What is the workup and treatment for a patient with generalized itching (pruritus)?

Workup and Treatment of Generalized Pruritus

The workup for generalized pruritus should begin with laboratory investigations to identify underlying causes, followed by targeted treatment based on the specific etiology identified. 1

Initial Diagnostic Workup

• Complete blood count with differential to evaluate for hematologic disorders, infections, or malignancies 2, 3
• Liver function tests to assess for hepatic causes of pruritus 4
• Urea and electrolytes to evaluate renal function 4, 3
• Consider bile acids and antimitochondrial antibodies if liver disease is suspected 4
• Thyroid function tests to rule out thyroid disorders 2, 3
• Fasting glucose or A1C to screen for diabetes 2, 3
• Iron studies to evaluate for iron deficiency or iron overload 3
• HIV and hepatitis A, B, and C serology if risk factors are present 4
• Travel history and appropriate testing for parasitic infections (malaria, strongyloidiasis, schistosomiasis) if indicated 4
• Medication review to identify potential drug-induced pruritus 4

Treatment Algorithm Based on Underlying Cause

1. Generalized Pruritus of Unknown Origin (GPUO)

• First-line therapies:

  • Emollients to maintain skin hydration 1
  • Topical doxepin (limited to 8 days, 10% of body surface area) 1
  • Topical clobetasone butyrate or menthol preparations 1

• Second-line therapies:

  • Non-sedating antihistamines (fexofenadine 180 mg or loratadine 10 mg) 1
  • Mildly sedative antihistamines like cetirizine 10 mg 1
  • Hydroxyzine for short-term management of pruritus due to allergic conditions 5

• Third-line therapies:

  • Paroxetine, fluvoxamine, or mirtazapine 1
  • Gabapentin or pregabalin (except in hepatic pruritus) 1
  • Vitamin D supplementation may help some patients 4

2. Hepatic Pruritus

• First-line treatment: Rifampicin 4
• Second-line treatment: Cholestyramine 4
• Third-line treatment: Sertraline 4
• Fourth-line treatment: Naltrexone or nalmefene 4
• Fifth-line treatments:
  • Systemic dronabinol, phenobarbitone, propofol, or topical tacrolimus 4
  • Extracorporeal dialysis techniques, nasobiliary drainage, or liver transplantation for refractory cases 4
• Do not use gabapentin in hepatic pruritus 4
• Consider BB-UVB phototherapy or combined UVA and UVB for symptomatic relief 4

3. Uremic Pruritus

• Initial management:

  • Optimize dialysis parameters 4
  • Normalize calcium-phosphate balance 4
  • Control parathyroid hormone levels 4
  • Correct anemia with erythropoietin 4
  • Use simple emollients for xerosis 4

• Additional treatments:

  • BB-UVB phototherapy (Strength of recommendation A) 4
  • Consider capsaicin cream, topical calcipotriol, or oral gabapentin 4
  • Auricular acupressure or aromatherapy may provide relief 4
  • Renal transplantation is the only definitive treatment 4
  • Avoid cetirizine as it is not effective in uremic pruritus 4
  • Avoid long-term sedative antihistamines except in palliative care due to dementia risk 4

4. Hematologic Disorders

• Iron deficiency: Iron replacement therapy 4
• Iron overload: Venesection or desferrioxamine infusion 4
• Polycythemia vera:
  • Cytoreductive therapy, aspirin, interferon-α, SSRIs, cimetidine, or atenolol 4
  • UVB phototherapy, PUVA, or PUVA with sunlight (relapse common after stopping) 4
  • For aquagenic pruritus: NB-UVB, BB-UVB, or combined UVA and UVB 4

5. Lymphoma-Associated Pruritus

• Cimetidine, carbamazepine, gabapentin, or mirtazapine 4
• Oral corticosteroids for incurable lymphoma 4
• BB-UVB for Hodgkin lymphoma 4
• NB-UVB for non-Hodgkin lymphoma 4

6. Solid Cancer-Associated Pruritus

• Paroxetine, mirtazapine, granisetron, or aprepitant 4

7. Drug-Induced Pruritus

• Trial of medication cessation if risk-benefit analysis is acceptable 4, 1
• Naltrexone for opioid-induced pruritus if cessation not possible 1

Special Considerations

• In elderly patients, exclude asteatotic eczema with a 2-week trial of emollients and topical steroids 1
• For patients >60 years with diffuse itch <12 months duration and history of liver disease, maintain high suspicion for underlying malignancy 2
• Avoid long-term use of sedative antihistamines except in palliative care settings due to potential dementia risk 4, 1
• For neuropathic pruritus, consider skin biopsy to confirm small fiber neuropathy if suspected 4

Common Pitfalls to Avoid

• Failing to perform a thorough medication review to identify drug-induced pruritus 4, 6
• Using sedative antihistamines long-term outside of palliative care settings 4
• Using gabapentin in hepatic pruritus 4
• Using cetirizine in uremic pruritus 4
• Overlooking occult malignancy in older patients with chronic generalized pruritus 2, 3
• Neglecting to evaluate for systemic causes when no primary skin lesions are present 6, 3