Introduction

Frey syndrome is a disorder that occurs as a complication of surgery undertaken near the parotid glands. Its symptoms start after eating certain foods and include excessive sweating and blushing in areas of the face, around the cheeks, forehead, and behind the ears.¹ Previously, it was believed to be a rare disorder; however, recent research suggests that it can impact 4% to 62% of post-parotidectomy or facial surgery patients.²

The symptoms of Frey syndrome are very similar to those of other disorders/illnesses. As a result, a differential diagnosis is required to distinguish Frey syndrome from other conditions that have similar symptoms. A differential diagnosis refers to a method of analysis used by healthcare professionals that identifies a disease from other competing diagnoses based on clinical features.³ By eliminating other diseases, one can successfully diagnose and treat them. This must be done to prevent misdiagnosis and failed treatment. Differential diagnosis speeds up the rate of treatment, thus improving an individual's prognosis and quality of life.

Symptoms of frey’s syndrome

Frey syndrome damages both the parasympathetic and sympathetic axons of the auriculotemporal nerve. This nerve is responsible for bringing sensation to the face, including the jaw, ears and scalp.4 Parotidectomy, surgery to remove part or all of the parotid glands, can cause aberrant regeneration of parasympathetic fibres. This means that the parasympathetic nerves, which control digestion, grow alongside the sympathetic nerves, which are responsible for the control of blood vessels and sweat glands in the face. Consequently, when an individual with Frey syndrome eats, their sweat glands and blood vessels are activated too, causing symptoms of sweating and flushing.⁴

Common symptoms of Frey syndrome include:

• Sweating on areas of the face, including the cheek, forehead, and ears, induced by eating or thinking of foods¹ 
• Mostly, sour, spicy or salty foods are more likely to cause excessive sweating as they produce a strong salivary response
• Flushing, caused by dilated blood vessels, and warmth in facial areas are also symptoms

The degree of severity of symptoms varies between individuals and can range from mild to severe. This depends on the severity of the damage to the affected nerve during the parotidectomy.

How is frey syndrome diagnosed?

A combination of clinical evaluations and a diagnostic test are usually used to diagnose Frey syndrome.

• Clinical evaluation involves a detailed patient history of the symptoms, including onset, triggers and severity
• When was their surgery done?
• A minor starch-iodine test is carried out.⁴ The face is painted with iodine in the affected areas. Once this has dried, starch is also painted over the face. The patient is then presented with some sort of strong salivary-inducing food. If the patient has Frey syndrome, the starch on the face becomes moist and turns a bluish/brown colour²

Conditions that mimic Frey syndrome

Cluster headaches

• Description:
  • Severe unilateral headache with autonomic symptoms like tearing and sweating
  • Severe headaches that last for long periods, ranging from minutes to hours
  • They can occur multiple times a day and may persist for months. They are a stand-alone illness
  • Symptoms include a sharp, piercing pain around the eye, typically on one side only, abruptly starting and stopping headaches that come without warning, long-lasting headaches, nausea, drooping of the eye where there is pain, and facial sweating⁵
• Key Differences:
  • Cluster headaches are not linked to eating, and they typically occur during a cluster period, meaning at the same time each day or year
  • Moreover, headaches are the main symptom, but that is not the case in Frey syndrome⁵

Harlequin syndrome

• Description:
  • Harlequin syndrome affects the autonomic nervous system, which is responsible for controlling the body's natural responses of sweating, flushing, and pupils’s responses. When the autonomic nervous system is affected by Harlequin syndrome, one side of the body is unable to sweat or flush on the face, arms and chest. This symptom is most likely to occur after vigorous, sweat-inducing activity⁶
• Key Differences:
  • Harlequin syndrome is not induced by certain food stimuli, but instead exercise, or emotional situations. Additionally, this syndrome only impacts one side of the body, not both like Frey syndrome

Ross syndrome

• Description:
  • Ross syndrome is a nervous system disorder characterised by three features: tonic pupil, the absence of deep tendon reflexes, and an inability to sweat normally⁷
• Key Differences:
  • Ross syndrome has symptoms that involve more than sweating. It also impacts multiple body areas, not just the face

Idiopathic gustatory sweating

• Description:
  • Sweating occurs after eating spicy or sour foods, particularly in the facial region. There is no impact of surgery or anything near the parotid glands
• Key Differences:
  • Although similar to Frey syndrome, idiopathic gustatory sweating occurs without a history of parotid surgery. The reason behind it is typically unknown⁸

Conditions to be distinguished from frey syndrome

Hyperhidrosis

• Description:
  • Hyperhidrosis is a disorder of excessive sweating in the face, armpits, palms and soles⁹
• Key differences:
  • Primary hyperhidrosis is an autonomic disorder
  • Drugs, toxins, or disorders within the body can induce secondary hyperhidrosis
  • Neither of these types is caused postoperatively. Furthermore, Frey syndrome is localised on the face, whereas hyperhidrosis can occur in other parts of the body

Diabetic autonomic neuropathy

• Description:
  • Diabetes can cause nerve damage. Autonomic neuropathy refers to damage to the nerves that carry information to the glands.¹⁰ So, when the nerve that provides information to the sweat glands is damaged, miscommunication will occur, causing gustatory sweating¹¹
• Key Differences:
  • More generalised sweating, often bilateral, with other signs of diabetic neuropathy. Other symptoms of diabetes will accompany sweating, including thirst, weight loss or gain, frequent urination, blurred vision etc¹²

Temporal arteritis

• Description:
  • The large temporal arteries, particularly those at the temples of the head, become inflamed and narrow. This may lead to a throbbing headache, sweating, pain in the temples, and vision problems¹³
• Key Differences:
  • Unlike Frey syndrome, temporal arteritis presents with the above-mentioned symptoms

Management and treatment considerations

Treatment for frey syndrome

• Topical antiperspirants reduce sweat. They are easily accessible and cost-effective. They may contain high levels of aluminium chloride, which can obstruct the sweat gland ducts, preventing sweat. For higher doses of aluminium chloride, prescription antiperspirants may be prescribed¹⁴
• Botulinum injections work by paralysing the sweat glands, reducing their ability to produce sweat and flushing. The effects fade over time; therefore, repeat injections may be needed⁴
• Surgical intervention: As a last resort, some individuals may opt for surgery when other treatments have failed. This typically involves transection (cutting across) of the impacted nerve, barrier placement, and the removal of the affected skin⁴

Management of mimicking conditions

Treatment for mimicking conditions is specific based on the underlying condition:

• Cluster headaches may be treated with medications such as paracetamol and ibuprofen to ease the symptoms⁵
• Temporal arteritis can be treated with steroid medication like prednisolone. A high dose is first given, and gradually, the dose is lowered in the long term¹⁵

Correct treatment is imperative in ensuring a timely diagnosis and appropriate treatment and management. Not only will this quickly improve an individual's quality of life, but it will also avoid unnecessary and incorrect treatments.

Conclusion

In summary, an accurate diagnosis of Frey syndrome is essential for the successful management of the disorder due to its symptoms that overlap with many other disorders. Conditions such as Harlequin syndrome, cluster headaches, Ross syndrome, and idiopathic gustatory sweating can mimic Frey syndrome. Consequently, correct diagnosis becomes more difficult and more important. A combination of clinical evaluations and diagnostic tests is essential to reaching a diagnosis, implementing appropriate treatment and overall improving patient care. A differential diagnosis must be carried out to improve the quality of life of Frey syndrome patients.