The hallmark of EPP is the onset of skin photosensitivity at first exposure to the sun or ultraviolet light in the neonatal period or infancy [7]. Burning pain, pruritus and tingling sensation accompanied by edema after as little as few minutes of exposure are most frequent symptoms [1]. In some patients, pain may persist for several hours or even days and may be so excruciating that it affects normal sleeping habits [4]. Although blistering of the skin is rather uncommon, repeated exposure can lead to lichenification, loss of nail lunulae, development of pseudovesicles and other chronic skin changes [7]. Erythema of the skin and petechiae may be observed as well [2]. Additionally, approximately 20-30% have some form of liver impairment, most commonly gallstones and cholestasis due to accumulation of protoporphyrin in bile [7]. As a result, abdominal pain in the right upper quadrant may be observed [7]. 5% of patients progress to advanced liver failure, including cirrhosis and cholestasis [7].

• Splenomegaly

  Patients may display signs and symptoms of anemia usually hemolytic with splenomegaly and porphyrin rich gallstones. [tmg.org.rs]

  As hepatic complications worsen the patient will develop splenomegaly, leading to entrapment and hemolysis of erythrocytes. In rare cases, neurological symptoms such as progressive polyneuropathy have been reported. [clinicaladvisor.com]

  This disease is characterized by splenomegaly; anemia; photosensitivity; cutaneous lesions; accumulation of hydroxymethylbilane; and increased excretion of uroporphyrins and coproporphyrins. [icd10data.com]

  Porphyria erythropoietica: congenital photosensitive porphyria, usually associated with hemolytic anemia and splenomegaly. 2. Porphyria hepatica: hepatic disease or functional impairment frequent. [annals.org]

• Pain

  Effective treatment should reduce pain and increase time outdoors without pain. Afamelanotide, an α- melanocyte stimulating hormone given by subcutaneous implantation, has been reported to provide clinical effectiveness and safety in EPP. [dermnetnz.org]

  This medication increases pain-free sun exposure and has improved quality of life in those with EPP. [rarediseases.info.nih.gov]

  This can cause mild to severe burning pain on sun-exposed areas of the skin. Usually, these symptoms subside in 12 to 24 hours and heal without significant scarring. [porphyriafoundation.org]

  They typically manifest in infancy with itching or burning skin pain after even short exposure to sunlight. Gallstones are common later in life, and chronic liver disease occurs in about 10%. [merckmanuals.com]

• Swelling

  When skin is exposed to light, especially blue light, it results in excruciating pain, swelling and blistering that may lead to scarring. [youtube.com]

  We report the case of a 5-year-old Caucasian female with EPP who presented with a long-standing 3-year history of recurrent facial blisters and erythematous swelling and lesions of other sun-exposed areas of the skin. [ncbi.nlm.nih.gov]

  Sarah and Matthew Chapman suffer from Erythropoietic Protoporphyria, which causes their skin to swell after even a few seconds in the sunlight. [dailymail.co.uk]

  Severe skin pain and swelling develop soon after even brief exposure to sunlight. Crusting may develop around the lips and on the back of the hands after prolonged sun exposure. [merck.com]

• Burning Pain

  Exposure of Lyndal's skin to sunlight results in severe burning pain, swelling and scarring caused by a phototoxic reaction. Throughout her life, Lyndal has endured countless painful reactions to sunlight. [youtube.com]

  In severe cases the burning pain leads to an urgent need to cool the affected extremities. [orpha.net]

  A life in the shadow - Erythropoietic Protoporphyria (EPP) Continuing and persistent burning pain, isolation and a lack of understanding from peers has a long term impact on patients ... [xn--h1adkbo.xn--p1ai]

• Severe Pain

  These symptoms serve as warning signs as longer exposure can result in severe pain. [rarediseases.org]

  Brief exposure to sunlight can cause severe pain, burning, erythema, and edema of the exposed skin. Usually, an infant or young child cries for hours after even short exposure to sun. [merckmanuals.com]

