Thursday, April 19, 2007

What provokes palmar hyperhidrosis?

ABSTRACT

In this work, we try to find out why some types of physical or mental effort of the every day life activities provoke excessive sweating in hyperhidrotic individuals but other types do not. We compared (i) the palmar and forearm electrodermal activity (EDA) of hyperhidrotic in palms and normal individuals when they performed mental arithmetic: a. in recumbent position, without moving or speaking, and b. in standing position, while they vocalized the solutions to the same mental arithmetic task (ii) the amount of palmar and forearm sweat of the same individuals while they were bicycling a. normally, b. with distress, and c. after reducing the distress. Forearm EDA was recorded in order to check the supposition that an over-function of sympathetic nervous fibers, which innervate both palmar and forearm sweat glands, is responsible for palmar hyperhidrosis. The lack of forearm electrodermal responses during mental arithmetic for both groups, as well as the insignificant correlation between palmar and forearm sweating, especially for hyperhidrotics, indicate that the theory of over-function of sympathetic nervous fibers is not tenable. The finding that palmar EDA of both hyperhidrotic and normal individuals in standing position was much higher than that in recumbent position indicate that the muscle tension is a decisive factor for the magnitude of palmar sweating during mental effort. The finding that the amount of palmar sweat of hyperhidrotics was increased during the second and decreased during the third bicycling task, indicate that the distress is a decisive factor for hyperhidrotic sweating during physical effort. We concluded that the necessary and effective ingredient of a mental or physical effort, in order to provoke palmar hyperhidrosis, is the combination of distress with muscle tension.

INTRODUCTION

From our investigation on palmar hyperhidrosis, we already know that: (i) it is not controlled by a thermoregulatory mechanism [1], (ii) extended clinical and laboratory tests did not reveal any type of organic disease (hematological abnormality, electrolytic or glucose imbalance, thyroid gland dysfunction, neurological abnormality, autonomic imbalance, etc.) or a higher density of sweat glands on palm, but only a higher score in Neuroticism scale of Eysenck's Personality Questionnaire of hyperhidrotics as compared to normal palmar sweating individuals (unpublished data), (iii) hyperhidrotics presented higher scores in Psychasthenia, Social Introversion, and Depression of Minnesota Multiphasic Personality Inventory [2]. These findings were in agreement with those of Lerer, Jacobowitz and Wahba [3] and of Lerer and Jacobowitz [4] that hyperhidrotic individuals are characterized by lower overall ability to cope with stress and a strong proclivity to avoid problems, in the sense that they suggest that personality traits may be responsible for palmar hyperhidrosis.
From extended interviews about everyday life of hyperhidrotics we know that in many cases mental efforts do not cause hyperhidrosis and that hyperhidrotics may not sweat at all on their palms when they perform calm a hard handiwork. In the present work, we try to determine what is effective, what is necessary for palmar hyperhidrosis expression. This information could help in the understanding of the nature of the disorder as well as in its treatment, given the lack of investigation on the etiology of palmar hyperhidrosis (see the reviews by Sato, Kang, Saga, and Sato [5] on the disorders of sweat glands, by Lerer [6], Lerer, Jacobowitz and Wahba [3] on the psychological aspects of palmar hyperhidrosis, and by Fotopoulos and Sunderland [7] on the treatment of psychophysiological disorders). We subjected hyperhidrotic and normal palmar sweating individuals to 2 mental arithmetic (mental effort) and 3 bicycling (physical effort) tasks. The mental arithmetic tasks aimed to check the role of muscle tension on palmar sweating caused by the same mental effort. The bicycling tasks aimed to check the role of the distress on palmar sweating caused by the same physical effort.
Electrodermal recordings of forearm have been also performed in order to check the theory of Shih, Wu and Lin [19], that the over-function of sympathetic fibers passing through T2,3 ganglia is responsible for palmar hyperhidrosis. Since these ganglia innervate both palmar and forearm sweat glands, a kind of forearm hyperhidrosis, or at least a significant correlation between palmar and forearm sweating should be expected in the case of hyperhidrotics.
Before the presentation of the work, we should mention that the old view of general or sympathetic arousal, according to which palmar hyperhidrosis follows mass sympathetic discharge at fight and flight reactions (Cannon's theory), must not be considered as an answer to the question concerning the palmar hyperhidrosis expression. Former and recent studies [8-12] from different fields of research have challenged the view of a diffusely acting sympathetic system. Besides, it is well known that autonomic manifestations (and EDA) differ considerably among psychological disorders [13-15] and also in relation to stimulus presentation, or condition of performance [16-18], which means that no arousal theory can overcome the question why a specific sympathetic function is triggered under specific conditions. In addition, we repeatedly recorded slight or no palmar sweat glands activation during human orgasm (mass sympathetic activation took place), and we concluded that palmar sweating cannot be considered as a simple following of sympathetic discharge (unpublished data).

