The suggestion of Shih et al.  that palmar hyperhidrotics have an over-functioning of sympathetic nervous fibers passing through the 2 and 3 thoracic ganglia, is probably the only pathophysiological suggestion on palmar hyperhidrosis disorder. Considering the weakness of this suggestion to explain the relation between palmar and plantar hyperhidrosis, in the present work, we examine the validity of this. We performed simultaneous recording of palmar and forearm electrodermal activity during behavioural tests, heart rate and blood pressure recordings between tests, and heart rate variability analysis after a 24hour Holter electrocardiogram recording, on hyperhidrotic and normal individuals. We did not find either any correlation of forearm with palmar sweating, neither higher cardiac sympathetic activity on hyperhidrotic in relation to normal individuals. We consider that there are not findings justifying the suggestion that the antecedent of palmar hyperhidrosis is the over-function of sympathetic nervous fibers which pass through the 2,3 thoracic ganglia.
Key words: palmar sweating, hyperhidrotic, autonomic, heart rate variability analysis.
The palmar hyperhidrosis-excessive sweating on the palms of the hands-is a very little investigated disorder. As Sato et al.  have mentioned, although some publications on palmar hyperhidrosis are available, most of them focus on therapy rather than the pathophysiology of the problem.The only clear pathophysiological suggestion is probably that of Shih et al. , according to which, palmar hyperhidrotics have an over-functioning of the sympathetic nervous fibers which pass through the 2 and 3 thoracic (T2,3) ganglia. Doubts concerning the validity of this theory are raised, in the first place, by its weakness to explain the relation between palmar and plantar hyperhidrosis. Palmar hyperhidrotics usually express plantar hyperhidrosis too, but there is not any suggestion for a simultaneous over-functioning of the sympathetic nervous fibers passing through the 1 and 2 lumbar (L1,2) ganglia, which innervate the sweat glands of the soles. The suggestion of Shih et al.  that the over-functioning of the sympathetic fibers passing through the T2,3 ganglia play an important role in the elaboration or modulation of autonomic function elsewhere, refers to the upper extremities, chest, heart etc. and not to the soles. In the present study, we tested the validity of that theory, by (i) recording, simultaneously with palm, the electrodermal activity (EDA) of forearm, during behavioural tests (according to Shih et al. , forearm must exhibit hyperhidrosis too, since sympathetic fibers passing through T2,3 ganglia innervate both palm and forearm) (ii) heart rate (HR) and blood pressure (BP) recordings between behavioural tests, and (iii) analysis of heart rate variability (HRV) (according to Shih et al.  hyperhidrotics must have higher sympathetic cardiovascular activity). In this point, we have to notice that the aim of the HRV analysis is the quantitative assessment of autonomic balance [10,11,13,14]. Although the HRV analysis is subject to some controversy, the method has revealed autonomic dysfunction not only in cardiac diseases  but also in multiple sclerosis  and in functional abdominal pain ; Jorgensen et al.  found significant differences to the beat-to-beat variation to an experimental psychological stressor even in healthy subjects.
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.Individuals with palmar hyperhidrosis were recruited by advertisements in 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. The authors, among people who reported never having suffered from excessive palmar sweating, selected normal palmar sweating individuals. 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. Although these 2 persons participated in all the tests, their scores were excluded from the analysis since they did not have the electrodermal behaviour they had declared. 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 participant’s electrodermal behaviour.
Materials and procedure The behavioural tasks (auditory stimulation, 2 sessions of mental arithmetic, handgrip, and 3 sessions of bicycling) were performed early in the afternoon in a room with dim light and low ambient noise. The skin conductance of the palm and forearm of the right hand was recorded by means of computer assisted J&J Modules (Unicomp). During bicycling, we used sweat collecting plasters  to measure the amount of sweat, because the excessive sweating could cause artefacts to electrodermal recordings. We will not describe in detail the procedure (concerning the psychological aspect) of the behavioural tasks. In this work, we are interested only in the HR and BP recordings and in the relation between the palmar and forearm sweating during the tasks. Blood pressure and heart rate were measured at the beginning of the experimental procedure, as well as before and after the handgrip task and the three bicycling tasks. All blood pressure and heart rate measurements were recorded at the same position (recumbent), in order the influence of postural changes to be excluded, using a Philips semi-automatic gauge. The experimenter inflated the tube and the values of heart rate and blood pressure were automatically calculated and presented in the screen of the instrument.Twenty four hours electrocardiogram recording by a Holter unit was performed on every participant, during her/his ordinary activities. The heart rate variability, reflected in these recordings, was estimated by power spectral analysis using a computer of Marquette Electronics. As it was mentioned, the aim of this analysis was the quantitative assessment of autonomic balance.
