RARE DISEASE
Frey syndrome
Frey syndrome
Frey syndrome
Synonyms: Auriculo-temporal syndrome, Auriculotemporal syndrome, Baillarger syndrome, Dupuy syndrome, Gustatory hyperhidrosis
Synonyms: Auriculo-temporal syndrome, Auriculotemporal syndrome, Baillarger syndrome, Dupuy syndrome, Gustatory hyperhidrosis
Synonyms: Auriculo-temporal syndrome, Auriculotemporal syndrome, Baillarger syndrome, Dupuy syndrome, Gustatory hyperhidrosis
Drug discovery
1
drug
With orphan designation
Overview
Frey syndrome is a neurologic disorder caused by auriculotemporal nerve damage, leading to aberrant reinnervation of parasympathetic fibers. This results in gustatory sweating, flushing, and occasional warmth/pain in the preauricular region during mastication. Most cases follow parotid surgery (~30-50% incidence) or trauma. Diagnosis is confirmed via Minor’s starch-iodine test. Management includes botulinum toxin injections (gold standard), topical anticholinergics, and surgical barriers to reduce nerve miswiring [1][6][12].
Burden
Reduces quality of life due to social embarrassment (gustatory sweating) and facial discomfort [4][11][15].
Requires repeated treatments (45% need ≥2 BTX-A injections annually) [2][5].
Chronic management costs and psychosocial impacts disproportionately affect post-oncologic surgery patients [6][11].
Therapies
Categories: rare neurological diseases
Research Papers
407 drug discovery papers about Frey syndrome, with 1 next-in-class emerging drug candidate forecasted to outperform the average preclinical success rate. Recent publications:
407 drug discovery papers about Frey syndrome, with 1 next-in-class emerging drug candidate forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-05-30 | A Case Report of a Patient with Delayed Recovery from Peripheral Facial Palsy Treated with <italic>Gami-Soyo-san</italic> (加味逍遙散) and Facial Acupuncture
Introduction: Peripheral facial palsy with delayed recovery beyond 3 months is associated with reduced rates of complete spontaneous recovery, particularly in older adults with metabolic comorbidities. This report presents a case of integrative Korean medicine treatment for persistent peripheral facial palsy with delayed recovery, in which long-standing suspected Frey’s syndrome also improved.Case Presentation: An 81-year-old woman with diabetes and dyslipidemia presented with right peripheral facial palsy of 4 months’ duration. She also reported gustatory sweating suggestive of Frey’s syndrome that had persisted for approximately 19 years following parotidectomy in 2005. The patient received 56 sessions of manual acupuncture combined with oral Gami-Soyo-san (加味逍遙散) extract granules over 5 months at a public health center branch. The House-Brackmann grade improved from V to II, and the Yanagihara score increased from 17 to 26. The suspected Frey’s syndrome symptoms subjectively improved after approximately 4 weeks, with severity decreasing from 10 to below 5 on a self-rated 10-point scale. Mild subjective synkinesis appeared at week 9 and was considered a natural sequela of aberrant reinnervation. No adverse events were observed. At telephone follow-up 3 months after treatment completion, the clinical improvement was reported to be maintained.Discussion: This case suggests that integrative Korean medicine treatment may be associated with a favorable clinical course in persistent peripheral facial palsy with delayed recovery in a primary care setting, with concurrent improvement in long-standing suspected Frey’s syndrome as a secondary finding. Further case accumulation and prospective studies incorporating objective measures are warranted.
2025-03-31 | Frey syndrome after surgery for the treatment of temporomandibular joint ankylosis: case report
Introduction: Frey's syndrome is characterized by signs of flushing and sweating in the preauricular region following gustatory stimuli. There are few reports in the literature regarding the development of Frey’s syndrome after temporomandibular joint surgeries, and the incidence following such surgeries is uncertain. Case report: A 9-year-old patient was diagnosed with ankylosis of the left temporomandibular joint, following a left condylar fracture that occurred three years prior. The patient underwent Puricelli biconvex arthroplasty as treatment for the ankylosis. Two and a half years after the intervention, the patient developed signs of flushing, sweating, and erythema in the left preauricular region during meals. The proposed treatment involved the topical application of antiperspirant agents containing aluminum chloride, resulting in improvement of the symptoms reported by the patient. Conclusion: Patients should be informed about the risk of developing Frey’s syndrome following open temporomandibular joint surgeries, and further studies are needed to assess the likelihood of this condition occurring.
