What is the best initial bloodwork panel for evaluating generalized pruritus?

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Last updated: November 6, 2025View editorial policy

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Initial Bloodwork for Generalized Pruritus

The essential initial bloodwork panel for generalized pruritus should include: complete blood count (CBC) with ferritin, liver function tests (LFTs), and renal function tests (urea and electrolytes). 1, 2

Core Laboratory Panel (Order for All Patients)

The British Association of Dermatologists provides clear guidance on the foundational workup:

  • CBC and ferritin levels are mandatory in all patients with chronic generalized pruritus without rash, as iron deficiency is one of the most common treatable causes (accounting for 25% of systemic disease-related pruritus). 1, 2

  • Liver function tests must be included to screen for cholestatic liver disease and hepatic causes of pruritus. 1, 2

  • Urea and electrolytes (renal function) are essential to evaluate for uremic pruritus from chronic kidney disease. 1, 2

This three-part panel (CBC/ferritin, LFTs, renal function) forms the backbone of your initial investigation and should be ordered universally. 2, 3

Additional Tests Based on Clinical Suspicion

Do not order these routinely—only when specific clinical features are present:

Hematologic Concerns

  • Blood film, lactate dehydrogenase (LDH), and erythrocyte sedimentation rate (ESR) if you suspect lymphoma (night sweats, weight loss, lymphadenopathy) or polycythemia vera (aquagenic pruritus). 1, 2

  • JAK2 V617F mutation if polycythemia vera is suspected based on elevated hemoglobin/hematocrit, especially with microcytosis or aquagenic pruritus. 1, 2

Infectious Etiologies

  • HIV and hepatitis A, B, C serology should be considered with relevant risk factors or unexplained pruritus, particularly with travel history. 1, 2

What NOT to Order Routinely

Avoid these common pitfalls:

  • Do not order thyroid function tests unless the patient has specific clinical features suggesting thyroid disease, diabetes, or other endocrinopathy—routine endocrine screening is not recommended. 1, 2

  • Do not pursue extensive malignancy workups without specific systemic symptoms; thorough history and physical examination should guide targeted investigations rather than shotgun testing. 1, 2

  • Do not forget to check ferritin even if CBC is normal—this is explicitly recommended for all chronic cases. 1, 2

Special Considerations

When Ferritin Appears "Normal"

If iron deficiency is clinically suspected but ferritin is in the normal range, remember that ferritin is an acute-phase reactant and can be falsely elevated during inflammation. In this scenario, check serum iron and total iron binding capacity. 1, 2

Persistent Unexplained Pruritus

For patients with persistent, unexplained generalized pruritus despite negative initial workup, consider skin biopsy to exclude cutaneous lymphoma, as patients rarely present with pruritus and normal-appearing skin that proves to be lymphoma on biopsy. 1, 2

Medication Review

Always perform a thorough medication review, as drug-induced pruritus requires cessation trials rather than laboratory testing. 1

Clinical Algorithm Summary

  1. Order universally: CBC with ferritin + LFTs + renal function 1, 2
  2. Add selectively: Blood film/LDH/ESR (if hematologic concern), JAK2 mutation (if polycythemia suspected), infectious serologies (if risk factors present) 1, 2
  3. Avoid routinely: Thyroid tests, extensive cancer screening without clinical indicators 1, 2
  4. Consider biopsy: If pruritus persists despite negative workup 1, 2

This streamlined approach balances comprehensive evaluation with cost-effectiveness, focusing resources where evidence demonstrates the highest diagnostic yield. 2, 3

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Initial Laboratory Workup for Generalized Pruritus Without Urticaria

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Pruritus: Diagnosis and Management.

American family physician, 2022

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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