Acute intermittent porphyria is an INHERITED condition. It is passed on from generation to generation in what is called an autosomal dominant pattern. This means that it may be passed on from parents to their children; there is a 50% chance that an affected parent will pass the affected gene to each of their children. Both boys and girls stand an equal chance of being affected. The 50% chance of being affected is the same even if the affected person has never had any symptoms of porphyria. Thus, the disease often appears to have skipped a generation. (Please see our Testing and Inheritance page and handy testing leaflet for more information.)
AIP is one of four porphyrias that may present with acute attacks. These attacks are uncommon and are often difficult to diagnose. In AIP only acute attacks occur – the skin is never affected.
The condition cannot be cured, however, symptoms and their severity will vary from patient to patient. Some people will be asymptomatic (without any symptoms) throughout their lives. Most people have only one or a few acute attacks; whereas a minority suffer repeated attacks, sometimes over several years. Attacks occur in about one in five patients, more often in females than males. The most common age for an attack is from the late teens to the early forties and attacks are extremely rare in children before puberty.
Although acute attacks can be very severe, nowadays they are rarely fatal and most people make a full recovery. However, everyone with AIP is at risk of acute attacks, therefore it is vital to take a few simple precautions to reduce the risk of attacks.
For more information on AIP, please see the acute porphyria FAQs.
Variegate porphyria is an INHERITED condition. It is passed on from generation to generation in what is called an autosomal dominant pattern. This means that it may be passed on from parents to their children; there is a 50% chance that an affected parent will pass the affected gene to each of their children. Both boys and girls stand an equal chance of being affected. The 50% chance of being affected is the same even if the affected person has never had any symptoms of porphyria. Thus, the disease often appears to have skipped a generation. (Please see our Testing and Inheritance page and handy testing leaflet for more information.)
Attacks are uncommon and often difficult to diagnose. In addition to acute symptoms, in VP the skin may also be affected. VP may cause areas of skin exposed to sunlight to become fragile, leading to blistering — skin should therefore be protected. In VP, the skin changes and acute attacks may occur at different times.
The condition cannot be cured, however, symptoms and their severity will vary from patient to patient. Most people with VP will never have any problems. Around 3 in 5 of those that do will have skin sensitivity only, while 1 in 5 will have acute attacks only and the remaining 1 in 5 have both acute attacks and skin problems. Everyone with VP should avoid triggers for acute attacks (see third column for more detail).
VP is quite rare in the UK, but is particularly common in South African individuals of Dutch descent.
Although acute attacks can be very severe, nowadays they are rarely fatal and most people make a full recovery. However, everyone with VP is at risk of acute attacks, therefore it is vital to take a few simple precautions to reduce the risk of attacks.
What skin problems can occur in VP?
Porphyrins can build up in the skin at certain times, causing sensitivity in areas exposed to sunlight, particularly the backs of the hands, face and legs, the scalp and the tops of feet (due to wearing sandals). Small blisters can appear. When they break, they leave narrow brown hollows (often called ‘ice pick lesions’.) They gradually fill up and disappear. Occasionally, VP can cause larger blisters that may be mistaken for porphyria cutanea tarda (a skin porphyria). VP can also cause small white dots (milia) which don’t go away.
Skin fragility is common, and scrapes and cuts take time to heal. Wash wounds carefully and protect with a dressing to prevent infection. Hands can be protected with gloves when scrapes are likely. If you have skin problems, you should look after your skin carefully.
Avoid direct sunlight as much as possible, even sunlight that passes through window glass in your home or car.
Clothing: Protect your skin by wearing dark-coloured densely woven clothing with long sleeves, light cotton gloves and a wide-brimmed hat. Not everyone will find this necessary or acceptable; adjust your clothing as it suits you. Many companies provide sun protective clothing (see back page for examples).
Sunscreens: Ordinary sunscreens are not very effective. The ones that help the most are the thick, opaque preparations with high protection factors (often containing titanium dioxide) that block visible light. Dundee cream is designed for skin porphyrias. Your GP needs to prescribe it for you. Your GP/pharmacist will need to contact Dundee Pharmaceuticals (see back page).
In the UK, the SPF (sun protection factor) tells you how effective the sunscreen is for UVB, and the star rating provides a measure of the UVA protection. High star rating sun creams provide limited protection.
For more information on acute symptoms and ways to manage VP, please see the acute porphyrias FAQs and skin safety sections.
Hereditary coproporphyria is also an inherited condition. People with HCP are prone to acute attacks, and can have skin problems during an acute attack.
For more detail on the acute symptoms, please see the acute porphyria FAQs, while for more detail on the skin aspects, please see our cutaneous pages.
ALAD deficiency porphyria, also called plumboporphyria, is an extremely rare condition and in the few cases described is similar to AIP. Please see the above notes on AIP and the acute porphyria FAQs.
Cutaneous (skin) porphyrias
PCT is the most common of the skin porphyrias affecting about one in 25,000 people in the UK (still quite rare), and is the only porphyria which is not always inherited. Very rarely, PCT is inherited. However, most people with PCT did not inherit the disorder and will not pass it on to their children. Here, PCT is secondary to another condition. It can be triggered later in life by heavy drinking, iron tablets, oestrogens, certain drugs or by liver infections.
Most people with PCT acquire / develop it (known as sporadic or Type I PCT), because an excess of iron in the liver, or the systems using iron, slow down the relevant enzyme (uroporphyrinogen decarboxylase – or UROD) and cause a build up of porphyrins.
This is often triggered by alcohol (moderately heavy drinking), though some people are sensitive to iron supplements, artificial oestrogens (found in the pill, HRT and prostate cancer treatment) or other drugs. Viral infections such as hepatitis C and HIV can also trigger it and in 20% of UK patients, it is caused by hereditary haemochromatosis, another genetic condition.
