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Harlequin Syndrome

Progressive Isolated Segmental Anhidrosis

Harlequin syndrome is a condition describing the asymmetric flushing and sweating of the face. In this rare disorder of the autonomic nervous system, most cases are idiopathic while some occur as a consequence of thoracic surgery. Harlequin syndrome is diagnosed by the clinical appearance, physical exam, and the related testing.


Presentation

Harlequin syndrome is defined by the presence of hemifacial flushing and diaphoresis [1]. This rare condition is likely a malfunction of the sympathetic network in the upper thoracic region (with the exception of the first segment) [1] [2]. Although the exact cause of this disorder is not clear and the majority of cases are idiopathic, some are iatrogenic [2] [3]. For example, Harlequin syndrome is associated with the removal of neck lesions, lung resection, paravertebral thoracic block, catheterization of the jugular vein, dissection of the carotid artery, and thoracic sympathectomy [3] [4]. Moreover, cases have been described to develop after resection of superior mediastinal neurinoma [5] and other types of compression tumors on the sympathetic chain [6] [7]. Additionally, Harlequin syndrome can also result following a stroke, Horner's syndrome [1], and even autoimmune hyperthyroidism [4].

Report of a patient who underwent resection of a ganglioneuroma located on the thoracic spine developing a midline mark on the face with asymmetric flushing and warmth appearing on half of the face, neck, as well as the chest has been highlighted in the literature [3]. The onset in such situation was shortly after surgery and discovered in the postoperative unit. Crying worsened these findings [3], which is consistent with the fact that Harlequin syndrome is precipitated by emotion, physical activity, and elevated temperature [1] [2] [3]. Symptoms resolved 3 hours following surgery and did not recur. While this ailment is generally benign and resolves without medical intervention a few hours after onset, some patients have been spoken about to have chronic symptoms [3].

Physical exam

In the case discussed above, there were no abnormalities in vital signs or the neurologic or cranial nerve exams [3]. Note that a thorough neurologic exam, including the pupillary response as well as the deep tendon reflexes, should be performed [8].

