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Frey Syndrome
Introduction
Frey syndrome, also known as Baillarger’s syndrome, auriculotemporal syndrome, Dupuy syndrome, or gustatory hyperhidrosis, represents aberrant reinnervation following injury to the auriculotemporal nerve. The auriculotemporal nerve, a branch of the trigeminal nerve, consists of parasympathetic fibers that signal the parotid gland to produce saliva and sympathetic fibers that innervate the sweat glands of the face and scalp. When an insult to the parasympathetic and sympathetic nerve fibers of the auriculotemporal nerve in the parotid region occurs, the resulting aberrant regeneration of post-ganglionic parasympathetic nerve fibers (responsible for salivary secretion) along the pre-existing sympathetic pathways to the vessels and sweat glands of the skin leads to the development of Frey syndrome.[1][2] Patients with Frey syndrome often present with facial warmth, flushing, and sweating in the territory of the auriculotemporal nerve overlying the parotid gland, which may include the preauricular skin, the temporal skin, the scalp, and the temporomandibular joint region.[3] Symptoms occur during meals, especially with spicy and sour foods.[4] Frey syndrome most commonly arises as a complication of parotidectomy. Still, it can also be associated with submandibular gland surgery, repair of mandibular fractures, temporomandibular joint injury, neck lymph node dissection, infection, and trauma to the parotid region.[5][6][7]
Dr. Jules Baillarger first reported the phenomenon in 1853, describing 2 patients who underwent incision and drainage for parotid abscesses. The patients later developed facial sweating during meals. At that time, he misinterpreted the facial fluid as saliva overflowing through the skin due to a blocked Stenson’s duct.[1] Previously, Dupuy described gustatory sweating over the cheek area as being related to experimental sectioning of cervical sympathetic nerves in horses around 1816.[1] Then, in 1897, Weber described bilateral gustatory sweating and flushing in a patient who had undergone bilateral parotid abscess drainage, the first reported case of bilateral Frey syndrome.[1] It was not until 1923 that the first accurate description of this phenomenon was provided by Dr. Lucja Frey, a Polish physician and 1 of the first female academic neurologists in Europe. She described a 25-year-old female who sustained a gunshot wound to the parotid region and subsequently developed facial flushing and sweating 5 months afterward. She accurately identified the autonomic innervation of the parotid gland and the auriculotemporal nerve as the link between gustatory stimulation and facial sweat production.[1] In 1927, Dr. Andre Thomas theorized that the pathophysiology of the disease involved aberrant nerve regeneration.[1] Five years later, Dr. Peter Bassoe reported the first case of Frey syndrome after a parotidectomy, which has since become the most common cause of the condition.[1]
Etiology
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Etiology
Frey syndrome usually occurs in adults with auriculotemporal nerve injury due to surgical manipulation or trauma in the parotid region. The auriculotemporal nerve consists of 2 roots. The superior somatosensory root arises from the mandibular branch of the trigeminal nerve, providing innervation to the auricle, external auditory canal, temporomandibular joint, lateral tympanic membrane, and temporal scalp. The inferior parasympathetic root arises from the postganglionic fibers at the otic ganglion, originating from the glossopharyngeal nerve; it is responsible for the visceral secretomotor actions of the parotid gland.[8] After the 2 roots join, the auriculotemporal nerve travels posterior to the mandible and parotid, where it gives off the secretomotor parotid branch before coursing across the superior border of the mandibular condyle below the temporomandibular joint and terminating in the temporal region. Frey syndrome can occur if the auriculotemporal nerve is proximal to the parotid branch or the parotid branch is injured.[8][9] More recently, a rare variant characterized by symptoms distal to the parotid region in the temporoparietal scalp has been described, even when the injury occurs in the parotid region.[7]
Salivary gland neoplasms comprise 3-10% of all head and neck tumors and up to 86% of tumors located in the parotid gland.[10][11][12] Parotidectomy is the first-line treatment in patients with salivary gland neoplasms and the most common cause of Frey syndrome in adults.[13][14][15] Other complications after parotidectomy include facial paralysis, face contour asymmetry, scarring, salivary fistula, first bite syndrome, pain and discomfort, xerostomia, and hypoesthesia of the skin innervated by the great auricular nerve.[16][17][18] Larger parotid tumors are associated with more extensive dissection and parasympathetic nerve fiber exposure and damage, resulting in a higher risk for Frey syndrome.[19] Aside from parotidectomy, other causes of Frey syndrome include direct trauma to the parotid region, mandibular condyle fractures, temporomandibular joint fractures, infection, submandibular gland excision, and radical neck dissections.[5][6][9][20][21]
Frey syndrome is less common in children and may occur during early infancy without a history of trauma or surgery. Symptoms usually occur around 5 months and can be misdiagnosed as food allergies since the Frey syndrome appears during the same period as food diversification. It can be distinguished from allergies, especially if there is a history notable for instrumented vaginal delivery, quick onset after a meal compared with allergic reactions, occurrence with specific foods (sweet and sour) not related to common food allergens, rapid recovery without treatment, consistent and persistent location, and absence of other atopic symptoms.[22][3] During traumatic instrumentation delivery using forceps and spatula, the auriculotemporal nerve is more liable to be crushed than severed, resulting in less aberrant nerve regeneration, the absence of sweating in certain patients, and the occasional possibility of recovery.[3] Bilateral symptoms are more likely idiopathic in origin. Familial bilateral Frey syndrome has been described in patients without a history of trauma, leading to the hypothesis that congenital dysfunction of the auriculotemporal nerve is the culprit.[23]
Epidemiology
The published incidence of Frey syndrome after parotidectomy varies from 4% to 96%.[24][25] The wide range of rates reported in the literature reflects great heterogeneity of symptom severity, reporting, and diagnosis.[6][19] The incidence of Frey syndrome approaches 80% in parotidectomy patients based on the Minor starch-iodine test. Still, it ranges from 30% to 60% based on subjective patient reports, indicating that there is likely a population of asymptomatic Frey syndrome patients or patients with non-bothersome symptoms.[26] There do not appear to be age or gender predispositions for the development of Frey syndrome.
