See “Management of Cholestatic Pruritus in Paediatric Patients With Alagille Syndrome: The King's College Hospital Experience” by Kronsten et al on page 149.
Pruritus is a common complication of cholestatic liver disease, which significantly affects patient's and caregiver's quality of life because of constant scratching, irritability, poor sleep, and appetite. It can occur in any liver disease, but it is most commonly observed in intrahepatic cholestasis such as in Alagille syndrome and progressive familial intrahepatic cholestasis. In these disorders, pruritus may be severe, and good symptom control is paramount if liver transplantation is to be avoided. Large randomized controlled studies of treatment of pruritus in children do not exist, with many reports being small case series.
The pathophysiology of pruritus remains poorly understood, and therapeutic options therefore limited. It is likely multifactorial, with increased bile acid levels in serum and skin being implicated along with upregulation of central nervous system opioid receptors (1). Therapeutic agents may target the bile acid pool, such as the binding agent cholestyramine and the synthetic bile acid ursodeoxycholic acid, which stimulates bile flow. Other options include the opioid receptor antagonist naltrexone (2) and rifampicin, which induce hepatic enzymes, facilitating renal bile acid excretion. Sedating antihistamines may be helpful to promote sleep. Ultimately, multiple concomitant medications may be the most useful approach, especially when single agents prove insufficient.
Surgical options to manage pruritus have expanded in recent years. Biliary diversion procedures such as ileal exclusion and partial external biliary drainage (3) can reduce terminal ileal reabsorption and hence circulating bile acids. Biliary diversion does not always work, involves abdominal surgery, and may lead to or worsen malabsorptive diarrhea. Molecular adsorbent recirculation system dialysis has been effective in small pediatric studies by adsorbing bile acids onto a dedicated dialysis filter (4) and can be repeated sequentially. Nonetheless, it is invasive and requires recurrent hospitalization.
In this issue of the Journal of Pediatric Gastroenterology and Nutrition, Kronsten et al (5) describe their experience with pharmacologic therapy of intractable pruritus in a retrospective analysis of a large series of children with Alagille syndrome. Of 62 children, 82% reported pruritus, of whom 98% underwent treatment with various antipruritic medications. Pruritus severity and drug efficacy were graded retrospectively according to case note entries. Although the authors acknowledge the retrospective nature of the study and subjectivity of the grading systems, their work makes sober reading. Most children required concomitant use of several, and up to 5, medications, with control of pruritus by medications alone being achieved in only 41%. Of the 39% in whom pruritus resolved completely, in more than half this was achieved only with liver transplantation. The common most drugs used were ursodeoxycholic acid, which was of some reported benefit in 65%, and rifampicin, which had a good effect in just less than half. Cholestyramine was poorly tolerated because of unpalatability. Naltrexone, ondansetron, and antihistamines were used less frequently but with good effect, albeit in small numbers of children.
This study includes a suggested algorithm for treating pruritus, which we believe is the first of its kind. The study should prove a useful guide in the management of this perplexing conundrum. The onus is, however, on the as a community of pediatric hepatologists to advance the understanding of pruritus and its treatment by driving clinical research with larger, prospective, placebo-controlled trials.
1. Cies JJ, Giamalis JN. Treatment of cholestatic pruritus in children. Am J Health Syst Pharm
2. Zellos A, Roy A, Schwarz KB. Use of oral naltrexone for severe pruritus due to cholestatic liver disease in children. J Pediatr Gastroenterol Nutr
3. Schukfeh N, Metzelder ML, Petersen C, et al. Normalization of serum bile acids after partial external biliary diversion indicates an excellent long-term outcome in children with progressive familial intrahepatic cholestasis. J Pediatr Surg
4. Schaefer B, Schaefer F, Wittmer D, et al. Molecular adsorbents recirculating system dialysis in children with cholestatic pruritus. Pediatr Nephrol
5. Kronsten V, Fitzpatrick E, Baker A. Management of cholestatic pruritus in paediatric patients with Alagille syndrome: the King's College Hospital Experience. J Pediatr Gastroenterol Nutr