Ibuprofen Associated Acute Vanishing Bile Duct Syndrome and Toxic Epidermal Necrolysis in an Infant
A 7-month-old girl was hospitalized with complaints of fever and erythematous rashes on body. Two days earlier, she had fever and received ibuprofen at conventional pediatric doses (maximum of 30 mg/kg/day). She had no history of allergic disease. Three months ago, she had been treated with one-dose of ibuprofen (10 mg/kg) for sporadic fever. There was no family history of atopic disease, immunodeficiency or hepatobiliary disease. On admission, physical examination revealed macular erythematous eruption on her face, trunk, and arms, which progressed within 8 hours into the bullae around the arms, and involved the face and trunk. Skin lesion covered more than 30 percent of her body surface area. There were no lesions in the lips or in the eyes. A diagnosis of toxic epidermal necrolysis was made.\nThe initial peripheral white cell count was 5910/mm3 with 69.7% neutrophils, 20.3% lymphocytes, and 3% eosinophils. Hemoglobin level was 12.2 g/dL, platelets count 250000/mm3, erythrocyte sedimentation rate of 120 mm/h, and C-reactive protein 9 mg/dL. Aspartate aminotransferase (AST) level was 716 IU/L, alanine aminotransferase (ALT) 523 IU/L, alkaline phosphatase (ALP) 500 IU/L, total bilirubin (TB) 0.52 mg/dL and direct bilirubin (DB) 0.15 mg/dL. Serological test for hepatitis A, B, and C, Epstein Barr virus, parvovirus B19, herpes virus, adenovirus, cytomegalovirus, human immunodeficiency virus, leptospira, and mycoplasma were negative.\nAt hospital day 6, fever and cutaneous lesion resolved after supportive care but cholestatic picture was presented. AST level was 879 IU/L, ALT 723 IU/L, ALP 890 IU/L, TB 8.5 mg/dL, DB 5.7 mg/dL, gamma-glutamyl transferase 270 IU/L, and total cholesterol 760 mg/dL. The following laboratory findings were normal: amylase, lipase, prothrombin and partial thromboplastin time, α1-antitrypsin, immunoglobulins, complement levels, antinuclear antibody, anti-DNA antibody, anti-smooth muscle antibody, antimitochondrial antibody, anti-liver/kidney microsomal, anti-cytosol antibody, and antineutrophil cytoplasmic antibody. Abdominal ultrasound showed that the liver had homogeneous texture with normal bile ducts and gallbladder. Ursodeoxycholic acid treatment (15 mg/kg per day) was administered.\nAt hospital day 20, skin lesion recovered, but the TB and DB levels were still high (TB 9.5 mg/dL, DB 7.7 mg/dL). Liver biopsy was performed 20 days after admission. It showed lymphocyte infiltrations, marked degeneration of the interlobular bile duct epithelium, and the destructive narrowing of the ductules in the portal tracts and no intralobar bile ducts in at least 10 portal areas on H&E stain, suggesting VBDS (). Neither an organism nor viral cytopathic effect was identified. There was no significant hepatocellular damage and no evidence of sclerosing cholangitis or autoimmune hepatitis.\nThe diagnosis of VBDS associated with TEN was made. During a follow-up period of 3 months, clinical symptoms and biochemical data had shown tendency for resolution. The ursodeoxycholic acid treatment was discontinued. During the next three years, she has a normal physical status with normal liver synthetic functions.