Pathophysiology
Frey syndrome is theorized to result from injured parasympathetic axons of the auriculotemporal nerve that undergo aberrant regeneration. The parasympathetic nerve fibers originate from the inferior salivatory nucleus and the glossopharyngeal nerve, pass through the inferior petrosal nerve, and synapse at the otic ganglion. From there, the postganglionic parasympathetic fibers join with the auriculotemporal nerve, which is responsible for the parotid gland's secretomotor control. Signal transduction in postganglionic parasympathetic nerve fibers to the parotid gland occurs via the neurotransmitter acetylcholine acting at muscarinic receptors. The sympathetic nerve fibers in the auriculotemporal nerve are responsible for vasomotor and sweat gland innervation in the overlying skin. Although most postganglionic sympathetic fibers are adrenergic and activated by noradrenaline, the postganglionic sympathetic fibers controlling the sweat glands are cholinergic, like the salivary secretomotor fibers, and are also activated by muscarinic receptors.[27] Both parasympathetic and sympathetic axons of the auriculotemporal nerve can be damaged in trauma or surgical procedures like parotidectomy. Aberrant nerve regeneration can occur, resulting in the postganglionic parasympathetic fibers growing along the sympathetic pathways to cross-innervate the vessels and sweat glands of the face.[28] This causes vessel dilation and sweat production in response to gustatory stimulation.[3][14] Because aberrant nerve regeneration takes time to produce gustatory sweating, the presentation of Frey syndrome is generally delayed by 6 to 18 months after surgery.[29][30]
Frey syndrome can also occur after submandibular excision and neck dissection due to aberrant nerve regeneration after damage to the postganglionic parasympathetic nerve fibers to the submandibular gland, postganglionic parasympathetic fibers to the sublingual gland, or postganglionic parasympathetic fibers arising from the cervical sympathetic ganglia to innervate the sweat glands of the skin.[30] Another theory regarding the development of Frey syndrome is that damaged sympathetic nerve fibers result in increased sweat gland sensitivity, which can then be stimulated by acetylcholine released from adjacent parasympathetic fibers. This theory may be more convincing in cases wherein gustatory sweating occurs shortly after surgery when nerve regeneration has yet to occur.[30]
Histopathology
There is a lack of histopathologic reports regarding Frey syndrome in the literature. An interesting example was published by Redleaf and McCabe of the University of Iowa, wherein they describe a rare case of Frey syndrome of the external auditory canal.[31] A 36-year-old patient had presented with a 6-month history of left watery otorrhea, eventually determined to be sweat, that occurred only with eating. Resection of the canal skin with split-thickness skin graft reconstruction led to the resolution of the symptoms. Histopathologic analysis of the canal skin after hematoxylin and eosin staining revealed marked thickening (4.2 mm compared to 0.8 mm for normal bony canal skin) with hyperplasia and hypertrophy of sweat glands, which are absent in normal bony canal skin. This finding was postulated to be a result of aberrant parasympathetic influence.
History and Physical
Patients with Frey syndrome often have a history of prior parotid surgery, neck surgery, trauma, or infection of the parotid region, although idiopathic and infantile presentations may also occur. After gustatory stimuli, they report unilateral sweating, flushing, neuralgia, pruritus, and warmth over the preauricular and temporal areas, especially with sour and spicy foods.[4][28] The severity of symptoms can range from non-bothersome to mild annoyance to social anxiety and avoidance of eating in public.[29] Symptoms can appear weeks, months, or even years after the initial insult.[3][32][33] The physical examination may show signs of prior surgical intervention or trauma in the parotid region.
Evaluation
Historically, Frey syndrome was a clinical diagnosis based on patients' reports of symptoms. Today, objective methods, such as the Minor starch-iodine test, serve as more sensitive ways of confirming the diagnosis of Frey syndrome.[19] During the Minor test, the affected facial area is painted with iodine. Once dry, starch is applied over the painted area, and the patient is presented with a salivary stimulus, such as a sour candy. If the gustatory stimulus causes activation of the sweat glands, the starch becomes moist and turn blue/brown in the presence of iodine.[29]
Treatment / Management
Preventative Techniques
The main method of preventing Frey syndrome is to create a barrier during surgery that hinders aberrant nerve regeneration between the parasympathetic secretomotor fibers and the sweat glands in the parotid region. Several techniques have been described in the literature; all have associated risks and disadvantages, including creating a donor site, prolonged operative time, variable efficacy in preventing Frey syndrome, wound infection, rejection, and postoperative complications.[24][26] (A1)
- Thick skin flap. Increasing the thickness of the skin flap raised over the parotid gland during surgery by including fat and superficial musculoaponeurotic tissue can theoretically protect the sweat glands and their nerve fibers from being exposed. Because the sweat glands reside at the level of the hair follicles, a thickened flap reduces the chance of their exposure to aberrantly regenerating parasympathetic axons. While some recent studies have shown that increased flap thickness does not significantly lower the incidence of Frey syndrome, there was a trend towards a decrease in the total skin surface area affected and the overall severity of the symptoms.[34][35]
- Acellular dermal matrix (ADM): An extracellular connective tissue graft generated via a decellularization process wherein the cellular components of the dermis are removed. ADMs can be biological barriers between the parotid bed and the overlying skin. Zeng et al utilized an ADM as a barrier between the skin and the operated parotid gland, resulting in a reduction of Frey syndrome by 85% on objective starch-iodine testing and 68% on subjective assessment of symptoms.[17] However, other studies have found the effectiveness of ADM placement in reducing clinical symptoms and positive starch-iodine tests to be mixed.[29][36] Although large-scale studies are still lacking, placing a biological barrier to prevent Frey syndrome may be considered for high-risk patients.[19]
- Autologous fat implantation. This technique is commonly used to alleviate postsurgical contour defects and improve cosmesis in many body parts. Some studies investigating the effect of abdominal fat implantation on preventing Frey syndrome have shown it successful, whereas others have failed to substantiate its usefulness.[16][37][29] Furthermore, the potential for donor site morbidity of an abdominal fat harvest (hematoma, infection, and seroma) may make it a less attractive option for Frey syndrome prophylaxis.
