Porphyria Cutanea Tarda 

  • Author: Maureen B Poh-Fitzpatrick, MD; Chief Editor: Dirk M Elston, MD   more...
 
Updated: May 28, 2010
 

Background

Porphyria cutanea tarda (PCT) is a term encompassing a group of familial and acquired disorders in which activity of the heme synthetic enzyme uroporphyrinogen decarboxylase (UROD) is deficient.[1] Approximately 80% of all cases of porphyria cutanea tarda are acquired; 20% of porphyria cutanea tarda cases are familial, although the ratio may vary among different geographic regions and ethnic groups.

Familial porphyria cutanea tarda most often arises from autosomal dominant inheritance of a single mutation at the UROD locus. A rare recessive familial type of porphyria cutanea tarda in which both UROD alleles are mutated is termed hepatoerythropoietic porphyria.[2] Familial porphyria cutanea tarda without detectable UROD mutations has been reported.[3, 4]

The common acquired form, sporadic porphyria cutanea tarda, occurs in individuals whose UROD DNA sequences are normal, but who may have other genetically determined susceptibilities to inhibition of UROD activity. Acquired porphyria in large populations exposed to polyhalogenated aromatic hydrocarbon hepatotoxins[5] has been referred to as "epidemic” porphyria cutanea tarda. Hepatic tumors producing excess porphyrins are rare causes of porphyria cutanea tarda–like disorders.

Clinical expression of both familial and acquired porphyria cutanea tarda most often requires exposure to environmental or infectious agents or the presence of coexisting conditions that adversely affect hepatocytes and result in hepatic siderosis. Ethanol intake, estrogen therapies, hemochromatosis genes, and hepatitis and human immunodeficiency viral infections are among these contributory factors.[1] Excess iron enhances formation of toxic oxygen species, increasing oxidative stress and apparently facilitating porphyrinogenesis by catalyzing the formation of oxidation products that inhibit UROD.[6] Partial oxidation of uroporphyrinogen to the UROD inhibitor uroporphomethene occurs in murine porphyria cutanea tarda models and may also be a pathogenic mechanism in the human disease.[7] Reduction of hepatic UROD activity to approximately 25% of normal is required for clinical disease expression.[8, 9]

Other porphyria-related eMedicine articles include Erythropoietic Porphyria, Erythropoietic Protoporphyria, Pseudoporphyria, and Variegate Porphyria.

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Pathophysiology

When hepatic UROD activity falls below the critical threshold, porphyrin by-products of the heme biosynthetic pathway with 4-8 carboxyl group substituents are overproduced. These porphyrins are reddish pigments that accumulate in the liver and are disseminated in plasma to other organs. Porphyrins with high carboxyl group numbers are water soluble and excreted primarily by renal mechanisms. The porphyrin with 8 carboxyl groups is termed uroporphyrin; 4-carboxyl porphyrins include coproporphyrin and isocoproporphyrin, which are chiefly excreted in feces. Porphyrins are photoactive molecules that efficiently absorb energy in the visible violet spectrum. Photoexcited porphyrins in the skin mediate oxidative damage to biomolecular targets, causing cutaneous lesions.

The most common photocutaneous manifestations of porphyria cutanea tarda are due to increased mechanical fragility after sunlight exposure; erosions and blisters form painful indolent sores that heal with milia, dyspigmentation, and scarring (see images below).

Thickened skin with blisters, scars, and milia. CoThickened skin with blisters, scars, and milia. Courtesy of Dirk Elston, MD. Close-up image of blisters, scarring, and milia. CClose-up image of blisters, scarring, and milia. Courtesy of Dirk Elston, MD.

Other common features of porphyria cutanea tarda include hypertrichosis, sclerodermalike plaques that may develop dystrophic calcification, and excretion of discolored urine that resembles port wine or tea, which is due to the presence of porphyrin pigments.[10]

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Epidemiology

Frequency

United States

A United States porphyria registry will soon be available to support more accurate enumeration of cases, but, at present, the prevalence of porphyria cutanea tarda can still only be estimated at 1 case in 25,000-50,000 population. Porphyria cutanea tarda is the most common porphyria seen in clinical practice.

International

Higher prevalences of porphyria cutanea tarda have been reported in some European populations. A high prevalence of porphyria cutanea tarda among South African Bantu people has been linked with a propensity for hepatic siderosis. Fractions of studied porphyria cutanea tarda cases reported as familial vary widely: 14.6% in Spain,[11] 24% in Denmark,[12] and f50% in Chile.[13]

Mortality/Morbidity

The major morbidity of porphyria cutanea tarda is due to skin fragility and blistering, which preclude manual labor and hamper daily activities. The subsequent erosions represent full-thickness epidermal loss; they are painful and often become thickly crusted and secondarily infected. Healing is slow and leaves pigmentary changes, milia, and atrophic scars.

