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[Physiopathology and management of cholestatic pruritus in children]
A Thébaut1, D Debray2, E Gonzales1
1Service d'hépatologie et transplantation hépatique pédiatriques, hôpital Bicêtre, centre de référence de maladies rares du foie de l'enfant, DHU Hepatinov, université Paris-Saclay, 78, rue du Général Leclerc, 94270 Le Kremlin-Bicêtre, France; Groupe francophone d'hépatologie, gastroentérologie et nutrition pédiatriques, 330, avenue de Grande-Bretagne, TSA 70034, 31000 Toulouse, France; Inserm UMR-S 1174, university Paris-Saclay, 91405 Orsay, France.
Insights
Childhood cholestatic pruritus management lacks consensus. Rifampicin is the first-line treatment, with second-line options like sertraline or naloxone for severe cases, alongside supportive care.
Area of Science:
- Pediatric Gastroenterology
- Hepatology
- Dermatology
Background:
- Cholestatic pruritus is a debilitating symptom in children, often poorly understood.
- Current treatment guidelines for pediatric cholestatic pruritus are not well-established, unlike in adults.
- Refractory cases may necessitate invasive interventions like liver transplantation.
Purpose of the Study:
- To review and outline the current therapeutic strategies for managing pruritus in pediatric cholestatic liver disease.
- To highlight the challenges in pediatric clinical studies for pruritus management.
- To provide a stepwise approach to treatment, from supportive care to advanced therapies.
Main Methods:
- Review of existing literature and clinical guidelines for pediatric cholestatic pruritus.
- Discussion of the proposed pathogenetic mechanisms involving bile acids, opioids, serotonin, and lysophosphatidic acid.
- Outline of a multi-line therapeutic strategy including local care, ursodeoxycholic acid, and specific anti-pruritic agents.
Main Results:
- Rifampicin is identified as the first-line specific treatment for cholestatic pruritus in children.
- Second-line therapies, including selective serotonin reuptake inhibitors (sertraline) and opioid antagonists (naloxone), are considered in expert centers.
- Objective assessment of pruritus is crucial between therapeutic steps.
Conclusions:
- A structured, stepwise approach is recommended for managing pediatric cholestatic pruritus.
- Supportive care and ursodeoxycholic acid are foundational, with rifampicin as the primary targeted therapy.
- Individualized treatment plans, potentially involving expert consultation and advanced therapies, are necessary for refractory cases.
Abstract:
Pruritus is a disabling symptom accompanying chronic cholestasis. In some cases, refractory pruritus may require invasive therapies including liver transplantation. The pathogenesis of pruritus in cholestatic disease is poorly understood. It may involve a specific neural pathway and 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 adult patients, there is no consensus in children, given the difficulty in conducting controlled clinical studies. The currently recommended strategy to manage cholestatic pruritus in children is based on several lines of therapy that should always be associated with local cutaneous care and with nonspecific treatment of cholestasis including ursodeoxycholic acid therapy. Pruritus should be assessed as objectively as possible between each therapeutic step. Rifampicin, an enzyme inducer, is the specific first-line treatment of cholestatic pruritus. The 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, the experience of the center and the will of the child and his family. It could be inhibitors of serotonin reuptake (sertraline) or an opioid antagonist (naloxone). Invasive therapies such as biliary diversion or liver transplantation can also be proposed in the most severe cases.
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