Cholestatic pruritus: Emerging mechanisms and therapeutics

Patients suffering from cholestasis often report experiencing a debilitating, unrelenting itch. In contrast to conditions, such as urticaria, in which histamine primarily drives itch (pruritus), cholestatic pruritus is multifactorial and more difficult to treat. Existing therapies are not always effective and have undesirable adverse effect profiles. Here, we conducted a systematic literature review to evaluate conventional treatment strategy, current pathophysiologic understanding, and the role of new therapies in the context of cholestatic pruritus. We discuss novel findings implicating bile acids, lysophosphatidic acid, and bilirubin as potential important mediators of cholestatic itch. New therapies that aim to remove or modulate pruritogens have been supported in observational cohort studies and randomized controlled trials. Although these new therapies show promise, further research is needed to confirm the pathophysiology of cholestatic pruritus so that targeted therapy can be developed. Patients suffering from cholestasis often report experiencing a debilitating, unrelenting itch. In contrast to conditions, such as urticaria, in which histamine primarily drives itch (pruritus), cholestatic pruritus is multifactorial and more difficult to treat. Existing therapies are not always effective and have undesirable adverse effect profiles. Here, we conducted a systematic literature review to evaluate conventional treatment strategy, current pathophysiologic understanding, and the role of new therapies in the context of cholestatic pruritus. We discuss novel findings implicating bile acids, lysophosphatidic acid, and bilirubin as potential important mediators of cholestatic itch. New therapies that aim to remove or modulate pruritogens have been supported in observational cohort studies and randomized controlled trials. Although these new therapies show promise, further research is needed to confirm the pathophysiology of cholestatic pruritus so that targeted therapy can be developed.