Overview

Frey Syndrome, also known as Dupuy’s syndrome, Baillarger’s syndrome or auriculotemporal syndrome, is a rare neurological disorder associated with hyperhidrosis, or excessive sweating whilst eating or thinking about food. The precise aetiology and pathophysiology of the disease remain unelucidated, although scientists believe that it is caused by damaged nerve cells near the parotid glands (an example of salivary glands). It is theorised that these nerve cells regenerate abnormally to provoke neuronal misactivation of sweat glands in response to food consumption that would normally cause dilation of parotid glands. The activated sweat glands would therefore cause sweating. The precise mechanism of its theorised pathophysiology will be discussed later.

What is Frey syndrome?

Signs and symptoms

Symptoms of Frey Syndrome typically include:

• Excessive sweating on the cheek, forehead or around ears while eating
• Flushing and warmth in the same area

Such symptoms are more likely to occur when the person eats something sour or spicy, which is usually associated with a greater release of saliva compared to normal foods.¹ It is also frequently reported that symptoms greatly vary amongst individuals, resulting in inconsistent diagnosis and reporting.

Patients may also report pain in the affected area, however, this is likely to be a result of the underlying damage to the nervous system caused by trauma or surgery (National Organization for Rare Diseases). 

Prevalence

The exact prevalence of Frey Syndrome is unknown. One of its primary causes is parotid gland surgery, or parotidectomy, which is scientifically revealed to have a high likelihood of causing post-surgery Frey syndrome. Contrastingly, though, there is a very low number of patients who report symptoms.² This disagreement prevents a commonly accepted interpretation of the disease pathology from being established. Prevalence rates studied by researchers range from single digits to nearly 90%, which perhaps reflects the heterogeneity of symptom severity.³ There is a disagreement between self-reported rates and the studied percentage, indicating that a reasonable number of the population are unaware of the disease, or are unbothered by the symptoms.⁴ Therefore, people may have Frey syndrome but do not notice it, although this is not a critical issue as Frey syndrome is benign.

Anatomy and physiology of the parotid gland and facial nerve

Structure and function of the parotid gland

Parotid glands are located near the ear, one in front of and below each ear. It is a type of salivary gland, which is used to produce saliva and aid digestion of food in the mouth. They also have anti-microbial effects, which help to prevent oral infection and tooth decay. The Stensen duct carries the saliva secreted by the parotid gland and releases it near the upper molar teeth.

The facial nerve

The facial nerve has 6 segments: 

• Intracranial segment, 
• Meatal (canalicular) segment, 
• Labyrinthine segment, 
• Tympanic segment, 
• Mastoid segment and 
• Extratemporal segment⁵ 

Parotid gland function is associated with the extratemporal segment. Once this segment enters the facial nerve, it separates into the superiorly directed temporofacial and the inferiorly directed cervicofacial branches.⁶ It is worth noting, though, that the facial nerve does not neurologically control parotid gland activity; instead, it merely branches away within the gland – its function is focused on controlling facial muscles. Nonetheless, this anatomical intimacy results in complications during parotidectomy that are thought to trigger Frey Syndrome.

Pathophysiology of Frey syndrome

There are many unanswered questions regarding the pathophysiology of Frey syndrome, although it is theorised that simultaneous damage of the sympathetic and parasympathetic nerves near the parotid glands causes the disease (National Organization for Rare Diseases). 

The function of sympathetic and parasympathetic nerves within this context is as follows:

• Parasympathetic nerves trigger the release of saliva from parotid glands
• Sympathetic nerves control the activity of sweat glands

When nerves are damaged through trauma or surgery, they attempt to remodel themselves, a process known as reinnervation. When damaged parasympathetic nerves near the parotid glands reinnervate themselves, there is a small chance that they incorrectly connect themselves to the nearby sweat glands.⁷ This causes the sweat glands to be controlled by neurons that were previously controlling parotid glands, resulting in sweating when consuming food. Typically, the nerve damaged in Frey syndrome is the auriculotemporal nerve located in front of the ear, which also contains parasympathetic nerve fibres. Similar processes can occur in other salivary glands such as submandibular or sublingual glands. 

