The Cutaneous Porphyrias

  • Robert P. E. SarkanyEmail author


The porphyrias are a group of disorders caused by defects in the biosynthesis of haem. Their relevance to the skin arises from the phototoxic properties of the accumulated porphyrins.

The majority of the porphyrias are inherited. Many of them affect other organs as well as the skin. Some may cause dangerous acute attacks.

The porphyrias that commonly present to dermatologists are congenital erythropoietic porphyria (CEP), erythropoietic protoporphyria (EPP), porphyria cutanea tarda (PCT) and variegate porphyria (VP). Hereditary coproporphyria (HC) less commonly presents in the skin. Porphyrias present in the skin in three ways: mutilating photosensitivity (congenital erythropoietic porphyria), immediate painful photosensitivity (erythropoietic protoporphyria) or bullae and skin fragility (porphyria cutanea tarda, variegate porphyria). Diagnosis depends on laboratory analysis of body fluids for porphyrins by an experienced laboratory. Porphyria cutanea tarda is an acquired disease; the rest are hereditary. PCT is frequently caused by a variety of systemic and hepatological diseases. PCT and EPP may be complicated by liver disease; CEP has severe and multiple internal complications; VP can cause life-threatening acute attacks. Management involves visible light photoprotection for all the porphyrias. PCT is fully treatable by low-dose antimalarial drugs or venesection.


Porphyria Porphyria cutanea tarda Protoporphyria Variegate Gunther’s Erythropoietic 


  1. Allo G, del Carmen Garrido-Astray M, Méndez M, et al. Bone mineral density and vitamin D levels in erythropoietic protoporphyria. Endocrine. 2013;44:803–7Google Scholar
  2. Ashton RE, Hawk JLM, Magnus IA. Low-dose oral chloroquine in the treatment of porphyria cutanea tarda. Br J Dermatol. 1984;111:609–13.PubMedCrossRefGoogle Scholar
  3. Blauvelt A, Ross Harris H, Hogan DJ, et al. Porphyria cutanea tarda and human immunodeficiency virus infection. Int J Dermatol. 1992;31:474–9.PubMedCrossRefGoogle Scholar
  4. Bruguera M. Liver involvement in porphyria. Semin Dermatol. 1986;5:178–85.Google Scholar
  5. Brun A, Sandberg S. Mechanisms of photosensitivity in porphyric patients with special emphasis on erythropoietic protoporphyria. J Photochem Photobiol B. 1991;10:285–302.PubMedCrossRefGoogle Scholar
  6. Bulaj ZJ, Phillips JD, Ajioka RS, et al. Hemochromatosis genes and other factors contributing to the pathogenesis of porphyria cutanea tarda. Blood. 2000a;95:1565–71.PubMedGoogle Scholar
  7. Bulaj ZJ, Franklin MR, Phillips JD, et al. Transdermal estrogen replacement therapy in postmenopausal women previously treated for porphyria cutanea tarda. J Lab Clin Med. 2000b;136:482–8.PubMedCrossRefGoogle Scholar
  8. Caputo R, Berti E, Gasparini G, Monti M. The morphologic events of blister formation in porphyria cutanea tarda. Int J Dermatol. 1983;22:467–72.PubMedCrossRefGoogle Scholar
  9. Collins P, Ferguson J. Narrow-band UVB (TL-01) phototherapy. An effective preventative treatment for the photodermatoses. Br J Dermatol. 1995;132:956–63.PubMedCrossRefGoogle Scholar
  10. Da Silva V, Simonin S, Deybach JC, et al. Variegate porphyria: diagnostic value of fluorometric scanning of plasma porphyrins. Clin Chim Acta. 1995;238:163–8.PubMedCrossRefGoogle Scholar
  11. Day RS. Variegate porphyria. Semin Dermatol. 1986;5:138–54.Google Scholar