2023-12-08 | Botulinum Toxin Treatment for Cancer-Related Disorders: A Systematic Review
This systematic review investigates the effect of botulinum neurotoxin (BoNT) therapy on cancer-related disorders. A major bulk of the literature is focused on BoNT’s effect on pain at the site of surgery or radiation. All 13 published studies on this issue indicated reduction or cessation of pain at these sites after local injection of BoNTs. Twelve studies addressed the effect of BoNT injection into the pylorus (sphincter between the stomach and the first part of the gut) for the prevention of gastroparesis after local resection of esophageal cancer. In eight studies, BoNT injection was superior to no intervention; three studies found no difference between the two approaches. One study compared the result of intra-pyloric BoNT injection with preventive pyloromyotomy (resection of pyloric muscle fibers). Both approaches reduced gastroparesis, but the surgical approach had more serious side effects. BoNT injection was superior to saline injection in the prevention of esophageal stricture after surgery (34% versus 6%, respectively, p = 0.02) and produced better results (30% versus 40% stricture) compared to steroid (triamcinolone) injection close to the surgical region. All 12 reported studies on the effect of BoNT injection into the parotid region for the reduction in facial sweating during eating (gustatory hyperhidrosis) found that BoNT injections stopped or significantly reduced facial sweating that developed after parotid gland surgery. Six studies showed that BoNT injection into the parotid region prevented the development of or healed the fistulas that developed after parotid gland resection—parotidectomy gustatory hyperhidrosis (Frey syndrome), post-surgical parotid fistula, and sialocele. Eight studies suggested that BoNT injection into masseter muscle reduced or stopped severe jaw pain after the first bite (first bite syndrome) that may develop as a complication of parotidectomy.
2023-11-09 | Treatment of Frey Syndrome with Botulinum Toxin-A: A Practical Approach from Minor’s Test to Injection
Abstract Introduction Frey's syndrome, described by Lucy Frey in 1923, is a unique condition characterized by sweating, flushing, and reddening as a direct response to mastication. This phenomenon results from the aberrant regeneration of postganglionic parasympathetic neurons originating from the auriculotemporal nerve and the subsequent acetylcholine secretion induced by masticatory stimuli. Although rare, this syndrome can have multiple underlying causes and is frequently observed, occurring in up to 65% of cases following lateral parotid resections. Additionally, it can less commonly manifest after neck dissection, facelift procedures, or be associated with diabetes mellitus. Method This article outlines a comprehensive diagnostic algorithm for Frey's syndrome, which includes the utilization of the Minor-Starch-Iodine Test. This test is a key component in diagnosing the syndrome and is discussed in detail, providing insights into its procedure and interpretation. Additionally, the gold standard of treatment for established Frey's syndrome, botulinum toxin A, is thoroughly described, including its mechanism of action, administration, and potential side effects. Discussion Finally, the article underscores the need for further research to enhance our understanding of Frey's syndrome, leading to better diagnostic methods and more tailored treatment options for patients.
2023-05-08 | The Minor's test in Frey syndrome treated with botulinum toxin: Methodology and efficacy.
In this paper, we aimed at methodologically presenting a video-case of Frey Syndrome occurred after parotidectomy, assessed by means of Minor's Test and treated with intradermic botulinum toxin A (BoNT-A) injection. Although largely described in the literature, a detailed explanation of both the procedures has not been previously elucidated. In a more original approach, we also highlighted the role of the Minor's test in identifying the most affected skin areas and new insight on the patient-tailored approach provided by multiple injections of botulinum toxin. Six months after the procedure, the patient's symptoms were resolved, and no evident signs of Frey syndrome were detectable through the Minor's test.
cell therapies
2026-02-23 | Soft tissue augmentation options for volume replacement following parotidectomy: A review of the literature.
Salivary gland tumors primarily arise in the parotid gland with surgery representing the cornerstone of treatment. Parotidectomies often lead to a soft tissue deficit that may benefit from reconstruction to reduce incidence of Frey's syndrome, improve aesthetic outcomes, and allow for appropriate postoperative therapies. Several options exist including avascular tissue transfer, locoregional tissue flaps, and microvascular free flaps. This paper is a literature review exploring the efficacy of the various reconstructive options, and includes randomized control trials, prospective studies, and retrospective studies from 1999 to 2024. The literature demonstrates that any reconstructive option is superior to no reconstruction in reducing the risk of FS and in improving cosmetic outcomes without increasing the risk of postoperative complications including hematomas and sialoceles. While literature demonstrates that reconstruction is beneficial in parotidectomies, the existing literature does not provide an adequate comparison of options to guide surgeons in making an informed choice.
2025-10-20 | Aesthetic and Functional Outcomes After Superficial Parotidectomy - Comparison of Three Reconstruction Techniques: An Interventional Clinical Study.
Preauricular defects is one of the main concerns after superficial parotidectomy. Plastic surgeons have described many filling techniques to overcome the problem. To discuss and compare the esthetic and functional outcomes of three postsuperficial parotidectomy reconstruction techniques: partial-thickness, superiorly based sternocleidomastoid muscle flap, en-bloc fat grafting, and platelet-rich fibrin gel. We included 29 adult patients submitted to reconstruction after superficial parotidectomy by partial-thickness, superiorly based sternocleidomastoid muscle flap, en-bloc fat grafting, and platelet-rich fibrin gel. A subjective evaluation of the overall facial appearance was conducted through a 5-point visual analog scale filled out by the patient, a close relative, and 3 blind staff members. Regarding the visual analog scale, in the comparison between the three groups (at the sixth and the twelfth months), the fat group reported the highest mean for satisfaction (3.4 ± 1.1 and 3.83 ± 0.97 respectively) and showed a highly-significant difference when compared to the sternocleidomastoid muscle flap and the platelet-rich fibrin gel groups ( p = 0.0001 and 0.016 respectively). Parotidectomy with immediate reconstruction of the surgical defect with an en-block fat graft provides better esthetic outcomes than sternocleidomastoid muscle flap and platelet-rich fibrin gel after 1 year. The sternocleidomastoid muscle flap and fat techniques resulted in minimal surgical-site morbidity and lower likelihood of developing Frey's syndrome. The fat graft yielded the best degree of cosmetic satisfaction with minimal morbidity. Fat overcorrection is recommended.Level of Evidence : 4.
