eMedicine Specialties > Dermatology > Metabolic Diseases

Porphyria Cutanea Tarda

Author: Maureen B Poh-Fitzpatrick, MD, Professor Emerita of Dermatology and Special Lecturer, Columbia University; Professor of Medicine (Dermatology), University of Tennessee
Contributor Information and Disclosures

Updated: Jan 7, 2009

Introduction

Background

Porphyria cutanea tarda (PCT) is a term encompassing a group of disorders in which activity of the heme synthetic enzyme uroporphyrinogen decarboxylase (UROD) is deficient.1 Porphyria cutanea tarda includes familial types with UROD gene mutations and acquired types that may occur in individuals with a genetic predisposition (sporadic porphyria cutanea tarda), after exposure to hepatotoxins, or in the context of hepatic tumors. Familial porphyria cutanea tarda most often reflects the presence of one mutation at the UROD locus. A rare familial type with two such mutations has been termed hepatoerythropoietic porphyria.2

Clinical expression of both familial and acquired porphyria cutanea tarda often follows exposure to agents or conditions that adversely affect hepatocytes and lead to hepatosiderosis. These agents or conditions include ethanol, estrogen, hepatitis and human immunodeficiency viruses, and hemochromatosis genes.1 Excess iron enhances the formation of toxic oxygen species and increases oxidative stress and apparently facilitates porphyrinogenesis by catalyzing the formation of oxidation products that inhibit UROD.3 Reduction of UROD activity to approximately 25% of normal leads to clinical expression of the disease. Environmental exposure to polyhalogenated aromatic hydrocarbon compounds has caused acquired toxic porphyric disorders in large populations,4 referred to as "epidemic porphyria." Hepatic tumors producing excess porphyrins are rare causes of porphyria cutanea tarda–like disorders.

The following is a selection of other porphyria-related eMedicine articles:

Pathophysiology

When hepatic UROD activity falls below a 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 Media File 2). 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 due to the porphyrin pigments present.5

Frequency

United States

No porphyria registry is available in the United States; thus, the prevalence of porphyria cutanea tarda is not accurately known but is estimated at 1 case in 25,000-50,000 population. It is the most common porphyria.

International

Higher prevalences of porphyria cutanea tarda have been reported in some European populations. A high prevalence among South African Bantu people has been linked with a propensity for hepatic siderosis.

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.6

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 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 have also been reported in heterozygote children.7 When 2 mutations are present (homozygotes or compound heterozygotes), onset is typically in childhood.8
  • Porphyria cutanea tarda – like disorders resulting from exposure of large numbers of people to hepatotoxic chemicals have afflicted people of all ages.4

Clinical

History

  • The most common initial symptoms 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 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 are unaware of the familial nature of their disease.
  • In both familial and sporadic porphyria cutanea tarda, a history of exposure to environmental inducers (eg, ethanol, estrogens, hepatitis) can often be elicited. In symptomatic familial porphyria cutanea tarda, none of the common inducing agents may be discoverable. Paradoxically, proven carriers of the same mutation may remain clinically and biochemically silent despite exposure to such agents.
  • 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.

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.

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.9 Various risk factors, acting alone or in concert, can inhibit UROD activity to that point of insufficiency.10
  • Hepatitis virus infections are frequently associated with porphyria cutanea tarda.11,12,13,14   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.15
  • Association with human immunodeficiency virus infection has also been reported.16
  • A strong association between porphyria cutanea tarda and the presence of 1 or 2 hereditary hemochromatosis genes has been established.10,11,17,18,19

More on Porphyria Cutanea Tarda

Overview: Porphyria Cutanea Tarda
Differential Diagnoses & Workup: Porphyria Cutanea Tarda
Treatment & Medication: Porphyria Cutanea Tarda
Follow-up: Porphyria Cutanea Tarda
Multimedia: Porphyria Cutanea Tarda
References
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Further Reading

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Keywords

porphyria cutanea tarda, PCT, hepatic porphyria, chronic porphyria, idiosyncratic porphyria, acquired porphyria, sporadic porphyria, symptomatic porphyria, constitutional porphyria, hereditary porphyria, urocoproporphyria, cutaneous hepatic porphyria, uroporphyrinogen decarboxylase, UROD, hepatoerythropoietic porphyria, epidemic porphyria

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Contributor Information and Disclosures

Author

Maureen B Poh-Fitzpatrick, MD, Professor Emerita of Dermatology and Special Lecturer, Columbia University; Professor of Medicine (Dermatology), University of Tennessee
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

Medical Editor

Craig A Elmets, MD, Director of Dermatology, Departments of Dermatology, Pathology, and Environmental Health Sciences; Professor, The Kirklin Clinic, University of Alabama at Birmingham
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

Pharmacy Editor

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.

Managing Editor

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: Johnson and Johnson stock holder dividends; Amgen stock holder dividends; Forest Lab, Inc stock holder dividends; Galaxo Smith Klein stock holder dividends; Covidien stock holder dividends; Novartis Grant/research funds Consulting; Biolex  sub-investigator

CME Editor

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.

 
 
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