  12. Deacon A. The porphyrias and their investigation. CPD Bull Clin Biochem. 1999;1:122–6.Google Scholar
  13. Deacon AC, Elder GH. ACP Best Practice No 165: front line tests for the investigation of suspected porphyria. J Clin Pathol. 2001;54:500–7.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Dean G. The Turkish epidemic of porphyria. In: Dean G, editor. The porphyrias: a story of inheritance and environment. 2nd ed. London: Pitman Medical; 1971. p. 67–72.Google Scholar
  15. Deleo VA, Poh-Fitzpatrick M, Mathews-Roth M, Harber LC. Erythropoietic protoporphyria. Ten years experience. Am J Med. 1976;60:8–22.PubMedCrossRefGoogle Scholar
  16. Doss MO, Frank M. Hepatobiliary implications and complications in protoporphyria, a 20-year study. Clin Biochem. 1989;22:223–9.PubMedCrossRefGoogle Scholar
  17. Elder GH. Porphyria cutanea tarda. Semin Liver Dis. 1998;18:67–75.PubMedCrossRefGoogle Scholar
  18. Elder GH. The cutaneous porphyrias. In: Hawk JLM, editor. Photodermatology. London: Arnold; 1999a. p. 171–99.Google Scholar
  19. Elder GH. Alcohol intake and porphyria cutanea tarda. Clin Dermatol. 1999b;17:431–6.PubMedCrossRefGoogle Scholar
  20. Elder GH, Urquhart AJ, De Salamanca RE, et al. Immunoreactive uroporphyrinogen decarboxylase in the liver in porphyria cutanea tarda. Lancet. 1985;​2:229–33.PubMedCrossRefGoogle Scholar
  21. Elder GH, Hift RJ, Meissner PN. The acute porphyrias. Lancet. 1997;349:1613–7.PubMedCrossRefGoogle Scholar
  22. Elder G, Harper P, Badminton M, et al. The incidence of inherited porphyrias in Europe. J Inherit Metab Dis. 2013;36:849–57.PubMedCrossRefGoogle Scholar
  23. Epstein JH, Tuffanelli DL, Epstein WL. Cutaneous changes in the porphyrias. A microscopic study. Arch Dermatol. 1973;107:689–98.PubMedCrossRefGoogle Scholar
  24. Fargion S, Piperno A, Cappellini MD, et al. Hepatitis C virus and porphyria cutanea tarda: evidence of a strong association. Hepatology. 1992;16:1322–6.PubMedCrossRefGoogle Scholar
  25. Gisbert JP, Garcia-Buey L, Alonso A, et al. Hepatocellular carcinoma risk in patients with porphyria cutanea tarda. Eur J Gastroenterol Hepatol. 2004;16:689–92.PubMedCrossRefGoogle Scholar
  26. Glover RA, Bailey CS, Barrett KE, et al. Histamine release from rodent and human mast cells induced by protoporphyrin and ultraviolet light: studies of the mechanism of mast-cell activation in erythropoietic protoporphyria. Br J Dermatol. 1990;122:501–12.PubMedCrossRefGoogle Scholar
  27. Gouya L, Puy H, Robreau AM, et al. The penetrance of dominant erythropoietic protoporphyria is modulated by expression of wildtype FECH. Nat Genet. 2002;30:27–8.PubMedCrossRefGoogle Scholar
  28. Grandchamp B, Phung N, Nordmann Y. Homozygous case of hereditary coproporphyria. Lancet. 1977;2:1348–9.PubMedCrossRefGoogle Scholar
  29. Grossman ME, Bickers DR, Poh-Fitzpatrick MB, et al. Porphyria cutanea tarda: clinical features and laboratory findings in 40 patients. Am J Med. 1979;67:277–86.PubMedCrossRefGoogle Scholar
  30. Gschnait FG, Wolff K, Konrad K. Erythropoietic protoprophyria—submicroscopic events during the acute photosensitivity flare. Br J Dermatol. 1975;92:545–57.CrossRefGoogle Scholar
  31. Haberman HF, Rosenberg F, Menon IA. Porphyria cutanea tarda. Comparison of cases precipitated by alcohol and estrogens. Can Med Assoc J. 1975;113:653–5.PubMedPubMedCentralGoogle Scholar
