Diabetic gustatory sweating.

ABSTRACT: Gustatory sweating is a potential manifestation of autonomic dysfunction in diabetes. This syndrome is seen in long-standing diabetes and is associated with nephropathy, peripheral neuropathy, and other signs of dysautonomia. Symptoms of profuse head and neck diaphoresis with eating may suggest this clinical diagnosis. We present a patient who had complicated diabetes with symptoms of gustatory sweating and other evidence of dysautonomia. Diagnosis and treatment possibilities are discussed, with a review of the literature and an emphasis on bedside testing.

GUSTATORY SWEATING is a known manifestation of autonomic dysfunction in diabetes mellitus. (1-5) This syndrome is not only symptomatically disturbing to affected people, but also can affect glycemic control. (1) Recognition of gustatory sweating is significant in that it provides an explanation for the symptoms, indicates possible concurrent diabetic complications, and allows the consideration of specific treatment modalities. Given the nonspecific diagnosis of diabetic gustatory sweating, familiarity with this entity and other manifestations of autonomic dysfunction can help to elucidate the appropriate clinical context.

CASE REPORT

A 63-year-old African American man had a 20-year history of type 2 diabetes mellitus treated with insulin. Glycemic control had been suboptimal, with home blood-glucose values ranging from 150 to 250 mg/dL and recent [HbA.sub.1c], level of 8%. Microvascular complications of the diabetes had been present for more than 10 years. He had peripheral neuropathy and vascular insufficiency, the latter requiring left below-the-knee amputation and right greattoe amputation. Serum creatinine level had ranged from 1.6 to 1.8 mg/dL for many years, and a urinary microalbumin-to-creatinine ratio was also high at 51 mg/g. Proliferative retinopathy had been treated with laser therapy. He also reported a several-year history of erectile dysfunction. He had an ejection fraction of 30% after a recent inferior myocardial infarction. In addition, he had had a cerebrovascular accident, with residual right upper neuron facial paresis and partial ptosis. There was no other evidence of a Horner's syndrome.

The patient was admitted to the Veterans Affairs hospital with volume depletion accompanied by fatigue and dizziness. While management of the acute issues was addressed, a 4- to 5-year history of excessive diaphoresis with eating was elicited. The distribution of the sweating was in the head, neck, and upper chest and occurred 1 to 10 minutes after starting to eat any type of food. The diaphoresis lasted for 5 to 10 minutes after cessation of eating and was without related symptoms, except for a tendency to feel chilled. Environmental temperature did not appear to be related to the symptoms, and these episodes were not related to hypoglycemia (according to home glucose-monitoring). Sweating occurred at practically every meal and became enough of a social issue that the patient limited dining away from home. The patient was observed on several occasions to sweat with eating in the distribution and time frame described. Photographs were taken but did not clearly capture the findings, and no indicator substance was applied.

On physical examination, he was initially orthostatic by blood pressure level and pulse rate with presyncope. Upon position change from supine to standing, the heart rate increased from 75 to 90 beats per minute, while systolic blood pressure fell from 122 to 77 mm Hg. After cautious volume repletion, these heart rate and blood pressure changes remained, though asymptomatically. To further investigate these findings, several basic tests of autonomic function were done (Table). The results supported the presence of dysautonomia.

This sweating continued to be a concern to the patient, and he requested therapy. Considering the multiple comorbid conditions and the patient's age in this case, systemic anticholinergic agents were undesirable. The patient was offered topical glycopyrrolate as a treatment for the gustatory sweating. Because of multiple reasons, he declined this option. Therefore, the efficacy of that modality cannot be assessed in this case.

DISCUSSION

Sweating is a normal physiologic function controlled by sympathetic cholinergic pathways. (8) Thermoregulation is the priority of this autonomic function. (8) There are several conditions where sweating activity is inappropriate, ranging from hyperhidrosis to anhidrosis. Gustatory sweating itself is a unique entity characterized by profuse sweating of the face, scalp, and neck during or immediately after ingestion of food or drink. (1-3) No specific foods are consistently related to symptoms and reactions are variable. (3,4) This occurrence may be a source of embarrassment to patients and, in diabetic patients, may disturb eating patterns and thus impair glycemic control. (1) Pathophysiologically, this phenomenon has been explained as previously-denervated sweat glands becoming reinnervated with sympathetic or parasympathetic nerve function. (1-1,12) There is an apparent overcompensation response from axonal regeneration that allows vasodilatory cholinergic sympathetic nerves to accomplish transmission. (3,4 ,12) Taste buds appear to be related to triggering symptoms, since placing food directly into the stomach does not evoke sweating. (3)

