For Healthcare Professionals: Disorders In-Depth

Disorder Definitions

There are four acute hepatic porphyrias, Acute intermittent porphyria (AIP), Hereditary coproporphyria (HCP), Variegate porphyria (VP), and δ-aminolevulinic acid dehydratase porphyria (ADP), that cause acute neurovisceral symptoms. They are not common and may be difficult to diagnose due to their rarity. The combined prevalence of these diseases is approximately 5 cases per 100,000 persons. It is estimated that about 1 in 10,000 Europeans or people of European ancestry carries a mutation in one of the genes for acute porphyria, although mutations have been found in all races and many other ethnicities.

Treatment and Prognosis for the Acute Porphyrias

Hospitalization is often necessary for acute attacks. Medications for pain, nausea and vomiting, and close observation are generally required with monitoring of salt and water balance. Harmful drugs, which can be identified using online drug databases, should be discontinued immediately. These include barbiturates, sulfonamide antibiotics, progestins, anticonvulsants and many others. Attacks can be prevented in many cases by avoiding harmful drugs and adverse dietary practices. Avoidance of sunlight is recommended for all individuals diagnosed with Hereditary Coproporphyria (HCP) or Variegate Porphyria (VP) who have porphyria-related photosensitivity.

Acute porphyria is particularly dangerous if the diagnosis has not been made and if harmful drugs are administered. The prognosis is usually good if the disease is recognized and if treatment and preventive measures are started before severe nerve damage has occurred. Although symptoms usually resolve after an attack, nerve damage and associated muscle weakness can improve over a period of months or longer after a severe attack. Mental symptoms, such as hallucinations, may occur during attacks but are usually not chronic.

Panhematin® (hemin) is the most effective treatment for acute neurovisceral attacks currently available and it is administered intravenously. Panhematin®, from Recordati Rare Diseases, is the only FDA approved hemin preparation available in the United States (Normosang® (heme arginate) is another preparation available in Europe and South Africa). Panhematin® can be reconstituted with albumin to help stabilize the product as well as decrease the risk of phlebitis. Intravenous glucose is usually given as a 10% solution while hemin is being prepared but should not delay the administration of hemin.

Although Panhematin® has few side effects, it does act as a mild anticoagulant. Thus, concurrent use of other anticoagulants such as heparin or Coumadin® (warfarin) should be avoided. Panhematin® may also produce superficial thrombophlebitis, especially if infused into a small vein. Panhematin® is less likely to produce phlebitis if it is mixed with human albumin before it is given. Before Panhematin® is used, it should be clear that the patient indeed suffers from one of the acute porphyrias (AIP, HCP, VP, ADP) and that the patient's symptoms are due to an acute attack. Panhematin® therapy may not be indicated unless the diagnosis of acute porphyria is proven by a marked increase in urine PBG.

The physician or hospital pharmacy can order Panhematin® through a wholesaler of choice. Healthcare professionals can call 1-800-746-6273 to receive help with regular and emergency shipments. For full prescribing information, including Boxed Warning, please refer to:

Prevention and Management

Attacks can be prevented in many cases by avoiding known triggers including certain medications, alcohol, stress, smoking, illicit drugs, exogenous hormones and hypocaloric diet or fasting. Wearing a Medic Alert bracelet is recommended, particularly for patients who have had recurrent attacks. Recurrent attacks related to the menstrual cycle can be prevented by a gonadotropin-releasing hormone (GnRH) analogue administered with expert guidance. In selected cases, frequent noncyclic attacks can be prevented by prophylactic infusions of hemin, which are titrated to patient response. Patients with chronic kidney disease should have regular monitoring with a nephrologist. HCC surveillance is recommended starting at the age of 50 years old for early detection. Additionally, Hepatitis B and A vaccines are recommended to avoid preventable infections of the liver. Liver transplantation has been shown to be an effective treatment for AIP patients with recurrent attacks who were resistant to conventional treatment including Panhematin®. However, experience with this treatment modality is still limited. 

Cutaneous porphyrias primarily affect the skin. Areas of skin exposed to the sun become fragile and blistered, and these complications can lead to infection, scarring, changes in skin coloring (pigmentation), and increased hair growth. Cutaneous porphyrias include congenital erythropoietic porphyria, erythropoietic protoporphyria and X-linked protoporphyria, porphyria cutanea tarda, and hepatoerythropoietic porphyria.


