Porphyria Cutanea Tarda

• Porphyria Cutanea Tarda is a metabolic disorder affecting heme production, leading to porphyrin accumulation.
• It is primarily characterized by severe skin photosensitivity, blistering, and fragility.
• Common triggers include alcohol consumption, iron overload, hepatitis C infection, and certain medications.
• Diagnosis involves measuring porphyrin levels in urine, blood, and stool.
• Treatment focuses on reducing porphyrin levels through phlebotomy or low-dose antimalarials, and managing underlying triggers.

What is Porphyria Cutanea Tarda?

Porphyria Cutanea Tarda (PCT) is a chronic metabolic disorder caused by a deficiency in uroporphyrinogen decarboxylase (UROD), an enzyme essential for heme production. This leads to an accumulation of porphyrins, intermediate compounds in the heme synthesis pathway, primarily in the liver and skin. These accumulated porphyrins make the skin highly sensitive to light, resulting in characteristic dermatological symptoms.

PCT exists in two forms: Type I (sporadic), acquired and accounting for about 80% of cases, and Type II (familial), an inherited UROD gene mutation. Both present similarly, though familial PCT may appear earlier. The National Organization for Rare Disorders (NORD) estimates PCT prevalence at approximately 1 in 10,000 to 1 in 25,000 people, making it the most common porphyria.

Causes and Symptoms of Porphyria Cutanea Tarda

The underlying cause of porphyria cutanea tarda is an inherited or acquired deficiency in the uroporphyrinogen decarboxylase (UROD) enzyme. While familial PCT involves a genetic mutation, sporadic PCT is triggered by environmental and lifestyle factors inhibiting liver UROD activity. Understanding the causes of porphyria cutanea tarda is vital for management. Common triggers include:

• Alcohol consumption
• Iron overload (e.g., hemochromatosis)
• Hepatitis C virus infection
• Estrogen use (e.g., oral contraceptives)
• Smoking
• HIV infection

The porphyria cutanea tarda symptoms primarily affect sun-exposed skin due to porphyrin photosensitization. These symptoms can significantly impact quality of life and include:

• Fragile skin, easily blistering with minor trauma
• Fluid-filled blisters (bullae) that heal slowly, often with scarring
• Small, white cysts (milia) on affected skin
• Skin darkening (hyperpigmentation)
• Increased hair growth (hirsutism), especially on face and forearms
• Skin thickening (sclerodermoid changes) from chronic exposure

Liver involvement, from mild abnormalities to cirrhosis or hepatocellular carcinoma, can occur, particularly if underlying liver disease is present and untreated.

Porphyria Cutanea Tarda Treatment Options

Effective porphyria cutanea tarda treatment aims to reduce porphyrin levels and manage underlying triggers. The primary goal is clinical remission, involving healing of skin lesions and normalization of porphyrin levels. Treatment is individually tailored.

The two main therapeutic strategies are:

1. Therapeutic Phlebotomy: This involves regular blood removal to reduce iron stores, thereby decreasing porphyrin production. This first-line treatment continues until iron and porphyrin levels normalize.
2. Low-Dose Antimalarials: Medications such as chloroquine or hydroxychloroquine are used for patients unable to tolerate phlebotomy. These drugs facilitate porphyrin excretion, but require low doses to avoid temporary symptom worsening.

Managing precipitating factors is also vital, including:

• Abstaining from alcohol
• Avoiding iron supplements if iron overload exists
• Treating underlying conditions (e.g., hepatitis C, HIV)
• Discontinuing estrogen-containing medications if they are a trigger
• Strict sun protection (clothing, hats, sunscreen)

Regular monitoring of porphyrin levels and liver function is essential during and after treatment to ensure sustained remission and detect recurrence. With proper management, most individuals achieve long-term remission and improved quality of life.