What is the initial treatment approach for generalized pruritus in a patient?

Treatment of Generalized Pruritus

Start all patients with generalized pruritus with self-care advice and emollients as the foundation of therapy, regardless of the underlying cause. 1, 2

Initial Management Algorithm

Step 1: Rule Out Underlying Causes First

Before treating symptomatically, investigate for systemic disease with these essential tests 1:

• Complete blood count (evaluate for hematologic malignancy) 1, 3
• Liver function tests and serum bile acids (cholestatic disease) 1, 3
• Renal function: creatinine and blood urea nitrogen (uremic pruritus) 1, 3
• Thyroid-stimulating hormone (thyroid disorders) 1, 3
• Ferritin (iron metabolism disorders) 1
• Fasting glucose (diabetes mellitus) 1, 3
• Chest X-ray if lymphoma suspected (Hodgkin disease causes pruritus in 30% of cases) 1, 3

Step 2: First-Line Topical Therapy

All patients should receive emollients immediately while awaiting diagnostic workup 1, 2:

• High lipid content moisturizers are preferred, especially in elderly patients 1, 2
• Add topical clobetasone butyrate or menthol preparations for additional relief 1, 2
• Topical doxepin can be used but strictly limit to 8 days, maximum 10% body surface area, and 12g daily maximum 1, 2

Important caveat: In elderly patients specifically, use emollients PLUS topical steroids for at least 2 weeks to exclude asteatotic eczema before proceeding further 1, 2

Avoid these topical agents as they are ineffective or harmful 1:

• Crotamiton cream (Strength of recommendation B against use) 1
• Topical capsaicin 1
• Calamine lotion 1

Step 3: Second-Line Oral Antihistamines

If topical therapy fails after 2 weeks, add non-sedating antihistamines 1, 2:

• Fexofenadine 180 mg daily OR loratadine 10 mg daily are preferred first choices 1, 2
• Cetirizine 10 mg daily is acceptable as a mildly sedative alternative 1, 2
• Consider combining H1 and H2 antagonists (e.g., fexofenadine + cimetidine) for enhanced effect 1

Critical warning: Sedative antihistamines like hydroxyzine should ONLY be used short-term or in palliative settings due to dementia risk, and should be completely avoided in elderly patients (Strength of recommendation C) 1, 2, 4

Step 4: Third-Line Systemic Medications

When antihistamines fail, escalate to these agents 1, 2:

Neuromodulators (choose one):

• Gabapentin (effective in elderly and neuropathic pruritus, but avoid in hepatic pruritus) 1, 2, 5
• Pregabalin 1, 2

Antidepressants (choose one):

• Paroxetine 1, 2
• Fluvoxamine 1, 2
• Mirtazapine 1, 2

Opioid receptor modulators:

• Naltrexone 1, 2
• Butorphanol 1, 2

Other options:

• Ondansetron 1, 2
• Aprepitant 1, 2

Disease-Specific Modifications

If Hepatic Pruritus Identified:

1. Rifampicin is first-line 2
2. Cholestyramine second-line 2
3. Sertraline third-line 2
4. Never use gabapentin in hepatic pruritus 2

If Uremic Pruritus Identified:

1. Optimize dialysis, normalize calcium-phosphate balance, control parathyroid hormone, correct anemia 2
2. BB-UVB phototherapy is highly effective (Strength of recommendation A) 2
3. Continue emollients 2

If Drug-Induced Pruritus:

For opioid-induced pruritus: Naltrexone is first-choice if opioid cessation impossible (Strength of recommendation B); methylnaltrexone is alternative 1, 2

For postoperative pruritus: Diclofenac 100 mg rectally 1, 2

For chloroquine-induced pruritus: Prednisolone 10 mg, niacin 50 mg, or combination; dapsone is alternative 1

When to Refer to Secondary Care

Refer immediately if 1:

• Diagnostic uncertainty exists 1
• Primary care management fails to relieve symptoms 1
• Patient is significantly distressed 1
• Elderly patients not responding to initial 2-week trial 1

Adjunctive Non-Pharmacologic Options

Consider as second-line complementary therapy 1:

• Acupuncture (alone or with Chinese herbal remedies) 1
• Behavioral interventions, relaxation techniques, cognitive restructuring for suspected psychogenic component 1, 2
• Patient support groups 1, 2

Common Pitfalls to Avoid

1. Never use sedative antihistamines long-term outside palliative care—dementia risk outweighs benefits 1, 2
2. Don't exceed topical doxepin limits (8 days, 10% BSA, 12g daily) due to systemic absorption risk 1, 2
3. Don't forget to reassess elderly patients who fail initial therapy—may have occult bullous pemphigoid 1
4. Ensure continuous follow-up when cause is not immediately evident, as systemic disease may emerge later 1