Harlequin Syndrome/Harlequin sign

From EyeWiki


In summary, clinicians should be aware that the Harlequin sign (ipsilateral facial anhidrosis or blanching with contralateral flushing and hyperhidrosis) may be accompanied by a Horner syndrome (ipsilateral ptosis, miosis, anhidrosis). Imaging of the sympathetic axis is recommended in the Harlequin sign to exclude treatable etiologies for the Harlequin syndrome.

Disease Entity

Disease

Harlequin sign is characterized by ipsilateral anhidrosis and facial and body blanching (chest, neck, and face) with contralateral flushing and hyperhidrosis.[1] Harlequin sign can occur in conjunction with Horner syndrome due to an ipsilateral lesion of the oculosympathetic vasodilator neurons combined with hemifacial or hemibody sympathetic anhidrosis.[2]

Harlequin Syndrome, first described by Lance et al in 1988[3], is the syndrome caused by autonomic nervous system dysfunction. Autonomic Harlequin syndrome should be distinguished from Harlequin ichthyosis (a genetic skin disorder). Autonomic nervous system dysfunction results in the clinical findings of anhidrosis, Horner syndrome, and facial blanching as well as contralateral sweating, and skin flushing. Harlequin syndrome is one of the diseases that can cause Harlequin sign.

Pathogenesis

The pathogenesis of Harlequin syndrome is unclear, but it is likely involves autonomic dysfunction and can even occur in conjunction with a Horner’s syndrome (ptosis, miosis, anhidrosis) as well.[4] The symptoms can be brought on by heat stress, exercise, or sudden emotion in the patient.

Diagnosis

History

Patients usually describe an intermittent unilateral facial flushing and sweating on physical or emotional exertion. In addition, a history of ptosis or miosis may be seen as a concomitant Horner syndrome can be found.[2][4]

Physical Exam

The main ophthalmic manifestation is the Horner syndrome. Sweat testing or skin perfusion testing with laser Doppler flowmetry can be conducted during exertion or with a body-warming suit to confirm anhidrosis and hyperhidrosis.[2] An ophthalmologic exam can also be done to assess pupil size, pupil response to light and dark, dilation lag, and eyelid ptosis or upside down ptosis.

Signs and Symptoms

On the flowmetry skin perfusion exam minor changes during exertion will be seen unilaterally whereas on the contralateral side a significant increase will be seen.[2] In addition, temperature on either side of the forehead can be taken and a unilateral increase with exertion will be found.[2] In addition, an iodine-starch test can also be used during exertion or body warming to demonstrate the differences in sweat response on each side of the head.[2]

Diagnostic procedures

A Horner syndrome with or without features of the Harlequin sign can be indicative of a lesion in the sympathetic pathway (e.g., trauma, arterial dissection, stroke or malignancy)[5], neuroimaging of the entire sympathetic axis is generally recommended. Targeted sympathetic nervous system imaging should be considered for any unexplained Horner syndrome (e.g., MRI of cervical spine, neck, head, and orbits to thoracic T2 in the chest).[2]

Differential Diagnosis

Other conditions on the differential can include:

  • Ross syndrome, in which there is a unilateral or bilateral tonic pupil, hyporeflexia, and segmental anhidrosis.[6][7]
  • Horner syndrome which consists of unilateral miosis, ptosis, and anhidrosis and can sometimes accompany the Harlequin syndrome (up to 46% of patients in one series).[4]
  • Holmes-Adie syndrome which consists of tonically dilated pupils with light-near dissociation and tendon areflexia.[7][8]

General Treatment and Prognosis

The treatment of Harlequin syndrome should be directed at the underlying etiology. Idiopathic Harlequin syndrome (with or without concomitant Horner syndrome) may not require any therapy. Symptomatic patients should be advised to avoid overheating and overstimulation of the sympathetic axis. Patients who fail conservative therapy might require sympathectomy in extreme cases.

References

  1. Guilloton L, Demarquay G, Quesnel L, De Charry F, Drouet A, Zagnoli F. Syndromes dysautonomiques du visage avec signe et syndrome d'Harlequin : étude de trois cas et revue de la littérature [Dysautonomic syndrome of the face with Harlequin sign and syndrome: Three new cases and a review of the literature]. Rev Neurol (Paris). 2013;169(11):884-891. doi:10.1016/j.neurol.2013.01.628
  2. 2.0 2.1 2.2 2.3 2.4 2.5 2.6 Wasner G, Maag R, Ludwig J, et al. Harlequin syndrome--one face of many etiologies. Nat Clin Pract Neurol. 2005;1(1):54-59. doi:10.1038/ncpneuro0040
  3. Lance JW, Drummond PD, Gandevia SC, Morris JG. Harlequin syndrome: the sudden onset of unilateral flushing and sweating. J Neurol Neurosurg Psychiatry. 1988;51(5):635-642. doi:10.1136/jnnp.51.5.635
  4. 4.0 4.1 4.2 Bremner F, Smith S. Pupillographic findings in 39 consecutive cases of harlequin syndrome. J Neuroophthalmol. 2008;28(3):171-177. doi:10.1097/WNO.0b013e318183c885
  5. Umeki S, Tamai H, Yagi S, Soejima R, Higashi Y. Rinsho Shinkeigaku. 1990;30(1):94-99.
  6. Shin RK, Galetta SL, Ting TY, Armstrong K, Bird SJ. Ross syndrome plus: beyond horner, Holmes-Adie, and harlequin. Neurology. 2000;55(12):1841-1846. doi:10.1212/wnl.55.12.1841
  7. 7.0 7.1 Cheshire WP Jr, Low PA. Harlequin syndrome: still only half understood. J Neuroophthalmol. 2008;28(3):169-170. doi:10.1097/WNO.0b013e318183c1a0
  8. Sarao MS, Elnahry AG, Sharma S. Adie Syndrome. In: StatPearls. Treasure Island (FL): StatPearls Publishing; May 8, 2022.
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