What are the porphyrias?

The porphyrias are a group of metabolic conditions which can be either genetic or acquired. The porphyrin pathway is involved in haem synthesis. Haem is the red pigment in haemoglobin in blood cells and carries oxygen in the blood. A deficiency or block of one of the enzymes in the porphyrin pathway results in a build-up of the corresponding precursor protein or intermediate molecule.

The porphyrias can be broadly classified as acute or cutaneous.

What is porphyria cutanea tarda?

Porphyria cutanea tarda (PCT) is the most common type of porphyria.

The symptoms of PCT are limited to the skin. It does not cause people to become acutely unwell, as in the acute types of porphyria.

Who gets and what is the cause of porphyria cutanea tarda?

PCT is caused by a defect in a liver enzyme uroporphyrinogen decarboxylase (UROD).

It is hereditary in one-third of patients when there is usually a family history of the condition and symptoms begin in early adult life.

In other patients, PCT is due to underlying liver disease and patients present with symptoms in their 40s and 50s. The liver diseases associated with PCT include:

• Excessive alcohol consumption
• Hepatitis B and C
• Iron overload from haemochromatosis, multiple blood transfusions, or iron supplements

Hormones such as oral contraceptive or hormone replacement therapy may also trigger PCT.

Renal dialysis patients can also develop PCT as they cannot excrete the porphyrins.

Rarely, other conditions such as systemic lupus erythematosus (SLE) and human immunodeficiency virus (HIV) infection can cause PCT.

Many patients have more than one risk factor.

What are the clinical features of porphyria cutanea tarda?

Excess porphyrin in the skin results in photosensitivity. Individuals with PCT present with increasingly fragile skin on the back of the hands and the forearms. Other sun-exposed sites such as the face, scalp, neck, and arms may also be affected.

Features include:

• Slow to heal crusted erosions following minor injuries
• Fluid or blood-filled blisters
• Postinflammatory pigmentation and cysts (milia)
• Increased sensitivity to the sun
• Scleroderma-like changes on the neck, face or chest.

Characteristically, the urine is darker than usual, with a reddish or tea-coloured hue.

How is porphyria cutanea tarda diagnosed?

PCT may be clinically suspected but should always be confirmed by laboratory tests.

• Examination of the urine with a Wood's lamp may reveal coral pink fluorescence due to excessive porphyrins.
• A skin biopsy can be helpful to distinguish PCT from other blistering conditions. The skin changes are identical to variegate porphyria and hereditary coproporphyria.
• Blood, urine and faeces need to be sent to analyse the porphyrin levels, which will be elevated. In PCT, the presence of elevated isocoproporphyrin in the faeces is diagnostic. The specimens need to be protected from light with aluminium foil to ensure testing is accurate.

Tests to determine the cause of the porphyria may include:

• Blood count, liver function, and kidney function tests
• Iron studies (ferritin level)
• Hepatitis B, C, and human immunodeficiency virus (HIV) serology
• Transferrin saturation and genotyping for hereditary haemochromatosis
• Tests for cutaneous lupus erythematosus and diabetes
• Urodecarboxylase (UROD) enzyme levels and genetic tests

What is the treatment of porphyria cutanea tarda?

Treatment of an underlying liver problem may result in the resolution of PCT and may include reducing alcohol consumption, stopping oestrogen or hormone treatment, avoiding excessive iron intake, or antiviral treatment for underlying hepatitis C.

• Clothing when outdoors should include long sleeves, gloves and a hat.
• Sun protection with an opaque sunscreen that blocks visible light, such as zinc. Fake tan (containing dihydroxyacetone) can also provide some protection.
• Venesection is the main treatment for PCT. Approximately 500 ml of blood is removed every 2–4 weeks until the iron stores have returned to normal. This uses up excess iron by making new red blood cells.
• If venesection cannot be done, as in elderly patients or those who are anaemic, antimalarial tablets such as hydroxychloroquine are given in low dose to allow the porphyrins to be excreted more easily.

What is the outlook for porphyria cutanea tarda?

Once clear, PCT is unlikely to recur unless the underlying risk factors have not been addressed. If PCT is ongoing, there can be an increased risk of liver cancer.