What is the management of Porphyria Cutanea Tarda (PCT)?

Management of Porphyria Cutanea Tarda (PCT)

Therapeutic phlebotomy is the first-line treatment for Porphyria Cutanea Tarda and should be initiated in all patients with evidence of iron overload. 1

Disease Overview

Porphyria cutanea tarda (PCT) is the most common form of porphyria, characterized by:

• Low activity of uroporphyrinogen decarboxylase (URO-D) in the liver
• Typical cutaneous manifestations including:
  • Skin fragility and blistering on sun-exposed areas
  • Hyperpigmentation
  • Facial hypertrichosis
  • Sclerodermoid plaques in late stages

PCT can be classified as:

• Familial (hereditary) - enzyme defect present in hepatocytes and other cells
• Sporadic (acquired) - more common, with URO-D activity decreased to 50% predominantly in hepatocytes 1

Diagnostic Approach

Diagnosis of PCT requires demonstration of:

• Elevated levels of serum and urinary porphyrins
• URO-D deficiency
• Typical cutaneous lesions on sun-exposed areas 1

Treatment Algorithm

First-Line Treatment: Iron Depletion via Phlebotomy

1. Initiate therapeutic phlebotomy:

   • Remove 400-500 ml of blood (equivalent to 200-250 mg iron) weekly or every two weeks
   • Continue until serum ferritin levels reach approximately 20 ng/mL
   • Ensure adequate hydration before and after treatment
   • Advise patients to avoid vigorous physical activity for 24 hours after phlebotomy 1

2. Monitor response:

   • Median time to remission with phlebotomy: 6.9 months 2
   • Continue until normalization of plasma porphyrin levels

Alternative Treatment: Low-Dose Hydroxychloroquine

For patients who cannot tolerate phlebotomy or have contraindications:

• Administer 100 mg hydroxychloroquine twice weekly
• Continue until at least one month after normalization of plasma porphyrin levels
• Median time to remission: 6.1 months 2

Low-dose hydroxychloroquine has shown comparable efficacy to phlebotomy with:

• Better patient compliance
• Lower projected costs
• No significant side effects at this low dosage 2

Management of Contributing Factors

1. Eliminate triggering factors:

   • Alcohol abstinence
   • Discontinue estrogens
   • Avoid sun exposure
   • Treat underlying hepatitis C infection if present 1, 3

2. Address comorbidities:

   • Screen for and treat hepatitis C infection
   • Evaluate for hemochromatosis (HFE gene mutations)
   • Assess liver function 3

Special Considerations

Hepatitis C-Associated PCT

• HCV infection is a significant trigger for PCT in some geographical areas
• Treating the underlying HCV infection may improve PCT manifestations
• Consider antiviral therapy after initial iron depletion 1, 3

Hemochromatosis and PCT

• Screen patients for HFE gene mutations
• Patients with both conditions may require more intensive phlebotomy regimens
• Long-term maintenance phlebotomy may be necessary 1, 3

Monitoring and Follow-up

• Regular assessment of serum ferritin levels
• Monitor plasma and urinary porphyrin levels
• Maintain mildly iron-reduced state without anemia
• Evaluate for improvement in cutaneous manifestations

Treatment Efficacy

Both phlebotomy and low-dose hydroxychloroquine have demonstrated effectiveness:

• Phlebotomy works by decreasing total body iron levels
• Hydroxychloroquine reduces hepatic porphyrin content through increased porphyrin excretion 4, 2

Pitfalls and Caveats

1. Avoid vitamin C supplements in patients undergoing phlebotomy for PCT 1

2. Caution with high-dose antimalarials: Higher doses of hydroxychloroquine have more side effects without additional benefit 2

3. Special populations:

   • Patients on chronic hemodialysis may require alternative approaches as chloroquine is ineffective
   • Childhood PCT is rare and may require body weight-adapted therapy 5

4. Long-term monitoring: Even after successful treatment, patients should be monitored for recurrence and development of associated conditions, particularly liver disease

By addressing both the iron overload and triggering factors, most patients with PCT can achieve complete remission with appropriate treatment.