17.1 Introduction

Frey syndrome (FS), also known as gustatory sweating or auriculotemporal syndrome, is characterized by excessive facial sweating, erythema, and/or warmth that is stimulated by the thought, sight, or consumption of food. Although originally described in 1757 by Duphenix ¹ and later in 1853 by Baillarger, ² this syndrome is named after Lucja Frey, a Polish neurologist, who first described gustatory sweating following traumatic parotid injury in 1923 and coined the term “auriculotemporal syndrome.” ³ This phenomenon typically occurs following surgery or trauma to the parotid gland, facial nerve, submandibular gland, or thoracic sympathetic chain. It can be associated with polyneuropathies which result in maladaptive parasympathetic cholinergic innervation of cutaneous sympathetic receptors. ^{4 ,​ 5}

17.2 Etiology

Frey syndrome is thought to be due to aberrant regeneration of postganglionic parasympathetic fibers from the auriculotemporal nerve that reinnervate superficial facial eccrine sweat glands and cutaneous blood vessels. ⁶ Due to this faulty reinnervation, vasodilation and localized sweating occurs in response to gustatory stimuli. This phenomenon is usually due to trauma to these fibers or iatrogenic disruption following parotidectomy where these fibers are surgically separated and become aberrantly connected to the superficial vasculature and sweat glands. As nerve regeneration typically occurs 3 to 6 months following injury, this is the typical timeline for presentation to the physician with classic symptoms and conversion to a positive minor iodine starch test (MIST). ⁷

A 2017 retrospective review of 100 patients with FS reported a history of parotidectomy in 96% with a minority of remaining cases due to trauma (2%) or mumps (1%). ⁷ Conversely, the rate of clinical prevalence of FS following parotidectomy ranges from 4 to 62%. ⁸ A 2011 study highlighted the subclinical nature of FS as the prevalence of a positive MIST was 62% in postparotidectomy patients, but only 23% reported symptoms. ⁹ Indeed, this corresponds well with the 1958 classic report that MIST can be positive in up to 100% of postparotidectomy patients, while only 15 to 30% report clinical symptoms. ¹⁰ This decline in incidence of positive MIST and FS over the past five decades may be due in part to improved understanding of the disorder and resultant prophylactic measures taken during parotidectomy, such as increased skin flap thickness, although this reasoning is unproven. Ultimately, FS remains the most common long-term self-perceived consequence of surgical intervention in patients undergoing parotidectomy for benign disease. ¹¹

17.3 Workup

A complete history and physical exam is necessary to elucidate the underlying pathology and initiate treatment planning. Symptoms such as flushing, sweating, burning, and pruritus are usually mild but can result in social anxiety, social isolation, and discomfort. Although the diagnosis is clinical, confirmatory testing is performed with the MIST. It is important to note that this test typically becomes positive 3 to 6 months after surgery. During the MIST, the suspected region is painted with a thin layer of povidone-iodine solution. After the solution dries, dried starch (a mixture of 10–20% amylose and 80–90% amylopectin) is applied to the painted area. An oral sialogogue (lemon juice, citrus candy, etc.) is then provided to the patient to stimulate the gustatory cortex. When hydrated with sweat, the iodine molecules form a linear polyiodide ion complex that binds to the inside of the amylose helical polymer. The amylose-iodine complex absorbs a different light wavelength than the polypeptide alone, and the complex becomes discolored (dark blue/brown). Typically, a punctate pattern of sweat will first appear in affected areas within the prepared field, followed by coalescence of the droplets into a solid blue region. Some areas will take longer to appear than others, and care should be taken to avoid dripping sweat from discoloring areas that are not exhibiting sweating (Fig. 17‑1).

An alternative to the MIST is medical infrared thermography. This technique allows for isolation not only of the area of hyperhidrosis but also that of local facial flushing. ¹² However, at the time of this publication, thermography remains experimental and is not widely available for clinical use.