Treatment of Porphyria Cutanea Tarda
Therapeutic phlebotomy is the first-line treatment for porphyria cutanea tarda (PCT) to reduce hepatic iron stores, which is essential for disease resolution. 1, 2
Diagnosis and Pathophysiology
- PCT is characterized by elevated uro- and heptacarboxyl porphyrins in urine, requiring biochemical testing for definitive diagnosis 1
- The disease results from inhibition of uroporphyrinogen decarboxylase (UROD) in the presence of hepatic iron and oxidative stress 3
- Liver iron overload is present in approximately 95% of PCT cases, making iron reduction a cornerstone of treatment 4
- Diagnosis requires fractionation of porphyrins in urine, not just total porphyrin measurements 1
First-Line Treatment: Phlebotomy
- Regular phlebotomies should be performed until iron stores are depleted, followed by maintenance therapy guided by serum ferritin levels 5
- The goal of phlebotomy is to achieve mild iron deficiency without causing anemia 6
- Typical phlebotomy regimen involves removing 450-500 mL of blood every 1-2 weeks until serum ferritin is in the low-normal range 2
- Biochemical monitoring of urinary porphyrin levels should guide treatment duration 2
Alternative Treatment: Antimalarials
- Low-dose antimalarial drugs (chloroquine or hydroxychloroquine) are effective alternatives when phlebotomy is contraindicated or poorly tolerated 2, 7
- Antimalarials work by promoting porphyrin elimination from the liver 8
- Standard dosing is typically low-dose chloroquine (125 mg twice weekly) to avoid hepatotoxicity 7
- Combined approach using both phlebotomy and low-dose antimalarials may be beneficial in difficult cases 2
Management of Underlying Risk Factors
- Treatment of hepatitis C virus (HCV) infection with direct-acting antivirals is essential if present 2, 6
- Complete alcohol cessation is critical as it is a common trigger for PCT 2
- Avoidance of estrogens, liver toxins, and other medications that can exacerbate PCT 2
- Iron supplementation and vitamin C supplements should be avoided 5
Adjunctive Measures
- Strict photoprotection is necessary to prevent cutaneous manifestations 2
- Sun avoidance and protective clothing for sun-exposed areas, particularly hands and face 2
- Care of vulnerable skin to prevent blisters and erosions 8
- Patients with cirrhosis should undergo regular screening for hepatocellular carcinoma 5
Special Considerations
- In patients with renal failure on hemodialysis, erythropoietin, desferroxamine, and small-volume phlebotomy may be needed 7
- For patients with HFE gene mutations (hereditary hemochromatosis), more intensive phlebotomy regimens may be required 7
- Treatment should continue until complete normalization of urinary porphyrin levels, not just clinical improvement 1