Management of Wilson Disease
The management of Wilson Disease requires lifelong copper-chelating therapy with D-penicillamine as first-line treatment, or alternative agents like trientine, zinc salts, or tetrathiomolybdate based on clinical presentation and patient factors. 1
Diagnosis Confirmation
Before initiating treatment, confirm diagnosis through:
- Clinical findings: Liver disease, neurological manifestations, Kayser-Fleischer rings
- Laboratory tests: Decreased serum ceruloplasmin, elevated 24-hour urinary copper excretion
- Liver biopsy: Elevated hepatic copper concentration
- Genetic testing: ATP7B mutations on chromosome 13
Treatment Algorithm
Initial Treatment Selection
For symptomatic liver disease without neurological symptoms:
- D-penicillamine (first-line): 20 mg/kg/day divided into 2-4 doses
- Monitor for side effects: hypersensitivity reactions, bone marrow suppression, nephrotoxicity
For neurological manifestations:
- Trientine: 20 mg/kg/day divided into 2-3 doses
- OR zinc salts: 150 mg elemental zinc daily in three divided doses
- Avoid D-penicillamine due to risk of neurological worsening
For acute liver failure:
- Immediate liver transplantation evaluation
- Supportive care while awaiting transplant
For asymptomatic patients (early detection):
- Zinc salts as maintenance therapy
- Consider lower doses of chelators
Monitoring Treatment
- Clinical assessment every 3-6 months
- Liver function tests monthly initially, then every 3 months
- 24-hour urinary copper excretion (target: 200-500 μg/24h during chelation)
- Complete blood count, urinalysis, serum copper and ceruloplasmin levels
- Neurological evaluation for patients with CNS involvement
Special Considerations
Pregnancy
- Continue treatment during pregnancy
- Consider dose reduction of D-penicillamine to 25-50% of standard dose
- Trientine may be preferred during pregnancy
Surgical Procedures
- Continue copper-chelating therapy perioperatively
- Monitor for wound healing complications with D-penicillamine
Diet Recommendations
- Avoid copper-rich foods (shellfish, nuts, chocolate, mushrooms, liver)
- Avoid vitamin/mineral supplements containing copper
- Use demineralized water if residential water contains high copper levels
Treatment Complications and Management
D-penicillamine Complications
- Early hypersensitivity: Fever, rash, lymphadenopathy, neutropenia
- Manage with temporary dose reduction and antihistamines
- Consider desensitization protocols
- Late complications: Nephrotoxicity, bone marrow suppression, autoimmune disorders
- Switch to alternative agent if severe
Neurological Worsening
- Occurs in approximately 10-50% of neurologically symptomatic patients starting D-penicillamine
- If deterioration occurs:
- Consider switching to trientine or zinc therapy
- Slower titration of chelating agents
Long-term Considerations
- Lifelong therapy is required
- Non-compliance is the most common cause of treatment failure
- Regular monitoring for complications of both disease and treatment
- Family screening for early detection in first-degree relatives
Liver Transplantation
Indications:
- Fulminant hepatic failure
- Decompensated cirrhosis unresponsive to medical therapy
- Severe neurological disease unresponsive to medical therapy
Liver transplantation is curative for the hepatic manifestations of Wilson Disease but may not reverse established neurological damage.
Pitfalls to Avoid
- Misdiagnosis due to atypical presentations
- Discontinuation of therapy once symptoms improve
- Inadequate monitoring of treatment efficacy and side effects
- Failure to screen family members
- Overlooking zinc-induced gastric irritation (take with food)
- Neglecting the need for vitamin B6 supplementation with D-penicillamine
Remember that early diagnosis and prompt initiation of therapy are crucial for preventing irreversible organ damage and improving long-term outcomes in Wilson Disease.