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Gustatory sweating and diabetes
The Netherlands Journal of Medicine 2000;56:159–162
Brief report
Gustatory sweating and diabetes J. van der Linden a , H.A.W. Sinnige b , M.A. van den Dorpel a , * a
Department of Internal Medicine, St. Clara Hospital Rotterdam, Olympiaweg 350, 3078 HT Rotterdam, The Netherlands b Department of Nephrology, St. Clara Hospital Rotterdam, Olympiaweg 350, 3078 HT Rotterdam, The Netherlands Received 27 October 1999; received in revised form 21 December 1999; accepted 11 January 2000
Abstract Gustatory sweating as a feature of autonomic neuropathy is an unusual phenomenon in diabetes mellitus. We describe a patient with type 1 diabetes mellitus complicated by retinopathy, nephropathy and neuropathy. This patient presented with bilateral diffuse facial sweating during eating. She was treated with the antimuscarine agent oxybutynine, which provided a striking relief from the gustatory sweating. 2000 Elsevier Science B.V. All rights reserved. Keywords: Diabetes mellitus; Thermoregulation; Gustatory sweating
Introduction Most physicians are aware that the autonomous nervous system may be impaired in diabetes mellitus patients. However, the thermoregulatory disorders that may evolve in the course of this disease, are less well known. These disorders are caused by disturbances in sudomotor (sweat production) and vasomotor (vascular tonus) function. Anhidrosis (29– 74%) and hyperhidrosis (10–40%) are frequent manifestations of diabetic neuropathy [1]. Gustatory sweating, however, is an unusual neurological complication, which usually develops in patients with severe diabetic neuropathy. Aagenaes first noted diabetic gustatory sweating in 1962 and it was first described in detail by Watkins in 1973 [2,3]. Gustatory sweating is characterised by sweating on the face and neck, often accompanied by flushing, in response *Corresponding author. Tel.: 1 31-10-291-1911; fax: 1 31-10291-1080.
to eating. This phenomenon is considered to be caused by degeneration of autonomic nerve fibres followed by axonal regeneration [1–7]. In this report we describe a patient with severely complicated diabetes mellitus who developed gustatory sweating. The different types of gustatory sweating and the therapeutic options of this entity are also discussed.
Case report A 39-year-old woman with chronic renal failure caused by diabetic nephropathy presented with an 8-month history of gradually progressive bilateral facial sweating. It occurred whenever she ate, but was more pronounced during eating of warm meals. Perspiration was first felt, and became visible after 10–20 s on the forehead and extended to the base of her neck (3rd cervical dermatome). To the patient’s embarrassment, often streams of sweat ran down her face. It persisted for about 5 min after eating.
0300-2977 / 00 / $ – see front matter 2000 Elsevier Science B.V. All rights reserved. PII: S0300-2977( 00 )00004-8
160
J. van der Linden et al. / Gustatory sweating and diabetes
Since the age of 2, the patient was known with brittle type 1 diabetes mellitus. She underwent a pancreatic transplantation at the age of 30, which was lost by chronic rejection and removed 1 year later. Because of persistently uncontrolled blood glucose levels during subcutaneous insulin therapy, a CAPD-catheter was placed for intraperitoneal insulin administration. For approximately 10 years she was known with diabetic nephropathy, which finally progressed into chronic renal failure 2 years ago. Consequently, peritoneal dialysis was started. The disease was complicated by a proliferative retinopathy with retinal detachment causing near-blindness at the age of 33, peripheral vascular disease, peripheral neuropathy and she also suffered from multiple transient ischemic attacks. Calcium carbonate, algeldrate and aspirin were prescribed. Folic acid, vitamin B complex, vitamin B12, ascorbic acid and iron were supplemented. Physical examination showed a blood pressure of 170 / 75 mm Hg and the heart rate was 84 bpm. She had no orthostatic hypotension. She had an upper quadrant anopsia of the left eye. Pulsations of the distal arteries of both legs were absent. Areflexia at both feet was found. EMG showed a symmetrical demyelinating neuropathy. Laboratory tests revealed a HbA1c of 8.7% (normal range 4.0–6.0%), a haemoglobin level of 7.5 mmol / l (7.4–9.4 mmol / l), a white blood cell count of 9.7 G / l, a platelet count of 348 G / l, a creatinin of 1125 mmol / l (60–105 mmol / l), a blood urea nitrogen level of 16.4 mmol / l (2.5–6.4 mmol / l), a sodium level of 142 mmol / l (135–145 mmol / l), a potassium level of 3.5 mmol / l (3.6–5.1 mmol / l), a calcium level of 2.66 mmol / l (2.20–2.62 mmol / l), a phosphate level of 1.98 mmol / l (0.80–1.60 mmol / l), an aspartate aminotransferase level of 27 U / l, an alanine aminotransferase level of 21 U / l, a lactic dehydrogenase (LDH) level of 413 U / l and an albumin level of 38.4 g / l. During the facial sweating no hypoglycaemia was observed. The distribution of sweating was examined by application of an iodine and starch combination to the skin, resulting in a blue–black discoloration whenever sweating occurs (Fig. 1). She was treated with 5 mg of oxybutynine once daily, which resulted in a substantial reduction of the gustatory sweating, without significant side effects.
