How should I evaluate and manage pruritus in an adult with new‑onset itching?

Evaluation and Management of New-Onset Pruritus in Adults

For an adult with new-onset itching, begin with a thorough skin examination to determine if primary skin lesions are present—if absent, proceed with systematic laboratory screening including CBC with differential, ferritin, renal function (BUN/creatinine), liver function tests, and thyroid function, as generalized pruritus without rash suggests underlying systemic disease in approximately 2% of cases and requires targeted investigation based on clinical clues. 1

Initial Clinical Assessment

Key History Elements to Elicit

• Timing and triggers: Aquagenic pruritus (itching after water contact) strongly suggests polycythemia vera 1
• Systemic symptoms: Night sweats, fever, weight loss point toward lymphoma 1
• Medication review: Many drugs cause pruritus; trial cessation if risk-benefit allows 1
• Travel history: Consider parasitic infections (malaria, strongyloidiasis, schistosomiasis) and HIV 1

Physical Examination Focus

Examine the entire skin surface including finger webs, anogenital region, nails, and scalp 2. Distinguish between:

• Primary lesions = diseased skin requiring dermatologic diagnosis
• Secondary lesions = excoriations from scratching, indicating pruritus without underlying dermatosis 2

If no primary skin lesions are present, you are dealing with generalized pruritus without rash (GPWOR), which requires systemic investigation 1.

Systematic Laboratory Investigation

First-Line Testing (All Patients with GPWOR)

• Complete blood count with differential and blood film 1
• Ferritin level (both deficiency and overload cause pruritus) 1
• Renal function: BUN and creatinine 1
• Liver function tests: Consider bile acids and antimitochondrial antibodies 1
• Thyroid-stimulating hormone (only if clinical features suggest endocrinopathy) 1

Additional Testing Based on Clinical Suspicion

For hematologic causes (approximately 2% of generalized pruritus) 1:

• Lactate dehydrogenase and ESR
• If polycythemia suspected (elevated hemoglobin/hematocrit with microcytosis, raised WBC/platelets, low ESR): JAK2 V617F mutation (present in 97% of polycythemia vera cases) 1
• If lymphoma suspected: Excision or ultrasound-guided core biopsy of enlarged nodes 1

For iron deficiency (ferritin <15-25 μg/L or unexplained anemia/microcytosis):

• Tissue transglutaminase (TTG) antibodies (assuming no gluten exclusion for 6+ weeks) 1
• Note: IgA deficiency causes false-negative TTG; consider this if testing negative 1

For infectious causes:

• HIV and hepatitis A, B, C serology
• Malaria, strongyloidiasis, schistosomiasis screening if travel history warrants 1

When to Consider Skin Biopsy

In persistent unexplained pruritus with normal-appearing skin, consider trunk biopsy to exclude cutaneous lymphoma, as patients rarely present with pruritus before visible lesions develop 1

Common Pitfalls to Avoid

1. Do NOT perform routine endocrine screening (including thyroid tests) unless additional clinical features suggest endocrinopathy 1
2. Do NOT routinely investigate for malignancy unless systemic symptoms are present 1
3. Immunoglobulins and urinary paraproteins have low yield as myeloma rarely causes generalized pruritus 1

Management Algorithm by Etiology

Iron Deficiency

Iron replacement therapy 1

Iron Overload

Venesection or desferrioxamine infusion 1

Polycythemia Vera

• Aspirin 300 mg daily for pruritus relief 1
• Cytoreductive therapy, interferon-α, SSRIs, or phototherapy (NB-UVB, BB-UVB, PUVA) 1
• Ruxolitinib (JAK1/JAK2 inhibitor) produces rapid pruritus reduction in RCT evidence 1

Lymphoma-Associated Pruritus

• Cimetidine, carbamazepine, gabapentin, or mirtazapine 1
• High-dose oral corticosteroids for palliative relief in incurable disease 1
• Phototherapy (BB-UVB for Hodgkin's, NB-UVB for non-Hodgkin's) 1

Uraemic Pruritus

• Optimize dialysis adequacy, normalize calcium-phosphate balance, control PTH, correct anemia with erythropoietin 1
• BB-UVB phototherapy (Strength A recommendation) 1
• Consider capsaicin cream, topical calcipotriol, or oral gabapentin 1
• Avoid sedative antihistamines long-term (dementia risk except in palliative care) 1
• Cetirizine is NOT effective in uraemic pruritus 1

Hepatic Pruritus

Stepwise treatment approach 1:

1. First-line: Rifampicin (Strength A)
2. Second-line: Cholestyramine
3. Third-line: Sertraline
4. Fourth-line: Naltrexone or nalmefene
5. Fifth-line: Dronabinol, phenobarbitone, propofol, or topical tacrolimus

Do NOT use gabapentin in hepatic pruritus 1

Drug-Induced Pruritus

• Trial cessation if risk-benefit acceptable 1
• Opioid-induced: Naltrexone first-line (Strength B); alternatives include methylnaltrexone, ondansetron, droperidol, mirtazapine, gabapentin 1
• Chloroquine-induced: Prednisolone 10 mg, niacin 50 mg, or combination; consider dapsone 1

Pruritus of Unknown Origin (After Negative Workup)

• Emollients and self-care advice 1
• Topical doxepin (limit to 8 days, 10% body surface area, 12 g daily) 1
• Consider topical clobetasone butyrate or menthol 1
• Do NOT use crotamiton cream (Strength B), topical capsaicin, or calamine lotion 1
• Nonsedative antihistamines (fexofenadine 180 mg, loratadine 10 mg) or mildly sedative (cetirizine 10 mg) 1
• Consider H1 + H2 antagonist combination (e.g., fexofenadine + cimetidine) 1

When to Refer

• Refer to secondary care if diagnostic doubt exists or primary management fails 1
• Refer to hepatology if significant hepatic impairment suggested 1
• Refer to hematology if JAK2 mutation positive or polycythemia suspected 1
• Refer for specialist biopsy if enlarged lymph nodes or masses present 1