From the Guidelines
Porphyria cutanea tarda (PCT) is a condition characterized by skin fragility, blistering, and hyperpigmentation in sun-exposed areas, and its primary treatment involves phlebotomy to reduce iron levels, as well as avoidance of triggers such as alcohol, estrogens, and iron supplements. The condition is caused by decreased activity of uroporphyrinogen decarboxylase enzyme in the liver, leading to accumulation of photosensitizing porphyrins that cause skin damage when exposed to light 1. Key characteristics of PCT include:
- Skin fragility and blistering in sun-exposed areas
- Hyperpigmentation
- Accumulation of uro- and heptacarboxyl porphyrins in urine and hepta-, penta- and isocoproporphyrins in faeces 1
- Decreased activity of uroporphyrinogen decarboxylase enzyme in the liver Treatment of PCT typically involves:
- Phlebotomy to reduce iron levels, typically 450-500 mL every 2 weeks until ferritin levels normalize
- Low-dose hydroxychloroquine (100 mg twice weekly or 200 mg twice weekly) as an alternative treatment to mobilize porphyrins from the liver
- Avoidance of triggers such as alcohol, estrogens, and iron supplements
- Sun protection, including wearing protective clothing, using high SPF sunscreen, and avoiding direct sunlight, especially between 10 AM and 4 PM Underlying causes such as hepatitis C, HIV, or hemochromatosis should be identified and treated, as they may contribute to the development of PCT 1. Most patients respond well to treatment within 6-12 months, though some may require maintenance therapy. It is essential to note that PCT can be categorized into two different subtypes: familial and sporadic, with the sporadic subtype being more common and often associated with hepatotropic virus infection, such as HCV 1.
From the Research
Overview of Porphyria Cutanea Tarda
- Porphyria cutanea tarda (PCT) is a disorder of heme biosynthesis, characterized by an enzymatic defect in the heme biosynthetic pathway 2.
- PCT arises due to the inhibition of uroporphyrinogen decarboxylase (UROD) in the presence of hepatic iron and oxidative stress 2.
- The disease manifests as skin fragility, blistering cutaneous lesions on sun-exposed areas, dark urine, and elevated plasma and urine porphyrins 2.
Factors Contributing to the Development of PCT
- Factors contributing to the development of PCT include alcohol use, hepatitis C virus infection, human immunodeficiency virus, estrogen use, UROD pathogenic variants, and hereditary hemochromatosis 2.
- Iron overload is a critical factor in the development of PCT, and iron depletion is a key component of treatment 3, 4.
Treatment of PCT
- Treatment of PCT includes therapeutic phlebotomy to decrease total body iron levels and low-dose hydroxychloroquine, which reduces hepatic porphyrin content 2, 5.
- Phlebotomy is consistently effective in treating PCT, and its effect is mainly due to the reduction of iron stores 3.
- Low-dose hydroxychloroquine is as effective as phlebotomy in treating PCT, with better compliance and lower projected costs 5.
- The treatment is safe and effective, but has its limits in cases with haemochromatosis (HFE) gene mutations, where iron depletion needs additional phlebotomy 4.
Clinical Manifestations and Relapse
- PCT clinically manifests with increased skin fragility and blistering skin lesions on sun-exposed areas, and can occasionally develop into advanced fibrosis and cirrhosis with hepatocellular carcinoma (HCC) 6.
- Screening for HCC using ultrasound examination is recommended in PCT patients, especially with cirrhosis and advanced fibrosis 6.
- After the achievement of remission of PCT, there remains a potential for relapse, especially when the susceptibility factors are not adequately controlled 6.