||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, and much of the description of EPP is incorrect. Exposure to powerful surgical lights is 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.
Prolonged exposure to the sun can lead to edema of the hands, face, and feet, rarely with blistering and petechiae. Skin thickening can sometimes occur over time.
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. Unless there is liver failure, it is not a life-limiting disease.
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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