  Erythropoietic protoporphyria is a photodermatosis presenting in childhood with severe pain on sun exposure. The diagnosis is often delayed because of the lack of awareness among pediatricians. [ncbi.nlm.nih.gov]

• Weakness

  Some of their children will have EPP if the other parent has a copy of the weak mutation. Rarely, the weak mutation is absent in an EPP family and two severe mutations are found, with at least one producing some ferrochelatase. [porphyriafoundation.org]

  Finally, profound muscle weakness may be a manifestation of critical illness polyneuropathy. [anesthesiology.pubs.asahq.org]

  During this episode, he also complained of various neurological symptoms, including reduced mental alertness, weakness of extremities, constipation, profound sweating, and urinary retention. [ncbi.nlm.nih.gov]

  Nine out of ten partners will not carry this weak gene and for such couples the risk of having a child with EPP is very low, less than one in a 100. But if your partner does carry the weak gene, the risk becomes much higher at one in 4. [porphyria.eu]

• Abdominal Pain

  Build up of protoporphyrin can cause extreme sensitivity to sunlight, liver damage, abdominal pain, gallstones, and enlargement of the spleen.[1] Inheritance is autosomal recessive .[1][2] Treatment includes avoiding sun and UV light exposure, vitamin [rarediseases.info.nih.gov]

  On the third hospital day, the intensity of the upper abdominal pain increased, concomitantly with elevated levels of serum amylase. Ultrasonography and computed tomography scanning revealed a slightly enlarged pancreas. [ncbi.nlm.nih.gov]

• Nausea

  The patient, a 33-year-old man, was admitted to our hospital complaining of upper abdominal pain, nausea, and vomiting of 3 days' duration. Laboratory tests on admission demonstrated liver dysfunction, anemia, and thrombocytopenia. [ncbi.nlm.nih.gov]

  Symptoms of infection include Nausea or vomiting Severe abdominal cramps Watery or very bloody diarrhea Fatigue Fever To help avoid food poisoning and prevent infection, handle food safely. [medlineplus.gov]

  Some strains of E. coli infection can include nausea, vomiting, and fever. [medicalnewstoday.com]

  Autonomic disturbance can cause nausea, vomiting and constipation. Sympathetic overactivity causes tachycardia, hypertension and postural hypotension. Muscular weakness can occur. [patient.info]

• Vomiting

  The patient, a 33-year-old man, was admitted to our hospital complaining of upper abdominal pain, nausea, and vomiting of 3 days' duration. Laboratory tests on admission demonstrated liver dysfunction, anemia, and thrombocytopenia. [ncbi.nlm.nih.gov]

  Symptoms include having diarrhoea, which may either seem mild or contain blood, experiencing painful stomach cramping, feeling nauseous or vomiting. [independent.co.uk]

  Symptoms include pain in the chest or abdomen, vomiting, and diarrhea or constipation. During an attack, symptoms can include muscle numbness, tingling, paralysis, cramping, and personality or mental changes. [icd9data.com]

  Some strains of E. coli infection can include nausea, vomiting, and fever. [medicalnewstoday.com]

  Symptoms of infection include Nausea or vomiting Severe abdominal cramps Watery or very bloody diarrhea Fatigue Fever To help avoid food poisoning and prevent infection, handle food safely. [medlineplus.gov]

• Right Upper Quadrant Pain

  It is more likely to occur in patients with high levels of protoporphyrins and presents acutely as jaundice, nausea, right upper quadrant pain, and vomiting. [ncbi.nlm.nih.gov]

  Protoporphyrin hepatopathy is rare, occurring in <5% of patients with protoporphyrias,1 who often present with an acute and rapidly progressive form of liver disease with severe right-upper quadrant pain, jaundice, nausea, and vomiting.18 Such patients [pediatrics.aappublications.org]

• Jaundice

  Afterwards, the jaundice, liver dysfunction and abdominal symptoms improved and UDCA, cimetidine, and lactulose administration was continued. [ncbi.nlm.nih.gov]

  Progressive hepatocellular disease : Symptoms include upper abdominal pain and jaundice. [flipper.diff.org]

