ON THE ANTECEDENTS OF PALMAR HYPERHIDROSIS

ABSTRACT
We compared hyperhidrotic and normal individuals on the parameters that have been related, or could be, to excessive sweating, in order to fill the research gap on the antecedents of palmar hyperhidrosis. We performed neurological examination, general hematological test, and measurements of blood levels of thyroid hormones FT3, FT4, TSH, glucose, and electrolytes Na, K, P, Ca, Mg. The participants also fill in the Eysenck Personality, as well as a laboratory constructed Questionnaire. In addition, we compared the palmar sweat glands density of the participants using the iontophoresis of pilocarpine technique. We found that palmar hyperhidrosis cannot be attributed to any of the examined pathological parameters, or to higher density of palmar sweat glands. However hyperhidrotics scored significantly higher in Neuroticism scale of personality test. We concluded that the dysfunction is possibly related to personality traits while a genetic predisposition is also possible.


Key words: hyperhidrotic, palmar sweating, sweat glands.


Stelios Kerassidis

INTRODUCTION
Palmar hyperhidrosis refers to excessive local sweating on the palms of the hands. Although the disorder is a socially and an occupationally distressing, and sometimes disabling, condition [1], there is minimal research data on this, probably because it has not life threatening consequences. The reviews by Sato et al. [1) on the disorders of sweat glands, by Lerer [2], Lerer et al. [3] on the psychological aspects of palmar hyperhidrosis, and by Fotopoulos & Sunderland [4] on the treatment of psychophysiological disorders, underline the lack of publications on the etiology of palmar hyperhidrosis. In opposition to this lack, and probably because of this, some one can find plenty of “public opinions”. Actually, every physician, dermatologist and psychiatrist treats the patients having in mind her/his own theory concerning the antecedents of palmar hyperhidrosis. In the present work we compare hyperhidrotic and normal individuals on any of the parameters which have been related, or could be, to excessive sweating (not only of the palms) as a possible antecedent of palmar hyperhidrosis.
Laboratory and clinical tests, including the following, were performed:
1. standard neurological examination, in order to check for dysautonomy or neurological damage,
2. general hematological, investigating for a possible association of palmar hyperhidrosis with a blood abnormality,
3. measurement of blood levels of hormones FT3, FT4, TSH, investigating for a possible association of palmar hyperhidrosis with thyroid gland over-function (which can cause excessive sweating by accelerating the metabolic process),
4. measurement of blood glucose levels, in order to check for a possible association of palmar hyperhidrosis with hypoglycemia (and to exclude diabetic individuals),
5. measurement of blood levels of Na, K, P, Ca, Mg, investigating for a possible association of palmar hyperhidrosis with electrolyte imbalance [Edelberg [5] suggested that skin may have a role as an accessory kidney in control of water and electrolyte balance], or parathyroidism,
6. filling in of the Eysenck Personality Questionnaire (EPQ), in order to examine whether personality traits could differentiate hyperhidrotics from normal individuals,
7. filling in of a laboratory constructed questionnaire, in order to examine whether some habits, diseases or heredity could differentiate hyperhidrotics from normal individuals,
8. palmar sweat glands count, in order to examine whether palmar hyperhidrosis is the result of a higher sweat glands density on the palms. (The greater skin conductance activity at the distal, relative to the medial, phalanx had been attributed by Freedman et al. [6] to the greater density of sweat glands at the distal, relative to the medial, site. They suggested that there is a positive relationship between sweat glands count and skin conductance activity. This relationship holds for different areas within the palm but it could not be excluded that differences in palmar sweating between hyperhidrotic and normal individuals are caused by differences in the density of their palmar sweat glands.)
MATERIAL AND METHODS
Participants
Forty individuals participated in the tests. 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 and of the normal females was 27.3 years. The mean age of the hyperhidrotic males was 35 and of the normal males was 34.3 years. The mean body weight of the hyperhidrotic females was 60.3 (50-73) kg and of the normal females was 56.4 (45-70) kg. The mean body weight of the hyperhidrotic males was 75.6 (62-87) kg and of the normal males was 76.2 (62-102) kg. The educational level of hyperhidrotics/normal was: 11/12 higher education, 3/4 students, 6/4 secondary-lower. No individual of our study was alcohol or drug addicted, or under medication.
Twenty-four individuals (out of the previous forty) participated in the sweat gland density measurement. Twelve were hyperhidrotic and 12 normal palmar sweating individuals. Seven females and 5 males were included in each group. The mean age of the hyperhidrotic females was 28 and of the normal females was 28 years also. The mean age of the hyperhidrotic males was 33 and of the normal males was 23 years.
Individuals with palmar hyperhidrosis were recruited by the local mass media. Among those who volunteered to participate, 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 excluded of the research. Normal palmar sweating individuals were selected by the authors, among people who reported never having suffered from excessive palmar sweating. In order to confirm the participants' estimation of the degree of their palmar sweating, a sweat collecting plaster was attached to 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 3.1 mg (S.D. 2.3, range 0-7). Out of the 42 individuals who were subjected to this confirmation test, one from the hyperhidrotic group had 4 mg palmar sweat and one from the normal group had 12 mg palmar sweat. The scores of these two persons were excluded from the analysis.
