What is the best course of treatment for a patient with pruritus (itching) without visible skin lesions?

Treatment of Pruritus Without Visible Skin Lesions

Begin immediately with emollients and self-care advice as first-line therapy, then escalate systematically based on response using a stepwise algorithmic approach. 1, 2

Initial Management (Start Here for All Patients)

First-Line Therapy

• Apply high lipid-content emollients liberally to maintain skin hydration and restore the skin barrier 1, 2
• Provide self-care advice: avoid hot water, irritants, and known triggers 2
• Consider a trial of medication cessation if drug-induced pruritus is suspected and the risk-benefit ratio is acceptable 1

Topical Options (First-Line)

• Topical doxepin can be used but strictly limit to 8 days maximum, covering no more than 10% body surface area, with a maximum of 12g daily 1, 2
• Topical clobetasone butyrate or menthol preparations are alternative first-line topical options 1, 2
• Avoid crotamiton cream, topical capsaicin, and calamine lotion (these are not recommended) 2

Second-Line Therapy (If First-Line Fails After 2 Weeks)

Oral Antihistamines

• Use non-sedating H1 antagonists as preferred second-line therapy: fexofenadine 180 mg or loratadine 10 mg daily 1, 2
• Mildly sedative agents such as cetirizine 10 mg can be considered 1
• Consider combining H1 and H2 antagonists (e.g., fexofenadine plus cimetidine) for enhanced effect 2

Critical Caveat

• Avoid long-term use of sedative antihistamines (like hydroxyzine) except in palliative care settings due to dementia risk, particularly in elderly patients 1, 2

Third-Line Therapy (If Second-Line Fails)

Systemic Medications

• Systemic antidepressants: paroxetine, fluvoxamine, or mirtazapine 1
• Opioid antagonists: naltrexone or butorphanol 1
• Anticonvulsants: gabapentin or pregabalin (but avoid gabapentin in hepatic pruritus) 1

Investigate for Underlying Causes Concurrently

While treating symptomatically, conduct a thorough investigation for systemic diseases 1:

Key Systemic Causes to Rule Out

• Hepatic pruritus (cholestasis): If identified, use rifampicin as first-line treatment (Strength A recommendation), cholestyramine as second-line, and sertraline as third-line 1
• Uremic pruritus (chronic kidney disease): Optimize dialysis parameters, normalize calcium-phosphate balance, control parathyroid hormone, correct anemia, and use BB-UVB phototherapy (Strength A recommendation) 1
• Drug-induced pruritus: If opioid-induced and cessation is not possible, use naltrexone as first-line (Strength B recommendation) or methylnaltrexone as alternative 1
• Disorders of iron metabolism, endocrine/metabolic diseases, hematological disorders, and malignancies 3

Special Population: Elderly Patients

• Mandatory initial approach: 2-week trial of emollients plus topical steroids to exclude asteatotic eczema 1, 2
• Use moisturizers with high lipid content 1, 2
• Absolutely avoid sedative antihistamines due to dementia risk (Strength C recommendation against) 2
• Consider gabapentin if initial therapy fails 2

Additional Supportive Measures

• Behavioral interventions, relaxation techniques, and cognitive restructuring can be beneficial if psychological factors are suspected 1
• Patient support groups may help with chronic pruritus management 1

Common Pitfalls to Avoid

• Do not use nonsedating antihistamines as first-line therapy—they are second-line after emollients and topical therapies fail 1, 2
• Do not prescribe sedating antihistamines for long-term use outside palliative care, especially in elderly patients 1, 2
• Do not overlook the mandatory 2-week trial of emollients plus topical steroids in elderly patients before escalating therapy 2
• Do not use gabapentin if hepatic pruritus is identified or suspected 1