Statistics Two factor (sex and hyperhidrosis) analysis of variance (ANOVA) was used for comparisons of the palmar and forearm EDA, as well as of the HRV analysis values between hyperhidrotic and normal, male and female individuals. Correlational analyses were performed between palmar and forearm sweating. Heart rate variability during the night and daytime was calculated using fast-Fourier transform. Parasympathetic efferent activity has been interpreted as being primarily responsible for the high frequency, and both sympathetic and parasympathetic for the low-frequency component of HRV. This way, power spectra were quantified in 2 frequency bandwidths: 0.04-0.15 Hz (low-frequency power [LF]) and 0.15-0.40 Hz (high-frequency [HF]). The log (HF) was used as an index of parasympathetic nervous system activity, and the log (LF/HF) as an index of sympathetic [9,10,12,13]. Three factor ANOVA/MANOVA with sex and hyperhidrosis as between-subject factors and repeated measures as within subject factor was performed for comparisons of the blood pressure and heart rate measurements.
The forearm, in opposition to the palm, did not respond electrodermally to noise stimulation and to the mental arithmetic tasks. In both mental arithmetic tasks, the correlation between palmar and forearm SCL (the mean skin conductance level was calculated by the computer every 4s, while the SCL over the experimental period was taken as the average of all 4s periods) was significant (P<.05) only for normal individuals (r1=.468 and r2=.487) and insignificant for hyperhidrotic individuals (r1=.386 and r2=.09). During handgrip, the correlation between palmar and forearm SCL was also significant (P<.05) only for normal individuals (r=.432) and insignificant for hyperhidrotic individuals (r=.11).No significant difference was found in forearm weight of sweat between hyperhidrotic and normal individuals, during the bicycling tasks. As expected from a thermoregulatory aspect, forearm sweating was augmented within the total bicycling time to both hyperhidrotic and normal individuals. In contrast, palmar sweating in hyperhidrotics displayed a maximum during the second bicycling task (physical exercise combined with social stressor) and a significant diminution during the third bicycling task (physical exercise after reducing the stressor). Females displayed higher palmar but lower forearm sweating than males during all 3 bicycling tasks. Correlation analysis indicated a lack of general patterns of correlation between palmar and forearm sweating in either hyperhidrotic and normal or male and female individuals during the bicycling tasks.Two out of the 24 female individuals (1 hyperhidrotic and 1 normal) were not included in the analysis of heart rate variability because of technical problems. Neither the parameters of Time and Frequency Domain Analysis nor the log (LF/HF) and the log (HF), as defined in the methods section, were significantly different in hyperhidrotic compared to normal individuals. The sex factor did not result in any significant difference within the total of the recorded 24hour analysis, but the analysis within each hour separately on any of the above mentioned parameters revealed that males displayed significantly higher log (LF/HF) values (index of sympathetic nervous activity) compared to females for 5 of the 1hour periods.No significant difference was found between hyperhidrotic and normal individuals in any measurement of systolic blood pressure (SBP). Males displayed significantly higher SBP than females in all measurements. The bicycling tasks caused a significant augmentation in SBP in hyperhidrotics (F=6.39, P<.02). The augmentation in SBP, caused by the bicycling tasks in normal individuals was not statistically significant.In contrast to SBP, diastolic blood pressure (DBP) was significantly higher in hyperhidrotics compared to normal individuals even from the beginning of the experimental procedure (F=6.63, P<.014). Males displayed significantly higher DBP than females in all measurements. No task caused any significant augmentation in DBP to either hyperhidrotic or normal individuals.No significant difference was found in any measurement of heart rate (HR) in hyperhidrotic compared to normal individuals. The bicycling tasks caused a significant augmentation in HR both in hyperhidrotics (F=10.18, P<.005) and normal individuals (F=4.65, P<.05).
