The term protoporphyria now encompasses three clinically similar disorders that most often result from hereditary mutations in one of three different genes. The most common is erythropoietic protoporphyria, (EPP, OMIM 177000), caused by impaired activity of ferrochelatase (FECH), the ultimate enzyme of heme biosynthesis. [1, 2, 3] The resultant accumulated excess of its substrate, metal-free protoporphyrin, causes two principal manifestations: (1) an acute cutaneous photosensitivity typically first appearing during childhood and (2) hepatobiliary disease. [1, 4, 5, 6]
The predominant genotype associated with phenotypic expression of EPP is one mutant ferrochelatase allele (FECH) encoding a defective enzyme protein with little or no function, paired with a relatively common polymorphic allele (IVS3-48T>C) with low gene expression that only mildly affects heme synthesis. [7, 8] This type of inheritance has been termed pseudodominant [9, 10] or semidominant,  but is often referred to as autosomal recessive  in that anomalies in both paired FECH alleles are required for disease expression, even though one alteration causes marked reduction or abrogation of residual enzyme activity while the polymorphism causes little clinically noticeable harm when unpaired with a severely dysfunctional allele. Infrequently, two deleterious FECH mutations are paired in a recessive genotype of EPP that may impart a higher risk for hepatic dysfunction. [13, 14] Rarely, acquired somatic mutation or deletion of a ferrochelatase gene secondary to myelodysplastic or myeloproliferative disorders leads to an adult-onset protoporphyric disorder. [15, 16, 17]
A far less frequent type (<10%) of hereditary protoporphyria, now recognized as a separate disorder, is X-linked dominant protoporphyria (XLDPP, OMIM 300752), or simply XLP. XLP arises from C-terminal deletions or alterations in the gene encoding the erythroid-specific enzyme 5-aminolevulinic acid synthase-2 (ALAS2), increased function of which leads to overproduction of protoporphyrin. [12, 18] Like EPP, XLP is caused by bone marrow heme synthetic dysfunction, but most often results in a greater ratio of accumulated erythrocyte zinc-protoporphyrin to metal-free protoporphyrin than is typical for EPP. XLP manifests as an acute, childhood-onset, cutaneous photosensitivity indistinguishable from that of EPP, but appears to have a higher risk for hepatic dysfunction.  An adult-onset case of XLP in an 89-year-old man with evolving myelodysplasia exhibited somatic mosaicism in erythroid hematopoietic cells associated with an ALAS2 mutation that predicted a C-terminal deletion. 
Mutation in a third gene, CLPX, which encodes the mitochondrial AAA+ unfoldase ClpX, has been linked to a familial disorder with biochemical and clinical features of protoporphyria in individuals without either FECH or ALAS2 mutations.  ClpX acts to control ALAS activation and degradation during heme synthesis. Defective CLPX leads to increased ALAS post-translational stability, which results in excess accumulation of erythrocyte protoporphyrin. 
Protoporphyrin is a lipophilic molecule capable of transformation to excited states by absorption of light energy. Excited-state protoporphyrin mediates photoxidative damage to biomolecular targets in the skin,  resulting in immediate phototoxic symptoms variously described as tingling, stinging, or burning that may be followed by the appearance of erythema, edema, and purpura. [4, 21] Excess protoporphyrin is formed during maturation of erythroid cells in the bone marrow and is present at the highest levels in reticulocytes and young erythrocytes.  Metal-free protoporphyrin escapes from red blood cells into the plasma, from which it is cleared by the liver and secreted into bile. Protoporphyrin-rich bile facilitates gallstone formation.  Toxic effects of protoporphyrin deposition in the liver may lead to life-threatening hepatic dysfunction. [23, 24, 25]
Loss of activity by as much as 50% as the result of 1 FECH mutant gene is generally insufficient to cause overt disease when its complementary allele has normal function.  FECH genotypes composed of either 2 mutant alleles (<1-4% of cases) or 1 mutation and a variant allele with a specific intronic single nucleotide polymorphism (IVS3-48C) (~82-94% of cases) have been found in most symptomatic individuals. [3, 10, 13, 14, 27] This polymorphism enhances aberrant splicing and rapid degradation of FECH mRNA, with resultant low expression.  The allele frequency of this polymorphism varies widely in diverse populations studied, as follows:
Southeast Asian – 31% 
White French – 11.3% 
North African – 2.7% 
Black West African – < 1% 
United States – 3.5% 
South Africans of European descent – 9% 
United Kingdom – 6.5% 
Chinese (different regions) – 28-41.4% 
Swedish – 8% 
The pairing of a mutated allele encoding a severely impaired enzyme protein with this low-expressing polymorphic allele typically yields enzyme activity diminished to less than 30% of normal, low enough to cause protoporphyrin accumulation. Individuals with no FECH mutation but who are heterozygous for this polymorphism typically do not have sufficiently diminished FECH activity to cause clinical abnormalities.  Individuals with no FECH mutation, but who are homozygous for this polymorphism, may exhibit slightly abnormal erythrocyte protoporphyrin levels and mild photosensitivity. 