  32. Hanneken S, Siegesmund M, Bolsen K, et al. The prognostic value of cord blood analysis in erythropoietic protoporphyria: the ‘Duesseldorf Cord Blood Study’. Photodermatol Photoimmunol Photomed. 2010;26:7–9.PubMedCrossRefGoogle Scholar
  33. Harms J, Lautenschlager S, Minder CE, et al. An alpha-melanocyte-stimulating hormone analogue in erythropoietic protoporphyria. N Engl J Med. 2009;360:306–7.PubMedCrossRefGoogle Scholar
  34. Hawk JL, Magnus IA, Parkes A, et al. Deficiency of hepatic coproporphyrinogen oxidase in hereditary coproporphyria. J R Soc Med. 1978;71:775–7.PubMedPubMedCentralCrossRefGoogle Scholar
  35. Herrmann G, Wlaschek M, Bolsen K, et al. Photosensitization of uroporphyrin augments the ultraviolet A-induced synthesis of matrix metalloproteinases in human dermal fibroblasts. J Invest Dermatol. 1996;107:398–403.PubMedCrossRefGoogle Scholar
  36. Hift RJ, Meissner PN, Todd G, et al. Homozygous variegate porphyria: an evolving clinical syndrome. Postgrad Med J. 1993;69:781–6.PubMedPubMedCentralCrossRefGoogle Scholar
  37. Hift RJ, Davidson BP, van der Hooft C, et al. Plasma fluorescence scanning and fecal porphyrin analysis for the diagnosis of variegate porphyria: precise determination of sensitivity and specificity with detection of protoporphyrinogen oxidase mutations as a reference standard. Clin Chem. 2004;50:915–23.PubMedCrossRefGoogle Scholar
  38. Holme SA, Anstey AV, Finlay AY, et al. Erythropoietic protoporphyria in the U.K.: clinical features and effect on quality of life. Br J Dermatol. 2006;155:574–81.PubMedCrossRefGoogle Scholar
  39. Holme SA, Anstey AV, Badminton MN, et al. Serum 25-hydroxyvitamin D in erythropoietic protoporphyria. Br J Dermatol. 2008;159:211–3.PubMedCrossRefGoogle Scholar
  40. Holme SA, Whatley SD, Roberts AG, et al. Seasonal palmar keratoderma in erythropoietic protoporphyria indicates autosomal recessive inheritance. J Invest Dermatol. 2009;129:599–605.PubMedCrossRefGoogle Scholar
  41. Inglese MJ, Bergamo BM. Large, nonhealing scalp ulcer associated with scarring alopecia and sclerodermatous change in a patient with porphyria cutanea tarda. Cutis. 2005;76:329–33.PubMedGoogle Scholar
  42. Johnson JA. Durable protection against long-wavelength UV-A radiation and blue light. Arch Dermatol. 1992;128:409.PubMedCrossRefGoogle Scholar
  43. Katugampola RP, Badminton MN, Finlay AY, et al. Congenital erythropoietic porphyria: a single-observer clinical study of 29 cases. Br J Dermatol. 2012a;167:901–13.PubMedCrossRefGoogle Scholar
  44. Katugampola RP, Anstey AV, Finlay AY, et al. A management algorithm for congenital erythropoietic porphyria derived from a study of 29 cases. Br J Dermatol. 2012b;167:888–900.PubMedCrossRefGoogle Scholar
  45. Kaye ET, Levin JA, Blank IH, et al. Efficiency of opaque photoprotective agents in the visible light range. Arch Dermatol. 1991;127:351–5.PubMedCrossRefGoogle Scholar
  46. Kordac V, Kotal JP, Kalab M. Agents affecting porphyrin formation and secretion: implications for porphyria cutanea tarda treatment. Semin Hematol. 1989;26:16–23.PubMedGoogle Scholar
  47. Kuhnel A, Gross U, Doss MO. Hereditary coproporphyria in Germany: clinical-biochemical studies in 53 patients. Clin Biochem. 2000;33:465–73.PubMedCrossRefGoogle Scholar
  48. Lim HW, Poh-Fitzpatrick M, Gigli I. Activation of the complement system in patients with porphyrias after irradiation in vivo. J Clin Invest. 1984;74:1961–5.PubMedPubMedCentralCrossRefGoogle Scholar
