What are the treatment options for Wilson disease?

Treatment Options for Wilson Disease

The first-line treatment for symptomatic Wilson disease is trientine, due to its better safety profile compared to other options, at a dose of 750-1500 mg/day in 2-3 divided doses for adults. 1

Initial Treatment Approach

Chelating Agents

• Trientine (first-line):

  • Dosage: 750-1500 mg/day in 2-3 divided doses for adults
  • Administration: Take 1 hour before or 2 hours after meals
  • Advantages: Better safety profile than D-penicillamine
  • Monitoring: 24-hour urinary copper excretion (target: 200-500 μg/day)

• D-penicillamine (alternative):

  • Dosage: 750-1500 mg/day in 2-3 divided doses
  • Administration: Take 1 hour before meals
  • Caution: High rate of adverse effects (30% of patients)
  • Side effects: Neurological worsening (10-50%), proteinuria, rash, bone marrow depression 2, 1
  • Supplementation: Add pyridoxine (25-50 mg/day) to prevent deficiency 2

Zinc Therapy

• Role: Primarily for maintenance therapy or asymptomatic patients
• Mechanism: Induces intestinal metallothionein, blocking copper absorption 1
• Dosage: 150 mg elemental zinc/day in three divided doses
• Administration: Take 30 minutes before meals 2
• Monitoring: 24-hour urinary copper excretion (target: <75 μg/day) 1

Treatment by Clinical Presentation

Symptomatic Patients (Hepatic or Neurological)

1. Start with a chelating agent (preferably trientine)
2. Monitor for clinical improvement and adverse effects
3. After 1-5 years of successful chelation, may transition to zinc maintenance therapy 1

Decompensated Cirrhosis

• Consider combination therapy with both chelator and zinc (temporally separated by 5-6 hours) 2
• Typical regimen: Zinc (50 mg elemental) as first and third doses, trientine (500 mg) as second and fourth doses 2
• This is an intensive induction regimen; may transition to monotherapy after 3-6 months if responding 2

Acute Liver Failure

• Liver transplantation is life-saving and the only effective option 2
• While awaiting transplant, consider plasmapheresis, hemofiltration, or albumin dialysis to protect kidneys from copper damage 2

Special Considerations

Pregnancy

• Treatment must be maintained throughout pregnancy
• For zinc: maintain usual dosage
• For chelators: consider reducing dose by 25-50% in the last trimester
• D-penicillamine: avoid breastfeeding as it's excreted in breast milk 2

Pediatric Patients

• D-penicillamine: 20 mg/kg/day
• Trientine: 10 mg/kg/day
• Zinc may be preferable for presymptomatic children due to better safety profile 1

Monitoring Treatment Efficacy

• Clinical improvement: Neurological symptoms, liver function
• Laboratory parameters:
  • 24-hour urinary copper excretion
  • Non-ceruloplasmin bound copper (should normalize)
  • Liver function tests
  • Complete blood count
• Long-term follow-up: Regular monitoring is essential as treatment must be lifelong 2, 1

Important Caveats

1. Never discontinue treatment - this can lead to hepatic decompensation within months 1

2. Medication interactions:

   • Avoid iron supplements with trientine (forms toxic complex)
   • Separate zinc and chelator administration by 5-6 hours 1

3. Dietary management:

   • Avoid high-copper foods (shellfish, nuts, chocolate, mushrooms, organ meats)
   • Check copper content of water if using copper pipes
   • Avoid copper cookware 1

4. Treatment challenges:

   • Neurological symptoms may worsen initially with D-penicillamine (occurs in 10-50% of patients)
   • Trientine may cause neurological deterioration more frequently than D-penicillamine 3
   • Some patients may require liver transplantation despite medical therapy 2

Wilson disease treatment requires lifelong commitment and careful monitoring, but with appropriate therapy, patients can achieve normal life expectancy and significant improvement in both hepatic and neurologic manifestations 4.