Fig. 1. The dark starch–iodine complex revealed the diffuse sweating 2 min after eating a mixture of fresh fruit (photograph published with patient’s permission).
Discussion Clinical presentation The gustatory sweating syndrome is characterised by an increased sweating of the face and neck area, often accompanied by flushing, during and immediately after eating. In most patients the introduction per se of food into the mouth causes this phenomenon [3,8]. Interestingly, the smell of food or feeding via a nasogastric tube does not provoke sweating or flushing. However, the nature of the food also matters, as chewing of inert substances like Parafilm is never followed by any symptoms [3]. Mild symmetrical sweating of the head and neck is a common physiological response to spicy foods [9]. Sometimes it occurs as an idiosyncrasy to certain kinds of food, like cheese or chocolate [10]. The
The Netherlands Journal of Medicine 2000;56:159 – 162
J. van der Linden et al. / Gustatory sweating and diabetes
most commonly reported cause of gustatory sweating is Frey’s syndrome, also known as auriculotemporal syndrome, which is caused by surgical or traumatic damage to the auriculotemporal nerve as it passes through the parotid gland [11,12]. Unilateral gustatory sweating occurs in the area distributed by the auriculotemporal branch of the mandibular nerve [4,13]. In 10% of all cases pain is experienced over the same area [1]. Diabetic gustatory sweating occurs most often in patients with longstanding diabetes with advanced complications. Unlike Frey’s syndrome, in which sweating is localised, diabetic gustatory sweating is symmetrical and limited to the area innervated by the superior cervical ganglion. Epidemiology Frey’s syndrome develops in up to 60% of patients undergoing parotidectomy [11,12]. Clinical experience suggests that diabetic gustatory sweating is much more common than previously believed. Freedman found it in two of 200 consecutive patients with diabetes [15]. Gustatory sweating was found in 13% of black diabetics [16]. More recently Shaw showed that it occurs in 69% of patients with diabetic nephropathy and 36% of patients with diabetic neuropathy [5]. Pathogenesis It is presumed that reanastomosis of the interrupted parasympathetic fibres innervating secretory cells of the parotid gland with sympathetic fibres destined for the preauricular skin is responsible for the gustatory sweating in Frey’s syndrome [14]. The aetiology of gustatory sweating associated with diabetes is uncertain. It is hypothesised that gustatory sweating is a physiological compensatory response to anhidrosis induced by diabetic autonomic neuropathy [17–20]. Watkins demonstrated autonomic neuropathy in all six patients with gustatory sweating [3]. A more recent study reported autonomous neuropathy in most patients with diabetic gustatory sweating and also demonstrated a clear association with the degree of neuropathy [5]. It has been suggested that gustatory sweating results from bilateral intermingling of parasympathetic and sympathetic nerve fibres due to abnormal sprouting of
161
nerve fibres preceded by axonal degeneration [3,4]. However, resolution of gustatory sweating is noted in patients after renal transplantation, making the hypothesis of aberrant regrowth less likely [21]. Shaw suggested that a functional abnormality was responsible for the excessive sweating. He demonstrated that gustatory sweating is closely related to diabetic nephropathy. Although most patients with diabetic nephropathy had clear evidence of neuropathy, still 50% of patients without neuropathy showed gustatory sweating, suggesting an etiologic role of nephropathy