Porphyria cutanea tarda: a unique iron-related disorder

The por phyr ias are a group of dis or ders of heme bio syn the sis, each char ac ter ized by an enzy matic defect in the heme biosynthetic pathway. Porphyria cutanea tarda (PCT) arises due to the inhi bi tion of uroporphyrinogen decarboxylase (UROD) in the pres ence of hepatic iron and oxi da tive stress. Most patients with PCT have evi dence of siderosis on liver biopsy, and the dis ease resolves with iron deple tion. PCT man i fests as skin fra gil ity, blis ter ing cuta ne ous lesions on sun-exposed areas, dark urine, and ele vated plasma and urine por phy rins. Factors con trib ut ing to the devel op ment of PCT include alco hol use, hep a ti tis C virus infec tion, human immunodeficiency virus, estro gen use, UROD path o genic vari ants, and hereditary hemochromatosis. Treatment includes therapeutic phlebotomy to decrease total body iron levels and low-dose hydroxychloroquine, which reduces hepatic por phy rin con tent. The fol low ing review explores the biol ogy of PCT, the crit i cal role of iron in dis ease path o gen e sis, and our approach to the man age ment of these patients.