Design and materials
The participants underwent a standard neurological examination and were subjected to the laboratory blood tests: general hematological, blood glucose concentration as well as blood levels of thyroid hormones (FT3, FT4, TSH) and electrolytes (Na, K, P, Ca, Mg). The participants answered many kinds of questions including: alcohol and drug consuming, medication, habits of sleep, state of digestive system, feelings of palpitation, suffocation, dizziness, skin problems, diseases in general, the time of the first appearance of hyperhidrosis, its expression in every day life, relatives suffering from hyperhidrosis etc. The Greek translation of the Eysenck Personality Questionnaire [7], comprising 84 questions and 4 scales (Neuroticism, Psychotism, Extroversion and Lying), was completed after the end of the tests.
For the sweat glands density count, the iontophoresis of pilocarpine technique [8, 9] was used as it is described below. A 3x5 cm sheet of blotting paper was soaked in 4% w/v pilocarpine chloride in benzalkonium chloride (Alkon-Courreur, Sterile ophthalmic solution) and applied to the test area of the palmar skin. Two 2x3 cm gauze pads soaked in sterile normal saline served as conductive materials. One was placed over the blotting paper, on the hypothenar eminence of the left palm and the other on the exterior side of the palm of the same hand. Two 1.5x2.5 cm copper pieces served as electrodes. The electrodes were placed over the gauze pads so that the positive electrode was over the pilocarpine. A current of 1 mA was applied for 5 min. We used 3 batteries (9V each one), connected in series, to form an electric source. The regulation of current at the value of 1 mA (provided that the individuals did not present the same value of palmar resistance due to the different thickness and wetting of stratum cormeum) was accomplished by a potentiometer connected in series with palmar resistance. After a 5 min iontophoresis of pilocarpine in the hypothenar eminence of the left palm of the individual, the palm was dried, painted with alcohol iodine and dried again. At this time the palm was placed on a paper sheet and it was firmly placed on a sloping glass, so that the testing area was laid over the paper. The experimenter looked carefully at the opposite side of the glass so that she could watch spots appearing on the paper (which turned black in the presence of sweat and iodine, because of the containing polysaccharides) in the points the sweat came out of the pores of the testing area. When it was estimated that the sweat spots were clearly distinguished, the individual was asked to remove carefully its palm from the paper sheet. This procedure of taking an imprint of the testing area on the paper sheet was repeated. Four imprints of the testing area were taken for each individual (see Fig.). Then, the paper sheets were clearly photocopied on transparent membranes and counted using the Microcomputer Imaging Device (MCID, Imaging Research INC). (The photostats were additionally necessary because fainting of the imprints on the papers would happen a few weeks later.)
The time between the placement of the palm on the paper and its removal from it was different for each individual. In order to see if there were sweat glands that they had not produced sweat till the removal of the palm (because they may have been less activated), we occasionally left the palm on the paper sheet, for longer time than that we estimated as necessary. Many sweat traces joined this way and the imprint became muddy, but no increase in the number of spots was observed.
Statistics
Two factor (sex and hyperhidrosis) analysis of variance (ANOVA) was used for comparisons between hyperhidrotic and normal individuals and between females and males in clinical tests.
The counting of the spots was accomplished via the Microcomputer Imaging Device. The device could count the spots in any selected area. We measured and compared areas of any magnitude, but we present the comparison on 1 cm2 area of hypothenar eminence (near the sulcus, indicated by the arrow in Fig.). This was the area with the higher density of spots for all individuals. The differences in the density of spots on this area (and the very adjacent) between the 4 imprints of the same individual were small (0-5%) and the higher measured value was selected for the statistical analysis. We compared the number of spots (active sweat glands) in the counted area of hypothenar eminence, by a two factor (sex and hyperhidrosis) Analysis of Variance (ANOVA).
RESULTS
Eight out of the 20 hyperhidrotics and 1 out of the 20 normal individuals declared that they had at least one close relative suffering from palmar or plantar hyperhidrosis. This difference is significant, F=6.40, P<.004. No other systematic difference between hyperhidrotic and normal individuals was revealed by the laboratory constructed questionnaire .
The neurological examination did not reveal any neurological damage or dysautonomy to any individual of both groups. No significant differences were found between hyperhidrotic and normal individuals in the general blood test, or in blood concentrations of thyroid hormones, glucose, or electrolytes. However, hyperhidrotics displayed higher scores than normal individuals (13.35 / 9.75) in EPQ Neuroticism scale (F=6.352, P<.01). There was no significant difference in any of the 3 other EPQ scales (Psychotism, Extroversion and Lying). Differences between females and males were not significant.
