Harlequin Syndrome Explained: Causes, Treatment, and More

Medically Reviewed By Mia Armstrong, MD
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Harlequin syndrome is a disorder that affects the autonomic nervous system. The autonomic nervous system is responsible for many of the body’s processes. Therefore, the disorder can result in impairment or differences in processes such as sweating, skin flushing, and pupil response to stimuli. It affects the body unilaterally, meaning symptoms occur on one side of the body. Symptoms of Harlequin syndrome may particularly affect a person’s face, arms, and chest.

Treatment may not be necessary. However, symptoms can sometimes subside upon removing a potential lesion or benign tumor.

This article will discuss how and why Harlequin syndrome occurs. It will also discuss symptoms, effects, treatment, frequently asked questions, and more.

What is Harlequin syndrome? 

A person with flushed facial skin applies red lipstick while looking in the mirror.
Lucas Ottone/Stocksy United

Harlequin syndrome is a rare autonomic disorder, meaning that the condition stems from the autonomic nervous system. The autonomic part of the nervous system is responsible for unconscious bodily processes.

Researchers first described Harlequin syndrome in 1988. They studied five individuals who experienced an absence of facial flushing and sweating on one side of their faces. These symptoms occurred when these people would exercise or were in hot conditions. 

This is because Harlequin syndrome can affect the body unilaterally, meaning either the left or the right side of the body. As a result, people with this disorder may experience unilateral sweating and flushing.

Clinicians may also refer to Harlequin syndrome by using medical descriptions of the symptoms. Other terms for this condition are progressive isolated segmental anhidrosis and sudden onset of unilateral flushing and sweating.

Although similarly named, Harlequin syndrome varies from Harlequin ichthyosis.

Harlequin ichthyosis appears in infants and results from the mutation in the ABCA12 gene. Infants with this inherited condition are born with areas of thick skin that are prone to cracking and splitting. This condition can impact the infant’s ability to eat or breathe. 

Signs and symptoms

In some reported cases, symptoms of Harlequin syndrome begin appearing in adulthood. However, researchers note that the syndrome is common in newborns and can appear from birth.

The most characteristic signs of Harlequin syndrome are the absence of both perspiration and skin flushing on one side of the body or face.

These symptoms tend to be most noticeable following times when one might expect natural sweating or flushing. These times can include physical exertion, emotional response, and exposure to heat.

Symptoms of Harlequin syndrome may have the following characteristics:

  • absence of perspiration or flushing on one side
  • typical or expected sweating and flushing on the other side of the body
  • profuse sweating or flushing on the unaffected side as compensation
  • tonic pupils, pupils which may dilate more than usual, do not constrict well in response to light, or are no longer perfectly circular
  • impaired reflexes on the affected side

Clinicians may refer to the asymmetrical facial sweating and flushing as the “Harlequin sign.”

Less commonly, individuals may also experience conditions such as Holmes-Adie syndrome and Ross syndrome. Both of these syndromes are autonomic disorders.

Below are some images of what Harlequin syndrome can look like.

harlequin-syndrome-1.jpg

Harlequin syndrome can cause one side of the face or body to experience an absence of sweating or flushing.

© 2016 by The Korean Pediatric Society/NBCI

harlequin-syndrome-2.jpg

The body may compensate for the side of the face which does not perspire or flush. As a result, the face may flush and perspire more on the unaffected side.

Hans-Bittner NR, Bittner GC, Hans Filho G. Do you know this syndrome? Harlequin syndrome. An Bras Dermtatol. 2018;93(4):585-6. CC-BY-NC

Causes 

Clinicians are still working to understand all of the causes of Harlequin syndrome.

According to a 2016 study, around 6% of Harlequin syndrome cases are congenital, meaning present from birth.

However, there may be no genetic association or cause of the condition.

Harlequin syndrome can also occur in two different ways. Primary Harlequin syndrome can occur spontaneously. In contrast, secondary Harlequin syndrome occurs as an effect of an underlying condition.

Researchers from a 2017 case report now suggest that a condition called hemifacial cutaneous sympathetic denervation causes primary cases of Harlequin syndrome. 

Rarely, primary Harlequin syndrome is idiopathic, meaning clinicians do not know the cause.

Secondary instances of Harlequin syndrome may account for 1 in 4 cases.

Causes of secondary Harlequin syndrome may include:

  • presence of a benign tumor or lesion
  • local trauma
  • neurotropic viral infection, a viral infection that affects nerve tissue
  • medical intervention, such as medication or surgery

Conditions that affect autonomic nervous system function may cause Harlequin syndrome. This is because the conditions can prohibit autonomic nervous system cells from interacting with one side of the body.

The Harlequin sign may also appear in other conditions as a symptom or coexisting condition.

Risk factors and related conditions

Researchers have not yet identified any definite risk factors for Harlequin syndrome.

