What is the treatment for generalized itching?

Treatment of Generalized Itching

Start with emollients and self-care advice as first-line therapy for all patients with generalized pruritus, then escalate treatment based on the underlying cause using a systematic algorithmic approach. 1

Initial Management: First-Line Therapy

All patients should receive:

• Emollients with high lipid content to maintain skin hydration and restore the skin barrier 1, 2
• Self-care advice including avoidance of hot water, irritants, and triggers 1, 3
• For elderly patients specifically, initiate a 2-week trial of emollients plus topical steroids to exclude asteatotic eczema before proceeding further 1, 2

Topical Therapies for Generalized Pruritus of Unknown Origin (GPUO)

If emollients alone are insufficient:

• Topical doxepin (limit to 8 days, maximum 10% body surface area, 12g daily maximum) 1, 2
• Topical clobetasone butyrate or menthol preparations as alternatives 1, 2

Avoid these topical agents:

• Do not use crotamiton cream (Strength B recommendation against) 1
• Do not use topical capsaicin or calamine lotion 1

Systemic Therapies: Stepwise Escalation

Second-Line: Antihistamines

Non-sedating H1 antagonists are preferred:

• Fexofenadine 180 mg or loratadine 10 mg daily 1, 2, 4
• Mildly sedative cetirizine 10 mg may be considered 1, 3
• Consider combining H1 and H2 antagonists (e.g., fexofenadine plus cimetidine) for enhanced effect 1

Critical caveat: Sedative antihistamines (hydroxyzine) should only be used short-term or in palliative settings due to dementia risk, particularly in elderly patients 1, 2, 3

Third-Line: Neuromodulators and Psychotropics

When antihistamines fail, consider:

• SSRIs: Paroxetine or fluvoxamine 1, 2, 3
• Mirtazapine (dual serotonergic/noradrenergic action) 1, 2, 3
• Gabapentin or pregabalin (except in hepatic pruritus—see below) 1, 3
• Opioid modulators: Naltrexone or butorphanol 1, 2
• Antiemetics: Ondansetron or aprepitant 1

Cause-Specific Treatment Algorithms

Hepatic Pruritus (Cholestatic Itch)

Follow this strict hierarchy:

1. First-line: Rifampicin (Strength A recommendation) 1, 2
2. Second-line: Cholestyramine 1, 2
3. Third-line: Sertraline 1, 2
4. Fourth-line: Naltrexone or nalmefene 1, 2
5. Fifth-line: Dronabinol, phenobarbitone, or topical tacrolimus 1

Critical pitfall: Do NOT use gabapentin in hepatic pruritus 1, 2

Uremic Pruritus (Chronic Kidney Disease)

Optimize dialysis parameters first:

• Normalize calcium-phosphate balance and control parathyroid hormone 2, 3
• Correct anemia 3
• BB-UVB phototherapy (Strength A recommendation—the highest quality evidence for uremic itch) 1, 2, 3

Avoid in uremic pruritus:

• Do not use cetirizine 2
• Do not use long-term sedative antihistamines except palliatively 2

Drug-Induced Pruritus

Opioid-induced:

• First choice: Naltrexone if opioid cessation impossible (Strength B) 1, 2
• Alternatives: Methylnaltrexone, ondansetron, droperidol, mirtazapine, or gabapentin 1

Postoperative pruritus:

• Diclofenac 100 mg rectally 1, 3

Chloroquine-induced:

• Prednisolone 10 mg, niacin 50 mg, or combination therapy 1
• Alternative: Dapsone 1

Hematologic Disorders

Iron deficiency:

• Iron replacement therapy 2

Polycythemia vera:

• Cytoreductive therapy, aspirin, interferon-α, SSRIs, cimetidine, or atenolol 2

Lymphoma-Associated Pruritus

Hodgkin lymphoma:

• BB-UVB phototherapy 2
• Cimetidine, carbamazepine, gabapentin, or mirtazapine 2

Non-Hodgkin lymphoma:

• NB-UVB phototherapy 2

Incurable lymphoma:

• Oral corticosteroids 2

Solid Cancer-Associated Pruritus

• Paroxetine, mirtazapine, granisetron, or aprepitant 2

Neuropathic Pruritus

• Refer to neurology or appropriate specialist for definitive management 1
• Consider skin biopsy to confirm small fiber neuropathy 2

Psychogenic Pruritus (Functional Itch Disorder)

• Psychosocial and behavioral interventions: Education, relaxation techniques, cognitive restructuring, habit reversal training 1, 3
• NB-UVB phototherapy may provide benefit 1
• Referral to liaison psychiatry or psychology in selected cases 1
• Patient support groups 1, 3

Special Population: Elderly Patients

Mandatory initial approach:

• 2-week trial of emollients plus topical steroids to exclude asteatotic eczema 1, 2, 3
• High lipid content moisturizers preferred 1, 2
• Gabapentin may be beneficial if initial therapy fails 1
• Absolutely avoid sedative antihistamines (Strength C recommendation against) due to dementia risk 1, 2

When to Refer to Secondary Care

Refer if:

• Diagnostic uncertainty exists 1
• Primary care management fails to relieve symptoms 1
• Specialized phototherapy or advanced systemic therapies needed 2, 3

Alternative/Adjunctive Therapies

Consider for GPUO:

• Acupuncture combined with Chinese herbal remedies 1
• Acupuncture alone as second-line therapy 1
• Auricular acupressure or aromatherapy for uremic pruritus 1