in the pathogenesis of gustatory sweating in diabetic patients. This could explain the disappearance of gustatory sweating in five patients immediately after renal transplantation [5]. The mechanism behind this is unknown. Antibodies directed against sympathetic ganglia were demonstrated in one patient with diabetic gustatory sweating, suggesting an autoimmune mechanism [22]. The use of immunosuppressants reducing the amount of these antibodies could be another explanation for the improvement of symptoms after transplantation, but strong evidence is lacking. Treatment Diabetic gustatory sweating can be treated successfully with oral anticholinergic drugs. Unfortunately, this treatment is frequently complicated by unpleasant side effects, like dry mouth, constipation and blurred vision [3]. It is reported that the majority of patients prefer to stay off medication because of significant side effects. The centrally acting alpha 2 agonist, clonidine, has also been used very successfully in diabetic gustatory sweating. A marked reduction of sweating was seen and a dose of 100 mg twice daily seemed to be tolerated without side effects [23]. One report demonstrates the benefit of oxybutynine, an antimuscarine compound, in the treatment of diabetic gustatory sweating [24]. At a dose of 5 mg once daily only mild dryness of the mouth was reported. Because of its antispasmodic effects on smooth muscle it may also be useful in the treatment of diabetic diarrhoea. The effect of topical use of glycopyrrolate, a quaternary amine anticholinergic agent, was demonstrated in patients with Frey’s syndrome [25]. In a randomised controlled trial the effectiveness of glycopyrrolate treatment for diabetic
The Netherlands Journal of Medicine 2000;56:159 – 162
162
J. van der Linden et al. / Gustatory sweating and diabetes
gustatory sweating was investigated. Topical use of glycopyrrolate, proved to be significantly more effective than placebo in reducing both severity and frequency of diabetic gustatory sweating, without significant side effects [26,27]. Unfortunately, this preparation is not easily available and is quite expensive [23]. In conclusion, diabetic gustatory sweating is a rather unknown feature in patients with longstanding diabetes. In severe cases it can disturb eating patterns and occasionally makes glycaemic control difficult [6]. Moreover, patients often find gustatory sweating socially embarrassing. Gustatory sweating can be successfully treated with oral clonidine or oxybutynine, or with topical treatment like glycopyrrolate or antiperspirant agents when oral therapy is poorly tolerated.
References [1] Sheehy TW. Diabetic gustatory sweating. Am J Gastroenterol 1991;86:1514–7. [2] Aagenaes O. Neurovascular examination of the lower extremities in young diabetics with special reference to the autonomic neuropathy. Copenhagen: Hay Burgers, Bogtrykkeri, A / S, 1962. [3] Watkins PJ. Facial sweating after food: a new sign of diabetic autonomic neuropathy. Br Med J 1973;1:583–7. [4] Bronshavag MM. Spectrum of gustatory sweating with special reference to its presence in diabetics with peripheral neuropathy. Am J Clin Med 1978;31:307–9. [5] Shaw JE, Parker R, Hollis S, Gokal R, Boulton AJM. Gustatory sweating in diabetes mellitus. Diab Med 1996;13:1033–7. [6] Hayes PC, Tulloch JA. An unusual case of gustatory sweating. Postgrad Med J 1982;58:656–7. [7] Mealey BL. Bilateral gustatory sweating as a sign of diabetic neuropathy. Oral Max Surg 1994;77:113–5. [8] Rundles RW. Diabetic neuropathy: general review with 125 cases. Medicine 1945;24:111–60. [9] Lee TS. Physiological gustatory sweating in a warm climate. J Physiol 1978;124:528–42.
