What is cholestatic pruritus?

Updated: Mar 03, 2020
  • Author: David F Butler, MD; Chief Editor: William D James, MD  more...
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Answer

Cholestasis, or a decrease or arrest in the flow of bile, is associated with pruritus. The deposition of bile salts in the skin was thought to directly cause a pruritogenic effect, but this theory has been proven incorrect. In addition, indirect hyperbilirubinemia does not induce pruritus. Pruritus is more common with intraheptic cholestasis than extrahepatic cholestasis. 

Other theories implicate elevated venous histamine levels, retention of pruritogenic intermediates in bile salt synthesis, and high hepatic concentrations of bile salts resulting in hepatic injury and release of a pruritogenic substance. In support of the last point, rifampin and ursodeoxycholic acid decrease intrahepatic concentrations of bile salts and provide some relief of cholestatic pruritus.

One study has proposed that autotaxin, the enzyme that converts lysophosphatidylcholine into lysophosphatidic acid, may be a potential mediator of cholestatic pruritus. [15]

The accumulation of endogenous opioids, which modulate pruritus and increase opioidergic tone in the brain, is of recent interest because opioid antagonists have been shown to partially relieve cholestatic pruritus. In support of this theory, treatment with opioid antagonists may induce an opioid withdrawal–like syndrome.

Perhaps some combination of the pruritogenic substances mentioned above (ie, bile salts, histamine, opioids) induces cholestatic pruritus.


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