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Paraffin-embedded sections of the exfoliated skin stained with hematoxylin-eosin showed a pink amorphous substance within the stratum corneum, with overlying parakeratosis. A periodic acid–Schiff stain was negative for fungal elements, and bile and Ulex europaeus agglutinin stains were negative for bile and for erythrocyte glycoprotein, respectively. Benzidine, which selectively stains hemoglobin,1 focally stained the outlines of ovoid anucleate bodies within the amorphous, intracorneal substance.
The patient underwent elective cholecystectomy, revealing adenocarcinoma of the gallbladder. Within 2 months, the skin lesions had entirely resolved. The patient did not experience any recurrence of such skin lesions; he died of unrelated causes 1 year later.
The patient's eruption appeared to be an uncommon presentation of cutaneous bile pigment deposition. The temporal association of green pigmentation with marked hyperbilirubinemia and its resolution on correction of the serum abnormality support deposition of bilirubin and/or bilirubin metabolites into the skin as the mechanism for the clinical presentation. Kanzaki and Tsuda,2 who first described this eruption in 1992, regarded it as a form of eccrine chromhidrosis. They hypothesized that direct (water-soluble) bilirubin is secreted into the stratum corneum through the eccrine glands and then oxidized to biliverdin. This hypothesis may explain the presence of yellow papules at the periphery of the eruption, the expected color of bilirubin as is seen in jaundice. However, jaundice, which may vary from a faint golden color to green-yellow, is generalized and ill-defined as a rule. Fever and perspiration are possible contributing factors in the development of this eruption, but are not found in all cases.3 The eruption may be macular or papular. In addition to adenocarcinoma of the gallbladder, the eruption has been associated with acute viral hepatitis and cholelithiasis. The common denominator in all cases is obstruction of hepatobiliary drainage that results in hyperbilirubinemia. Why the vast majority of hyperbilirubinemic individuals do not develop these cutaneous findings is unknown.
Our initial histologic impression of intracorneal hemorrhage on routine stain was not confirmed by the results of guaiac screening or by staining with U europaeus agglutinin and benzidine. Techniques for the identification of bilirubin metabolites in skin are not readily available.
The authors thank Gunter Burg, MD, and Jurg Hafner, MD, for kindly providing and performing the benzidine stain.
Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature
Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal
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