Introduction

Frey syndrome, also known as Baillarger’s syndrome, auriculotemporal syndrome, Dupuy syndrome, or gustatory hyperhidrosis, represents aberrant reinnervation (regeneration) following injury to the auriculotemporal nerve in the face and head.¹ It is associated by facial sweating near the cheek and ear region during eating. 

Causes and mechanism of Frey syndrome

There are 3 pairs of major salivary glands:

• Parotid glands
• Submandibular glands 
• Sublingual glands

Parotid glands: Parotid glands are the largest salivary glands,located just beneath and in front of your ears on both the sides of your face. These glands have a major contribution in the production of saliva in the mouth. Parotid glands receive nerve supply from the auriculotemporal nerve, which is responsible for stimulation of saliva production in the glands.

The auriculotemporal nerve, which is a branch of the trigeminal nerve, consists of parasympathetic fibers and sympathetic fibres. The parasympathetic fibres signal the parotid gland to produce saliva, and sympathetic fibers innervate the sweat glands of the face and scalp. 

When there is damage to the nerves in the parotid region occurs, the aberrant regeneration of postganglionic parasympathetic nerve fibers (responsible for salivary secretion) along the pre-existing sympathetic pathways to the vessels and sweat glands of the skin can lead to the development of Frey syndrome.¹ 

• Trauma or surgical procedures involving parotid glands could be the cause of damage to the auriculotemporal nerve. The aberant nerve regeneration leads to dilation of vessels and production of sweat in response to gustatory stimulation

Symptoms and diagnosis

Primary symptoms of Frey syndrome

The common symptoms of Frey syndrome are:

• flushing
• sweating
• burning
• neuralgia
• itching 

The patient may experience excess sweating while eating, or even when thinking about food,around the ear, cheek and temple region. Additionally, some patients may suffer from flushing of the face, showing skin redness or discoloration. Generally, the symptoms are mild. However, symptoms can be uncomfortable and embarrassing for the patient, resulting in social anxiety and avoidance.

Diagnostic tests

Frey syndrome is a condition that often develops in people who have had surgery on their parotid gland, such as a parotidectomy, which regulates saliva production. After a parotidectomy, some nerves may connect to sweat glands present on the face instead of joining with the salivary glands. As a result, rather than producing saliva when eating or thinking about food, these nerves trigger sweating in the affected area. Therefore, sweating while eating is called gustatory sweating.

Diagnosing Frey syndrome typically involves reviewing the patient's clinical history, particularly any previous surgeries involving the parotid gland. Most cases of Frey syndrome are seen in patients who have had a parotidectomy to treat a problem with the parotid gland.

To confirm the presence of Frey syndrome, doctors often use the Minor starch iodine test ², which is a simple and effective method. Here’s how the test works:

• Preparation: The affected area of the patient's face is painted with an iodine solution
• Drying: The iodine is allowed to dry completely
• Application of Starch: Once the iodine is dry, a dry starch powder (like cornstarch) is applied to the same area
• Saliva stimulation: The patient is then given a substance that stimulates saliva production, known as a sialogogue. Common examples include lemon juice or chewing gum
• Observation: If the patient has Frey syndrome, the area where the nerves are miswired will sweat. When this sweat comes into contact with the starch and iodine, it will cause the starch to change color, usually turning blue or brown

This color change clearly shows the areas affected by gustatory sweating, confirming the diagnosis of Frey syndrome.

Impact of gustatory sweating on patients

Physical and emotional effects

Gustatory sweating causes a person to sweat while eating. Sweating most commonly occurs on the facial and neck region and may cause the patient to feel sticky or wet. If this happens while eating with other people, the changes to the patient's facial colour and moisture could be noticed, which could be embarrassing for the patient. Therefore, this can make the patient feel anxious and socially awkward, and lead to them avoiding eating in public. Ultimately, these factors could lead to social isolation and can impact a patient’s quality of life.

Treatment options

Non-surgical approaches

• Antiperspirants: Topical antiperspirants, containing aluminum chloride, can be applied directly to the skin to reduce sweating. The effect of these topical agents is temporarily seen due to blockage of sweat glands, which helps in relieving gustatory sweating. They are safe and effective for mild use, however,the side effects include skin irritation when used in excess
• Anticholinergic medications: These oral medications, such as glycopyrrolate or scopolamine, work by blocking the nerve signals that stimulate sweat production. However, this is only advised for certain patients due to its side effects, which includes;
  • Dry mouth 
  • Blurred vision 
  • Urinary retention 
• Dietary modifications: Since gustatory sweating is often triggered by specific foods, patients are advised to avoid spicy, acidic, or hot foods that can exacerbate symptoms. Adjusting the diet to eliminate or reduce these triggers can help manage sweating episodes, though this may limit dietary choices

Surgical and minimally invasive treatments

• Botox injections: Botulinum toxin (Botox) injections are a widely used treatment for Frey syndrome. Botulinum toxins, produced by Clostridium botulinum (a bacterial species), are a family of neurotoxins that includes several subtypes. Botulinum toxin type A (BTXA) is the most common subtype, which causes blockage of neurotransmission by preventing the release of acetylcholine to nerve endings.³ Nowadays, the intracutaneous injection (into skin) of BTXA is the treatment of choice for Frey syndrome because it is simple, effective, reliable, fast, and there are no apparent side effects³
• Dermal grafting: In dermal grafting, a part of skin or tissue is taken from one area of the body, and attached over the area of skin with abnormal sweating

The graft acts as a barrier to prevent the nerves from reaching the sweat glands. The advantage of dermal grafting is that it is a long term solution. A disadvantage is that it is an invasive procedure, which requires a long recovery time. 

Prevention and management 

Techniques used during a parotidectomy to reduce the risk of Frey syndrome

Frey syndrome often develops after parotidectomy surgery, which can involve removing the parotid gland; this is caused by the mixing of nerves that regulate sweating and salivation during the healing period.

There are several surgical techniques that can help reduce the risk of developing Frey syndrome:

Interpositional tissue grafts

The main method used for prevention is the interposition of a graft between the skin flap and the parotid bed during surgery. Biomaterials, allograft, or autograft can be used for this purpose.⁴ 

Common graft materials include:

• Temporoparietal fascia flap (TPF): A layer of tissue taken from the side of the head
• Sternocleidomastoid muscle flap: A piece of muscle from the neck

Use of alloplastic materials

When a patient's own tissue cannot be used, synthetic materials, such as acellular dermal matrix (ADM), are used as barriers. The alloplastic materials will help prevent the nerves from mixing after the surgery. 

Intraoperative nerve monitoring

During surgery, nerve monitors help identify and protect critical nerves, reducing accidental nerve damage that could lead to Frey syndrome.

Modified surgical techniques

Surgeons may use more conservative surgical approaches, removing only the necessary parts of the gland, and sparing as much of the surrounding nerves as possible. This method reduces the chance of nerve damage, and the subsequent development of Frey syndrome.

Summary

Frey syndrome is a condition that often occurs after surgery involving the parotid gland, leading to sweating and flushing of the cheeks when eating;this is caused by nerve damage during surgery, resulting in the mixing of nerves that regulate sweating with the nerves that regulate salivation. The main symptom is gustatory sweating, which is sweating triggered by eating or thinking about food.

Frey syndrome is not life-threatening, but can significantly impact a person’s daily life and self-confidence. To reduce the risk of Frey syndrome, surgeons can use specialised techniques during the initial surgery, like placing tissue grafts. Other treatment options include,topical antiperspirants, botox injections,dietary changes,and surgery