METHODS
PARTICIPANTS

Forty individuals participated in the present work. Twenty individuals were hyperhidrotic in their palms (and, usually, in their soles as well), whereas the remaining 20 individuals were normal in terms of palmar sweating. Twelve females and 8 males were included in each group. The mean age of the hyperhidrotic females was 31.4 (17-63) and of the normal females was 27.3 (20-42) years. The mean age of the hyperhidrotic males was 35 (21-56) and of the normal males was 34.3 (22-61) years. The mean body weight of the hyperhidrotic females was 60.3 (50-73) and of the normal females was 56.4 (45-70) kg. The mean body weight of the hyperhidrotic males was 75.6 (62-87) and of the normal males was 76.2 (62-102) kg. The educational level of hyperhidrotics/normals was: 11/12 higher education, 3/4 students, and 6/4 secondary-lower.
Individuals with palmar hyperhidrosis were recruited by advertisements in the local mass media. They participated voluntarily in the research. Six persons who manifested excessive sweating all over the body, or predominantly in other areas of the body, like the forehead and the armpits, were not included in this study. The authors from people who reported never having suffered from excessive palmar sweating selected normal palmar sweating individuals. Attention was paid to the equivalence on gender, age, and educational level to the hyperhidrotic group.
In order to confirm the participants' estimate of the degree of their palmar sweating, a sweat collecting plaster was attached on each participant's left palm, while she/he was writing for two minutes on a paper with the right hand. The mean weight of the sweat collected from the palm of hyperhidrotics was 20 mg (S.D. 14.9, range 7-65 mg) and from that of normal individuals was 3.1 mg (S.D. 2.3, range 0-7). We did not exclude any individual from the research. The participation of 2 individuals, one from the hyperhidrotic group with 4 mg palmar sweating and one from the normal group with 12 mg palmar sweating, confirmed that they did not have the electrodermal behavior they had declared. Their scores in the tests were excluded from the analysis. This way, the simple method of measuring the palmar sweating during writing was proved to be a good confirmation tool of the declared by the participants’ electrodermal behavior.

MATERIALS

We used the voltage coupler 9878 of the Beckman R 511A polygraph for chart recording of palmar skin conductance, during mental arithmetic tests. The recorded voltage was received from the ends of a resistor (1000 Ω) which was in series connection with the individual and an external stabilized voltage source (0.5 V). The J&J Modules, designed to support the B45 biofeedback program of Unicomp, were used for the recording of palmar and forearm skin conductance. German 3M, Ag-AgCl electrodes, 8 mm diameter were used; after each session their polarity was changed and they were replaced after two sessions, in order to prevent polarization. Electrolytic paste of Hewlett Packard was used as electrolytic medium.
A gravimetric method was used during bicycling task, because the profuse sweating, especially of hyperhidrotics, and the movement demands of the task, could cause artificial recordings. Sweat collecting plasters were attached on the palm and forearm during bicycling. The sweat collecting plaster consisted of a leucoplast (5Χ5) cm with a small sponge (2Χ2) cm attached to its center. A waterproof membrane on its outer surface was used to prevent any evaporation of the collected sweat. The sweat collecting plaster weighed about 580 mg and could absorb more than 500 mg of sweat almost immediately. The weight of plasters was measured by an electronic balance (Shimadzu) with 1 mg readability and 340 g weighing capacity.

