User:Apers0n/EPP

Translation from http://de.wikipedia.org/wiki/Erythropoetische_Protoporphyrie

The erythropoetische Protoporphyrie (EPP) is a metabolic disturbance from the group of the Porphyrien. The erythropoetische Protoporphyrie is based on a rare genetic defect, which affects the blood formation. The illness accompanies with an extremely painful (suns -)luminous sensivity, why a "sun allergy" is often falsely assumed. The first symptoms mostly show up between first and 10. Lebensjahr and express themselves in avoidance behavior in relation to sunlight and hyperactivity of the children. Since with most concerning no visible symptoms on the skin arise, the patients often one does not believe. The adjustment pressure resulting from it leads, despite pain, frequently to hiding the symptoms (Dissimilieren). Beside the Hautsymptomen liver complications arise in up to 10 % of the cases, which can run deadly.

The name "Erythropoeti Protoporphyrie" means that the education (Greek: Poiesis) of the red blood corpuscles (grch.: Erythrozyten) is concerned. The chemical substance Protoporphyrin, a forerunner enriches itself among other things. the red blood coloring material, in the red blood corpuscles, the blood plasma, the liver and the cell walls of the containers off. The circular Protoporphyrin is responsible for the light incompatibility.

Cause
A cause of the EPP is the partial loss of the function of an enzyme, the Ferrochelatase. The Ferrochelatase is responsible for the last step of the production of the red blood coloring material, the Haemgroup. The Haem group results from the installation of an iron atom in the Protoporphyrinring, their major task is the transport of the oxygen in the blood. If the activity of the Ferrochelatase is e.g. reduced by a mutation, sufficient iron atoms cannot be inserted and the forerunner substance, names the giving Protoporphyrin, enriches itself in the red blood corpuscles.

Light incompatibility (photo toxicity): Protoporphyrin is able to take up light of the wavelength 400-410 nanometers (UV-A radiation and violet portion of the visible light). From delivery of the energy result oxygen radicals, which can attack and destroy structures in the fabric (oxidative stress). Inflammation reactions and inclusion of the immune system are the result (itching and swelling that the sunlight suspended skin).

Symptoms
Few minutes sunlight are sufficient: Dependent on the weather and the personal tolerance threshold opposite sunlight sometimes few minutes begin to itch the exposed skin areas after the sun exposition to burn kribbeln and. The tolerance is stood from patient some concerning only few minutes sunlight to patient differently, other several hours. Besides can a preceding stay in the sun, which Menstruation increase among other things factors sensitivity.

Artificial sources of light: Particularly to note it is that in extreme cases also artificial light will not stand! This can lead bspw. with operations to heavy burns.

No outside indications: If the concerning of the personal threshold dose at light was suspended, also different attractions are felt such as draft of air or cold weather than unpleasantly and painfully; Wind can aggravate the symptoms. Particularly nose, lips and handruecken are described as very sensitive, with some patients become the meat under the fingernails palely and impact-sensitively. If the stay in the sun cannot be broken off, the symptoms increase to an extremely painful, burning heat feeling, which can be heavily described (quotations: "as be called needles, which puncture the skin", "burning ants under the skin"). The concerning try the symptoms by cooling too lindern, articles made of metal or glass by the Hautstellen concerned are kept frequent or with (flowing) cold water or moisten winding the places cooled. Warmth, also (the own!) Body warmth, is felt as painful heat. In this stage no changes of the skin are visible, in some cases can a spotted turning red or the education of small blisters on the skin be observed with most concerning. Frequently accompaniments arise such as sleeplessness, motor unrest, provokingness or aggressiveness.

Swelling: If the stay in the sun (force-measured) lasts to for a long time, usually over night, edema-like swelling of the skin areas arise, which were exposed to the sun. The border of the sun tolerance, until swelling arise, is individually different also here. The water storages often accompanied of a low-red discoloration of the skin and to be able over days until several weeks existing to remain. In very extreme cases even the fabric under the skin portions in can be pulled and be made necessary a plastic surgical interference.

Durable changes: Some concerning develop exposed skin portions durably visible changes to that chronically the sunlight like the coarsing of the skin relief around nose and mouth, folds, deviating pigmentation or small, waxlike scars.


 * Characteristics

Most concerning do not develop any visible symptoms on the skin, even if strong pain began Only those are the light suspended Hautstellen concerned.

In addition, the symptoms arise particularly in the spring and summer, can by reflecting snow, in regions with increased radiation intensity like to the high mountains or reflecting water surfaces being released. Also indirect radiation, as it arises under sun screens or on cloudy days, can lead to the outbreak of the symptoms. The stay behind windowpanes does not offer sufficient protection, since visible light is a main trip of the symptoms. For the same reason most sun creams are ineffective, since they filter above all UVBLEACHED.

