the hypersensitivity syndrome , described as drug rash with eosinophilia and systemic symptoms ( dress ) syndrome is a severe , acute , drug reaction , defined by the presence of fever , cutaneous eruption , and systemic findings including enlarged lymph nodes , hepatitis , or hematologic abnormalities with eosinophilia and atypical lymphocytes1,2 ) .
the syndrome can involve several sites , leading to findings such as pneumonitis , renal failure , myocarditis , thyroiditis , or neurologic symptoms , but the liver is the most commonly affected internal organ3 ) .
this reaction can be life threatening , with a mortality rate of approximately 10% , most commonly secondary to liver failure1 ) .
here we report the first pediatric case of liver transplantation for the treatment of acute liver failure caused by vancomycin - induced dress syndrome in korea .
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 .
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 .
laboratory tests showed a total eosinophil count of 3,150/mm ( normal , < 500 mm ) , 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 ) .
serologic tests for hepatitis a , b , and c , as well as cytomegalovirus , epstein - barr virus , and autoimmune hepatitis were all 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 elsewhere4,5 ) .
after 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 .
we here report a pediatric case of acute liver failure resulting from dress syndrome , which was treated by liver transplantation .
most reported cases of dress syndrome show that a cure can be achieved by the immediate withdrawal of the causative agent and the administration of methylprednisolone6 ) .
liver involvement in dress syndrome is common and may range from a transitory increase in liver enzymes to liver necrosis with acute liver failure . to our knowledge , acute liver failure caused by dress syndrome has been reported at least twice in other european countries8,9 ) . in one of these cases9 ) , the patient died waiting for a liver transplant , whereas in the other case8 ) , fatal recurrence occurred after liver transplantation despite potent immunosuppression and cessation of the precipitating factors .
the pathogenesis of dress syndrome is not fully understood , and may be multifactorial10 ) .
although it is most commonly associated with antiepileptic drugs , dress syndrome has also been reported after exposure to a range of medications , including sulfasalazine , doxycycline , allopurinol , linezolid , and vancomycin1,8,10 ) .
the differential diagnosis includes stevens - johnson syndrome ( sjs ) , life - threatening , cutaneous adverse reaction .
the two syndromes overlap clinically , but have different characteristics , treatments and prognoses11 ) .
therefore , a high index of suspicion and rapid diagnosis may be necessary to save the patient 's life . the only undisputed way to treat
the use of systemic corticosteroids is common , although evidence regarding their effectiveness is scant12 ) . in our case
, we replaced vancomycin with ciprofloxacin approximately 6 days after symptoms of dress syndrome were evident , and immediately began corticosteroid treatments after the switch to ciprofloxacin therapy .
although ciprofloxacin is also known to cause dress13 ) , we finally chose that agent to control infection because other several antibiotics aggravated skin rash as well .
these measures were ineffective in preventing liver failure . to our knowledge , this is the first pediatric case report to describe vancomycin - induced acute liver failure occurring as a component of the dress syndrome in korea .
we highlight the need for awareness of the association between drugs , dress syndrome and liver failure . given the absence of reports describing the outcomes of liver transplantation in patients with dress syndrome , particular attention should be devoted to identification of its possible recurrence after liver transplantation .
 drug rash with eosinophilia and systemic symptoms ( dress ) syndrome is characterized by a severe idiosyncratic reaction including rash and fever , often with associated hepatitis , arthralgias , lymph node enlargement , or hematologic abnormalities . 
 the mortality rate is approximately 10% , primarily owing to liver failure with massive or multiple disseminated focal necrosis . here , we report a case of a 14-year - old girl treated with vancomycin because of a wound infection by methicillin - resistant staphylococcus aureus , who presented with non - specific symptoms , which progressed to acute liver failure , displaying the hallmarks of dress syndrome . with the presence of aggravated hepatic encephalopathy and azotemia , the patient was refractory to medical treatments 
 , she received a living - donor liver transplantation , and a cure was achieved without any sign of recurrence . 
 vancomycin can be a cause of dress syndrome . 
 a high index of suspicion and rapid diagnosis are necessary not to miss this potentially lethal disease . 
Introduction
Case report
Discussion