What are the treatment options for pruritus?

Treatment of Pruritus

Begin with emollients for all patients and identify the underlying cause to guide specific therapy, using topical corticosteroids for inflammatory pruritus and gabapentinoids for neuropathic pruritus as first-line systemic agents. 1, 2

Initial Management for All Patients

• Apply emollients liberally to wash and moisturize the skin as the foundation of all pruritus treatment, regardless of etiology 1, 2
• Avoid soaps and physical triggers such as wool clothing 1
• Investigate for underlying causes including systemic diseases, medications, infections, or dermatological conditions 2, 3

Treatment Based on Etiology

Inflammatory Pruritus (60% of cases)

For mild-to-moderate localized pruritus:

• Use moderate-to-high potency topical corticosteroids (mometasone furoate 0.1% or betamethasone valerate 0.1% ointment) twice daily for 1-2 weeks 1, 4
• Alternatively, use hydrocortisone 2.5% or triamcinolone 0.1% 3
• Add topical menthol 0.5% preparations for additional counter-irritant effect 1

Caution: Limit topical corticosteroid use to 2-4 weeks maximum to avoid skin atrophy and tachyphylaxis 4

For widespread or refractory inflammatory pruritus:

• Refer to dermatology for systemic therapies such as dupilumab or methotrexate 3

Neuropathic Pruritus (25% of cases)

First-line topical agents:

• Menthol, pramoxine, or lidocaine preparations, used alone or combined with topical steroids 3

First-line systemic agents:

• Gabapentin 900-3600 mg daily in divided doses 1, 2
• Pregabalin 25-150 mg daily 1, 2

Second-line systemic agents:

• Antidepressants: sertraline, doxepin, paroxetine, fluvoxamine, or mirtazapine 2, 3
• Opioid receptor modulators: naltrexone or butorphanol 2, 3

Hepatic/Cholestatic Pruritus

Use a stepwise approach:

1. Rifampicin 150 mg twice daily (first-line), can increase to 600 mg twice daily with hepatotoxicity monitoring 5, 2
2. Cholestyramine 9 g daily orally (second-line) 5, 2
3. Sertraline 75-100 mg daily (third-line) 5, 2
4. Naltrexone or nalmefeno (fourth-line) 5

Critical caveat: Do NOT use gabapentin for hepatic pruritus—it is ineffective 5, 2

Uremic Pruritus

Optimize dialysis parameters first:

• Ensure adequate dialysis and normalize calcium-phosphate balance 5, 2
• Control parathyroid hormone levels and correct anemia 2

Specific treatments:

• Gabapentin 100-300 mg after dialysis (three times weekly) 5, 2
• Broadband UVB phototherapy (highly effective, Strength of recommendation A) 2
• Activated charcoal orally has shown significant symptom improvement 5

Drug-Induced Pruritus

For opioid-induced pruritus:

• Naltrexone is first-line when opioid cessation is not possible 5, 2
• Methylnaltrexone is an alternative 2
• Mirtazapine 30 mg daily or gabapentin 1200 mg daily can prevent morphine-induced pruritus in surgical settings 1

For postoperative pruritus:

• Diclofenac 100 mg rectally 1, 5

For cancer therapy-induced pruritus:

• Treat the underlying rash first, as this often decreases pruritic symptoms 1
• Non-sedating antihistamines (loratadine 10 mg daily) for daytime use 1
• First-generation antihistamines (diphenhydramine 25-50 mg or hydroxyzine 25-50 mg) for nighttime use due to sedative properties 1
• GABA agonists (pregabalin/gabapentin) as second-line 1
• Aprepitant (NK-1 receptor antagonist) has shown benefit for EGFR inhibitor-related pruritus 1

Hematologic Malignancy-Associated Pruritus

For lymphoma-associated pruritus:

• Cimetidine, gabapentin, carbamazepine, mirtazapine, or phototherapy 1
• High-dose oral corticosteroids for incurable lymphoma (palliative setting) 1

For polycythemia vera-associated pruritus:

• Ruxolitinib (JAK1/JAK2 inhibitor) produces rapid reductions in pruritus scores 1
• Aspirin 300 mg daily is effective for many patients 1
• Alternative options: interferon-alpha, SSRIs, PUVA/UVB phototherapy, cimetidine, or atenolol 1

Generalized Pruritus of Unknown Origin (GPUO)

Use a stepwise escalation approach:

Step 1 - Topical therapies:

• Emollients and self-care advice 1, 2
• Topical doxepin (limit to 8 days, 10% body surface area, maximum 12 g daily) 1, 2
• Topical clobetasone butyrate or menthol preparations 2

Step 2 - Non-sedating antihistamines:

• Fexofenadine 180 mg or loratadine 10 mg daily 2, 6
• Mildly sedative cetirizine 10 mg can be considered 2

Step 3 - Systemic medications:

• Antidepressants: paroxetine, fluvoxamine, or mirtazapine 2
• Opioid modulators: naltrexone or butorphanol 2
• Gabapentinoids: gabapentin or pregabalin 2
• Ondansetron or aprepitant 2

Critical caveat: Avoid long-term use of sedative antihistamines except in palliative care settings due to potential dementia risk 5, 2

Special Populations

Elderly Patients

• Start with emollients and topical steroids for at least 2 weeks to exclude asteatotic eczema 2
• Use moisturizers with high lipid content 2
• Exercise extreme caution with sedative antihistamines due to cognitive impairment risk 4

When to Reassess or Refer

• Reassess after 2 weeks if no improvement with initial therapy 1, 4
• Refer to dermatology if diagnosis is uncertain, symptoms persist despite appropriate treatment, or systemic therapy is needed 4, 2, 3
• Consider skin biopsy for refractory cases 4
• Keep an open mind to new symptoms suggesting secondary causes that may develop over time 1

Common Pitfalls to Avoid

• Do not use calamine lotion—there is no evidence supporting its use in pruritus 1
• Do not use topical capsaicin for GPUO—evidence does not support its use except in uremic pruritus 1
• Do not use ondansetron or 5-HT3 antagonists for opioid-induced pruritus prevention—they are ineffective 1
• Avoid topical antihistamines other than doxepin due to lack of efficacy and risk of allergic contact dermatitis 1
• Do not continue ineffective treatments beyond 2 weeks without reassessment 1, 4