varicella - zoster virus ( vzv ) infection is a self - limited childhood disease1,2 ) .
however , it sometimes can be a life - threatening condition , especially in immunocompromised patients such as bone marrow transplant recipients , who are receiving corticosteroids therapy or chemotherapy and patients with human immune deficiency virus infection1,2,3,4,5,6,7,8 ) .
although , it is very rare , vzv infection can be also lead to severe illness in immunocompetent persons2,3,6,7 ) .
we report a case of primary vzv infection with very rare complications of acute respiratory distress syndrome ( ards ) , acute hepatitis , disseminated intravascular coagulation ( dic ) , and encephalopathy in an 8-year - old boy undergoing chemotherapy for acute lymphoblastic leukemia ( all ) .
an 8-year - old boy was admitted to the catholic university of korea , seoul st .
he was diagnosed with all ( l3 ) 4 years ago . after first relapse ,
the patient received a bone marrow transplant 3 years ago , but second relapse occurred unfortunately .
it had been three weeks since his last chemotherapy , which included a high dose of methotraxate .
a complete blood count showed hemoglobin of 12.1 g / dl , white blood cells ( wbcs ) count of 3,490/mm with segmented neutrophils of 80.0% , and platelet count of 135,000/mm .
liver function tests showed slightly increased levels of aspartate aminotransferase ( ast , 78 u / l ) and alanine aminotransferase ( alt , 135 u / l ) ( fig .
1 ) . chest , abdomen x - rays and abdomen and pelvis computed tomography scans appeared normal .
the next day , the patient was running a fever of up to 39.0 , so empirical intravenous antibiotics were started .
his abdominal pain remained constant . on his third day , multiple erythematous vesicles formed on his trunk .
consequently , 1,500 mg / m of acyclovir divided into three doses per day was administered . on hospital day 5 , the vesicles developed across the whole body and he complained of dyspnea . a chest x - ray ( fig .
2a ) showed numerous small nodules in the entire both lungs , which lead to a diagnosis of varicella pneumonia .
laboratory tests revealed wbcs of 5,090/mm , platelet count of 32,000/mm , ast of 931 u / l , alt of 788 u / l , lactate dehydrogenase ( ldh ) of 3,196 u / l ( fig .
we continued administration of intravenous acyclovir , changed the intravenous antibiotics , and added intravenous immunoglobulin ( ivig , 500 mg / kg / day ) , single donor platelets , fresh frozen plasma , and antithrombin iii .
the next evening , the patient began to show drowsy mental state and dyspnea was aggravated .
we increased the dose of ivig to 1 g / kg / day . on hospital day 7 , a chest x - ray showed marked improvements in the lung , but cardiomegaly was noted .
platelet count was 69,000/mm , and ast and alt were 224 u / l and 280 u / l ( fig .
we used ivig for a total of four days , however fever persisted and the vesicular skin lesions showed no change . on echocardiography ,
cardiac function was normal . on hospital day 9 , the patient 's blood pressure ( bp ) began to increase up to systolic pressure of 150 mm / hg and diastrolic pressure of 125 mm / hg . we continuously administered an intravenous labetarol , however no definite effect was observed .
using by real - time polymerase chain reaction ( pcr ) , vzv was detected in patient serum that had had been sampled at the onset of skin lesions .
we decided to administer ivig for two more days . on the morning of hospital day 11 , the patient experienced a generalized tonic - clonic seizure that lasted 30 minutes which we thought was a sign of hypertensive crisis or vzv involvement in central nerve system .
no more seizures were occurred thereafter . by hospital day 13 and the ninth day after intubation , the patient 's pulmonary condition was stable .
he no longer had a fever , and all skin lesions reached the scarring stage . on hospital day 17 , the patient was transferred from the icu to the general ward .
lymphocyte subset showed cd3 of 87.0% ( normal range [ nr ] , 61%-85% ) , cd4 of 14.8% ( nr , 23%-58% ) , cd8 of 70.6% ( nr , 19%-48% ) , cd19 of 9.6% ( nr , 7%-23% ) , and cd56 of 3.0% .
these results suggested that the patient 's cellular immunity was not yet recovered . due to the patient 's history of seizure
, we performed brain magnetic resonance imaging ( mri ) and electroencephalogram ( eeg ) .