  49. Linde Y, Harper P, Floderus Y, Ros AM. The prevalence of hepatitis C in patients with porphyria cutanea tarda in Stockholm, Sweden. Acta Derm Venereol. 2005;85:164–6.PubMedCrossRefGoogle Scholar
  50. Long C, Smyth SJ, Woolf J, et al. Detection of latent variegate porphyria by fluorescence emission spectroscopy of plasma. Br J Dermatol. 1993;129:9–13.PubMedCrossRefGoogle Scholar
  51. Malina L, Chlumsky J. A comparative study of the results of phlebotomy therapy and low-dose chloroquine treatment in porphyria cutanea tarda. Acta Derm Venereol Suppl (Stockh). 1981;61:346–50.Google Scholar
  52. Marsden RA, Dawber RP. Erythropoietic protoporphyria with onycholysis. Proc R Soc Med. 1977;70:572–4.PubMedPubMedCentralGoogle Scholar
  53. Mascaro JM, Herrero C, Lecha M, et al. Uroporphyrinogen-decarboxylase deficiencies: porphyria cutanea tarda and related conditions. Semin Dermatol. 1986;5:115–24.Google Scholar
  54. Minder EI, Gouya L, Schneider-Yin X, Deybach JC. A genotype–phenotype correlation between null-allele mutations in the ferrochelatase gene and liver complication in patients with erythropoietic protoporphyria. Cell Mol Biol (Noisy-le-Grand). 2002;48:91–6.Google Scholar
  55. Moseley H, Cameron H, MacLeod T, et al. New sunscreens confer improved protection for photosensitive patients in the blue light region. Br J Dermatol. 2001;145:789–94.PubMedCrossRefGoogle Scholar
  56. Murphy GM, Hawk JL, Magnus IA. Late-onset erythropoietic protoporphyria with unusual cutaneous features. Arch Dermatol. 1985;121:1309–12.PubMedCrossRefGoogle Scholar
  57. Murphy A, Dooley S, Hillary IB, Murphy GM. HCV infection in porphyria cutanea tarda. Lancet. 1993;341:1534–5.PubMedCrossRefGoogle Scholar
  58. Mustajoki P. Variegate porphyria. Twelve years’ experience in Finland. QJM. 1980;49:191–203.PubMedGoogle Scholar
  59. Norris PG, Baker CS, Roberts JE, Hawk JL. Treatment of erythropoietic protoporphyria with N-acetylcysteine. Arch Dermatol. 1995;131:354–5.PubMedCrossRefGoogle Scholar
  60. Park AJ, Webster GF, Penne RB, Raber IM. Porphyria cutanea tarda presenting as cicatricial conjunctivitis. Am J Ophthalmol. 2002;134:619–21.PubMedCrossRefGoogle Scholar
  61. Phillips JD, Bergonia HA, Reilly CA, et al. A porphomethene inhibitor of uroporphyrinogen decarboxylase causes porphyria cutanea tarda. Proc Natl Acad Sci. 2007;104:5079–84.PubMedCrossRefGoogle Scholar
  62. Pitche P, Corrin E, Wolkenstein P, et al. Successful treatment of haemodialysis-related porphyria cutanea tarda with deferoxamine. Ann Dermatol Venereol. 2003;130:37–9.PubMedGoogle Scholar
  63. Poh-Fitzpatrick MB. The ‘priming phenomenon’ in the acute phototoxicity of erythropoietic protoporphyria. J Am Acad Dermatol. 1989;21:311.PubMedCrossRefGoogle Scholar
  64. Poh-Fitzpatrick MB. Human protoporphyria: reduced cutaneous photosensitivity and lower erythrocyte porphyrin levels during pregnancy. J Am Acad Dermatol. 1997;36:40–3.PubMedCrossRefGoogle Scholar
  65. Quecedo L, Costa J, Enriquez de Salamanca R. Role of hepatitis C virus in porphyria cutanea tarda hepatopathy. Med Clin (Barc). 1996;106:321–4.Google Scholar
  66. Rand EB, Bunin N, Cochran W, Ruchelli E, et al. Sequential liver and bone marrow transplantation for treatment of erythropoietic protoporphyria. Pediatrics. 2006;118:e1896–9.PubMedCrossRefGoogle Scholar
  67. Rank JM, Straka JG, Weimer MK, et al. Hematin therapy in late onset congenital erythropoietic porphyria. Br J Haematol. 1990;75:617–8.PubMedCrossRefGoogle Scholar