[10] Brown-Sequard CE. Production de suer sons l’influence d’un excitation vive des nerfs du gout Comptis Renous des Seauces de la Societe de Biologie 1849:1–104. [11] Frey L. Le syndrome du nerf auriculotemporal. Rev Neurol 1923;2:97–104. [12] Langdon JD. Complication of parotid gland surgery. J Maxillofac Surg 1984;12:225–9. [13] Braunius WW, Gerrits MA. Behandeling van het syndroom van Frey met botuline A toxine. Ned Tijdschr Geneesk 1998;142:859–63. [14] Friedman WH, Pomarico JM. The intratympanic correction of Frey’s syndrome. Arch Surg 1974;108:366–8. [15] Freedman A. Facial sweating after food in diabetics. Br Med J 1973;3:291. [16] Morley JE, Asvat MS, Klein C, Lowenthal MN. Autonomic neuropathy in black diabetic patients. S Afr Med J 1977;52:115–6. [17] Stuart DD. Diabetic gustatory sweating. Ann Intern Med 1978;89:223–4. [18] Hosking DJ, Bennett T, Hampton JR. Diabetic autonomic neuropathy. Diabetes 1978;27:1043–55. [19] Clark BF, Ewing DJ, Cambell R. Diabetic autonomic neuropathy. Diabetologia 1979;17:195–212. [20] Goodman JT. Diabetic anhidrosis. Am J Med 1966;41:831– 5. [21] Boulton AJM, Shaw JE, Parker R, Hollis R, Gokal R. Gustatory sweating in diabetes (abstract). Diabetologia 1995;A238:291. [22] Ho KKL, Rabinowe SL. Anti-sympathetic ganglia antibodies in a patient with gustatory sweating. J Diabetes Comp 1990;4:193–5. [23] Davies MJ, McNally PG, Hall AP. Consensus guidelines for the management of insulin-dependent (type 1) diabetes mellitus (IDDM) in childhood and adolescence. Diab Med 1995;595–597. [24] Chideckel EW. Oxybutynin for diabetic complications (letter). Am Med Assoc 1990;264:2994. [25] Stegehuis HR, Ellis B. Treatment of Frey’s syndrome (gustatory sweating) with topical glycopyrrolate: case report (letter). New Zealand Med J 1989;102:479. [26] Shaw JE, Abbott CA, Tindle K, Hollis S, Boulton AJM. A randomised controlled trial of topical glycopyrrolate, the first specific treatment for diabetic gustatory sweating. Diabetologia 1997;40:299–301. [27] Atkin SL, Brown PM. Treatment of diabetic gustatory sweating with topical glycopyrrolate cream. Diab Med 1996;13:493–4.
The Netherlands Journal of Medicine 2000;56:159 – 162
Brief report
Gustatory sweating and diabetes J. van der Linden a , H.A.W. Sinnige b , M.A. van den Dorpel a , * a
Department of Internal Medicine, St. Clara Hospital Rotterdam, Olympiaweg 350, 3078 HT Rotterdam, The Netherlands b Department of Nephrology, St. Clara Hospital Rotterdam, Olympiaweg 350, 3078 HT Rotterdam, The Netherlands Received 27 October 1999; received in revised form 21 December 1999; accepted 11 January 2000
Abstract Gustatory sweating as a feature of autonomic neuropathy is an unusual phenomenon in diabetes mellitus. We describe a patient with type 1 diabetes mellitus complicated by retinopathy, nephropathy and neuropathy. This patient presented with bilateral diffuse facial sweating during eating. She was treated with the antimuscarine agent oxybutynine, which provided a striking relief from the gustatory sweating. 2000 Elsevier Science B.V. All rights reserved. Keywords: Diabetes mellitus; Thermoregulation; Gustatory sweating
Introduction Most physicians are aware that the autonomous nervous system may be impaired in diabetes mellitus patients. However, the thermoregulatory disorders that may evolve in the course of this disease, are less well known. These disorders are caused by disturbances in sudomotor (sweat production) and vasomotor (vascular tonus) function. Anhidrosis (29– 74%) and hyperhidrosis (10–40%) are frequent manifestations of diabetic neuropathy [1]. Gustatory sweating, however, is an unusual neurological complication, which usually develops in patients with severe diabetic neuropathy. Aagenaes first noted diabetic gustatory sweating in 1962 and it was first described in detail by Watkins in 1973 [2,3]. Gustatory sweating is characterised by sweating on the face and neck, often accompanied by flushing, in response *Corresponding author. Tel.: 1 31-10-291-1911; fax: 1 31-10291-1080.
to eating. This phenomenon is considered to be caused by degeneration of autonomic nerve fibres followed by axonal regeneration [1–7]. In this report we describe a patient with severely complicated diabetes mellitus who developed gustatory sweating. The different types of gustatory sweating and the therapeutic options of this entity are also discussed.
