Erythropoietic protoporphyria (EPP) is a rare hereditary disease that is classified as a porphyria. In this condition, protoporphyrin accumulates in the blood and liver as a precursor of heme. If the liver is involved, the disease can be fatal.
What is erythropoietic protoporphyria?
Erythropoietic protoporphyria is characterized by an accumulation of protoporphyrin in erythrocytes. It is a very rare hereditary disorder belonging to the group of porphyrias. It occurs with a frequency of 1 per 100,000 in newborns. In EPP, the chelation of an iron II ion with protoporphyrin is disturbed. As a result, protoporphyrin accumulates in the blood vessels and partially in the liver. It is responsible for the severe photosensitivity of affected individuals. In most patients, exposure to sunlight without visible skin changes causes burning and itching of the skin. Since nothing is visible, the affected persons are usually not believed to have the symptoms. There is a high pressure to adapt, which leads to hiding the pain. The first symptoms appear between the first and the tenth year of life. In ten percent of cases, the liver may also be involved.
Causes
Erythropoietic protoporphyria is caused by decreased functioning of the enzyme ferrochelatase. Ferrochelatase is responsible for the incorporation of the iron II ion into the porphyrin ring of protoporphyrin. This produces the red blood pigment heme, which is responsible for oxygen transport in erythrocytes. However, the formation of heme is deficient, and at the same time protoporphyrin accumulates in the erythrocytes, in the blood vessels and partially in the liver. The enriched protoporphyrin absorbs sunlight in the range of wavelengths from 400 to 410 nanometers. When the energy is released, oxygen radicals are produced that can attack the affected tissue. The result is itching and burning of the exposed skin. The reduced activity of the enzyme ferrochelatase is caused by a mutation of the gene responsible for it. The inheritance of the disease is autosomal dominant. However, cases of autosomal recessive inheritance also occur. In two cases so far, a mutation of a gene on the sex-related X chromosome has been identified. The mode of inheritance does not always follow the typical pattern of dominant/recessive inheritance. To date, approximately 70 mutations have been described that can cause EPP. The gene for ferrochelatase on the long arm of chromosome 18 is said to be mainly affected. However, other alterations affecting the heme biosynthesis system may also lead to erythropoietic protoporphyria.
Symptoms, complaints, and signs
Erythropoietic protoporphyria often manifests as severe pain in the exposed areas after only a few minutes of sun exposure. In this case, the tolerance level varies from person to person. It depends on how much protoporphyrin is stored. In some patients, even artificial light sources are dangerous. In the acute phase, however, no external visible symptoms appear. Patients complain only of severe and stabbing pain in the exposed areas. At the same time, patients also become highly sensitive to touch. Any slightest stimulus such as a draft of air or cold is perceived as extremely painful. According to patients, it feels as if hot needles pierce the skin or burning ants run under the skin. If the stay in the sunlight is prolonged due to external coercion, swelling may occur after a delay of several hours. In parallel, the skin turns deep red. This condition may last for several weeks. Permanent changes in the skin can manifest themselves in waxy scars, deviating pigmentation or coarsening of the relief of the skin. Ten percent of affected individuals may develop life-threatening liver changes if the liver is unable to adequately break down porphyrias. In these cases, protoporphyrin is also stored in the liver, eventually leading to life-threatening cirrhosis.
Diagnosis
Because of the rarity of erythropoietic protoporphyria, a diagnosis of the disease is often made very late. On average, 16 years elapse for this after the first symptoms appear.Outsiders often do not take the children’s complaints seriously, especially since the disease is not very well known even in general medicine. A confirmed diagnosis can only be made by a blood test for porphyrins.
Complications
If the liver is also affected in this disease, death will occur in most cases if treatment is not initiated. In most cases, relatively severe pain on the skin occurs in this case even after a very short exposure to the sun. The pain can become unbearable, and in many people artificial light can also cause pain. As a result, the patient’s everyday life is extremely limited and the quality of life decreases considerably due to the disease. It is no longer possible for the affected person to be outdoors in daylight without pain and without wearing clothing. Even light touch can cause severe pain, which can lead to sleep problems. The irradiated areas also show swelling and redness. Often these are also other pigmented, so that it comes to aesthetic discomfort. It is not possible to cure the disease, so the affected person must avoid direct sunlight for the rest of his life. In severe cases, a liver transplant may be necessary to prevent the patient’s death. Furthermore, the affected person must stay in dark and cows rooms, which has an extremely negative effect on the psyche and the quality of life.
