||This article needs attention from an expert in Pathology. (March 2011)|
|Classification and external resources|
Chronic skin lesions of EPP
|ICD-10||E80.0 (ILDS E80.010)|
Erythropoietic protoporphyria (EPP) is a form of porphyria, which varies in severity and can be very painful. It arises from a deficiency in the enzyme ferrochelatase, leading to abnormally high levels of protoporphyrin in the tissue.:525 The severity varies significantly from individual to individual.
Both autosomal dominant and autosomal recessive inheritance have been reported with this disorder as has an acquired form of the disease. A clinically similar form of porphyria, known as X-Linked dominant protoporphyria, was identified in 2008.
A common symptom is very painful photosensitivity, manifesting itself as a burning and itching sensation on the surface of the skin. At times the itching sensations are almost unbearable. Rubbing the affected areas with ice can be the only relief, and that is only temporary. The usual anti-itch remedies, including cortisone anti-histamine topical preparations, and Calomine lotion generally provide little or no relief. If a patient presents with a history of anti-itch preparation inefficacy, EPP should be considered.
EPP usually first presents in childhood, and most often affects the face and the upper surfaces of the arms, hands, and feet and the exposed surfaces of the legs. Most patients, if the EPP is not as severe, manifest symptoms with onset of puberty when the male and female hormone levels elevate during sexual development and maintenance. More severe EPP can manifest in infancy. Exposure to even indoor light sources can cause the reaction, and the infant, if clothed only in a diaper, will break out everywhere except under the diaper. EPP can be triggered through exposure to sun even though the patient is behind glass. Even the UV emissions from arc welding with the use of full protective mask have been known to trigger EPP. EPP can also manifest between the ages of 3 and 6.
EPP is so rare that it has been mentioned on an episode of the popular American TV show, HOUSE M.D. It is over-dramatized, but the facts are essentially correct. Exposure to powerful surgical lights is more than enough to trigger the reaction. As a precaution, individuals with EPP should tell their close friends and family to make sure that if they ever are taken to the hospital for emergency surgery that the staff be notified of the condition so they can adjust the lighting accordingly.
In the late 1990s, EPP was cured in rats. More than likely it will be cured as a byproduct of another more common disease being cured.
Prolonged exposure to the sun can lead to edema and blistering, especially on the nose. At times the immediate damage can be so severe that the individual can lose the skin in sheets. After many years, chronically sun-exposed skin may become thick and wrinkled if no beta carotene and other carotenoids and no lutein and other xanthophylls are ingested.
EPP can lead to abdominal pain, which may manifest as generalized pain, or may imitate an appendicitis. Some healthy appendices have been removed due to this mimic. Since porphyria is not that common, most doctors don't even think to do blood porphyrin levels when symptoms present. For doctors that are familiar with porphyria, it is generally considered insignificant and irrelevant compared to the possibility of a pending burst appendix, especially since porphyrin levels cannot be generally be received back immediately due to lab protocols.
Moderate and severe cases can present with pelvic and shoulder girdle muscle weakness. This is because porphyrins are poisonous to the body and produce nerve damage. Damage to nerves of the digestive system not only cause nerve pain in the abdominal area, but also cause slow movement of the bowels, especially the large bowel. Patients can therefore develop a larger than normal diameter of the large bowel, at times causing a condition called megacolon. The damage of nerves to the esophagus and to the stomach valve muscles (sphincters) can cause stomach reflux. One of the ironies of these digestive condition is that one of the medical treatments of these digestive conditions is Reglan, to which some porphyrics have a very strong adverse reaction.
Porphyrin toxins are neurotropic and shut down the nerve trunks one by one until the individual has difficulty with fine motor tasks, like turning phonebook pages, has difficulty speaking (develops dystonic speech that is almost unintelligible), and develops difficulty breathing. The porphyrin neurotoxins have caused some patients to present to the Emergency Room not only in pain but also seeming to be neurotic, or even psychotic. Once glucose is infused, those episodes subside, and if they don't, healthy red blood cell infusion in whole also helps, due to the naturally occurring glucose in the infused blood. These patients will often present with a very enlarged spleen due to having to process defective red blood cells. At times poking around on the spleen can cause elevation of body temperature by at least two degrees Fahrenheit. The liver may also be tender.
Liver failure in EPP
In a small percentage of cases, protoporphyrin accumulates to toxic levels in the liver, leading to liver failure. A lack of diagnostic markers for liver failure make it difficult to predict which patients may experience liver failure and the mechanism of liver failure is poorly understood. A retrospective European study identified 31 EPP patients receiving a liver transplantation between 1983 and 2008 with phototoxic reactions in 25% of patients who were unprotected by surgical light filters. The same study noted a 69% recurrence of the disease in the grafted organ. Five UK liver transplants for EPP have been identified between 1987 and 2009.
Frequent liver testing is recommended in EPP patients where no effective therapy has been identified to manage liver failure to date.
Case reports suggest that EPP is prevalent globally. The prevalence has been estimated somewhere between 1 in 75,000 and 1 in 200,000 however it has been noted that the prevalence of EPP may be increasing due to a better understanding of the disease and improved diagnosis. An estimated 5,000-10,000 individuals worldwide have EPP. EPP is considered the most common form of porphyria in children. The prevalence in Sweden has been published as 1:180,000.
EPP and pregnancy
EPP photosensitivity symptoms are reported to lessen in some female patients during pregnancy and menstruation, although this is not consistent and the mechanism is not understood.
Treatment and prognosis
There is no cure for this disorder; however, symptoms can usually be managed by limiting sun exposure. Protective clothing is also very helpful. Since the photosensitivity results from light in the visible spectrum, most sunscreens (with the exception of light-reflecting substances such as zinc oxide) are of little use. Some individuals may decrease their sun sensitivity with daily doses of beta carotene, though a recent meta analysis of carotene treatment has called its effectiveness into question. Some patients gradually build a protective layer of melanin by regularly exposing themselves for short times to ultraviolet radiation.
EPP is considered one of the least severe of the porphyrias. The ferrochelatase enzyme is the last step before actual heme production and then actual hemoglobin production. The steps before protoporphyrin production also have enzymes that produce intermediaries. If the first enzyme in the production process is defective, that porphyria is generally the most severe. If the next enzyme in the step-wise process is the defective one, the porphyria is generally less severe, and-so-on until the ferrochelatase step. One thing to keep in mind is the fact that low blood sugar activates the cytochrome p450 system. The cytochrome p450 system is the system that contains the subsystem that produces the porphyrin ring. Therefore infusion of glucose into the blood stream to produce slightly higher than normal blood sugar produces relief. Transfusion of healthy blood cells in whole blood into the patient also gives relief. Protoporphyrins sometimes accumulate to toxic levels in the liver, causing liver failure; if this occurs, a liver transplant becomes necessary.
The individual symptoms of this condition are multiple, and many of those symptoms can occur in other conditions. Therefore other diagnoses are often made and the patient can go through life as an undiagnosed and untreated person with EPP.
Clinuvel Pharmaceuticals Ltd., an Australian pharmaceutical company, has successfully completed Phase III clinical trials  with a melanocyte-stimulating hormone called afamelanotide (SCENESSE) (formerly CUV1647). In May 2010 afamelanotide (SCENESSE) was approved by the Italian Medicines Agency (AIFA) for reimbursement, for the treatment of EPP. The treatment is also available in Switzerland.
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