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

Management of Porphyria Cutanea Tarda (PCT)

Therapeutic phlebotomy is the first-line treatment for PCT, removing 400-500 ml of blood weekly or biweekly until serum ferritin levels reach approximately 20 ng/mL. 1

Understanding PCT

Porphyria cutanea tarda is the most common type of porphyria, characterized by:

• Decreased activity of uroporphyrinogen decarboxylase (UROD) enzyme
• Manifestation of skin fragility and blistering lesions on sun-exposed areas
• Classification as either familial (hereditary/type II) or sporadic (acquired/type I), with the latter being more common 2

Diagnostic Confirmation

Diagnosis requires:

• Elevated levels of serum and urinary porphyrins
• Demonstration of UROD deficiency
• Typical cutaneous lesions on sun-exposed areas 1
• Characteristic red to brown urine in natural light and pink to red in fluorescent light 3

Treatment Algorithm

First-line Treatment

• Therapeutic phlebotomy: Remove 400-500 ml of blood (equivalent to 200-250 mg iron) weekly or every two weeks until serum ferritin reaches approximately 20 ng/mL 1
  • Continue until clinical remission and normalization of porphyrin levels
  • Monitor ferritin levels regularly to prevent anemia

Alternative Treatment

• Low-dose hydroxychloroquine: 100 mg twice weekly for patients who:
  • Cannot tolerate phlebotomy
  • Have contraindications to phlebotomy
  • Continue until at least one month after normalization of plasma porphyrin levels 1

Management of Triggering Factors

1. Eliminate exacerbating factors:

   • Complete alcohol abstinence
   • Discontinue estrogen-containing medications
   • Avoid sun exposure and use sun protection
   • Treat underlying hepatitis C infection if present 1

2. Additional measures:

   • Avoid vitamin C supplements during phlebotomy treatment 1
   • Screen for HFE gene mutations (hemochromatosis) 1
   • Monitor for liver disease progression, as PCT can be associated with advanced fibrosis, cirrhosis, and hepatocellular carcinoma 2

Long-term Management

• Regular assessment of serum ferritin levels
• Monitoring of plasma and urinary porphyrin levels
• Maintenance of mildly iron-reduced state without anemia 1
• Patients with both PCT and HFE mutations may require more intensive phlebotomy regimens and long-term maintenance phlebotomy 1

Special Considerations

• Relapse prevention: After achieving remission, control of susceptibility factors is crucial as relapse rates may be higher after hydroxychloroquine treatment compared to phlebotomy 2
• Hepatitis C co-infection: With the advent of direct-acting antivirals, treatment of concomitant HCV has become safer and more effective 2
• Liver monitoring: Consider screening for hepatocellular carcinoma using ultrasound in PCT patients with cirrhosis or advanced fibrosis 2

Treatment Efficacy

Both phlebotomy and low-dose hydroxychloroquine are considered equally effective and safe for PCT treatment 2, but phlebotomy is generally preferred as first-line therapy due to its safety profile and effectiveness in reducing iron overload, which is a critical pathogenic factor in PCT 1.