Development of porphyria cutanea tarda after treatment with cyclophosphamide.
Porphyria cutanea tarda, a metabolic disorder of heme biosynthesis, is characterized by cutaneous hyperpigmentation, facial hypertrichosis, dark urine, and a distinctive pattern of excess porphyrin production. Hepatic uroporphyrinogen decarboxylase activity is markedly reduced in patients with this disorder. Although porphyria cutanea tarda may be familial, it is more often sporadic in occurrence, and has been associated with excess alcohol ingestion, estrogen administration, iron overload, and several environmental hepatotoxins. It has also been associated on occasion with malignancy. We report a 46-yr-old woman with ovarian carcinoma who developed porphyria cutanea tarda while undergoing treatment with cisplatin and cyclophosphamide. The temporal course of the porphyrin abnormality suggested that cyclophosphamide was the pathogenic agent, and symptoms regressed after cessation of this drug with continued administration of cisplatin. The pathogenesis of the porphyria is not clear; however, cyclophosphamide is a substrate for cytochrome P450, and may produce metabolites that destroy this protein. The resulting increased turnover of heme might then result in overproduction of porphyrin precursors, resulting in the clinical syndrome. Studies of porphyrin metabolism in patients treated with cyclophosphamide may help to elucidate this possibility.
Manzione
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Department of Medicine, Albert Einstein College of Medicine, Bronx, New York.
Wolkoff
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Sassa
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D002945:Cisplatin / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000009:adverse effects* / Q000627:therapeutic use; D003536:Cystadenocarcinoma / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D011164:Porphyrias / Q000139:chemically induced* / Q000652:urine; D011166:Porphyrins / Q000652:urine; D012871:Skin Diseases / Q000139:chemically induced* / Q000652:urine
D011166:Porphyrins; D003520:Cyclophosphamide; D002945:Cisplatin