Porphyria Dr Trisha Macnair Although uncommon, porphyria is quite well known because it's thought to have been the cause of the 'madness' of George III. However, this is a distorted picture of a condition that rarely causes extreme illness.

In this article

What causes it? What are the symptoms?

What's the treatment? Advice and support

Chemicals in the body called porphyrins are key to producing haem - a molecule that's vital in red blood cells for carrying oxygen. Two substances known as porphyrin precursors are converted into haem, via a series of steps, each step controlled by a particular protein enzyme.

In porphyria there is a deficiency of these enzymes, so the process is blocked and porphyrins (and their precursors) accumulate to toxic levels in the body.

Most types of porphyria are due to an inherited enzyme defect but some (including the most common, PCT) develop during life.

Drug treatments are one of the major causes of acquired porphyria and are also a major trigger of acute attacks in inherited porphyria.

There are at least seven types of porphyria. Each is caused by a slightly different enzyme deficiency and has a different pattern of symptoms.

The different types are usually classified as acute or non-acute. People with acute porphyria experience episodes of pain and disruption of the nervous system that may develop very rapidly, over several hours, and may be severe, causing a wide range of symptoms throughout the body. Acute types include:

• Acute intermittent porphyria (AIP), also called Swedish porphyria - the most severe type. Attacks may be triggered by factors such as drugs and medicines, alcohol, dieting, and hormonal changes.
• Variegate porphyria (VP), also called South African genetic porphyria - there may be skin symptoms as well as acute attacks.
• Hereditary coproporphyria (HC) - can lead to skin photosensitivity as well as acute attacks.
• ALAD-deficiency porphyria (also called plumboporphyria or PP) - very rare.

An acute attack is triggered when levels of porphyrins and porphyrin precursors escalate. This may be due to drugs that interfere with porphyrin metabolism in the body, alcohol, smoking, infection and reduced calorie intake. Pregnancy may also trigger an attack as hormone levels change, while some women have regular attacks prior to their periods.

Symptoms include abdominal pain, stomach cramps, nausea, vomiting and constipation. There may be pain elsewhere in the body, especially in the back and limbs, and muscle weakness.

In extreme cases there may be heart palpitations and a rapid heartbeat, high blood pressure, anxiety, confusion, seizures and paralysis.

An acute attack of porphyria can be fatal, although this is very rare. Severe attacks need to be treated in hospital but mild attacks may go unnoticed or be misdiagnosed.

In non-acute porphyria, the primary problem is with the skin. The most common type is porphyria cutanea tarda (PCT, cutaneous hepatic porphyria or symptomatic porphyria). It's acquired, probably as a result of factors including alcohol, iron, oestrogens and hepatitis infections that combine to cause an enzyme deficiency in the liver.

Erythropoietic protoporphyria (EPP or erythrohepatic porphyria) is an inherited porphyria that causes skin problems, although the liver may be involved in later life. Congenital porphyria (CP, Gunther's disease or erythropoietic porphyria) is extremely rare and may cause severe skin problems.

There may be a variety of skin problems in porphyria. Sensitivity to sunlight plays a key part. In PCT, VP and HC, skin exposed to light (such as hands, feet and face) becomes fragile and develops blisters and sores. The skin may be easily damaged, and even the slightest knock causes it to break open, while healing is slow.

These changes tend to develop during adult life. Chronic damage leads to thin, darkened and scarred skin that may become unusually hairy.

In EPP and CP the skin problems start in early childhood and tend to be more severe. Reaction to the sun is swift, with burning and stinging occurring soon after exposure.

There's no cure for porphyria but careful control of trigger factors means most people lead a normal life.

A large number of medicines, including many common antibiotics and sleeping pills, may precipitate an acute attack of porphyria. In general, people with porphyria should:

• Only take medication when absolutely necessary
• Never take a new medicine unless it's been checked as suitable for people with porphyria
• Be careful with over-the-counter treatments, such as vitamins or herbal therapies
• Inform doctors they have porphyria before being given anaesthetic

For those whose skin is affected, avoiding the sun and protecting the skin from injury is essential. Meticulous skin care can reduce long-term damage. It's vital for those with PCT to avoid triggers such as alcohol or certain medicines (such as the contraceptive pill).

Treatment using venesection (removal of a unit of blood at regular intervals) may also help in PCT.

All the genetic problems causing porphyria have now been identified, and genetic testing for carriers can now be done.

British Porphyria Association

Tel: 01474 369231
Email: helpline@porphyria.org.uk
Website: www.porphyria.org.uk

This article was last medically reviewed by Dr Rob Hicks in July 2006.