2025-06-12 | An innovative use of the buccal fat pad in parotidectomy for prevention of facial depression and Frey's syndrome.
The surgical treatment of parotid tumors often leads to complications such as facial depression and Frey's syndrome. Traditional reconstruction techniques, including muscle flaps and dermal-fat grafts, are associated with significant limitations. This technical report explores the innovative use of the buccal fat pad (BFP) as a vascularized graft for restoring facial symmetry and reducing Frey's syndrome risk. Its proximity to the surgical site, consistent vascularity, and minimal donor morbidity make the BFP an ideal reconstructive material. Surgical application in two patients with accessory lobe tumors demonstrated effective restoration of facial contours and defect coverage without complications. The BFP serves as a versatile, biocompatible solution that addresses both aesthetic and functional outcomes, offering a reliable alternative to traditional methods for managing parotidectomy defects.
2025-04-28 | Esthetic and Functional Outcomes of Superficial Parotidectomy Comparing Three Reconstruction Techniques: An Interventional Clinical Study.
Introduction Preauricular defect is one of the main concerns after superficial parotidectomy. Plastic surgeons have described many filling techniques to overcome the problem. Objective To discuss three reconstruction techniques after superficial parotidectomy: partial-thickness, superiorly based sternocleidomastoid muscle flap; en-bloc fat graft; and platelet-rich fibrin gel, with a comparison of aesthetic and functional outcomes. Methods The present study included 29 adult patients submitted to reconstruction after superficial parotidectomy by partial-thickness, superiorly based sternocleidomastoid muscle flap, en-bloc fat graft, and platelet-rich fibrin gel. A subjective evaluation of the facial nerve functions was conducted through a visual analog scale (VAS) with scores from 0 to 5, which was completed by the patient, a close relative, and 3 blinded staff members. Results Regarding the VAS, in the comparison of the 3 groups at the sixth and twelfth postoperative months, the fat-graft group reported the highest mean values for satisfaction (3.4 ± 1.1 and 3.83 ± 0.97 respectively). The fat-graft group also showed highly significant differences when compared with the groups submitted to the sternocleidomastoid muscle flap ( p = 0.0001) and the platelet-rich fibrin gel techniques ( p = 0.016). Conclusion Parotidectomy with immediate reconstruction of the surgical defect through an en-block fat graft provides better esthetic outcomes than sternocleidomastoid muscle flap and platelet-rich fibrin gel after one year. The patients submitted to the sternocleidomastoid muscle flap and fat-graft techniques reported minimal surgical site morbidity and a lower chance of developing Frey syndrome. The fat graft resulted in the best degree of cosmetic satisfaction, with minimal morbidity. Fat overcorrection is recommended.
2024-12-02 | Management of Aesthetical and Functional Complications after Total Parotidectomy. First Long-Term Experiences with Dermal Matrix Surgimend ® in Patient Affected by Malignant Parotid Tumors.
This is an observational cohort study on patients affected by malignant parotid tumors treated with total parotidectomy. The aim of our work is to analyze and compare the effects and complications after parotidectomy, using or not SurgiMend ®. 40 patients were retrospectively enrolled between September 2014 and June 2020. Basing on the placement of SurgiMend ® for parotid lodge reconstruction, the samples were divided into two groups. Thus, the incidence rate of complications after the surgical procedure was analyzed between the two groups. Patients in whom SurgiMend ® was used reported a lower rate of complications. The ANOVA test (p = 0.05) revealed a significant difference of Vancouver Scar Scale (VSS) between the two groups, representation as vascularity and pigmentation improvement, changing scar color, scar height reduction, and increased pliability. Although many techniques are available to fill the parotidectomy defect, improve facial contour and prevent Frey's syndrome, the use of SurgiMend ® matrix is one of most effective and reliable method to address these complications, with the advantage of decreased operative time due to not require an additional surgical donor site.
proteins
2026-06-30 | USE OF BOTULINUM TOXIN IN THE MANAGEMENT OF POST-PAROTIDECTOMY COMPLICATIONS: FREY SYNDROME, SIALOCELE AND SALIVARY FISTULA
Background: Parotidectomy is a commonly performed procedure associated with postoperative complications such as Frey syndrome, sialocele, and salivary fistula, which may significantly impair patient quality of life and require additional management. Botulinum toxin is increasingly used as a minimally invasive therapeutic option in this setting. Aim: The aim of this study was to evaluate current evidence regarding the use of botulinum toxin in the prevention and treatment of complications following parotidectomy. Material and methods: This study was designed as a narrative review based on previously published scientific literature. A comprehensive search of PubMed, Scopus, and Google Scholar databases was conducted, including studies published up to 2025. Articles addressing the use of botulinum toxin in Frey syndrome, sialocele, and salivary fistula were included and analyzed qualitatively. Results: The reviewed studies consistently demonstrated high clinical effectiveness of botulinum toxin in the management of post-parotidectomy complications. In Frey syndrome, most patients achieved substantial or complete reduction of gustatory sweating, with therapeutic effects typically lasting 6–12 months. In cases of sialocele and salivary fistula, botulinum toxin reduced salivary secretion, promoted lesion closure, and shortened recovery time compared to conservative management. Reported adverse effects were uncommon and generally mild and transient. Conclusions: Botulinum toxin is an effective and safe option in the management of post-parotidectomy complications. Despite the need for repeated administration in some cases, it represents a minimally invasive alternative to surgical treatment. Further prospective studies are required to establish standardized protocols and long-term outcomes.
