Mark K. Wax, MD, Section Editor
MANAGEMENT OF FREY SYNDROME
Remco de Bree, MD, PhD,1 Isaac van der Waal, DDS, PhD,2 C. Rene Leemans, MD, PhD1
1 Department of Otolaryngology/Head and Neck Surgery, VU University Medical Center,Amsterdam, The Netherlands. E-mail: firstname.lastname@example.org Department of Oral and Maxillofacial Surgery/Oral Pathology, VU University Medical Center,Amsterdam, The Netherlands
Accepted 7 October 2006Published online 17 January 2007 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/hed.20568
Abstract: Almost all patients who undergo parotidectomy will to
some extent develop Frey syndrome (auriculotemporal syn-
drome or gustatory sweating) after surgery, because of aberrant
regeneration of cut parasympathetic bers between otic gan-
glion and subcutaneous vessels. However, only the minority of
these patients needs treatment. The syndrome consists of gus-
tatory sweating, ushing, and warming over the preauricular and
temporal areas. Thick skin ap and partial supercial parotidec-
tomy are the most important techniques to minimize the risk of
developing symptomatic Frey syndrome. Intracutaneous injec-
tion of botulinum toxin A is an effective, long-lasting, and well-
tolerated treatment of Frey syndrome. If recurrence occurs, the
treatment can be repeated. VVC 2007 Wiley Periodicals, Inc.
Head Neck 29: 773778, 2007
Keywords: Frey syndrome; gustatory sweating management;
quality of life; prevention; treatment
Frey syndrome, also known as auriculotemporalsyndrome or gustatory sweating, is probably themost frequently occurring sequela of parotidec-tomy. The condition is characterized by sweatingand erythema, and ushing of the facial skin overthe parotid bed or neck which occurs during mas-tication and is often accompanied by general dis-comfort in the region.
Gustatory sweating was rst described byBaillarger1 in 1853, in 2 patients after drainage ofparotid abscesses. Rouyer,2 Botkin,3 Weber,4 andNew and Bozer5 reported patients who had gusta-tory sweating after drainage of a parotid abscess,a bullet wound, and other traumatic injuries ofthe parotid region. Later, in 1923, Lucja Frey,6 aPolish neurologist, drew attention to the role ofthe auriculotemporal nerve in gustatory sweatingand provided the missing link between eating andgustatory stimulation on 1 side and facial skinsweat production on the other. In 1927, Thomas7
explained the physiopathology by postulating theaberrant regeneration theory. The pathophysio-logical mechanism of this theory is the misdirec-tion of regenerating parasymphathetic bersinnervating sweat glands. The presumed processentails aberrant regeneration of cut parasympa-thetic bers between otic ganglion and the sali-vary gland tissue, leading to innervation of sweatglands and subcutaneous vessels. Gustatorystimulation then results in sweating and rednessof the involved skin. Bassoe8 reported in 1932 therst case of Frey syndrome following parotidec-tomy, which is currently the most frequentetiologic factor. Frey syndrome may also occurafter extirpation of the submandibular gland,
Correspondence to: R. de Bree
VVC 2007 Wiley Periodicals, Inc.
Management of Frey Syndrome HEAD & NECKDOI 10.1002/hed August 2007 773
mandibular condylar fracture, and obstetrictrauma caused by a forceps.911 Other nontrau-matic causes are sympathectomy, autonomic neu-ropathy in diabetes mellitus, herpes zoster infec-tion, andmetabolic diseases.12
The incidence of Frey syndrome varies accordingto the diligence with which the diagnosis is soughtfor and the elapsed time after the parotidectomy.If not explicitly asked for, the complaint isreported by patients in approximately 10% ofcases. If asked for, approximately 30% to 40% ofpatients will admit to gustatory sweating. If aobjective starch-iodine test according to Minor isperformed, about 95% of all patients who under-went parotidectomy show evidence of Frey syn-drome. In the starch-iodine test according toMinor, the affected skin area is covered withiodine solution. After the iodine solution haddried, the area is dusted with starch powder andthe patient is given a lemon sweet. As a result ofabsorption of the wet iodine by starch, the affectedarea will color deep blue-purple.13
Regeneration of postganglionic parasympa-thetic nerve bers in the skin takes a certainamount of time, suggesting a latent periodbetween intraoperative auriculotemporal nerveinjury and the onset of Frey syndrome. In mostreports, this interval ranges from 2 weeks to2 years, but latent periods of >8 years have beenreported.14
In a study of Bremerich et al,15 Frey syndromewas diagnosed after parotidectomy in 372 patientswithin 12 months in 52% and within 24 monthsin 83%. The remaining 17% diagnosis of Freysyndrome after parotidectomy occurred after 24months.