Adult-onset protoporphyric photosensitivity and increased protoporphyrin levels have been associated with an acquired somatic mutation or deletion of a FECH gene due to myelodysplastic or myeloproliferative disorders. [15, 16, 17]
Eight families were described in 2008  with a protoporphyric disorder indistinguishable clinically from the predominant form of the disease, but without FECH mutations, that is now called X-linked dominant protoporphyria or X-linked protoporphyria (XLDPP, XLP or XLEPP [OMIM 300752]). Two different C-terminal deletions in the gene encoding the erythroid-specific isoform of aminolevulinic acid synthase were identified among these families.
The locus for this gene was identified on the X-chromosome, and the inheritance pattern in the families was consistent with X-linked dominant transmission. Both mutations caused a marked increase in activity of ALAS2 that eventuated in large accumulations of erythrocyte metal-free protoporphyrin and zinc-protoporphyrin. Seventeen percent of affected individuals in that study exhibited overt liver disease (40% of affected males), a significantly greater number than the 2-5% of individuals with ferrochelatase-deficient protoporphyria who develop this complication.
Additional cases of XLP and novel associated gain-of-function ALAS2 mutations have subsequently been recognized. [3, 10, 12, 19, 33, 34, 35] A higher prevalence (~10%) of XLP was found among 226 North American individuals with the protoporphyria phenotype; this is 2-5 times greater than observed among Western Europeans previously studied. [3, 12]
Until the recently established registry for protoporphyria sponsored by the American Porphyria Foundation collects sufficient data, accurate enumeration in the United States cannot be provided, but it is probably similar to data from European countries. A study of 226 North American individuals exhibiting the protoporphyria phenotype identified 22 with ALAS2 mutations and 187 with FECH anomalies.  The ALAS2/FECH ratio of approximately 10% in this study is greater than ratios reported elsewhere.
Estimates of one EPP case in populations of 75,000-200,000 have been reported for several Western European populations and in the South African population of European ancestry. [2, 6, 36, 37, 38] XLP remains rare but has been identified in increasing numbers. [10, 12, 18, 33, 34, 35, 39]
EPP has been reported most often in people with white heritage, but it has also been reported in persons with Japanese, Chinese, East Indian, or north or central African ancestry. XLP has been identified chiefly among individuals of Western European ancestry but also in an African American and Pacific Islander  and a Japanese boy. 
EPP and XLP occur in both males and females.
Photocutaneous symptoms usually appear during childhood,  but they also may be noted for the first time in adult life. [15, 16, 17, 19, 39] Gallstones may become symptomatic in young adulthood or in middle age.  Liver failure and its complications, sufficiently severe to result in liver transplantation and/or death, may develop in children and adolescents as well as adults. [23, 25, 40, 41, 42]
In the absence of hepatic failure, individuals with EPP have normal life expectancies.
Painful cutaneous photosensitivity reduces the sunlight tolerance of individuals with protoporphyria and may influence their lifestyles over entire lifetimes. 
Hepatotoxic effects of excess protoporphyrin deposition have led to liver dysfunction that progressed to life-threatening severity in approximately 2-5% of known cases of protoporphyria. 
