What is it?
The porphyrias are a group of uncommon diseases that cause either disease affecting the skin, disease affecting the nervous system, or both.
Porphyria results from accumulation of porphyrins either in the skin, which results in sensitivity to sunlight, or in the liver, which results in acute attacks of porphyria. Normally, porphyrins are converted from one type of porphyrin to another, in a sequence of chemical reactions, each one under the control of a specific enzyme. The end product of this sequence is haem, an essential component of haemoglobin, which is responsible for transporting oxygen around our body. If one of these enzymes is deficient or defective, there is a build up of porphyrins which may accumulate to toxic levels. In all, there are seven types of porphyria of which four are acute porphyrias, the others affect the skin predominantly.
Porphyria cutanea tarda
The most common type of porphyria is called porphyria cutanea tarda or PCT. PCT does not usually occur until middle age and affects the skin in sun-affected areas causing fluid-filled blisters. Over time the skin becomes scarred, brown and blotchy and fragile. Sometimes excess hair grows in the affected areas. Unlike the other porphyrias, PCT is rarely inherited and is usually triggered by some other factor or condition. Even in cases where it appears to be inherited from a parent, another factor is usually required before it causes symptoms. The most common factor is excessive alcohol consumption but the presence of other diseases such as haemochromatosis, hepatitis C and HIV infection or some drugs, eg oestrogens may precipitate PCT symptoms.
Acute intermittent porphyria
The next most common form of porphyria is acute intermittent porphyria or AIP. AIP causes only neurological symptoms and does not affect the skin. AIP is inherited in an autosomal dominant fashion which means that half of an affected parent's children are likely to have the condition. However, it may appear to skip generations as many people who inherit the disease never get any symptoms. AIP virtually never appears prior to puberty. Affected people get attacks that develop over hours or days and can last for days or weeks if untreated.
The most common symptom is pain in the abdomen, often severe, but the pain may affect other areas of the body as well. Muscle weakness of the arms and legs may occur and in severe cases weakness of the breathing muscles may require the person to be placed on a ventilator. A variety of other symptoms may occur due to various parts of nervous system being affected, these include, loss of sensation, confusion, fits, palpitations, high blood pressure and constipation or diarrhoea. AIP is often precipitated by factors such as drugs (see the list in the links at the end of this article), hormones, starvation and dieting and stress caused by infections, surgery, accidents or even psychological stress.
Erythropoietic protoporphyria
The third most common form of porphyria is erythropoietic protoporphyria or EPP. EPP affects the skin mainly and is unusual in that it often starts in childhood. Children with EPP are unusually sensitive to the sun and develop itching, burning pain and swelling in sun-exposed skin often within minutes of sun exposure. Over time the skin becomes thickened and waxy in appearance and permanent spots, scars and other changes may appear. A small number of affected children also develop liver disease and gallstones and rarely the liver disease can be very serious.
Other forms of porphyria are very rare. Variegate porphyria or VP, (more common in white people of South African ancestry) and hereditary coproporphyria or HCP can both cause neurological symptoms like AIP and skin symptoms like PCT. Aminolevulinate dehydratase deficiency porphyria (ADP) is an extremely rare condition and in the few cases described is similar to AIP. Congenital Erythropoietic Porphyria (CEP) is the rarest of the porphyrias. It is primarily a skin condition and uniquely is inherited as a recessive condition. That means that both parents are asymptomatic carriers.
Measurement of porphyrins and porphyrin precursors in blood, urine and faeces are the main tests for assessing patients with symptoms that may be caused by porphyria. Measurement of enzyme activities in cells and DNA testing for mutations are most useful for assessing people who may be affected but do not currently have symptoms and close relatives of affected persons.
- Measurement of porphobilinogen or PBG in urine is the most important test for diagnosing an acute neurological porphyria.
- Measurement of porphyrins in urine, faeces, red blood cells and blood plasma are used to differentiate the various types of porphyrias that may have the same symptoms.
- Measurement of enzyme activity in red blood cells may be used to identify relatives of persons with AIP who also are potentially affected.
- Identification of individual porphyrias by specialist biochemical and/or genetic testing is available through Porphyria Specialist Laboratories (see the European Porphyria Network (EPNET) link at the end of this article).
Once a person is known to have a particular porphyria, or a relative who carries the same gene but has not yet been affected is identified, there are precautions that can be taken to prevent recurrence or a first attack. For the acute neurological porphyrias i.e. AIP (acute intermittent porphyria), VP (variegate porphyria) and HCP (hereditary coproporphyria) the most important precaution is avoiding using drugs that are known to precipitate attacks. Lists of known and suspected drugs are available (see the links at the end of this article). If attacks occur regularly related to the menstrual cycle then hormone manipulation to change the menstrual cycle may prevent attacks. Strict dieting is not recommended in people with one of the acute porphyrias and, in females, avoidance of the contraceptive pill is advised.
Treatment of acute neurological porphyrias involves identifying and removing any precipitating factors, giving an intravenous infusion of a haem derivative such as haematin or haem arginate and supplying enough nutrition, particularly glucose, by intravenous infusion if necessary. Intensive medical care may be required in severe cases. The National Acute Porphyria Service (NAPS) was commissioned by NHS England in 2012 to provide acute care support and clinical advice to patients with one of the acute porphyrias (AIP, VP or HCP).
People with PCT (porphyria cutanea tarda) need to avoid alcohol consumption. Sun protection with clothing and complete sunblock lotions is also very important. Occasionally, venesection, or removal of blood, may be used. Removal of blood removes iron from the body as excess iron exacerbates PCT. People who cannot tolerate venesection may be treated with chloroquine to help remove excess porphyrins.
Children and adults with EPP (erythropoietic protoporphyria) benefit from sun protection using thick clothing. Conventional sunscreens have limited effectiveness. Treatment with beta-carotene reduces sun sensitivity and skin symptoms.
People with VP and HCP need to take the same precautions as people with AIP to avoid neurological symptoms. They also need sun protection with clothing and complete sunblock lotions if they suffer from sun sensitivity.
1. My mother was diagnosed as having porphyria many years ago but has not had any symptoms since then. Why is this?
It may be that her disease has been quiet all this time. It is also possible that the diagnosis made back then was incorrect. Testing for porphyria many years ago was not as accurate and some people may have been labelled incorrectly.
2. When I look on the internet for information about safe and unsafe drugs different sites use different classifications and the lists are not the same. Why is this?
Information on the safety of drugs in porphyria is incomplete. Porphyria is a rare disease and many new drugs have been introduced in recent years. Thus it is often not possible to be sure that a drug is safe until it has been used safely in many patients with porphyria and this may take years to establish.