable cotton, use mild non-alkaline soaps, apply moisturiser daily after bathing and take short lukewarm baths. Gabapentinoids carry a caution in kidney disease: a large registry analysis linked them to altered mental status, falls and fractures.
What else is high yield about pruritus?
- Pregnancy: intrahepatic cholestasis of pregnancy is a cholestatic itch, and raised serum autotaxin has been shown in it, as in other cholestatic disorders; see intrahepatic cholestasis of pregnancy.
- Elderly: chronic itch is reported in about one in four geriatric patients (23.4% in one prospective study); winter itch from dry skin is common.
- Paraneoplastic itch: chronic itch without skin changes is a risk factor for undiagnosed haematological and bile-duct malignancy (population-based cohort, 8,744 patients).
- Post-herpetic itch: chronic itch occurs in about 4% of herpes zoster patients.
- Drugs: always review the drug list in group II itch; stopping the offending drug is the treatment.
Systemic itch is often the first presentation of the underlying illness. The practical lesson for the exam is to move from the skin to the blood tests quickly. Related diseases with itch include scabies, urticaria and anaemia, where iron deficiency can underlie itch.