Cox TM. Erythropoietic protoporphyria. J Inherit Metab Dis. 1997 Jun. 20(2):258-69. [Medline].
Parker M, Corrigall AV, Hift RJ, Meissner PN. Molecular characterization of erythropoietic protoporphyria in South Africa. Br J Dermatol. 2008 Jul. 159(1):182-91. [Medline].
Balwani M, Naik H, Anderson KE, Bissell DM, Bloomer J, Bonkovsky HL, et al. Clinical, biochemical, and genetic characterization of north american patients with erythropoietic protoporphyria and X-linked Protoporphyria. JAMA Dermatol. 2017 Aug 1. 153 (8):789-796. [Medline].
DeLeo VA, Poh-Fitzpatrick M, Mathews-Roth M, Harber LC. Erythropoietic protoporphyria. 10 years experience. Am J Med. 1976 Jan. 60(1):8-22. [Medline].
Baart de la Faille H, Bijlmer-Iest JC, van Hattum J, Koningsberger J, Rademakers LH, van Weelden H. Erythropoietic protoporphyria: clinical aspects with emphasis on the skin. Curr Probl Dermatol. 1991. 20:123-34. [Medline].
Todd DJ. Erythropoietic protoporphyria. Br J Dermatol. 1994 Dec. 131(6):751-66. [Medline].
Gouya L, Puy H, Lamoril J, et al. Inheritance in erythropoietic protoporphyria: a common wild-type ferrochelatase allelic variant with low expression accounts for clinical manifestation. Blood. 1999 Mar 15. 93(6):2105-10. [Medline].
Gouya L, Puy H, Robreau AM, et al. The penetrance of dominant erythropoietic protoporphyria is modulated by expression of wildtype FECH. Nat Genet. 2002 Jan. 30(1):27-8. [Medline].
Schmitt C, Ducamp S, Gouya L, Deybach JC, Puy H. [Inheritance in erythropoietic protoporphyria]. Pathol Biol (Paris). 2010 Oct. 58(5):372-80. [Medline].
Whatley SD, Mason NG, Holme SA, Anstey AV, Elder GH, Badminton MN. Molecular epidemiology of erythropoietic protoporphyria in the U.K. Br J Dermatol. 2010 Mar. 162(3):642-6. [Medline].
Frank J, Poblete-Gutiérrez P. Delayed diagnosis and diminished quality of life in erythropoietic protoporphyria: results of a cross-sectional study in Sweden. J Intern Med. 2011 Mar. 269(3):270-4. [Medline].
Balwani M, Doheny D, Bishop DF, Nazarenko I, Yasuda M, Dailey HA. Loss-of-function ferrochelatase and gain-of-function erythroid-specific 5-aminolevulinate synthase mutations causing erythropoietic protoporphyria and x-linked protoporphyria in North American patients reveal novel mutations and a high prevalence of X-linked protoporphyria. Mol Med. 2013. 19:26-35. [Medline].
Whatley SD, Mason NG, Khan M, et al. Autosomal recessive erythropoietic protoporphyria in the United Kingdom: prevalence and relationship to liver disease. J Med Genet. 2004 Aug. 41(8):e105. [Medline].
Gouya L, Martin-Schmitt C, Robreau AM, et al. Contribution of a common single-nucleotide polymorphism to the genetic predisposition for erythropoietic protoporphyria. Am J Hum Genet. 2006 Jan. 78(1):2-14. [Medline].
Goodwin RG, Kell WJ, Laidler P, et al. Photosensitivity and acute liver injury in myeloproliferative disorder secondary to late-onset protoporphyria caused by deletion of a ferrochelatase gene in hematopoietic cells. Blood. 2006 Jan 1. 107(1):60-2. [Medline].
Poh-Fitzpatrick MB, Wang X, Anderson KE, Bloomer JR, Bolwell B, Lichtin AE. Erythropoietic protoporphyria: altered phenotype after bone marrow transplantation for myelogenous leukemia in a patient heteroallelic for ferrochelatase gene mutations. J Am Acad Dermatol. 2002 Jun. 46(6):861-6. [Medline].