Pallor
  • Unilateral facial flushing and contralateral facial pallor with sharp midline demarcation. Within 4–5 h the patient had complete resolution of the left hand paresthesia, facial flushing, and pallor. The epidural infusion was continued at 4 mL/h.[ncbi.nlm.nih.gov]
  • Isolated ipsilateral facial pallor, complicated by thermally induced systemic sympathetic vasodilatation, and preferential lateral decubitus positioning, mimics harlequin colour change.[ncbi.nlm.nih.gov]
  • In this case a well-demarcated contralateral hemifacial flushing and ipsilateral pallor developed, without the distinctive ipsilateral Horner's syndrome.[academic.oup.com]
  • (B) Hypohidrosis and pallor, on the right side of the face.[doi.org]
Euthyroid
  • A 74-year-old woman with known euthyroid multinodular retrosternal goiter necessitated an urgent intubation at home, due to acute respiratory distress evoked by tracheal compression.[ncbi.nlm.nih.gov]
Foreign Body Aspiration
  • Rigid bronchoscopy excluded foreign body aspiration and echocardiography showed normal heart structure and function. As all measures failed and oxygen index remained low, ECMO was initiated.[doi.org]
Cough
  • Keywords: Harlequin syndrome, Mediastinal tumor, Ganglioneuroma Case report A previously healthy 6-year-old boy visited Samsung Medical Center with complaints of dyspnea and a barking cough lasting for 3 days.[ncbi.nlm.nih.gov]
  • There was no history of trauma, smoking, cough, loss of appetite or weight, or exposure to any procedure or surgery. Her past, family, and social history were unremarkable.[ncbi.nlm.nih.gov]
Tachypnea
  • Case report: A 9-month-old child presented to the Royal Hospital, Oman, with a 1-day history of tachypnea and potential case of chocking, which rapidly progressed into ARDS and refractory respiratory failure despite providing maximum supportive measures[doi.org]
Loss of Appetite
  • There was no history of trauma, smoking, cough, loss of appetite or weight, or exposure to any procedure or surgery. Her past, family, and social history were unremarkable.[ncbi.nlm.nih.gov]
Orthostatic Hypotension
  • The symptoms of autonomic dysfunction include orthostatic hypotension, abnormal sweating, urinary incontinence, and irregular papillary movement.[doi.org]
Pupillary Abnormality
  • Specifically, there were no pupillary abnormalities, including Horner syndrome. The patient was instructed to exercise for more than an hour and report immediately to the clinic for physical examination.[ncbi.nlm.nih.gov]
Neck Mass
  • An 11-year-old boy presented with complaint of a right neck mass of 1-month duration. The preoperative diagnosis was neurogenic tumor of vagus nerve or sympathetic nerve. We performed right neck mass removal under general anesthesia.[ncbi.nlm.nih.gov]
  • Patient concern: An 11-year-old boy presented with complaint of a right neck mass of 1-month duration. Diagnosis: The preoperative diagnosis was neurogenic tumor of vagus nerve or sympathetic nerve.[ingentaconnect.com]
  • In the perioperative setting, Harlequin syndrome has been reported postoperatively after the resection of a neck mass as well as after internal jugular venous catheter placement ( 5,6 ).[journals.lww.com]
  • 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.[doi.org]
  • Thus far, 10 cases have been reported in the literature: following a paravertebral thoracic block (5 patients), resection of a neck mass (3 patients), jugular vein catheterization (1 patient), thoracic sympathectomy (1 patient), and lung resection (1[ncbi.nlm.nih.gov]
Areflexia
  • Five (13%) patients had tonic pupils, most of whom also had tendon areflexia but no other neurologic findings, a pattern consistent with Holmes-Adie syndrome. In 2 of these patients, tonic and Horner pupils coexisted.[ncbi.nlm.nih.gov]
  • She also had areflexia in the lower limbs and slow pupillary reactions to light and darkness, as seen in Adie's syndrome.[ncbi.nlm.nih.gov]
  • […] parasympathetic neurons of the ciliary ganglion. 2 Caparrous-Lefebvre et al described a 45 year old woman with unilateral facial loss of facial flushing and sweating with contralateral anhidrosis induced by exercise. 3 She also had tonic pupils and areflexia[doi.org]
Guillain-Barré Syndrome
  • The finding of cholinergic supersensitivity in the iris muscles of patients with harlequin syndrome indicates a relationship with Holmes-Adie syndrome, Ross's syndrome, and the persistent autonomic deficit occasionally associated with Guillain-Barré syndrome[ncbi.nlm.nih.gov]
  • Harlequin syndrome is related to the Holmes-Adie and Ross syndromes and the persisting autonomic neuropathy of Guillain-Barré syndrome.[doi.org]
  • Harlequin syndrome is usually idiopathic but could be the first manifestation of several disorders such as Guillain-Barré syndrome, Bradbury-Eggleston syndrome, and diabetic neuropathy.[ncbi.nlm.nih.gov]
Paresthesia
  • The patient also reported a paresthesia in his left hand and fingertips. The paresthesia was located in a C7 and C8 dermatomal distribution. The remainder of the neurologic exam was normal.[ncbi.nlm.nih.gov]
Focal Neurologic Deficit
  • Patients were not in distress, and physical examination revealed neither focal neurological deficits nor ocular involvement.[ncbi.nlm.nih.gov]
Urinary Incontinence
  • The symptoms of autonomic dysfunction include orthostatic hypotension, abnormal sweating, urinary incontinence, and irregular papillary movement.[doi.org]

Workup

Anyone who appears with asymmetric facial flushing and sweating following thoracic surgery warrants assessment of the clinical presentation, a physical exam with a neurologic focus, imaging, and possibly other studies. The laboratory tests are usually normal [3]

Imaging

The workup should include imaging modalities to rule out other conditions that may cause a clinical picture similar to Harlequin syndrome. Specifically, the brain and the cervicothoracic segments of the spine should be assessed for tumors or other pathologies with computed tomography (CT) scan and magnetic resonance imaging (MRI) [8] [9].

