Increased fragility and bulla formation on the dorsal surface of the hand

Abstract

Discussion The cutaneous signs of porphyria cutanea tarda (PCT) include increased skin fragility and bruising after minor trauma to the dorsal surfaces of the hands, erythema, vesicles, bulla, scarring, and milia in sun-exposed areas. A subset of patients develop these PCT-like features after having a history of ingesting certain drugs like nonsteroidal antiinflammatory drugs, furosemide, nalidixic acid, and tetracycline, or patients who have chronic renal failure or are undergoing hemodialysis. Although the cutaneous findings are similar to PCT, this group of patients has no detectable abnormality in porphyrin-heme biochemistry and porphyrin excretion is completely normal. They are therefore diagnosed as having ‘‘pseudoporphyria.’’ Histopathologically, PCT and pseudoporphyria have similar changes. There is a subepidermal cleft or blister under a normal epidermis, thickening of the basement membrane/vessels, and a slight perivascular lymphocytic infiltrate in the papillary and mid dermis. Perivascular deposits of C3 and immunoglobulin G can be detected by direct immunofluorescence. The exact mechanism by which cutaneous lesions occur in pseudoporphyria is unknown. There is evidence that exposure to ultraviolet A (UVA) light plays a crucial role. There are two theories to explain how UVA light contributes to drug-induced pseudoporphyria. One theory states that the drug accumulates in the skin and acts as a phototoxic agent through the creation of reactive oxygen intermediates like superoxide and hydrogen peroxide. Blisters develop because of damage to the basement membrane by the oxidation of cellular and subcellular membrane components by these reactive oxygen intermediates. A second theory is based on immunoreactants deposited along the endothelium of both lesional and nonlesional skin. The primary treatment approach to PCT and pseudoporphyria is to eliminate the exposure of the offending agents if possible. In drug-induced pseudoporphyria, the skin findings can persist for many months after discontinuing the offending agent. For this series, the recommended choices are: 10, c; 11, a; 12, e.