What is the best approach for managing pruritis in a patient with cholestatic jaundice?

Management of Pruritus in Cholestatic Jaundice

Cholestyramine should be used as first-line therapy for pruritus in cholestatic jaundice patients, followed by rifampicin as second-line therapy if cholestyramine is ineffective. 1, 2

Stepwise Treatment Algorithm

First-Line Therapy

• Cholestyramine: 4 g/day initially, titrating up to maximum 16 g/day as tolerated 1
  • Administration guidelines:
    • Must be given 2-4 hours before or after UDCA (typically give UDCA at night)
    • Best given at breakfast time (1 hour before or after eating) if gallbladder is in situ
    • Mixing with orange squash and refrigerating overnight improves palatability
    • Monitor for constipation as common side effect 1, 3
  • Mechanism: Adsorbs and combines with bile acids in intestine to form insoluble complex excreted in feces 3

Second-Line Therapy

• Rifampicin: 150-300 mg/day, maximum 600 mg daily 1, 2
  • Start at 150 mg once to twice daily, then titrate upwards based on symptoms
  • Safety monitoring:
    • Check LFTs after 2-4 weeks of treatment and periodically thereafter
    • Use with caution in advanced liver disease
    • Consider vitamin K supplementation if patient is jaundiced 1, 2
  • Risk of hepatotoxicity in up to 12% of cholestatic patients after 4-12 weeks 2

Third-Line Options

• Naltrexone: Start at 12.5 mg/day, titrate slowly to 50 mg/day 1, 2

  • Start at low dose to avoid opiate withdrawal-like reactions
  • Monitor for reduced pain threshold with long-term use
  • Some patients may require intravenous induction 1

• Sertraline: Titrate to 100 mg/day as tolerated 1

  • Monitor for dry mouth as side effect
  • Consider interactions with other medications 1

• Gabapentin: Dose titrate according to side effects and efficacy 1

  • Limited evidence but clinical experience supports use in some patients

Recent Evidence

• Bezafibrate (400 mg/day) has emerged as an effective option for moderate to severe pruritus with additional anticholestatic effects when combined with UDCA 2
  • Monitor for potential side effects:
    • Mild increase in serum creatinine
    • Myalgia/myopathies
    • Increased serum transaminases

Non-Pharmacological Interventions

• Use emollients to prevent skin dryness
• Avoid hot baths or showers
• Apply cooling gels (e.g., menthol) to affected areas
• Keep nails short to minimize skin damage from scratching 2

Refractory Cases

For patients with severe, intractable pruritus not responding to pharmacological therapy:

1. Experimental therapies to consider:

   • Nasobiliary drainage (provides transient relief but technically complicated)
   • Molecular absorbance recirculating system (MARS)
   • Ultraviolet light therapy (relatively easy to access)
   • Plasmapheresis or albumin exchange for temporary relief 1, 2

2. Liver transplantation: Highly effective last resort option for intractable pruritus with rapid reduction in severity, often within 24 hours 1, 2

Important Clinical Considerations

• Always exclude and treat underlying causes of cholestasis when possible (e.g., biliary strictures) 2, 4
• Response to treatment should be evaluated after 2-4 weeks 2
• In patients with methimazole-induced cholestatic jaundice, immediate discontinuation of the medication is crucial 5, 6
• UDCA may be beneficial in certain cholestatic conditions like primary biliary cirrhosis, with 40% of patients experiencing pruritus resolution compared to 19% with placebo 7
• Prolonged cholestatic jaundice and pruritus can occur with certain medications (e.g., fosinopril) and may require extended treatment 8

Monitoring

• Regular assessment of pruritus severity
• Monitor liver function tests, particularly with rifampicin therapy
• Evaluate treatment response after 2-4 weeks and adjust therapy accordingly
• Consider vitamin K supplementation if patient is jaundiced while on rifampicin 1, 2

The stepwise approach allows for systematic management of pruritus in cholestatic jaundice, with clear progression through therapeutic options based on treatment response.