Other

Chronic idiopathic cases may require a sweat test for evaluation of involved body parts [10]. Other studies include cardiovascular autonomic reflex tests, microneurography for assessment of sympathetic nerve function, and biopsy of affected skin [10]. Very importantly, the pupillary and deep tendon reflexes should be tested as noted earlier [8].

Posterior Mediastinal Mass
  • (A) Chest computed tomography showed a well-defined right posterior mediastinal mass measuring 4 cm.[ncbi.nlm.nih.gov]

Treatment

  • Treatment is advised due to possible rupture and airway compression by the resulting hematoma. Endovascular treatment was scheduled.[ncbi.nlm.nih.gov]
  • If no lesion is present and the syndrome is not interfering with a person’s daily living, treatment may not be necessary. [6] Last updated: 8/1/2017[rarediseases.info.nih.gov]
  • Repeated stellate ganglion blocks might be used either as a preoperative screen for sympathectomy or as a less invasive alternative treatment [ 9 ].[ncbi.nlm.nih.gov]
  • An autoimmune etiology should be considered in patients with Harlequin syndrome and immunomodulatory treatment could be attempted, especially when there is evidence of a more generalized autoimmune autonomic ganglionopathy.[ncbi.nlm.nih.gov]

Prognosis

  • Prognosis - Harlequin syndrome Not supplied. Treatment - Harlequin syndrome Not supplied. Resources - Harlequin syndrome Not supplied.[checkorphan.org]
  • If a structural lesion has been excluded the probable diagnosis is a restricted autonomic neuropathy with a benign prognosis. Sympathetic fibers innervating the face, and possible lesion sites as indicated by scissors.[ncbi.nlm.nih.gov]
  • Follow up Follow up of Horner’s syndrome depends on the etiology of Horner’s syndrome Prognosis Prognosis depends on the etiology of Horner’s syndrome AAO, Basic and Clinical Science Course. Section 5: Neuro-ophthalmology, 2015-2016.[eyewiki.aao.org]

Etiology

  • An autoimmune etiology should be considered in patients with Harlequin syndrome and immunomodulatory treatment could be attempted, especially when there is evidence of a more generalized autoimmune autonomic ganglionopathy.[ncbi.nlm.nih.gov]
  • The young age and lack of clinical antecedents suggest a congenital etiology for this fistula. The treatment was postponed until cardiopulmonary repercussions of the arterio-arterial fistula could be assessed.[ncbi.nlm.nih.gov]
  • Etiologies are varied but essentially idiopathic. Its association with others dysautonomic facial syndromes is possible. Main differential diagnosis is the Frey's syndrome. Treatment is not clearly codified.[unboundmedicine.com]
  • It is important to perform CT and MRI of the brain and cervicothoracic spine with the area of the thoracic sympathetic chain to exclude space-occupying lesions, infarction, or other etiologies [ 8 ].[ncbi.nlm.nih.gov]
  • Harlequin syndrome: one face of many etiologies: case study. Nat Clin Pract Neurol 2005 ; 1 : 54 –59. Sarikaya H, Georgiadis D, Baumgartner R. Harlequin syndrome in spontaneous dissection of the cervical carotid artery. Neurology 2008 ; 71 : 1459 .[n.neurology.org]

Epidemiology

  • ICD-9 337.9 Epidemiology In a population based study of Horner’s syndrome in the pediatric age group, the incidence of Horner’s syndrome was estimated to be 1.42 per 100 000 patients younger than 19 years, with a birth prevalence of 1 in 6250 for those[eyewiki.aao.org]
  • An epidemiological study of hyperhidrosis. Dermatol Surg. 2007; 33 :S69–S75. [ PubMed ] [ Google Scholar ] e25. Birner P, Heinzl H, Schindl M, Pumprla J, Schnider P. Cardiac autonomic function in patients suffering from primary focal hyperhidrosis.[ncbi.nlm.nih.gov]
Sex distribution
Age distribution

