Introduction

Frey syndrome (FS) is a rare condition that affects children and adults. This condition is due to postoperative complications, particularly following surgery of the salivary glands.¹ This neurological condition leads to excessive sweating when eating. This sweating typically occurs on the scalp and other parts of the head when eating or thinking about food. This is termed gustatory sweating. 

The glands that are mainly affected are the parotid glands, a type of salivary gland. The excessive sweating is termed hyperhidrosis, this causes anxiety and distress for those affected.² It is important to understand the prevalence of this syndrome and the epidemiological data. By understanding this data, managing patients will be easier and healthcare planning will be more efficient and effective. This article focuses on Frey Syndrome, the causes and the factors that influence the epidemiological data. Future areas of research will also be explored.

Understanding Frey syndrome

There are a few underlying mechanisms and risk factors that lead to the pathophysiology of FS. Frey syndrome typically occurs after parotidectomy which, as previously mentioned is when the parotid gland is surgically removed.³ This surgery causes incorrect nerve regeneration as nerve fibres that are part of the parasympathetic nervous system connect with sympathetic nerve fibres connected to sweat glands. This leads to sweat glands being stimulated following salivation due to misdirected nerve regeneration.⁴ 

It has been hypothesised that neurturin, a neurotrophic factor is responsible for FS presentation. These proteins contribute to neurone development. Neurturin is released by salivary glands and sweat glands, therefore this factor may link these glands leading to FS.⁵

There are other risk factors and some population groups are at higher risk. Surgeries such as a parotidectomy increase FS risk but other factors such as having tumours, particularly benign tumours increase the risk of developing FS.⁶ Trauma of the parotid gland which occurs due to head trauma and accidents such as car crashes greatly increases FS likelihood.⁷ Infections in this same region, referred to as parotitis (inflammation caused by bacteria) is another key risk factor and is strongly associated with this syndrome. This is caused by bacteria such as Staphylococcus aureus as well as other bacteria including Escherichia coli.⁸ Some studies have shown that whilst FS prevalence is higher in women than in men this is not significant however having facial surgeries and having benign tumours greatly increases the risk.⁹ Facial trauma as previously established is a contributing factor. It is still yet to be fully established whether ethnicity affects FS prevalence.

Incidence of Frey syndrome

There are different incidence rates in different parts of the world, demographic factors can also lead to variation in the incidence of FS. As FS is a rare condition, the incidence rates that supposedly vary by region are not well documented and there are not many FS incidence rate statistics. It has been suggested that FS prevalence is likely to be higher in high-income countries in comparison to low-income countries and newly emerging economies. This is due to FS prevalence being very high amongst patients who have undergone parotid surgery. Richer countries that have greater access to healthcare would have a higher FS prevalence. 

An American census showed that Afro-Caribbeans, African Americans, and Latinos had a disproportionately high prevalence of hyperhidrosis which implies that FS is likely to be more prevalent in these ethnic groups.¹⁰ Another hyperhidrosis study suggested that Japanese people have an increased prevalence of FS compared to other ethnic groups.¹¹ This suggests that parotidectomy may be higher in Japan than in other countries, however, certain ethnic groups may be more genetically predisposed to FS.

As salivary gland tumours lead to parotidectomy this is likely to be indicative of FS prevalence. As previously established, benign tumours are linked to FS prevalence. Pleomorphic adenoma, the most common salivary gland tumour type was shown to have a much higher prevalence in Africa, Asia, and South America compared to the UK and the rest of Europe.¹² These tumours may be more common in these regions, however, as surgeries mainly occur in Europe and North America, the prevalence of FS is strongly linked to economic factors. Females had higher benign salivary tumour prevalence in this study with 40-59 being the modal age group therefore FS is likely to affect middle-aged people more than young people.¹² 

It has been well established that most patients who undergo parotidectomy show some FS symptoms in the parotid region, however, it is difficult to conclude in many of these cases whether it is clearly FS.¹³ It has been estimated that up to half of the patients who have parotid gland surgery eventually develop FS. Other medical interventions such as neck dissections and facelift surgeries have also been linked to increased FS incidence, however, this is to a much lower extent than parotidectomy.¹

Prevalence of Frey syndrome

It is difficult to establish the prevalence of FS in different countries and populations as these statistics are not available. This is due to FS being so rare and therefore, the confirmed case numbers are small and the data is limited. Other factors such as the type of surgery/medical intervention and the time since the surgery influence FS prevalence. The length of the operation corresponds to the risk of FS as longer operations are a risk factor. Age and size also influence FS likelihood.¹⁴ Sometimes FS does not present itself until months after the surgery, therefore parotidectomy symptoms need to be monitored. 