  An 8-year-old boy was referred to the Hepatology Clinic after an abrupt onset of jaundice with a longstanding history of dermatitis. [pediatrics.aappublications.org]

• Hepatomegaly

  In our case, the patient came to our hospital with jaundice and hepatomegaly without evidence of biliary obstruction by imaging, triggering the liver biopsy. [pediatrics.aappublications.org]

  Patients can also present with splenomegaly and hepatomegaly. Liver biopsy in such patients may reveal features of appreciable hepatocellular injury. Progressive hepatocellular disease : Symptoms include upper abdominal pain and jaundice. [flipper.diff.org]

  Patients can also present with splenomegaly and hepatomegaly. Liver biopsy in such patients may reveal features of appreciable hepatocellular injury[ 5, 13, 22 - 24 ]. [doi.org]

• Hepatosplenomegaly

  An abdominal computed tomography scan showed hepatosplenomegaly. For further investigation, needle biopsy of the liver was performed. On hematoxylin-eosin staining (Figure A), the liver specimen showed slightly distorted lobular architecture. [cghjournal.org]

  Although abnormal erythrocyte protoporphyrin and total plasma porphyrins may be diagnostic of the disease, children with hepatosplenomegaly or cholestatic hepatitis merit a liver biopsy, which is the gold standard to determine the degree of liver injury [pediatrics.aappublications.org]

• Back Pain

  They suffered from back pain, difficulty urinating, psychosis, tachycardia and cramps. [house.wikia.com]

  In CUV029 and CUV039, the majority of adverse events that occurred during the study period were mild to moderate in severity; the most common side effects were headache, nausea, nasopharyngitis, and back pain.34 Between-group differences in adverse events [dovepress.com]

  Protoporphyric liver disease may cause severe abdominal pain (especially in the right upper quadrant) and back pain. [ncbi.nlm.nih.gov]

  Adverse events that occurred during the study period were generally mild to moderate in severity; in both trials, the most common adverse events were headache, nausea, nasopharyngitis, and back pain ( Table 5 ). [nejm.org]

• Photosensitivity

  They should avoid iron supplementation (unless severely iron deficient ), as iron can increase photosensitivity in EPP. Colestyramine reduces hepatic protoporphyrin content but does not reduce photosensitivity. [dermnetnz.org]

  Pathogenesis of demage: Erythropoietic protoporphyria, 2009 Pathogenesis of Photosensitivity in the Cutaneous Porphyrias, 2005 Protoporphyrin is highly toxic, independently of the photosensitized reactions. [flipper.diff.org]

  The severity and degree of photosensitivity is different from case to case. Photosensitivity is often seen during infancy; however, in some cases, it may not occur until adolescence or adulthood. [porphyriafoundation.org]

  Magnus et al[3] and is clinically characterized by photosensitivity to visible light with subsequent physical cutaneous signs in the skin exposed to sun. Photosensitivity with cutaneous lesions usually presents in infancy or early childhood. [jcadonline.com]

• Erythema

  Sometimes skin swelling and erythema may be subtle or absent, and EPP and XLPP may go undiagnosed longer than any other of the porphyrias. [merckmanuals.com]

  Skin PpIX was associated with erythrocyte PpIX (P = 0·002, R 2 = 0·34), skin erythema (P = 0·001, R 2 = 0·47) and symptoms during illumination. Furthermore, skin PpIX increased during the hours after illumination. [ncbi.nlm.nih.gov]

  […] dominant disorder, a form of erythropoietic porphyria, characterized by increased levels of protoporphyrin in the erythrocytes, plasma, liver, and feces and a wide variety of photosensitive skin changes, ranging from a burning or pruritic sensation to erythema [medical-dictionary.thefreedictionary.com]

  There was mottled reticulate violaceous erythema that involved the dorsal surface of the hands that extended a few centimeters above the wrist. There was no evidence of permanent poikilodermatous changes. [journals.sagepub.com]

• Blister

  Symptoms usually start in childhood, but diagnosis is often delayed since blistering is not common and, because the porphyrins are insoluble, they usually escape detection on urinanalysis. [porphyriafoundation.org]

