What is porphyria cutanea tarda (PCT) and how is it treated and diagnosed?

Porphyria Cutanea Tarda: Diagnosis and Treatment

Porphyria cutanea tarda (PCT) is the most common type of porphyria characterized by deficient uroporphyrinogen decarboxylase (URO-D) activity, resulting in characteristic skin lesions that can be effectively treated with phlebotomy or low-dose hydroxychloroquine. 1

What is PCT?

PCT is a metabolic disorder of heme biosynthesis caused by reduced activity of the enzyme uroporphyrinogen decarboxylase (URO-D) in the liver. It can be categorized into two main types:

• Sporadic PCT (most common): URO-D activity is decreased to about 50%, primarily affecting hepatocytes
• Familial PCT: Inherited in an autosomal dominant pattern, with enzyme defects present in multiple cell types 1

The URO-D deficiency leads to accumulation of porphyrins in the skin, causing photosensitivity and characteristic cutaneous manifestations.

Clinical Presentation

Typical skin findings include:

• Bullae (blisters) on sun-exposed areas, particularly hands and face
• Skin fragility and erosions
• Hyperpigmentation
• Hypertrichosis (excessive hair growth)
• Scarring 1, 2

The disease typically presents in the 5th to 6th decade of life and is slightly more common in males 2.

Diagnostic Testing

Diagnosis requires biochemical confirmation as clinical features alone are not specific enough 1. The diagnostic approach should include:

1. Biochemical testing (first-line):

   • Elevated levels of serum and urinary porphyrins
   • Demonstration of URO-D deficiency
   • Pattern analysis of porphyrin excretion in urine, feces, and blood 1

2. Genetic testing (second-line):

   • Should NOT be used for initial diagnostic screening
   • Only performed after biochemical testing confirms increased porphyria-related markers
   • Useful for genetic counseling in familial cases 1

Precipitating Factors

Several factors can trigger or exacerbate PCT:

• Hepatitis C virus (HCV) infection
• Alcohol consumption
• Iron overload/hemochromatosis (HFE gene mutations)
• Estrogen use
• HIV infection
• Smoking 1, 2, 3

Treatment Approach

Treatment of PCT focuses on three key elements:

1. Avoidance of triggering factors:

   • Discontinue alcohol consumption
   • Avoid estrogens and other triggering medications
   • Minimize sun exposure 4

2. Iron depletion:

   • Phlebotomy: Removal of 450-500 mL of blood every 2 weeks until serum ferritin normalizes
   • Particularly important in patients with hemochromatosis gene mutations 2, 4

3. Porphyrin elimination:

   • Low-dose hydroxychloroquine: 100 mg twice weekly
   • Works by increasing porphyrin excretion 2, 4, 5

Both phlebotomy and hydroxychloroquine are equally effective and safe treatment options 2. The choice between them should be based on:

• Presence of iron overload (favors phlebotomy)
• Hepatitis C-related liver disease (favors phlebotomy)
• Patient comorbidities and preferences 5

Monitoring and Follow-up

• Liver assessment is essential as PCT is associated with liver disease
• Screening for hepatocellular carcinoma using ultrasound is recommended, especially in patients with cirrhosis or advanced fibrosis 2
• Long-term follow-up is necessary to monitor for disease relapse 5
• Relapse rates may be higher after hydroxychloroquine treatment compared to phlebotomy 2

Associated Conditions Requiring Evaluation

All patients with PCT should be screened for:

• Hepatitis C virus infection
• Hereditary hemochromatosis
• Liver disease (consider liver biopsy if clinically indicated)
• HIV infection in high-risk individuals 5, 3

Treatment of Underlying Conditions

• Treat hepatitis C with direct-acting antivirals
• Address alcohol use disorder
• Manage iron overload in hemochromatosis 2, 3

By addressing both the porphyria and its underlying triggers, most patients can achieve complete remission with appropriate treatment.