  68. Ratnaike S, Blake D, Campbell D, et al. Plasma ferritin levels as a guide to the treatment of porphyria cutanea tarda by venesection. Australas J Dermatol. 1988;29:3–7.PubMedCrossRefGoogle Scholar
  69. Roberts AG, Whatley SD, Morgan RR, et al. Increased frequency of the haemochromatosis Cys282Tyr mutation in sporadic porphyria cutanea tarda. Lancet. 1997;349:321–3.PubMedCrossRefGoogle Scholar
  70. Rocchi E, Gibertini P, Cassanelli M, et al. Serum ferritin in the assessment of liver iron overload and iron removal therapy in porphyria cutanea tarda. J Lab Clin Med. 1986a;107:36–42.PubMedGoogle Scholar
  71. Rocchi E, Gibertini P, Cassanelli M, et al. Iron removal therapy in porphyria cutanea tarda: phlebotomy versus slow subcutaneous desferrioxamine infusion. Br J Dermatol. 1986b;114:621–9.PubMedCrossRefGoogle Scholar
  72. Roelandts R. Photo (chemo) therapy and general management of erythropoietic protoporphyria. Dermatology. 1995;190:330–1.PubMedCrossRefGoogle Scholar
  73. Ryan EA, Madill GT. Electron microscopy of the skin in erythropoietic protoporphyria. Br J Dermatol. 1968;80:561–70.PubMedCrossRefGoogle Scholar
  74. Sarkany RPE. The management of porphyria cutanea tarda. Clin Exp Dermatol. 2001;26:225–32.PubMedCrossRefGoogle Scholar
  75. Sarkany RPE. Making sense of the porphyrias. Photodermatol Photoimmunol Photomed. 2008;24:102–8.PubMedCrossRefGoogle Scholar
  76. Sarkany RPE, Cox TM. Autosomal recessive erythropoietic protoporphyria: a syndrome of severe photosensitivity and hepatic failure. QJM. 1995;88:541–9.PubMedGoogle Scholar
  77. Sarkany RP, Ross G, Willis F. Acquired erythropoietic protoporphyria as a result of myelodysplasia causing loss of chromosome 18. Br J Dermatol. 2006;155:464–6.PubMedCrossRefGoogle Scholar
  78. Sarkany RP, Ibbotson SH, Whatley SD, et al. Erythropoietic uroporphyria associated with myeloid malignancy is likely distinct from autosomal recessive congenital erythropoietic porphyria. J Invest Dermatol. 2011;131:1172–5.PubMedCrossRefGoogle Scholar
  79. Sarkell B, Patterson JW. Treatment of porphyria cutanea tarda of end-stage renal disease with erythropoietin. J Am Acad Dermatol. 1993;29:499–500.PubMedCrossRefGoogle Scholar
  80. Schneider-Yin X, Van Tuyll van Serooskerken AM, Went P, et al. Hepatocellular carcinoma in variegate porphyria: a serious complication. Acta Derm Venereol. 2010;90:512–5.PubMedCrossRefGoogle Scholar
  81. Scholnick PL, Epstein J, Marver HS. The molecular basis of the action of chloroquine in porphyria cutanea tarda. J Invest Dermatol. 1973;61:226–32.PubMedCrossRefGoogle Scholar
  82. Shaffrali FC, McDonagh AJ, Messenger AG. Hair darkening in porphyria cutanea tarda. Br J Dermatol. 2002;146:325–9.PubMedCrossRefGoogle Scholar
  83. Shaw PH, Mancini AJ, McConnell JP, et al. Treatment of congenital erythropoietic porphyria in children by allogeneic stem cell transplantation: a case report and review of the literature. Bone Marrow Transplant. 2001;27:101–5.PubMedCrossRefGoogle Scholar
  84. Sheikh MY, Wright RA, Burruss JB. Dramatic resolution of skin lesions associated with porphyria cutanea tarda after interferon-alpha therapy in a case of chronic hepatitis C. Dig Dis Sci. 1998;43:529–33.PubMedCrossRefGoogle Scholar
  85. Siersema PD, ten Kate FJW, Mulder PGH, Wilson JHP. Hepatocellular carcinoma in porphyria cutanea tarda: frequency and factors related to its occurrence. Liver. 1992;12:56–61.PubMedCrossRefGoogle Scholar
