chronic eosinophilic pneumonia ( cep ) , a rare eosinophilic lung disease of unknown etiology , is characterized by peripheral blood eosinophilia and abnormal eosinophil accumulation in the lungs ( 1 ) .
cep most commonly affects middle - aged women and is accompanied by asthma in more than 50% of cases .
symptoms of cep can be easily relieved by systemic corticosteroid therapy ; however , in most cases , recurrences are frequent after the end or tapering off of systemic corticosteroids , especially in those with a prior diagnosis of asthma ( 2 , 3 ) .
anti - ige treatment reduces circulating free ige level , down - regulates high - affinity ige receptors ( fcri ) expression in inflammatory cells , and decreases serum and tissue eosinophil counts in many allergic diseases , including asthma , rhinitis , chronic urticaria and eosinophilic gastrointestinal disorders ( 4 - 7 ) .
however , the efficacy of anti - ige therapy in cep has not been studied . here ,
we first report two cases of cep that were successfully treated with anti - ige therapy .
a 17-yr - old non - smoking male presented with a 2-week history of dry cough and dyspnea on exertion at august 2009 .
the patient had a cough and shortness of breath during running at school 9 months prior and was diagnosed with bronchial asthma . however , his asthma was not well controlled since he did not use regular maintenance therapy . during initial physical examination , coarse breathing was heard in both lower lung fields .
the patient 's white blood cell count was 12,100 cells / ml with 29.6% eosinophils .
ground glass opacities were found in the patient 's lungs by chest computerized tomography ( ct ) .
the patient 's total ige level was 1,758 iu / ml and he was sensitized to birch pollen by an allergy skin prick test .
serological testing for parasites ( toxocara , anisakis , cysticercus , paragonimus , sparganum , and clonorchis ) produced negative results .
after 14 weeks of systemic ( 0.5 - 1 mg / kg ) and regular inhaled corticosteroids , the patient 's serum eosinophil count was normalized ( 50 cells / ml ) .
however , after tapering off of the oral corticosteroid dose , the patient 's peripheral eosinophil count was increased again to 2,200 cells / ml and multiple new patchy consolidations were found by chest x - ray and ct . to reduce steroid requirement and eosinophil activation , 300 mg
( 4 mg / kg of body weight ) of anti - ige antibodies were administered by injection every 2 weeks .
after 10 cycles of anti - ige therapy , the patient stopped taking oral corticosteroid .
the patient maintained a normal peripheral eosinophil count with no evidences of eosinophilic infiltration on radiologic findings .
after 18 cycles of therapy , his asthmatic symptoms have been well controlled for more than 2 yr using only an ics / laba inhaler as maintenance medication .
the patient 's peripheral eosinophil counts remain normal with no evidence of relapse , and he continued to have normal chest x - rays ( table 1 ) . a 19-yr - old non - smoking male presented with a history of cough , sputum , dyspnea on exertion and weight loss at august 2007 .
the patient had a white blood cell count of 10,900 cells / ml with 7.2% eosinophils .
a ground glass opacity was found in the patient 's right middle and left lower lobes on ct ; high sputum eosinophil counts were also found ( 56% ) .
the patient 's total ige level was 368 iu / ml , and he was sensitized to house dust mite on skin prick test .
serological testing for parasites ( toxocara , anisakis , cysticercus , paragonimus , sparganum , and clonorchis ) produced negative results .
after using a budesonide / formoterol inhaler and systemic oral corticosteroid , the patient 's lung infiltration and peripheral eosinophil count decreased ; however , when we tried to reduce the systemic steroid dose , the patient suffered recurrent respiratory symptoms with newly generated peripheral and lung eosinophilia several times over a 12-month period . to reduce the patient 's systemic steroid requirement and peripheral eosinophil activation , injections of 225 mg ( 4 mg / kg of body weight ) of anti - ige antibodies were administered every 2 weeks . after two injections
, the patient noticed significant improvement in his asthma symptoms and stopped taking systemic steroid . in total , the patient received 10 cycles of therapy .
his asthmatic symptoms , peripheral eosinophil count , and radiologic finding have been well maintained using an ics / laba inhaler with no evidence of relapse for 15 months ( table 1 , fig .
a 17-yr - old non - smoking male presented with a 2-week history of dry cough and dyspnea on exertion at august 2009 .
the patient had a cough and shortness of breath during running at school 9 months prior and was diagnosed with bronchial asthma . however , his asthma was not well controlled since he did not use regular maintenance therapy . during initial physical examination , coarse breathing was heard in both lower lung fields .
the patient 's white blood cell count was 12,100 cells / ml with 29.6% eosinophils .
ground glass opacities were found in the patient 's lungs by chest computerized tomography ( ct ) .
the patient 's total ige level was 1,758 iu / ml and he was sensitized to birch pollen by an allergy skin prick test .
serological testing for parasites ( toxocara , anisakis , cysticercus , paragonimus , sparganum , and clonorchis ) produced negative results .
after 14 weeks of systemic ( 0.5 - 1 mg / kg ) and regular inhaled corticosteroids , the patient 's serum eosinophil count was normalized ( 50 cells / ml ) .
however , after tapering off of the oral corticosteroid dose , the patient 's peripheral eosinophil count was increased again to 2,200 cells / ml and multiple new patchy consolidations were found by chest x - ray and ct . to reduce steroid requirement and eosinophil activation , 300 mg
( 4 mg / kg of body weight ) of anti - ige antibodies were administered by injection every 2 weeks .
after 10 cycles of anti - ige therapy , the patient stopped taking oral corticosteroid .
the patient maintained a normal peripheral eosinophil count with no evidences of eosinophilic infiltration on radiologic findings .