Aplin C, Whatley SD, Thompson P, et al. Late-onset erythropoietic porphyria caused by a chromosome 18q deletion in erythroid cells. J Invest Dermatol. 2001 Dec. 117(6):1647-9. [Medline].
Whatley SD, Ducamp S, Gouya L, Grandchamp B, Beaumont C, Badminton MN. C-terminal deletions in the ALAS2 gene lead to gain of function and cause X-linked dominant protoporphyria without anemia or iron overload. Am J Hum Genet. 2008 Sep. 83(3):408-14. [Medline].
Livideanu CB, Ducamp S, Lamant L, Gouya L, Rauzy OB, Deybach JC. Late-onset X-linked dominant protoporphyria: an etiology of photosensitivity in the elderly. J Invest Dermatol. 2013 Jun. 133(6):1688-90. [Medline].
Yien YY, Ducamp S, van der Vorm LN, Kardon JR, Manceau H, Kannengiesser C, et al. Mutation in human CLPX elevates levels of δ-aminolevulinate synthase and protoporphyrin IX to promote erythropoietic protoporphyria. Proc Natl Acad Sci U S A. 2017 Sep 19. 114 (38):E8045-E8052. [Medline].
Poh-Fitzpatrick MB. Porphyrin-sensitized cutaneous photosensitivity: pathogenesis and treatment. Clin Dermatol. 1985 Apr-Jun. 3(2):41-82. [Medline].
Piomelli S, Lamola AA, Poh-Fitzpatrick MF, Seaman C, Harber LC. Erythropoietic protoporphyria and lead intoxication: the molecular basis for difference in cutaneous photosensitivity. I. Different rates of disappearance of protoporphyrin from the erythrocytes, both in vivo and in vitro. J Clin Invest. 1975 Dec. 56(6):1519-27. [Medline].
Bloomer JR. The liver in protoporphyria. Hepatology. 1988 Mar-Apr. 8(2):402-7. [Medline].
Gross U, Frank M, Doss MO. Hepatic complications of erythropoietic protoporphyria. Photodermatol Photoimmunol Photomed. 1998 Apr. 14(2):52-7. [Medline].
Anstey AV, Hift RJ. Liver disease in erythropoietic protoporphyria: insights and implications for management. Gut. 2007 Jul. 56(7):1009-18. [Medline].
Brenner DA, Didier JM, Frasier F, Christensen SR, Evans GA, Dailey HA. A molecular defect in human protoporphyria. Am J Hum Genet. 1992 Jun. 50(6):1203-10. [Medline].
Saruwatari H, Ueki Y, Yotsumoto S, Shimada T, Fukumaru S, Kanekura T, et al. Genetic analysis of the ferrochelatase gene in eight Japanese patients from seven families with erythropoietic protoporphyria. J Dermatol. 2006 Sep. 33(9):603-8. [Medline].
Nakano H, Nakano A, Toyomaki Y, Ohashi S, Harada K, Moritsugu R, et al. Novel ferrochelatase mutations in Japanese patients with erythropoietic protoporphyria: high frequency of the splice site modulator IVS3-48C polymorphism in the Japanese population. J Invest Dermatol. 2006 Dec. 126 (12):2717-9. [Medline].
Risheg H, Chen FP, Bloomer JR. Genotypic determinants of phenotype in North American patients with erythropoietic protoporphyria. Mol Genet Metab. 2003 Sep-Oct. 80(1-2):196-206. [Medline].
Lau K, Lam C. DNA-based diagnosis of erythropoietic protoporphyria in two families and the frequency of a low-expression FECH allele in a Chinese population. Clin Chim Acta. 2009. 400:132-4. [Full Text].
Wiman A, Floderus Y, Harper P. Novel mutations and phenotypic effect of the splice site modulator IVS3-48C in nine Swedish families with erythropoietic protoporphyria. J Hum Genet. 2003. 48(2):70-6. [Medline].
