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 .