Is Harlequin Syndrome Serious? An In-Depth Look at This Rare Neurological Condition

October 1, 2025 •

4 min read

Affecting fewer than 1 in 1,000,000 people, Harlequin syndrome is a rare neurological condition that causes dramatic unilateral flushing and sweating. While the sudden, stark visual signs can be alarming, a central question for those experiencing symptoms is: is Harlequin syndrome serious?

Quick Summary

Harlequin syndrome, a condition causing unilateral facial flushing and sweating, is typically benign and not life-threatening. A medical evaluation is essential, however, to rule out potentially serious underlying causes like tumors or injuries.

Key Points

Generally not serious: Idiopathic Harlequin syndrome is medically benign and poses no risk to life.
Underlying causes are key: The seriousness depends on whether it's primary (no cause) or secondary (caused by another condition like a tumor).
Look for associated signs: If Harlequin sign appears with other neurological symptoms like drooping eyelids (Horner syndrome), it warrants further investigation.
Not Harlequin ichthyosis: It is a completely different, non-genetic condition than Harlequin ichthyosis, a severe, life-threatening genetic skin disorder.
Diagnosis is crucial: A medical evaluation is needed to rule out serious underlying causes, even if the primary condition is benign.
Management is personalized: Treatment often involves reassurance and trigger avoidance, but options like Botox or surgery exist for severe cosmetic concerns or when an underlying cause is found.

What is Harlequin Syndrome?

Harlequin syndrome is a rare dysautonomic condition that affects the autonomic nervous system (ANS). The ANS controls involuntary bodily processes, such as heart rate, blood pressure, and body temperature regulation through sweating and flushing. When a person with Harlequin syndrome exercises, feels intense emotion, or is exposed to heat, the sympathetic nerves on one side of the face, neck, and upper chest malfunction. This results in one side of the body sweating and flushing as expected, while the other side remains pale, cool, and dry—a striking visual phenomenon often called the "Harlequin sign".

The Spectrum of Seriousness: Idiopathic vs. Secondary Cases

Determining the seriousness of Harlequin syndrome depends on its cause. The condition can be categorized into two types: primary and secondary.

Primary (Idiopathic) Harlequin Syndrome: This is the most common form, where there is no identifiable underlying cause. It is considered benign, meaning it is not dangerous or life-threatening and may not require any treatment. For many people, the symptoms may even resolve on their own over time.
Secondary Harlequin Syndrome: In these cases, the Harlequin sign is a symptom of another, more serious underlying issue. A medical evaluation is crucial to uncover and address these root causes, which can include nerve damage from trauma, surgical procedures, or the presence of a lesion or tumor compressing the sympathetic nerve fibers.

Diagnosis and Investigation

If you experience symptoms of Harlequin syndrome, it is important to consult a healthcare provider. While the visible signs may be the main indicator, a comprehensive evaluation is necessary to rule out a secondary cause. The diagnostic process typically involves:

Physical Examination: Your doctor will observe your symptoms during or after a triggering event like exercise.
Stress Test: A controlled physical stress test can be used to reliably reproduce the unilateral flushing and sweating for confirmation.
Imaging Tests: To investigate potential underlying causes, your provider may order imaging tests like a chest X-ray, computed tomography (CT) scan, or magnetic resonance imaging (MRI) of the head, neck, and chest. These scans help visualize the sympathetic nerve pathway and detect any lesions, tumors, or other abnormalities.
Autonomic Function Tests: Specialized tests, such as quantitative sudomotor axon reflex testing (QSART) or thermoregulatory sweat tests (TST), can be performed to evaluate the integrity of the sympathetic nerve function.

Harlequin Syndrome vs. Harlequin Ichthyosis

A critical point of confusion exists between Harlequin syndrome and Harlequin ichthyosis. Despite their similar names, they are two completely unrelated and very different conditions. Harlequin ichthyosis is a severe, life-threatening genetic skin disorder that primarily affects newborns. Infants are born with thick, plate-like scales on their skin that can crack and cause serious complications with breathing, feeding, and infection. Harlequin syndrome, conversely, is a neurological condition that is not life-threatening and carries a favorable prognosis.

