Porphyria cutanea tarda and hepatitis C virus infection
- Steven Flamm, MD
Steven Flamm, MD
- Chief, Liver Transplantation Program
- Professor of Medicine
- Feinberg School of Medicine
- Northwestern University
- Sanjiv Chopra, MD, MACP
Sanjiv Chopra, MD, MACP
- Editor-in-Chief — Gastroenterology/Hepatology
- Section Editor — General Hepatology
- Section Editor — Gallbladder and Biliary Tract Disease
- Professor of Medicine
- Harvard Medical School
- Senior Consultant in Hepatology
- James Tullis Firm Chief
- Beth Israel Deaconess Medical Center
Porphyria cutanea tarda (PCT) is the most common of the hepatic porphyrias. It is due to reduced activity of the enzyme uroporphyrinogen decarboxylase (UROD), causing the subsequent build-up of uroporphyrinogen in the blood and urine (figure 1) . PCT has both sporadic and inherited (autosomal dominant) forms that are indistinguishable clinically. Hepatic UROD enzyme activity is diminished in both disorders. However, erythrocyte UROD activity levels are reduced only in the inherited form .
The clinical manifestations of PCT and the etiologic relation of the sporadic form to hepatitis C virus (HCV) infection will be reviewed here. General characteristics of PCT and the inherited porphyrias, including diagnosis and treatment, are discussed elsewhere. (See "Porphyrias: An overview" and "Porphyria cutanea tarda and hepatoerythropoietic porphyria: Clinical manifestations and diagnosis".)
The skin and the liver are the two main sites affected in sporadic PCT as the classic presentation consists of photosensitivity and uroporphyrinuria in the setting of chronic liver disease. Several observations support the hypothesis that environmental triggers are necessary to provoke an attack of PCT. When families of patients with inherited PCT have been studied, for example, first-degree relatives often have decreased uroporphyrinogen decarboxylase (UROD) activity despite having no symptoms of PCT . Patients with sporadic PCT, on the other hand, may have normal UROD activity in between attacks . Possible triggers of PCT include polyhalogenated hydrocarbons (such as hexachlorobenzene), alcohol, estrogens, and iron overload [4-8]. (See "Porphyria cutanea tarda and hepatoerythropoietic porphyria: Clinical manifestations and diagnosis", section on 'Pathogenesis'.)
Skin lesions — Skin lesions are frequently the reason that patients with either form of PCT first seek medical attention. Exposure to the sun and/or minor trauma can lead to skin erythema and the development of vesicles and bullae that may become hemorrhagic. Hyperpigmentation, hypopigmentation, hirsutism, and sclerodermatous changes may develop with the passage of time (picture 1) .
Liver disease — Chronic liver disease is common in sporadic PCT. Liver biopsy shows a wide range of changes, including steatosis, mild to severe inflammation, hepatic fibrosis, and cirrhosis . Hepatocellular carcinoma, usually in the presence of cirrhosis, also occurs with increased frequency . In contrast, liver involvement appears to be infrequent in inherited PCT . One small study, for example, found no liver disease in five such patients .
- Kushner JP, Barbuto AJ, Lee GR. An inherited enzymatic defect in porphyria cutanea tarda: decreased uroporphyrinogen decarboxylase activity. J Clin Invest 1976; 58:1089.
- Elder GH, Sheppard DM, Tovey JA, Urquhart AJ. Immunoreactive uroporphyrinogen decarboxylase in porphyria cutanea tarda. Lancet 1983; 1:1301.
- de Verneuil H, Aitken G, Nordmann Y. Familial and sporadic porphyria cutanea: two different diseases. Hum Genet 1978; 44:145.
- CAN C, NIGOGOSYAN G. Acquired toxic porphyria cutanea tarda due to hexachlorobenzene. Report of 348 cases caused by this fungicide. JAMA 1963; 183:88.
- Cripps DJ, Peters HA, Gocmen A, Dogramici I. Porphyria turcica due to hexachlorobenzene: a 20 to 30 year follow-up study on 204 patients. Br J Dermatol 1984; 111:413.
- Cripps DJ. Diet and alcohol effects on the manifestation of hepatic porphyrias. Fed Proc 1987; 46:1894.
- Haberman HF, Rosenberg F, Menon IA. Porphyria cutanea tarda: comparison of cases precipitated by alcohol and estrogens. Can Med Assoc J 1975; 113:653.
- 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.
- Di Padova C, Marchesi L, Cainelli T, et al. Effects of phlebotomy on urinary porphyrin pattern and liver histology in patients with porphyria cutanea tarda. Am J Med Sci 1983; 285:2.
- Siersema PD, ten Kate FJ, Mulder PG, Wilson JH. Hepatocellular carcinoma in porphyria cutanea tarda: frequency and factors related to its occurrence. Liver 1992; 12:56.
- de Verneuil H, Nordmann Y, Phung N, et al. Familial and sporadic porphyria cutanea: two different diseases.. Int J Biochem 1978; 9:927.
- Herrero C, Vicente A, Bruguera M, et al. Is hepatitis C virus infection a trigger of porphyria cutanea tarda? Lancet 1993; 341:788.
- Felsher BF, Jones ML, Redeker AG. Iron and hepatic uroporphyrin synthesis. Relation in porphyria cutanea tarda. JAMA 1973; 226:663.
- Gisbert JP, García-Buey L, Pajares JM, Moreno-Otero R. Prevalence of hepatitis C virus infection in porphyria cutanea tarda: systematic review and meta-analysis. J Hepatol 2003; 39:620.
- Gumber SC, Chopra S. Hepatitis C: a multifaceted disease. Review of extrahepatic manifestations. Ann Intern Med 1995; 123:615.
- Sinclair PR, Bement WJ, Bonkovsky HL, Sinclair JF. Inhibition of uroporphyrinogen decarboxylase by halogenated biphenyls in chick hepatocyte cultures. Essential role for induction of cytochrome P-448. Biochem J 1984; 222:737.
- Smith AG, Francis JE. Chemically-induced formation of an inhibitor of hepatic uroporphyrinogen decarboxylase in inbred mice with iron overload. Biochem J 1987; 246:221.
- Suarez M, Beloqui O, Ferrer J, et al. Glutation reducido linfocitazio y hepatitis cronica activa por virus C. Gastroenterol Hepatol 1992; 15:272.
- Bonkovsky HL, Poh-Fitzpatrick M, Pimstone N, et al. Porphyria cutanea tarda, hepatitis C, and HFE gene mutations in North America. Hepatology 1998; 27:1661.
- Bulaj ZJ, Phillips JD, Ajioka RS, et al. Hemochromatosis genes and other factors contributing to the pathogenesis of porphyria cutanea tarda. Blood 2000; 95:1565.
- Roberts AG, Whatley SD, Morgan RR, et al. Increased frequency of the haemochromatosis Cys282Tyr mutation in sporadic porphyria cutanea tarda. Lancet 1997; 349:321.
- Bissel DM. Haem metabolism and the porphyrias. In: Liver and Biliary Disease, Wright R, Millward-Sadler GH, Alberti KG, Karran S (Eds), Saunders, Philadelphia 1985. p.398.