2026-06-29 | Botulinum Toxin A in Frey Syndrome: An Integrated Review of Diagnosis, Treatment Technique, and Clinical Outcomes
Background: Frey syndrome, also known as auriculotemporal syndrome or gustatory sweating, is a benign but socially distressing condition characterized by sweating, flushing, warmth, or erythema over the preauricular, temporal, or cheek region during eating. It most commonly follows parotidectomy or trauma involving the parotid region. Its pathophysiology is generally attributed to aberrant regeneration of parasympathetic fibers toward sweat glands and cutaneous vessels rather than salivary tissue. Objective: This article synthesizes the supplied case reports, technical guidance, and their consolidated bibliography to present a practical, evidence-informed article on the diagnosis and management of Frey syndrome, with emphasis on botulinum toxin A. Main discussion: The Minor starch-iodine test remains the most useful bedside method for mapping symptomatic sweating. Botulinum toxin A has become the preferred treatment for established Frey syndrome because it is minimally invasive, targeted, repeatable, and generally well tolerated. Published protocols commonly divide the affected region into 1 cm² grids and administer intradermal injections, often around 2 units per cm² for botulinum toxin A, though reported dosing varies by formulation and clinical context. Clinical improvement usually begins within several days and may last months; repeat injections can be used for recurrence. Conclusion: Frey syndrome should be actively recognized after parotid surgery, even when symptoms appear many years later. Botulinum toxin A offers a practical and durable therapeutic option when correctly mapped by Minor’s test and injected intradermally with attention to anatomy, dose, and follow-up
2026-06-09 | Incidence of Frey's syndrome after submandibular gland excision: Minor's test-based evaluation.
To evaluate the incidence and clinical characteristics of Frey's syndrome following submandibular gland excision using objective diagnostic methods. Medical records of 28 patients who underwent submandibular gland excision between January 2016 and December 2018 were reviewed. Frey's syndrome was diagnosed using the Minor's starch-iodine test, and symptom severity was graded according to the Luna-Ortiz scoring system, which incorporates symptom perception, affected area, and sweating intensity. Patients with less than six weeks of follow-up or with a history of head and neck trauma or unrelated surgical procedures were excluded. Frey's syndrome was identified in 3 of 28 patients (10.7%). Two cases were classified as mild (7.1%) and one as severe (3.6%). While one patient reported subjective symptoms, the other two were diagnosed solely through Minor's starch-iodine test. The average time to diagnosis was 31.7 months postoperatively. No association was observed between Frey's syndrome and patient age, sex, or underlying pathology. The severe case responded well to botulinum toxin injection, resulting in complete resolution of symptoms. Although Frey's syndrome is a well-known complication of parotid gland surgery, it may also occur after submandibular gland excision, often in subclinical forms that are easily overlooked. This study highlights the diagnostic value of Minor's starch-iodine test in detecting such cases. Future studies should focus on identifying surgical techniques and patient factors associated with increased risk to guide selective postoperative surveillance and informed patient counseling following submandibular gland excision.
2026-02-15 | Frey's syndrome in an infant misdiagnosed as food allergy.
Frey's syndrome (auriculotemporal syndrome) is characterized by gustatory flushing and sweating in the distribution of the auriculotemporal nerve. Although classically described after parotid surgery in adults, congenital and idiopathic forms are increasingly recognized in infants. Because symptoms occur during feeding, the condition can closely mimic IgE-mediated food allergy, leading to unnecessary dietary restrictions and anxiety. We report an 8-month-old boy referred for evaluation of suspected multiple food allergies after several emergency department visits for feeding-associated facial redness, interpreted by caregivers as "hives", and accompanied by significant parental anxiety and progressive dietary avoidance. On detailed reassessment, reactions were found to consist of localized, unilateral flushing and sweating of the right cheek, without urticaria or systemic features. Skin prick testing and serum-specific IgE testing to common food allergens were negative. During a supervised baked milk oral food challenge, a similar unilateral cutaneous reaction was observed, confirming the diagnosis of Frey's syndrome. A home-recorded video demonstrated comparable findings during feeding with formula. Frey's syndrome is an important and under-recognized mimic of food allergy in infancy. Careful attention to laterality, absence of systemic involvement, and reproducibility across foods can prevent misdiagnosis, reduce unnecessary dietary restriction, and alleviate family anxiety. Frey's syndrome should be considered in infants with reproducible unilateral flushing during feeding. Awareness among allergists can prevent misdiagnosis, reduce unnecessary food avoidance, and support safe nutritional and developmental outcomes.
2025-10-15 | [Benign parotid tumors : Surgery and management of perioperative complications].