Pathophysiology

  • Explanation of pathophysiology and benign nature of the condition.[ncbi.nlm.nih.gov]
  • In this review, new information about the neural pathways and stimuli which influence facial sweating and blood flow is summarized, and this is followed by a discussion of the pathophysiology of extracranial vascular disturbances and facial sweating in[ncbi.nlm.nih.gov]
  • An understanding of the pathophysiology of this condition and reassurance are vital factors for successful management of this condition.[ncbi.nlm.nih.gov]
  • Management Explanation of pathophysiology and benign nature of the condition. Access options Access options Subscribe to Journal Get full journal access for 1 year 73,78 only 6,15 per issue All prices include VAT for Germany.[doi.org]

Prevention

  • Symptoms - Harlequin syndrome Causes - Harlequin syndrome Prevention - Harlequin syndrome Not supplied. Diagnosis - Harlequin syndrome Urinalysis for 5-HIAA should be done if carcinoid syndrome is suspected.[checkorphan.org]
  • Transplantation Substance Use and Addiction Surgery Surgical Innovation Surgical Pearls Teachable Moment Technology and Finance The Rational Clinical Examination Tobacco and e-Cigarettes Toxicology Trauma and Injury Treatment Adherence United States Preventive[jamanetwork.com]
  • Surgical sympathectomy ipsilateral to the affected side may be performed to prevent compensatory flushing and sweating.[ncbi.nlm.nih.gov]
  • Some mutations in the ABCA12 gene prevent the cell from making any ABCA12 protein. Other mutations lead to the production of an abnormally small version of the protein that cannot transport lipids properly.[ghr.nlm.nih.gov]
  • Primary prevention Prevention strategies depend on the etiology of Horner’s syndrome. These may include prevention of trauma (especially head trauma), control of cardiovascular risk factors and smoking cessation.[eyewiki.aao.org]

References

Article

  1. 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.
  2. Duddy EM, Baker MR. Images in clinical medicine. Harlequin's darker side. N Engl J Med. 2007;357(20):e22.
  3. Jeon YJ, Son J, Cho JH. Harlequin Syndrome Following Resection of Mediastinal Ganglioneuroma. Korean J Thorac Cardiovasc Surg. 2017;50(2):130-132.
  4. Pradeep PV, Benede AK, Harshita SS, Jayashree B. Harlequin Syndrome in a Case of Toxic Goitre: A Rare Association. Case Rep Med. 2011;2011:293076.
  5. Noda S. Harlequin syndrome due to superior mediastinal neurinoma. J Neurol Neurosurg Psychiatry. 1991;54(8):744.
  6. Tascilar N, Tekin NS, Erdem Z, Alpay A, Emre U. Unnoticed dysautonomic syndrome of the face: Harlequin syndrome. Auton Neurosci. 2007;137(1-2):1-9.
  7. Willaert WI, Scheltinga MR, Steenhuisen SF, Hiel JA. Harlequin syndrome: two new cases and a management proposal. Acta Neurol Belg. 2009;109(3):214–220.
  8. Biondi A, Persiani R, Zoccali M, et al. Harlequin syndrome. Ann Thorac Surg. 2009; 88(1):304.
  9. Wasner G, Maag R, Ludwig J, et al. Harlequin syndrome—one face of many etiologies. Nat Clin Pract Neurol. Neurology. 2005;1(1):54–59.
  10. Algahtani H, Shirah B, Algahtani R, Alkahtani A. Idiopathic Harlequin Syndrome Manifesting during Exercise: A Case Report and Review of the Literature. Case Rep Med. 2017;2017:5342593.

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Last updated: 2019-06-28 11:28