  We report the case of a 42-year-old man with a 5-year history of myelodysplastic syndrome and photosensitivity who had developed painful erythema and blisters on sun-exposed sites. [ncbi.nlm.nih.gov]

  Patients do not develop the erosions and blisters typical of other forms of porphyria. [porphyria-professionals.uct.ac.za]

  The affected skin may become red and swollen and blistered. Later there are pitted scars and sometimes crusty thickened skin, particularly over the cheeks, nose and knuckles of the hands. [dermnetnz.org]

• Urticaria

  […] disorder of porphyrin metabolism due to a deficiency of ferrochelatase associated with enhanced fecal excretion of protoporphyrin, red-purple urine, and increased protoporphyrin IX in red blood cells, plasma, and feces; characterized by acute solar urticaria [medical-dictionary.thefreedictionary.com]

  This is sometimes described as solar urticaria. Typically patients have an individual threshold for sun-exposure. [porphyria-professionals.uct.ac.za]

  Differential diagnosis includes phototoxic drug reactions, hydroa vacciniforme, solar urticaria, contact dermatitis, angio-oedema and, in some cases, other types of porphyria. [ncbi.nlm.nih.gov]

  Differential diagnosis Differential diagnosis includes phototoxic drug reactions, hydroa vacciniforme, solar urticaria, contact dermatitis, angioedema and, in some cases, other types of porphyria (see these terms). [orpha.net]

• Cutaneous Manifestation

  Erythropoietic protoporphyria (EPP) is an inherited disorder of the haem metabolic pathway characterised by accumulation of protoporphyrin in blood, erythrocytes and tissues, and cutaneous manifestations of photosensitivity. [ncbi.nlm.nih.gov]

  EPP is characterized by cutaneous manifestations of acute painful photosensitivity with erythema and edema, sometimes with petechiae, together with stinging and burning sensations without blistering, upon exposure to sunlight or artificial light (400- [orpha.net]

• Facial Swelling

  However, the patient’s father reported a prior history of “recurrent” episodes of hand and facial swelling that also seemed to occur from prolonged exposure to sunlight and/or heat. [jcadonline.com]

• Tingling

  Burning pain, pruritus and tingling sensation accompanied by edema after as little as few minutes of exposure are most frequent symptoms. [symptoma.com]

  When the skin is exposed to sun, patients first develop tingling, itching, and/or burning of the skin. These symptoms serve as warning signs as longer exposure can result in severe pain. [rarediseases.org]

  During an attack, symptoms can include muscle numbness, tingling, paralysis, cramping, and personality or mental changes. Certain triggers can cause an attack, including some medicines, smoking, drinking alcohol, infections, stress and sun exposure. [icd9data.com]

  Once patients learn to recognize early symptoms including tingling, burning, and itching, they avoid further sun exposure, with major implications for their daily activities, careers and quality of life. [news-medical.net]

  The three hallmark symptoms of EM are: Redness, caused by excessive blood flow to the area Heat, meaning that the skin will feel warm or hot to the touch, also due to increased blood flow Pain, which may range from mild tingling to severe burning Additional [erythromelalgia.org]

• Polyneuropathy

  His OLT was uneventful, and he developed neither polyneuropathy nor exacerbation of photosensitivity. [ncbi.nlm.nih.gov]

  In addition to polyneuropathy, our patient also experienced photosensitivity. [anesthesiology.pubs.asahq.org]

  포르피린성 다발신경병증(∼性 多發神經病症) porphyric polyneuropathy 포르피린성 다발신경병증. porphyrin neuritis 포르피린신경염 (∼神經炎). porphyrin neuritis 포르피린신경염(∼神經炎) porphyrinemia 포르피린혈증(∼血症) 옛 대한의협 3 의학용어 사전 검색 유사 검색 결과 : 15 페이지: 1 acquired porphyria cutanea tarda 후천성 지연성 피부 포르피린증(~症 [kmle.co.kr]