Tumors of the parotid gland are rare and predominantly benign. The surgical management is challenging due to the close anatomical relationship to the facial nerve. Pleomorphic adenoma and cystadenolymphoma are among the most frequently occurring lesions. The surgical approach depends on the location, size and suspected diagnosis of the lesion. While radical surgical techniques were favored in the past, current practice emphasizes reducing surgical morbidity through less invasive resection methods. In this context, extracapsular dissection offers functional advantages over more extensive resections, with similarly low recurrence rates. Complications such as facial nerve palsy, salivary fistulas and Frey's syndrome occur less frequently with milder severity and are generally well-treatable, for example, with botulinum toxin. In selected cases, such as confirmed bilateral cystadenolymphoma, a conservative wait-and-scan approach may be considered as an alternative to surgery. The goal remains the complete resection of the lesion with maximum preservation of function.
small molecules
2026-05-30 | A Case Report of a Patient with Delayed Recovery from Peripheral Facial Palsy Treated with <italic>Gami-Soyo-san</italic> (加味逍遙散) and Facial Acupuncture
Introduction: Peripheral facial palsy with delayed recovery beyond 3 months is associated with reduced rates of complete spontaneous recovery, particularly in older adults with metabolic comorbidities. This report presents a case of integrative Korean medicine treatment for persistent peripheral facial palsy with delayed recovery, in which long-standing suspected Frey’s syndrome also improved.Case Presentation: An 81-year-old woman with diabetes and dyslipidemia presented with right peripheral facial palsy of 4 months’ duration. She also reported gustatory sweating suggestive of Frey’s syndrome that had persisted for approximately 19 years following parotidectomy in 2005. The patient received 56 sessions of manual acupuncture combined with oral Gami-Soyo-san (加味逍遙散) extract granules over 5 months at a public health center branch. The House-Brackmann grade improved from V to II, and the Yanagihara score increased from 17 to 26. The suspected Frey’s syndrome symptoms subjectively improved after approximately 4 weeks, with severity decreasing from 10 to below 5 on a self-rated 10-point scale. Mild subjective synkinesis appeared at week 9 and was considered a natural sequela of aberrant reinnervation. No adverse events were observed. At telephone follow-up 3 months after treatment completion, the clinical improvement was reported to be maintained.Discussion: This case suggests that integrative Korean medicine treatment may be associated with a favorable clinical course in persistent peripheral facial palsy with delayed recovery in a primary care setting, with concurrent improvement in long-standing suspected Frey’s syndrome as a secondary finding. Further case accumulation and prospective studies incorporating objective measures are warranted.
2025-03-31 | Frey syndrome after surgery for the treatment of temporomandibular joint ankylosis: case report
Introduction: Frey's syndrome is characterized by signs of flushing and sweating in the preauricular region following gustatory stimuli. There are few reports in the literature regarding the development of Frey’s syndrome after temporomandibular joint surgeries, and the incidence following such surgeries is uncertain. Case report: A 9-year-old patient was diagnosed with ankylosis of the left temporomandibular joint, following a left condylar fracture that occurred three years prior. The patient underwent Puricelli biconvex arthroplasty as treatment for the ankylosis. Two and a half years after the intervention, the patient developed signs of flushing, sweating, and erythema in the left preauricular region during meals. The proposed treatment involved the topical application of antiperspirant agents containing aluminum chloride, resulting in improvement of the symptoms reported by the patient. Conclusion: Patients should be informed about the risk of developing Frey’s syndrome following open temporomandibular joint surgeries, and further studies are needed to assess the likelihood of this condition occurring.
2023-12-08 | Botulinum Toxin Treatment for Cancer-Related Disorders: A Systematic Review
This systematic review investigates the effect of botulinum neurotoxin (BoNT) therapy on cancer-related disorders. A major bulk of the literature is focused on BoNT’s effect on pain at the site of surgery or radiation. All 13 published studies on this issue indicated reduction or cessation of pain at these sites after local injection of BoNTs. Twelve studies addressed the effect of BoNT injection into the pylorus (sphincter between the stomach and the first part of the gut) for the prevention of gastroparesis after local resection of esophageal cancer. In eight studies, BoNT injection was superior to no intervention; three studies found no difference between the two approaches. One study compared the result of intra-pyloric BoNT injection with preventive pyloromyotomy (resection of pyloric muscle fibers). Both approaches reduced gastroparesis, but the surgical approach had more serious side effects. BoNT injection was superior to saline injection in the prevention of esophageal stricture after surgery (34% versus 6%, respectively, p = 0.02) and produced better results (30% versus 40% stricture) compared to steroid (triamcinolone) injection close to the surgical region. All 12 reported studies on the effect of BoNT injection into the parotid region for the reduction in facial sweating during eating (gustatory hyperhidrosis) found that BoNT injections stopped or significantly reduced facial sweating that developed after parotid gland surgery. Six studies showed that BoNT injection into the parotid region prevented the development of or healed the fistulas that developed after parotid gland resection—parotidectomy gustatory hyperhidrosis (Frey syndrome), post-surgical parotid fistula, and sialocele. Eight studies suggested that BoNT injection into masseter muscle reduced or stopped severe jaw pain after the first bite (first bite syndrome) that may develop as a complication of parotidectomy.
