Porphyria Cutanea Tarda Clinical Presentation

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

History

The most common initial symptoms of porphyria cutanea tarda are cutaneous fragility and blistering of the hands, forearms, and, sometimes, the face. Discolored urine may also be reported, but this information may need to be elicited. Changes in hair growth and pigmentation may be noted spontaneously or only after inquiry. Patients with porphyria cutanea tarda often do not realize the role of sunlight exposure in the subsequent appearance of lesions.

In familial porphyria cutanea tarda, other affected relatives may be known. However, most related carriers of the mutant gene remain silent, and patients may be unaware of the familial nature of their disease.

In both familial and sporadic porphyria cutanea tarda, a history of exposure to one or more environmental inducers (eg, ethanol, estrogens, hepatitis) can often be elicited. Paradoxically, proven carriers of the same mutation as that of a symptomatic relative with exposure to a known inducer may remain clinically and biochemically silent despite similar exposure. In symptomatic familial porphyria cutanea tarda, occasionally none of the common inducing agents is discoverable. Childhood onset of porphyria cutanea tarda should suggest either heterozygous or homozygous familial forms of the disease, unless observed in the context of environmental exposure to a chemical hepatotoxin.

Porphyria cutanea tarda–like disease in multiple members of populations exposed to polyhalogenated aromatic hydrocarbons should suggest epidemic toxic porphyria.

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Physical

The most common presenting sign of porphyria cutanea tarda is fragility of sun-exposed skin after mechanical trauma, leading to erosions and bullae, typically on hands and forearms and occasionally on face or feet. Healing of crusted erosions and blisters leaves milia, hyperpigmented patches, and hypopigmented atrophic scars.

Hypertrichosis is often observed over temporal and malar facial areas and may also involve arms and legs. Pigmentary changes include melasmalike hyperpigmentation of the face. An erythematous suffusion or plethora of the central face, neck, upper chest, and shoulders may be present. Scarring alopecia and separation of nail plates from their beds (photo-onycholysis) can be seen in more severely affected patients.

Indurated, waxy, yellowish plaques that resemble lesions of scleroderma can develop over the chest and the back but are most prominent in the preauricular and nuchal areas. These plaques may develop dystrophic calcification. Rarely, the only physical sign of porphyria cutanea tarda is a hyperpigmented sclerodermoid appearance.

In severely affected individuals, particularly familial hepatoerythropoietic or toxic epidemic cases in children, digital shortening, atrophy, and contractures resembling those of dystrophic epidermolysis bullosa have occurred.

A urine sample is often, but not always, grossly discolored with a tea- or wine-colored tint.

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Causes

The unifying underlying cause of all forms of porphyria cutanea tarda is reduction of UROD activity to a critical point during hepatic heme synthesis.[19, 8, 9] Genetic, environmental or infectious contributory or susceptibility factors, acting singly or more often in concert,[20, 21, 22] inhibit UROD activity to that point of insufficiency, resulting in the onset of clinical symptoms. Note the following:

  • Alcohol effects on hepatocytes may precipitate porphyria cutanea tarda by making stored hepatic iron more available for catalyzing oxidation reactions, by generation of reactive oxygen species, or by induction of hepatic cytochromes, all of which may facilitate oxidation of uroporphyrinogen to a UROD inhibitor.[23]
  • The role of estrogen in inhibition of UROD activity is not firmly established, it but may be similar to that of alcohol in generating toxic oxygen or inducing cytochromes, thus potentiating uroporphyrinogen oxidation.
  • A strong association between porphyria cutanea tarda and hereditary hemochromatosis genes causing hepatic siderosis has been established.[5, 20, 24, 25, 26, 27]
  • Hepatitis virus infections are frequently associated with porphyria cutanea tarda.[24, 28, 29, 30] Hepatitis C occurs with a rate of greater than 50% in populations studied in several European countries and in the United States, while in other regions, the concordance is less frequent.[31] Increased hepatic iron often is found in patients with hepatitis C infection.
  • Association with HIV infection has been noted.[32] Although multiple risk factors are often present among individuals with HIV infection and porphyria cutanea tarda, leading to some uncertainty whether HIV infection is an independent risk factor, some investigators argue that the association is more than simply coincidental.[33]
  • Tobacco smoking is a behavioral characteristic frequently observed among patients with porphyria cutanea tarda.[20, 22] Smoking has been associated with earlier onset of symptoms in sporadic porphyria cutanea tarda, with a putative mechanism involving induction of an hepatic cytochrome that may contribute to oxidation of uroporphyringen,[34] but evidence for smoking is an independent pathogenic factor is not yet robust.
  • Environmental exposure to aromatic polyhalogenated hepatotoxins also induces hepatic cytochromes, thus potentiating production of oxidation products capable of inhibiting UROD activity.
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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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