What is the treatment for Porphyria Cutanea Tarda (PCT)?

Treatment of Porphyria Cutanea Tarda

The first-line treatment for porphyria cutanea tarda is therapeutic phlebotomy (450 mL every 2 weeks) until serum ferritin reaches 20 ng/mL, with low-dose hydroxychloroquine (100 mg twice weekly) serving as an equally effective alternative, particularly when phlebotomy is contraindicated or poorly tolerated. 1, 2

Initial Management Approach

Photo-Protection and Trigger Avoidance

• Strict sun avoidance and photo-protection are essential first steps, as PCT manifests with photosensitivity and blistering lesions on sun-exposed areas 1, 3
• Immediately discontinue alcohol consumption, as it is a critical triggering factor 1, 4
• Avoid estrogens, liver toxins, and other medications that can exacerbate PCT 1, 4

Address Underlying Causes

• Screen for and treat hepatitis C virus infection if present, using direct-acting antivirals (DAAs) without interferon or ribavirin, as these are preferred over older regimens that could worsen PCT 1, 5
• Evaluate for hereditary hemochromatosis and iron overload, as hepatic iron is central to PCT pathogenesis 6, 3

First-Line Therapeutic Options

Therapeutic Phlebotomy (Primary Treatment)

• Perform phlebotomy of 450 mL every 2 weeks until serum ferritin reaches 20 ng/mL 2, 1
• Continue with maintenance therapy guided by serum ferritin levels after initial iron depletion 1
• Expected time to remission (normal plasma porphyrin levels) is approximately 6.9 months 2
• Monitor urinary porphyrin levels biochemically to guide treatment duration 1
• Phlebotomy remains the treatment of choice due to ease of administration and proven efficacy 4, 7

Low-Dose Hydroxychloroquine (Alternative or Adjunctive)

• Administer hydroxychloroquine 100 mg orally twice weekly until plasma porphyrin levels normalize (typically continuing for at least 1 month after normalization) 2, 1
• This regimen achieves remission in approximately 6.1 months, comparable to phlebotomy 2
• Hydroxychloroquine is particularly useful when phlebotomy is contraindicated (e.g., anemia, cardiovascular disease, minor thalassemia) or poorly tolerated 1, 4
• Patient compliance is substantially better with hydroxychloroquine compared to phlebotomy 2
• Avoid higher-dose hydroxychloroquine regimens, as they have more side effects without additional benefit 2
• Note that chloroquine (an alternative antimalarial) is ineffective in patients with chronic hemodialysis-associated PCT 4

Important Caveats and Pitfalls

When Antimalarials Have Limitations

• In patients with HFE gene mutations (hereditary hemochromatosis), low-dose antimalarials alone may be insufficient; additional phlebotomy is required for adequate iron depletion 4
• For chronic hemodialysis-associated PCT, chloroquine is ineffective; consider erythropoietin, desferrioxamine, or small-volume phlebotomy instead 4

Special Populations

• In childhood PCT (very rare), use body weight-adapted chloroquine therapy or small-volume phlebotomy 4
• Avoid iron supplementation and vitamin C supplements, as these can exacerbate the disease 1

Monitoring and Long-Term Management

• Protect samples for porphyrin testing from light to avoid falsely low results 1, 6
• In patients with cirrhosis, perform regular screening for hepatocellular carcinoma 1
• Both phlebotomy and hydroxychloroquine are safe with no significant side effects reported in clinical studies 2, 7

Alternative Iron Removal

• Slow subcutaneous desferrioxamine infusion (1.5 g, 5 days per week) achieves recovery in approximately 11.2 months and is recommended when severe associated diseases contraindicate phlebotomy, though it is expensive 7