2023-11-09 | Treatment of Frey Syndrome with Botulinum Toxin-A: A Practical Approach from Minor’s Test to Injection
Abstract Introduction Frey's syndrome, described by Lucy Frey in 1923, is a unique condition characterized by sweating, flushing, and reddening as a direct response to mastication. This phenomenon results from the aberrant regeneration of postganglionic parasympathetic neurons originating from the auriculotemporal nerve and the subsequent acetylcholine secretion induced by masticatory stimuli. Although rare, this syndrome can have multiple underlying causes and is frequently observed, occurring in up to 65% of cases following lateral parotid resections. Additionally, it can less commonly manifest after neck dissection, facelift procedures, or be associated with diabetes mellitus. Method This article outlines a comprehensive diagnostic algorithm for Frey's syndrome, which includes the utilization of the Minor-Starch-Iodine Test. This test is a key component in diagnosing the syndrome and is discussed in detail, providing insights into its procedure and interpretation. Additionally, the gold standard of treatment for established Frey's syndrome, botulinum toxin A, is thoroughly described, including its mechanism of action, administration, and potential side effects. Discussion Finally, the article underscores the need for further research to enhance our understanding of Frey's syndrome, leading to better diagnostic methods and more tailored treatment options for patients.
2023-05-08 | The Minor's test in Frey syndrome treated with botulinum toxin: Methodology and efficacy.
In this paper, we aimed at methodologically presenting a video-case of Frey Syndrome occurred after parotidectomy, assessed by means of Minor's Test and treated with intradermic botulinum toxin A (BoNT-A) injection. Although largely described in the literature, a detailed explanation of both the procedures has not been previously elucidated. In a more original approach, we also highlighted the role of the Minor's test in identifying the most affected skin areas and new insight on the patient-tailored approach provided by multiple injections of botulinum toxin. Six months after the procedure, the patient's symptoms were resolved, and no evident signs of Frey syndrome were detectable through the Minor's test.
cell therapies
2026-02-23 | Soft tissue augmentation options for volume replacement following parotidectomy: A review of the literature.
Salivary gland tumors primarily arise in the parotid gland with surgery representing the cornerstone of treatment. Parotidectomies often lead to a soft tissue deficit that may benefit from reconstruction to reduce incidence of Frey's syndrome, improve aesthetic outcomes, and allow for appropriate postoperative therapies. Several options exist including avascular tissue transfer, locoregional tissue flaps, and microvascular free flaps. This paper is a literature review exploring the efficacy of the various reconstructive options, and includes randomized control trials, prospective studies, and retrospective studies from 1999 to 2024. The literature demonstrates that any reconstructive option is superior to no reconstruction in reducing the risk of FS and in improving cosmetic outcomes without increasing the risk of postoperative complications including hematomas and sialoceles. While literature demonstrates that reconstruction is beneficial in parotidectomies, the existing literature does not provide an adequate comparison of options to guide surgeons in making an informed choice.
2025-10-20 | Aesthetic and Functional Outcomes After Superficial Parotidectomy - Comparison of Three Reconstruction Techniques: An Interventional Clinical Study.
Preauricular defects is one of the main concerns after superficial parotidectomy. Plastic surgeons have described many filling techniques to overcome the problem. To discuss and compare the esthetic and functional outcomes of three postsuperficial parotidectomy reconstruction techniques: partial-thickness, superiorly based sternocleidomastoid muscle flap, en-bloc fat grafting, and platelet-rich fibrin gel. We included 29 adult patients submitted to reconstruction after superficial parotidectomy by partial-thickness, superiorly based sternocleidomastoid muscle flap, en-bloc fat grafting, and platelet-rich fibrin gel. A subjective evaluation of the overall facial appearance was conducted through a 5-point visual analog scale filled out by the patient, a close relative, and 3 blind staff members. Regarding the visual analog scale, in the comparison between the three groups (at the sixth and the twelfth months), the fat group reported the highest mean for satisfaction (3.4 ± 1.1 and 3.83 ± 0.97 respectively) and showed a highly-significant difference when compared to the sternocleidomastoid muscle flap and the platelet-rich fibrin gel groups ( p = 0.0001 and 0.016 respectively). Parotidectomy with immediate reconstruction of the surgical defect with an en-block fat graft provides better esthetic outcomes than sternocleidomastoid muscle flap and platelet-rich fibrin gel after 1 year. The sternocleidomastoid muscle flap and fat techniques resulted in minimal surgical-site morbidity and lower likelihood of developing Frey's syndrome. The fat graft yielded the best degree of cosmetic satisfaction with minimal morbidity. Fat overcorrection is recommended.Level of Evidence : 4.
2025-06-12 | An innovative use of the buccal fat pad in parotidectomy for prevention of facial depression and Frey's syndrome.
The surgical treatment of parotid tumors often leads to complications such as facial depression and Frey's syndrome. Traditional reconstruction techniques, including muscle flaps and dermal-fat grafts, are associated with significant limitations. This technical report explores the innovative use of the buccal fat pad (BFP) as a vascularized graft for restoring facial symmetry and reducing Frey's syndrome risk. Its proximity to the surgical site, consistent vascularity, and minimal donor morbidity make the BFP an ideal reconstructive material. Surgical application in two patients with accessory lobe tumors demonstrated effective restoration of facial contours and defect coverage without complications. The BFP serves as a versatile, biocompatible solution that addresses both aesthetic and functional outcomes, offering a reliable alternative to traditional methods for managing parotidectomy defects.
