Brief overview: Porphyria
- Symptoms: Depending on the form, severe abdominal pain, gastrointestinal problems, muscle weakness and paralysis, cardiovascular problems, high photosensitivity of the skin, reddish urine
- Forms: There are seven different forms, four of which are acute, i.e. lead to very sudden symptoms.
- Causes: Porphyria is caused by changes in the genetic material; triggers include alcohol, certain medications and infections.
- Treatment: The most important thing is to consistently avoid the triggers (e.g. alcohol, medication); depending on the form, various medications and consistent skin protection can also help.
- Progression: Varies depending on the form, but a largely normal life is usually possible if those affected consistently observe certain precautionary measures and avoid the triggers
- Prevention: As the disease is genetic, it is not possible to prevent it. However, flare-ups can often be prevented with simple measures.
What is porphyria?
The term metabolism describes the sum of all biochemical processes in the body in which substances are built up, broken down and converted. Enzymes are involved in these processes. These are specialized proteins that each process one step in the reaction chain.
Many different metabolic pathways take place in the human body – one of them is the formation of what is known as heme. This is a chemical compound that the body needs, among other things, for red blood cells and the red blood pigment they contain.
Due to their chemical structure, these precursors are also porphyrins and have given porphyrias their name. Porphyrins accumulate particularly in the skin and liver.
Why is the porphyrin heme important?
Heme is an important component of hemoglobin – the red blood pigment in red blood cells. Hemoglobin is made up of a protein complex with a central heme group. The iron ion contained in haem binds molecular oxygen. This enables the red blood cells to supply the organism with oxygen via the blood.
Porphyria: Frequency
There are a total of seven different forms of porphyria, but only two, porphyria cutanea tarda (PCT) and acute intermittent porphyria (AIP), occur with any significant frequency in adults. Around two in 100,000 people suffer from PCT and around one in 1,000,000 people suffer from AIP.
Erythropoietic protoporphyria is the third most common porphyria overall: around one in 200,000 people are affected. All other forms are very rare.
What are the symptoms of porphyria?
Symptoms of acute intermittent porphyria (AIP)
Acute intermittent porphyria is the most common acute porphyria. Women are affected three times more frequently than men. As a rule, this form of porphyria only becomes noticeable between the ages of 20 and 40. Acute intermittent porphyria is characterized by a variety of symptoms, which is why it is often difficult for doctors to make the correct diagnosis.
The disease primarily causes acute abdominal pain as well as neurological and psychiatric symptoms. As the term intermittent suggests, these often occur in episodes. Such acute attacks are usually triggered by alcohol, medication, hormonal changes such as pregnancy and menstruation, stress or a lack of carbohydrates due to dieting or fasting.
An acute attack usually lasts one to two weeks. If symptoms of paralysis occur, this period may be significantly longer.
Typical symptoms of an acute attack are
- Fever
- Vomiting and chronic constipation that is difficult to treat
- Reddish urine that becomes darker after a while (dark stains in the underwear!)
- Neurological symptoms such as incomplete or complete paralysis, muscle weakness and disorders of the sensory organs and sense of balance (sensory disorders)
- Mood swings, delusions, coma and states of confusion (delirium)
- Cardiovascular problems such as rapid heartbeat (tachycardia) and high blood pressure (hypertension)
Symptoms of porphyria cutanea tarda (PCT)
However, problems usually only occur when the liver is heavily stressed. The heme precursors (porphyrins) then accumulate in the liver, enter the bloodstream and thus reach the skin. The result is severe photosensitivity: the UV rays in sunlight cause blisters to form on unprotected areas of the skin, for example on the hands, face and neck.
In addition, some sufferers are excessively hairy on the forehead, cheeks and around the eyes (hypertrichosis). The urine may be brown-red in color due to the porphyrins excreted above it.
Symptoms of erythropoietic protoporphyria (EPP)
EPP begins in childhood. In this form of porphyria, the skin is extremely sensitive to light, as the accumulating porphyrins form oxygen radicals in the skin under the influence of sunlight. These are aggressive chemical compounds that lead to burn-like symptoms with itching and pain.
What forms of porphyria are there?
The formation of heme takes place in eight different reaction steps. A specific enzyme is required for each one. An enzyme defect in seven of these eight enzymes leads to porphyria.
Experts therefore distinguish between a total of seven different forms of porphyria. Four of these are acute, while the other three are non-acute variants. Acute means that the symptoms typical of the disease occur very suddenly.
The four acute forms of porphyria are
- acute intermittent porphyria,
- porphyria variegata,
- the very rare Doss porphyria.
The three non-acute types of porphyria, on the other hand, do not cause acute abdominal pain and mainly affect the skin. They include:
- Porphyria cutanea tarda,
- erythropoietic protoporphyria and
- the rare congenital erythropoietic porphyria (Günther’s disease).
