Snapshot A 25-year-old woman, on oral contraceptives, comes to the dermatologist’s office complaining of a rash on her hands, forearms, and face. On exam, her arms and dorsal hands are covered with oozing erosions and ulcers. Alongside these ulcers are patches of hyperpigmented skin. On questioning, we find that her mother has had similar episodes. Introduction Blistering cutaneous photosensitivity caused by hepatotoxic triggers Autosomal dominant or sporadic defect in heme synthesis deficiency of hepatic uroporphyrinogen decarboxylase accumulation of uroporphyrin 1 Recurrent flares triggered by hepatotoxins that upregulate heme/P450 synthesis alcohol and estrogen = most common triggers viral hepatitis HIV iron Associated conditions alcoholism liver disease hemochromatosis chronic hepatitis C oral contraceptives Epidemiology Most common form of porphyria Middle-aged men and women Younger women on oral contraceptives Presentation Skin findings skin fragility erythema, edema, vesicles progressing to non-healing blisters, erosions, ulcers in sun-exposed areas (face, neck, dorsal hands, forearms) hypertrichosis of face hyperpigmentation of skin scleroderma-like plaques Non-skin findings no abdominal pain (as in other porphyrias) red-brown urine (port-wine urine) from porphyrin pigment Evaluation Diagnosis by skin biopsy subepidermal split (bullae) linear, eosinophilic acid-Schifff positive globules ("Caterpillar bodies") direct immunofluorescence deposition of IgG, IgM, C3 in papillary dermis Or diagnosis by urine ↑ urine uroporphyrin levels (2-5x above coproporphyrins) Wood’s lamp distinctive orange-pink color due to ↑ uroporphyrin To monitor LFTs, iron studies, renal function test, HIV, hepatitis serologies Differential Diagnosis Pseudoporphyria (from NSAIDs) Porphyria variegata Acute intermittent porphyria Erythropoietic protoporphyria burning pain, erythema, and swelling 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, primidone, other hepatotoxins) Sunscreen use Iron removal by phlebotomy – first line reduces hepatic iron stores – produces remission if phlebotomy not available, deferoxamine Hydroxychloroquine increases excretion of uroporphyrin Prevention & Complications Prevention avoid triggers Prognosis Complete clinical clearing in between 2 months and 2 years after stopping triggers exposures