Porphyria cutanea tarda has been associated with the development of hepatocellular carcinoma, chiefly in populations of older men with long-standing active disease, heavy ethanol intake, and cirrhosis. Most studies predate recognition of hepatitis C prevalence in populations with porphyria cutanea tarda or hepatocellular carcinoma; many reported cancers may have been, at least in part, sequelae of chronic hepatitis viral infection.[14]

Race

Porphyria cutanea tarda occurs in persons of all ethnic groups.

Sex

Porphyria cutanea tarda occurs in both sexes. Older reports indicated a great preponderance of porphyria cutanea tarda in men; more recent surveys include many women.

Age

Sporadic porphyria cutanea tarda typically manifests in adulthood. Symptoms of familial porphyria cutanea tarda typically first appear in adults heterozygous for a UROD gene mutation, but they have also been reported in heterozygote children.[15] When 2 mutations are present (homozygotes or compound heterozygotes), symptoms may be severe, with onset in early childhood.[16] Milder phenotypes with somewhat later onset have also been observed.[17, 18]

Porphyria cutanea tarda–like disorders resulting from exposure of large numbers of people to hepatotoxic chemicals have afflicted people of all ages.[5]

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Contributor Information and Disclosures
Author

Maureen B Poh-Fitzpatrick, MD  Professor Emerita of Dermatology and Special Lecturer, Columbia University College of Physicians and Surgeons; Professor of Medicine (Dermatology), University of Tennessee Health Science Center College of Medicine

Maureen B Poh-Fitzpatrick, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, and New York Academy of Medicine

Disclosure: Lundbeck, Inc. Honoraria Review panel membership; Clinuvel Pharmaceuticals, Ltd. Honoraria Consulting

Specialty Editor Board

Craig A Elmets, MD  Professor and Chair, Department of Dermatology, Director, UAB Skin Diseases Research Center, University of Alabama at Birmingham School of Medicine

Craig A Elmets, MD is a member of the following medical societies: American Academy of Dermatology, American Association of Immunologists, American College of Physicians, American Federation for Medical Research, and Society for Investigative Dermatology

Disclosure: Palomar Medical Technologies Stock None; Amgen Consulting fee Review panel membership; Astellas Consulting fee Review panel membership; Massachusetts Medical Society Salary Employment; Abbott Laboratories Grant/research funds Independent contractor

Richard P Vinson, MD  Assistant Clinical Professor, Department of Dermatology, Texas Tech University School of Medicine; Consulting Staff, Mountain View Dermatology, PA

Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Association of Military Dermatologists, Texas Dermatological Society, and Texas Medical Association

Disclosure: Nothing to disclose.

Julia R Nunley, MD  Professor, Program Director, Dermatology Residency, Department of Dermatology, Virginia Commonwealth University Medical Center

Julia R Nunley, MD is a member of the following medical societies: American Academy of Dermatology, American College of Physicians, American Society of Nephrology, International Society of Nephrology, Medical Dermatology Society, Medical Society of Virginia, National Kidney Foundation, Phi Beta Kappa, and Women's Dermatologic Society

Disclosure: Novartis Grant/research funds Consulting; Biolex Grant/research funds sub-investigator

Catherine M Quirk, MD  Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania

Catherine M Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD  Director, Department of Dermatology, Geisinger Medical Center

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

References

  1. Kappas A, Sassa S, Galbraith RA, et al. The porphyrias. In: CR Scriver, et al, eds. The Metabolic Basis of Inherited Disease. New York, NY: McGraw-Hill; 1995:2103-59.

  2. Moran-Jimenez MJ, Ged C, Romana M, et al. Uroporphyrinogen decarboxylase: complete human gene sequence and molecular study of three families with hepatoerythropoietic porphyria. Am J Hum Genet. Apr 1996;58(4):712-21. [Medline]. [Full Text].

  3. Elder GH, Roberts AG, de Salamanca RE. Genetics and pathogenesis of human uroporphyrinogen decarboxylase defects. Clin Biochem. Jun 1989;22(3):163-8. [Medline].

