What is the workup for a patient presenting with pruritus (itching)?

Workup for Generalized Pruritus

Begin with a focused history (including medication review, travel history, and family history) and complete skin examination, then proceed with first-tier laboratory testing including CBC with differential, comprehensive metabolic panel (renal and liver function), thyroid function tests, and fasting glucose or A1C. 1, 2, 3

Initial Clinical Assessment

History Taking

• Medication history: Review all current medications, as 20-30% of generalized pruritus cases have a significant underlying systemic cause 1
• Travel history: Screen for infectious causes including malaria, strongyloidiasis, and schistosomiasis in appropriate contexts 1
• Duration and pattern: Note if pruritus is <12 months duration, especially in patients >60 years (heightened malignancy concern) 2
• Triggers: Identify specific triggers including water exposure (aquagenic pruritus suggests polycythemia vera) 1
• Associated symptoms: Ask about weight loss, night sweats, fatigue, jaundice, or neurologic symptoms 1, 3

Physical Examination

• Complete skin examination: Visualize finger webs, anogenital region, nails, and scalp 3
• Distinguish primary vs. secondary lesions: Primary lesions indicate diseased skin; secondary lesions (excoriations, lichenification) result from scratching 3, 4
• Absence of primary skin lesions: This finding mandates systemic workup for underlying disease 1, 3

First-Tier Laboratory Testing

Order these tests for all patients with generalized pruritus without obvious dermatologic cause: 2, 3

• Complete blood count with differential: Look for anemia (iron deficiency), eosinophilia (T-helper-2 polarization, potential biomarker for immunomodulator response), elevated hemoglobin/hematocrit with microcytosis (polycythemia vera) 1, 2
• Comprehensive metabolic panel: Assess renal function (BUN, creatinine for uremic pruritus) and liver function (alkaline phosphatase, bilirubin, transaminases for hepatic/cholestatic pruritus) 2, 3
• Thyroid-stimulating hormone (TSH): Screen for thyroid dysfunction 2, 3
• Fasting glucose or hemoglobin A1C: Screen for diabetes 2, 3
• Iron studies: Check ferritin, iron, TIBC to identify iron deficiency or overload 1

Second-Tier Testing (Based on Clinical Suspicion)

If Polycythemia Vera Suspected

• JAK2 V617F mutation: Present in up to 97% of PV cases; order if elevated hemoglobin/hematocrit with low ESR 1
• Serum erythropoietin level: If JAK2 negative, investigate secondary causes 1
• Oxygen saturation, chest X-ray, abdominal ultrasound: Rule out secondary polycythemia 1

If Infection/Infestation Suspected

• HIV serology: Consider in all patients with generalized pruritus 1
• Hepatitis A, B, C serology: Screen for viral hepatitis 1
• Parasite screening: Based on travel history (malaria, strongyloidiasis, schistosomiasis) 1

If Malignancy Suspected (Age >60, Liver Disease History, Diffuse Itch <12 Months)

• Erythrocyte sedimentation rate (ESR): Nonspecific inflammatory marker 3
• Chest radiography: Screen for lymphoma or solid tumors 1, 3
• Consider CT imaging: If clinical suspicion remains high despite negative initial workup 1

If Cholestatic Pruritus Suspected

• Alkaline phosphatase and gamma-GT: Elevated in cholestasis 1
• Bile acids: May be elevated even with normal liver enzymes 1

If Neuropathic Pruritus Suspected

• Refer to neurology: For specialized evaluation and nerve conduction studies 1

Special Populations

Elderly Patients (>65 Years)

• Initial 2-week trial: Emollients plus topical steroids to exclude asteatotic eczema before extensive workup 1, 5
• Consider bullous pemphigoid: Pruritus alone can be presenting feature; may need skin biopsy and indirect immunofluorescence 1
• Avoid sedating antihistamines: Associated with dementia risk (Strength C recommendation against) 1, 5

Drug-Induced Pruritus

• Trial of medication cessation: If risk-benefit analysis acceptable, discontinue suspected medications 1
• Review biologics: Common with epidermal growth factor inhibitors in oncology patients 1

Follow-Up Strategy

• Regular follow-up: Essential when underlying cause not immediately evident, as systemic causes may not be apparent initially 1
• Refer to secondary care: If diagnostic doubt exists or primary care management fails to relieve symptoms 1
• Reassess if initial treatment fails: Particularly in elderly patients after 2-week emollient/steroid trial 1

Common Pitfalls to Avoid

• Don't overlook medication history: Drug-induced pruritus is common and reversible 1
• Don't use sedating antihistamines long-term: Especially in elderly (dementia risk) and uremic patients (cetirizine ineffective) 1
• Don't dismiss pruritus in elderly: May be first sign of bullous pemphigoid or malignancy 1, 2
• Don't order extensive testing without clinical suspicion: Use history and physical to guide second-tier testing 3, 4