harlequin syndrome ( hs ) is an uncommon disorder of the sympathetic nervous system characterized by unilateral diminished flushing and contralateral sweating of the face in response to heat , exercise or emotional stimuli12 ) .
more than 100 cases have been reported in the literature since the initial description of hs by lance et al . in 19883 ) .
most reported cases of hs are primary ( idiopathic ) in which no underlying etiology could be identified , and hs is more commonly seen in female4 ) .
in contrast , most of the reported cases of hs in children have been heterogeneous secondary causes5 ) .
although this disorder is usually benign and does not need any specific treatment , physicians should consider performing a detailed clinical examination , testing autonomic functions , and conducting appropriate imaging techniques to find underlying organic causes5 ) . to our knowledge ,
a 6-year - old boy visited the pediatric outpatient clinic , complaining of unilateral hemifacial flushing and sweating occurring within minutes during or after physical exercise or heat . over the past 2 years
his neurological examination showed normal findings , including normal pupil responses , cranial nerve functions , and muscle stretch reflexes .
his blood pressure and heart rate were normal , and no signs of asymmetric flushing or sweating at rest were noticed .
laboratory tests , including the white blood count ; levels of hemoglobin , glucose , and electrolytes ; and renal , liver , and thyroid function were normal .
to objectify hemifacial flushing and sweating , we performed a provocation test ( i.e. , running for 90 seconds in direct sunlight outdoors ) .
after exercise - induced sweating , there was pale and nearly complete anhidrosis on the right side of the face with compensatory hyperhidrosis and flushing on the opposite side with sharp demarcation ( fig .
, we found that the oil - paper firmly stuck to the left side of the patient 's face owing to sweating , but that it immediately slipped off the right side of his face ( fig .
the right pupil was 1.5 mm in size , while the left pupil was 2.5 mm in size ; however , no ptosis , miosis , or enophthalmos was noted , and both pupils responded normally to light and accommodation .
magnetic resonance imaging ( mri ) was performed to exclude lesions in the cerebrum and cervicothoracic spinal cord , and no abnormalities were noted . in summary ,
the child and his parents were explained the benign nature of this condition , and we advised regular follow - ups without medication .
classically , hs is defined as unilateral facial flushing and sweating with normal ocular sympathetic innervation , but it has been gradually considered a spectrum of partial dysautonomias affecting sudomotor , pupillary , and vasomotor responses in the facial or facio - brachial region5 ) .
the nonflushing side of the face has autonomic dysfunction , while the flushing side of the face has normal autonomic function .
the sympathetic hyperactivity of the flushing side may be a kind of compensatory reaction that provides normal heat regulation of the whole face17 ) .
although listed as a rare disease , hs has been reported more widely in the literature in the past 20 years , particularly in adults124567 ) . since 1990 ,
pediatric cases of hs have been sporadically published in other countries ; however , this is the first pediatric case in korea , except for that reported in a newborn .
congenital hs is regarded as a sympathetic autonomic dysfunction in the control of peripheral capillary bed tonus , probably because of the hypothalamic functional immaturity in the newborns8 ) .
some authors have suggested that an anterior radicular artery at the third thoracic segment is occluded during strenuous exertion3 ) or asymmetric migration of the neural crest cell occurs during embryogenesis , but these can not explain the symptom arising in adulthood9 ) .
conversely , others have speculated that microvascular ischemia mediated by an autoimmune process or infectious agent such as the herpes simplex virus , cytomegalovirus , and parvovirus and human herpes virus 6 may be responsible79 ) .
the dysfunction seen in this disease , even though it is predominantly idiopathic , occurs by an alteration of sympathetic nervous system activity , secondary to the lesion of the preganglionic fibers , and superior cervical ganglion or postganglionic fibers in the external carotid plexus such as the brainstem infarct and superior mediastinum neurinoma6 ) .
in addition , most cases of iatrogenic hs have been reported to be caused by injury of the sympathetic nervous system and neural damage at t2 or t31 ) .
