What is the primary treatment for hemochromatosis?

Treatment of Hemochromatosis

Therapeutic phlebotomy is the first-line treatment for hemochromatosis with evidence of iron overload, and should be initiated in all patients to prevent complications and improve survival. 1

Clinical Manifestations of Hemochromatosis

Hemochromatosis presents with various symptoms related to iron accumulation in organs:

• Fatigue and malaise (responsive to treatment) 1
• Skin pigmentation (responsive to treatment) 1
• Abdominal pain (responsive to treatment) 1
• Arthropathy (less responsive to treatment) 1
• Diabetes mellitus (insulin requirements may improve with treatment) 1
• Liver disease (fibrosis may regress with early treatment) 1
• Cardiac abnormalities (may improve with treatment) 1
• Hypogonadism (less responsive to treatment) 1

Treatment Protocol

Therapeutic Phlebotomy

Phlebotomy is the mainstay of treatment for hemochromatosis and consists of two phases:

1. Induction Phase:

   • Remove one unit of blood (450-500 mL) weekly or biweekly as tolerated 1
   • Check hemoglobin/hematocrit before each phlebotomy 1
   • Avoid reducing hemoglobin/hematocrit by more than 20% of starting value 1
   • Monitor serum ferritin every 10-12 phlebotomies (approximately every 3 months) 1, 2
   • Continue until serum ferritin reaches 50-100 μg/L 1

2. Maintenance Phase:

   • Continue periodic phlebotomy to maintain serum ferritin between 50-100 μg/L 1
   • Frequency varies among individuals based on iron reaccumulation rate 1
   • Some patients require monthly maintenance phlebotomy, while others may need only 1-2 units removed per year 1

Alternative Treatments

• Erythrocytapheresis: Alternative to phlebotomy that selectively removes red blood cells 1, 3

  • Requires fewer procedures and shorter treatment duration 1, 3
  • May be cost-effective in the induction phase 1
  • Availability depends on local resources 1

• Iron Chelation Therapy: Second-line option when phlebotomy is not possible 1

  • Deferasirox (DFX) is most studied but not approved for hemochromatosis by European Medicines Agency 1
  • Should not be used in patients with advanced liver disease 1
  • Associated with gastrointestinal side effects and potential kidney function impairment 1

Dietary and Lifestyle Recommendations

• Avoid iron supplements and iron-fortified foods 1, 2
• Avoid supplemental vitamin C, especially before iron depletion 1
• Limit red meat consumption 1
• Restrict alcohol intake, particularly during iron depletion phase 1
  • Patients with iron overload and liver abnormalities should consume very little or no alcohol 1
  • Patients with cirrhosis should abstain completely from alcohol 1
• Avoid raw or undercooked shellfish due to risk of Vibrio vulnificus infection 1, 2
• Avoid wound exposure to seawater 1

Monitoring and Long-term Management

• Early diagnosis and treatment significantly improve survival when initiated before development of cirrhosis and diabetes 1, 2
• Patients with cirrhosis should undergo regular screening for hepatocellular carcinoma (HCC) 1
• HCC accounts for approximately 30% of hemochromatosis-related deaths 1
• HCC is exceptionally rare in non-cirrhotic hemochromatosis patients 1
• Some patients show regression of hepatic fibrosis after phlebotomy 1

Clinical Pitfalls and Special Considerations

• Established cirrhosis does not reverse with phlebotomy 1
• Arthropathy shows minimal or no improvement with iron removal 1
• Rapid mobilization of iron in patients with cardiac abnormalities may increase risk of arrhythmias 1
• Compliance with maintenance therapy tends to decrease over time (approximately 6.8% annually) 4
• Treatment should be initiated before organ damage occurs for best outcomes 1, 2
• Blood acquired through therapeutic phlebotomy may be used for blood donation in some institutions 1

Treatment of Secondary Iron Overload

• Treatment approach should be tailored to the underlying cause 1, 2
• Phlebotomy is useful in certain forms of secondary iron overload (e.g., porphyria cutanea tarda) 1
• In secondary iron overload associated with ineffective erythropoiesis, iron chelation therapy is the treatment of choice 1