  4. Mendez M, Poblete-Gutierrez P, Garcia-Bravo M, et al. Molecular heterogeneity of familial porphyria cutanea tarda in Spain: characterization of 10 novel mutations in the UROD gene. Br J Dermatol. Sep 2007;157(3):501-7. [Medline].

  5. Can C, Nigogosyan G. Acquired toxic porphyria cutanea tarda due to hexachlorobenzene. Report of 348 cases caused by this fungicide. JAMA. Jan 12 1963;183:88-91. [Medline].

  6. Bonkovsky HL, Lambrecht RW, Shan Y. Iron as a co-morbid factor in nonhemochromatotic liver disease. Alcohol. Jun 2003;30(2):137-44. [Medline].

  7. Phillips JD, Bergonia HA, Reilly CA, Franklin MR, Kushner JP. A porphomethene inhibitor of uroporphyrinogen decarboxylase causes porphyria cutanea tarda. Proc Natl Acad Sci U S A. Mar 20 2007;104(12):5079-84. [Medline]. [Full Text].

  8. Kushner JP, Barbuto AJ, Lee GR. An inherited enzymatic defect in porphyria cutanea tarda: decreased uroporphyrinogen decarboxylase activity. J Clin Invest. Nov 1976;58(5):1089-97. [Medline]. [Full Text].

  9. Elder GH, Lee GB, Tovey JA. Decreased activity of hepatic uroporphyrinogen decarboxylase in sporadic porphyria cutanea tarda. N Engl J Med. Aug 10 1978;299(6):274-8. [Medline].

  10. Grossman ME, Bickers DR, Poh-Fitzpatrick MB, Deleo VA, Harber LC. Porphyria cutanea tarda. Clinical features and laboratory findings in 40 patients. Am J Med. Aug 1979;67(2):277-86. [Medline].

  11. Badenas C, To-Figueras J, Phillips JD, Warby CA, Munoz C, Herrero C. Identification and characterization of novel uroporphyrinogen decarboxylase gene mutations in a large series of porphyria cutanea tarda patients and relatives. Clin Genet. Apr 2009;75(4):346-53. [Medline].

  12. Christiansen L, Brøns-Poulsen J, Horder M, Brock A, Petersen NE. Expression and characterization of six clinically relevant uroporphyrinogen decarboxylase gene mutations. Scand J Clin Lab Invest. 2005;65(3):227-35. [Medline].

  13. Poblete-Gutierrez P, Mendez M, Wiederholt T, et al. The molecular basis of porphyria cutanea tarda in Chile: identification and functional characterization of mutations in the uroporphyrinogen decarboxylase gene. Exp Dermatol. Jun 2004;13(6):372-9. [Medline].

  14. Gisbert JP, Garcia-Buey L, Alonso A, et al. Hepatocellular carcinoma risk in patients with porphyria cutanea tarda. Eur J Gastroenterol Hepatol. Jul 2004;16(7):689-92. [Medline].

  15. Elder GH. Hepatic porphyrias in children. J Inherit Metab Dis. Jun 1997;20(2):237-46. [Medline].

  16. Elder GH, Smith SG, Herrero C, et al. Hepatoerythropoietic porphyria: a new uroporphyrinogen decarboxylase defect or homozygous porphyria cutanea tarda?. Lancet. Apr 25 1981;1(8226):916-9. [Medline].

  17. Toback AC, Sassa S, Poh-Fitzpatrick MB, et al. Hepatoerythropoietic porphyria: clinical, biochemical, and enzymatic studies in a three-generation family lineage. N Engl J Med. Mar 12 1987;316(11):645-50. [Medline].

  18. Armstrong DK, Sharpe PC, Chambers CR, Whatley SD, Roberts AG, Elder GH. Hepatoerythropoietic porphyria: a missense mutation in the UROD gene is associated with mild disease and an unusual porphyrin excretion pattern. Br J Dermatol. Oct 2004;151(4):920-3. [Medline].

  19. Elder GH, Roberts AG. Uroporphyrinogen decarboxylase. J Bioenerg Biomembr. Apr 1995;27(2):207-14. [Medline].

  20. Egger NG, Goeger DE, Payne DA, Miskovsky EP, Weinman SA, Anderson KE. Porphyria cutanea tarda: multiplicity of risk factors including HFE mutations, hepatitis C, and inherited uroporphyrinogen decarboxylase deficiency. Dig Dis Sci. Feb 2002;47(2):419-26. [Medline].

  21. Cruz-Rojo J, Fontanellas A, Moran-Jimenez MJ, et al. Precipitating/aggravating factors of porphyria cutanea tarda in Spanish patients. Cell Mol Biol (Noisy-le-grand). Dec 2002;48(8):845-52. [Medline].

