Harlequin Syndrome: Symptoms, Types, Causes and Treatment

Harlequin syndrome is a rare but fascinating neurological disorder that presents with striking and sometimes socially distressing symptoms. Understanding its clinical presentation, underlying mechanisms, and management options is essential for healthcare professionals and patients alike. This comprehensive article explores the main aspects of Harlequin syndrome: its symptoms, types, causes, and treatment strategies, providing a clear and evidence-based overview.

Symptoms of Harlequin Syndrome

Harlequin syndrome is most recognized for its distinctive presentation, but its symptoms can be complex and occasionally overlap with other neurological conditions. Knowing what to look for is the first step toward accurate diagnosis and reassurance for those affected.

Symptom	Description	Frequency/Notes	Source(s)
Unilateral Flushing	Redness on one side of the face, neck, or upper chest	Triggered by heat, exercise, or emotion; sharply demarcated	1 2 4 5 8 13
Unilateral Sweating	Sweating on only one side of the face or upper body	May be accompanied by compensatory dryness on the other side	1 2 4 5 8 13
Contralateral Pallor/Anhidrosis	Absence of flushing and sweating on the affected side	The other side may overcompensate	2 4 5
Ocular Symptoms	Ptosis, miosis, or tonic pupils, often ipsilateral	Frequently co-occurs with Horner syndrome	5 6

Table 1: Key Symptoms of Harlequin Syndrome

Unilateral Flushing and Sweating

The hallmark feature of Harlequin syndrome is a sudden, sharply demarcated redness (flushing) and sweating (hyperhidrosis) that occurs on only one side of the face, neck, and sometimes upper chest or even arm. These symptoms typically arise in response to heat, physical activity, or strong emotions, and are often quite dramatic in appearance. The unaffected side remains pale and dry, creating a stark contrast that is both visually and socially significant for patients 1 2 4 5 8 13.

Contralateral Pallor and Anhidrosis

While one side of the face flushes and sweats excessively, the other side fails to respond, resulting in pallor (paleness) and anhidrosis (lack of sweating). This asymmetry is due to an interruption or dysfunction in the sympathetic nerve supply, leading to an imbalance in autonomic function 2 4 5.

Ocular and Neurological Symptoms

In about half of cases, particularly those with more extensive autonomic involvement, ocular symptoms such as ptosis (drooping eyelid), miosis (constricted pupil), and tonic pupils may occur, often as part of coexisting Horner syndrome or Holmes-Adie syndrome 5 6. Pupillary abnormalities, when present, are usually on the same side as the impaired facial sweating and flushing.

Other Associated Features

• Some patients may experience symptoms extending to the trunk or upper limb 2 3 4 5.
• Rarely, patients report social embarrassment or psychological distress due to the conspicuous nature of their symptoms 8.

Types of Harlequin Syndrome

Harlequin syndrome is not a one-size-fits-all condition. Its types are defined by their underlying causes, patterns of nerve involvement, and associated features. Understanding these subcategories helps guide investigation and management.

Type	Defining Feature	Frequency/Notes	Source(s)
Primary	Idiopathic or no clear cause	Most common; often benign	4 5 6 8
Secondary	Linked to trauma, tumor, surgery, or disease	Up to 1/6 of cases; may need further workup	3 4 5 8
Iatrogenic	Caused by medical procedures	Increasingly reported; anesthesia, surgery	2 8 11 13
Overlap Syndromes	Coexists with other autonomic disorders	Holmes-Adie, Ross, or Horner syndromes	5 6 7

Table 2: Types of Harlequin Syndrome

Primary (Idiopathic) Harlequin Syndrome

This is the most frequent type, where no identifiable cause can be found despite thorough evaluation. Patients generally have a benign course, and symptoms are often stable over time 4 5 6 8. Primary Harlequin syndrome is more common in women and often presents in childhood or early adulthood 5.

Secondary Harlequin Syndrome

Secondary cases are linked to an identifiable underlying cause, such as:

• Tumors (e.g., schwannomas of the cervical sympathetic chain) 3
• Traumatic injuries to the neck or upper chest
• Infections or inflammatory disorders
• Vascular abnormalities (e.g., carotid artery dissection) 4 9

Secondary Harlequin syndrome represents about one-sixth of all cases and may require more extensive investigation for underlying pathology 3 4 5 6 8.

Iatrogenic Harlequin Syndrome

A significant subset of patients develops symptoms following medical interventions, particularly:

• Surgical removal of tumors in the neck or chest 8 11
• Regional anesthesia (e.g., epidural or paravertebral blocks) 2 8 13
• Catheterization or sympathectomy procedures 8 11 13

Iatrogenic cases are increasingly recognized due to advances in medical and surgical techniques 2 8 13.

Overlap Syndromes

Harlequin syndrome can coexist or overlap with other autonomic nervous system disorders, notably:

• Horner syndrome (ptosis, miosis, anhidrosis) 5 6
• Holmes-Adie syndrome (tonic pupils, areflexia) 6
• Ross syndrome (segmental anhidrosis, areflexia, tonic pupils) 5 6 7

These overlap syndromes suggest a broader or more selective autonomic neuropathy depending on the nerve pathways involved.

Causes of Harlequin Syndrome

While the symptoms of Harlequin syndrome are striking, the mechanisms and triggers are varied and sometimes mysterious. Understanding these causes is essential for diagnosis, prognosis, and management.