The mean values and standard deviations of the number of active sweat glands in the counted area of hypothenar eminence are shown in the Table. The two factor ANOVA revealed no statistically significant difference between hyperhidrotic and normal individuals (F=1.7, P<.20). Females presented a higher number of active sweat glands on the counted area (425 s.g./ cm2) than males (383 s.g./ cm2), but the difference was not statistically significant (F=3.1, P<0.09). This difference may due to the more injuries of the male palm which probably cause more destroys of sweat glands. The correlation coefficient between age and number of sweat glands count was also insignificant (r=0.079), probably because of the narrow range of the ages of participants.
DISCUSSION
The finding that significantly more hyperhidrotics than normal individuals had a close relative suffering from palmar hyperhidrosis (40% of hyperhidrotics, and only 5% of normal individuals) suggests that a genetic predisposition to excessive palmar sweating may exists. This conclusion is also supported by works like that of Adar et al in which 53% of the patients had some family history of hyperhidrosis, while 21% had first-degree hyperhidrotic, of Kwon et al. [12] in which hyperhidrotics had 30.9% familial hyperhidrosis in first degree relatives while James et al [........] studied “a family with hereditary emotional hyperhidrosis”.
According to our laboratory tests, there was no indication that the hyperhidrotics were characterised by neurological damage, dysautonomy, hematological abnormality, electrolytic or blood glucose imbalance, and thyroid gland dysfunction. We also found no statistically significant difference in the density of palmar sweat glands between hyperhidrotic and normal individuals. The hypothenar eminence is the area that touches the paper when an individual writes. It is well known that hyperhidrotics sweat so much in this area that usually need to use a napkin for writing. In the confirmation test of the participants' estimate of the degree of their palmar sweating (methods section), we found that the mean weight of palmar sweat of hyperhidrotic was 6-7 times more than that of normal individuals. If this difference was due to higher density of palmar active sweat glands, hyperhidrotics should have 6-7 times higher density compared to normal individuals. Our finding suggests that the difference in palmar sweating between hyperhidrotic and normal individuals cannot, by any means, be attributed to a difference of sweat gland density.
However, hyperhidrotics displayed higher scores than normal individuals in Neuroticism scale of Eysenck Personality Questionnaire. In another work (10), we have also found higher scores for hyperhidrotics than normal individuals in Psychotism, Depression and Social Introversion of Minnesota Multifasic Personality Inventory. We consider that these findings are in line with the suggestion of Lerer, et al. [3] and of Lerer and Jacobowitz [11] 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 all suggest that personality traits may be responsible for the palmar hyperhidrosis disorder. There is also the alternative view, that individuals who suffer from palmar hyperhidrosis may develop pathological personality traits as a consequence of this condition. Of course, the possibility of a feedback influence of hyperhidrosis on the personality of hyperhidrotic cannot be excluded, but we suggest that this is a secondary effect. The fact that some individuals started to exhibit excessive palmar sweating when they faced a serious problem, and other expressed palmar hyperhidrosis only for a transient, limited, hard period of their life (data from interviews), indicates that psychological stressors may be responsible for the disorder.
We have to mention that Kwon et al. [12] found no evidence of abnormal personality features using the EPQ on hyperhidrotics on palms, soles, and axillae. We suppose that the discrepancy between this and the present work is deceptive and it is due to the different methodology which was used. Kwon et al. [12] used only hyperhidrotics without any control group, while we used a normal palmar sweating group, matched to the group of hyperhidrotics, for comparisons. The higher score on EPQ Neuroticism scale between our matched groups of hyperhidrotic and normal individuals, do not automatically put hyperhidrotics in a psychiatric patients group, and for this reason there is not discrepancy between our work and that of Kwon et al. This difference cannot also be considered accidental. Hyperhidrotic in relation to normal individuals may probably are more anxious, with more intense emotional reactions, and a proclivity in psychosomatic disorders [13]. It is somehow like a test group to present statistically significant higher blood pressure values than a control group, without the test group to be hypertensive.
Conclusively, the findings indicate that palmar hyperhidrosis cannot be attributed either to the pathological parameters, which could be considered to be related to excessive sweating, or to higher density of palmar sweat glands. The dysfunction is possibly related to personality traits, while a genetic predisposition is also possible.
ACKNOWLEDGEMENT
The present work is one of a series of studies on palmar sweating and hyperhidrosis conducted at the Laboratory of Physiology, School of Health Sciences, University of Crete, in collaboration and with the support of the University Hospital of Crete. The present work was especially supported by the Laboratories of Clinical Chemistry and Biochemistry as well as the Nuclear Medicine of the University Hospital of Crete.

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TABLE

Mean values and standard deviations (in parentheses) of the number of active sweat glands on an area 1 cm2 of the hypothenar eminence of the palm.

Hyperhidrotics Normal Total

Female 420 (62) 429 (57) 425 (58)

Male 356 (11) 410 (78) 383 (60)

Total 393 (57) 421 (64)