  22. Jalil S, Grady JJ, Lee C, Anderson KE. Associations among behavior-related susceptibility factors in porphyria cutanea tarda. Clin Gastroenterol Hepatol. Mar 2010;8(3):297-302, 302.e1. [Medline]. [Full Text].

  23. Elder GH. Alcohol intake and porphyria cutanea tarda. Clin Dermatol. Jul-Aug 1999;17(4):431-6. [Medline].

  24. Bonkovsky HL, Poh-Fitzpatrick M, Pimstone N, et al. Porphyria cutanea tarda, hepatitis C, and HFE gene mutations in North America. Hepatology. Jun 1998;27(6):1661-9. [Medline].

  25. Edwards CQ, Griffen LM, Goldgar DE, Skolnick MH, Kushner JP. HLA-linked hemochromatosis alleles in sporadic porphyria cutanea tarda. Gastroenterology. Oct 1989;97(4):972-81. [Medline].

  26. Toll A, Celis R, Ozalla MD, Bruguera M, Herrero C, Ercilla MG. The prevalence of HFE C282Y gene mutation is increased in Spanish patients with porphyria cutanea tarda without hepatitis C virus infection. J Eur Acad Dermatol Venereol. Nov 2006;20(10):1201-6. [Medline].

  27. Lambrecht RW, Bonkovsky HL. Hemochromatosis and porphyria. Semin Gastrointest Dis. Apr 2002;13(2):109-19. [Medline].

  28. Stransky J, Malina L, Cieslarova B, Stritesky J, Putova I, Horak J. Overt and hidden coinfection with hepatitis B and C viruses in chronic liver disease and porphyria cutanea tarda. Acta Virol. Feb 2000;44(1):23-8. [Medline].

  29. Oubina JR, Quarleri JF, Sawicki MA, et al. Hepatitis C virus and GBV-C/hepatitis G virus in Argentine patients with porphyria cutanea tarda. Intervirology. 2001;44(4):215-8. [Medline].

  30. Hift RJ, Meissner PN, Todd G. Hepatoerythropoietic porphyria precipitated by viral hepatitis. Gut. Nov 1993;34(11):1632-4. [Medline]. [Full Text].

  31. Gisbert JP, Garcia-Buey L, Pajares JM, Moreno-Otero R. Prevalence of hepatitis C virus infection in porphyria cutanea tarda: systematic review and meta-analysis. J Hepatol. Oct 2003;39(4):620-7. [Medline].

  32. Blauvelt A, Harris HR, Hogan DJ, Jimenez-Acosta F, Ponce I, Pardo RJ. Porphyria cutanea tarda and human immunodeficiency virus infection. Int J Dermatol. Jul 1992;31(7):474-9. [Medline].

  33. Mansourati FF, Stone VE, Mayer KH. Porphyria cutanea tarda and HIV/AIDS: a review of pathogenesis, clinical manifestations and management. Int J STD AIDS. Jan 1999;10(1):51-6. [Medline].

  34. Fontanellas A, Martinez-Fresno M, Garrido-Astray MC, et al. Smoking but not homozygosity for CYP1A2 g-163A allelic variant leads to earlier disease onset in patients with sporadic porphyria cutanea tarda. Exp Dermatol. Feb 16 2010;[Medline].

  35. Sinclair PR, Gorman N, Shedlofsky SI, et al. Ascorbic acid deficiency in porphyria cutanea tarda. J Lab Clin Med. Aug 1997;130(2):197-201. [Medline].

  36. Tatsumi C, Kudo M, Ueshima K, et al. Noninvasive evaluation of hepatic fibrosis using serum fibrotic markers, transient elastography (FibroScan) and real-time tissue elastography. Intervirology. 2008;51 Suppl 1:27-33. [Medline].

  37. Epstein JH, Tuffanelli DL, Epstein WL. Cutaneous changes in the porphyrias. A microscopic study. Arch Dermatol. May 1973;107(5):689-98. [Medline].

  38. Fung MA, Murphy MJ, Hoss DM, Berke A, Grant-Kels JM. The sensitivity and specificity of "caterpillar bodies" in the differential diagnosis of subepidermal blistering disorders. Am J Dermatopathol. Aug 2003;25(4):287-90. [Medline].

  39. 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].