Case report A 39-year-old woman with chronic renal failure caused by diabetic nephropathy presented with an 8-month history of gradually progressive bilateral facial sweating. It occurred whenever she ate, but was more pronounced during eating of warm meals. Perspiration was first felt, and became visible after 10–20 s on the forehead and extended to the base of her neck (3rd cervical dermatome). To the patient’s embarrassment, often streams of sweat ran down her face. It persisted for about 5 min after eating.
0300-2977 / 00 / $ – see front matter 2000 Elsevier Science B.V. All rights reserved. PII: S0300-2977( 00 )00004-8
160
J. van der Linden et al. / Gustatory sweating and diabetes
Since the age of 2, the patient was known with brittle type 1 diabetes mellitus. She underwent a pancreatic transplantation at the age of 30, which was lost by chronic rejection and removed 1 year later. Because of persistently uncontrolled blood glucose levels during subcutaneous insulin therapy, a CAPD-catheter was placed for intraperitoneal insulin administration. For approximately 10 years she was known with diabetic nephropathy, which finally progressed into chronic renal failure 2 years ago. Consequently, peritoneal dialysis was started. The disease was complicated by a proliferative retinopathy with retinal detachment causing near-blindness at the age of 33, peripheral vascular disease, peripheral neuropathy and she also suffered from multiple transient ischemic attacks. Calcium carbonate, algeldrate and aspirin were prescribed. Folic acid, vitamin B complex, vitamin B12, ascorbic acid and iron were supplemented. Physical examination showed a blood pressure of 170 / 75 mm Hg and the heart rate was 84 bpm. She had no orthostatic hypotension. She had an upper quadrant anopsia of the left eye. Pulsations of the distal arteries of both legs were absent. Areflexia at both feet was found. EMG showed a symmetrical demyelinating neuropathy. Laboratory tests revealed a HbA1c of 8.7% (normal range 4.0–6.0%), a haemoglobin level of 7.5 mmol / l (7.4–9.4 mmol / l), a white blood cell count of 9.7 G / l, a platelet count of 348 G / l, a creatinin of 1125 mmol / l (60–105 mmol / l), a blood urea nitrogen level of 16.4 mmol / l (2.5–6.4 mmol / l), a sodium level of 142 mmol / l (135–145 mmol / l), a potassium level of 3.5 mmol / l (3.6–5.1 mmol / l), a calcium level of 2.66 mmol / l (2.20–2.62 mmol / l), a phosphate level of 1.98 mmol / l (0.80–1.60 mmol / l), an aspartate aminotransferase level of 27 U / l, an alanine aminotransferase level of 21 U / l, a lactic dehydrogenase (LDH) level of 413 U / l and an albumin level of 38.4 g / l. During the facial sweating no hypoglycaemia was observed. The distribution of sweating was examined by application of an iodine and starch combination to the skin, resulting in a blue–black discoloration whenever sweating occurs (Fig. 1). She was treated with 5 mg of oxybutynine once daily, which resulted in a substantial reduction of the gustatory sweating, without significant side effects.
Fig. 1. The dark starch–iodine complex revealed the diffuse sweating 2 min after eating a mixture of fresh fruit (photograph published with patient’s permission).
