Pruritus is a disabling symptom accompanying chronic
cholestasis. In extreme cases, the refractory nature of
pruritus can result in a need for invasive
therapies including
liver transplantation. The pathogenesis of
pruritus in cholestatic disease is poorly understood. It may involve a specific neural pathway (similar to that associated with
pain) regulated by several pruritogenic substances such as
bile acids,
opioids,
serotonin, and the more recently identified
lysophosphatidic acid. While the therapeutic management of cholestatic
pruritus is well established in adults, there is no consensus in children, in light of the difficulty of conducting controlled clinical studies. The currently recommended strategy to manage cholestatic
pruritus in children is based on several lines of specific
therapies that should be associated with skin hydration and with non-specific treatment of
cholestasis including
ursodeoxycholic acid.
Pruritus should be assessed as objectively as possible between each line of
therapy.
Rifampicin, a potent
CYP3A4 inducer, is the first-line treatment of cholestatic
pruritus. Second-line
therapies require evaluation of the child in an expert center and are discussed on a case-by-case basis depending on the underlying disease and the experience of the center. These include inhibitors of
serotonin reuptake (
sertraline),
opioid antagonists (
naloxone), or ASBT inhibitors. Invasive
therapies such as biliary diversion or
liver transplantation can also be proposed in the most severe cases. The aim of the current update is to review the physiopathologic mechanisms implicated in cholestatic
pruritus and to propose potential therapeutic strategies in children.