Causes of Generalized Itching Without Rash

Primary Causes to Investigate

The British Journal of Dermatology recommends that iron deficiency anemia, chronic kidney disease, cholestatic liver disease, or polycythemia vera should be considered as primary causes of generalized pruritus without rash 1
Iron deficiency is the most common systemic cause of pruritus, accounting for 25% of all patients with pruritus due to systemic disease 1
The British Journal of Dermatology suggests that iron replacement often leads to complete cessation of pruritus shortly after starting therapy, and iron overload can also cause generalized pruritus 2
Uremia and chronic kidney disease are well-established causes of generalized pruritus, and urea and electrolytes should be part of the initial investigation 1, 3
Cholestatic liver disease is a major cause of generalized pruritus, particularly primary biliary cholangitis, and liver function tests should be performed in all cases 1, 3
Polycythemia vera presents with characteristic aquagenic pruritus, and hematological causes account for approximately 2% of cases 2
The British Journal of Dermatology recommends that routine endocrine testing is not recommended unless clinical features suggest specific endocrinopathy 3

The British Journal of Dermatology recommends ordering full blood count and ferritin levels, liver function tests, urea and electrolytes, and other investigations in all patients with chronic generalized pruritus without rash 2, 3, 4
Ferritin is an acute-phase protein and may be falsely elevated despite iron deficiency; check serum iron and total iron binding capacity if iron deficiency is suspected 2

Ferritin levels may be falsely elevated due to its role as an acute-phase protein, and serum iron and total iron binding capacity should be checked if iron deficiency is suspected 2
The Praxis Medical Insights guideline suggests avoiding long-term sedative antihistamines except in palliative care due to potential dementia risk 4