DESIGN AND PROCEDURE

All participants washed their hands. Each individual was asked to read the instructions describing the procedure and to avoid speaking until completion of the tasks. Electrodes for skin conductance recording were attached on the two palms as well as on the forearm of the right hand, while the individual was laid on an examination table. The electrodes were not removed during the mental arithmetic tasks, in order to avoid artificial differences in skin conductance levels. The blood pressure and heart rate measurements, which were interposed, will not be presented in this work.
Three minutes after relaxing on the examination table, the participant was asked to perform the first out of the two mental arithmetic tasks, that is, to add continuously the number 7 for 72 s, without speaking or contracting any muscle. The participant reported the found sum at the end of the 72 s period. After this task and during the 3 min intertask break that followed, the participant was asked to sit for 2 min and then to stand for 1 min, in order to accustom to the standing position before performing the second mental arithmetic task. This second task was the same with the previous one in terms of mental effort, starting from another number. The two mental arithmetic tasks were designed to be the same, apart from the body posture and speaking, in order to check the role of muscle tension in palmar sweating caused by the same mental effort.
Some min later, the participant performed 3 bicycling tasks. During the first task, the participants bicycled for 4 min, in order to compare the palmar sweating of hyperhidrotic and normal individuals during physical exercise. Sweat collecting plasters were attached (after wiping the area) on the palm (hypothenar eminence) and forearm of the individual's left hand. The plasters were weighed immediately before and after each bicycling task. A clothing support around the neck prevented sweat secreted by other areas from reaching the plasters. The participant was asked to keep bicycling at a constant rate of 10-15 miles per hour, using a tachometer. Before the second bicycling task, which was identical to the first one in terms of physical exercise, the shoes and the socks of the participant were taken off by the experimenter, in order to investigate the influence of distress in the EDA caused by physical effort. The unwarned removal of the shoes and socks caused psychological distress, especially in hyperhidrotics (they all mentioned that, after a relevant question at the end of the tasks), because of the revelation of their wet soles, soaked socks with probably unpleasant odor, and of the difficulty in bicycling with naked their wet soles. Before the third bicycling task, socks and shoes were replaced and absorbing gloves were put on both palms, in order the distress of profuse sweating to be eliminated.

STATISTICS

We compared the number of electrodermal responses (EDRs) and the skin conductance level (SCL) in mental arithmetic, and weight of sweat in bicycling, using three factor ANOVA, with sex and hyperhidrosis as between-subject factors and repeated measures as within subject factor.

