What are the European guidelines for managing Wilson disease?

European Guidelines for Wilson Disease Management

According to European guidelines, symptomatic Wilson disease patients should initially receive a chelating agent (penicillamine or trientine) as first-line therapy, while zinc may be used as first-line therapy in neurological patients or for maintenance treatment after initial chelation therapy. 1

Initial Treatment Approach

Symptomatic Patients

• Chelating agents are recommended as first-line treatment for symptomatic patients 1:
  • Trientine: 750-1500 mg/day in 2-3 divided doses (preferred due to better safety profile) 2
  • D-penicillamine: 750-1500 mg/day in 2-3 divided doses (alternative but with higher rate of adverse effects) 1, 2

Special Considerations for Neurological Patients

• Zinc may have a role as first-line therapy in patients with neurological manifestations 1
• Caution with chelating agents in neurological patients as neurological deterioration occurs in 10-50% of patients during initial treatment with D-penicillamine 2

Presymptomatic/Asymptomatic Patients

• Either chelating agents or zinc can be used effectively 1
• Zinc acetate at 150 mg elemental zinc/day in three divided doses 2

Monitoring Treatment Efficacy

• 24-hour urinary copper excretion:
  • Target for chelation therapy: 200-500 μg/day 2
  • Target for zinc therapy: <75 μg/day 2
• Non-ceruloplasmin bound copper should be monitored and normalized 1, 2
• Liver function tests every 3 months during the first year 2
• Urinary zinc excretion (~2 mg/24 hours) to check compliance with zinc therapy 1

Maintenance Therapy

• After 1-5 years of successful chelation therapy, patients may be transitioned to zinc maintenance therapy 1, 2
• Criteria for transition to maintenance therapy:
  • Clinically well patient
  • Normal liver function tests
  • Normal non-ceruloplasmin bound copper
  • 24-hour urinary copper in the range of 200-500 μg/day on treatment 1

Dietary Management

• Avoid foods with high copper content (shellfish, nuts, chocolate, mushrooms, organ meats) 1
• Check copper content of water if using copper pipes 1
• Dietary management alone is not sufficient and should be used in conjunction with medical treatment 1

Special Situations

Pregnancy

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

Fulminant Hepatic Failure

• Liver transplantation is life-saving and the definitive treatment 1
• While awaiting transplant, plasmapheresis, hemofiltration, or albumin dialysis can protect kidneys from copper damage 1
• The Nazer prognostic score (components: serum bilirubin, serum AST, and prolongation of prothrombin time) helps determine which patients will need transplantation; patients with a score ≥7 have poor survival without transplant 1

Adjunctive Treatments

• Vitamin E may have a role as adjunctive treatment due to low serum and hepatic vitamin E levels in Wilson disease 1
• Antioxidants may be beneficial, though rigorous studies are lacking 1

Important Precautions

• Never discontinue treatment indefinitely - patients who stop treatment risk developing intractable hepatic decompensation 1, 2
• Zinc and chelators should not be administered simultaneously - separate by at least 5-6 hours 2
• Monitor for side effects:
  • D-penicillamine: proteinuria, rash, bone marrow depression (30% of patients experience adverse effects) 2
  • Zinc: gastric irritation (most common side effect) 2, 3
  • Trientine: sideroblastic anemia with overtreatment 2

Emerging Therapies

• Tetrathiomolybdate shows promise for initial treatment of neurological patients with less risk of neurological worsening, but remains experimental in Europe and the US 1, 2

By following these European guidelines for Wilson disease management, clinicians can optimize treatment outcomes while minimizing treatment-related complications, ultimately improving morbidity, mortality, and quality of life for patients with this rare but treatable disorder.