Discussion Clinical presentation The gustatory sweating syndrome is characterised by an increased sweating of the face and neck area, often accompanied by flushing, during and immediately after eating. In most patients the introduction per se of food into the mouth causes this phenomenon [3,8]. Interestingly, the smell of food or feeding via a nasogastric tube does not provoke sweating or flushing. However, the nature of the food also matters, as chewing of inert substances like Parafilm is never followed by any symptoms [3]. Mild symmetrical sweating of the head and neck is a common physiological response to spicy foods [9]. Sometimes it occurs as an idiosyncrasy to certain kinds of food, like cheese or chocolate [10]. The
The Netherlands Journal of Medicine 2000;56:159 – 162
J. van der Linden et al. / Gustatory sweating and diabetes
most commonly reported cause of gustatory sweating is Frey’s syndrome, also known as auriculotemporal syndrome, which is caused by surgical or traumatic damage to the auriculotemporal nerve as it passes through the parotid gland [11,12]. Unilateral gustatory sweating occurs in the area distributed by the auriculotemporal branch of the mandibular nerve [4,13]. In 10% of all cases pain is experienced over the same area [1]. Diabetic gustatory sweating occurs most often in patients with longstanding diabetes with advanced complications. Unlike Frey’s syndrome, in which sweating is localised, diabetic gustatory sweating is symmetrical and limited to the area innervated by the superior cervical ganglion. Epidemiology Frey’s syndrome develops in up to 60% of patients undergoing parotidectomy [11,12]. Clinical experience suggests that diabetic gustatory sweating is much more common than previously believed. Freedman found it in two of 200 consecutive patients with diabetes [15]. Gustatory sweating was found in 13% of black diabetics [16]. More recently Shaw showed that it occurs in 69% of patients with diabetic nephropathy and 36% of patients with diabetic neuropathy [5]. Pathogenesis It is presumed that reanastomosis of the interrupted parasympathetic fibres innervating secretory cells of the parotid gland with sympathetic fibres destined for the preauricular skin is responsible for the gustatory sweating in Frey’s syndrome [14]. The aetiology of gustatory sweating associated with diabetes is uncertain. It is hypothesised that gustatory sweating is a physiological compensatory response to anhidrosis induced by diabetic autonomic neuropathy [17–20]. Watkins demonstrated autonomic neuropathy in all six patients with gustatory sweating [3]. A more recent study reported autonomous neuropathy in most patients with diabetic gustatory sweating and also demonstrated a clear association with the degree of neuropathy [5]. It has been suggested that gustatory sweating results from bilateral intermingling of parasympathetic and sympathetic nerve fibres due to abnormal sprouting of
161
nerve fibres preceded by axonal degeneration [3,4]. However, resolution of gustatory sweating is noted in patients after renal transplantation, making the hypothesis of aberrant regrowth less likely [21]. Shaw suggested that a functional abnormality was responsible for the excessive sweating. He demonstrated that gustatory sweating is closely related to diabetic nephropathy. Although most patients with diabetic nephropathy had clear evidence of neuropathy, still 50% of patients without neuropathy showed gustatory sweating, suggesting an etiologic role of nephropathy in the pathogenesis of gustatory sweating in diabetic patients. This could explain the disappearance of gustatory sweating in five patients immediately after renal transplantation [5]. The mechanism behind this is unknown. Antibodies directed against sympathetic ganglia were demonstrated in one patient with diabetic gustatory sweating, suggesting an autoimmune mechanism [22]. The use of immunosuppressants reducing the amount of these antibodies could be another explanation for the improvement of symptoms after transplantation, but strong evidence is lacking. Treatment Diabetic gustatory sweating can be treated successfully with oral anticholinergic drugs. Unfortunately, this treatment is frequently complicated by unpleasant side effects, like dry mouth, constipation and blurred vision [3]. It is reported that the majority of patients prefer to stay off medication because of significant side effects. The centrally acting alpha 2 agonist, clonidine, has also been used very successfully in diabetic gustatory sweating. A marked reduction of sweating was seen and a dose of 100 mg twice daily seemed to be tolerated without side effects [23]. One report demonstrates the benefit of oxybutynine, an antimuscarine compound, in the treatment of diabetic gustatory sweating [24]. At a dose of 5 mg once daily only mild dryness of the mouth was reported. Because of its antispasmodic effects on smooth muscle it may also be useful in the treatment of diabetic diarrhoea. The effect of topical use of glycopyrrolate, a quaternary amine anticholinergic agent, was demonstrated in patients with Frey’s syndrome [25]. In a randomised controlled trial the effectiveness of glycopyrrolate treatment for diabetic
The Netherlands Journal of Medicine 2000;56:159 – 162
162
J. van der Linden et al. / Gustatory sweating and diabetes
gustatory sweating was investigated. Topical use of glycopyrrolate, proved to be significantly more effective than placebo in reducing both severity and frequency of diabetic gustatory sweating, without significant side effects [26,27]. Unfortunately, this preparation is not easily available and is quite expensive [23]. In conclusion, diabetic gustatory sweating is a rather unknown feature in patients with longstanding diabetes. In severe cases it can disturb eating patterns and occasionally makes glycaemic control difficult [6]. Moreover, patients often find gustatory sweating socially embarrassing. Gustatory sweating can be successfully treated with oral clonidine or oxybutynine, or with topical treatment like glycopyrrolate or antiperspirant agents when oral therapy is poorly tolerated.
