infantile hemangioma ( ih ) is the most common benign tumor of infancy,1 affecting nearly 10% of children under 1 year old and 30% of premature babies . prematurity , older maternal age , preeclampsia , and multiple gestations have been suggested to be risk factors of the development of ih.2 approximately 60% of hemangiomas are located at the head and neck regions,3 and they present with a 2.4:1 ratio of females to males.4 their large size , facial location , and/or segmental morphology are the major risk factors associated with the development of complications including ulceration , functional impairment , and permanent disfigurement.5 as most ihs can involute spontaneously , there is still great controversy over the management of ih . however , consensus was achieved in that when the tumor gives rise to infection , ulceration , necrosis and bleeding resulting in serious disfigurement , dysfunctions and even threatening life , treatment is urgently required . the lesions that potentially impair vital function or cause life - threatening complications are described as  alarming hemangiomas.6 there is no gold standard for alarming hemangioma . recombinant interferon alpha ( ifn- ) , an inhibitor of angiogenesis , has been used successfully in treating complicated ih , particularly in hemangiomas that have failed to respond to oral propranolol.7,8 however , concerns of irreversible neurotoxicity , especially spastic diplegia , handicap the application of ifn-.911 here , we present a study where we treated eleven chinese cases of alarming hemangioma with ifn-2a . the study was approved by the ethics committee at the ninth people s hospital , shanghai jiao tong university ( shanghai , people s republic of china ) . eleven consecutive infants ( nine girls and two boys ) with alarming hemangiomas in the head and neck region who failed to respond to a 2-week course of propranolol or corticosteroid therapy , and who received a subcutaneous injection of ifn- in our institution between january 2009 and december 2010 were enrolled in this study . all patients had large ( > 5 cm in diameter ) or multiple hemangiomas ( 2 sites ) in the head and neck region ; in three patients , the hemangioma caused airway obstruction . the demographic data regarding each patient s age , sex , site of lesion , and duration of treatment are shown in table 1 . the diagnosis of hemangiomas was established mainly by obtaining the patient s history , noting clinical manifestations , and performing a physical examination . all patients underwent ultrasonography , and four patients had a magnetic resonance imaging ( mri ) examination to obtain more details of the lesion ( when the diagnosis was uncertain , mri was performed ) . after informed consent had been obtained from the parents according to institutional guidelines , the patients were treated with ifn-2a for a period of 24.5 months . ifn-2a was administrated subcutaneously once daily at a dose of 310 units / m per day . periodical baseline electrocardiogram , neurologic examination , and laboratory evaluations of hepatic transaminases were performed . the size and extent of the deep - seated lesions were monitored by serial color doppler ultrasonography ; the percent change of the superficial lesions compared the pre- and posttreatment tumor size using photographs . the patients were observed at an interval of 3 weeks during the therapy course ; follow - up visits were continued for up to 2 years . the final results were assessed by two other physicians from the department of oral oncology , depending on the clinical examinations , photographs , and doppler ultrasonography taken before and after treatment ; the response to ifn-2a therapy was evaluated according to the following scale ( that was modified following achauer et al12 ) : scale 1 , poor response ( shrinkage 0%25% ) ; scale 2 , fair response ( shrinkage 26%50% ) ; scale 3 , good response ( shrinkage 51%75% ) ; scale 4 , excellent response ( shrinkage 76%100% ) . eleven consecutive infants ( nine girls and two boys ) with alarming hemangiomas in the head and neck region who failed to respond to a 2-week course of propranolol or corticosteroid therapy , and who received a subcutaneous injection of ifn- in our institution between january 2009 and december 2010 were enrolled in this study . all patients had large ( > 5 cm in diameter ) or multiple hemangiomas ( 2 sites ) in the head and neck region ; in three patients , the hemangioma caused airway obstruction . the demographic data regarding each patient s age , sex , site of lesion , and duration of treatment are shown in table 1 . the diagnosis of hemangiomas was established mainly by obtaining the patient s history , noting clinical manifestations , and performing a physical examination . all patients underwent ultrasonography , and four patients had a magnetic resonance imaging ( mri ) examination to obtain more details of the lesion ( when the diagnosis was uncertain , mri was performed ) . after informed consent had been obtained from the parents according to institutional guidelines , the patients were treated with ifn-2a for a period of 24.5 months . ifn-2a was administrated subcutaneously once daily at a dose of 310 units / m per day . periodical baseline electrocardiogram , neurologic examination , and laboratory evaluations of hepatic transaminases were