  • Acute Intermittent Porphyria
  • Hereditary Coproporphyria
  • Variegate Porphyria
  • Aminolevulinate-dehydratase
    Deficiency Porphyria
  • Porphyria Cutanea Tarda
  • Hepatoerythropoietic Porphyria
  • Congenital Erythropoietic Porphyria
  • Erythropoietic Protoporphyria
    and X-Linked Protoporphyria

Acute Intermittent Porphyria (AIP)

AIP is the most common of the acute porphyrias, with a world-wide prevalence of approximately 1 to 2 per 20,000. AIP results from autosomal dominant inheritance of a mutation in the gene for the enzyme hydroxymethylbilane-synthase (HMB-synthase), which is also known as porphobilinogen deaminase or uroporphyrinogen I synthase.  The enzyme deficiency alone is not sufficient to produce the symptoms of AIP, and other activating factors, such as drugs, hormones, and dietary changes, must be present. Sometimes, activating factors cannot be identified.


Most people who have a mutation in the gene for AIP never develop symptoms; this is referred to as “latent” AIP. Symptoms may develop after puberty, especially in women. Acute attacks almost always start with severe pain in the abdomen but sometimes in the chest, back, or thighs, and are often accompanied by nausea, vomiting, and constipation.  Heart rate and blood pressure are commonly increased.  These symptoms and signs are all due to the effects of the disease on the nervous system. Confusion, convulsions, and muscular weakness, due to impairment of the nerves controlling the muscles, may lead to paralysis. An acute attack usually lasts for days or weeks.  Recovery from severe paralysis is generally slow.

Acute attacks are often provoked by drugs such as barbiturates, sulfonamide antibiotics, anti-seizure drugs, rifampin, metoclopramide, and alcohol.  Attacks in women may occur after ovulation and during the last part of the menstrual cycle when progesterone levels are high.  Reduced food intake, often in an effort to lose weight, as well as infections, surgery, and stressful situations may also precipitate attacks.  Risk for developing chronic renal disease and liver cancer (hepatocellular carcinoma) is increased in AIP.  The skin is not affected, except in some AIP patients who have developed kidney failure.


The finding of a substantial increase of porphobilinogen (PBG) in urine establishes that one of the three most common acute porphyrias (AIP, HCP or VP) is present.  Therefore, measuring PBG in urine is the most important test for diagnosing acute porphyria, especially in an acutely ill patient.  Deficiency of HMB-synthase activity in red blood cells helps to establish the diagnosis of AIP. However, normal HMB-synthase activity in red blood cells does not exclude AIP.  A diagnosis of AIP is established in a patient by DNA studies, which can demonstrate a HMB-synthase gene mutation in almost all cases.

Many different mutations have been identified in the HMB-synthase gene.  Almost every family with AIP has a different mutation in this gene. Within one family, however, everyone who inherits a deficiency of HMB-synthase has the same mutation. Knowing the mutation that causes AIP in a particular family member means that others who carry the mutation can be reliably identified and counseled to avoid drugs, dietary practices, etc. that may trigger symptoms.  Measuring red blood cell HMB-synthase activity has been useful in family studies but is less accurate than DNA analysis. 

Treatment and Prognosis

The prognosis is usually good if the disease is recognized and if treatment is prompt, before severe nerve develops. Although symptoms usually resolve after an attack, repair of nerve damage and associated muscle weakness may require several months or longer. Mental symptoms may occur during attacks but are not chronic.  Premenstrual attacks often resolve quickly with the onset of menses. 

Hospitalization is often necessary for acute attacks. Medications for pain, nausea, and vomiting and close observation are generally required. During treatment of an attack, attention should be given to sodium (salt) and water balance. Harmful drugs should be stopped.

Attacks are treated with either glucose loading or hemin. These are specific treatments that lower the production of heme pathway intermediates by the liver.  Glucose or other carbohydrates are given by mouth if possible, otherwise by vein. Intravenous glucose is usually given as a 10% solution, at least 3 liters daily. However, unless an attack is mild, it is now common practice to begin treatment with hemin, which is more effective than glucose loading. Hemin therapy can be started after a trial of glucose therapy, but the response to hemin therapy is best if started early in an attack.