References [1] Sheehy TW. Diabetic gustatory sweating. Am J Gastroenterol 1991;86:1514–7. [2] Aagenaes O. Neurovascular examination of the lower extremities in young diabetics with special reference to the autonomic neuropathy. Copenhagen: Hay Burgers, Bogtrykkeri, A / S, 1962. [3] Watkins PJ. Facial sweating after food: a new sign of diabetic autonomic neuropathy. Br Med J 1973;1:583–7. [4] Bronshavag MM. Spectrum of gustatory sweating with special reference to its presence in diabetics with peripheral neuropathy. Am J Clin Med 1978;31:307–9. [5] Shaw JE, Parker R, Hollis S, Gokal R, Boulton AJM. Gustatory sweating in diabetes mellitus. Diab Med 1996;13:1033–7. [6] Hayes PC, Tulloch JA. An unusual case of gustatory sweating. Postgrad Med J 1982;58:656–7. [7] Mealey BL. Bilateral gustatory sweating as a sign of diabetic neuropathy. Oral Max Surg 1994;77:113–5. [8] Rundles RW. Diabetic neuropathy: general review with 125 cases. Medicine 1945;24:111–60. [9] Lee TS. Physiological gustatory sweating in a warm climate. J Physiol 1978;124:528–42.
[10] Brown-Sequard CE. Production de suer sons l’influence d’un excitation vive des nerfs du gout Comptis Renous des Seauces de la Societe de Biologie 1849:1–104. [11] Frey L. Le syndrome du nerf auriculotemporal. Rev Neurol 1923;2:97–104. [12] Langdon JD. Complication of parotid gland surgery. J Maxillofac Surg 1984;12:225–9. [13] Braunius WW, Gerrits MA. Behandeling van het syndroom van Frey met botuline A toxine. Ned Tijdschr Geneesk 1998;142:859–63. [14] Friedman WH, Pomarico JM. The intratympanic correction of Frey’s syndrome. Arch Surg 1974;108:366–8. [15] Freedman A. Facial sweating after food in diabetics. Br Med J 1973;3:291. [16] Morley JE, Asvat MS, Klein C, Lowenthal MN. Autonomic neuropathy in black diabetic patients. S Afr Med J 1977;52:115–6. [17] Stuart DD. Diabetic gustatory sweating. Ann Intern Med 1978;89:223–4. [18] Hosking DJ, Bennett T, Hampton JR. Diabetic autonomic neuropathy. Diabetes 1978;27:1043–55. [19] Clark BF, Ewing DJ, Cambell R. Diabetic autonomic neuropathy. Diabetologia 1979;17:195–212. [20] Goodman JT. Diabetic anhidrosis. Am J Med 1966;41:831– 5. [21] Boulton AJM, Shaw JE, Parker R, Hollis R, Gokal R. Gustatory sweating in diabetes (abstract). Diabetologia 1995;A238:291. [22] Ho KKL, Rabinowe SL. Anti-sympathetic ganglia antibodies in a patient with gustatory sweating. J Diabetes Comp 1990;4:193–5. [23] Davies MJ, McNally PG, Hall AP. Consensus guidelines for the management of insulin-dependent (type 1) diabetes mellitus (IDDM) in childhood and adolescence. Diab Med 1995;595–597. [24] Chideckel EW. Oxybutynin for diabetic complications (letter). Am Med Assoc 1990;264:2994. [25] Stegehuis HR, Ellis B. Treatment of Frey’s syndrome (gustatory sweating) with topical glycopyrrolate: case report (letter). New Zealand Med J 1989;102:479. [26] Shaw JE, Abbott CA, Tindle K, Hollis S, Boulton AJM. A randomised controlled trial of topical glycopyrrolate, the first specific treatment for diabetic gustatory sweating. Diabetologia 1997;40:299–301. [27] Atkin SL, Brown PM. Treatment of diabetic gustatory sweating with topical glycopyrrolate cream. Diab Med 1996;13:493–4.
The Netherlands Journal of Medicine 2000;56:159 – 162