What are the symptoms and treatment of copper toxicity?

Copper Toxicity: Symptoms and Treatment

Copper toxicity can cause severe multi-organ damage including hematemesis, hypotension, melena, coma, headaches, behavioral changes, fever, diarrhea, abdominal cramps, Kayser-Fleischer rings in the eyes, and jaundice, requiring prompt treatment with chelating agents such as D-penicillamine. 1

Symptoms of Copper Toxicity

Copper toxicity manifests with a range of symptoms affecting multiple organ systems:

Gastrointestinal Symptoms

• Hematemesis (vomiting blood) 1
• Melena (black "tarry" feces) 1
• Severe hemorrhagic gastroenteritis 2
• Diarrhea and abdominal cramps 1

Neurological and Behavioral Symptoms

• Headaches and behavioral changes 1
• Coma in severe cases 1
• Neurological deterioration 1

Cardiovascular Symptoms

• Hypotension 1
• Potential cardiac arrhythmias in acute toxicity 2

Hepatic and Renal Manifestations

• Jaundice 1
• Liver failure (often the first organ affected) 1
• Renal failure 2

Hematological Effects

• Intravascular hemolysis 2
• Hemolytic anemia 1
• Coagulopathy unresponsive to vitamin K 1

Ocular Signs

• Kayser-Fleischer rings (brown ring-shaped markings in eyes) - pathognomonic finding 1

Other Symptoms

• Fever 1
• Adrenal insufficiency in severe cases 2

Causes of Copper Toxicity

Copper toxicity can occur through several mechanisms:

• Industrial exposure to copper dust or fumes 1
• Ingestion of contaminated water 1
• Dietary supplements with excessive copper 1
• Genetic disorders (Wilson's disease, Menke's syndrome) 1
• Cholestasis affecting liver's ability to excrete copper 1
• Massive ingestion (including coins containing copper) 3
• Inhalation of copper dust 4

Diagnosis

Diagnosis of copper toxicity involves:

• Measurement of serum copper and ceruloplasmin levels 1
• CRP determination (to differentiate from inflammatory conditions) 1
• Liver function tests 1
• Slit-lamp examination for Kayser-Fleischer rings 1
• 24-hour urinary copper measurement 1
• Liver biopsy in suspected cases (copper concentration >250 mcg/g dry weight is diagnostic) 5

Treatment Approach

Acute Copper Toxicity

1. Immediate Interventions

   • Early gastric lavage for recent ingestions 2
   • Fluid replacement for dehydration 2
   • Supportive care including vasoactive drugs if needed 2

2. Antidotes and Chelation Therapy

   • D-penicillamine (250-500 mg/day initially, then increased by 250 mg increments every 4-7 days to a maximum of 1000-1500 mg daily in divided doses) 1, 5
   • 2,3-dimercaptopropane-1-sulphonate (DMPS) in severe cases 2
   • Methylene blue for methemoglobinemia if present 2
   • In severe neurological symptoms, consider short courses of 2,3-dimercaprol (BAL) while continuing penicillamine 1

3. Management of Complications

   • Hemodialysis for severe renal failure 2
   • Hydrocortisone for adrenal insufficiency 2
   • Blood transfusions for severe hemolytic anemia 2
   • Antiemetics and ranitidine for gastrointestinal symptoms 2

Chronic Copper Toxicity (Wilson's Disease)

1. Dietary Management

   • Restrict foods high in copper (chocolate, nuts, shellfish, mushrooms, liver, molasses, broccoli, and copper-enriched cereals) 5
   • Use distilled or demineralized water if drinking water contains >0.1 mg/L copper 5

2. Pharmacological Treatment

   • Lifelong therapy with copper chelating agents 1
   • Zinc administration (competes with copper for absorption) 1
   • Regular monitoring of copper levels 1

Special Considerations

• Temporary worsening of neurological symptoms may occur during initial treatment with penicillamine but should not lead to drug discontinuation 5
• Liver transplantation may be considered in severe cases of Wilson's disease 1
• First-degree relatives of patients with Wilson's disease should be screened 1
• Chronic copper toxicity is rare outside of genetic disorders but may contribute to neurodegenerative diseases of aging 6

Monitoring and Follow-up

• Regular monitoring of liver and renal function 1
• Periodic measurement of serum copper levels 1
• In patients on parenteral nutrition, copper levels should be checked every 6-12 months 1
• Long-term follow-up is essential as mild renal and liver impairment may persist 2