In a small percentage of patients, PCT may be partially due to an inherited mutation in the UROD gene, also called familial (or Type II) PCT. Not all family members who inherit a UROD mutation will develop the condition, as PCT requires the same triggering factors to be present as well.
For more detail on PCT, please see the PCT FAQs and skin safety section.
This is a less common form of porphyria. Like the acute porphyrias it is an inherited disorder that is passed on from parents to their children. However, the inheritance of EPP is rather complex. It is currently believed that the faulty gene, paired with one particular ‘normal’ variant of the gene can cause EPP. In combination with other variants the EPP gene gives no problems.
What causes EPP?
In EPP, there is a shortage of a particular enzyme (ferrochelatase), which normally helps to convert protoporphyrin into haem by adding iron to it. This deficiency leads protoporphyrin levels to build up in the blood. As blood passes through the skin, the protoporphyrin absorbs energy from sunlight which sets off a chemical reaction that can damage the surrounding tissues and causes itching and burning.
The light that protoporphyrin absorbs is different from that which causes ordinary sunburn. Sunburn is usually caused by the shorter wavelengths of ultraviolet light (UVB), but in EPP the skin is more sensitive to longer ultraviolet wavelengths (UVA) and to visible light.
What are the symptoms of EPP?
EPP is rather different from the other cutaneous porphyrias, as it doesn’t usually cause blistering. In sunlight, the skin becomes very painful (itching and burning) and sometimes swells up slightly. Exposure to bright sunlight, for as little as a few minutes in the worst affected patients, causes burning pain in exposed skin, which may be so severe and persistent that it prevents sleep for several nights. The time of exposure to sunlight, before the pain starts, varies from one person to another, as does the time taken to recover once out of the light. It is important to remember that light does not always need to be direct – light reflected off water, sand or snow, or passing through window glass may also cause symptoms.
Some people get reddening of the skin, but many have nothing visibly wrong. Over time, the skin can thicken on the knuckles and there can be scarring on the face.
EPP normally develops in early childhood. An affected baby will often get fractious if taken outside, or put near bright lights, or by a window during daylight. The pain makes some scream. Even when brought indoors, the baby can still be fractious while the skin recovers.
What can be done to relieve the pain?
Patients usually attempt to relieve the pain by cold water or cold compresses. Some have suggested that fanned air helps relieve the pain to a certain extent.
What about treatment?
Unfortunately, there is no easy treatment.
Mostly it is a matter of: avoiding being out in the sun, under bright artificial light or close to a window (tinted film can be attached to windows, very useful in cars); covering up with a hat and light-dense clothing when outside; and using a special sunblock cream (e.g. Dundee cream). Sun block can be mixed with normal cosmetics to get a more realistic colour.
Please see our skin safety page for further information on sunscreens, light protective clothing and window films.
Beta-carotene: Some people respond to high doses of beta-carotene, which is available on prescription. The capsules are taken by mouth and may turn the skin slightly orange. Self treatment is not recommended as foods and some supplements may contain chemicals dangerous in the high doses needed. This medicine is considered to be safe, but may cause tummy upsets in some people. Studies showed some health benefits, eg fewer strokes, but also increased risk of lung cancer in smokers.
Phototherapy: phototherapy involves exposure to artificial ultraviolet light, usually for a few times a week for a few weeks in the spring to allow the skin to thicken slightly and develop a tan. This acts as a natural sunblock and may improve tolerance to sunlight. Please see your porphyria specialist/dermatologist for more information on this treatment.
Clinuvel trials: Clinical trials are currently being undertaken by a company called Clinuvel. The trials are currently in the third phase and so far appear to be delivering positive results. Afamelanotide (trade name SCENESSE®) increases the levels of melanin in the skin and therefore shields against UV radiation (UVR) and the visible light in sunlight that triggers acute photosensitivity. The drug is delivered by a small subcutaneous dissolving implant. Increased pigmentation of the skin appears after two days and lasts up to two months.
Around 100 patients were given either Scenesse or a placebo (12-month period) and were asked to complete a diary of pain/sun exposure. The individual daily pain scores appear to be significantly lower in patients receiving Scenesse compared to those receiving the placebo. The trial results are due to be finalised in the next few months; we will keep you updated on further information.
EPP does not cause acute attacks, so there is no need to stick to the “safe” drugs list. However, it is not advisable to drink excessively, as the combination of alcohol with EPP can affect the liver. Annual blood tests are needed to monitor the liver, as a few people (around 5%) develop liver problems.
Due to the lack of sunlight, EPP patients can suffer from a vitamin D deficiency, so this should be monitored.
Please see our other publications page for links to the British Association of Dermatologists leaflet on EPP and a link to Clinuvel’s information.
Despite being clinically similar to EPP in that both conditions cause phototoxicity, XLDPP is caused by activation of a gene which leads to overproduction and accumulation of the phototoxic enzyme protoporphyrin IX (PPIX) in the blood.
In terms of symptoms, please see the EPP section for more details.
This 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.
As this is such a rare disorder, data is very scarce regarding clinical traits and the resulting impact on quality of life for its sufferers.
Patients with certain gene mutations have a late onset of the condition and are able to manage their lives successfully with photoprotection. These patients regard the impact of CEP on their quality of life to be minimal. However, those who have other gene mutations develop early onset of the condition and their quality of life is severely impaired. They suffer with a wide array of chronic symptoms including severe photosensitivity to all visible light, photophobia, photomutilation, blindness, haemolytic anaemia and osteoporosis, among others.
For some, bone marrow transplantation can be successful; however this treatment is associated with severe complications. Although research is still ongoing, all CEP patients, including those with milder versions, should be regularly monitored for complications and encouraged to protect their skin and eyes at all times from visible light.