Mizawa M, Makino T, Nakano H, Sawamura D, Shimizu T. Incomplete erythropoietic protoporphyria caused by a splice site modulator homozygous IVS3-48C polymorphism in the ferrochelatase gene. Br J Dermatol. 2016 Jan. 174 (1):172-5. [Medline].
Ducamp S, Schneider-Yin X, de Rooij F, Clayton J, Fratz EJ, Rudd A. Molecular and functional analysis of the C-terminal region of human erythroid-specific 5-aminolevulinic synthase associated with X-linked dominant protoporphyria (XLDPP). Hum Mol Genet. 2013 Apr 1. 22(7):1280-8. [Medline].
Ninomiya Y, Kokunai Y, Tanizaki H, Akasaka E, Nakano H, Moriwaki S. X-linked dominant protoporphyria: The first reported Japanese case. J Dermatol. 2015 Sep 21. 42:1-5. [Medline].
Landefeld C, Kentouche K, Gruhn B, Stauch T, Rößler S, Schuppan D, et al. X-linked protoporphyria: Iron supplementation improves protoporphyrin overload, liver damage and anaemia. Br J Haematol. 2015 Jul 20. [Medline].
Lecha M, Puy H, Deybach J-C. Erythropoietic protoporphyria. Orphanet Journal of Rare Diseases. 10 September 2009. 4:1-19. [Full Text].
Poh-Fitzpatrick MB. Human protoporphyria: reduced cutaneous photosensitivity and lower erythrocyte porphyrin levels during pregnancy. J Am Acad Dermatol. 1997 Jan. 36(1):40-3. [Medline].
Whalin S, Floderus Y, Stal P, Harper P. Erythropietic protoporphyria in Sweden: demographic, clinical, biochemical and genetic characteristics. J Intern Med. 2010. 269:278-288.
Livideanu CB, Ducamp S, Lamant L, Gouya L, Rauzy OB, Deybach JC, et al. Late-onset X-linked dominant protoporphyria: an etiology of photosensitivity in the elderly. J Invest Dermatol. 2013 Jun. 133 (6):1688-90. [Medline].
Cripps DJ, Gilbert LA, Goldfarb SS. Erythropoietic protoporphyria: juvenile protoporphyrin hepatopathy cirrhosis and death. J Pediatr. 1977 Nov. 91(5):744-8. [Medline].
Rand EB, Bunin N, Cochran W, Ruchelli E, Olthoff KM, Bloomer JR. Sequential liver and bone marrow transplantation for treatment of erythropoietic protoporphyria. Pediatrics. 2006 Dec. 118(6):e1896-9. [Medline].
McGuire BM, Bonkovsky HL, Carithers RL Jr, et al. Liver transplantation for erythropoietic protoporphyria liver disease. Liver Transpl. 2005 Dec. 11(12):1590-6. [Medline].
Méndez M, Poblete-Gutiérrez P, Morán-Jiménez MJ, Rodriguez ME, Garrido-Astray MC, Fontanellas A. A homozygous mutation in the ferrochelatase gene underlies erythropoietic protoporphyria associated with palmar keratoderma. Br J Dermatol. 2009 Jun. 160(6):1330-4. [Medline].
Holme SA, Whatley SD, Roberts AG, Anstey AV, Elder GH, Ead RD. Seasonal palmar keratoderma in erythropoietic protoporphyria indicates autosomal recessive inheritance. J Invest Dermatol. 2009 Mar. 129(3):599-605. [Medline].
Shehade SA, Chalmers RJ, Prescott RJ. Predictable and unpredictable hazards of erythropoietic protoporphyria. Clin Exp Dermatol. 1991 May. 16(3):185-7. [Medline].
Herbert A, Corbin D, Williams A, Thompson D, Buckels J, Elias E. Erythropoietic protoporphyria: unusual skin and neurological problems after liver transplantation. Gastroenterology. 1991 Jun. 100(6):1753-7. [Medline].
Rank JM, Carithers R, Bloomer J. Evidence for neurological dysfunction in end-stage protoporphyric liver disease. Hepatology. 1993 Dec. 18(6):1404-9. [Medline].
