episodic angioedema with eosinophilia ( eae ) , originally described by gleich et al . in 19841 ) , is a syndrome characterized by recurrent episodes of angioedema , fever , leukocytosis , eosinophilia , elevated serum igm , increased body weight , and a benign clinical course lacking any internal organ involvement .
many other cases have been detected since this initial report , and this syndrome has been recognized as a distinct clinical entity2 , 3 ) .
more than 40 cases with symptomatic presentations and laboratory findings similar to eae have been reported , but these cases have not involved recurrent attacks , and thus have been subsequently designated as nonepisodic angioedema with eosinophilia ( neae)4 - 8 ) .
the majority of these neae cases have been reported in japanese patients , with the exception of three cases reported in the korean literature7 - 9 ) .
this ethnic or regional distribution may be an important characteristic of neae . in this paper ,
we describe a patient whose clinical and laboratory features were similar to those observed in previous cases of neae , and also present our review of cases thus far reported in korea .
a 26-year - old korean woman presented with edema of her hands and lower legs , which had developed 2 weeks prior to her hospital visit . her body weight had increased by 2 kg over those 2 weeks , and this was her first episode of the reported symptoms .
the edema was distributed symmetrically on both of the patient 's upper and lower extremities , and was pitted .
she denied any febrile sensation and had a pruritic rash on her lower legs ( figure 1a-1c ) , and had also experienced mild joint pain in both knees 1 week after the onset of the edema .
she also denied taking any drugs , including oriental medications , with the exception of one acetaminophen tablet ( 300 mg ) 1 week prior to the onset of edema .
laboratory tests revealed leukocytosis ( 12,250/mm ; normal range : 4,000 - 10,000/mm ) with 51.5% eosinophils ( normal range : 0~7% ) in the peripheral blood .
serum ige had increased to 1,423 iu / ml ( normal range : 0 - 170 iu / ml ) , but iga , igg , and igm levels were all within normal limits .
no abnormal findings were observed in the serum chemistry that would be reflective of renal or hepatic dysfunction .
the rash on the patient 's lower legs was examined histologically , and identified as perivascular eosinophil infiltration ( figure 2 ) .
lymphocyte phenotyping was conducted , but did not indicate the presence of any abnormal lymphocyte clones .
we diagnosed the patient with neae , and prescribed an oral antihistamine to control the pruritus .
one week after the patient began taking antihistamines , the edema and rash began to evidence improvements .
the eosinophil count decreased to 1,530/mm after 2 weeks and to 736/mm after 8 weeks .
the patient was free of symptoms at 4 months , and had an eosinophil count of 550/mm .
we followed the patient for 18 months , and observed no recurrence of either the symptoms or the eosinophilia ( the eosinophil count was 180/mm ) .
our patient presented with eosinophilia with angioedema localized to the upper and lower extremities , and evidenced features typical of the neae cases thus far reported in japan .
that is , the patient was a young female exhibiting a mild weight gain , and her condition lacked internal organ involvement , improved without corticosteroids , involved no increase in igm levels , and did not recur over the course of 18 months .
eae is characterized by recurrent edema and requires the administration of corticosteroids , and has also been reported principally in europe and the united states . however , in japan and korea , more than 40 cases have been reported with clinical symptoms similar to those observed in eae , but without recurrent episodes ; these patients recovered without corticosteroid treatment4 - 8 ) .
first gave this distinct form of eae the designation neae4 ) , which has been loosely identified as a less severe form of eae6 ) .
the most notable aspect of neae is the absence of recurrence , but several other differences also exist with regard to the clinical features of neae and eae .
the angioedema is normally localized to the hands and the proximal portion of the lower legs , as in the present case , whereas in eae , the angioedema frequently extends farther down the extremities , sometimes including the face10 ) .
an increase in serum igm levels is also normally detected in cases of eae , but is seldom observed in neae6 , 10 ) .
almost all eae patients require corticosteroid therapy , whereas spontaneous remission frequently occurs in patients suffering from neae . additionally , all neae patients thus far have been young females , as in the case described herein4 - 8 ) .
the cause of the sudden increase of eosinophils remains unknown , as with idiopathic hypereosinophilic syndrome .
the identification of abnormal clonal cd3 cd4 cells in the blood of some eae sufferers11 ) indicates that eae and neae may be , in some if not all patients , a disease that involves abnormal t cell clones , similarly to the lymphocytic variant of hypereosinophilic syndrome12 ) .
the predilection to affect the skin with an absence of internal organ involvement in eae and neae is also a clinical feature reminiscent of the lymphocytic variant of hypereosinophilic syndrome12 ) . in the case
described herein , we conducted lymphocyte phenotyping in order to determine the presence of any aberrant clonal lymphocytes , as has been observed in cases of the lymphocytic variant of hypereosinophilic syndrome13 ) .
the angioedema of eae and neae is likely associated with a temporal increase in the vascular permeability of local capillaries via some mediators , including antiendothelial cell antibodies and cytokines3 , 14 - 16 ) .
several reports have shown that histamine levels are within normal limits , and that il-1 , il-5 , and il-6 generated by monocytes , endothelial cells , t cells , and eosinophils increase during the acute phase of eae3 , 5 , 11 , 15 , 16 ) . according to a recent report
, il-5 levels were determined to be lower , and tnf-levels were higher in the acute phase of neae than in the acute phase of eae . thus , the cytokine profile may be related with the existence or absence of recurrent attacks5 ) . recently ,
several cases of eae and neae have been reported in korea7 - 9 , 17 ) .
table 1 shows these six cases of eae and neae , including the case described in this paper .
cases 1 , 2 , and the present case were readily diagnosed as neae , whereas cases 3 and 5 were thought to be eae . in case 4 , certain aspects , such as the elevated serum igm level and the necessity for corticosteroid therapy to control the symptoms , supported a diagnosis of eae . however , the presence of other aspects , including the fact that it occurred in a young female , the absence of weight gain , and the absence of a previous episode or recurrence , was suggestive of neae .
this series of neae and eae case reports from korea demonstrates that neae and eae are not rare diseases within the korean population , and also suggests that neae may have a racial predisposition toward asian populations . in this work ,
we have described the case of a korean patient with neae and have reviewed five other cases of neae and eae occurring in korean patients .
as in the japanese population , neae is not an uncommon disease within the korean population .
 episodic angioedema with eosinophilia ( eae ) is characterized by recurrent angioedema , peripheral eosinophilia , elevated serum igm , fever , weight gain , and a benign course lacking any internal organ involvement . 
 dozens of cases of the nonepisodic variant ( neae ) , which is limited to a single attack , have been reported in japan . 
 these neae cases normally have been less severe than the episodic type . in this paper 
 , we describe the case of a korean patient whose clinical and laboratory findings were consistent with neae , and review five other cases of eae and neae reported in the korean literature . 
 the korean neae cases outlined in this paper demonstrate that , as in japan , neae is not uncommon in korea , and also suggest that this disease exhibits a cultural predilection for asian populations . 
INTRODUCTION
CASE REPORT
DISCUSSION