  86. Singal AK, Kormos-Hallberg C, Lee C, et al. Low-dose hydroxychloroquine is as effective as phlebotomy in treatment of patients with porphyria cutanea tarda. Clin Gastroenterol Hepatol. 2012;10:1402–9.PubMedPubMedCentralCrossRefGoogle Scholar
  87. Stojeba N, Meyer C, Jeanpierre C, et al. Recovery from a variegate porphyria by a liver transplantation. Liver Transpl. 2004;10:935–8.PubMedCrossRefGoogle Scholar
  88. Sturrock ED, Meissner PN, Maeder DL, Kirsch RE. Uroporphyrinogen decarboxylase and protoporphyrinogen oxidase in dual porphyria. S Afr Med J. 1989;76:405–8.PubMedGoogle Scholar
  89. Takeshita K, Takajo T, Hirata H, et al. In vivo oxygen radical generation in the skin of the protoporphyria model mouse with visible light exposure: an L-band ESR study. J Invest Dermatol. 2004;122:1463–70.PubMedCrossRefGoogle Scholar
  90. Tewari A, Marsden J, Naik H, et al. Oral cholestyramine is not an effective treatment for uncomplicated erythropoietic protoporphyria. J Am Acad Dermatol. 2012;67:1383–4.PubMedCrossRefGoogle Scholar
  91. The European Porphyria Network.
  92. Timonen K, Niemi KM, Mustajoki P, Tenhunen R. Skin changes in variegate porphyria. Clinical, histopathological, and ultrastructural study. Arch Dermatol Res. 1990;282:108–14.PubMedCrossRefGoogle Scholar
  93. Valls V, Ena J, Enriquez-de-Salamanca R. Low-dose oral chloroquine in patients with porphyria cutanea tarda and low-moderate iron overload. J Dermatol Sci. 1994;7:164–75.CrossRefGoogle Scholar
  94. Van Tuyll van Serooskerken AM, Drögemöller BI, et al. Extended haplotype studies in South African and Dutch variegate porphyria families carrying the recurrent p.R59W mutation confirm a common ancestry. Br J Dermatol. 2012;166:261–5.PubMedCrossRefGoogle Scholar
  95. Von und zu Fraunberg M, Timonen K, et al. Clinical and biochemical characteristics and genotype-phenotype correlation in Finnish variegate porphyria patients. Eur J Hum Genet. 2002;10:649–57.PubMedCrossRefGoogle Scholar
  96. Wahlin S, Aschan J, Bjornstedt M, et al. Curative bone marrow transplantation in erythropoietic protoporphyria after reversal of severe cholestasis. J Hepatol. 2007;46:174–9.PubMedCrossRefGoogle Scholar
  97. Wahlin S, Srikanthan N, Hamre B, et al. Protection from phototoxic injury during surgery and endoscopy in erythropoietic protoporphyria. Liver Transpl. 2008;14:1340–6.PubMedCrossRefGoogle Scholar
  98. Wahlin S, Stal P, Adam R, et al. Liver transplantation for erythropoietic protoporphyria in Europe. Liver Transpl. 2011;17:1021–6.PubMedGoogle Scholar
  99. 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;41:e105.PubMedPubMedCentralCrossRefGoogle Scholar
  100. Whatley SD, Ducamp S, Gouya L, et al. 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;83:408–14.PubMedPubMedCentralCrossRefGoogle Scholar
  101. Wick G, Honigsmann H, Timpl R. Immunofluorescence demonstration of type IV collagen and a noncollagenous glycoprotein in thickened vascular basal membranes in protoporphyria. J Invest Dermatol. 1979;73:335–8.PubMedCrossRefGoogle Scholar
  102. Wolff K, Hönigsmann H, Rauschmeier W, et al. Microscopic and fine structural aspects of porphyrias. Acta Derm Venereol Suppl (Stockh). 1982;100:17–28.Google Scholar

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© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  1. 1.Photodermatology Unit, St John’s Institute of DermatologyLondonUK

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