Cause Category	Examples/Mechanism	Notes/Associations	Source(s)
Autonomic Neuropathy (Sympathetic)	Disruption of sympathetic fibers (T2-T3)	Most common mechanism	1 2 4 5 6 8
Tumors	Schwannoma, other neoplasms in sympathetic chain	Can be secondary cause	3 6 8
Trauma/Surgery	Neck/chest trauma, thoracic surgery, anesthesia	Iatrogenic, direct nerve injury	2 8 11 13
Vascular Lesions	Carotid artery dissection, vascular impairment	Rare, may affect nerve supply	4 9
Autoimmune/Other Disorders	Autoimmune, ophthalmic, sleep disorders	Occasionally reported	4
Parasympathetic Neuropathy	Isolated or combined with sympathetic involvement	Rare, unique presentations	7

Table 3: Causes of Harlequin Syndrome

Sympathetic Nervous System Injury

The most common cause of Harlequin syndrome is disruption of the sympathetic nervous system fibers that control vasodilation and sweating on the face and upper body. These fibers originate from the hypothalamus, descend through the spinal cord (especially T2–T3), and travel via the cervical sympathetic chain to the face 1 2 4 5 6 8. Injury or dysfunction at any point along this pathway can result in the classic hemifacial symptoms.

Secondary Causes: Tumors and Lesions

Tumors such as schwannomas or other neoplasms can press on or infiltrate the sympathetic chain, leading to secondary Harlequin syndrome. These cases are important to identify, as they may require specific treatments for the underlying mass 3 6 8.

Trauma and Iatrogenic Injury

Direct trauma or surgical interventions in the neck, chest, or upper thoracic region can damage the sympathetic nerves. Iatrogenic causes are increasingly reported, especially after:

• Paravertebral anesthetic blocks (e.g., for mastectomy) 2 8
• Thoracic or neck surgeries 8 11
• Placement of catheters or after sympathectomy 8 13

Symptoms typically manifest shortly after the procedure and may resolve over time, though persistent cases have been reported.

Vascular and Other Causes

Vascular insults such as carotid artery dissection or other impairments can also lead to Harlequin syndrome, though these are rare 4 9. Less commonly, autoimmune diseases, ophthalmic or sleep disorders, and idiopathic dysautonomias have been linked to Harlequin-like phenomena 4.

Parasympathetic Involvement

In rare instances, isolated parasympathetic neuropathy may produce a Harlequin-like picture, with symptoms triggered specifically by emotional stress (such as crying) rather than heat or exercise 7. These cases highlight the complexity of facial autonomic innervation.

Treatment of Harlequin Syndrome

Treatment of Harlequin syndrome is tailored to the type and severity of symptoms, as well as to any underlying cause. Most cases are benign and require minimal intervention, but some patients may benefit from targeted therapies.

Treatment	Indication	Outcome/Considerations	Source(s)
Reassurance	Most primary/benign or iatrogenic cases	Symptoms are often self-limiting; no intervention needed	2 4 5 8 13
Treat Underlying Cause	Secondary cases (tumor, vascular, etc.)	May require surgery, tumor removal, or specific therapy	3 4 6 8
Sympathectomy	Severe or refractory symptoms	Can be surgical (contralateral) or via nerve block	8 11
Botulinum Toxin	Persistent hyperhidrosis/flushing	Case reports of good response	12
Stellate Ganglion Block	Alternative to surgery	Less invasive; can reduce symptoms	8
Discontinue/Adjust Anesthesia	Iatrogenic cases post-anesthesia	Symptoms often resolve	13

Table 4: Treatment Approaches for Harlequin Syndrome

Observation and Reassurance

For the majority of patients—especially those with idiopathic or mild iatrogenic Harlequin syndrome—reassurance is the mainstay of management. The condition is usually benign and symptoms often diminish or stabilize over time. Education about the syndrome helps alleviate anxiety and social embarrassment 2 4 5 8 13.

Addressing the Underlying Cause

If a secondary cause is identified (e.g., tumor, mass lesion, vascular anomaly), targeted treatment such as surgical removal, vascular intervention, or specific medical therapy is indicated. In these cases, resolution of Harlequin syndrome depends on successful management of the underlying condition 3 4 6 8.

Sympathectomy and Nerve Block

For patients with severe, persistent, or socially disabling symptoms, more invasive options may be considered:

• Contralateral sympathectomy: Surgical interruption of the sympathetic fibers on the unaffected side to restore facial symmetry 8 11.
• Stellate ganglion block: A less invasive alternative, sometimes used for temporary or recurrent relief 8.

These procedures carry risks and are generally reserved for select cases.

Botulinum Toxin

There are case reports of successful use of botulinum toxin injections to treat areas of excessive sweating and flushing, particularly in patients with prominent hyperhidrosis 12. This approach can be considered for those who do not respond to conservative measures.

Management of Iatrogenic Cases

In iatrogenic cases related to anesthesia or surgical procedures, symptoms often resolve spontaneously when the offending agent is discontinued or modified. Monitoring and supportive care are usually sufficient 13.

Conclusion

Harlequin syndrome, though rare, is a unique and memorable disorder of the autonomic nervous system. It is important for clinicians and patients to recognize its symptoms, understand its diverse causes, and know when further investigation or intervention is needed.

Key Points:

• Harlequin syndrome is characterized by unilateral facial flushing and sweating, with clear demarcation and compensatory symptoms on the opposite side.
• Types include primary (idiopathic), secondary (due to tumors, trauma, vascular lesions), iatrogenic (from medical procedures), and overlap syndromes with other autonomic neuropathies.
• Causes range from benign idiopathic dysfunction to underlying structural lesions, trauma, or iatrogenic injury.
• Most cases require only reassurance; treatment is reserved for severe, persistent, or secondary cases and may include sympathectomy, nerve blocks, or botulinum toxin.
• Early identification of underlying causes and appropriate management can improve outcomes and reduce patient distress.

Harlequin syndrome serves as a reminder of the complexity and subtlety of the human autonomic nervous system—and the importance of a careful, patient-centered approach to rare but impactful neurological disorders.