What is the initial treatment and follow-up plan for a patient diagnosed with Wilson's disease?

Treatment and Follow-up of Wilson's Disease

The first-line treatment for symptomatic Wilson's disease is chelation therapy with trientine (750-1500 mg/day in 2-3 divided doses) due to its better safety profile compared to D-penicillamine, with regular monitoring at least twice yearly. 1

Initial Treatment Selection

Treatment choice depends on clinical presentation:

1. Symptomatic patients with hepatic or neurological manifestations:

   • First-line: Trientine 750-1500 mg/day in 2-3 divided doses 1
   • Alternative: D-penicillamine 750-1500 mg/day in 2-3 divided doses (note: associated with severe side effects in ~30% of patients, including hypersensitivity reactions and neurological worsening) 1

2. Presymptomatic patients:

   • Children under 3 years: Zinc therapy preferred 1
   • Others: Either chelating agents or zinc therapy 1

3. Patients with decompensated cirrhosis without encephalopathy:

   • Combination therapy: Chelator and zinc, separated by 5-6 hours
   • Example regimen: Zinc (50 mg elemental) as first and third doses, trientine (500 mg) as second and fourth doses 1

4. Maintenance therapy:

   • Zinc acetate is FDA-approved for maintenance therapy after initial chelation 2, 1
   • Typical dosage: 50 mg three times daily 2

Monitoring Protocol

Frequency

• Minimum twice yearly for all patients 3, 1
• More frequent monitoring during:
  • Initial treatment phase
  • When experiencing worsening symptoms
  • When experiencing medication side effects
  • When non-compliance is suspected 3

Clinical Monitoring

• Physical examination for:
  • Evidence of liver disease
  • Neurological symptoms
  • Kayser-Fleischer rings (reappearance may indicate non-compliance)
  • Cutaneous changes (for patients on penicillamine)
  • Psychiatric symptoms, especially depression 3

Laboratory Monitoring

• Liver biochemistries including tests of hepatic synthetic function
• Serum copper and ceruloplasmin
• Estimated serum non-ceruloplasmin bound copper (best guide to treatment efficacy)
• 24-hour urinary copper excretion (reflects compliance) 3, 1

Target Laboratory Values

• For patients on chelation therapy (D-penicillamine or trientine):
  • 24-hour urinary copper: 200-500 μg/day (3-8 μmol/day)
• For patients on zinc therapy:
  • 24-hour urinary copper: <75 μg/day (1.2 μmol/day)
  • Urinary zinc excretion: ~2 mg/24 hours 3, 1
• Complete blood count for all patients on chelators
• Regular urinalysis to ensure safety 3

Important Considerations and Pitfalls

Medication Administration

• Critical pitfall: Zinc and chelators should NOT be administered simultaneously; they must be separated by at least 5-6 hours 1

Diet and Lifestyle

• Avoid foods high in copper: shellfish, nuts, chocolate, mushrooms, and organ meats 1
• Check copper content of water if using copper pipes; flush stagnant water before use 1
• Dietary management alone is insufficient and must be used with medical treatment 1

Medication Side Effects

• D-penicillamine: Monitor for early hypersensitivity reactions, proteinuria, rash, bone marrow depression, and neurological worsening 1
• Trientine: Watch for potential sideroblastic anemia (rare) 1
• Zinc: Main side effect is gastric irritation 1, 4

Treatment Compliance

• Non-compliance can lead to serious complications including fulminant hepatic failure 1
• Elevated urinary copper on chelation therapy may suggest non-adherence 3
• Low urinary copper on chelation therapy can indicate overtreatment 3

Special Situations

• Pregnancy: Treatment must be maintained throughout pregnancy

  • Consider reducing chelator dose by 25-50% in the last trimester
  • Zinc salts can be maintained at the same dosage 1

• Liver failure: Liver transplantation is life-saving and definitive for patients with acute liver failure 1

Treatment Interpretation

• High urinary copper with hepatic deterioration may indicate non-adherence to treatment 3
• Low urinary copper with very low non-ceruloplasmin bound copper may indicate overtreatment, potentially causing neutropenia, anemia, or hyperferritinemia 3
• Low urinary copper with elevated non-ceruloplasmin bound copper may indicate subtherapeutic dosing or treatment cessation 3

Remember that Wilson's disease requires lifelong treatment, and never discontinue therapy indefinitely as this can lead to serious complications including fulminant hepatic failure 1.