the epstein  barr virus ( ebv ) infects b cells . in most cases , ebv - positive patients develop a severe form of infectious mononucleosis which typically manifests with fever , tonsillopharyngitis , lymphadenopathy and hepatosplenomegaly .
deficiencies may be characterized by abnormal activity of lymphocyte function leading to hemophagocytosis and multi - organ failure .
although ebv - associated hlh carries a high mortality rate , quick diagnosis and appropriate treatment can subside the disease .
we describe here a patient who developed hepatosplenomegaly and pancytopenia at 2 years of age but achieved automatic recovery .
, there was a clinical suspicion of ebv - induced hlh and the patient was given the option of treatment with rituximab .
she received antibiotic treatment due to fever and chills . during the hospitalization period , the patient recovered and developed hemophagocytosis with pancytopenia as well as sores on the lip .
the patient underwent bma and nothing abnormal was found . in spite of treatment , the disease did not subside and she developed fever , abdominal distention and edema in her lower extremities .
physical examination showed that the patient had decreased deep - tendon reflexes ( dtr ) and was unable to walk .
clindamycin , ceftazidime , dexamethasone , ivig ( intravenous immunoglobulin ) and g - csf were administered .
since the patient did not achieve full recovery , she was transferred to our center .
based on clinical symptoms and lab tests ( table 1 ) , bma was performed once again and the result raised suspicion of ebv - induced secondary hlh .
rituximab was injected once and the patient developed a blood ebv load of zero within one week . in order to control abnormal stimulation of the immune system ,
the patient was investigated for mutations in il-2-inducible t cell kinase ( itk ) and negative test results were received .
( the patient was negative for mutations in il-2-inducible t cell kinase ( itk ) ) .
she is now considered to be an acceptable candidate for transplantation from an hla matched sibling donor . 
 
hlh can be divided into two subgroups : primary or familial hlh and secondary hlh .
the primary form is an inflammatory disease which is similar to secondary one on the basis of symptoms .
primary hlh usually arises in young children less than one year old ( 70% cases ) ; however , in rare cases it can also occur in adults ( perforin gene mutations have been identified in patients with primary hlh ) .
for example , type 2 is caused by mutations in genes 21 - 22 and type 5 is due to mutations in the munc18 - 20 that may be accompanied by hypogammaglobulinemia .
hypogammaglobulinemia was not confirmed in the patient because it was not possible to check mutation ( the related tests were sent to germany to examine the type 5 disease ) .
ebv may also be accompanied by hypogammaglobulinemia for a certain period secondary hlh is associated with immunologic stimulation caused by malignancies and bacterial or congenital infections .
the most common causes of secondary hlh are viral infections by ebv , cmv , prob19 and hiv .
however , it may also be seen in patients with immune system defects . , 4 secondary hlh is a known complication of ebv infection , particularly in patients with x - linked lymphoproliferative disease .
the incidence of x - linked lymphoproliferative syndrome is 1 in 1,000,000 male infants . 
 
diagnostic criteria for hlh disease diagnosis of hlh requires the presence of all 5 major criteria .
if the patient meets only 4criteria but the clinical suspicion for hlh is high , one should initiate treatment , because delays may be fatal .
alternative criteria 1 or a combination of 2 and 3 may substitute for 1 major criterion . adapted from henter ji , elinder g , ost a.semin oncol . 1991 ; 18:29 - 33 .
it means that ebv - infected b cells stimulate cytotoxic t lymphocytes leading to hypercytokinemia and stimulation of histolytic cells .
more recently , it has been found that chronic stimulation by ebv may cause chronic hlh in the patient . on the other hand
, ebv causes stimulation , generation and uncontrolled secretion of t - and nk- cells , as well as generation of il2 , infa and il6 .
there is another mechanism by which ebv stimulates membrane protein ( lmp-1 ) in cells .
similar to xlp , lmp-1 may cause acquired immune deficiency , leading to hlh accordingly . 
 
treatment follows two goals : first , to suppress immune response using ivig , steroid and hlh protocol .
second , to inhibit undesirable influence of immune response and cytokine - stimulated cell activation using immunochemotherapy . in cases with neurological symptoms
the level of viral dna which is measured by quantitative pcr may be useful to demonstrate treatment response predicting mortality .
the dna level reached zero in our patient . using ivig prior to start of protocol 2004
it has also been recommended in the treatment of ebv - induced secondary hlh monthly . 
 
decrease of b cells , which have been contaminated by ebv , actually causes decrease of viruses , as it may be useful for our patient as well .
finally , treatment - refractory patients , transplant candidates , patients with familial type of hlh , or recurrent disease undergo chemotherapy for 8 weeks .
patients who respond favorably to treatment do not undergo transplantation but those who experience relapse and exhibit neurological symptoms are considered for transplantation .
severe infection of ebv is not associated with life - threatening condition , but our case study needs urgent treatment . in patients with long - term ebv infection , pancytopenia , coagulopathy and hepatosplenomegaly ,
bma will be performed and the serum ferritin level will be measured as well . for patients with secondary hlh ,
rituximab can be used when hlh is associated with ebv to inhibit the immune response .
thus , the main aim of treatment is to reduce the rate of mortality in patients with hlh .
 hemophagocytic lymphohistiocytosis ( hlh ) is one of the complications of epstein - barr virus ( ebv ) infection . 
 although the patients who have developed hlh following ebv have normal immune system , there are a few patients with ebv - induced immune deficiency who develop hlh as well . here 
 , we describe the case of a 10-year - old girl with neurological complications caused by ebv - induced hlh . 
 the patient received rituximab , leading to weakening inflammation associated with ebv infection and suppression of disease through quick treatment . 
INTRODUCTION
INTRODUCING THE CASE
DISCUSSION
CONCLUSION