CLINICAL CASE

INTRORDUCTION

Frey’s syndrome (auriculotemporal nerve syndrome) is a type of gustatory hyperhidrosis characterized by sweating, warmth, flushing, and redness in the skin area supplied by the auriculotemporal nerve. These symptoms are triggered by eating or even thinking about food. It most often occurs after parotidectomy but can also happen following other injuries to the parotid region.1-4

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The earliest descriptions of gustatory sweating linked it to parotid disease and treatment in the 19th and early 20th centuries. In 1853, Charles-Philippe Robin and Jules Félix Baillarger first noted facial sweating associated with parotid disease and drainage procedures, but without precise anatomic correlation. In 1923, Lucja Frey published the classic clinico-anatomic description, correlating gustatory symptoms with injury to the auriculotemporal nerve and coining “auriculotemporal syndrome.” V. Minor later developed the starch-iodine test (1928), a standard objective method used to confirm and map gustatory sweating.1-4

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The incidence of symptoms after parotidectomy or parotid gland injury varies depending on the method of assessment. Objective tests, such as the Minor starch-iodine test, often reveal high rates of occurrence, typically ranging from 30% to 80%. However, the proportion of patients who report symptoms themselves tends to be lower, typically ranging from 10% to 30%. This discrepancy suggests that many cases are mild or unrecognized by patients, and that detection rates depend significantly on the testing methods used. Across different studies and diagnostic techniques, the reported incidence ranges widely from approximately 4% to as high as 96%.2,3,5-7

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The time to onset of symptoms following surgery usually occurs within six to twelve months. Nevertheless, there are cases where symptoms may appear years after the procedure. Although pediatric and congenital forms of this condition are pretty rare, they have been documented in the literature.2,3

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The anatomic distribution of the symptoms predominantly involves the skin regions adjacent to the parotid gland. This includes the preauricular area (in front of the ear), the temporal region (side of the head), and the malar skin (over the cheekbone), corresponding to the territory innervated by the auriculotemporal nerve. Less commonly, similar symptoms may be seen in the submandibular area, particularly following surgeries involving the submandibular gland.2,3,6

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The underlying mechanism relates to auriculotemporal nerve injury. Specifically, damage occurs to the postganglionic parasympathetic fibers that originate from the otic ganglion and travel via the auriculotemporal nerve, as well as nearby sympathetic fibers or their target tissues. During the nerve regeneration process, the cholinergic parasympathetic fibers aberrantly reinnervate structures such as the eccrine sweat glands, which possess M3 muscarinic receptors, and vasodilator targets in the skin over the affected area. As a result, stimuli that typically provoke salivary secretion, such as gustatory (taste) stimuli, can also trigger sweating and flushing in the skin. Alternative hypotheses, like ephaptic transmission (abnormal electrical cross-talk between nerve fibers), have been proposed; however, the concept of abnormal reinnervation best accounts for the clinical presentation and the observed response to therapies. Treatments such as anticholinergic medications and botulinum toxin injections have proven effective, supporting this mechanism.2,3,8

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The clinical presentation of the condition includes core symptoms, such as gustatory sweating, characterized by localized, unilateral perspiration precipitated by eating, thinking about food, or gustatory stimulation. Additionally, flushing and warmth occur as transient erythema and heat in the same distribution. Common triggers for these symptoms include sour and spicy foods, with citrus, vinegar, and peppers often eliciting robust responses. The affected area typically has sharp borders, presenting as a patch or field over the preauricular–malar area corresponding to the parotid bed. The quality-of-life impact can be significant, as the visible sweating and flushing may cause psychosocial burden; the severity ranges from incidental to socially disabling.2,3,6 Differential diagnosis to consider includes primary focal hyperhidrosis, which is non-gustatory and has a different distribution; Harlequin syndrome, characterized by sympathetic denervation with contralateral compensatory flushing and sweating; Horner syndrome, identified by the ptosis, miosis, and anhidrosis triad; medication- or systemic-induced sweating, which presents with a diffuse pattern; and gustatory tearing, or crocodile tears, seen when facial nerve injuries involve the lacrimal pathway.2,3