- Superficial muscular aponeurotic system (SMAS) flap: The SMAS is a fascial layer that interdigitates with the facial muscles and protects the facial nerve. During a parotidectomy, the SMAS flap can be elevated separately from the underlying parotid fascia and the overlying dermis, then sutured tightly to the auricular perichondrium and sternocleidomastoid muscle to act as a physical barrier to aberrant innervation of the sweat glands. It can also help improve contour deformities resulting from loss of parotid volume. Bonanno et al found this technique effective in preventing Frey syndrome.[38] Although some studies using the SMAS flap have failed to reproduce these results, others have shown a significant decrease in symptom severity and total skin surface area affected.[39][40][41][42]
- Temporoparietal fascia (TPF) flap: This is a vascularized fascial flap supplied by branches of the superficial temporal artery. The prophylactic placement of a TPF flap between the skin and the defect aims to serve as a physical barrier to the development of Frey syndrome. Sultan et al found that using the TPF flap reduced the contour deformity after parotid surgery and decreased the incidence of Frey syndrome from 17% to 4%.[43] Disadvantages of this technique include an extended skin incision towards the temple, risk to the frontal branch of the facial nerve during flap harvest, and increased operative time.[29]
- Sternocleidomastoid muscle (SCM) flap: The occipital, superior thyroid and suprascapular arteries supply the SCM.[44] Given the heterogeneity of results between studies, its efficacy in preventing Frey syndrome is unclear.[16] Filho et al demonstrated that 24 parotidectomies with SCM flap reconstruction resulted in no Frey syndrome compared to 52.6% and 63.2% by clinical and starch-iodine testing, respectively, in a control group without SCM flap reconstruction.[45] A 2009 meta-analysis by Curry et al also concluded that SCM flaps decrease the incidence of Frey syndrome after parotidectomy.[46] However, other studies have shown that the SCM muscle flap is ineffective at preventing Frey syndrome.[47][48] (A1)
Medical Treatment
Medical therapies for Frey syndrome have included topical antiperspirants and local injections using alcohol, atropine, scopolamine, glycopyrrolate, or botulinum toxin A (BTA).[49][50][51] Since postganglionic cholinergic pathways innervate the sweat glands, treatment has traditionally involved anticholinergics.[27]
- Topical antiperspirants are ineffective in completely controlling gustatory sweating. Studies have shown that less than 50% of patients report any benefits, and for those who do, the duration of improvement is less than a day.[52]
- Injection of alcohol to the otic ganglion has historically been employed. Still, it can result in anesthesia to the mandibular branch of the trigeminal nerve, which can cause even more bothersome symptoms than Frey syndrome.[53] Systemic atropine is not effective in preventing sweating; if anhidrosis occurs with its use, it is usually a sign of atropine overdose, which can also present with other undesirable side effects such as tachycardia, blurred vision, disorientation, respiratory distress, and coma.[49][53] Periodic topical application of scopolamine hydrobromide or glycopyrrolate cream to the affected skin is effective without significant side effects but can be particularly inconvenient for patients.[52][54][55]
- Botulinum toxin is the most widely used agent for local injection, dosing between 1.9 and 2.5 U/cm2 in the involved area.[56][57][58] Botulinum toxin acts as an anticholinergic and blocks acetylcholine release at the neuromuscular junction by breaking down synaptosomal-associated protein 25 (SNAP-25).[59][60] The injection produces chemical denervation and paralysis of striated muscles and sweat glands.[61][62] Peak effects are apparent within 4 to 7 days, and patients report improvement in gustatory sweating, flushing, and overall quality of life.[58][62][63][64] However, the chemical denervation diminishes over time with the absorption of the denatured SNAP-25 and the restoration of the relationship between the nerve ending and the lamina terminalis.[60][65] Thus, repeat injections are often necessary as symptoms can recur in 27% and 92% of patients at 1 and 3 years, respectively.[66] Repeat injections are safe, decrease the area of the affected skin, and increase the symptom-free duration.[58][67][68] (A1)
Surgical Treatment
After its onset, surgical management of Frey syndrome is rarely indicated and is reserved for refractory cases where conservative or medical therapies are no longer effective. Options for surgical management include transection of the auriculotemporal nerve, tympanic nerve, glossopharyngeal nerve, or greater auricular nerve, the placement of a barrier, and excision of the affected skin with grafting for the defect.[55] Sectioning of the auriculotemporal nerve in a previously operated field can be technically challenging. In addition, the auriculotemporal nerve can regenerate, which may ultimately reduce any initial benefits obtained.[49][53][69] Many patients and surgeons feel that the risk of an intracranial procedure to divide the glossopharyngeal nerve is not justified for a benign entity such as Frey syndrome.[49][53][69] Excision of the affected skin can create an unacceptable cosmetic defect for patients.[55] Dai et al reported a study of 17 patients with Frey syndrome who underwent SCM and temporalis fascia transposition, with 53% of patients showing complete resolution on starch-iodine testing and a reduction in the affected skin surface area from 12.80 cm2 to 1.32 cm2.[70] However, disadvantages include the need for a second operation, flap failure, poor cosmesis, and risk to the facial nerve. Placement of ADM, autologous fat, and TPF flaps can also be used as treatment methods and are not solely limited to prevention.[71][72](B2)
Jacobson’s neurectomy, which involves resectioning the tympanic nerve (a branch of the glossopharyngeal nerve), can be performed by raising a tympanomeatal flap inferiorly and identifying Jacobson’s nerve as it emerges from the inferior tympanic canaliculus, coursing across the promontory anterior to the round window. The nerve is sectioned, and the canaliculus is obliterated to prevent the regeneration of the nerve fibers.[53][55] Limited studies have shown relief of gustatory sweating in up to 82% of cases but without complete resolution.[52][55] Other parasympathetic innervation to the parotid is believed to exist and is responsible for this incomplete response. Two potential pathways postulated include 1) a connection between the chorda tympani and the otic ganglion or the facial nerve and 2) a connection between the greater superficial petrosal nerve and the lesser petrosal nerve.[69] Resection of the chorda tympani, in addition to Jacobson’s neurectomy, does increase the rate of gustatory sweating control but results in unilateral denervation of the major salivary glands and xerostomia as well as loss of taste sensation on the ipsilateral anterior two-thirds of the tongue. Thus, the division of the chorda tympani should only be offered to patients with debilitating, persistent gustatory sweating after Jacobson’s neurectomy.(A1)
Differential Diagnosis
- Food allergy. In children, Frey syndrome can present during early infancy at the same time as food diversification and be mistaken for food allergies. It can be distinguished from allergies predominantly if there is rapid onset after a meal compared with allergy reactions, specific food triggers (sweet and sour) unrelated to common food allergens, rapid recovery without allergy treatment, symptoms localized to the parotid region, and absence of other atopic symptoms. Frey syndrome should also be suspected if there is a history of instrumentation during delivery.[3]