Gross U, Frank M, Doss MO. Hepatic complications of erythropoietic protoporphyria. Photodermatol Photoimmunol Photomed. 1998 Apr. 14(2):52-7. [Medline].
Doss MO, Frank M. Hepatobiliary implications and complications in protoporphyria, a 20-year study. Clin Biochem. 1989 Jun. 22(3):223-9. [Medline].
Balwani M, Doheny D, Bishop DF, Nazarenko I, Yasuda M, Dailey HA, et al. Loss-of-function ferrochelatase and gain-of-function erythroid-specific 5-aminolevulinate synthase mutations causing erythropoietic protoporphyria and x-linked protoporphyria in North American patients reveal novel mutations and a high prevalence of X-linked protoporphyria. Mol Med. 2013 Apr 30. 19:26-35. [Medline].
Gou EW, Balwani M, Bissell DM, Bloomer JR, Bonkovsky HL, Desnick RJ, et al. Pitfalls in erythrocyte protoporphyrin measurement for diagnosis and monitoring of protoporphyrias. Clin Chem. 2015 Dec. 61 (12):1453-6. [Medline].
Poh-Fitzpatrick MB, Whitlock RT, Leftkowitch JH. Changes in protoporphyrin distribution dynamics during liver failure and recovery in a patient with protoporphyria and Epstein-Barr viral hepatitis. Am J Med. 1986 May. 80(5):943-50. [Medline].
Holme SA, Worwood M, Anstey AV, Elder GH, Badminton MN. Erythropoiesis and iron metabolism in dominant erythropoietic protoporphyria. Blood. 2007 Dec 1. 110 (12):4108-10. [Medline].
Mathews-Roth MM. Letter: Anemia in erythropoietic protoporphyria. JAMA. 1974 Nov 11. 230(6):824. [Medline].
Gordeuk VR, Brittenham GM, Hawkins CW, Mukhtar H, Bickers DR. Iron therapy for hepatic dysfunction in erythropoietic protoporphyria. Ann Intern Med. 1986 Jul. 105(1):27-31. [Medline].
Bentley DP, Meek EM. Clinical and biochemical improvement following low-dose intravenous iron therapy in a patient with erythropoietic protoporphyria. Br J Haematol. 2013 Oct. 163 (2):289-91. [Medline].
Holme SA, Thomas CL, Whatley SD, Bentley DP, Anstey AV, Badminton MN. Symptomatic response of erythropoietic protoporphyria to iron supplementation. J Am Acad Dermatol. 2007 Jun. 56 (6):1070-2. [Medline].
McClements BM, Bingham A, Callender ME, Trimble ER. Erythropoietic protoporphyria and iron therapy. Br J Dermatol. 1990 Mar. 122(3):423-4. [Medline].
Milligan A, Graham-Brown RA, Sarkany I, Baker H. Erythropoietic protoporphyria exacerbated by oral iron therapy. Br J Dermatol. 1988 Jul. 119 (1):63-6. [Medline].
Spelt JM, de Rooij FW, Wilson JH, Zandbergen AA. Vitamin D deficiency in patients with erythropoietic protoporphyria. J Inherit Metab Dis. 2010 Dec. 33 Suppl 3:S1-4. [Medline].
Allo G, del Carmen Garrido-Astray M, De Salamanca RE, Martínez G, Hawkins F. Bone mineral density and vitamin D levels in erythropoietic protoporphyria. Endocrine. 2013 Dec. 44(3):803-7. [Medline].
Wahlin S, Aschan J, Bjornstedt M, Broomé U, Harper P. Curative bone marrow transplantation in erythropoietic protoporphyria after reversal of severe cholestasis. J Hepatol. 2007 Jan. 46(1):174-9. [Medline].
Wahlin S, Stal P, Adam R, Karam V, Porte R, Seehofer D. Liver transplantation for erythropoietic protoporphyria in Europe. Liver Transpl. 2011 Sep. 17(9):1021-6. [Medline].
Wolff K, Honigsmann H, Rauschmeier W, Schuler G, Pechlaner R. Microscopic and fine structural aspects of porphyrias. Acta Derm Venereol Suppl (Stockh). 1982. 100:17-28. [Medline].