In some cases the symptoms partly or completely disappear during the pregnancy, return however to the birth of the child again. This refers to an influence of hormones on the symptoms of the EPP, the mechanism is however not yet clarified.

There are some unverstandene cases of patients, whom of symptom-free stays in countries with high sun intensity such as Brazil, Egypt and India report, while they have problems with the sun in Europe regularly.

Liver involvement
Protoporphyrin is soluble not in water and cannot be removed therefore not with the urine from the body. In the liver the Protoporphyrin is converted into a transportable form and separated then with the chair. If too much Protoporphyrin from the blood is washed into the liver, the capacity of the organ can be overloaded and it comes to crystalline storages in the liver cells. These deposits damage the cells of the Gallenkanaelchen and impair thereby the delivery of the Gallenfluessigkeit. Frequently Gallensteine develop.

Up to 10% of the concerning beyond that life-threatening liver complications develop. In an early stage of the liver participation the concentration of the Protoporphyrins in the red blood corpuscles and the blood plasma rises demonstrably, besides is increases the conversion product Koproporphyrin isomer I in the urine. In the advanced stage a jaundice develops, without Transplantation leads the progressive liver contraction (living ore erring trousers) within 3-4 months to death.

Why only 1-10% from EPP of the concerning develop a heavy liver malfunction, is not finally clarified yet. There are references on it that liver cells possess decontamination mechanisms, in order to be able to tolerate a increased load. If this ability is missing, the liver is more sensitive for the toxic effect of the Protoporphyrins. Mutations in certain sections of the Ferrochelatase gene seem to favour a liver participation.

Treatment
A real healing does not give it! Already existing symptoms fade away with the stay in dark, cool areas within hours to days again. Of the skin areas with water, concerned by a cooling, one advises against, since the skin drains and tears easily. With some patients the symptoms can be decreased by gift by high beta Carotin doses.

Most important measure remains the consistent avoidance of sunlight by reasonable behaviors and appropriate clothes (gloves, hat, long sleeves, screen etc..) Carrying UVIMPERMEABLE textiles and UV protective plastic films for windowpanes helps some patients. Sun cream with high light protection factor in the UV-A range and micro pigments as well as taking off Kosmetik is recommended.

The investigation of liver values, Protoporphyrinspiegel and composition (in the blood) is recommended at least once annually. Alcohol and other liver loading substances urgently one advises against; to a advanced damage of the liver can be met only by Transplantation.

Psychosocial aspects
Since with most concerning no visible changes of the skin arise, the presence of genuine pain is often doubted by the social surrounding field and even by physicians. The social obligations resulting from it particularly lead with children to adjustment behavior and displacement mechanisms. Although the very most concerning know the fact that the sun does not do to them well exposes itself again and again it to potentially dangerous situations. Making more difficult the often very late diagnosis at the adult age works itself out ("have a name for it..."). But also after according to a diagnosis the concerning are excluded from many manipulation in the free one and/or are always dependent on remarkable protective clothing and the understanding of the group members. This can lead to depressions and particularly work with young people isolating.

Diagnosis
Due to its rarity and the nonspecific symptoms the Erythropoeti Protoporphyrie is often only diagnosed after many years, mostly only after that 20. Lebensjahr. Since the diagnosis of the EPP succeeds only over a special blood investigation (Porphyrindifferenzierung), which is world-wide accomplished only by few laboratories, the gotten sick ones often fall by the usual diagnostic raster. The largest problem however the doubts about the reliability of the descriptions of the symptoms represent by child physicians and dermatologists, no visible symptoms particularly there are present often.

The test is unproblematic and can be accomplished on the basis a blood test, which should be kept dark.

Frequency and occurrence
The symptoms of the EPP arise usually in the first life months to - to years, rarely also later in the life. Pronounced sun fires, hyperactivity and the avoidance of sunlight refer to the luminous sensivity. The occurrence of a EPP is independent of Ethnie (except black African) or sex. On the basis the spreading of the genetic assessment roughly humans of 100.000 at EPP are get sick in Germany. With 80 millions humans in Germany would be that 800 patients.

Inheritance
Against original acceptance, the EPP is not only dominant but also rezessiv leavable, does not follow however in every case the simple sample of other dominant/rezessiver hereditary courses: Usually a loss of activity of the enzyme of 50% (equivalently to the total failure one of the two genes )does not lead yet to the outbreak of a EPP, only if the activity of both Ferrochelatase enzymes falls together under 50% (i.e. both genes are concerned) shows up the symptoms. It is assumed that beside the defective gene for the Ferrochelatase further factor for the emergence of EPP is jointly responsible.

Patients with one dominant left form of the EPP show usually stronger symptoms and suffer more frequently from a liver participation. The gene of the Ferrochelatase relatively large with 40.000 pairs of cousins lies on the long arm of the chromosoms 18. Over 70 different mutations, which lead to EPP, are so far described.