RESULTS

Mental arithmetic tasks: The hyperhidrotics presented a significantly higher number of palmar EDRs as compared to normal individuals during the performance of the mental arithmetic tasks F=9.62, DF=1, P<.004. No statistically significant differences were found between males and females. A significantly higher number of palmar EDRs was found during the performance of mental arithmetic in standing position as compared to recumbent position, for hyperhidrotics F=36.40, DF=1, P<.000, and for normal individuals F=21,28, DF=1, P<.000. The number of EDRs was about 70% higher in the standing position than in the recumbent one, in both hyperhidrotic and normal individuals, indicating that muscular tension causes a marked augmentation in the number of EDRs. Seven hyperhidrotics presented a smaller number of EDRs than the average of that of normal individuals, during the performance of mental arithmetic task in the recumbent position, but no one in the standing position. Forearm did not present any EDR during the performance of the mental arithmetic tasks.
Mean SCL was calculated by the computer every 4 s, while the SCL over the experimental period was taken as the average of 18 periods. Τhe hyperhidrotics presented significantly higher palmar SCL as compared to control individuals during the performance of the mental arithmetic F=32,42, DF=1, P<.000. No statistically significant differences were found between males and females. Significantly higher palmar SCL was observed during the execution of mental arithmetic in standing position in relation to that in recumbent position, for hyperhidrotics F=22.56, DF=1, P<.000, and for normal individuals F=20.26, DF=1, P<.000. The interaction of hyperhidrosis X execution position was also significant F=6.31, DF=1, P<.02. The augmentation of SCL of palms in the standing position in relation to SCL in the recumbent position was about 30% for hyperhidrotic and 43% for normal individuals. The higher augmentation of palmar SCL of normal individuals (in spite of the same augmentation of EDRs) in relation to that of hyperhidrotics was due to the smaller prior wetting of their palmar stratum corneum. Only one hyperhidrotic presented a smaller palmar SCL than the average of normal individuals SCL, during the performance of mental arithmetic task in the recumbent position but no one in the standing position.
Significantly higher forearm SCL was found in hyperhidrotic as compared to normal palmar sweating individuals during the performance of the mental arithmetic tasks F=8.78, DF=1, P<.005. This finding was probably the result of higher thermoregulatory sweating in the whole body of hyperhidrotics, because when the heat load in the bicycling tasks induced profuse thermoregulatory sweating in both groups, sweat product of forearm of hyperhidrotic and normal individuals was the same, while sweat product of palms was very different. There was no significant difference between forearm SCL during the execution of mental arithmetic in standing position in relation to that in recumbent position, in either group. The correlation between palmar and forearm SCL was significant (P<.05) only for normal individuals (r1=.468 and r2=.487) and insignificant for hyperhydrotic individuals (r1=.386 and r2=.09) in both tasks, respectively.
Bicycling: The weight of palmar sweat secreted during the performance of all 3 bicycling tasks was significantly higher in hyperhidrotic as compared to normal individuals F=14.41, DF=1, P<.001 (Fig. 1). Gender differences on palmar sweat were not significant, but the interaction of hyperhidrosis X sex was significant F=4.98, DF=1, P<.032. No significant difference was found in forearm weight of sweat between hyperhidrotic and normal individuals (Fig. 2). The weight of forearm sweat of males was higher than that of females during the bicycling tasks F=7.08, DF=1, P<.01. Palmar sweating of hyperhidrotics was significantly higher than forearm sweating during all 3 bicycling tasks. Palmar sweating of normal individuals was significantly higher than forearm sweating only during the first bicycling task.
Palmar sweating of hyperhidrotics was augmented from the first to the second bicycling task and was significantly reduced from the second to the third F=16.49, DF=1, P<.001 (Fig. 1). Palmar sweating of normal individuals was augmented significantly during the second bicycling task F=10.32, DF=1, P<.005 and remained at the same level during the third. Forearm sweating was augmented significantly from one to the next bicycling task for both hyperhidrotic (F=38.54, DF=1, P<.000, F=11.90, DF=1, P<.003), and normal individuals (F=44.54, DF=1, P<.000, F=13.93, DF=1, P<.002).
As expected from a thermoregulatory aspect, forearm sweating was augmented within the total bicycling time in both hyperhidrotic and normal individuals. In contrast, palmar sweating of hyperhidrotics displayed a maximum during the second bicycling task when physical exercise was combined with distress, and a significant diminution during the third bicycling task after reducing the distress (Figure 1). It is also noteworthy that all hyperhidrotics displayed higher values of weight of palmar sweat than the average of that of normal individuals, during only the second bicycling task.
Females displayed more palmar sweating than males during all 3 bicycling tasks (with the difference being significant in the second task) and less forearm sweating during all 3 bicycling tasks (with significant differences in the second and third task). Correlation analysis indicated a lack of general pattern of correlation between palmar and forearm sweating in either hyperhidrotic and normal or male and female individuals