- Hyperhidrosis. Primary hyperhidrosis is an autonomic disorder that affects 0.6-1% of the population.[73] Most cases are idiopathic, and patients usually present with at least 6 months of excessive bilateral and symmetrical sweating, age younger than 25 years old, family history, or cessation of sweating during sleep.[74][75] Secondary hyperhidrosis can be induced by drugs, toxins, thyroid dysfunction, pituitary dysfunction, metabolic disorders, malignancy, central nervous system dysfunction, and congenital disorders such as Riley-Day syndrome.[74][76]
- Emotional stimuli activate emotional sweating and affect primarily the palms, soles, and sometimes the axilla. It does not occur when the patient is sleeping or sedated.[76]
- Compensatory hyperhidrosis is a sequela of thoracic sympathectomy. Sympathectomy is used to treat primary hyperhidrosis but can disrupt the thermoregulatory function of the sympathetic nervous system; this results in uncontrolled sweating in untreated areas, usually below the level of the sympathectomy.[76]
- Gustatory tearing (crocodile tears or Bogorad syndrome) presents with unilateral tearing in response to gustatory stimuli. It is commonly associated with recovery from facial paralysis, Duane syndrome, and trauma. It is theorized that damage to facial and glossopharyngeal nerve fibers leads to aberrant nerve regeneration of the postganglionic parasympathetic secretomotor nerve fibers along the greater superficial petrosal nerve, which sends branches to the lacrimal gland. Treatment involves subtotal lacrimal gland excision, anticholinergics, transection of the facial or glossopharyngeal nerves, alcohol injection to the sphenopalatine ganglion, or botulinum toxin injection into the lacrimal gland.[77][78]
- Gustatory rhinorrhea has a similar etiology to gustatory tearing. After trauma, the postganglionic parasympathetic secretomotor fibers that innervate the parotid gland undergo aberrant regeneration and grow along the greater superficial petrosal nerve and Vidian nerve, which innervates not only the lacrimal glands but also the glands of the nasal and palatine mucosa. This results in patients presenting with unilateral rhinorrhea in response to gustatory stimuli.[79]
- First bite syndrome is yet another nerve injury syndrome in which damaged postganglionic sympathetic fibers cannot modulate parasympathetic-mediated supramaximal myoepithelial cell contraction, which can cause pain with eating and drinking; the pain is typically most noticeable at the beginning of a meal and fades rapidly after that. First bite syndrome is most commonly seen following parotid and parapharyngeal surgery but may occur in carotid endarterectomy and face lifting as well.[80][81][82]
Treatment Planning
Frey syndrome usually occurs after parotid surgery. Asymptomatic patients do not require any intervention.[19] When possible, prophylactic barriers should be employed during surgery, particularly for high-risk patients, including those with large (>4 cm) parotid tumors or extensive parotid injury.[19][26] Patients who present with postoperative gustatory sweating should be treated initially with conservative medical management. Topical antiperspirants and anticholinergic ointments can provide symptomatic relief with minimal systemic side effects but require frequent applications.[52][55]
Serial botulinum toxin injections provide an extended duration of control without the need for frequent re-applications, as is required with antiperspirant and anticholinergic ointments.[58][66] If patients have persistent or refractory symptoms to medical management, surgical options, including Jacobsen’s neurectomy, chorda tympani resection, muscle flap reconstruction, or excision of involved skin with graft reconstruction, may be offered to the patient. Patients should be counseled that surgical intervention has a higher risk of complications such as xerostomia, facial nerve injury, flap rejection, and cosmetic defects.[24][55][70]
Toxicity and Adverse Effect Management
Although topical anticholinergic use has been found to have no significant side effects, anticholinergic agents can be extremely toxic if ingested. Symptoms may include delirium, hallucinations, and coma. In addition, their use is contraindicated in patients with narrow-angle glaucoma.[52] Botulinum toxin injection may result in facial muscle weakness/paralysis, eyelid ptosis, localized pain, edema, erythema, and ecchymosis.[83] It is contraindicated in patients with motor neuron disease, myasthenia gravis, Eaton-Lambert syndrome, neuropathies, psychological instability, history of an allergic reaction to the toxin or albumin, pregnancy, and infection at the affected skin site.[84]
Prognosis
Frey syndrome is a benign condition and tends not to progress once established. Asymptomatic patients are rarely treated and are studied only for academic purposes.[19] Most patients with symptoms can be treated effectively with conservative medical management, including topical antiperspirants, anticholinergics, and botulinum toxin. Those with severe or refractory cases can be treated with surgery.[29] In children, spontaneous symptom regression occurs in 69% of unilateral presentations. The bilateral form is usually unrelated to postnatal trauma and resolves during the first year of life in 58% of patients.[3]
Complications
Although no significant medical complications are associated with Frey syndrome, it can significantly reduce the patient's quality of life. Subjective perception and discomfort associated with Frey syndrome can persist beyond 5 years after surgery.[85] Quality of life questionnaires showed a statistically significant correlation between decreased social functioning, economic difficulties, speech defects, reduced sexuality, poor oral nutrition, and Frey syndrome.[86]
Consultations
Frey syndrome is a complication that results from aberrant axonal regeneration that triggers sweating via stimulation of axons that originally controlled salivary secretomotor function. Diagnosis and management are improved through the cooperation of an interprofessional team, including an otolaryngologist, primary care provider, nurse, and pharmacist.
Deterrence and Patient Education
Frey syndrome is often seen as a minor complication, and surgeons frequently underestimate its significance to patients. When surveyed, many patients do not recall being adequately educated on the risk of developing Frey syndrome after parotid surgery.[19] Preoperative counseling and education regarding Frey syndrome are critical during the informed consent process to ensure a timely diagnosis, initiate proper treatment, and manage patients' perioperative expectations. Postoperative symptoms of facial warmth, flushing, and sweating in the setting of acidic or spicy foods should be reported to the operating surgeon. The social impact of Frey syndrome should not be overlooked. In a questionnaire given to patients who underwent parotidectomy for benign salivary diseases, gustatory sweating was identified as the most serious and concerning complication. Patients reported reduced quality of life, difficulty enjoying meals, and overall discomfort that worsened over time.[19][85] Early patient education and timely diagnosis and treatment are key to alleviating and addressing the associated social concerns.
