Treatment of Frey's syndrome with botulinum toxin.

BACKGROUND: Frey s syndrome or Gustatory sweating was first described by Baillarger in 1853. Lucie Frey had described a patient as "auriculotemporal syndrome" in 1923. The explanation for this symptom has been an aberrant regeneration of postganglionic parasympathetic fibers feeding the parotid gland that are severed during parotidectomy. After parotidectomy, these cholinergic parasympathetic fibers regenerate and anastomosis with postganglionic sympathetic fibers that supply vessel and sweat gland of the skin. According to a recent study, the treatment of Frey's syndrome has no treatment of choice. The authors investigated the effectiveness of botulinum toxin type A in the treatment of Frey's syndrome for the first time in Thai patients. MATERIAL AND METHOD: The present study was a prospective non-randomized, exploratory study. Nine patients with a median involvement skin area of 4.2 cm2 (1-16.3) were injected intradermal with botulinum toxin type A 2 unit in every 1 cm2 of involved skin. The mean total dose was 10.6 units (range 2-32 unit). RESULTS: All of the patients showed improvement after 4-7 days. Five patients have no Gustatory sweating. In the same way, four patients present with a dramatic decrease in Gustatory sweating. When comparing the skin involvement area, indicated by Minor's iodine starch test and calculated by program ImageJ 1.34s, between before and after injection of botulinum toxin type A using sign test, the result is statistically significant with p = 0.0039. The result lasted for 9.2 months (7-10 months). CONCLUSION: Intradermal injection of botulinum toxin type A for patients with Frey's syndrome is not only effective with no side effect but also minimally invasive. The present report supports that intradermal injection of botulinum toxin type A should be the treatment of choice for Frey's syndrome.

Síndrome de Frey por submaxilectomía y tratamiento con toxina botulínica / Frey syndrome secondary to submaxillectomy and botulinic treatment

El síndrome de Frey (SF) se caracteriza por rubor, calor y sudación en la región maseterina y geniana durante las comidas. El SF se observa en el 20-60% de los pacientes sometidos a parotidectomía. Presentamos un caso con SF secundario a la ablación de la glándula submaxilar en un varón de 30 años de edad, sin antecedentes patológicos, que consultó en el año 2000 por adenopatía cervical izquierda. La misma fue biopsiada y la anatomía patológica informó carcinoma medular de tiroides. El paciente presentaba múltiples metástasis hepáticas y pulmonares, motivo por el cual recibió tratamiento quimioterápico con cisplatino plus doxorrubicina (seis ciclos) con respuesta completa, finalizando dicho esquema en marzo del 2002. En julio del 2002 se realizó tiroidectomía total más vaciamiento ganglionar izquierdo con resección de la glándula submaxilar. Durante la cirugía se lesionó la rama mentoniana del nervio cervicofacial, rama del VII par craneal. En septiembre del 2004 consultó por episodios de sudación durante las comidas en la región submaxilar izquierda. Se realizó prueba de Minor y luego se procedió a aplicar toxina botulínica tipo A en la región afectada, a razón de 2.5 UI por punto (cm2), a un total de 17 puntos. El control a los 21 días demostró más de un 95% de efectividad en la resolución del SF. El efecto duró un año, y una segunda reinfiltración mostró similar respuesta. No hallamos descripciones anteriores de SF en región submaxilar; se presenta su tratamiento satisfactorio con toxina botulínica tipo A.

A case of Frey syndrome (FS) secondary to submaxillar gland exeresis is presented and the results of the treatment with botulinum toxin (BTX) type A. FS is a condition of sweating cheek and preauricular area during mealtime as a sequel detected in about 20-60% of patients after parotidectomy. The clinical symptoms include swelling, flushing and hyperhidrosis. The treatment choice for this condition is intracutaneous injection of BTX type A which blocks acetylcholine release at the sweat glands. A 30-year-old man, with thyroid medullar carcinoma diagnosed in 2002 received 6 cicles of cisplatin plus doxorubicin previous to the thyroidectomy with anterolateral neck dissection. During surgery the left ramus marginalis mandibulae was damaged. Two years later the patient referred sweating in submaxillar region during meals. CT scan demonstrated the absence of left submaxillar gland. Minor's test disclosed the affected area and BTX type A was injected (2.5 U/cm2/17 points). A twenty-one-day control showed a 95% reduction of the affected skin area. Persistent efficacy was observed up to one year followup time when he was reinjected. The FS, also known as "gustatory hyperhidrosis", was probably first reported by M. Duphenix in 1757. Lucja Frey considered its physiopathology as a disorder of both sympathetic and parasympathetic innervation. In our case the FS was caused by a misdirected regeneration of postganglionic parasympathetic nerve fibers that arrised from the nervus lingualis rami ganglionares of the nervus trigeminus. After nerve injury the colinergic parasympathetic fibers seek out colinergic receptors -sympathetic receptors of the skin- innervating sweat glands and small skin vessels. All previous cases were located at masseter region post-parotidectomy. We have not found any description of FS in the submaxillary region. The self-assessed efficacy of the treatment with a hyperhidrosis disease severity scale revealed a very satisfied patient at 20 months follow-up after being injected twice with BTX type A.

Treatment of Compensatory Gustatory Hyperhidrosis with Topical Glycopyrrolate

Gustatory hyperhidrosis is facial sweating usually associated with the eating of hot spicy food or even smelling this food. Current options of treatment include oral anticholinergic drugs, the topical application of anticholinergics or aluminum chloride, and the injection of botulinum toxin. Thirteen patients have been treated to date with 1.5% or 2% topical glycopyrrolate. All patients had gustatory hyperhidrosis, which interfered with their social activities, after transthroacic endoscopic sympathectomy, and which was associated with compensatory focal hyperhidrosis. After applying topical glycopyrrolate, the subjective effect was excellent (no sweating after eating hot spicy food) in 10 patients (77%), and fair (clearly reduced sweating) in 3 patients (23%). All had reported incidents of being very embrasssed whilst eating hot spicy foods. Adverse effects included a mildly dry mouth and a sore throat in 2 patients (2% glycopyrrolate), a light headache in 1 patient (1.5% glycopyrrolate). The topical application of a glycopyrrolate pad appeared to be safe, efficacious, well tolerated, and a convenient method of treatment for moderate to severe symptoms of gustatory hyperhidrosis in post transthoracic endoscopic sympathectomy or sympathicotomy patients, with few side effects.