  40. Lefkowitch JH, Grossman ME. Hepatic pathology in porphyria cutanea tarda. Liver. Feb 1983;3(1):19-29. [Medline].

  41. Ippen H. Treatment of porphyria cutanea tarda by phlebotomy. Semin Hematol. Apr 1977;14(2):253-9. [Medline].

  42. Ramsay CA, Magnus IA, Turnbull A, Baker H. The treatment of porphyria cutanea tarda by venesection. Q J Med. Jan 1974;43(169):1-24. [Medline].

  43. Poh-Fitzpatrick MB, Honig PJ, Kim HC, Sassa S. Childhood-onset familial porphyria cutanea tarda: effects of therapeutic phlebotomy. J Am Acad Dermatol. Nov 1992;27(5 Pt 2):896-900. [Medline].

  44. Ratnaike S, Blake D, Campbell D, Cowen P, Varigos G. Plasma ferritin levels as a guide to the treatment of porphyria cutanea tarda by venesection. Australas J Dermatol. Apr 1988;29(1):3-8. [Medline].

  45. Fernandez I, Castellano G, de Salamanca RE, et al. Porphyria cutanea tarda as a predictor of poor response to interferon alfa therapy in chronic hepatitis C. Scand J Gastroenterol. Mar 2003;38(3):314-9. [Medline].

  46. Taljaard JJ, Shanley BC, Stewart-Wynne EG, Deppe WM, Joubert SM. Studies on low dose chloroquine therapy and the action of chloroquine in symptomatic porphyria. Br J Dermatol. Sep 1972;87(3):261-9. [Medline].

  47. Kordac V, Semradova M. Treatment of porphyria cutanea tarda with chloroquine. Br J Dermatol. Jan 1974;90(1):95-100. [Medline].

  48. Malkinson FD, Levitt L. Hydroxychloroquine treatment of porphyria cutanea tarda. Arch Dermatol. Oct 1980;116(10):1147-50. [Medline].

  49. Battle AM, Stella AM, De Kaminsky AR, Kaminsky C, Mariano HG. Two cases of infantile porphyria cutanea tarda: successful treatment with oral S-adenosyl-L-methionine and low-dose oral chloroquine. Br J Dermatol. Mar 1987;116(3):407-15. [Medline].

  50. Bruce AJ, Ahmed I. Childhood-onset porphyria cutanea tarda: successful therapy with low-dose hydroxychloroquine (Plaquenil). J Am Acad Dermatol. May 1998;38(5 Pt 2):810-4. [Medline].

  51. Stolzel U, Kostler E, Schuppan D, et al. Hemochromatosis (HFE) gene mutations and response to chloroquine in porphyria cutanea tarda. Arch Dermatol. Mar 2003;139(3):309-13. [Medline].

  52. Seubert S, Seubert A, Stella AM, Guzman H, Batlle A. [Results of treatment of porphyria cutanea tarda with bloodletting and chloroquine]. Z Hautkr. Mar 1990;65(3):223-5. [Medline].

  53. Rocchi E, Cassanelli M, Borghi A, et al. Liver iron overload and desferrioxamine treatment of porphyria cutanea tarda. Dermatologica. 1991;182(1):27-31. [Medline].

  54. Anderson KE, Goeger DE, Carson RW, Lee SM, Stead RB. Erythropoietin for the treatment of porphyria cutanea tarda in a patient on long-term hemodialysis. N Engl J Med. Feb 1 1990;322(5):315-7. [Medline].

  55. Loret de Mola JR, Muise KL, Duchon MA. Porphyria cutanea tarda and pregnancy. Obstet Gynecol Surv. Aug 1996;51(8):493-7. [Medline].

  56. Agarwal R, Peters TJ, Coombes RC, Vigushin DM. Tamoxifen-related porphyria cutanea tarda. Med Oncol. 2002;19(2):121-3. [Medline].

  57. Poh-Fitzpatrick MB, Bellet N, DeLeo VA, Grossman ME, Bickers DR. Porphyria cutanea tardia in two patients treated with hemodialysis for chronic renal failure. N Engl J Med. Aug 10 1978;299(6):292-4. [Medline].

 
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Thickened skin with blisters, scars, and milia. Courtesy of Dirk Elston, MD.
Close-up image of blisters, scarring, and milia. Courtesy of Dirk Elston, MD.
Subepidermal bulla, festooning of rete ridges, hyalinization of blood vessel walls, solar elastosis, and caterpillar bodies. Courtesy of Dirk Elston, MD.
Fluorescence of urine with a Wood light examination. Courtesy of Brooke Army Medical Center Teaching File.
 
 
 
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