performed . the size and extent of the deep - seated lesions were monitored by serial color doppler ultrasonography ; the percent change of the superficial lesions compared the pre- and posttreatment tumor size using photographs . the patients were observed at an interval of 3 weeks during the therapy course ; follow - up visits were continued for up to 2 years . the final results were assessed by two other physicians from the department of oral oncology , depending on the clinical examinations , photographs , and doppler ultrasonography taken before and after treatment ; the response to ifn-2a therapy was evaluated according to the following scale ( that was modified following achauer et al12 ) : scale 1 , poor response ( shrinkage 0%25% ) ; scale 2 , fair response ( shrinkage 26%50% ) ; scale 3 , good response ( shrinkage 51%75% ) ; scale 4 , excellent response ( shrinkage 76%100% ) . all eleven patients received the treatment for a duration of 24.5 months ( median : 3 months ) . eight patients had received medication for 3 months , one for 4.5 months , and two for 2 months . the age at initiation of ifn-2a therapy ranged from 3 days to 8 months ( median : 4 months ) . it was observed that the most apparent regression of tumors happened at 1 month after medication administration ; the tumor shrank further with the red color fading . nine patients ( 82% ) achieved scale 4 ( figures 1a , b , 2a , and b ) and two patients ( 18% ) achieved scale 3 . the adverse effects included low fever ( six cases ; 54.5% ) , diarrhea ( two cases ; 18.2% ) , and anorexia ( one case ; 9.1% ) , as well as neutropenia and high levels of aminotransferases to varying degrees , which resolved after stopping the medication . neurotoxicity such as spastic diplegia and other motor developmental disturbances were not found in this series . no patients experienced the rebound phenomenon , and no patients required the restarting of ifn or another therapy in the following 2 years . in this series of eleven infants with alarming hemangiomas treated with ifn-2a , rapid and good response to treatment was obtained with few reversible adverse effects . in addition to its antiviral effect , ifn- was also used as an inhibitor of angiogenesis given its antiangiogenic properties.13 since its efficacy in pulmonary hemangiomatosis was first reported by white et al14 in 1989 , ifn- was chosen as a therapeutic modality for hemangiomas , especially for life - threatening cases or steroids - insensitive patients . according to other reports,1517 the rate of response to ifn in hemangiomas varies from 80%100% , which is very similar to our overall response rate of 100% ; our result was as good as those found in these studies ( p>0.05 ) , and the duration time was shorter ( p<0.05 ) . the common adverse effects of ifn include influenza - like symptoms of fever , somnolence , anorexia , diarrhea or constipation , and a high level of aminotransferases ; these symptoms are always slight and they can be reversed following the discontinuation of ifn . although exceptional , neurotoxicity is still the main concern in the treatment of ih with ifn . epilepsy , spastic diplegia , and lower limb disability had been reported after ifn injection . chang et al16 first reported in 1997 that one patient who received treatment with ifn-2b developed mild gross motor delay , which improved 2 months after the cessation of therapy . the pathogenesis of ifn - related neurotoxic effects is unclear , but given its potential seriousness , many experts have limited the use of ifn- for alarming hemangiomas . according to a meta - analysis of a large sample , which was carried out by michaud et al9 in 2004 , eleven of 441 children ( 2.5% ) receiving ifn therapy for the treatment of vascular lesions developed spastic diplegia ; perhaps there were not enough patients in our study to see this outcome , or it is also possible that the short duration of therapy decreased the risk for these children . considering that the durations we used were only 24.5 months ( median : 3 months ) , we suggest that the short - term use of ifn- should be safe . the current treatments of ihs include drug therapy , cryosurgery , laser therapy , and surgical excision . oral corticosteroids ( for example , prednisolone , prednisone ) used to be the mainstay of therapy for hemangiomas , but their clinical application was limited by the adverse effects such as cushing s syndrome and growth retardation . since the impressive effect of propranolol in treating hemangioma was reported by laut - labrze et al18 in 2008 , many studies ( including our own experiences ) have confirmed its effectiveness and have reported few side effects in hemangiomas.1922 nowadays , propranolol has been our first - line medicine for treating ih , but there are still some patients with alarming hemangiomas who may be concomitant with a contraindication for propranolol such as asthma , cardiac failure , or failure to respond to this medicine . for these cases , the rapid and impressive responses , as well as the few side effects observed in this series without relapse after treatment with ifn-2a prompts us to suggest that the short - term ( < 4.5 months ) use of ifn-2a can be chosen as an alternative option for alarming hemangiomas in the head and neck region , which are resistant to corticosteroid or propranolol treatment .