  Polyneuropathy and quadriparesis may occur. Excessive protoporphyrin is excreted in bile, and hence in feces, but not in urine because protoporphyrin is only poorly water-soluble. [accessanesthesiology.mhmedical.com]

• Encephalopathy

  Very occasionally, acute attacks are accompanied by a severe adrenergic crisis with dangerous hypertension, encephalopathy, seizures and ischaemic changes on a CT brain scan. [ 1 ] Liver transplantation has been carried out successfully in severe cases [patient.info]

  […] sinensis, liver flukes, distomatosis hepatis, hepatodistomiasis 肝静脈閉塞 hepatic veno occlusive disease 肝性骨髄性ポルフィリン症 hepatoerythropoietic porphyria 肝腎型チロシン血症 hepatorenal tyrosinemia 肝腎症候群 hepatorenal syndrome 肝性骨ジストロフィー hepatic osteodystrophy 肝性脳症 hepatic encephalopathy [jsge.or.jp]

• Paresis

  […] the addition of hematin or heme arginate or even Tin Mesoporphyrin as these are signs of impending syndrome of inappropriate antidiuretic hormone (SIADH) or peripheral nervous system involvement that may be localized or severe progressing to bulbar paresis [house.wikia.com]

Clinical suspicion toward EPP can be made based on clinical criteria only, implying that a thorough patient history and a detailed physical examination are most important steps in workup. To confirm the diagnosis, microscopic evaluation of erythrocytes on a fresh blood smear and visualization of fluorescent RBCs (fluorocytes) is recommended [2]. Measurement of protoporphyrin in serum and stool is also a useful diagnostic procedure, as it will be invariably elevated in these samples [2]. Liver examination is mandatory for all patients in whom EPP is suspected. Abdominal ultrasonography and liver function tests, including transaminases (ALT and AST), gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP) must be performed to exclude cholestasis [2].

• Microcytic Anemia

  Microcytic anemia occurs in 20% to 60% of patients. We investigated 178 patients with dominant EPP confirmed by molecular analysis. [ncbi.nlm.nih.gov]

• Free Erythrocyte Protoporphyrin

  Porphyrin analysis revealed elevated free erythrocyte protoporphyrin (FEP) levels confirming the diagnosis of EPP. [ncbi.nlm.nih.gov]

  Fluorescence of a significant proportion of red blood cells is detectable by ultraviolet microscopy because of the presence of free erythrocyte protoporphyrin. [accessanesthesiology.mhmedical.com]

  Sometimes laboratories have measured only zinc protoporphyrin and reported results incorrectly as “protoporphyrin” or “free erythrocyte protoporphyrin (FEP)”. [porphyriafoundation.org]

• Hyponatremia

  Heme Arginate (NormoSang) is used during crises but also in preventive treatment to avoid crises, one treatment every 10 days Any sign of low blood sodium (hyponatremia) or weakness should be treated with the addition of hematin or heme arginate or even [house.wikia.com]

• Liver Function Tests Abnormal

  The present report describes the clinical features of a patient with erythropoietic protoporphyria and liver function test abnormalities associated with treatment with beta-carotene. [ncbi.nlm.nih.gov]

• Protoporphyrin Increased

  RCE decreased RBC protoporphyrin levels from 2,879 to 1,225 μg/dL but plasma protoporphyrin increased from 180.4 to 1,044.1 μg/dL, and liver function failed to improve. [ncbi.nlm.nih.gov]

Symptomatic measures and liver transplantation are current therapeutic strategies, as there is no cure for this condition. Application of wet and cold compresses to skin areas that are affected is recommended to for pain reduction [2]., whereas the role of β-carotene in improving light tolerance has been disputed. However, some benefit has been reported in many patients, which is why it is often used in doses of 90-120 mg/day in children and 180-300 mg/day in adults [2]. Recent trials have shown that an analog of α-MSH, afamelanotide, can be of great use in patients suffering from EPP [5]. In the case of extensive liver damage, the main therapeutic strategy is liver transplantation, with the idea of removing the accumulated protoporphyrin and good post-transplantation survival rates have been observed [10]. This procedure does not affect the production of protoporphyrin from the bone marrow, however, which is why liver recipients are at a severe risk of disease recurrence [11]. For this reason, concomitant bone marrow transplantation may be performed. As light exposure during the operating room may induce skin damage, placement of filters on lights in the operating room are necessary measures. Additionally, the use of hematin and/or plasmapheresis in the setting of severe neuropathy and pain is advocated by certain authors [10].

