Bloodwork for Generalized Itching Without Rash
All patients with chronic generalized itching should have a complete blood count (CBC) with differential, ferritin, liver function tests (LFTs), and renal function tests (urea and electrolytes) as baseline screening. 1
Essential First-Line Tests
The British Association of Dermatologists provides clear guidance on initial bloodwork for generalized pruritus:
- CBC with differential and blood film - screens for polycythemia vera, lymphoma, eosinophilia, and other hematological disorders 1
- Ferritin levels - both iron deficiency and iron overload can cause itching; this is mandatory testing 1
- Liver function tests - evaluates for cholestatic liver disease and hepatic causes 1
- Renal function (urea and electrolytes) - screens for uremic pruritus from kidney disease 1
Additional Tests Based on Clinical Context
When Hematological Disease is Suspected
If you observe aquagenic pruritus (itching triggered by water contact), night sweats, weight loss, or abnormal CBC findings:
- Lactate dehydrogenase (LDH) 1
- Erythrocyte sedimentation rate (ESR) 1
- JAK2 V617F mutation analysis - if polycythemia vera suspected (raised hemoglobin/hematocrit, microcytosis, elevated platelets or white cells) 1
Important caveat: Immunoglobulins and urinary paraproteins have low yield since myeloma rarely causes generalized pruritus 1
When Iron Deficiency is Found
- Tissue transglutaminase (TTG) antibodies - screens for celiac disease in unexplained iron deficiency 1
- Note: IgA deficiency can cause false-negative TTG results; patients must not have excluded gluten for at least 6 weeks before testing 1
When Liver Disease is Suspected
- Bile acids - may be elevated in cholestatic pruritus 1
- Antimitochondrial antibodies - screens for primary biliary cholangitis 1
Tests NOT Routinely Recommended
Do not order routine endocrine investigations (including thyroid function tests) unless the patient has additional clinical features suggesting diabetes, thyroid disease, or other endocrinopathy. 1 This is a common pitfall - thyroid testing should be reserved for patients with systemic symptoms or signs of thyroid dysfunction, not ordered reflexively for all itching.
Do not perform extensive malignancy screening in all patients. 1 A thorough history and physical examination should guide any cancer-directed investigations; full malignancy workup is not routinely recommended unless specific systemic symptoms are present.
Special Populations and Considerations
Older Adults (>60 years)
- Heightened concern for malignancy if diffuse itch duration is less than 12 months, especially with history of liver disease 2
- Consider more aggressive evaluation in this population 2
When to Consider Additional Testing
- HIV and hepatitis serology (A, B, C) - if risk factors present or travel history suggests exposure 1
- Vitamin D levels - supplementation may help some patients with generalized pruritus 1
- Fasting glucose or HbA1c - if diabetes suspected clinically 3
Critical Pitfalls to Avoid
Don't skip ferritin testing - both low and high ferritin can cause itching, and this is specifically recommended for all chronic cases 1
Don't order thyroid tests reflexively - only test when clinically indicated by additional symptoms 1
Interpret elevated hemoglobin carefully - microcytosis with elevated hemoglobin suggests polycythemia vera with secondary iron deficiency; this requires JAK2 mutation testing 1
Consider eosinophilia as a biomarker - increased blood eosinophils may indicate T helper cell type 2 polarization and predict response to immunomodulator therapies 2
Remember that most patients with mild itching responding to antihistamines need no investigations at all 1 - reserve extensive workup for nonresponders or those with severe disease