Snapshot A 50-year-old man complains of open, non-healing blisters on the dorsal surfaces of his hands. He has a history of untreated chronic hepatitis C infection. While he tries not to drink, he admits to having one glass of wine over the holidays. He denies any abdominal pain. Introduction Blistering cutaneous photosensitivity caused by hepatotoxic triggers Autosomal dominant or sporadic defect in heme synthesis deficiency of hepatic uroporphyrinogen decarboxylase accumulation of uroporphyrinogen III Recurrent flares triggered by hepatotoxins that upregulate heme/P450 synthesis alcohol and estrogen = most common triggers viral hepatitis HIV iron Epidemiology most common form of porphyria middle-aged men and women younger women on oral contraceptives Presentation Skin findings non-healing blisters, erosions, and ulcers in sun-exposed areas (face, neck, dorsal hands, forearms) hypertrichosis of face hyperpigmentation of skin Non-skin findings no abdominal pain (as in other porphyrias) red-brown urine (port-wine urine) from porphyrin pigment Evaluation Diagnosis by urine studies ↑ urine uroporphyrin levels (2-5x above coproporphyrins) Differential Diagnosis Pseudoporphyria (from NSAIDs) Porphyria variegata Acute intermittent porphyria Erythropoietic protoporphyria burning pain and erythema develops on skin minutes after sun exposure no scarring or blistering protoporphyrins elevated in plasma and RBCs treatment: limit sun exposure; beta-carotene reduces photosensitivity Treatment Avoid exposures (alcohol, estrogen, other hepatotoxins) Sunscreen use Iron removal by phlebotomy Chloroquine Prognosis, Prevention, and Complications Prognosis complete clinical clearing in between 2 months and 2 years after stopping triggers exposures Prevention avoid triggers