There are physiologic and nonphysiologic variants of gustatory sweating. (3) Physiologically, gustatory sweating may occur in temperate climates or with the ingestion of certain substances, including spicy foods.(1,3,12) Nonphysiologic forms include the auriculotemporal (Frey's) syndrome and diabetic gustatory sweating. The most commonly reported form is Frey's syndrome, which results from surgical or traumatic damage to the auriculotemporal nerve as it passes through the parotid gland. (1-4) In this case, symptoms are localized unilaterally to the distribution of the affected nerve. Frey's syndrome is not uncommon in certain surgical arenas, since it occurs in up to 60% of patients having parotidectomy with facial-nerve dissection. (3,12)

Given that sweating is under autonomic control, abnormalities in people with advanced diabetes should not be surprising. (1,2,4,9,10) Dysautonomia is strongly related to duration and overall control of diabetes and portends an overall poor prognosis. (10) Extremes of anhidrosis and hyperhidrosis occur in 10% to 75% of people with diabetic autonomic neuropathy. (3) Upper body "compensotory hyperhidrosis" is observed in patients with peripheral neuropathy with distal anhidrosis. This is unrelated to eating or drinking, whereas diabetic gustatory sweating is a specific thermoregulatory disturbance directly related to oral intake. (3) Although the precise prevalence of gustatory sweating in diabetes is unknown, (3) it is documented much less commonly than surgical causes. This may be due in part to less frequent occurrence but is likely compounded by underrecognition and underreporting. Diagnosis of diabetic gustatory sweating relies on a high level of suspicion in an appropriate clinical setting. This phenomeno n is bilateral and is seen in long-standing diabetes with complications and other signs of dysautonomia. (3) No data suggest that level of glycemic control is related to severity of symptoms, though autonomic dysfunction in general is related to the level of metabolic stability. (4) One study of 196 patients with diabetes found some degree of gustatory sweating in 69% of patients with nephropathy and 36% of those with peripheral neuropathy. (4) In patients with renal insufficiency, gustatory sweating has been reversed with renal transplantation, though it occurs in the absence of diabetic nephropathy as well. (4) While no single test confirms the diagnosis of diabetic gustatory sweating, supporting evidence may be obtained by documenting the presence and distribution of diaphoresis. The increased moisture should appear during or after eating and be restricted to the head and neck region. This may be documented by application of a variety of indicator substances, including iodine starch and cobalt chloride str ips. (3,12)

Treatment of diabetic gustatory sweating has drawn on experience from surgical cases of Frey's syndrome. These approaches focus on symptomatic relief only and have no documented impact on the course of the syndrome or directly on glycemic control. Tight glycemic control also does not reverse existing dysautonomia. (9) Several systemic therapies have been used with varying degrees of success. Oral anticholinergic agents, including scopolamine, oxybutynin, propantheline, and glycopyrrolate, have improved symptoms (3,12); however, concurrent illnesses and adverse reactions, including mouth dryness, constipation, potential worsening of gastroparesis, and confusion, limit the use of systemic therapies. Clonidine has also been used with some success but is also limited by side effects such as dry mouth and hypotension. (3) Such intolerability led to the investigation of nonsystemic approaches. Noting the efficacy of oral antimuscarinic agents, several investigators have used topical glycopyrrolate. (1,2,4,5,12) Th is quaternary ammonium compound has been shown to significantly decrease the incidence, severity, and frequency of sweating with eating' and is tolerated well. (2,12) Botulinum toxin has been used for gustatory sweating, though in most literature it is limited to use in unilateral, surgical-related cases. (13) In cases in which more conservative measures have failed and symptoms are disabling, surgery may be done; however, tympanic neurectomy or subdermal fascia grafts are invasive, difficult procedures and have varying, and often temporary, efficacy. (12)

CONCLUSION

Gustatory sweating is a common, albeit underrecognized, manifestation of diabetic autonomic dysfunction. This should be considered in any presentation of excessive diaphoresis in a patient with a long duration of diabetes mellitus. Diagnosis, although nonspecific, relies on taking a careful history and exploration for other evidence of dysautonomia. Symptomatic treatments with well-documented efficacy are available in various dosage forms.

TABLE.

Selected Bedside Evaluations of Autonomic Nervous System Function


Type of Test     Name of Test         How Test Performed

Parasympathetic  Basal HR (6,7)       Compare resting HR
CV system                             with control
testing
                 Valsalva             Have patient bear
                 ratio (6,8-10)       down for 15-30 seconds
                                      or blow against
                                      manometer to 40 mL
                                      for 10-15 seconds
                                      and compare R-R
                                      interval on marked
                                      EGG with baseline
                 HR changes           Monitor HR on marked
                 with deep            ECG while patient
                 inspiration (6,8-9)  takes 6 deep breaths
                                      per minute
                 Postural HR          Obtain HR after
                 changes (6,8-11)     standing from supine
                                      position






