Laboratory Evaluation for Pruritic Rash of Unknown Cause
Order a focused initial panel including complete blood count with differential, serum ferritin, liver function tests with bilirubin and bile acids, renal function (urea and electrolytes), and thyroid-stimulating hormone. 1, 2
Essential First-Line Laboratory Tests
The British Association of Dermatologists provides clear guidance on the initial workup for generalized pruritus without an obvious dermatologic cause:
Core Metabolic and Hematologic Studies
- Complete blood count with differential and peripheral smear to detect polycythemia vera (elevated hemoglobin/hematocrit), lymphoma (lymphocytosis), or other hematological disorders 1, 2, 3
- Serum ferritin is mandatory, as iron deficiency causes pruritus in approximately 25% of systemic pruritus cases and responds dramatically to iron replacement 1, 2, 3
- Liver function tests including total bilirubin and serum bile acids to identify cholestatic liver disease, a major cause of generalized pruritus 1, 2
- Urea and electrolytes (renal function panel) to detect uremia and chronic kidney disease 1, 2
Additional Initial Studies
- Thyroid-stimulating hormone (TSH) should be included if clinical features suggest thyroid disease, though routine endocrine testing is not recommended without specific clinical indicators 2
- Erythrocyte sedimentation rate (ESR) and lactate dehydrogenase (LDH) help evaluate for hematological malignancy 3
Second-Tier Testing Based on Clinical Context
When Specific Conditions Are Suspected
- Antimitochondrial antibodies if liver function tests are abnormal, to evaluate for primary biliary cholangitis 1, 2
- JAK2 V617F mutation analysis if polycythemia vera is suspected, particularly with aquagenic pruritus (water-induced itching) or elevated blood counts 2, 3
- HIV and hepatitis A, B, and C serology with appropriate travel or risk history 1, 2
- Chest radiography when Hodgkin lymphoma is suspected, as it causes pruritus in up to 30% of cases and is the malignancy most strongly associated with pruritus 4
Iron Studies Nuance
If ferritin is normal but clinical suspicion for iron deficiency remains high (especially with concurrent inflammation), order serum iron and total iron-binding capacity (TIBC), as ferritin is an acute-phase reactant and can be falsely normal. 1, 3
Critical Clinical Context That Guides Testing
Red Flag Features Requiring Expanded Workup
- Nocturnal predominance with weight loss, fever, or night sweats strongly suggests lymphoma and warrants hematology referral 3
- Aquagenic pruritus (water-induced itching) is pathognomonic for polycythemia vera and mandates JAK2 testing 2, 3
- Elevated hemoglobin/hematocrit with microcytosis suggests polycythemia vera with concurrent iron deficiency 3
Medication Review Is Essential
Conduct a thorough medication review before extensive testing, as drug-induced pruritus is common and reversible; consider a trial cessation of suspected medications if the risk-benefit analysis is acceptable. 1, 2
Common Pitfalls to Avoid
- Do not skip ferritin testing—iron deficiency is frequently overlooked but highly treatable, with complete resolution of pruritus shortly after iron replacement begins 2, 3
- Do not order skin biopsy initially unless persistent unexplained pruritus continues despite negative workup, at which point it evaluates for cutaneous lymphoma or small fiber neuropathy 2
- Do not perform extensive endocrine panels routinely—only order TSH if clinical features specifically suggest thyroid disease 2
- Avoid sedating antihistamines for long-term use as they may predispose to dementia; use non-sedating antihistamines like cetirizine, loratadine, or fexofenadine instead 1, 3
When to Refer
Refer to dermatology if pruritus persists beyond 2 weeks despite initial management or if diagnosis remains uncertain. 5 Refer to hematology if laboratory findings suggest polycythemia vera or lymphoma, or if adenopathies or masses require biopsy. 3 Refer to hepatology if significant hepatic impairment or persistent liver enzyme elevation is present. 2