Enhancing Healthcare Team Outcomes
Patients with Frey syndrome should be managed in consultation with an interprofessional team comprising otolaryngologists, plastic surgeons, dermatologists, neurologists, primary clinicians, nurses, pharmacists, and allergy specialists. Patients at high risk for developing Frey syndrome, such as those with large parotid tumors or extensive trauma to the parotid region, may benefit from prophylactic surgical reconstruction to prevent aberrant nerve regeneration. Without surgical or traumatic history, primary care providers and allergists should closely follow and evaluate children with gustatory sweating to rule out food hypersensitivity. As the onset of Frey syndrome can be delayed for months to years after surgery or injury, primary clinicians must remain vigilant for its development and refer patients back to the operating surgeon in a prompt manner. Collaboration among dermatologists, otolaryngologists, and plastic surgeons can provide patients with first-line conservative medical treatment such as topical antiperspirants, anticholinergics, botulinum toxin injections, or a surgical solution if necessary. Finally, since patients may develop social anxiety and avoidance due to the visible presentation of the condition, especially in public settings, formal peer support groups can aid patients in addressing their concerns.
References
Dulguerov P, Marchal F, Gysin C. Frey syndrome before Frey: the correct history. The Laryngoscope. 1999 Sep:109(9):1471-3 [PubMed PMID: 10499057]
Dulguerov P, Marchal F, Gysin C. The bullet that hit a nerve: the history of Lucja Frey and her syndrome. The Journal of laryngology and otology. 2006 Dec:120(12):1087; author reply 1087 [PubMed PMID: 17059631]
Level 3 (low-level) evidenceBlanc S, Bourrier T, Boralevi F, Sabouraud-Leclerc D, Pham-Thi N, Couderc L, Deschildre A, Dutau G, Albertini M, Tran A, Giovannini-Chami L, Frey Syndrome Collaborators. Frey Syndrome. The Journal of pediatrics. 2016 Jul:174():211-217.e2. doi: 10.1016/j.jpeds.2016.03.070. Epub 2016 May 2 [PubMed PMID: 27157448]
Scully C,Langdon J,Evans J, Marathon of eponyms: 6 Frey syndrome (Gustatory sweating). Oral diseases. 2009 Nov; [PubMed PMID: 19824940]
Bonanno PC, Casson PR. Frey's syndrome: a preventable phenomenon. Plastic and reconstructive surgery. 1992 Mar:89(3):452-6; discussion 457-8 [PubMed PMID: 1741468]
O'Neill JP, Condron C, Curran A, Walsh A. Lucja Frey--historical relevance and syndrome review. The surgeon : journal of the Royal Colleges of Surgeons of Edinburgh and Ireland. 2008 Jun:6(3):178-81 [PubMed PMID: 18581755]
Wood CB, Netterville JL. Temporoparietal frey syndrome: An uncommon variant of a common syndrome. The Laryngoscope. 2019 Sep:129(9):2071-2075. doi: 10.1002/lary.27632. Epub 2018 Dec 20 [PubMed PMID: 30570147]
Greenberg JS,Breiner MJ, Anatomy, Head and Neck, Auriculotemporal Nerve 2020 Jan; [PubMed PMID: 31334960]
Iwanaga J, Fisahn C, Watanabe K, Bobek SL, Ogata K, Tanoue R, Kusukawa J, Oskouian RJ, Tubbs RS. Parotid Branches of the Auriculotemporal Nerve: An Anatomical Study With Implications for Frey Syndrome. The Journal of craniofacial surgery. 2017 Jan:28(1):262-264. doi: 10.1097/SCS.0000000000003260. Epub [PubMed PMID: 27930465]
Ansari MH. Salivary gland tumors in an Iranian population: a retrospective study of 130 cases. Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons. 2007 Nov:65(11):2187-94 [PubMed PMID: 17954313]
Level 2 (mid-level) evidenceVuhahula EA. Salivary gland tumors in Uganda: clinical pathological study. African health sciences. 2004 Apr:4(1):15-23 [PubMed PMID: 15126188]
Pinkston JA,Cole P, Incidence rates of salivary gland tumors: results from a population-based study. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery. 1999 Jun; [PubMed PMID: 10352436]
SMIDDY FG. Treatment of mixed parotid tumours. British medical journal. 1956 Feb 11:1(4962):322-5 [PubMed PMID: 13284314]
Singh N, Kohli M, Kohli H. Innovative technique to reduce incidence of Frey's syndrome after parotid surgery. The American surgeon. 2011 Mar:77(3):351-4 [PubMed PMID: 21375851]
Level 2 (mid-level) evidenceNeumann A, Rosenberger D, Vorsprach O, Dazert S. [The incidence of Frey syndrome following parotidectomy: results of a survey and follow-up]. HNO. 2011 Feb:59(2):173-8. doi: 10.1007/s00106-010-2223-6. Epub [PubMed PMID: 21181391]
Level 3 (low-level) evidenceFiacchini G,Cerchiai N,Tricò D,Sellari-Franceschini S,Casani AP,Dallan I,Seccia V, Frey Syndrome, First Bite Syndrome, great auricular nerve morbidity, and quality of life following parotidectomy. European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery. 2018 Jul; [PubMed PMID: 29804129]
Level 2 (mid-level) evidenceZeng XT, Tang XJ, Wang XJ, Li MZ, Guo Y, Huang W, Niu YM, Leng WD. AlloDerm implants for prevention of Frey syndrome after parotidectomy: a systematic review and meta-analysis. Molecular medicine reports. 2012 Apr:5(4):974-80. doi: 10.3892/mmr.2012.762. Epub 2012 Jan 20 [PubMed PMID: 22266670]
Level 1 (high-level) evidenceHohman MH, Bhama PK, Hadlock TA. Epidemiology of iatrogenic facial nerve injury: a decade of experience. The Laryngoscope. 2014 Jan:124(1):260-5. doi: 10.1002/lary.24117. Epub 2013 Apr 18 [PubMed PMID: 23606475]