Treatment and Management Options

Treatment for Harlequin syndrome varies based on its cause and the patient's individual needs. For the common idiopathic form, treatment may not be necessary at all.

Observation and Reassurance: If the condition is benign, managing it often involves patient reassurance and counseling to help with any anxiety or social embarrassment associated with the visible symptoms.
Addressing the Underlying Cause: If the Harlequin sign is secondary to a tumor, lesion, or infection, treating the root cause is the primary focus. This may involve surgery, radiation, or other targeted therapies.
Symptomatic Treatment: For patients whose symptoms are particularly distressing or cosmetically concerning, other options may be explored, such as botulinum toxin (Botox) injections to reduce sweating or flushing on the compensating side. In refractory cases, a surgical procedure called contralateral sympathectomy may be performed, but it carries a risk of compensatory sweating in other areas.

Comparison of Harlequin Syndrome vs. Harlequin Ichthyosis


Feature	Harlequin Syndrome	Harlequin Ichthyosis
Seriousness	Not life-threatening; typically benign.	Severe and life-threatening, especially for newborns.
Affected System	Autonomic nervous system.	The skin; a genetic skin disorder.
Primary Symptoms	Unilateral flushing, sweating, and paleness.	Hard, thick skin plates covering the body.
Cause	Injury to sympathetic nerves, often idiopathic.	Genetic mutation in the ABCA12 gene.
Prognosis	Favorable; often resolves spontaneously.	Poor without intensive neonatal care; survivors face ongoing management.
Associated Conditions	Can coexist with Horner syndrome.	No association with neurological syndromes.

Living with Harlequin Syndrome and Long-Term Outlook

For most people with Harlequin syndrome, the prognosis is excellent. The condition itself does not shorten life expectancy or lead to long-term health problems. The primary challenges often relate to managing the social and emotional impact of the symptoms, which can be addressed through counseling and open communication with a doctor. If the syndrome is linked to an underlying condition, the long-term outlook depends on the prognosis of that specific disease. While there is no known way to prevent the idiopathic form of Harlequin syndrome, avoiding specific triggers can help minimize the frequency and severity of symptomatic episodes.

Conclusion

So, is Harlequin syndrome serious? In most cases, it is not. The condition is usually a benign, self-resolving neurological phenomenon, causing no lasting physical harm. The visual display of unilateral flushing and sweating can be distressing, but it is not dangerous. However, because the Harlequin sign can be a symptom of a more significant underlying problem like a tumor or nerve injury, a thorough medical examination is always warranted to confirm the diagnosis and ensure no serious pathology is present. Ultimately, distinguishing between the benign idiopathic form and a symptom of a serious secondary cause is the most important step for anyone concerned about Harlequin syndrome.

Frequently Asked Questions

No, Harlequin syndrome is not dangerous and is not life-threatening. In most cases, particularly when idiopathic, it is considered benign. However, a medical evaluation is recommended to ensure there isn't a serious underlying cause.

The syndrome is caused by a disruption of the sympathetic nerves that control sweating and blood vessel dilation on one side of the face, neck, and upper chest. Causes can be idiopathic (unknown) or secondary, linked to trauma, surgery, or underlying issues like tumors.

Diagnosis is based on clinical observation of the unilateral flushing and sweating, often triggered by exercise or heat. A doctor may perform a stress test and use imaging (MRI, CT) to rule out underlying causes like tumors.

For many with the idiopathic form of the condition, symptoms may resolve on their own over time. The episodes are often temporary, lasting from a few minutes to hours, until the trigger is removed.

There is no specific cure for the idiopathic form, but treatment is often unnecessary. For secondary cases, treating the underlying condition is the focus. Cosmetic treatments like Botox or surgery can address symptoms if they are severely distressing.

No, they are completely different conditions. Harlequin syndrome is a benign neurological disorder, while Harlequin ichthyosis is a severe and life-threatening genetic skin disorder.

No, Harlequin syndrome does not affect a person's life expectancy. The prognosis for the condition itself is favorable, although it's important to investigate potential underlying causes that might have an impact.