Hemin must be administered intravenously. Panhematin®, from Lundbeck Pharmaceuticals, is the only hemin preparation available in the United States. Panhematin® is more stable and less likely to produce phlebitis (an inflammation of the vein; a reported possible side effect of Hemin therapy) if it is mixed with human albumin before it is given.


Individuals with AIP who are prone to attacks should eat a normal or high carbohydrate diet and should not greatly restrict their intake of carbohydrate and calories, even for short periods of time. If weight loss is desired, it is advisable to consult a physician and a dietitian to have them prescribe an individualized diet that is approximately 10% below the normal level of calories for the patient. This should result in a gradual weight loss and usually will not cause an attack of porphyria.


Pregnancy is usually well tolerated, but the hormonal changes may exacerbate AIP is some women. Proper nutrition and hydration are important during pregnancy and labor, after delivery, and for the duration of breastfeeding. As always, only drugs and anesthetics classified as safe in porphyria should be used. Acute attacks are treated with glucose or hemin; there is no evidence of adverse effects of hemin therapy on the mother or fetus.


Attacks can be prevented in many cases by avoiding harmful drugs and adverse dietary practices. Wearing a Medic Alert bracelet is advisable for patients who have had attacks, but is probably not warranted in most latent cases. Very frequent premenstrual attacks can be prevented by a gonadotropin-releasing hormone (GnRH) analogue administered with expert guidance. In selected cases, frequent noncyclic attacks can be prevented by once- or twice-weekly infusions of hemin. Patients with severe renal disease tolerate hemodialysis or kidney transplantation. Liver transplantation has been very effective for patients with AIP who have repeated attacks and who are resistant to other treatments. However, experience with transplantation as a treatment for AIP is still limited. 

Because AIP is an autosomal dominant disorder, a person with a mutation in his or her HMB-synthase gene has a 50% chance with each pregnancy of passing that mutation on to his/her offspring. The outlook for such offspring is generally good, since most individuals who inherit an HMB-synthase gene mutation never become ill or have only a few attacks.

Hereditary Coproporphyria (HCP)

HCP is an autosomal dominant acute porphyria with a clinical presentation similar to that of AIP, except that some patients (about 20%) develop blistering photosensitivity. The incidence of HCP appears to be at most 2 per 1,000,000. The deficient enzyme is coproporphyrinogen oxidase (CPOX). Urinary ALA and PBG are increased, especially during acute attacks, but generally to a lesser degree than in AIP. The diagnostic finding is a definite increase in urine PBG and coproporphyrin, with a copro III/I isomer ratio >1.5. Plasma porphyrin levels are usually normal but may be increased in patients with skin lesions. Elevation of urine coproporphyrin only is not diagnostic, because it occurs in a number of other medical conditions, notably liver disease. Elevation of ALA and coproporphyrin (with normal PBG) is typical of lead poisoning, which should be confirmed with a blood test for heavy metals (lead, mercury, arsenic). A marked elevation in fecal coproporphyrin III is suggestive of HCP, but should be confirmed by analysis of DNA for a disease-causing CPOX mutation. Treatment, complications, and preventive measures for HCP are the same as for AIP.

Variegate Porphyria (VP)

VP is caused by one of several mutations in the enzyme protoporphyinogen oxidase (PPOX). Over most of the world, it is less common than AIP. In South Africa, however, a prevalence of 3 in 1,000 individuals has been estimated, most of the cases arising in whites of Dutch ancestry. The PPOX mutation in this group has been traced to a couple who were among the original Dutch immigrants to the Cape of Good Hope in the late 17th century. Acute attacks in VP are identical to those in AIP, and their management and prevention are the same. Blistering skin lesions are much more common than in HCP, are indistinguishable from those of PCT and may be chronic. There is no remedy for VP photosensitivity other than use of protective clothing. Unlike PCT, iron-depletion and chloroquine are not helpful. Urine ALA and PBG are increased during attacks, but as in HCP, these may increase to a lesser degree and decrease more rapidly than in AIP. Plasma porphyrins are frequently increased in VP, in contrast to AIP and HCP, and the plasma of VP patients displays a distinctive fluorescence peak, which is diagnostic. Fecal porphyrins are also elevated and are predominantly coproporphyrin III and protoporphyrin. Long term complications are the same as in AIP.

δ-Aminolevulinic Acid Dehydratase Porphyria (ADP)

ADP is the least common of all the porphyrias with less than 10 cases documented to date.  This is an autosomal recessive disease, whereas the other three acute porphyrias are autosomal dominant.  All of the reported cases have been males, in contrast to the other acute porphyrias.