Remodelling of neural networks is a slow process, therefore symptoms of Frey syndrome can show up after up to 18 months following the originating injury.⁸ Another theory is that lesions at the sympathetic nerves result in the hypersensitisation of sympathetic nerves, causing excessive sweating. This scenario is more likely when the symptoms show relatively quickly, as reinnervation of nerves does not occur.⁸

Factors influencing the development of Frey syndrome

History of surgery

As mentioned previously, the primary causes of Frey Syndrome are thought to be lesions at the facial nerves due to injury of surgery. Parotidectomy is usually conducted when the patient suffers from a neck tumour, facial paralysis, xerostomia, salivary fistula and a range of other neurological disorders.⁹ Studies generally suggest that surgeries with more excessive invasion increase the likelihood of having Frey Syndrome.³ Non-surgical Frey symptoms are rare, with only a few cases observed among young people.¹⁰ They are typically found shortly after birth. Frey syndrome in infants may have a history of instrumented vaginal surgery.¹¹

Injuries

Other than direct injury to the area near the parotid glands, temporomandibular joint injury caused by teeth grinding and arthritis can also cause Frey syndrome.

Genetic factors

Although there is a possibility that newborn Frey syndrome is familiarly inherited, especially when there is no history of fetal surgery, there is a lack of scientific papers that discuss the precise genetic mechanism that results in Frey syndrome.¹²

How is Frey syndrome managed?

Management of Frey syndrome typically focuses on controlling symptoms rather than curing the cause of disease. Clinics may provide the following to reduce hyperhidrosis –

• Botox injections – this blocks neuronal activation of sweat glands, preventing sweating. The effect lasts for around half a year, so additional injections are required
• Topical anticholinergics and antiperspirants – both treatments require frequent administration. Anticholinergics are more effective than antiperspirants

Another approach is to prevent the damage of neurons during parotidectomy by creating a barrier between the parasympathetic nerves and the sweat glands to block abnormal reinnervation.⁹ There are various types of such measures, each with its risks and disadvantages, such as prolonged operation time, wound infection and varying effectiveness. Examples include thick skin flap, acellular dermal matrix (ADM) and autologous fat implantation.⁹

FAQs

How is Frey syndrome different to allergic reactions?

Allergic reactions occur when consuming more specific foods such as peanuts or seafood, and usually have a broader affected area.¹³ Additionally, symptoms of allergies are more long-lasting than Frey syndrome and usually occur together with other atopic symptoms including dry skin, itchiness and thickened skin.

How is Frey syndrome diagnosed?

Clinicians may ask for surgical or trauma history to distinguish symptoms from other sweating disorders or allergies. In addition, they can conduct a starch iodine test, where starch and iodine are painted on the patient’s face. The colour would turn from brown to blue in response to sweating, indicating the region affected by Frey syndrome. 

Can Frey syndrome become worse?

Frey syndrome is a benign disease that does not worsen or cause other physiological diseases after establishment. However, patients may experience reduced sexuality and speech defects due to social anxiety caused by excessive sweating.⁹ This can significantly reduce the patient’s quality of life.

Can Frey syndrome occur due to infection?

Studies report that very few cases of Frey syndrome are caused by infections. With that said, an in-depth examination of such cases typically indicates surgical operations as the underlying cause, which reduces the significance of microbial infection in the development of Frey syndrome.¹⁴

Summary

Frey syndrome develops from neurological damage near the parotid gland, caused by either surgical operations or injuries. Its precise pathophysiology remains unelucidated, however, it is thought that there is aberrant reinnervation of parasympathetic nerves that remodels itself to interfere with parotid gland activity, causing excessive sweating during eating spicy or sour foods. Frey syndrome mainly occurs post-surgery in adults, or in newborns following prenatal operations. At a much lower prevalence, injuries directly to the parotid gland or temporomandibular joint can cause the disease too. Symptoms are diverse and physiologically harmless, although they can still affect the patient’s quality of life. For this reason, clinics may conduct preventive measures or give medications that can reduce sweating.