Epstein JH, Tuffanelli DL, Epstein WL. Cutaneous changes in the porphyrias. A microscopic study. Arch Dermatol. 1973 May. 107(5):689-98. [Medline].
Bloomer JR, Rank JM, Payne WD, et al. Follow-up after liver transplantation for protoporphyric liver disease. Liver Transpl Surg. 1996 Jul. 2(4):269-75. [Medline].
Johnson JA, Fusaro RM. Broad-spectrum photoprotection: the roles of tinted auto windows, sunscreens and browning agents in the diagnosis and treatment of photosensitivity. Dermatology. 1992. 185(4):237-41. [Medline].
Roelandts R. Photo(chemo)therapy and general management of erythropoietic protoporphyria. Dermatology. 1995. 190(4):330-1. [Medline].
Minder EI. Afamelanotide, an agonistic analog of a-melanocyte-stimulating hormone, in dermal phototoxicity of erythropoietic protoporphyria. Expert Opin Investig Drugs. 2010 Dec. 19(12):1591-602. [Medline].
Kim ES, Garnock-Jones KP. Afamelanotide: a review in erythropoietic protoporphyria. Am J Clin Dermatol. 2016 Apr. 17 (2):179-85. [Medline].
Minder EI, Barman-Aksoezen J, Schneider-Yin X. Pharmacokinetics and pharmacodynamics of afamelanotide and its clinical use in treating dermatologic disorders. Clin Pharmacokinet. 2017 Aug. 56 (8):815-823. [Medline].
Mathews-Roth MM, Pathak UA, Fitzpatrick TB, Harber LC, Kass EH. Beta-carotene as an oral photoprotective agent in erythropoietic protoporphyria. JAMA. 1974 May 20. 228(8):1004-8. [Medline].
Mathews-Roth MM. Carotenoid functions in photoprotection and cancer prevention. J Environ Pathol Toxicol Oncol. 1990 Jul-Oct. 10(4-5):181-92. [Medline].
Mathews-Roth MM, Rosner B. Long-term treatment of erythropoietic protoporphyria with cysteine. Photodermatol Photoimmunol Photomed. 2002 Dec. 18(6):307-9. [Medline].
Ross JB, Moss MA. Relief of the photosensitivity of erythropoietic protoporphyria by pyridoxine. J Am Acad Dermatol. 1990 Feb. 22(2 Pt 2):340-2. [Medline].
Farr PM, Diffey BL, Matthews JN. Inhibition of photosensitivity in erythropoietic protoporphyria with terfenadine. Br J Dermatol. 1990 Jun. 122(6):809-15. [Medline].
Yamamoto S, Hirano Y, Horie Y. Cimetidine reduces erythrocyte protoporphyrin in erythropoietic protoporphyria. Am J Gastroenterol. 1993 Sep. 88(9):1465-6. [Medline].
Tu JH, Sheu SL, Teng JM. Novel Treatment Using Cimetidine for Erythropoietic Protoporphyria in Children. JAMA Dermatol. 2016 Nov 1. 152 (11):1258-1261. [Medline].
Tishler PV, Rosner B. Treatment of erythropoietic protoporphyria with the oral sorbent colestipol: A proof-of-concept clinical trial. J Amer Acad Dermatol. 2014. 70 (2):391-2.
McCullough AJ, Barron D, Mullen KD, et al. Fecal protoporphyrin excretion in erythropoietic protoporphyria: effect of cholestyramine and bile acid feeding. Gastroenterology. 1988 Jan. 94(1):177-81. [Medline].
Gorchein A, Foster GR. Liver failure in protoporphyria: long-term treatment with oral charcoal. Hepatology. 1999 Mar. 29(3):995-6. [Medline].
van Wijk HJ, van Hattum J, Baart de la Faille H, van den Berg JW, Edixhoven-Bosdijk A, Wilson JH. Blood exchange and transfusion therapy for acute cholestasis in protoporphyria. Dig Dis Sci. 1988 Dec. 33(12):1621-5. [Medline].
