How are copper excess symptoms treated?

Treatment of Copper Excess Symptoms (Wilson's Disease)

The first-line treatment for symptomatic copper excess (Wilson's disease) should be chelation therapy with trientine at a dose of 750-1500 mg/day in 2-3 divided doses, due to its better safety profile compared to D-penicillamine. 1

First-Line Treatment Options

Chelating Agents

1. Trientine (First Choice)

   • Dosage: 750-1500 mg/day in 2-3 divided doses for adults
   • Administration: Take 1 hour before or 2 hours after meals
   • Mechanism: Forms stable complex with copper using four constituent nitrogens in a planar ring
   • Advantages: Fewer side effects than D-penicillamine, less neurological worsening 2

2. D-Penicillamine (Alternative)

   • Dosage: 750-1500 mg/day in 2-3 divided doses
   • Administration: Take 1 hour before or 2 hours after meals
   • Mechanism: Promotes urinary copper excretion
   • Caution: Associated with severe side effects in ~30% of patients, including early hypersensitivity reactions and neurological worsening 2
   • Requires: Pyridoxine (vitamin B6) supplementation at 25-50 mg daily 2

Zinc Therapy

• Primarily for:
  • Maintenance therapy after initial chelation
  • Presymptomatic patients
  • Neurological patients (as alternative first-line)
• Mechanism: Induces intestinal metallothionein which binds copper and prevents absorption 2
• Advantages: Very few side effects, minimal neurological deterioration 2
• Monitoring: Urinary copper excretion should be <75 μg/day on stable treatment 2

Monitoring Treatment Efficacy

For Chelation Therapy

• Target urinary copper excretion: 200-500 μg (3-8 μmol) per day on maintenance treatment 2
• Non-ceruloplasmin bound copper: Should normalize with effective treatment 2
• Warning signs:
  • Urinary copper <200 μg/day may indicate non-adherence or overtreatment 2
  • Non-ceruloplasmin bound copper >15 μg/dL suggests non-adherence 2

For Zinc Therapy

• Target urinary copper excretion: <75 μg (1.2 μmol) per day 2
• Urinary zinc excretion: ~2 mg/24 hours (to check compliance) 1

Dietary Management (as adjunctive therapy)

• Avoid foods high in copper:
  • Shellfish
  • Nuts
  • Chocolate
  • Mushrooms
  • Organ meats 2
• Important: Dietary management alone is insufficient and must be used with medication 1

Potential Complications and Management

Overtreatment Risks

• Copper deficiency: Can lead to anemia and paradoxical liver dysfunction 3
• Signs of overtreatment: Very low non-ceruloplasmin bound copper (<5 μg/dL) 2

Side Effect Management

• For D-penicillamine reactions: Switch to trientine immediately if early sensitivity reactions occur 2
• For trientine: Monitor for potential sideroblastic anemia (rare) 2
• For zinc: Watch for gastric irritation (main side effect) 2

Treatment Duration and Monitoring

• Treatment is lifelong: Never discontinue therapy indefinitely 1
• Monitoring frequency:
  • Liver function tests: Every 3 months during first year, then every 3-6 months 1
  • 24-hour urinary copper excretion: Regularly to assess treatment adequacy 2

Special Considerations

Neurological Symptoms

• Trientine preferred: Less risk of neurological worsening compared to D-penicillamine 2
• Gradual dose escalation: For D-penicillamine, start with 125-250 mg/day and increase gradually to reduce risk of neurological deterioration 2

Pregnancy

• Maintain treatment: Therapy must continue throughout pregnancy 1
• Dose adjustment: Consider reducing chelator dose by 25-50% in last trimester 1

Adjunctive Treatments

• Vitamin E supplementation: May be beneficial due to low vitamin E levels in Wilson's disease 1
• Antioxidants: May have a role, though rigorous studies are lacking 1

Recent research suggests that trientine may have additional mechanisms beyond urinary copper excretion, including inhibition of intestinal copper absorption, which may explain its effectiveness despite lower urinary copper excretion compared to penicillamine 4.