A severe deficiency of the enzyme δ-aminolevulinic acid dehydratase (ALAD) causes an increase of 5’-aminolevulinic acid (ALA) in the liver, other tissues, blood plasma, and urine. In addition, urine coproporphyrin and erythrocyte protoporphyrin are increased. Treatment is the same as in the other acute porphyrias.

Porphyria Cutanea Tarda (PCT)

Porphyria cutanea tarda (PCT) is the most common type of porphyria, with a prevalence of approximately 1 case for every 10,000 people. PCT develops when the activity of an enzyme involved in synthesis of heme, uroporphyrinogen decarboxylase (URO-decarboxylase), becomes severely deficient (less than 20% of normal activity) in the liver. In most cases of PCT, patients do not have inherited URO-decarboxylase gene mutations and are said to have sporadic (or Type I) PCT (s-PCT) A URO-decarboxylase inhibitor generated only in the liver accounts for the severely deficient enzyme activity in s-PCT. About 20 percent of cases have familial (or Type II) PCT (f-PCT). Such individuals have inherited a URO-decarboxylase gene mutation from one parent, which has reduced the amount of URO-decarboxylase in all tissues from birth. However, to develop PCT symptoms, other factors must be present to further reduce URO-decarboxylase level in the liver to less than 20% of normal. Such f-PCT patients may develop blisters at an early age or have relatives with the disease. Excess iron and multiple other susceptibility factors contribute to the development of PCT. These susceptibility factors include excess use of alcohol, use of estrogens, chronic hepatitis C, smoking, HIV (human immunodeficiency virus) infections, and mutations of the HFE gene which is associated with the disease hemochromatosis in which excess iron accumulates in the liver. Other susceptibility factors exist but are as of yet unidentified.


In PCT the cutaneous blisters develop on sun-exposed areas of the skin, such as the hands and face. The skin in these areas may blister or peel after minor trauma. Increased hair growth, as well as darkening and thickening of the skin may also occur. Neurological and abdominal symptoms are not characteristic of PCT.

Liver function abnormalities are common, but are usually mild. PCT is often associated with hepatitis C infection, which also can cause these liver complications. However, liver tests are generally abnormal even in PCT patients without hepatitis C infection. Progression to cirrhosis and even liver cancer occurs in some patients.


The diagnosis of PCT is made by demonstrating an abnormally high concentration of porphyrins in urine or plasma, with a predominance of uroporphyrinogen and heptacarboxylporphyrin. Porphobilinogen (PBG) is normal and aminolevulinic acid (ALA) may be slightly elevated. Fecal porphyrins may be normal or somewhat greater than normal, with a predominance of isocoproporphyrins. Patients with f-PCT usually have no family history of the disease, but these patients can be distinguished from patients with s-PCT by = finding half-normal URO-decarboxylase activity in red blood cells, or preferably by DNA studies. In all patients, it is important to look for all known susceptibility factors, as susceptibility factors should be eliminated as part of the management plan.

Treatment and Prognosis

PCT is the most treatable of the porphyrias. Treatment seems to be equally effective in f-PCT and s-PCT. Factors that tend to activate the disease (i. e., susceptibility factors) should be removed. The most widely recommended treatment is a schedule of repeated phlebotomies (removal of blood), with the aim of reducing iron in the liver. The target of this treatment is a serum ferritin near the lower limit of normal. Another treatment approach is a low dose regimen of the drug hydroxychloroquine. This drug mobilizes porphyrins from the liver. There is some risk of liver injury when PCT is treated with hydroxychloroquine, but this adverse effect is minimized by treating with a low-dose regimen. Relapses that occur after the initial treatment can be treated successfully using the same approach as for initial treatment.

PCT is difficult to treat while the patient is also being treated for hepatitis C with interferon and ribavirin. Therefore, PCT is generally treated first in cases where the two diseases occur together. Patients with marked iron overload should be treated by phlebotomy rather than hydroxychloroquine. PCT is often more severe and difficult to treat in patients with end-stage renal disease. Iron supplements should be stopped and erythropoietin administered to support small volume phlebotomies to reduce the serum ferritin level. Hydroxychloroquine is not effective in this setting.