Acute hepatic failure as a result of protoporphyrin accumulation in the liver is the most important and most serious complication in these patients, as it may be rapidly fatal without appropriate treatment [4]. From social and individual aspects, EPP has shown to be a severely debilitating disease because of its distinctive clinical features that can significantly impact the quality of life among patients afflicted this illness [9]. For these reasons, prompt recognition in early life is vital.

Many controversies have existed regarding the mode of EPP inheritance, but it was determined that both autosomal dominant and recessive patterns were identified in patients [2]. Mutations of FECH on one allele and a hypomorphic FECH allele in trans position are most frequently observed, but various types of mutations have been identified in EPP, including missense, nonsense, deletions, insertions and splicing [6]. Inciting factors leading to this phenomenon, however, are still not known.

EPP is considered to be one of the most common types of porphyria, occurring in 2-5 per 1,000,000 individuals, and it is the most frequent porphyria identified in children [7]. Studies in the Netherlands and Wales have established prevalence rates of 1 per 75,000 and 1 per 200,000 individuals, respectively [7]. Similar rates were observed in Sweden, where prevalence rates of 1 per 180,000 were observed [8]. EPP is equally distributed across gender and cases of EPP have been diagnosed across all continents. Being of African ancestry has shown to be a negative risk factor for the development of EPP [2] [6].

The pathogenesis of EPP starts with genetic mutations that cause reduced activity (below 35% of normal) of ferrochelatase, the enzyme that mediates the last step of heme biosynthesis - insertion of ferrous iron to protoporphyrin in the mitochondria [6]. Since protoporphyrin is not degraded, it accumulates in bone marrow reticulocytes, after which it is released into the circulation from both the bone marrow and matured erythrocytes [3]. Additionally, a small proportion of protoporphyrin is produced in the liver, the site of secondary erythropoiesis. This molecule is excreted in the bile and feces and deposits in the liver parenchyma because it cannot be eliminate by the kidneys due to water insolubility. Liver disease ensues due to hepatotoxic effects of protoporphyrin, such as reduction of bile formation and obstruction of its flow, together with inhibition of cellular metabolism and induction of cell fragility [1] [3]. When it comes to the main clinical feature of EPP, skin photosensitivity, the reaction of visible blue-violet light near 400 nm to protoporphyrin triggers the release of free radicals that are responsible for the appearance of symptoms [3] [7].

Prevention of EPP is currently not possible, but long-term follow-up and implementation of various strategies may be of significant benefit in this group of patients. Avoidance of sun exposure is equally important both in therapy and in prevention, together with frequent use of vitamin D, since the production of this vital nutrient necessitates exposure of the skin to sunlight [7]. Additionally, regular evaluations of hepatic function is advocated in all patients, to prevent liver failure as a result of protoporhyrin accumulation [7]. Although the chance of transferring the disease from a parent with the classical form of FECH allele mutations is less than 2.5% [2]., genetic counselling and prenatal testing is advised for families in whom EPP is already diagnosed [7].

