Steroid therapy for a case of severe drug-induced cholestasis.
OBJECTIVE
To report a severe case of cholestatic liver disease successfully treated with corticosteroids following combined therapy with clarithromycin and nimesulide.


METHODS
A 15-year-old girl was admitted with cholestasis probably related to treatment with clarithromycin and nimesulide for an upper respiratory tract infection. Other causes of liver disease (infections, metabolic liver disorders, genetic cholestatic syndromes, autoimmune diseases, primary biliary tract disorders) were excluded. Liver biopsy showed a severe canalicular cholestasis with bile plugs in dilated bile canaliculi, giant cell transformation, and portal and lobular infiltrate. An objective causality assessment suggested that cholestasis was probably related to clarithromycin and/or nimesulide use. No benefit was derived from a course of ursodeoxycholic acid therapy. Since the patient experienced a progressive worsening in cholestasis, prednisone was started after 20 days. This therapy was promptly followed by improvement in clinical and laboratory test results. After 2 months of prednisone treatment, the patient became symptom-free with normal liver function tests.


CONCLUSIONS
The manifestations of drug-induced hepatotoxicity are highly variable, ranging from asymptomatic hypertransaminemia to fulminant hepatic failure. No specific treatment for drug-induced hepatotoxicity exists. Early recognition and drug withdrawal are the keys to management of hepatotoxicity, but in some cases, liver disease may persist despite discontinuation of the drug. Possible advantages of corticosteroid therapy have not been well demonstrated.


CONCLUSIONS
Application of the Naranjo probability scale indicates a probable relationship between cholestasis and nimesulide plus clarithromycin use. This case draws attention to a possible therapeutic option for some cases of drug-induced hepatotoxicity that show a severe course without any sign of improvement.
Giannattasio
Antonietta
A
Department of Pediatrics, University of Naples Federico II, Italy.
D'Ambrosi
Mariangela
M
Volpicelli
Monica
M
Iorio
Raffaele
R
D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000473:pathology; D002779:Cholestasis / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D017291:Clarithromycin / Q000009:adverse effects* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008099:Liver / Q000473:pathology; D008111:Liver Function Tests; D012141:Respiratory Tract Infections / Q000150:complications / Q000188:drug therapy; D013449:Sulfonamides / Q000009:adverse effects* / Q000627:therapeutic use
D000305:Adrenal Cortex Hormones; D000900:Anti-Bacterial Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D013449:Sulfonamides; D017291:Clarithromycin; C012655:nimesulide