When should one go to the doctor?
In any case, this disease must be examined and treated by a doctor. There is no self-healing and the disease can lead to serious and especially dangerous complaints of the skin or internal organs. As a rule, a visit to the doctor is necessary if the affected person suffers from severe pain after direct exposure to the sun. Artificial light sources can also cause these symptoms in some sufferers. The pain is burning or stabbing. Many sufferers are also very sensitive to touch. This symptom may also indicate the disease and should be investigated. Furthermore, swelling or discoloration of the skin also occurs. In addition to the symptoms, many affected individuals also suffer from unusual pigmentation. To avoid damage to the liver, a doctor should always be consulted. Diagnosis of the disease can be performed by a dermatologist or by a general practitioner. Since it is not curable, the affected person must protect himself from direct light exposure to avoid the symptoms. Furthermore, sufferers are also dependent on regular checks of their internal organs.
Treatment and therapy
Erythropoietic protoporphyria is not curable. In this regard, the most important therapy when symptoms appear is for the patient to stay in cool and dark rooms for some time. Then the symptoms subside by themselves. Prolonged contact with sunlight should be avoided as much as possible. Furthermore, liver and blood values should be constantly examined. In the case of advanced liver cirrhosis, a liver transplant may be necessary. Psychological care is often recommended as an accompanying measure, since the patient’s long suffering and social constraints can lead to severe limitations in quality of life. If the liver is not involved, there is a normal life expectancy.
Outlook and prognosis
Since this is a hereditary disease, no causal treatment can be given in this case, only a purely symptomatic treatment. A complete cure cannot be achieved in this case, so the affected person will suffer from the symptoms of the disease throughout his or her life. If the disease also affects the liver, the affected person may die. The patient must cool down and go to dark rooms to relieve the discomfort. Furthermore, regular examinations of the blood values are necessary, since the liver must be permanently monitored. The daily life of the affected person is therefore significantly restricted. If the disease remains completely untreated, the patient usually dies. The quality of life is generally severely restricted. In some cases, the transplantation of a liver is necessary to alleviate the symptoms. If the liver is not affected by the disease, life expectancy is usually not reduced.In some cases, patients may also experience psychological distress or depressive moods because they are unable to participate in ordinary daily life and are therefore excluded from many social settings.
Prevention
Erythropoietic protoporphyria cannot be prevented because the disease is genetic. However, consistent avoidance of sunlight can prevent the onset of symptoms. According to some reports, symptoms could be prevented by administering high doses of beta-carotene. However, the effect has not been proven. Sunscreen with a high SPF in the UV-A range is recommended for sun protection.
Aftercare
Since this is a hereditary disease, it cannot be treated causally, but only purely symptomatically. Therefore, there can be no complete cure, so the affected person is primarily dependent on early and rapid diagnosis. A self-healing can also not occur. If the affected person wishes to have children, genetic counseling and testing may be useful. This may prevent the disease from being passed on to descendants. If this disease is not treated, the worst case scenario may be the death of the affected person. In this disease, the affected person should stay in cool and in dark rooms. This is the only way to prevent the symptoms and complications. Further measures of a treatment or an aftercare are not possible in this case. In case of severe damage, liver transplantation may be necessary. After such a transplant, the patient should take it easy and rest. The liver should be particularly spared. In most cases, this disease results in a reduced life expectancy of the affected person.
What you can do yourself
Sufferers must learn to talk openly about their disease. Since their complaints are usually not visible, the patient’s credibility is often doubted by relatives or other fellow human beings. Nevertheless, the patient can make himself heard through his own appearance and the form of communication and should not be dissuaded from doing so even if other people have doubts. It is helpful to point out the complaints again and again and to ask for medical support. Erythropoietic protoporphyria is manifested by increased sensitivity to light. The affected person can therefore comprehensively protect himself from unwanted exposure to light in everyday life to alleviate his symptoms. Wearing clothing that covers as many parts of the body as possible and using accessories such as hats, caps or scarves are particularly recommended. Since the disease is associated with severe pain, sunshades have also proven effective for many patients in order to provide good protection for the skin areas on the face. A long stay outdoors during the day is not recommended. Nevertheless, in order to maintain the quality of life, sufficient leisure activities should take place, which bring variety and increase the zest for life. An adequate supply of oxygen should also be provided, as it is important for maintaining health.