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Diagnostic modalities for the condition include bedside confirmation through a provocation test, where a citrus or gustatory stimulus is used to reproduce symptoms and confirm gustatory specificity in a focal area. Objective mapping can be performed using the Minor starch-iodine test, which involves applying iodine to the skin, allowing it to dry, dusting starch over the area, and then applying a gustatory stimulus. The involved skin turns blue-black as sweat appears, enabling precise mapping for documentation and treatment planning. This method has high sensitivity, allowing for the quantification of the response area and intensity over time.4 Adjunctive tools include infrared thermography, which detects localized heat changes corresponding to flushing and is particularly helpful in cases where flushing predominates. Gravimetric or evaporimetry methods may be used to quantify sweat production for research purposes or in refractory cases. Imaging studies are not routinely required unless alternative diagnoses, such as a recurrent tumor, are suspected based on the patient's history or examination findings.2,3,6,7

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Treatment options for the condition include both non-surgical management and surgical interventions. Non-surgical management begins with counseling and dietary modification, emphasizing expectation setting since many cases are mild, and avoidance of potent triggers can reduce episodes. Topical antiperspirants, such as aluminum chloride hexahydrate (15-20%), work by obstructing eccrine ducts; they are inexpensive and accessible, but can cause irritation, require frequent application, and may have limited efficacy for moderate to severe cases.2,3 Topical anticholinergics, such as glycopyrronium or scopolamine (compounded into wipes or gels), act by muscarinic blockade at eccrine glands and help treat focal fields. However, overuse or application over large areas may lead to anticholinergic side effects.2,3 Systemic anticholinergics, such as low-dose oxybutynin or glycopyrrolate, can be considered for multifocal or refractory cases when topical therapy fails and botulinum toxin is unavailable. However, systemic side effects, including dry mouth, constipation, and urinary retention, may limit long-term use.2,3

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Botulinum toxin injections are considered first-line treatment for moderate to severe symptoms. OnabotulinumtoxinA is most commonly used, with rimabotulinumtoxinB as an alternative. The technique involves mapping the affected area using the Minor starch-iodine test and administering intradermal injections in a 1-1.5 cm grid with small aliquots per site (e.g., 1–2.5 units of onabotulinumtoxin A per injection), avoiding intramuscular placement. The total dose is individualized based on the size of the affected field. Botulinum toxin yields high response rates, providing near-complete control in most patients, with onset occurring within days and peak effect typically reached within two weeks. The duration of benefit usually lasts 6 to 12 months, and repeat injections maintain efficacy with a favorable safety profile. Adverse effects are generally mild and transient, including injection-site discomfort and, in rare cases, transient muscle weakness if the toxin spreads to the surrounding muscles.2,3,6,9-11

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Surgical treatment is reserved for cases that are refractory to other forms of treatment. Procedures such as auriculotemporal or tympanic neurectomy aim to interrupt aberrant parasympathetic pathways but have variable durability due to nerve regeneration and carry risks such as sensory changes and dry mouth.2,3 Interpositional barrier procedures used in revisional surgery include options such as superficial musculoaponeurotic system (SMAS) advancement, temporoparietal fascia flap, sternocleidomastoid fascia, dermofat or free fat grafts, and acellular dermal matrix. These create a barrier between the parotid bed and the overlying skin, disrupting aberrant cholinergic signaling. While evidence exists to support their therapeutic use, it is less robust than that for preventive strategies.2,6,7

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Preventive strategies employed at the time of index parotid surgery include barrier or interposition techniques, such as SMAS advancement, fascia flaps, and dermal or alloplastic barriers, which can reduce the incidence and extent of Frey’s syndrome by separating regenerating nerve fibers from sweat glands. Although multiple observational studies and some controlled trials suggest benefit, heterogeneity in study design and outcome definitions limits the certainty of conclusions. Reviews emphasize the need for higher-quality trials.6,7,12

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In practical terms, for established symptomatic Frey’s syndrome, botulinum toxin injections offer the best balance of efficacy, safety, and repeatability, with surgery reserved for highly selected refractory cases or when concurrent revisional surgery is indicated.

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The prognosis of Frey’s syndrome indicates that once established, the condition rarely resolves completely without intervention. Its severity may remain stable or slowly diminish over the years. Although medically benign, Frey’s syndrome can have significant social and professional impacts, making it important to manage patient expectations and provide effective, minimally invasive therapies. Long-term control is achievable with botulinum toxin, which offers reproducible and durable relief through periodic reinjections. Surgical options may be beneficial in select cases of refractory disease but involve trade-offs and variable durability.2,3,6,7,12