Level 2 (mid-level) evidenceLee CC, Chan RC, Chan JY. Predictors for Frey Syndrome Development After Parotidectomy. Annals of plastic surgery. 2017 Jul:79(1):39-41. doi: 10.1097/SAP.0000000000000993. Epub [PubMed PMID: 28609397]
Shah JS, Asrani VK. Post Herpetic Frey's Syndrome. Annals of maxillofacial surgery. 2017 Jul-Dec:7(2):278-281. doi: 10.4103/ams.ams_86_17. Epub [PubMed PMID: 29264298]
Kragstrup TW, Christensen J, Fejerskov K, Wenzel A. Frey syndrome-an underreported complication to closed treatment of mandibular condyle fracture? Case report and literature review. Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons. 2011 Aug:69(8):2211-6. doi: 10.1016/j.joms.2010.12.033. Epub 2011 Apr 15 [PubMed PMID: 21496996]
Level 3 (low-level) evidenceSmith A, Jonas N. Frey's Syndrome. The New England journal of medicine. 2020 Apr 9:382(15):1456. doi: 10.1056/NEJMicm1809117. Epub [PubMed PMID: 32268029]
Sethuraman G, Mancini AJ. Familial auriculotemporal nerve (Frey) syndrome. Pediatric dermatology. 2009 May-Jun:26(3):302-5. doi: 10.1111/j.1525-1470.2009.00909.x. Epub [PubMed PMID: 19706092]
Level 3 (low-level) evidenceGuntinas-Lichius O, Gabriel B, Klussmann JP. Risk of facial palsy and severe Frey's syndrome after conservative parotidectomy for benign disease: analysis of 610 operations. Acta oto-laryngologica. 2006 Oct:126(10):1104-9 [PubMed PMID: 16923718]
Level 2 (mid-level) evidenceLinder TE, Huber A, Schmid S. Frey's syndrome after parotidectomy: a retrospective and prospective analysis. The Laryngoscope. 1997 Nov:107(11 Pt 1):1496-501 [PubMed PMID: 9369396]
Level 2 (mid-level) evidenceDulguerov P, Quinodoz D, Cosendai G, Piletta P, Marchal F, Lehmann W. Prevention of Frey syndrome during parotidectomy. Archives of otolaryngology--head & neck surgery. 1999 Aug:125(8):833-9 [PubMed PMID: 10448728]
Level 1 (high-level) evidenceWatkins PJ. Facial sweating after food: a new sign of diabetic autonomic neuropathy. British medical journal. 1973 Mar 10:1(5853):583-7 [PubMed PMID: 4144374]
de Bree R, van der Waal I, Leemans CR. Management of Frey syndrome. Head & neck. 2007 Aug:29(8):773-8 [PubMed PMID: 17230557]
Motz KM, Kim YJ. Auriculotemporal Syndrome (Frey Syndrome). Otolaryngologic clinics of North America. 2016 Apr:49(2):501-9. doi: 10.1016/j.otc.2015.10.010. Epub 2016 Feb 20 [PubMed PMID: 26902982]
Myers EN, Conley J. Gustatory sweating after radical neck dissection. Archives of otolaryngology (Chicago, Ill. : 1960). 1970 Jun:91(6):534-42 [PubMed PMID: 4315319]
Redleaf MI, McCabe BF. Gustatory otorrhea: Frey's syndrome of the external auditory canal. The Annals of otology, rhinology, and laryngology. 1993 Jun:102(6):438-40 [PubMed PMID: 8512270]
Level 3 (low-level) evidenceBakke M, Max Thorsen N, Bardow A, Dalager T, Eckhart Thomsen C, Regeur L. Treatment of gustatory sweating with low-dose botulinum toxin A: a case report. Acta odontologica Scandinavica. 2006 Jun:64(3):129-33 [PubMed PMID: 16809188]
Level 3 (low-level) evidenceWenzel GI, Draf W. [Unusually long latency before the appearance of Frey's syndrome after parotidectomy]. HNO. 2004 Jun:52(6):554-6 [PubMed PMID: 15257402]
Level 3 (low-level) evidenceDurgut O, Basut O, Demir UL, Ozmen OA, Kasapoglu F, Coskun H. Association between skin flap thickness and Frey's syndrome in parotid surgery. Head & neck. 2013 Dec:35(12):1781-6. doi: 10.1002/hed.23233. Epub 2013 Mar 8 [PubMed PMID: 23471856]
Level 1 (high-level) evidenceTaylor SM, Yoo J, Matthews TW, Lampe HB, Trites JR. Frey's syndrome and parotidectomy flaps: A retrospective cohort study. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery. 2000 Feb:122(2):201-3 [PubMed PMID: 10652390]
Level 2 (mid-level) evidenceGovindaraj S, Cohen M, Genden EM, Costantino PD, Urken ML. The use of acellular dermis in the prevention of Frey's syndrome. The Laryngoscope. 2001 Nov:111(11 Pt 1):1993-8 [PubMed PMID: 11801985]
Level 2 (mid-level) evidenceBalasundaram I, Nasser NA. Paraumbilical fat graft for the correction of contour deformity following parotidectomy and prevention of Frey syndrome. International journal of oral and maxillofacial surgery. 2016 Mar:45(3):380-2. doi: 10.1016/j.ijom.2015.07.017. Epub 2015 Oct 4 [PubMed PMID: 26439758]
Bonanno PC, Palaia D, Rosenberg M, Casson P. Prophylaxis against Frey's syndrome in parotid surgery. Annals of plastic surgery. 2000 May:44(5):498-501 [PubMed PMID: 10805299]
Level 1 (high-level) evidenceWille-Bischofberger A,Rajan GP,Linder TE,Schmid S, Impact of the SMAS on Frey's syndrome after parotid surgery: a prospective, long-term study. Plastic and reconstructive surgery. 2007 Nov; [PubMed PMID: 18040182]
Yu LT, Hamilton R. Frey's syndrome: prevention with conservative parotidectomy and superficial musculoaponeurotic system preservation. Annals of plastic surgery. 1992 Sep:29(3):217-22 [PubMed PMID: 1326250]
Allison GR, Rappaport I. Prevention of Frey's syndrome with superficial musculoaponeurotic system interposition. American journal of surgery. 1993 Oct:166(4):407-10 [PubMed PMID: 8214303]
Barberá R, Castillo F, D'Oleo C, Benítez S, Cobeta I. Superficial musculoaponeurotic system flap in partial parotidectomy and clinical and subclinical Frey's syndrome. Cosmesis and quality of life. Head & neck. 2014 Jan:36(1):130-6. doi: 10.1002/hed.23215. Epub 2013 Feb 4 [PubMed PMID: 23378265]