2025-04-28 | Esthetic and Functional Outcomes of Superficial Parotidectomy Comparing Three Reconstruction Techniques: An Interventional Clinical Study.
Introduction Preauricular defect is one of the main concerns after superficial parotidectomy. Plastic surgeons have described many filling techniques to overcome the problem. Objective To discuss three reconstruction techniques after superficial parotidectomy: partial-thickness, superiorly based sternocleidomastoid muscle flap; en-bloc fat graft; and platelet-rich fibrin gel, with a comparison of aesthetic and functional outcomes. Methods The present study included 29 adult patients submitted to reconstruction after superficial parotidectomy by partial-thickness, superiorly based sternocleidomastoid muscle flap, en-bloc fat graft, and platelet-rich fibrin gel. A subjective evaluation of the facial nerve functions was conducted through a visual analog scale (VAS) with scores from 0 to 5, which was completed by the patient, a close relative, and 3 blinded staff members. Results Regarding the VAS, in the comparison of the 3 groups at the sixth and twelfth postoperative months, the fat-graft group reported the highest mean values for satisfaction (3.4 ± 1.1 and 3.83 ± 0.97 respectively). The fat-graft group also showed highly significant differences when compared with the groups submitted to the sternocleidomastoid muscle flap ( p = 0.0001) and the platelet-rich fibrin gel techniques ( p = 0.016). Conclusion Parotidectomy with immediate reconstruction of the surgical defect through an en-block fat graft provides better esthetic outcomes than sternocleidomastoid muscle flap and platelet-rich fibrin gel after one year. The patients submitted to the sternocleidomastoid muscle flap and fat-graft techniques reported minimal surgical site morbidity and a lower chance of developing Frey syndrome. The fat graft resulted in the best degree of cosmetic satisfaction, with minimal morbidity. Fat overcorrection is recommended.
2024-12-02 | Management of Aesthetical and Functional Complications after Total Parotidectomy. First Long-Term Experiences with Dermal Matrix Surgimend ® in Patient Affected by Malignant Parotid Tumors.
This is an observational cohort study on patients affected by malignant parotid tumors treated with total parotidectomy. The aim of our work is to analyze and compare the effects and complications after parotidectomy, using or not SurgiMend ®. 40 patients were retrospectively enrolled between September 2014 and June 2020. Basing on the placement of SurgiMend ® for parotid lodge reconstruction, the samples were divided into two groups. Thus, the incidence rate of complications after the surgical procedure was analyzed between the two groups. Patients in whom SurgiMend ® was used reported a lower rate of complications. The ANOVA test (p = 0.05) revealed a significant difference of Vancouver Scar Scale (VSS) between the two groups, representation as vascularity and pigmentation improvement, changing scar color, scar height reduction, and increased pliability. Although many techniques are available to fill the parotidectomy defect, improve facial contour and prevent Frey's syndrome, the use of SurgiMend ® matrix is one of most effective and reliable method to address these complications, with the advantage of decreased operative time due to not require an additional surgical donor site.
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2026-06-30 | USE OF BOTULINUM TOXIN IN THE MANAGEMENT OF POST-PAROTIDECTOMY COMPLICATIONS: FREY SYNDROME, SIALOCELE AND SALIVARY FISTULA
Background: Parotidectomy is a commonly performed procedure associated with postoperative complications such as Frey syndrome, sialocele, and salivary fistula, which may significantly impair patient quality of life and require additional management. Botulinum toxin is increasingly used as a minimally invasive therapeutic option in this setting. Aim: The aim of this study was to evaluate current evidence regarding the use of botulinum toxin in the prevention and treatment of complications following parotidectomy. Material and methods: This study was designed as a narrative review based on previously published scientific literature. A comprehensive search of PubMed, Scopus, and Google Scholar databases was conducted, including studies published up to 2025. Articles addressing the use of botulinum toxin in Frey syndrome, sialocele, and salivary fistula were included and analyzed qualitatively. Results: The reviewed studies consistently demonstrated high clinical effectiveness of botulinum toxin in the management of post-parotidectomy complications. In Frey syndrome, most patients achieved substantial or complete reduction of gustatory sweating, with therapeutic effects typically lasting 6–12 months. In cases of sialocele and salivary fistula, botulinum toxin reduced salivary secretion, promoted lesion closure, and shortened recovery time compared to conservative management. Reported adverse effects were uncommon and generally mild and transient. Conclusions: Botulinum toxin is an effective and safe option in the management of post-parotidectomy complications. Despite the need for repeated administration in some cases, it represents a minimally invasive alternative to surgical treatment. Further prospective studies are required to establish standardized protocols and long-term outcomes.