FS typically presents itself 12 months post-operation with some symptoms appearing after 18 months, many patients can also be asymptomatic for a long period.⁴ This demonstrates the importance of monitoring symptoms and why it is difficult to establish FS prevalence. The type of surgery is important with parotidectomy having the highest post-operative prevalence however other surgeries such as facelifts can also lead to FS long-term. A systematic review suggests that FS prevalence following mandibular fracture treatment is 0.01%, however, once again due to the rarity FS statistics are limited.¹⁵ Following parotidectomy, up to half of the patients develop FS therefore this needs to be monitored closely. Some studies suggest a much lower prevalence. The symptoms are typically benign however they can be lifelong.¹⁶ There are treatments such as special types of surgery however botulinum toxin is the most well-documented FS treatment.¹⁷

Epidemiological variability

Whilst the benign tumour prevalence, which could lead to FS following treatment tends to be higher in continents such as Africa and Asia, the FS incidence and prevalence are thought to be higher in Europe and North America due to higher healthcare accessibility. This increases the chance of post-operative complications causing FS. There is a shortage of data demonstrating geographic differences with much of the current research being speculative. One issue is the difference in methodology between studies. There are many studies on treatments for FS but these studies do not focus on the prevalence of this condition. Other studies are very specific such as the incidence following parotidectomy. 

There are very few studies comparing surgery types. These studies have limited cohort numbers and availability meaning that regional differences, let alone differences between countries are difficult to establish. There is a large disparity between self-reported and clinically diagnosed cases. When an iodine test was used in one study, more than double of the patients tested positive for symptoms when compared to self-reported incidences.¹ This shows that as the diagnosis is rare and not many people are aware of the condition, FS prevalence may be much higher than anticipated. If more people are clinically diagnosed this will provide more research opportunities and FS treatments.

Impact of Frey syndrome

Frey syndrome can largely impact the quality of life. FS leads to individuals feeling anxious when eating food due to the salivary glands being stimulated and leading to sweating. This may cause mental health problems and these impacts can lead to a large healthcare burden for healthcare services. Strategies to prevent FS following a parotidectomy are not particularly cost-effective such as using a free fat graft or an acellular dermis, both of which cost a significant amount of money.¹⁸ 

In regards to management, once a patient has FS, antiperspirants and ointments can prove effective temporarily. The main way to treat patients is by injecting the area with botulinum toxin. This helps with the sweating significantly in the long-term even though the condition is chronic, however, skin flushing is not resolved.¹⁹ Reconstructive surgeries are also available. FS may lead to patients needing long-term therapy depending on the severity of the symptoms. It is important to spread awareness of this condition as there is no treatment that is effective in treating all the symptoms. Botulinum toxin injections are likely to be utilised more as these are the most reliable way of treating the gustatory sweating associated with FS.

Summary

Currently, there is a lack of data on the incidence and prevalence of FS. Many more areas require epidemiological study. There needs to be more data on incidence and prevalence between countries and regions of the world as well as studies on how factors such as age and gender affect prevalence and incidence. It is important to standardise reporting as synergy in studies will allow more study comparisons, encouraging further analysis using more quantitative data. Whilst some data suggests FS differences due to socio-economic factors hence leading to different rates of incidence between continents, more epidemiological data will encourage standardised reports and studies. This will be significant in establishing treatments for those affected. Prevention can increase through being safer with parotidectomy and other procedures. This will also provide less financial strain to healthcare practices and the lives of many will be drastically improved.