after 18 cycles of therapy , his asthmatic symptoms have been well controlled for more than 2 yr using only an ics / laba inhaler as maintenance medication .
the patient 's peripheral eosinophil counts remain normal with no evidence of relapse , and he continued to have normal chest x - rays ( table 1 ) .
a 19-yr - old non - smoking male presented with a history of cough , sputum , dyspnea on exertion and weight loss at august 2007 .
the patient had a white blood cell count of 10,900 cells / ml with 7.2% eosinophils .
a ground glass opacity was found in the patient 's right middle and left lower lobes on ct ; high sputum eosinophil counts were also found ( 56% ) .
the patient 's total ige level was 368 iu / ml , and he was sensitized to house dust mite on skin prick test .
serological testing for parasites ( toxocara , anisakis , cysticercus , paragonimus , sparganum , and clonorchis ) produced negative results .
after using a budesonide / formoterol inhaler and systemic oral corticosteroid , the patient 's lung infiltration and peripheral eosinophil count decreased ; however , when we tried to reduce the systemic steroid dose , the patient suffered recurrent respiratory symptoms with newly generated peripheral and lung eosinophilia several times over a 12-month period . to reduce the patient 's systemic steroid requirement and peripheral eosinophil activation , injections of 225 mg
( 4 mg / kg of body weight ) of anti - ige antibodies were administered every 2 weeks .
after two injections , the patient noticed significant improvement in his asthma symptoms and stopped taking systemic steroid . in total , the patient received 10 cycles of therapy .
his asthmatic symptoms , peripheral eosinophil count , and radiologic finding have been well maintained using an ics / laba inhaler with no evidence of relapse for 15 months ( table 1 , fig .
the onset of the disease is usually insidious , and the symptoms appear at least a few months before diagnosis . both cases in this article diagnosed as having asthma several months ago before the onset of cep , and had insidious symptoms with peripheral and bronchial eosinophilia in sputum differential count and radiologic studies .
we diagnosed cep with above conditions , and treated with systemic corticosteroid in both cases .
although cep responds well to systemic corticosteroid therapy during its initial phase , there is limited consensus concerning the long - term natural history and associated treatment regimens . in 1993 , naughton et al .
( 3 ) reported on long - term ( 10 yr ) prognosis of patients with cep . seven of 9 patients who were tapered off steroids experienced clinical , hematologic , and radiologic relapses .
twenty - five percent of the patients were maintained on a regimen of low - dose steroid therapy ( 3 ) .
these data suggest that most of cep patients require long - term , low - dose systemic corticosteroid therapy in order to induce symptom remission and to prevent recurrent eosinophilic infiltration into the lungs .
the two cases presented in this study showed recurrent peripheral and pulmonary eosinophilia after the reduction of systemic oral steroid .
therefore , we tried anti - ige therapy to reduce the patients ' systemic steroid requirement and observed that they have maintained the remission state without relapse .
one of the most novel and striking new drugs in allergy field is anti - ige antibody , which has the ability to control many allergic diseases , including asthma , rhinitis , eosinophilic gastrointestinal disease , and refractory urticaria ( 4 - 7 ) .
anti - ige therapy results in a rapid reduction of free ige levels and the down - regulation of fcri on basophils , mast cells , and other inflammatory cells .
moreover , anti - ige therapy has profound and significant reducing effects on airway and tissue eosinophilia in patients with mild allergic asthma and on allergen - induced seasonal increases in circulating and tissue eosinophils in subjects with allergic rhinitis ( 4 , 7 ) .
although the exact mechanism underlying the reduction in eosinophils by anti - ige therapy remains unclear , some possible mechanisms have been suggested .
( 9 ) showed that the reduction in eosinophils was more significant in those who had a low post - treatment free ige level ( < 50 ng / ml ) than in those who had a relatively high post - treatment free ige level ( > 50 ng / ml ) after anti - ige injection .
this suggests that a direct interaction with ige receptors on eosinophils is a contributing factor .
( 10 ) found that the eosinophil apoptosis marker annexin v was significantly elevated in patients after anti - ige treatment .
additionally , the secretion of gm - csf , a vital cytokine for eosinophil survival , was reduced after anti - ige treatment compared to those taking a placebo .
these results suggest that eosinophil reductions during anti - ige therapy are caused by the induction of apoptosis through reduced gm - csf secretion by t lymphocytes .
anti - ige antibody therapy may give a beneficial effect for the patients with eosinophilia related conditions such as cep . in the present study , both patients benefited from anti - ige therapy .
neither patient suffered from cep - related respiratory symptom aggravation , and both stopped oral steroid use .
no evidence of eosinophil activation in peripheral blood or lung tissues has been shown in follow - up studies . to date , the only treatment modality for recurrent cep is systemic steroids .
considering the serious adverse reactions caused by long - term systemic steroid treatment , this study supports the use of anti - ige therapy for the induction of remission in patients with cep .
 anti - ige therapy , using recombinant humanized anti - ige antibodies , is clinically effective in patients with eosinophil - related disorders such as allergic asthma , allergic rhinitis , and chronic urticaria . 
 chronic eosinophilic pneumonia tends to respond promptly to systemic corticosteroid therapy , however ; relapses are common following corticosteroid tapering . 
 we treated two patients ( 17- and 19-yr - old males ) of chronic eosinophilic pneumonia whose symptoms were cough and dyspnea on exertion . 
 the symptoms were recurrent while tapering off corticosteroid . 
 they were treated with anti - ige antibody without recurrence for 2 yr and 15 months . here , 
 we first describe clinical experience of the 2 cases of chronic eosinophilic pneumonia . 
INTRODUCTION
CASE DESCRIPTION
Case 1
Case 2
DISCUSSION