Liver transplantation in a child with acute liver failure resulting from drug rash with eosinophilia and systemic symptoms syndrome
A 14-year-old girl was referred to Asan Medical Center Children's Hospital on the basis of test results that indicated abnormal liver function. She had been injured by a traffic accident 10 years earlier, and had undergone plastic surgery twice to heal wounds on her forehead. The second procedure included a free flap operation and craniectomy. Thereafter she had suffered from methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis, which had been treated with intravenous vancomycin over five weeks. Following this treatment, she developed fever and whole-body pruritic erythema, and abnormal liver function tests 6 days prior to her transfer. On admission, she presented with fever, nausea, vomiting, and abdominal discomfort. A generalized erythematous rash with variously sized, discrete lesions was noted on the face, trunk, and extremities. The patient reported an itching and heating sensation, which was aggravated after vancomycin injection. Marked hepatomegaly was also observed.\nLaboratory tests showed a total eosinophil count of 3,150/mm3 (normal, <500 mm3), C-reactive protein level of 15.1 mg/dL (normal, <0.6 mg/dL), creatinine level of 2.5 mg/dL (normal, 0.7 to 1.4 mg/dL), aspartate aminotransferase (AST) level of 320 IU/L (normal, <5 to 40 IU/L), alanine aminotransferase (ALT) level of 263 IU/L (normal, <5 to 40 IU/L), alkaline phosphatase level of 440 IU/L (normal, 40 to 120 IU/L), gamma glutamyl transpeptidase level of 321 IU/L (normal, 8 to 35 IU/L), lactate dehydrogenase level of 2,437 IU/L (normal, 120 to 250 IU/L), total bilirubin level of 3.3 mg/dL (normal, 0.2 to 1.2 mg/dL), direct bilirubin level of 1.8 mg/dL (normal, <0.5 mg/dL), prothrombin time (PT) international normalized ratio (INR) of 1.68 (normal, 0.8 to 1.3), and activated partial thromboplastin time of 34.5 (normal, 25 to 35).\nSerologic tests for hepatitis A, B, and C, as well as cytomegalovirus, Epstein-Barr virus, and autoimmune hepatitis were all negative. Screens for drugs, such as acetaminophen, were negative. The vancomycin level was 26.9 mg/L (normal, 20 to 40 mg/L). Treatment with vancomycin was stopped, and replaced with ciprofloxacin for the treatment of osteomyelitis. Intravenous delivery of a high dose of methylprednisolone was initiated upon an initial suspicion of DRESS syndrome. However, her liver function worsened progressively on hospital day 7, with an AST level of 1,285 IU/L, ALT level of 1,077 IU/L, total bilirubin level of 15.5 mg/dL, direct bilirubin level of 8.0 mg/dL, and PT INR of 4.8, all suggesting acute liver failure. Given the presence of aggravated hepatic encephalopathy, azotemia, and that the patient was refractory to medical treatments, she received a living-donor liver transplantation from her aunt on hospital day 9. The detailed care of preliver and postliver transplantation and care of acute liver failure in our program was described elsewhere,.\nAfter liver transplantation, the skin rash disappeared, with normalization of the eosinophil count and scores in liver and renal function tests. No severe clinical and surgical complications developed postoperatively. Serial liver biopsies showed no evidence of acute rejection. Over the course of a 25-month follow-up period, there has not been any definite recurrence of DRESS syndrome, with the exception of persistently elevated levels of liver enzymes and intermittent eosinophilia. The patient is currently suffering from iatrogenic Cushing's syndrome owing to the high dose of steroids administered to control her elevated levels of liver enzymes.