general adverse reactions to iodinated radiocontrast media ( rcm ) are divided into immediate ( occurring within 1 hour of administration ) and delayed reactions ( occurring from 1 hour to 1 week after administration).1 - 4 ) immediate hypersensitivity reactions are usually anaphylactoid reactions that range from rashes and a sensation of flushing to life - threatening severe reactions,1 - 4 ) while delayed reactions are predominantly exanthematous skin reactions that are self - limiting.1)3)5)6 ) non - cardiogenic pulmonary edema ( ncpe ) following intravascular injection of rcm is rare . furthermore , all reported cases of ncpe associated with non - ionic rcm were immediate reactions . herein , we report a rare case of ncpe presenting as a delayed - type manifestation with a review of the literature . a 56-year - old male was admitted to the outpatient clinic with a 6-day history of chest pain on exertion lasting for over 10 minutes per episode . the patient has been treated for hypertension and diabetes mellitus at our hospital since 2009 . he had no history of allergies . on admission , his blood pressure and pulse rate were 95/55 mm hg and 70 bpm , respectively . the electrocardiogram showed st - segment elevation with q - wave formation in ii , iii , and avf , and reciprocal st - segment depression in i , avl , and v 4 - 6 ( fig . his troponin - t level was elevated to 3.03 ng / ml ( reference range : 0 - 0.100 ng / ml ) , while creatine kinase - mb was within the normal limit . echocardiography showed hypokinesia from the base to the mid - inferior wall with preserved left ventricle ( lv ) systolic function ( ejection fraction=56% by biplane modified simpson 's formula ) . coronary angiography demonstrated a critical stenosis in the mid right coronary artery ( rca ) with thrombolysis in myocardial infarction grade i flow ( fig . he underwent stent placement ( a 4.018 mm everolimus - eluting stent ) in the mid rca ( fig . the patient was given 200 ml of iopamidol ( isovue-300 , dongkook pharmaceuticals , seoul , korea ) , a non - ionic , low osmolar ( 616 mosm / kg water ) rcm . about 3 hours after the procedure , he developed a fever of above 38. however , the patient was not experiencing a rash , itching , angioedema , rales or wheezing in the lung field . the patient did not complain of any other symptoms , such as dyspnea , and his vital signs were stable . the next day , high fever persisted and the patient started to complain of mild dyspnea . arterial blood gas analysis revealed a ph of 7.436 , a pco2 of 30.2 mm hg , a po2 of 75.9 mm hg , and an oxygen saturation of 95.7% , while receiving nasal cannula oxygen at a flow rate of 5 l / min . the patient 's white blood cell count was 9400/mm , but eosinophil levels were not raised . follow - up echocardiography revealed preserved lv systolic function without interval change , in comparison with the initial study . we did not perform invasive hemodynamic monitoring of swan - ganz catheterization or central line insertion . at first , we dealt the patient 's condition as cardiogenic pulmonary edema due to fluid or osmolar overload . however , he was still febrile ( up to 40 ) and pulmonary edema became progressively worse despite negative volume balance ( fig . subsequently , the patient was diagnosed with ncpe manifesting as a delayed reaction to rcm despite some limitations , such as the absence of eosinophilia and pulmonary wedge pressure monitoring . we cut his dosage of diuretics and discontinued antibiotic treatment after 48 hours when all of his cultures were negative . the patient 's fever stopped and the pulmonary edema started to improve one day after the initiation of steroid injection ( fig . the patient was discharged from the hospital 7 days after the index procedure with complete recovery from pulmonary edema ( fig . today , non - ionic , low osmolar rcm such as non - ionic monomer : iohexol ( omnipaque ) , iopamidol ( isovue ) , ioversol ( optiray ) and non - ionic dimer : iodixanol ( visipaque , iso - osmolar to plasma , 290 mosm / kg water ) are widely used , while ionic rcm are hardly available in clinical practice . non - ionic rcm significantly lowers the risk of mild to moderate adverse reactions compared to ionic rcm . mild to moderate immediate reactions have been reported in 3.8% to 12.7% of patients receiving ionic monomeric rcm and in 0.7% to 3.1% of patients receiving non - ionic rcm.1)3)4 ) severe immediate reactions , such as anaphylaxis and severe hemodynamic compromise , have been reported in 0.16% and 0.03% of patients with ionic and non - ionic rcm , respectively.1)3)4 ) in general , more severe hypersensitivity reactions to rcm manifest as immediate anaphylactic reactions.2)4 ) the onset of immediate reactions is very rapid , with about 70% occurring within 5 minutes after injection and 96% of severe or fatal reactions such as anaphylactic shock , severe angioedema , pulmonary edema , and cardiac arrest occurring within 20 minutes after injection.1 ) there are commonly recommended pretreatment protocols for immediate severe allergic reactions to rcm.4 ) it is also common to use an iso - osmolar agent , iodixanol , for purported safety , especially in the cardiac catheterization laboratory , even though a higher incidence of delayed skin reactions have been reported compared to low osmolar monomers.3)4 ) on the other hand , the most representative delayed adverse reaction is exanthematous skin eruption . such exanthemas have been reported to affect 1% to 3% of rcm - exposed patients and are usually mild to moderate in severity and self - limiting within 7 days , showing recovery in up to 75% of those affected within 3 days.1)5 - 8 ) prophylaxis is generally not recommended.1)5 - 7 ) non - cardiogenic pulmonary edema caused by non - ionic rcm is rare . only a few reports on ncpe caused by both ionic and non - ionic rcm have been published . moreover , they all were immediate reactions.9 - 13 ) although systemic symptoms with more immediate - type manifestations such as hypotension , dyspnea , abdominal pain and fever have been occasionally reported,1)8)14 ) a late - onset ncpe , such as our case has not yet been reported . such pulmonary edema could be caused by mediator release and complement activation resulting in endothelial damage or by a direct irritant effect of the drug on the lungs.12 ) the primary emergency treatment is oxygen with continuous positive airway pressure , or invasive ventilation with positive end expiratory pressure.15 ) treatment of anaphylaxis was not beneficial and diuretics should be given with caution.12 ) corticosteroids can be given to prevent or decrease the severity of the reaction , but should not be expected to be of immediate benefit.4 ) in conclusion , we experienced a rare case of ncpe of a delayed - type hypersensitivity reaction following non - ionic rcm exposure . it is important for clinicians to be aware of this entity , as manifestation can be quite unusual and life - threatening , and to distinguish the condition from cardiogenic pulmonary edema .
non - cardiogenic pulmonary edema ( ncpe ) is a rare adverse reaction to iodinated radiocontrast media ( rcm ) , in which all previous cases were immediate reactions . 
 a 56-year - old male was given iopamidol , a non - ionic , low osmolar rcm , during coronary artery angiography . 
 he developed pulmonary edema and fever a day after the procedure . despite diuretic therapy , the patient 's pulmonary edema worsened and his high fever persisted . 
 the patient 's pulmonary edema was eventually resolved with intravenous steroid treatment . 
 we interpreted the patient 's condition as ncpe manifesting as a delayed reaction to rcm . to our knowledge 
 , our case is the first to show ncpe as a delayed hypersensitivity reaction .