What is the initial treatment for Wilson disease?

Initial Treatment for Wilson Disease

Trientine is recommended as the first-line treatment for symptomatic Wilson disease patients due to its better safety profile compared to D-penicillamine, at a dose of 750-1500 mg/day in 2-3 divided doses for adults. 1

Treatment Algorithm Based on Clinical Presentation

For Symptomatic Patients:

1. Initial therapy with chelating agents:

   • First choice: Trientine 750-1500 mg/day in 2-3 divided doses, administered 1 hour before or 2 hours after meals 1
   • Alternative: D-penicillamine 750-1500 mg/day in 2-3 divided doses, with pyridoxine 25-50 mg daily supplementation 1

   Note: D-penicillamine has a high rate of adverse effects (approximately 30% of patients) and neurological worsening occurs in 10-50% of patients during initial treatment 1

2. Monitoring during initial therapy:

   • 24-hour urinary copper excretion (target: 200-500 μg/day for chelation therapy)
   • Non-ceruloplasmin bound copper concentration
   • Liver function tests every 3 months during the first year 2

For Presymptomatic/Asymptomatic Patients:

1. Either chelating agent or zinc therapy is appropriate: 2

   • Zinc acetate: 150 mg elemental zinc/day in three divided doses, taken 30 minutes before meals 1
   • Chelating agent (trientine or D-penicillamine) at doses listed above

2. Monitoring for zinc therapy:

   • 24-hour urinary copper excretion (target: <75 μg/day) 2
   • Urinary zinc excretion (~2 mg/24 hours) to check compliance 1

Special Considerations

For Fulminant Hepatic Failure:

• Liver transplantation is life-saving and the definitive treatment 1
• While awaiting transplant, plasmapheresis, hemofiltration, or albumin dialysis can be used to protect kidneys from copper damage 1

For Neurological Symptoms:

• Trientine is preferred over D-penicillamine as neurological worsening appears less common 2
• Ammonium tetrathiomolybdate (TM) shows promise for initial treatment of patients with neurologic symptoms with less risk of neurological deterioration, but remains experimental and is not commercially available 2, 1

Adjunctive Measures

Dietary Management:

• Avoid foods with high copper content (shellfish, nuts, chocolate, mushrooms, and organ meats) 2, 1
• Check copper content of water if using copper pipes 2
• Note: Dietary management alone is not sufficient therapy 1

Antioxidants:

• Vitamin E may have a role as adjunctive treatment, as serum and hepatic vitamin E levels have been found to be low in Wilson disease 2

Maintenance Therapy

After adequate initial treatment with a chelator (typically 1-5 years), patients may be transitioned to zinc therapy when they are:

• Clinically well
• Have normal liver function tests
• Have normal non-ceruloplasmin bound copper
• Have 24-hour urinary copper in the range of 200-500 μg/day on treatment 2

Important Cautions

1. Never discontinue treatment indefinitely - interruption of therapy can lead to serious complications, including fulminant hepatic failure 2, 1

2. Drug interactions:

   • Avoid co-administration of trientine and iron as they form a toxic complex 2
   • Separate zinc and chelator administration by 5-6 hours to prevent binding 1

3. Monitoring for adverse effects:

   • For D-penicillamine: proteinuria, rash, bone marrow depression, and gastric irritation 3
   • For trientine: sideroblastic anemia may occur with overtreatment 2
   • For zinc: gastric irritation is the most common side effect 4

4. Pregnancy considerations:

   • Treatment must be maintained throughout pregnancy
   • Consider reducing the dose of chelators by 25-50% in the last trimester 1
   • D-penicillamine should be limited to 750 mg daily during pregnancy for Wilson disease 3

The evidence strongly supports trientine as the initial treatment of choice for symptomatic Wilson disease patients due to its favorable safety profile compared to D-penicillamine, while zinc therapy is appropriate for presymptomatic patients or as maintenance therapy after initial chelation.