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At a glance

A disorder characterized by development of a gray-brown skin discoloration in neonates undergoing phototherapy for neonatal hyperbilirubinemia that may persist for weeks.

History

First described by the American physicians Arthur E. Kopelman, Ralph S. Brown, and Gerard B. Odell in 1972.

Incidence

Unknown, but rare.

Genetic inheritance

None.

Pathophysiology

The skin discoloration only occurs in newborns with cholestasis and elevated serum concentrations of both conjugated and unconjugated bilirubin. Thus, a combination of hepatocellular dysfunction and increased accumulation of bilirubin products from photodestruction during phototherapy is required for BBS. The exact source and nature of the pigment remain unknown. It has been suggested that phototherapy for hyperbilirubinemia acts as a catalyst for serum copper-bound porphyrins to undergo photodestruction sensitized by bilirubin, resulting in metabolites with light absorption in the near-ultraviolet and red spectral range, explaining the bronze skin discoloration. However, due to the fact that bilirubin is only a weak photosensitizer, this hypothesis has been questioned recently. Instead, bilirubin photoproducts, not copper-bound porphyrine metabolites, were considered to be responsible for the increased absorbance. Other reports suspected an accumulation of biliverdin to be the cause of the discoloration. In order to prevent kernicterus, exchange transfusion should be performed at a lower total bilirubin plasma concentration in the presence of BBS (particularly when associated with hemolysis) than is recommended for the treatment of hyperbilirubinemia alone. Instead or additionally, early administration of Sn-mesoporphyrin, a potent inhibitor of heme oxygenase and hence bilirubin production, should be considered.

Diagnosis

Based on the clinical symptoms (appearance of discoloration of the skin, mucous membranes, plasma, and urine during phototherapy) at the typical age. A liver biopsy would reveal signs of hepatocellular dysfunction with decreased excretion of bile constituents and photooxidation products at the level of biliary canaliculi, but it is rarely performed or necessary for the diagnosis. The causative factor of hyperbilirubinemia should be determined by appropriate tests.

Clinical aspects

The discoloration of skin, mucous membranes, plasma, and urine improves over time, but it can last a few weeks to completely resolve. The outcome is usually favorable in cases where hyperbilirubinemia is caused by classic neonatal jaundice. However, if there is an underlying liver disease, the prognosis will most likely depend on that. The plasma reserve of albumin for bilirubin binding is low in infants with decreased bilirubin excretion and BBS. Liver disease should be ruled out in infants who develop BBS, because hepatocellular disease may be present in patients with (conjugated) hyperbilirubinemia. Unbound, unconjugated hyperbilirubinemia can be the result of hypoalbuminemia, acidosis, or drugs with high plasma protein-binding (eg, salicylates, sulfonamides) that compete with bilirubin for albumin binding sites and displace it from the plasma into tissues including the central nervous system. Thus, these drugs ...

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