Porphyria cutanea tarda: a unique iron-related disorder.

Abstract

The porphyrias are a group of disorders of heme biosynthesis, each characterized by an enzymatic defect in the heme biosynthetic pathway. Porphyria cutanea tarda (PCT) arises due to the inhibition of uroporphyrinogen decarboxylase (UROD) in the presence of hepatic iron and oxidative stress. Most patients with PCT have evidence of siderosis on liver biopsy, and the disease resolves with iron depletion. PCT manifests as skin fragility, blistering cutaneous lesions on sun-exposed areas, dark urine, and elevated plasma and urine porphyrins. Factors contributing to the development of PCT include alcohol use, hepatitis C virus infection, human immunodeficiency virus, estrogen use, UROD pathogenic variants, and hereditary hemochromatosis. Treatment includes therapeutic phlebotomy to decrease total body iron levels and low-dose hydroxychloroquine, which reduces hepatic porphyrin content. The following review explores the biology of PCT, the critical role of iron in disease pathogenesis, and our approach to the management of these patients.