iatrogenic hs has also occurred after endoscopic surgery for the removal of a solitary pulmonary nodule , internal jugular vein catheterization , paravertebral thoracic anesthetic block , surgical resection of a neck mass , and thoracic sympathectomy1011 ) .
in addition , unlike many adults , most of the reported cases of hs in children have been secondary5 ) , and if present at birth , it may be associated with horner 's syndrome2 ) . a previous report presented 10 cases of asymmetric facial flushing in childhood and adolescence2 ) , and among them , 8 had organic lesions or structural defects , with 4 having preganglionic horner 's syndrome and one having postganglionic neuronal degeneration .
the lesions included a neurinoma in the mediastinum , a cystic hygroma in the right neck , and a cervical neck mass . moreover , 2 cases had unknown causes , and only 1 case had no lesion .
a diagnosis of hs is made on the basis of clinical observations and examination findings .
the neurons controlling sweating and blood flow in the face have been shown to innervate the same pupillary muscles ; therefore , damage to these muscles or the area around these muscles may result in dysfunction of the neurons2 ) .
these partial dysautonomias may indicate other diseases such as horner 's syndrome , adie 's syndrome , and ross ' syndrome5 ) .
horner 's syndrome is characterized by miosis , ptosis , enophthalmos , and anhidrosis , and these symptoms occur on the same side as that of the nerve injury1213 ) .
adie 's syndrome , also known as holmes - adie 's syndrome or adie 's tonic pupil , is a neurological disorder characterized by a tonically dilated pupil that reacts slowly to light but shows a more definite response to accommodation14 ) .
ross ' syndrome involves adie 's syndrome along with segmental anhidrosis4 ) . when a patient has the harlequin sign , it is important to rule out traumatic causes , identify other possible causes , and perform the autonomic function test to provide appropriate treatment .
the symptoms of autonomic dysfunction include orthostatic hypotension , abnormal sweating , urinary incontinence , and irregular papillary movement .
an autonomic function test is noninvasive and easy to perform , and can be used to detect autonomic dysfunction .
the autonomic function test includes the tilt table test , orthostatic blood pressure measurement , head - up test , valsalva maneuver , thermoregulatory sweat test , and electrocardiography15 ) .
an autonomic function test is necessary to rule out other causes of hs ; but it is difficult to perform in a young child .
reluctantly , we performed the provocation test for increasing body temperature by vigorous exercise instead of the treadmill test in this patient .
further examinations such as mri of the brain and spinal cord , mri angiography of the carotid arteries and imaging of the region adjacent to the stellate ganglion may be performed to distinguish between primary and secondary forms5 ) .
when a clinician encounters a patient with hemifacial flushing or sweating , the medical history of the patient should be carefully taken , and complete neurological and ophthalmological examinations should be performed .
primary hs does not involve structural abnormalities , and it can be either congenital or idiopathic .
idiopathic hs has a benign course , and therefore , medical treatment is not required ; however , counseling can be provided to the patient , and regular follow - up should be suggested .
surgical intervention may be performed in patients with structural lesions ; however , this should be carefully considered as it may result in other complications4 ) . to our knowledge
, a clinical presentation of idiopathic hs in children has not been previously reported in korean pediatric literature .
 harlequin syndrome , which is a rare disorder caused by dysfunction of the autonomic system , manifests as asymmetric facial flushing and sweating in response to heat , exercise , or emotional factors 
 . the syndrome may be primary ( idiopathic ) with a benign course , or can occur secondary to structural abnormalities or iatrogenic factors . 
 the precise mechanism underlying idiopathic harlequin syndrome remains unclear . 
 here , we describe a case of a 6-year - old boy who reported left hemifacial flushing and sweating after exercise . 
 he had an unremarkable birth history and no significant medical history . 
 complete ophthalmological and neurological examinations were performed , and no other abnormalities were identified . 
 magnetic resonance imaging was performed to exclude lesions of the cerebrum and cervicothoracic spinal cord , and no abnormalities were noted . 
 his final diagnosis was classic idiopathic harlequin syndrome . 
 herein , we report the first pediatric case of idiopathic harlequin syndrome in korea . 
Introduction
Case report
Discussion