However, while Harlequin syndrome can appear spontaneously, it can also appear alongside other disorders. Additionally, some other conditions can present the Harlequin sign as a symptom.

These coexisting disorders and conditions can include:

  • Horner’s syndrome
  • diabetic neuropathy
  • multiple system atrophy
  • pure autonomic failure, also known as Bradbury-Eggleston syndrome
  • Guillain-Barré syndrome
  • Holmes-Adie syndrome
  • Ross syndrome

Complications 

There are few reports of complications directly as a result of Harlequin syndrome.

However, people with Harlequin syndrome may not experience the full benefits of sweat.

Sweat is important for regulating body temperature. People who do not sweat on one side may need to avoid strenuous activity in hot conditions. 

Additionally, glycoproteins in human sweat may help to heal infections. Sweating may also help your body clear itself of heavy metals and toxins. 

Some complications may occur as a result of certain treatments. For example, surgical sympathectomy ipsilateral may treat the affected side. However, it may also produce compensatory flushing or sweating in other body parts.

Treatment

Clinical treatment for Harlequin syndrome may not be necessary, particularly in primary Harlequin syndrome. With primary Harlequin syndrome, clinicians cannot find the cause. In some cases, symptoms are not detrimental, distressing, or do not affect daily living.

If doctors can locate a tumor or lesion causing autonomic nervous system disruption, they may recommend surgery, radiation, or another treatment to remove it.

One experimental treatment that has shown some promise in treating symptoms is botulinum toxin (Botox). In one 2016 study of a single participant, researchers observed a positive response to botox injections to treat sweating associated with Harlequin syndrome.

Additionally, your doctor may be able to recommend treatment options and management tips to deal with the psychological impacts of the condition, such as anxiety and social embarrassment.

Individuals who wish to even the appearance of the flushing and sweating for cosmetic reasons can discuss surgical sympathectomy ipsilateral with their doctor.

In a sympathectomy, a surgeon will clamp or cut a section of sympathetic nerve to prevent it from passing signals to certain areas of the body. This will prevent sweating and blushing on the side of the face that perspires.

Although this is a minimally-invasive procedure, doctors may only suggest it if other treatments are unsuccessful, as it can have complications. For example, people who undergo this operation may experience excessive sweating in other areas as the body tries to compensate. 

Outlook 

Harlequin syndrome is rarely debilitating, and most people can have a good quality of life with the condition.

As the condition is medically benign, it has a favorable diagnosis. This means that Harlequin syndrome itself does not present a risk to life.

However, as it may result from a neurotropic infection, contact your doctor for symptoms of Harlequin syndrome alongside severe symptoms of infection.

Additionally, many associate the condition with anxiety and social embarrassment due to the visible appearance of the symptoms.

If your symptoms are inconvenient, distressing, or are affecting your daily life, contact your doctor to discuss your treatment and management options.

Read here for more information about viral disease, including symptoms and when to contact a doctor.

FAQ 

Below are some frequently asked questions regarding Harlequin syndrome.

How common is Harlequin syndrome?

There could be anywhere from 1–300 people with Harlequin syndrome currently in the United States.  

This means that Harlequin syndrome is rare.

Why is it called Harlequin syndrome? 

The term “Harlequin syndrome” takes its name from a popular character in medieval Italian theater called Harlequin.

The group of researchers that first described Harlequin syndrome named the syndrome after this character.

Can Harlequin syndrome go away? 

If clinicians know the cause of a particular case of Harlequin syndrome and can treat it, the condition may resolve completely.

For example, if the condition results from a lesion or benign tumor, removal may resolve the syndrome’s symptoms.

However, some cases of the condition are idiopathic, and treatment in these cases may not be successful. Many doctors suggest no treatment if the syndrome does not impact a person’s daily life.

Is Harlequin syndrome life threatening? 

Harlequin syndrome is not life threatening.

In many cases, doctors do not recommend treatment, as there may be no risk to life.

However, you may wish to seek support for certain symptoms you might experience, as these may affect your quality of life.

Summary

Harlequin syndrome is a rare nervous system condition that can affect the body unilaterally. One side of a person’s face or body may not sweat or flush as expected, while the other side may do so excessively.

Additional symptoms may involve the eye, such as the reduced constriction of the pupils.

Harlequin syndrome can either occur spontaneously or due to an underlying condition. These underlying causes can include local trauma, benign tumors, lesions, or infection.

People with this condition usually do not require treatment. However, treatment options, including surgery, may be available depending on the cause.

Contact your doctor if you are experiencing symptoms that affect your daily life. 

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Medical Reviewer: Mia Armstrong, MD
Last Review Date: 2022 Jun 24
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THIS TOOL DOES NOT PROVIDE MEDICAL ADVICE. It is intended for informational purposes only. It is not a substitute for professional medical advice, diagnosis or treatment. Never ignore professional medical advice in seeking treatment because of something you have read on the site. If you think you may have a medical emergency, immediately call your doctor or dial 911.
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