Hepatoerythropoietic Porphyria (HEP)

Hepatoerythropoietic Porphyria (HEP) is a very rare type of autosomal recessive porphyria, due to mutations in both copies of the UROD gene resulting in severe deficiency of UROD enzyme activity in all cells. The main manifestation of HEP is skin blistering and is more severe than that observed in PCT. The blistering begins in infancy and resembles other severe cutaneous porphyrias such as CEP. However, the porphyrin profile in plasma and urine is similar to what is seen in PCT. The diagnosis is confirmed by checking UROD activity level in red blood cells and by genetic testing.

Congenital Erythropoietic Porphyria (CEP)

CEP, also known as Gunther disease, is very rare, with only several hundred cases reported in the literature.  The prevalence is not known.  It is an autosomal recessive disorder due to a severe deficiency of uroporphyrinogen III synthase (URO-synthase). Various mutations in the gene for this enzyme have been identified in different families.


CEP is one of the most severe porphyrias. As is characteristic of the erythropoietic porphyrias, symptoms usually begin soon after birth or in early childhood. Newborns with red-colored urine in the diaper should not undergo phototherapy for hyperbilirubinemia.  Some severe cases have been diagnosed prenatally as a cause of hemolytic anemia and non-immune fetal hydrops. Severe early-onset patients typically become transfusion-dependent secondary to hemolytic anemia and ineffective erythropoiesis and have extreme photosensitivity. Less severe patients, who have more residual UROS enzyme activity, may only have clinical manifestations of varying degrees of photosensitivity. Adult-onset cases may occur due to myelodysplasia.

Cutaneous photosensitivity results in severe blistering and scarring and can lead to secondary infections of the skin and bone. The photomutilation can result in the loss of facial features (nose, ear and lids) and digits. Hypertrichosis on sun-exposed skin, reddish-brown colored teeth (erythrodontia), and reddish-colored urine are also common features. There may be bone fragility due to expansion of the bone marrow and vitamin D deficiency. Red blood cells in severe cases have a shortened life-span, and mild or severe hemolytic anemia often results, along with increased erythroid synthesis and  splenomegaly. 


Clinical diagnosis is based on anemia, transfusion-dependence, and remarkable photosensitivity. Porphyrins accumulate first in the bone marrow, are deposited in the teeth and bones, and are markedly increased in red blood cells, plasma, urine, and feces. Uroporphyrin I and coproporphyrin I predominate in red blood cells, plasma, and urine. Coproporphyrin I is strikingly increased in feces. In some milder cases, zinc protoporphyrin may predominate in red blood cells. Identifying the mutations by sequencing of the UROS gene confirms the diagnosis and can predict severity. Very rarely CEP is  due to a mutation in the X-linked GATA1 gene. 

Treatment and Prognosis

Avoidance of sunlight is most important in the management of CEP. Protective clothing is a must, and special tinted glass on house and car windows is strongly recommended. Chronic erythrocyte transfusions to maintain a hematocrit of ~35% are required in severe cases to reduce porphyrin production by the marrow. In transfusion-dependent patients, bone marrow transplant may be considered as this is a curative treatment for CEP. Identifying the causative UROS mutations in a family enables prenatal diagnosis of affected pregnancies.

Erythropoietic Protoporphyria (EPP) and X-Linked Protoporphyria (XLP)

Erythropoietic protoporphyria (EPP) is the third most common porphyria, with a prevalence of 1 in 200,000 to 1 in 75,000 in different populations, and is the most common porphyria in children. Most cases are due to the markedly reduced activity of the enzyme, ferrochelatase (20-30% of normal), which catalyzes the insertion of iron into protoporphyrin to form heme. This causes excess accumulation of protoporphyrin. The inheritance of EPP follows an autosomal recessive pattern. In about 95% of EPP cases, the individual has a severe mutation of the ferrochelatase (FECH) gene inherited from one parent, and a common genetic variation of the same gene, inherited from the other parent. This common genetic variation causes reduced production of the enzyme, but in the absence of a severe mutation does not cause disease. The frequency of this common genetic variation in the FECH gene varies by population. It is present in about 43% of Japanese, 31% of Southeast Asians, 10% of Caucasians, and 1 to 3% of African Americans. Alternatively, in about 5% of EPP cases, two severe FECH gene mutations, are found.

