What is the initial workup and treatment for a patient presenting with general pruritus?

Workup for General Pruritus

Initial Laboratory Investigations

All patients with generalized pruritus without an obvious dermatologic cause should receive a focused laboratory workup including complete blood count with ferritin, liver function tests, urea and electrolytes, and consideration of HIV/hepatitis serology based on risk factors. 1

Core Laboratory Tests

• Complete blood count and ferritin levels should be checked in all patients with chronic generalized pruritus without rash to screen for iron deficiency, polycythemia vera, and hematologic malignancies 1
• Liver function tests are essential to evaluate for hepatic causes, with consideration of bile acids and antimitochondrial antibodies if liver disease is suspected 1
• Urea and electrolytes must be obtained to assess for uremic pruritus from renal disease 1

Additional Investigations Based on Clinical Suspicion

• Blood film, lactate dehydrogenase, and erythrocyte sedimentation rate should be added if hematological involvement is suspected 1
• JAK2 V617F mutation analysis is indicated when polycythemia vera is suspected (elevated hemoglobin or hematocrit) 1
• HIV and hepatitis A, B, and C serology should be considered, particularly with relevant travel history or risk factors 1
• Thyroid function tests are NOT routinely recommended unless additional clinical features suggest endocrinopathy, diabetes, or renal disease 1

Important Caveats

• Routine endocrine investigations and extensive malignancy screening are not recommended in the absence of specific systemic symptoms 1
• Full investigation to rule out malignancy is not routinely recommended unless pruritus is accompanied by appropriate systemic symptoms suggesting specific cancers 1

Medication Review

A comprehensive medication review is mandatory, as drug-induced pruritus is a common and reversible cause. 1, 2

• Trial cessation of potentially causative medications should be undertaken when the risk-benefit analysis is acceptable to both clinician and patient 1, 3

When to Consider Additional Testing

• Skin biopsy should be considered in persistent, unexplained generalized pruritus to evaluate for cutaneous lymphoma or small fiber neuropathy in suspected neuropathic pruritus 1
• Chest X-ray and abdominal ultrasound may be warranted in the absence of JAK2 mutation when investigating secondary causes of polycythemia vera 1

Initial Treatment Approach

First-Line Management for Generalized Pruritus of Unknown Origin

Begin with self-care advice, emollients, and a short trial of non-sedating antihistamines rather than extensive investigations in primary care. 1, 2, 3

• Emollients should be prescribed to maintain skin hydration as initial therapy 1, 2, 3
• Non-sedating antihistamines (fexofenadine 180 mg or loratadine 10 mg) can be used as second-line therapy 2, 3
• Topical doxepin (limited to 8 days, 10% body surface area, 12g daily maximum) or topical clobetasone butyrate/menthol preparations can be considered as first-line topical therapies 2, 3

Special Considerations for Elderly Patients

In elderly patients, initiate a 2-week trial of emollients and topical steroids to exclude asteatotic eczema before pursuing extensive workup. 1, 2, 3

• Moisturizers with high lipid content are preferred in elderly patients 1, 3
• Sedating antihistamines should be avoided in elderly patients except in palliative care settings due to potential dementia risk 2, 3
• Gabapentin may benefit elderly patients with pruritus who have not responded to initial treatment 1

Referral Criteria

Refer to secondary care when there is diagnostic doubt, symptoms persist despite primary care management, or when specific underlying conditions require specialist input. 1

• Hematology referral is indicated for suspected polycythemia vera or lymphoma 1
• Hepatology referral should occur with any suggestion of significant hepatic impairment 1
• Dermatology referral is appropriate for refractory cases not responding to topical therapies (approximately 10% of patients) 4

Common Pitfalls to Avoid

• Do not order routine thyroid function tests without clinical features suggesting endocrinopathy 1
• Do not pursue extensive malignancy screening in the absence of specific systemic symptoms 1
• Do not use long-term sedative antihistamines except in palliative care due to dementia risk 2, 3
• Do not overlook medication review as a reversible cause 1, 2
• Regular follow-up is essential when the underlying cause is not immediately evident, as systemic causes may not be apparent initially 1