Case Report Vanishing Bile Duct Syndrome Associated with Azithromycin in a 62-Year-Old Man Juricic Danica 1 , Hrstic Irena 2 , Radic Davor 2 , Skegro Mate 3 , Coric Marijana 4 , Vucelic Boris 2 and Francetic Igor 1 1 Division of Clinical Pharmacology, Department of Internal Medicine, 2 Division of Gastroenterology, Department of Internal Medicine, 3 Division of Abdominal Surgery, Department of Surgery and 4 Department of Pathology and Cytology, Zagreb University Hospital Center, Zagreb, Croatia (Received 26 April 2009; Accepted 30 June 2009) Abstract: Vanishing bile duct syndrome is a severe cholestatic disease associated with toxic effects of medications. Stevens- Johnson syndrome is a hypersensitivity disorder that may also be caused by medications. We present a case of a 62-year-old male patient who developed vanishing bile duct syndrome a month after Stevens-Johnson syndrome. These adverse drug reactions were associated with the use of azithromycin (500 mg daily for 3 days). The patient was initially treated for Stevens- Johnson syndrome with steroids, antihistamines and proton pump inhibitors and fully recovered. However, a month after the beginning of Stevens-Johnson syndrome, he developed vanishing bile duct syndrome and was treated with steroids, ursodeoxycholic acid, antihistamines and tacrolimus. Unfortunately, the treatment was unsuccessful and he was listed for liver transplantation which was performed 7 months after the beginning of jaundice. This is the first case of vanishing bile duct syndrome associated with the use of azithromycin and one of few that reports vanishing bile duct syndrome and Stevens-Johnson syndrome co-occurrence. Vanishing bile duct syndrome is a severe cholestatic disease associated with toxic effects of medications. Stevens-Johnson syndrome is an immune-complex-mediated hypersensitivity disorder that may be caused by drugs, infections, malig- nancies, or it can be idiopathic. Rarely, vanishing bile duct syndrome and Stevens-Johnson syndrome can co-exist. Treatment for Stevens-Johnson syndrome is largely support- ive and symptomatic. The optimal treatment for vanishing bile duct syndrome has not yet been established. We report a case of a 62-year-old male who developed Stevens-Johnson syndrome after the use of azithromycin and, a month later, vanishing bile duct syndrome. Case Report A 62-year-old male patient was referred to the Department of Gastroenterology in March 2008 due to acute hepatic lesion. One month prior, he was treated in the Clinic for infectious diseases for Stevens-Johnson syndrome presented with skin rash and elevated liver enzymes. Stevens-Johnson syndrome developed 3 days after the use of azithromycin (500 mg daily for 3 days). He was treated with methylprednisolone, diphen- hydramine, pantoprazole and intravenous fluids. After 2 weeks of such treatment, skin rash disappeared and labora- tory findings returned to normal. He was discharged with instructions to take methylprednisolone in decreasing doses (32 mg for 3 days followed by 16 mg for 3 days, 8 mg for 3 days and finally 4 mg for 3 days) together with pantopraz- ole 40 mg daily. Two weeks after discharge, he experienced itching followed by jaundice. At the admission to the Depart- ment of Gastroenterology, physical examination revealed only jaundice with residual skin lesions. Liver enzymes were mark- edly elevated: alanine aminotransferase 1545 (<48 U ⁄ l), aspartate aminotransferase 1130 (<38 U ⁄ l), gamma-glutamyl transferase 1860 (<55 U ⁄ l), alkaline phosphatase 545 (<142 U ⁄ l), total bilirubin 259 (<20 lmol ⁄ l). Prothrombin time was within normal range (0.9). He denied allergies to previously used medications including antibiotics. Extensive laboratory and imaging work-up was performed which excluded viral, autoimmune, hereditary, metabolic, obstructive or neoplastic liver disease. Liver biopsy was per- formed 20 days after admission. Histology showed a decreased number of bile ducts which was consistent with vanishing bile duct syndrome (fig. 1). Initial therapy included ursodeoxycholic acid (15 mg ⁄ kg ⁄ daily), methyl- prednisolone 4–32 mg ⁄ daily, diazepam (5–10 mg orally) and antihistamines (chlorpheniramine 40 mg ⁄ daily or loratadine 10 mg orally ⁄ day). The itching subsided but the liver enzymes remained elevated. Author for correspondence: Danica Juricic, Division of Clinical Pharmacology, Department of Internal Medicine, Zagreb University Hospital Center, Kispaticeva 12, 10000 Zagreb, Croatia (fax +385 1 2421 875, e-mail danica.juricic@gmail.com). Ó 2009 The Authors Doi: 10.1111/j.1742-7843.2009.00474.x Journal compilation Ó 2009 Nordic Pharmacological Society. Basic & Clinical Pharmacology & Toxicology , 106, 62–65