Erythropoietic protoporphyria (EPP) is one of the types of porphyria, that are diseases of inadequate heme synthesis due to reduced activity of various enzymes necessary for its formation [1]. Specifically, EPP occurs due to reduced activity of ferrochelatase, an enzyme responsible for insertion of ferrous iron into protoporphyrin to form heme, which is the last step of heme synthesis [1]. EPP is a genetic disease and is transferred by both autosomal dominant and recessive patterns of inheritance [2]. Epidemiologic studies show that it is the most common pediatric porphyria and the pathogenesis starts with accumulation of protoporphyrin in the bone marrow (where 80% of heme is formed) and the liver [1]. Extensive production of protoporphyrin in reticulocytes situated in the bone marrow and hepatocytes triggers a progressive release of this molecule from these sites into plasma [3]. The liver is the principal site of its deposition, as it is not excreted through the renal system because of its water insolubility [3]. Apart from liver disease that is seen in 20-30% of patients (ranging from mild cholestasis to severe and life-threatening liver failure), skin sensitivity to light is the most important clinical manifestation of the disease [4]. When light rays (either from the sun or strong ultraviolet light) penetrate the skin, its interaction with protoporphyrin creates a severely painful reaction mediated by release of free radicals. Consequently, the main symptoms are pain, itching and tingling within minutes after exposure of the skin to light for the first time [2]. Erythema and petechiae are readily observed, but blistering lesions are not encountered in these patients [2]. Clinical criteria are sufficient for the initial diagnosis, but serum and fecal determination of EPP levels, as well as microscopic visualization of fluorescent erythrocytes (because of protoporphyrin reaction to light) are used for confirmation [2]. Liver function tests and abdominal ultrasonography must be performed to assess potential liver damage. Symptomatic treatment of photosensitivity by applying cold and wet compresses and β-carotene are useful techniques, but avoiding exposure to sunlight is the main therapeutic and preventive strategy [2]. In patients who develop liver failure, transplantation is recommended, but protoporphyrin production from the bone marrow is not resolved by this procedure, which is why concomitant bone marrow transplantation may be indicated. In recent years, the use of α-melanocytic stimulating hormone (α-MSH) analog, afamelanotide, has show to be of significant benefit for EPP patients [5]. Curative therapy, however, does not exist at this moment. As for many diseases, the principle of an early diagnosis of EPP is detrimental, especially in the setting of liver disease. Patients who are treated in a timely manner have a better prognosis.

Erythropoietic Protoporphyria (EPP) is an inherited disease that belongs to a group of porphyrias, conditions that arise as a result of either reduced activity or deficiency of enzymes responsible for production of heme, the main product of hemoglobin degradation. In the setting of EPP, the enzyme that binds iron and a precursor of heme, protoporphyrin, is minimally present (below 35% of its physiological activity), which leads to accumulation of this substance in the bone marrow (where it is principally produced) and the liver. EPP patients acquired mutated genes from one (or rarely both) of their parents and it's appearance in the population is estimated between 1 in 75,000 to 1 in 200,000 individuals. Once protoporphyrin accumulates in the bone marrow, it is stored in mature red blood cells and travels throughout the body. When it is situated in distal blood vessels close to the skin and exposed to sunlight, a reaction involving release of free radicals causes the most prominent clinical feature of EPP - skin photosensitivity. Namely, patients suffering from EPP develop a severe reaction of the skin during first exposure to sunlight, characterized by severe pain, itching and tingling. These symptoms may persist for hours or even days. Redness of the skin, as well as swelling, is frequently observed, while repeated exposure may cause chronic skin changes. In addition to photosensitivity, the liver is also affected, as protoporphyrin eventually deposits in the liver, where it should be excreted through bile and feces. Through unknown mechanisms, obstruction of bile flow and damage to liver cells, known as hepatocytes, is seen in approximately 20-30% of EPP patients and 5% of individuals develop severe and life-threatening liver failure. Based on findings obtained in patient history and during physical examination, the initial diagnosis should be made easily, whereas a confirmation can be obtained through determining values of protoporphyrin in blood and stool. Additionally, a detailed liver examination consisting of tests that evaluate its synthetic function and abdominal ultrasonography are necessary. Avoiding sun exposure is currently the single most important therapeutic measure, while symptomatic treatment through application of wet compresses on the skin and use of β-carotene have been shown to be beneficial. In patients with severe liver disease, transplantation is indicated in order to remove the stores of protoporphyrin in this organ, but because its production in the bone marrow is unaffected by this procedure, bone marrow transplantation should also be considered to prevent disease recurrence. Although it is considered to be rare in clinical practice, an early diagnosis of EPP carries a much better prognosis, which is why physicians must consider this disease among patients presenting with skin photosensitivity and liver damage.

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