CONCLUSIONS
From the forearm electrodermal recordings and sweating we have to stress that: (i) the forearm did not present measurable EDRs during mental arithmetic tasks, (ii) the sweating of forearm, for both normal and hyperhidrotic individuals, was augmented from the first to the third bicycling task, following the heat load, which indicate a thermoregulatory pattern of activation (iii) the sweating of forearm was not correlated to palmar sweating of hyperhidrotics in any task. These findings clearly demonstrate that palmar and forearm sweating is under of different central nervous control and do not support the theory of over-functioning sympathetic fibers, passing through the T2,3 ganglia (which, according to Shih, Wu and Lin [19] "play an important role in the elaboration or modulation of autonomic function elsewhere"), as the cause of palmar hyperhidrosis. It is worth mentioned that these authors have reported the following results which are in disagreement with their own theory: T2,3 ganglionectomized individuals displayed much less sweating, during physical exercise, in their forehead, upper chest, and upper extremities than normal individuals (indicating that fibers passing through T2,3 ganglia innervate all these areas), while hyperhidrotics displayed palmar but not forehead and chest hyperhidrosis. Obviously, the sweat glands of all these areas, especially for hyperhidrotics, are not activated by the sympathetic nervous system as a unit. Findings on the pathophysiology of palmar hyperhidrosis (and especially heart rate and blood pressure recordings, and heart rate variability analysis, as a quantitative assessment of autonomic balance) do not also give support to the over-functioning sympathetic fibers theory of palmar hyperhidrosis (unpublished data).
Based on the palmar EDA recordings, both hyperhidrotic and normal groups presented significantly higher palmar sweating during the mental arithmetic in the standing than in the recumbent position. This increase cannot be considered as thermoregulatory, since forearm sweating was not respectively augmented. This finding indicates that the muscular tension increases palmar sweating (both normal and hyperhidrotic) caused by mental process. It was also found that seven hyperhidrotics presented a smaller number of EDRs than the average number of normal individuals, during the performance of mental arithmetic task in the recumbent position, but no one in the standing position. This finding questions the ability of mental effort to cause palmar hyperhidrosis by itself, showing that the tension of the muscles may be a determinative factor for the magnitude of palmar sweating.
In the other side, the significant decrease of palmar sweating of hyperhidrotics in the third bicycling task (when the distress was reduced) questions the ability of physical effort, and therefore of muscle tension, to cause palmar hyperhidrosis by itself. Among the three bicycling tasks, all hyperhidrotics expressed excessive sweating (over the average of normal individuals) only during the second one, when the physical effort was combined with distress.
These findings suggest that neither mental nor physical effort may alone provoke hyperhidrosis. Considering the distress as the active ingredient of mental effort in provoking hyperhidrosis (a pleasant or calm thought has never been mentioned as sudorific) and the muscle tension as the active ingredient of physical effort, we consider that the combination of distress with muscle tension is the necessary and efficient factor for palmar hyperhidrosis expression. This conclusion is additionally supported by the following elements: (i) the relaxation is the active ingredient in the biofeedback treatment of palmar hyperhidrosis [20] (ii) the relation between palmar sweating and muscular tension is justified from a developmental point of view, because friction improvement [21] and abrasion prevention [22], which are the mechanical purposes of plantar sweating in mammals, are necessary only to the moving animal (iii) the hyperhidrotics may not sweat at all on their palms when they perform calm a hard handiwork or mental activity. Even in the case of a mentally acting hyperhidrotic individual, when facing difficulties of no handiwork demand, its excessive palmar sweating may also be considered as the result of the combination of mental effort or distress with muscle tension, since hidden muscular activity may accompany the mental processes [23].
In this point, we have to remind that the hyperhidrotics scored significantly higher than normal individuals on the Neuroticism scale of the Eysenck Personality Questionnaire (unpublished data) and in the scales of Depression, Social Introversion, and Psychasthenia of the Minnesota Multiphase Personality Inventory (MMPI) [2]. In agreement with the suggestion of Lerer, Jacobowitz and Wahba [3] and of Lerer and Jacobowitz [4] that hyperhidrotic individuals are characterized by lower overall ability to cope with stress and a strong proclivity to avoid problems, they may be more prone to distress feelings in their everyday life activities.
Conclusively, this work, in agreement with findings of former ones, suggests that (i) palmar hyperhidrosis is not caused by over-functioning of sympathetic fibers passing through T2,3 ganglia, and (ii) the combination of distress with muscle tension is the necessary and effective condition for palmar hyperhidrosis expression. Hyperhidrotics may be individuals who feel more easily distress, and perhaps produce higher tension of muscles (caused by the distress), than normal palmar sweating individuals.

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