Diagnostic Approach to Chronic Generalized Pruritus

Initial Evaluation and Most Likely Etiologies

The British Association of Dermatologists recommends specific initial investigations for all patients with chronic generalized pruritus without rash, including complete blood count with differential, ferritin levels and complete iron studies, liver function tests, urea and electrolytes/creatinine, and thyroid function tests if clinically indicated 1
Iron deficiency anemia causes generalized pruritus in many patients, with iron replacement therapy leading to complete cessation of pruritus shortly after treatment begins, particularly important in elderly females who may have occult gastrointestinal blood loss or poor dietary intake 1, 2
The British Association of Dermatologists recommends that investigations be guided by thorough history and physical examination, though full malignancy workup is not routinely recommended unless systemic symptoms are present 3, 4
Consider JAK2 V617F mutation analysis if polycythemia vera is suspected, particularly if aquagenic pruritus is present 1
If initial workup is unrevealing, consider additional investigations such as HIV and hepatitis serology, skin biopsy, and tissue transglutaminase antibodies 1, 2
Paraneoplastic pruritus may be relieved with paroxetine, mirtazapine, granisetron, or aprepitant 3, 4

The most critical pitfall is accepting "normal labs" at face value without verifying that comprehensive iron studies and all recommended screening tests were actually performed, as many patients with iron deficiency and pruritus have been missed because only ferritin was checked, which appeared falsely normal 2