Dellon ES, Szczepiorkowski ZM, Dzik WH, et al. Treatment of recurrent allograft dysfunction with intravenous hematin after liver transplantation for erythropoietic protoporphyria. Transplantation. 2002 Mar 27. 73(6):911-5. [Medline].
Do KD, Banner BF, Katz E, Szymanski IO, Bonkovsky HL. Benefits of chronic plasmapheresis and intravenous heme-albumin in erythropoietic protoporphyria after orthotopic liver transplantation. Transplantation. 2002 Feb 15. 73(3):469-72. [Medline].
Komatsu H, Ishii K, Imamura K, et al. A case of erythropoietic protoporphyria with liver cirrhosis suggesting a therapeutic value of supplementation with alpha-tocopherol. Hepatol Res. 2000 Nov. 18(3):298-309. [Medline].
Eichbaum QG, Dzik WH, Chung RT, Szczepiorkowski ZM. Red blood cell exchange transfusion in two patients with advanced erythropoietic protoporphyria. Transfusion. 2005 Feb. 45(2):208-13. [Medline].
Dowman JK, Gunson BK, Mirza DF, Badminton MN, Newsome PN,. UK experience of liver transplantation for erythropoietic protoporphyria. J Inherit Metab Dis. 2011 Apr. 34(2):539-45. [Medline].
Meerman L, Verwer R, Slooff MJ, et al. Perioperative measures during liver transplantation for erythropoietic protoporphyria. Transplantation. 1994 Jan. 57(1):155-8. [Medline].
Wahlin S, Srikanthan N, Hamre B, Harper P, Brun A. Protection from phototoxic injury during surgery and endoscopy in erythropoietic protoporphyria. Liver Transpl. 2008 Sep. 14(9):1340-6. [Medline].
Graham-Brown MP, Ilchyshyn A. Development of acute phototoxic reaction during surgery in a patient with erythropoietic protoporphyria. Clin Exp Dermatol. 2013 Jul. 38 (5):566-8; quiz 568. [Medline].
Morris SD, Mason NG, Elder GH, Hawk JL, Sarkany RP. Ferrochelatase gene polymorphism analysis for accurate genetic counselling in erythropoietic protoporphyria. Br J Dermatol. 2002 Sep. 147(3):572-4. [Medline].
Schneider-Yin X, Gouya L, Meier-Weinand A, Deybach JC, Minder EI. New insights into the pathogenesis of erythropoietic protoporphyria and their impact on patient care. Eur J Pediatr. 2000 Oct. 159(10):719-25. [Medline].
Redeker AG, Sterling RE. The “glucose effect” in erythropoietic protoporphyria. Arch Intern Med. 1968 May. 121(5):446-8. [Medline].
Bonkovsky HL, Schned AR. Fatal liver failure in protoporphyria. Synergism between ethanol excess and the genetic defect. Gastroenterology. 1986 Jan. 90(1):191-201. [Medline].
Maureen B Poh-Fitzpatrick, MD Professor Emerita of Dermatology and Special Lecturer, Columbia University College of Physicians and Surgeons
Disclosure: Nothing to disclose.
David F Butler, MD Former Section Chief of Dermatology, Central Texas Veterans Healthcare System; Professor of Dermatology, Texas A&M University College of Medicine; Founding Chair, Department of Dermatology, Scott and White Clinic
David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Society for MOHS Surgery, Association of Military Dermatologists, Phi Beta Kappa
Disclosure: Nothing to disclose.
Edward F Chan, MD Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania School of Medicine
Disclosure: Nothing to disclose.
William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine
Disclosure: Received income in an amount equal to or greater than $250 from: Elsevier; WebMD.
Günter Burg, MD Professor and Chairman Emeritus, Department of Dermatology, University of Zürich School of Medicine; Delegate of The Foundation for Modern Teaching and Learning in Medicine Faculty of Medicine, University of Zürich, Switzerland
Günter Burg, MD is a member of the following medical societies: American Academy of Dermatology, American Dermatological Association, International Society for Dermatologic Surgery, North American Clinical Dermatologic Society, and Pacific Dermatologic Association
Disclosure: Nothing to disclose.
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