2b ) showed multiple patchy high - signal - intensity lesions in the subcortical regions of the right frontal , parietal and occipital lobes as a results of vzv - induced encephalitis .
he was discharged on hospital day as he had been restored to a healthy appearance and most laboratory data showed improvement ( fig .
the follow - up brain mri was done three months later , multiple high - signal - intensity lesions due to vzv - induced encephalitis were disappeared .
however , dissemination of the primary infection can occur , particularly in immunocompromised children1,2,3,4,5,6,7 ) . the lungs , liver , brain and heart are usually involved in progressive varicella1 ) .
the mortality rate of disseminated varicella infection is extremely high in immunocompromised children because their clinical course is fulminant and atypical4,5 ) .
acyclovir is a highly potent inhibitor of vzv and early treatment with acyclovir has been shown to prevent dissemination and progression of disease9 ) .
however , acyclovir alone may not be able to fully fight disseminated vzv infection in immunocompromised patients4,5 ) , because immunocompromised children , who have lower t - cell responses , can not control vzv , resulting in both prolonged infection and reactivation9 ) .
although , it is very rare , vzv resistance to acyclovir has been reported in these patients9 ) . in this case , in spite of administration of acyclovir , vzv infection rapidly progressed to ards .
the recommended dosage for sepsis is 400 mg / kg / day administered as intravenous infusion for five days10 ) .
however , a dosage of 500 mg / kg / day was not sufficient . after increasing the dosage to 1 g / kg / day , the patient had no fever or new skin lesions .
ivig provides antibodies that neutralize virus invasion and suppress viremia , acting synergistically with acyclovir4 ) .
lu et al.4 ) used ivig with acyclovir in an immunocompromised child with disseminated varicella that had resulted in multiorgan failure .
various adverse effects of ivig like acute hypersensitivity , thromboembolism , renal failure , hypotension , aseptic meningitis and fluid overload are widely known11 ) .
however , most adverse effects associated with its administration are immediate , mild , and transient12 ) . and severe late adverse effects like renal toxicity and thromboembolic events were closely related with rate of infusion and patient 's underlying risk factors , not with dose12 ) .
we therefore suggest that clinicians should consider ivig with acyclovir to treat patients with disseminated vzv infection .
we did not chose corticosteroid because , it has the potential to lower the host 's resistance to infection and to suppress the host 's immune system10 ) . in rare case ,
cidofovir was used in hepatic failure due to vzv for antiviral activity against acyclovir and foscarnet - resistant vzv - strains13 ) .
the efficacy of alternative viral drugs alone or in combination with standard antiviral substances needs individual decision - making for situations13 ) .
varicella - zsoter immunoglobulin was also used some in solid - organ transplant recipients14 ) . in conclusion ,
however , early administration of acyclovir and high - dose of immunoglobulin may result in a positive outcome , as it did in this case .
 varicella - zoster virus infection can lead to severe illness in immunocompromised patients . 
 further the mortality rate of disseminated varicella infection is extremely high particularly in immunocompromised children . 
 we report a case of disseminated varicella infection in a child with acute lymphoblastic leukemia who was receiving chemotherapy , but was initially admitted with only for acute abdominal pain . 
 the patient rapidly developed severe complications , including acute respiratory distress syndrome , acute hepatitis , disseminated intravascular coagulation , and encephalopathy . 
 acyclovir is a highly potent inhibitor of varicella - zoster virus infection . 
 however , owing to rapid disease progression , it might not be sufficient to control a disseminated varicella infection , especially in immunocompromised patients . 
 immunoglobulin neutralize virus invasion and suppress viremia , acting synergistically with acyclovir . in this case , 
 early administration of acyclovir and a high - dose of immunoglobulin , combined with mechanical respiratory support , proved adequate for treatment of this severe illness . 
Introduction
Case report
Discussion