EFFICACY OF RIFAMPIN TREATMENT FOR SEVERE PRURITUS IN CHILDREN WITH CHRONIC CHOLESTASIS.

Abstract

200 Rifampin has been proposed to reduce pruritus in children and adults with chronic cholestasis and distressing interruption of normal activities and sleep. There are a paucity of published data regarding the use of rifampin in children. The purpose of this study was to determine the efficacy of rifampin therapy in an open trial for treatment of severe pruritus in children with chronic cholestasis. Twenty four children (ages 4 mos. to 17 yrs.; mean age = 4.2 yr.; 9 male) were evaluated over a 5-year period. Diagnoses included extrahepatic biliary atresia (n=13), Alagille syndrome (n=6), Byler's disease(n=3) and 1 each with primary sclerosing cholangitis and alpha-1 antitrypsin deficiency (A1AT). Seven pts. were awaiting liver transplantation. All pts. had severe pruritus that had failed to respond adequately to at least 2 months of therapy with ursodeoxycholic acid (n=20), phenobarbital (n=3), diphenhydramine (n=7) and local skin care measures (all pts.). At entry, serum bilirubin (mean ± SEM) was 8.0 ± 1.5 mg/dl, GGT 497 ± 132 U/L, alkaline phosphatase 792 ± 80 U/L and cholesterol 284 ± 38 mg/dL. Treatment was initiated with rifampin, 10 mg/kg/day in 2 divided doses, and pts. were evaluated by telephone contact or at clinic visits at least monthly thereafter. Severity of pruritus was graded retrospectively by the following new scoring system: grade 0 = none; grade 1 = mild itching, primarily in daytime; grade 2 = moderate, but does not interfere with sleep or activities, with or without excoriation; and grade 3 = severe, interferes with sleep or activities, excoriation present. Duration of rifampin therapy ranged from 2 to 60 months (20 ± 4 months). Of the 9 pts. with initial grade 3 pruritus, rifampin therapy led to a decrease to grade 2 in 2 pts., grade 1 in 5, and grade 0 in 1. Of the 15 pts. with initial grade 2 pruritus, rifampin led to decrease to grade 1 in 6 pts., and grade 0 in 8. No pt. had worsening of pruritus on therapy. Two pts. (grade 3 with biliary atresia and grade 2 with A1AT) showed no response to therapy after 1-3 months. Two pts. with Byler's disease underwent biliary diversion because of incomplete response to rifampin. No clinical or biochemical (CBC, liver blood tests, other chemistries) side effects of rifampin were identified. Conclusion: For over 90% of children with chronic cholestasis and severe pruritus unresponsive to other treatments, rifampin appears to be a safe and effective therapy. This therapy may improve the quality of life, allowing for more normal daily activities and function and improved sleep.