In some cases where the symptoms are the same as EPP, the genetic defect is a mutation in the δ-aminolevulinate synthase-2 (ALAS2) gene, which is located on the X chromosome in erythroid tissue. This is called X-Linked Protoporphyria (XLP). The ALAS2 gene mutation results in a “gain of function” in ALAS2 due to increased stability and/or activity of this enzyme. As a result, the bone marrow produces more protoporphyrin than is needed for hemoglobin synthesis.

In all cases of EPP and XLP, protoporphyrin accumulates in the marrow and is transported to the skin in the plasma and red blood cells, where it initiates a photosensitivity reaction when the skin is exposed to sunlight. Protoporphyrin is not excreted by the kidneys, but is taken up by the liver and excreted in bile. Clinical and experimental studies have shown that this can impair bile formation and cause hepatobiliary injury.


Photosensitivity begins in early childhood, and can be difficult to diagnose, since there is usually no skin blistering or physical findings on exam. Photosensitivity can present within minutes of exposure to sunlight with severe burning pain on the sun exposed areas of the skin (generally the dorsum of the hands, feet and face). These episodes of pain may last for 2–3 days, and are usually unresponsive to any analgesics. The pain may be accompanied by localized swelling and erythema of the affected areas depending on the length of sunlight exposure. Patients are also sensitive to sunlight that passes through window glass (long wave ultraviolet light, or UVA). These symptoms greatly impair quality of life and limit employment opportunities and life style. Large amounts of protoporphyrin in bile can cause a formation of gallstones rich in this porphyrin. Approximately 20% of patients have some degree of hepatobiliary injury, and 1-5% have severe hepatobiliary injury from protoporphyrin toxicity that may necessitate liver transplantation.


The diagnosis of EPP/XLP is established biochemically by demonstrating increased protoporphyrin in red blood cells, with a predominance of metal-free protoporphyrin rather than zinc protoporphyrin. In XLP, the fraction of zinc protoporphyrin is higher than in EPP, ~10-40% of the total amount of protoporphyrin. The test is called “Erythrocyte Protoporphyin” in many labs, and a fractionation of free and zinc protoporphyrins may need to be specified. Plasma porphyrins are also increased in most cases. Measurement of urine porphyrins is not helpful for biochemical diagnosis of EPP/XLP.

Treatment and Prognosis

Treatment with pharmaceutical grade β-carotene (Lumitene) or cysteine may improve sunlight tolerance but reports of their effectiveness vary and they do not lower porphyrin levels. Additional information on Lumitene is provided below. Most patients learn to avoid sunlight as much as possible. Patients should be routinely screened for iron and vitamin D deficiencies and started on supplementation if clinically indicated. To avoid preventable injuries to the liver, Hepatitis A and B vaccinations are recommended, as is the avoidance of excessive alcohol use and other potential hepatotoxins.

Protoporphyric liver failure can appear suddenly and progress rapidly. Liver function tests should be done annually. A rise in transaminases without other explanation should be evaluated by liver imaging or biopsy for evidence of protoporphyrin hepatopathy. The treatment regimen for this generally involves a combination of plasmapheresis, blood transfusion, intravenous hemin, cholestyramine, vitamin E, and ursodeoxycholic acid. Levels of porphyrins in plasma and red blood cells should be followed closely during treatment. Liver transplantation is sometimes necessary, but it remains difficult to predict which patients will develop liver failure. Bone marrow transplantation is potentially curative in both EPP and XLP and will prevent recurrent damage to the transplanted liver.


The pharmaceutical grade formulation having the highest effective absorption is the "dry beta-carotene beadlets, 10%" made by Roche and distributed by Tishcon with the trade name, LumiteneTM. LumiteneTM can be ordered by calling 1-800-848-8442 or via their website

The following is the recommended dosage schedule:

  • For ages 1-4 years: 2-3 30 mg capsules per day
  • For ages 4-8 years: 3-4 30 mg capsules per day
  • For ages 8-12 years: 4-5 30 mg capsules per day
  • For ages 12-16 years: 5-6 30 mg capsules per day
  • For ages 16 and older: 6-10 30 mg capsules per day

Future treatment

Clinical trials investigating the effectiveness and safety of Alfamelanotide, for the treatment of photosensitivity of the erythropoietic protoporphyrias have been conducted in the US and Europe. Alfamelanotide (SCENESSE®), manufactured by Clinuvel Pharmaceuticals, is administered as an implant inserted under the skin. This medication approved in Europe as a treatment for EPP/XLP.