The facial skinareaexhibiting gustatory sweat-ing gradually becomes larger during follow-up.This progressiveness is compatible with differentlengths of time required by regenerating nervebers to reach effector organs at varying distancesfrom the proximal nerve endings. Linder et al16
noticed also an increase in incidence of subjectivecomplaints, incidence of objective ndings andinvolved skin area during the rst 12months.
QUALITY OF LIFE
Frey syndrome may cause considerable socialembarrassment and social incapacity due to pro-fuse ushing and sweating when eating. Most
patients (80%) complain of gustatory sweatingonly, 40% notice erythema, and 20% experience araised skin temperature.9
Unfortunately, no standardized questionnairefor quality of life in Frey syndrome is available.Nitzan et al17 conducted a quality of life study inpatients undergoing parotidectomy to dene themorbidity and its impact on quality of life. In aquestionnaire, the mean score for local effects was77 (scale 0100): erythema or sweating duringeating but not bothersome. The importance tooverall quality of life was 2.7 on a scale from 1 to 5:a little bit to somewhat important.
Hays18 determined the severity of Frey syn-drome by the frequency of wiping: less or morethan 3 times a meal. Ahmed and Kohle19 includedalso the incidence (occasional every meal) andsocial embarrassment. Beerens and Snow20 intro-duced the Frey questionnaire card for answeringthe question \Did you, for the past 2 weeks, haveannoying ushing or perspiration of the cheekduring meals?" Luna-Ortiz et al21 proposed agrading system to determine the severity of Freysyndrome. According to this system, which scoresclinical perception of symptomatology by thepatient, extent of the affected area, intensity, andsmell of sweat, 12 of the 28 (43%) patients withFrey syndrome were classied as mild and 16(57%) as severe.21
Prevention. Probably the most important way toprevent Frey syndrome is to minimize the parotidwound bed while adequately removing the pathol-ogy.22 Therefore, partial supercial parotidec-tomy, if possible, is recommended to minimize therisk of Frey syndrome.
Singleton and Cassisi23 found a signicantlower incidence of Frey syndrome after parotidec-tomy if a thick skin ap is made using a scissordissection as compared to the use of a extremelythin skin ap at the level of the base of the hairfollicles made using a scalpel. Although in theirstudy only thick and extremely thin aps werecompared, it is likely that the thickness of theskin ap indeed inuences the incidence of Freysyndrome.
Radiotherapy signicantly reduces the inci-dence of gustatory sweating. In a study of Caslerand Conley,24 only 14% of 14 patients receivingradiotherapy complained of gustatory sweating,whereas, 51% of 93 patients who did not receiveradiotherapy had the same complaints. Althougheffective, prevention of gustatory sweating aloneis of course not justied as a single indication
774 Management of Frey Syndrome HEAD & NECKDOI 10.1002/hed August 2007
for postoperative radiotherapy because of sideeffects.
Interposition of barriers to prevent aberrantreinnervation of parasymphatetic bers havebeen described. The temporoparietal fascia ap isa reliable and versatile ap in close proximityto the parotid bed, which can be harvested byextending the parotidectomy incision well hiddenwithin the temporal hair line. Ahmed and Kohle19
reported a signicant lower subjective (8% of24 patients vs 44% of 23 patients) and objective(17% of 24 patients vs 57% of 23 patients) inci-dence of Frey syndrome after temporoparietalfascia ap interposition. Drawbacks are the riskof injury to the frontal branch and alopecia. Liga-tion of the supercial temporal artery duringparotidectomy limits the use of this ap.
Allison and Rappaport25 were the rst to de-scribe a rotation of the supercial musculoapo-neurotic system (SMAS) to ameliorate the defectafter parotidectomy. This technique involvesplicating the SMAS layer and the remaininggland capsule to the sternocleidomastoid muscleand perichondrium of the ear canal. The incidenceof Frey syndrome was only 1% in their series of112 patients. Casler and Conley24 found in none ofthe 16 patients with SMAS plication subjectivesymptoms, whereas 47% of the 104 patients with-out SMAS plication had subjective symptoms of
Frey syndrome. Honig26 proposed a hybrid SMAS,inwhich a vicrylmesh is embedded in foldedSMASto prevent the development of gustatory sweating.
The sternocleidomastoid muscle receives itsblood supply superiorly from the occipital artery,in the midportion from the superior thyroid arteryand inferiorly from the transversal cervical artery.This allows the muscle to be used as superiorly-or inferiorly-based ap. Kornblut et al27 were therst to report on the use of a superiorly-based ster-nocleidomastoid muscle ap to prevent Freysyndrome. In their in