Heme formation takes place mainly in the bone marrow and to a lesser extent in the liver. Therefore, the seven forms of porphyria can also be classified according to where the heme precursors mainly accumulate due to an enzyme defect:
- hepatic porphyrias (liver): acute intermittent porphyria, porphyria variegata, hereditary coproporphyria, Doss porphyria, porphyria cutanea tarda
Causes and risk factors
All forms of porphyria are caused by a change (mutation) in the part of the genetic material that contains the building instructions for one of the enzymes involved in heme formation. In most cases, one parent passes on the mutation to their offspring. Inheritance is usually autosomal dominant.
However, porphyria usually only manifests itself when certain external influences are added, such as alcohol consumption, nicotine consumption, certain medications, hormonal contraceptives, stress or infections. Infections with the hepatitis C virus and the human immunodeficiency virus (HIV) play a role in porphyria cutanea tarda.
In some cases, poisoning (such as lead poisoning) can also lead to porphyria.
Examinations and diagnosis
Due to the complexity of the disease and the wide range of symptoms, it is sometimes difficult even for an experienced doctor to make the correct diagnosis. The typical porphyria symptoms and information about similar clinical pictures in relatives are particularly important.
Other important diagnostic steps in the clarification of porphyria depend on the respective form of porphyria.
Acute intermittent porphyria
In acute intermittent porphyria, the urine turns red to dark red if it stands for a long time. However, this test is only successful in two thirds of cases.
Another test is the reverse Ehrlich aldehyde test. The doctor adds a drop of urine to one milliliter of a special solution, the so-called Ehrlich reagent. If acute intermittent porphyria is present, the result is a cherry red color.
It is characterized by an enlarged liver, which is usually palpable. An ultrasound examination usually reveals a fatty liver or liver cirrhosis. Sometimes a liver biopsy is informative. The doctor takes a small tissue sample with a hollow needle under local anesthesia.
Erythropoietic protoporphyria
The symptoms described often give rise to the suspicion of erythropoietic protoporphyria. This suspicion can be confirmed by a blood analysis. The doctor examines the blood for free protoporphyrin, a precursor of heme. Protoporphyrin can also be detected using a stool sample.
Treatment
Acute intermittent porphyria
With a confirmed diagnosis and severe attacks, it is often necessary to monitor patients in intensive care, as there is a risk of respiratory paralysis. It is particularly important to eliminate triggers of an acute attack, for example by discontinuing certain medications.
A causal therapy has also been available for the first time since 2020. The active ingredient inhibits the enzyme that enables the very first step of haem production. This prevents the harmful intermediates responsible for porphyria symptoms from forming and accumulating.
Porphyria cutanea tarda
In the case of porphyria cutanea tarda, it often helps to consistently avoid triggering factors such as alcohol and oestrogen (as in the pill). In addition, those affected should protect themselves from the sun with sun protection ointments and clothing.
Chloroquine therapy is recommended for severe cases. Chloroquine, originally a drug used to treat malaria, binds the porphyrin. In this form, the body is able to excrete it via the kidneys.
As those affected should avoid sunlight, they often develop a vitamin D deficiency, as vitamin D is mainly formed in the skin when exposed to sunlight. In this case, the doctor will also prescribe a vitamin D preparation.
Erythropoietic protoporphyria
In rare cases, the symptoms of erythropoietic protoporphyria can be alleviated by taking beta-carotene, an orange-colored natural pigment. It helps to render the reactive oxygen produced by light in the skin harmless and improve the symptoms. When taken, the skin usually turns a light orange color.
Some people with EPP suffer from impaired liver function. Those affected are then given medication to support the liver. In around two to five percent of cases, cirrhosis, a chronic disease of the liver, develops. In this case, a liver transplant may be necessary.
EPP also frequently leads to a vitamin D deficiency, which can be compensated for with a vitamin D preparation.
Course of the disease and prognosis
Acute intermittent porphyria
Most patients who suffer one or more relapses recover completely and only need to take a few precautions. In less than ten percent of cases, frequently recurring relapses occur. If symptoms of paralysis occur, it often takes several weeks to many months for them to disappear.
Erythropoietic protoporphyria
Porphyria cutanea tarda
The course of this form of porphyria is generally favorable, but depends on how severely the liver is damaged and whether those affected consistently avoid certain medications as triggers.
Prevention
Porphyria cannot be prevented as the disease is genetic. However, those affected can do a lot themselves to avoid or alleviate porphyria symptoms.
Acute intermittent porphyria
Most acute attacks can be avoided by taking consistent precautions.
Alcohol: It is advisable for those affected to avoid alcohol as much as possible.
Diet: Diets or fasting sometimes lead to an acute flare-up. It is therefore very important to maintain a regular diet and keep your weight down. Patients with severe porphyria who have already suffered several attacks should seek support from their doctor and a nutritionist.
Porphyria cutanea tarda and erythropoietic protoporphyria
With both forms of porphyria, it is important to avoid the sun as much as possible:
Sun cream: Normal sun creams are not suitable as they absorb light in the UV range, but not the blue component of visible light, which also damages the skin. Those affected should therefore only use special sun creams based on titanium dioxide and zinc oxide, as these protect against UVA, UVB and visible light.
