Chapter 057. Photosensitivity and Other Reactions to Light (Part 7)

Porphyria cutanea tarda is the most common type of human porphyria and is associated with decreased activity of the enzyme uroporphyrinogen decarboxylase associated with a number of gene mutations. There are two basic types of PCT: (1) the sporadic or acquired type, generally seen in individuals ingesting ethanol or receiving estrogens; and (2) the inherited type, in which there is autosomal dominant transmission of deficient enzyme activity. Both forms are associated with increased hepatic iron stores.In both types of PCT, the predominant feature is a chronic photosensitivity characterized by increased fragility of sun-exposed skin, particularly areas subject to repeated...
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Chapter 057. Photosensitivity and Other Reactions to Light (Part 7) Chapter 057. Photosensitivity and Other Reactions to Light (Part 7) Porphyria cutanea tarda is the most common type of human porphyria andis associated with decreased activity of the enzyme uroporphyrinogendecarboxylase associated with a number of gene mutations. There are two basictypes of PCT: (1) the sporadic or acquired type, generally seen in individualsingesting ethanol or receiving estrogens; and (2) the inherited type, in which thereis autosomal dominant transmission of deficient enzyme activity. Both forms areassociated with increased hepatic iron stores. In both types of PCT, the predominant feature is a chronic photosensitivitycharacterized by increased fragility of sun-exposed skin, particularly areas subjectto repeated trauma such as the dorsa of the hands, the forearms, the face, and theears. The predominant skin lesions are vesicles and bullae that rupture, producingmoist erosions, often with a hemorrhagic base, that heal slowly with crusting andpurplish discoloration of the affected skin. Hypertrichosis, mottled pigmentarychange, and scleroderma-like induration are associated features. Biochemicalconfirmation of the diagnosis can be obtained by measurement of urinaryporphyrin excretion, plasma porphyrin assay, and by assay of erythrocyte and/orhepatic uroporphyrinogen decarboxylase. Multiple mutations of theuroporphyrinogen decarboxylase gene have been identified in human populations,including exon skipping and base substitutions. Some patients with PCT haveassociated mutations in the HFE gene linked to hemochromatosis. This couldcontribute to the iron overload seen in PCT, although iron status as measured byserum ferritin, iron levels, and transferrin saturation is no different from that inPCT patients without HFE mutations. Prior hepatitis C virus infection appears tobe an independent risk factor for PCT. Treatment of PCT consists of repeated phlebotomies to diminish theexcessive hepatic iron stores and/or intermittent low doses of the antimalarialdrugs chloroquine and hydroxychloroquine. Long-term remission of the diseasecan be achieved if the patient eliminates exposure to porphyrinogenic agents. Erythropoietic protoporphyria originates in the bone marrow and is due toa decrease in the mitochondrial enzyme ferrochelatase secondary to numerousgene mutations. The major clinical features include an acute photosensitivitycharacterized by subjective burning and stinging of exposed skin that oftendevelops during or just after exposure. There may be associated skin swelling and,after repeated episodes, a waxlike scarring. The diagnosis is confirmed by demonstration of elevated levels of freeerythrocyte protoporphyrin. Detection of increased plasma protoporphyrin helps todifferentiate lead poisoning and iron-deficiency anemia, in both of which elevatederythrocyte protoporphyrin levels occur in the absence of cutaneousphotosensitivity and of elevated plasma protoporphyrin levels. Treatment consists of reducing sun exposure and the oral administration ofthe carotenoid β-carotene, which is an effective scavenger of free radicals. Thisdrug increases tolerance to sun exposure in many affected individuals, although ithas no effect on deficient ferrochelatase. An algorithm for managing patients with photosensitivity is illustrated inFig. 57-1. Figure 57-1An algorithm for the diagnosis of a patient with photosensitivity.Photoprotection Since photosensitivity of the skin results from exposure to sunlight, itfollows that absolute avoidance of the sun would eliminate these disorders.Unfortunately, contemporary life-styles make this an impractical alternative formost individuals, and this has led to a search for better approaches tophotoprotection.