What is the appropriate work‑up for a patient presenting with pruritus?

Workup of Pruritus

Begin with a focused laboratory panel including complete blood count with ferritin, liver function tests, and urea and electrolytes, while simultaneously conducting a thorough medication review and complete skin examination to identify reversible causes before pursuing extensive investigations. 1

Initial Clinical Assessment

History Taking

• Obtain specific details about timing and triggers: Ask specifically about nocturnal predominance (suggests lymphoma or polycythemia vera), water-induced pruritus (highly suggestive of polycythemia vera), and relationship to bathing 2
• Screen for systemic symptoms: Weight loss, fever, and night sweats strongly suggest lymphoma and warrant immediate hematologic workup 2
• Complete medication review is mandatory: Drug-induced pruritus is extremely common and reversible—systematically review all medications, especially in polypharmacy patients 1, 3
• Travel and exposure history: Essential for identifying infectious causes including HIV, hepatitis, malaria, strongyloidiasis, and schistosomiasis 4, 3

Physical Examination

• Perform complete skin examination: This is essential and may reveal unsuspected dermatologic conditions or cutaneous malignancies that would otherwise be missed 5
• Distinguish pruritus with versus without rash: This fundamentally changes your diagnostic approach—pruritus without rash requires systemic workup, while rash suggests primary dermatologic disease 1, 3
• Examine for lymphadenopathy and organomegaly: Palpable adenopathies or masses require biopsy to exclude lymphoma 2

Essential Laboratory Investigations

First-Line Tests (Obtain in All Patients)

• Complete blood count with peripheral smear: Screens for polycythemia vera, lymphoma, and other hematologic malignancies which account for 2% of generalized pruritus cases 2
• Serum ferritin: Check in all patients, as 25% of patients with systemic pruritus respond to iron replacement; note that ferritin is an acute-phase protein and may be falsely normal with concurrent inflammation 2
• Liver function tests: Essential to evaluate hepatic causes; consider adding bile acids and antimitochondrial antibodies if liver disease is suspected 4, 1
• Urea and electrolytes: Must be obtained to assess for uremic pruritus from renal disease 4, 1

Conditional Second-Line Tests (Based on Clinical Context)

• JAK2 V617F mutation: Order if elevated hemoglobin/hematocrit, microcytosis, or elevated leukocyte/platelet count with low ESR suggests polycythemia vera (present in up to 97% of cases) 3, 2
• HIV and hepatitis A/B/C serology: Obtain based on risk factors and clinical context 4, 1
• Lactate dehydrogenase and ESR: Evaluate when hematological disease is suspected 2
• Serum iron and total iron-binding capacity: If ferritin is borderline normal but clinical suspicion for iron deficiency remains high due to concurrent inflammation 2

Tests to AVOID Routinely

• Do not order thyroid function tests unless additional clinical features suggest endocrinopathy, diabetes, or renal disease 4, 1
• Do not pursue extensive malignancy screening in the absence of specific systemic symptoms—full investigation to rule out malignancy is not routinely recommended 4, 1

Special Population Considerations

Elderly Patients

• Initiate a 2-week trial of emollients and topical steroids first to exclude asteatotic eczema before pursuing extensive workup 1
• Use moisturizers with high lipid content as preferred formulation 1
• Consider cutaneous lymphoma if rash persists despite adequate treatment for 2 weeks or in elderly patients with unexplained persistent pruritus 3

Initial Symptomatic Management (While Awaiting Results)

• Prescribe emollients to maintain skin hydration as initial therapy 1
• Trial non-sedating antihistamines (fexofenadine or loratadine) as second-line therapy 1, 2
• Consider topical doxepin or clobetasone butyrate/menthol as first-line topical therapies 1
• Avoid sedating antihistamines except in palliative care settings due to potential dementia risk 1, 2

Medication Trial Strategy

If drug-induced pruritus is suspected, undertake trial cessation of potentially causative medications when the risk-benefit analysis is acceptable to both clinician and patient 4, 1

Referral Indications

Hematology Referral

• Refer for suspected polycythemia vera or lymphoma based on laboratory findings, nocturnal pruritus with systemic symptoms, or palpable adenopathies requiring biopsy 1, 2

Hepatology Referral

• Refer with any suggestion of significant hepatic impairment identified on liver function tests 4, 1

Dermatology Referral

• Refer when diagnostic doubt exists, symptoms persist despite primary care management, or when specific underlying conditions require specialist input 1, 2

Critical Pitfalls to Avoid

• Do not overlook iron deficiency: Even with "normal" ferritin in the setting of inflammation, pursue serum iron studies if clinical suspicion remains 2
• Do not miss medication review: This is a common and completely reversible cause that is frequently overlooked 1, 3
• Do not forget complete skin examination: Failure to examine the entire skin surface may miss cutaneous malignancies or primary dermatologic conditions 5
• Regular follow-up is essential when the underlying cause is not immediately evident, as systemic causes may not be apparent initially and may declare themselves over time 1