Level 2 (mid-level) evidenceSultan MR, Wider TM, Hugo NE. Frey's syndrome: prevention with temporoparietal fascial flap interposition. Annals of plastic surgery. 1995 Mar:34(3):292-6; discussion 296-7 [PubMed PMID: 7598387]
Kierner AC, Aigner M, Zelenka I, Riedl G, Burian M. The blood supply of the sternocleidomastoid muscle and its clinical implications. Archives of surgery (Chicago, Ill. : 1960). 1999 Feb:134(2):144-7 [PubMed PMID: 10025452]
Filho WQ,Dedivitis RA,Rapoport A,Guimarães AV, Sternocleidomastoid muscle flap preventing Frey syndrome following parotidectomy. World journal of surgery. 2004 Apr; [PubMed PMID: 15022023]
Curry JM, King N, Reiter D, Fisher K, Heffelfinger RN, Pribitkin EA. Meta-analysis of surgical techniques for preventing parotidectomy sequelae. Archives of facial plastic surgery. 2009 Sep-Oct:11(5):327-31. doi: 10.1001/archfacial.2009.62. Epub [PubMed PMID: 19797095]
Level 1 (high-level) evidenceKornblut AD. Sternocleidomastoid muscle transfer in the prevention of Frey's syndrome. The Laryngoscope. 1991 May:101(5):571-2 [PubMed PMID: 2030639]
Level 3 (low-level) evidenceSanabria A, Kowalski LP, Bradley PJ, Hartl DM, Bradford CR, de Bree R, Rinaldo A, Ferlito A. Sternocleidomastoid muscle flap in preventing Frey's syndrome after parotidectomy: a systematic review. Head & neck. 2012 Apr:34(4):589-98. doi: 10.1002/hed.21722. Epub 2011 Apr 5 [PubMed PMID: 21472880]
Level 1 (high-level) evidenceLAAGE-HELLMAN JE. Treatment of gustatory sweating and flushing. Acta oto-laryngologica. 1958 Mar-Apr:49(2):132-43 [PubMed PMID: 13532654]
Drobik C, Laskawi R. Frey's syndrome: treatment with botulinum toxin. Acta oto-laryngologica. 1995 May:115(3):459-61 [PubMed PMID: 7653272]
Clayman MA, Clayman SM, Seagle MB. A review of the surgical and medical treatment of Frey syndrome. Annals of plastic surgery. 2006 Nov:57(5):581-4 [PubMed PMID: 17060744]
Hays LL. The Frey syndrome: a review and double blind evaluation of the topical use of a new anticholinergic agent. The Laryngoscope. 1978 Nov:88(11):1796-824 [PubMed PMID: 362094]
Level 1 (high-level) evidenceHEMENWAY WG, Gustatory sweating and flushing. The auriculo-temporal syndrome--Frey's syndrome. The Laryngoscope. 1960 Jan; [PubMed PMID: 14400950]
May JS, McGuirt WF. Frey's syndrome: treatment with topical glycopyrrolate. Head & neck. 1989 Jan-Feb:11(1):85-9 [PubMed PMID: 2646246]
Level 1 (high-level) evidenceSmith RO Jr, Hemenway WG, Stevens KM, Ratzer ER. Jacobson's neurectomy for Frey's syndrome. American journal of surgery. 1970 Oct:120(4):478-81 [PubMed PMID: 4319212]
Arad-Cohen A, Blitzer A. Botulinum toxin treatment for symptomatic Frey's syndrome. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery. 2000 Feb:122(2):237-40 [PubMed PMID: 10652397]
Cantarella G, Berlusconi A, Mele V, Cogiamanian F, Barbieri S. Treatment of Frey's syndrome with botulinum toxin type B. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery. 2010 Aug:143(2):214-8. doi: 10.1016/j.otohns.2010.04.009. Epub [PubMed PMID: 20647122]
Beerens AJ, Snow GB. Botulinum toxin A in the treatment of patients with Frey syndrome. The British journal of surgery. 2002 Jan:89(1):116-9 [PubMed PMID: 11851676]
Khoo SG, Keogh IJ, Timon C. The use of botulinum toxin in Frey's Syndrome. Irish medical journal. 2006 May:99(5):136-7 [PubMed PMID: 16892916]
Lawrence GW, Ovsepian SV, Wang J, Aoki KR, Dolly JO. Therapeutic effectiveness of botulinum neurotoxin A: potent blockade of autonomic transmission by targeted cleavage of only the pertinent SNAP-25. Neuropharmacology. 2013 Jul:70():287-95. doi: 10.1016/j.neuropharm.2013.02.012. Epub 2013 Feb 26 [PubMed PMID: 23485402]
Level 3 (low-level) evidenceKreyden OP,Scheidegger EP, Anatomy of the sweat glands, pharmacology of botulinum toxin, and distinctive syndromes associated with hyperhidrosis. Clinics in dermatology. 2004 Jan-Feb; [PubMed PMID: 15158544]
Tugnoli V, Marchese Ragona R, Eleopra R, Quatrale R, Capone JG, Pastore A, Montecucco C, De Grandis D. The role of gustatory flushing in Frey's syndrome and its treatment with botulinum toxin type A. Clinical autonomic research : official journal of the Clinical Autonomic Research Society. 2002 Jun:12(3):174-8 [PubMed PMID: 12269549]
Pomprasit M, Chintrakarn C. Treatment of Frey's syndrome with botulinum toxin. Journal of the Medical Association of Thailand = Chotmaihet thangphaet. 2007 Nov:90(11):2397-402 [PubMed PMID: 18181326]
Level 3 (low-level) evidenceHartl DM, Julieron M, LeRidant AM, Janot F, Marandas P, Travagli JP. Botulinum toxin A for quality of life improvement in post-parotidectomy gustatory sweating (Frey's syndrome). The Journal of laryngology and otology. 2008 Oct:122(10):1100-4. doi: 10.1017/S0022215108001771. Epub 2008 Feb 21 [PubMed PMID: 18289458]
Level 2 (mid-level) evidenceMatak I, Riederer P, Lacković Z. Botulinum toxin's axonal transport from periphery to the spinal cord. Neurochemistry international. 2012 Jul:61(2):236-9. doi: 10.1016/j.neuint.2012.05.001. Epub 2012 May 8 [PubMed PMID: 22580329]
