From Volume 43, Issue 1, January 2016 | Pages 90-92
Harlequin syndrome is a rare, clinically striking syndrome characterized by distinctly demarcated asymmetric facial flushing and sweating. It may be of idiopathic aetiology or caused by demonstrable ipsilateral damage to the sympathetic nervous system.
Arlecchino (Harlequin) was a theatre character in 16th century Venice whose costume consisted of a grotesque mask, named a Harlequin mask (Figure 1). The initial masks were grotesque but were later refined with diamond-shaped colourful patterns, or blackening of one half of the face. Lance et al 1988 observed five patients who presented with unilateral diminished sweating and flushing of the facial skin in response to heat, exercise or stress.1 The unilateral mid-facial demarcation of the contralateral erythematous flushed skin contrasting with the ipsilateral non-flushed side was reminiscent of this mask, hence leading to the designation of the term Harlequin syndrome.2
A 45-year-old female presented to her general dental practitioner for routine dental care. She had rushed to the appointment and presented to her dentist with distinctly demarcated unilateral facial flushing and sweating. The dentist enquired further about this appearance with the patient reporting a one-year history of unilateral diminished sweating and flushing of the left facial skin in response to exercise. As the dentist considered this to be unusual, he organized a referral to the local oral medicine department.
On attendance at the oral medicine consultation, the patient confirmed the above-mentioned symptoms. A detailed history elicited, in addition, a sensation of numbness and fullness in the left side of her face (non-flushed side). She did not report a history of any sensory deficit or other symptoms. Her main concern centred on the social embarrassment caused by this asymmetric flushing when in company during exercise. Her previous medical history was clear. She was a non-smoker and consumed a small amount of alcohol irregularly.
Clinical examination revealed normal anatomy extra-orally and intra-orally. Cranial nerve examination was normal apart from a mild left-sided ptosis. Extra-orally there was tenderness of the muscles of mastication and intra-orally evidence of bruxism, all signs consistent with a diagnosis of myofascial pain dysfunction. At her next appointment, the patient attended with a photograph taken following exercise that clearly showed sweating and flushing (Figure 2). A provisional diagnosis of Harlequin syndrome was established. The case was discussed with a consultant neurologist and further investigations and a neurological consultation were organized.
Neurological examination revealed a mild left-sided ptosis. Pupillary size and reactions were equal. No asymmetry of sweating or facial flushing was evident at rest. After moderate exercise a clear asymmetry developed, with reduced sweating and flushing on the left side of the face, neck and upper thorax contrasting with compensatory increases contralaterally. The midline was respected and changes clearly demarcated. The remainder of the neurological examination was unremarkable.
General medical examination was normal, with no palpable masses or lymphadenopathy. A full blood count, thyroid function tests, liver function tests and random blood glucose were taken to exclude systemic disease. Other investigations included serum angiotensin converting enzyme levels (raised in sarcoidosis), auto antibodies and extractable nuclear antibodies (to exclude connective tissue disorders which can rarely cause lesions of the sympathetic chain), serum immunoglobulin levels and electrophoresis (abnormal if there is an underlying immunodeficiency) and C reactive protein (marker of inflammation). All the results were within normal limits. Imaging was arranged to exclude structural pathology impinging on the ipsilateral sympathetic chain in the upper thorax, neck or head. An MRI scan of the brain and cervical cord was normal. A CT scan of the chest revealed normal findings with no apical lesion. Correlation of the clinical findings with the investigations resulted in exclusion of significant pathology and confirmation of the diagnosis of primary Harlequin syndrome. The patient was reassured of the benign nature of the condition and annual follow-up with neurology was organized.
Harlequin syndrome is a result of damage to the autonomic nervous system. Within the autonomic nervous system there are two divisions; the sympathetic which involve stimulating the ‘fight or flight’ response and the parasympathetic responsible for the ‘rest and digest’ phase of the body. Harlequin syndrome is associated with damage to the sympathetic nervous system.
Considering sympathetic supply to the head and neck, the preganglionic neurons originate from the spinal cord in the thoracolumbar region, from the first thoracic to the second lumbar segment (T1–L2). They travel to one of three ganglia of the cervical sympathetic chain, synapse with a postganglionic neuron which then extends across the head and neck.3
The sympathetic nervous system to the head and neck is responsible for vasomotor, sudomotor, pupillodilator and secretory functions. Harlequin syndrome is associated with damage to the ipsilateral vasomotor and sudomotor sympathetic nervous system. This leads to an alteration in facial appearance in which a distinct line divides the asymmetric sweating and flushing when the patient is stressed, hot or during exercise. It is now known that the sympathetic neural damage is associated with the non-flushing side (left side in this particular case) and the side with excessive flushing is compensatory (right side in this particular case) to provide normal heat regulation in the face as a whole.2 Harlequin syndrome confined to the skin of the face is associated with damage between T2 and T3 neurons of the cervicothoracic sympathetic system but may be more widespread. In such occurrences, the lesion is proximal to T2 and T3 and can also affect the innervation to the arm, neck and trunk.4
The term Harlequin syndrome is reserved for patients that show sudden intermittent signs of hemifacial flushing and sweating without other neurological symptoms.1 Our patient also had a partial ptosis as the levator palpebrae muscle has a sympathetic innervation considered as a partial Horner's syndrome. Horner's syndrome, characterized by ipsilateral ptosis, miosis and anhidrosis and flushing of the affected side of the face is also as a result of damage to the sympathetic nervous system. By itself, Horner's syndrome is not a disease, but a sign of an underlying condition. It may be congenital, an iatrogenic consequence of medical intervention or acquired as a result of disease. Although most causes are relatively benign, serious conditions relating Horner's syndrome to the head and neck region include middle ear infections, cluster headaches, thyroid carcinomas, trauma to the base of the neck, cavernous sinus thrombosis and syringomyelia.
Harlequin syndrome is sometimes described as primary or secondary. When no underlying cause can be identified, Harlequin syndrome may be described as primary in nature. In approximately a sixth of patients an underlying disease or structural lesion is diagnosed (secondary Harlequin syndrome).5 In such instances, secondary Harlequin syndrome may be a manifestation of many disorders which cause unilateral sympathetic nervous system innervation impairment. Indeed, as noted in this case report, appropriate examination and investigations were carried out in order to exclude pathological causes of Harlequin syndrome. Random blood glucose levels were normal, excluding possible diabetic autonomic neuropathy and appropriate MRI excluded neoplastic and traumatic lesions of the stellate ganglion, which is located in the thorax.
In this case, Harlequin syndrome could not be explained by an organic cause and the patient was reassured by explaining the benign nature of the condition. Although the syndrome typically does not require medical treatment, the patient was made aware that spontaneous regression or progression of symptoms are unusual. The predominant factor in seeking medical treatment is due to the severe social embarrassment associated with the unilateral flushing. In such cases, contralateral sympathectomy, which involves interrupting the sympathetic nerves on the normally functioning side of the face, is a treatment option. This neurodestructive approach is habitually limited to patients whose quality of life is compromised as a result of the classic sign.6
Neurological disorders may present in various ways including unilateral facial flushing and sweating. This case report highlights the role of the general dental practitioner in recognizing signs and symptoms within the head and neck that may warrant appropriate medical attention.
It is important that general dental practitioners can recognize neurological signs and symptoms that may merit onward referral. Although Harlequin syndrome is usually of benign nature and does not require treatment, the signs and symptoms should be fully investigated and evaluated to exclude a serious underlying cause.
