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hypersensitivity to mosquito bites ( hmb ) is characterized by intense skin reactions at bite sites , which consist of not only erythema or bulla but also ulcer or scar , and is associated with general symptoms , such as high fever , general malaise , cramps and renal failure . while this disorder is very rare and reports are scarce in the western literature , some cases of hmb have been reported from japan and taiwan . more than 90% of adults have been exposed to epstein - barr virus ( ebv ) and the virus persists in b cells and epithelial cells in the oropharynx .
recently , ebv has been considered to be associated with not only b - cell malignancy but also t - cell malignancy and natural killer ( nk ) cell granular lymphocyte proliferative disorder ( glpd ) . here
we report the first case of hmb associated with nk cell - derived large granular lymphocyte ( nk - lgl ) lymphocytosis in korea .
a 19-year - old male was referred to our hospital with well - demarcated pustules on the erythematous base on the face / right ear ( figure 1 ) and with fever for 4 days .
he had suffered hypersensitive reactions to mosquito bites , such as skin lesions ( ex , nodules , pustules , ulcerations ) , edematous change on the whole body and the extremities and fever , from childhood .
laboratory tests showed white blood cell count 7.010/l , hemoglobin 15.0 g / dl , platelet 27210/l , biochemical profile , including lactate dehydrogenase , was in the normal range .
ebv anti - ea - dr igg , anti - ebna was positive and serum titer of igg against ebv vca increased .
immunophenotypic analysis demonstrated that cd16+cd56 + cells increased ( 79% ) and cd3 + , cd4 + , and cd8 + cells decreased ( 15% , 8% , 7% ) .
we found rearrangement of tcr-chain gene by pcr analysis in this case ( figure 3 ) , as in some cases of the glpd . in our case ,
pcr amplification with specific primers for tcr-chain gene demonstrated a single band of approximately 160190 bp for v-j products .
ebv , a widespread human herpes virus , infects > 90% of the population by adulthood and persists in b cells and epithelial cells in the oropharynx where reactivation and viral replication may intermittently occur . the virus has also been linked to various b cell , non - b cell neoplasms , such as endemic burkitt s lymphoma and nasopharyngeal carcinoma .
ebv can infect t cells and peripheral lymphoproliferation of cd3 + cells may occur under caebv and , also , ebv can infect nk cells and may induce nk cell lymphoproliferation in patients with caebv . if the activity of ebv is responsible for the lymphoproliferation , the anti - ebv antibody titers , especially anti - vca igg or anti - ea igg might be related with lymphoproliferation . however , if our patient 's data , such as ebv anti - vca igg and ebv anti - ea igg , could not indicate caebv directly , this patient may be considered as caebv because nk cell lymphocytosis associated with ebv infection is frequently detected . to confirm the caebv , further examination of ebv , serial check - up for serum levels of anti - vca igg , iga and igm , anti - ea igg , iga and igm , and anti - ebna are required . according to ishihara et al ,
31% of cases of caebv were complicated by hmb and suggested that the pathogenesis of hmb might be related to clonal lymphoproliferation of ebv dna - positive nk cells .
this immunohematological abnormality may induce the characteristic symptoms of hmb . on the other hand ,
ishihara et al suggested that hmb might be one of the factors that induce ebv - associated lymphoproliferative disease . in this study , while three patients who did not manifest lymphoproliferation did not exhibit this history of hmb , four of six patients who did manifest monoclonal or oligoclonal lymphoproliferation had hmb .
tokura et al have reported that nk cell - dominant mononuclear cells are infiltrated in mosquito bite sites of a severe hmb patient .
it could be speculated that accumulation of nk cells augments reactions on the skin and that these nk cells may directly or indirectly mediate the systemic symptoms by the mosquito bites .
recurrent and prolonged activated state of nk cells may induce additional genetic damage , including chromosomal changes that lead to the genesis of leukemias or lymphomas . in conclusion , we report the first case of hmb associated with nk - lgl lymphocytosis in korea , and further investigation of hmb pathogenesis and the relationship between ebv - infected nk cells and subsequent oncogenesis of nk - lgl lymphoma , including chronic nk - lgl lymphocytosis , is needed .
hypersensitivity to mosquito bites ( hmb ) is characterized by intense skin reactions at bite sites . 
 the pathogenesis of hmb might be related to clonal lymphoproliferation of epstein - barr virus dna - positive natural killer ( nk ) cells . 
 we report the first case of hmb possibly associated with nk cell - derived large granular lymphocyte ( nk - lgl ) lymphocytosis in korea .