Level 3 (low-level) evidenceLaccourreye O, Akl E, Gutierrez-Fonseca R, Garcia D, Brasnu D, Bonan B. Recurrent gustatory sweating (Frey syndrome) after intracutaneous injection of botulinum toxin type A: incidence, management, and outcome. Archives of otolaryngology--head & neck surgery. 1999 Mar:125(3):283-6 [PubMed PMID: 10190799]
Level 2 (mid-level) evidencede Bree R, Duyndam JE, Kuik DJ, Leemans CR. Repeated botulinum toxin type A injections to treat patients with Frey syndrome. Archives of otolaryngology--head & neck surgery. 2009 Mar:135(3):287-90. doi: 10.1001/archoto.2008.545. Epub [PubMed PMID: 19289708]
Level 2 (mid-level) evidenceLaskawi R, Drobik C, Schönebeck C. Up-to-date report of botulinum toxin type A treatment in patients with gustatory sweating (Frey's syndrome). The Laryngoscope. 1998 Mar:108(3):381-4 [PubMed PMID: 9504611]
Blumenfeld RJ, Friedman JE. Intratympanic surgical treatment of frey's syndrome. Archives of otolaryngology (Chicago, Ill. : 1960). 1967 Jul:86(1):2-7 [PubMed PMID: 4290826]
Dai XM, Liu H, He J, Tu MS, Yu LF, Liu L. Treatment of postparotidectomy Frey syndrome with the interposition of temporalis fascia and sternocleidomastoid flaps. Oral surgery, oral medicine, oral pathology and oral radiology. 2015 May:119(5):514-21. doi: 10.1016/j.oooo.2014.12.025. Epub 2015 Jan 20 [PubMed PMID: 25747175]
Level 2 (mid-level) evidenceRubinstein RY, Rosen A, Leeman D. Frey syndrome: treatment with temporoparietal fascia flap interposition. Archives of otolaryngology--head & neck surgery. 1999 Jul:125(7):808-11 [PubMed PMID: 10406323]
Level 3 (low-level) evidenceTorretta S, Pignataro L, Capaccio P, Brevi A, Mazzola R. Fat injections for the management of post-parotidectomy Frey syndrome: a technical note. Journal of cranio-maxillo-facial surgery : official publication of the European Association for Cranio-Maxillo-Facial Surgery. 2012 Feb:40(2):173-6. doi: 10.1016/j.jcms.2011.03.007. Epub 2011 Mar 31 [PubMed PMID: 21458286]
Level 3 (low-level) evidenceAdar R,Kurchin A,Zweig A,Mozes M, Palmar hyperhidrosis and its surgical treatment: a report of 100 cases. Annals of surgery. 1977 Jul; [PubMed PMID: 879872]
Level 3 (low-level) evidenceLeung AK, Chan PY, Choi MC. Hyperhidrosis. International journal of dermatology. 1999 Aug:38(8):561-7 [PubMed PMID: 10487442]
Hornberger J, Grimes K, Naumann M, Glaser DA, Lowe NJ, Naver H, Ahn S, Stolman LP, Multi-Specialty Working Group on the Recognition, Diagnosis, and Treatment of Primary Focal Hyperhidrosis. Recognition, diagnosis, and treatment of primary focal hyperhidrosis. Journal of the American Academy of Dermatology. 2004 Aug:51(2):274-86 [PubMed PMID: 15280848]
Lakraj AA, Moghimi N, Jabbari B. Hyperhidrosis: anatomy, pathophysiology and treatment with emphasis on the role of botulinum toxins. Toxins. 2013 Apr 23:5(4):821-40. doi: 10.3390/toxins5040821. Epub 2013 Apr 23 [PubMed PMID: 23612753]
Montoya FJ, Riddell CE, Caesar R, Hague S. Treatment of gustatory hyperlacrimation (crocodile tears) with injection of botulinum toxin into the lacrimal gland. Eye (London, England). 2002 Nov:16(6):705-9 [PubMed PMID: 12439663]
Level 3 (low-level) evidencede Oliveira D, Gomes-Ferreira PH, Carrasco LC, de Deus CB, Garcia-Júnior IR, Faverani LP. The Importance of Correct Diagnosis of Crocodile Tears Syndrome. The Journal of craniofacial surgery. 2016 Oct:27(7):e661-e662 [PubMed PMID: 27536922]
Boddie AW, Guillamondegui OM, Byers RM. Gustatory rhinorrhea developing after radical parotidectomy-a new syndrome? Archives of otolaryngology (Chicago, Ill. : 1960). 1976 Apr:102(4):248-50 [PubMed PMID: 1267711]
Level 3 (low-level) evidenceGunter AE, Llewellyn CM, Perez PB, Hohman MH, Roofe SB. First Bite Syndrome Following Rhytidectomy: A Case Report. The Annals of otology, rhinology, and laryngology. 2021 Jan:130(1):92-97. doi: 10.1177/0003489420936713. Epub 2020 Jun 21 [PubMed PMID: 32567395]
Level 3 (low-level) evidenceLinkov G, Morris LG, Shah JP, Kraus DH. First bite syndrome: incidence, risk factors, treatment, and outcomes. The Laryngoscope. 2012 Aug:122(8):1773-8. doi: 10.1002/lary.23372. Epub 2012 May 9 [PubMed PMID: 22573579]
Level 2 (mid-level) evidenceCharles-Harris H, Rodriguez B. First Bite Syndrome: Presentation of a Patient Status-Post Right Carotid Endarterectomy. Vascular and endovascular surgery. 2021 Jan:55(1):64-68. doi: 10.1177/1538574420954589. Epub 2020 Aug 31 [PubMed PMID: 32862800]
Gualberto GV, Sampaio FMS, Madureira NAB. Use of botulinum toxin type A in Frey's syndrome. Anais brasileiros de dermatologia. 2017 Nov-Dec:92(6):891-892. doi: 10.1590/abd1806-4841.20175702. Epub [PubMed PMID: 29364460]
Nigam PK, Nigam A. Botulinum toxin. Indian journal of dermatology. 2010:55(1):8-14. doi: 10.4103/0019-5154.60343. Epub [PubMed PMID: 20418969]
Baek CH,Chung MK,Jeong HS,Son YI,Jung SC,Jeon HK,Ryu NG,Cho HJ,Cho JK,Jang JY, Questionnaire evaluation of sequelae over 5 years after parotidectomy for benign diseases. Journal of plastic, reconstructive [PubMed PMID: 18314403]
Gunsoy B, Vuralkan E, Sonbay ND, Simsek G, Tokgoz SA, Akin I. Quality of life following surgical treatment of benign parotid disease. Indian journal of otolaryngology and head and neck surgery : official publication of the Association of Otolaryngologists of India. 2013 Jul:65(Suppl 1):105-11. doi: 10.1007/s12070-012-0585-7. Epub 2012 Oct 30 [PubMed PMID: 24427625]
Level 2 (mid-level) evidence