How to manage severe iron overload with skin lesions?

Management of Severe Iron Overload with Skin Lesions

Phlebotomy is the first-line treatment for severe iron overload with skin lesions, with a target of reducing ferritin to normal levels through weekly removal of one unit of blood until iron depletion is achieved.

Diagnosis Assessment

The laboratory values presented indicate severe iron overload:

• Ferritin >10,000 ng/mL (massively elevated)
• Transferrin saturation of 98% (normal is 20-50%)
• Low transferrin (90 mg/dL)
• Low TIBC (126.9 mg/dL)
• Serum iron of 112 μg/dL

These values, particularly the extremely high ferritin and transferrin saturation approaching 100%, represent severe iron overload. The presence of skin lesions suggests organ damage from iron deposition.

Treatment Algorithm

1. Initial Treatment: Phlebotomy

• Begin phlebotomy immediately at 1-2 units per week as tolerated 1
• Each unit removes approximately 200-250 mg of iron
• Continue until ferritin levels normalize (typically <50-100 ng/mL)
• Monitor hemoglobin before each phlebotomy to ensure it remains >12 g/dL

2. For Patients Unable to Tolerate Phlebotomy

• Iron chelation therapy with deferasirox (oral)
  • Initial dose: 14 mg/kg/day for patients with eGFR >60 mL/min/1.73m² 2
  • Monitor renal and hepatic function closely due to risk of:
    • Acute kidney injury
    • Hepatic toxicity
    • Gastrointestinal hemorrhage

3. Monitoring During Treatment

• Check serum ferritin, transferrin saturation monthly during initial treatment
• Monitor liver function tests every 2 weeks initially
• Assess cardiac function with echocardiography at baseline
• Consider cardiac MRI if signs of heart disease are present 1
• Evaluate skin lesions regularly for improvement

Diagnostic Workup

Given the extreme iron overload, further investigation is warranted:

1. Genetic testing for hereditary hemochromatosis (HFE gene mutations, particularly C282Y homozygosity)
2. Liver assessment:
   • MRI to quantify hepatic iron concentration 1
   • Consider liver biopsy if non-HFE hemochromatosis is suspected 1
3. Cardiac assessment:
   • Echocardiography
   • Cardiac MRI with T2* measurement if cardiac symptoms present 1
   • T2* <10 ms indicates high risk for cardiac decompensation 1

Expected Treatment Response

Several clinical features should improve with iron depletion therapy 1:

• Skin pigmentation/lesions
• Fatigue and malaise
• Abdominal pain
• Elevated liver enzymes
• Insulin requirements (if diabetic)

Features less likely to improve:

• Arthropathy
• Advanced cirrhosis
• Hypogonadism

Monitoring for Complications

1. Cardiac complications:

   • Iron overload cardiomyopathy is a leading cause of mortality 1, 3
   • Early signs include diastolic dysfunction and arrhythmias
   • Late stage presents as dilated cardiomyopathy

2. Liver complications:

   • Monitor for progression of fibrosis
   • Screen for hepatocellular carcinoma if cirrhosis is present 1
   • HCC accounts for approximately 30% of hemochromatosis-related deaths 1

3. Endocrine complications:

   • Monitor glucose tolerance
   • Assess thyroid and gonadal function

Pitfalls to Avoid

1. Do not delay treatment while awaiting genetic testing results - treatment should begin immediately based on phenotypic evidence of iron overload

2. Do not stop treatment prematurely - continue until ferritin normalizes, which may take 2-3 years in severe cases 1

3. Do not neglect cardiac monitoring - cardiac iron overload can progress rapidly and is a leading cause of mortality 1, 3

4. Be cautious with deferasirox - monitor for renal failure, hepatic failure, and GI hemorrhage as these can be fatal complications 2

5. Do not assume all skin lesions will resolve - some manifestations may be permanent despite adequate iron depletion

Regular follow-up is essential to ensure adequate iron depletion and to monitor for complications of both the disease and its treatment.