2026-06-29 | Botulinum Toxin A in Frey Syndrome: An Integrated Review of Diagnosis, Treatment Technique, and Clinical Outcomes
Background: Frey syndrome, also known as auriculotemporal syndrome or gustatory sweating, is a benign but socially distressing condition characterized by sweating, flushing, warmth, or erythema over the preauricular, temporal, or cheek region during eating. It most commonly follows parotidectomy or trauma involving the parotid region. Its pathophysiology is generally attributed to aberrant regeneration of parasympathetic fibers toward sweat glands and cutaneous vessels rather than salivary tissue. Objective: This article synthesizes the supplied case reports, technical guidance, and their consolidated bibliography to present a practical, evidence-informed article on the diagnosis and management of Frey syndrome, with emphasis on botulinum toxin A. Main discussion: The Minor starch-iodine test remains the most useful bedside method for mapping symptomatic sweating. Botulinum toxin A has become the preferred treatment for established Frey syndrome because it is minimally invasive, targeted, repeatable, and generally well tolerated. Published protocols commonly divide the affected region into 1 cm² grids and administer intradermal injections, often around 2 units per cm² for botulinum toxin A, though reported dosing varies by formulation and clinical context. Clinical improvement usually begins within several days and may last months; repeat injections can be used for recurrence. Conclusion: Frey syndrome should be actively recognized after parotid surgery, even when symptoms appear many years later. Botulinum toxin A offers a practical and durable therapeutic option when correctly mapped by Minor’s test and injected intradermally with attention to anatomy, dose, and follow-up
2026-06-09 | Incidence of Frey's syndrome after submandibular gland excision: Minor's test-based evaluation.
To evaluate the incidence and clinical characteristics of Frey's syndrome following submandibular gland excision using objective diagnostic methods. Medical records of 28 patients who underwent submandibular gland excision between January 2016 and December 2018 were reviewed. Frey's syndrome was diagnosed using the Minor's starch-iodine test, and symptom severity was graded according to the Luna-Ortiz scoring system, which incorporates symptom perception, affected area, and sweating intensity. Patients with less than six weeks of follow-up or with a history of head and neck trauma or unrelated surgical procedures were excluded. Frey's syndrome was identified in 3 of 28 patients (10.7%). Two cases were classified as mild (7.1%) and one as severe (3.6%). While one patient reported subjective symptoms, the other two were diagnosed solely through Minor's starch-iodine test. The average time to diagnosis was 31.7 months postoperatively. No association was observed between Frey's syndrome and patient age, sex, or underlying pathology. The severe case responded well to botulinum toxin injection, resulting in complete resolution of symptoms. Although Frey's syndrome is a well-known complication of parotid gland surgery, it may also occur after submandibular gland excision, often in subclinical forms that are easily overlooked. This study highlights the diagnostic value of Minor's starch-iodine test in detecting such cases. Future studies should focus on identifying surgical techniques and patient factors associated with increased risk to guide selective postoperative surveillance and informed patient counseling following submandibular gland excision.
2026-02-15 | Frey's syndrome in an infant misdiagnosed as food allergy.
Frey's syndrome (auriculotemporal syndrome) is characterized by gustatory flushing and sweating in the distribution of the auriculotemporal nerve. Although classically described after parotid surgery in adults, congenital and idiopathic forms are increasingly recognized in infants. Because symptoms occur during feeding, the condition can closely mimic IgE-mediated food allergy, leading to unnecessary dietary restrictions and anxiety. We report an 8-month-old boy referred for evaluation of suspected multiple food allergies after several emergency department visits for feeding-associated facial redness, interpreted by caregivers as "hives", and accompanied by significant parental anxiety and progressive dietary avoidance. On detailed reassessment, reactions were found to consist of localized, unilateral flushing and sweating of the right cheek, without urticaria or systemic features. Skin prick testing and serum-specific IgE testing to common food allergens were negative. During a supervised baked milk oral food challenge, a similar unilateral cutaneous reaction was observed, confirming the diagnosis of Frey's syndrome. A home-recorded video demonstrated comparable findings during feeding with formula. Frey's syndrome is an important and under-recognized mimic of food allergy in infancy. Careful attention to laterality, absence of systemic involvement, and reproducibility across foods can prevent misdiagnosis, reduce unnecessary dietary restriction, and alleviate family anxiety. Frey's syndrome should be considered in infants with reproducible unilateral flushing during feeding. Awareness among allergists can prevent misdiagnosis, reduce unnecessary food avoidance, and support safe nutritional and developmental outcomes.
2025-10-15 | [Benign parotid tumors : Surgery and management of perioperative complications].
Tumors of the parotid gland are rare and predominantly benign. The surgical management is challenging due to the close anatomical relationship to the facial nerve. Pleomorphic adenoma and cystadenolymphoma are among the most frequently occurring lesions. The surgical approach depends on the location, size and suspected diagnosis of the lesion. While radical surgical techniques were favored in the past, current practice emphasizes reducing surgical morbidity through less invasive resection methods. In this context, extracapsular dissection offers functional advantages over more extensive resections, with similarly low recurrence rates. Complications such as facial nerve palsy, salivary fistulas and Frey's syndrome occur less frequently with milder severity and are generally well-treatable, for example, with botulinum toxin. In selected cases, such as confirmed bilateral cystadenolymphoma, a conservative wait-and-scan approach may be considered as an alternative to surgery. The goal remains the complete resection of the lesion with maximum preservation of function.
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Drug Discovery Landscape
1 orphan drug designation for Frey syndrome.
1 orphan drug designation for Frey syndrome.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
glycopyrrolate 2% | small molecules | FDA | — | Wellesley Therapeutics, Inc. |
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