Workup for Generalized Pruritus
All patients with generalized pruritus should undergo a core laboratory workup including complete blood count with differential, ferritin, liver function tests, renal function (urea and electrolytes), and a thorough history and physical examination to identify underlying systemic causes. 1
Initial Clinical Assessment
Begin by determining whether primary skin lesions are present. If primary dermatologic disease is evident, the workup focuses on dermatologic causes. For generalized pruritus without an underlying dermatosis (GPWOR), a systematic approach to identify systemic causes is essential.
Core Laboratory Investigations
The British Association of Dermatologists 2018 guidelines provide clear direction on baseline testing 1:
Mandatory first-line tests:
- Complete blood count with differential - screens for hematologic disorders including polycythemia vera, lymphoma, and iron deficiency (Strength C-D)
- Ferritin levels - iron deficiency is a common treatable cause (Strength C) 1
- Liver function tests - identifies hepatobiliary disease (Strength D) 1
- Urea and electrolytes - screens for renal disease/uremia (Strength D) 1
Additional blood work based on clinical suspicion:
- Blood film, lactate dehydrogenase, and erythrocyte sedimentation rate if hematologic involvement suspected 1
- Bile acids and antimitochondrial antibodies if liver disease suspected 1
Condition-Specific Investigations
Hematologic Disorders
If elevated hemoglobin or hematocrit is found, send JAK2 V617F mutation analysis and refer to hematology to evaluate for polycythemia vera 1. This is critical as polycythemia vera commonly presents with pruritus, particularly aquagenic pruritus (itching after water exposure).
For persistent unexplained pruritus, consider skin biopsy to evaluate for cutaneous lymphoma 1. This is particularly important in older patients, as pruritus can be the presenting symptom of Hodgkin's or non-Hodgkin's lymphoma.
Malignancy Screening
Important caveat: Full investigation to rule out malignancy is NOT routinely recommended (Strength C) 1. However, tailor investigations when systemic symptoms suggest specific cancers. There should be heightened concern for malignancy in patients over 60 years with diffuse itch of less than 12 months duration, especially with liver disease history 2.
Endocrine Testing
Do NOT perform routine thyroid function tests or other endocrine investigations unless additional clinical features suggest diabetes, thyroid disease, or other endocrinopathy (Strength D) 1. This is a common pitfall - avoid shotgun endocrine testing without clinical indication.
Infectious Causes
When clinically indicated by history (particularly travel history) and examination, consider:
- HIV serology
- Hepatitis A, B, and C serology
- Screening for malaria, strongyloidiasis, and schistosomiasis 1
Neuropathic Pruritus
Detailed nervous system investigation is only advised if clinically indicated by history and examination 1. Consider skin biopsy if small fiber neuropathy is suspected, then refer to appropriate specialist.
Clinical Decision Algorithm
- History and examination - Look for primary skin lesions, medication history, travel history, systemic symptoms
- Core labs - CBC with differential, ferritin, LFTs, renal function
- If abnormal CBC → Blood film, LDH, ESR; if elevated Hgb/Hct → JAK2 mutation + hematology referral
- If abnormal LFTs → Consider bile acids, antimitochondrial antibodies; refer to hepatology if significant impairment
- If persistent and unexplained → Consider skin biopsy for cutaneous lymphoma
- Avoid routine thyroid testing, extensive malignancy screening, or neurologic workup without specific clinical indicators
Key Pitfalls to Avoid
- Don't order thyroid function tests reflexively - only when clinical features suggest endocrinopathy
- Don't pursue extensive cancer screening - use targeted investigations based on symptoms
- Don't forget iron studies - iron deficiency is a treatable cause often missed
- Don't overlook medication review - drug-induced pruritus is common and reversible
The strength of these recommendations is generally D (expert opinion), reflecting the limited high-quality evidence in this area. However, the systematic approach prevents both over-investigation and missed diagnoses of serious underlying conditions.