                 Carotid sinus        Firm pressure on
                 massage (8,10)       unilateral carotid
                                      artery and observe HR
Sympathetic      Postural BP          Obtain BP after
CV System        changes (7-11)       standing from
Testing                               supine position


                                      Dysautonomic
Type of Test     Normal Response      Response

Parasympathetic                       Higher basal HR
CV system
testing
                 Ratio of longest:    Valsalva ratio <1.4
                 shortest R-R
                 interval
                 (Valsalva ratio)
                 >1.4 when
                 comparing R-R
                 during rest and
                 during the Valsalva
                 R-R will increase    Minimal R-R
                 with inspiration     variability with
                                      respiration

                 R-R interval         30:15 ratio <1.04
                 should increase
                 11-29 bpm by
                 the 15th heartbeat
                 after standing and
                 then slow by the
                 30th beat (30:15
                 ratio should be
                 >1.04)
                 HR should fall       HR will not
                                      appreciably
                                      change
Sympathetic      SBP decreases        SBP decreases
CV System        <30 mm Hg and        >30 mm Hg or
Testing          DBP decreases        DBP decreases
                 <15 mm Hg            > l5 mm Hg

                 Case Study
Type of Test     Response

Parasympathetic  Average HR 80-85
CV system        bpm
testing
                 Valsalva ratio 1.0







                 No R-R variability
                 with deep inspiration


                 30:15 ratio = 0.90








                 No appreciable HR
                 changes

Sympathetic      SBP fell 45 mm Hg
CV System        upon standing from
Testing          supine position


CV = Cardiovascular,

HR = heart rate,

bpm = beats per minute,

R-R interval = measured distance between R waves on electrocardiogram
strips,

ECG = electrocardiogram,

BP = blood pressure,

SBP = systolic blood pressure,

DBP = diastolic blood pressure.

References

(1.) Atkin SL, Brown PM: Treatment of gustatory sweating with topical glycopyrrolate cream. Diabetic Med 1996; 13:493-494

(2.) Urman JD, Bobrove AM: Diabetic gustatory sweating successfully treated with topical glycopyrrolate. Arch Intern Med 1999; 159:877-878

(3.) Sheehy TW: Diabetic gustatory sweating. Am J Gastroenterol 1991; 86:15-17

(4.) Shaw JE, Parker R, Hollis S, et al: Gustatory sweating in diabetes mellitus. Diabetic Med 1996; 13:1033-1037

(5.) Shaw JE, Abbott GA, Tindle K, et al: A randomized, controlled trial of topical glycopyrrolate, the first specific treatment for diabetic gustatory sweating. Diabetologia 1997; 40:299-301

(6.) Dryberg T, Benn J, Christianson JS, et al: Prevalence of diabetic autonomic neuropathy measured by simple bedside tests. Diabetologia 1981; 20:190-194

(7.) Engstrom J, Martin JB: Disorders of the autonomic nervous system. Harrison s Principles of Internal Medicine. Fauci AS, Braunwald E, Isselbacher KJ, et al (eds). New York, McGraw-Hill, 14th Ed, 1998, pp 2372-2375

(8.) Saper CB: Autonomic disorders and their management. Cecil's Textbook of Medicine. Goldman L, Bennett JC (eds). Philadelphia, WB Saunders Go, 21st Ed, 2000, pp 2057-2066

(9.) Stevens MJ: Diabetic autonomic neuropathy. [On UpToDate CD-ROM]. UpToDate 1999; 7:1-11

(10.) Young JB, Landsberg L: Catecholamine and the adrenal medulla. Williams Textbook of Endocrinology. Wilson JD, Foster DW, Kronenberg HM, et al (eds). Philadelphia, WB Saunders Go, 9th Ed, 1998, pp 703-705

(11.) McLeod JG, Tuck RR: Disorders of the autonomic nervous system. Part 2: Investigation and treatment. Ann Neurol 1987; 21:519-529

(12.) Hays LL, Novack AJ, Worsham JC: The Frey syndrome: a simple, effective treatment. Otolaryngol Head Neck Surg 1982; 90:419-425

(13.) Naumann M: Evidence-based medicine: botulinum toxin in focal hyperhidrosis. J Neurology 2001; 248(suppl 1)31-33

RELATED ARTICLE: KEY POINTS

* Gustatory sweating is a unique clinical diagnosis.

* Gustatory sweating is potentially disabling to patients.

* Gustatory sweating is a sign of more generalized autonomic dysfunction in diabetes.

* Several treatment options exist for gustatory sweating.

From the Department of Internal Medicine, Medical University of South Carolina, Charleston.

Reprint requests to Dwight I. Blair, MD, Medical University of South Carolina, Department of Internal Medicine, 171 Ashley Aye, Charleston, SC 29425.