The sympathetic fibers which pass through the T2,3 ganglia innervate the sweat glands of both palms and forearm. If these fibers over-functioned in hyperhidrotics, they should cause forearm hyperhidrosis too. But, when the heat load, during bicycling tasks of the present work, caused profuse thermoregulatory sweating to both groups, the amount of sweat of the forearm of hyperhidrotic and normal individuals was the same, while the amount of the sweat of the palm was very different. It is worth mentioning that Shih et al.  reported an analogous finding, in opposition to their own theory: although T2,3 ganglionectomized individuals displayed much less sweating in their forehead, upper chest, and upper extremities, during physical exercise, than normal individuals (demonstrating that fibers passing through T2,3 ganglia innervate all these areas), hyperhidrotics displayed palmar but not forehead and chest hyperhidrosis during physical exercise. In addition, the lack of correlation between palmar and forearm EDA, or sweating in hyperhidrotics, in any task, diminishes the possibility of a common over-functioning fibers innervation. We have to remember that in normal individuals, the correlation between palmar and forearm EDA was significant for the first 3 tasks. These findings indicate not only that the sudomotor fibers passing through T2,3 ganglia are not generally overactive in hyperhidrotics, but also that the sudomotor triggering of their palms and forearms are extremely different.However, the higher DBP of hyperhidrotics throughout the tasks and the significant augmentation of SBP of hyperhidrotics after the bicycling are findings, which seem to agree with the over-functioning of sympathetic fibers theory. According to Shih et al. , who examined cardiovascular responses to Valsalva maneuver, the over-functioning of sympathetic fibers passing through T2,3 ganglia plays an important role in the modulation of autonomic function elsewhere. The higher BP measures of hyperhidrotics in the behavioral tasks of the present work could be due to the over-functioning of these sympathetic fibers. But the following findings contradict this view: (i) HR and SBP did not differ significantly between hyperhidrotic and normal individuals in any measurement, (ii) HR augmentations caused by tasks did not differ significantly between hyperhidrotic and normal individuals, and (iii) the HRV analysis of 24hour recording did not reveal any tonic sympathetic over-activity (not even a difference like the one found between males and females) among hyperhidrotics. The higher DBP and the significant increase of SBP of hyperhidrotics after bicycling were more likely caused by higher tonic sympathetic vasoconstrictor activity than by the over-function of sympathetic fibers passing through T2,3 ganglia. This interpretation is in agreement with findings of intraneural recordings which have shown that vasoconstrictor impulses may (or may not) accompany sudomotor ones.[17,18]. Finally, if the palmar hyperhidrosis is due to over-function of special thoracic sympathetic fibers and not due to some kind of central command, the following questions cannot be answered: (i) Why hyperhidrosis in palms is very often accompanied by hyperhidrosis in soles, given that soles are innervated by fibers passing through 1 and 2 lumbar ganglia (L1,2) and not T2,3 ganglia? (ii) Why the palmar hyperhidrotics, who underwent surgical treatment (bilateral upper dorsal sympathectomy), suffered postoperatively from plantar hyperhidrosis? . It seems much more reasonable to be supposed that there is a common central nervous system pathway to the sweat glands of palms and soles, which had been originated to serve friction improvement  and abrasion prevention  for mechanical purposes in mammals, which they have sweat glands only in these areas and not in the hairy skin. Probably, when the palmar peripheral section of this pathway is cut off, the other (plantar) substitutes its function. In opposition, there is no way to realize how the over-function of some thoracic sympathetic fibers could be replaced by the over-function of some other lumbar.We may suppose that the cardiovascular over-response of hyperhidrotics during the manoeuvres (Valsalva, face immersion etc.) of the work of Shih et al. , was due to a higher sympathetic activation (of the type of fight-flight reaction) caused by their personality characteristics [7,8,20] and it was not due to the over-function of sympathetic nervous fibers passing through T2,3 ganglia. We concluded that the suggestion of Shih et al. , that the over-function of sympathetic nervous fibers passing through T2,3 ganglia is the antecedent of palmar hyperhidrosis, is supported by no evidence.
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 Cardiology Department of the University Hospital of Crete. We thank Dr. Michael Kalaitzakis for his assistance in HRV analysis.
1. Adelman, S.,
Taylor, C. and Meglung, N., Sweating on paws and palms: what is its function? Am. J. Physiol., 229 (1975) 1400-2.
2. Ajiki, K., Murakawa, Y., Yanagiawa-Miwa, A., et al., Autonomic nervous system activity in idiopathic dilated cardiomyopathy and in hypertrophic cardiomyopathy, Am. J. Cardiol., 71 (1993) 1316-20.
3. Bogokowsky, H., Slutzki, S., Bacalu, L., et al., Surgical treatment of primary hyperhidrosis (a report of 42 cases), Arch. Surg., 18 (1983) 1065-7.
4. Jorgensen, L.S., Christiansen, P., Raundahl, U., et al., Autonomic nervous system function in patients with functional abdominal pain, Scand. J. Gastroenterol, 28 (1993) 63-86.
5. Jorgensen, L.S., Christiansen, P., Raundahl, U., et al., Autonomic response to an experimental psychological stressor in healthy subjects: measurement of sympathetic, parasympathetic, and pituitary-adrenal parameters: test-retest reliability, Scand. J. Clin. Lab. Invest., 50 (1990) 823-9.
6. Kerassidis, S., Is palmar and plantar sweating thermoregulatory? Acta Physiol. Scand., 52 (1994) 259-63.
7. Lerer, Β., Hyperhidrosis: A review of its psychological aspects, Psychosomatics, 18 (1977) 28-31.
8. Lerer, Β., Jacobowitz, J. and Wahba, A., Personality features in essential hyperhidrosis, Int. J. Psychiatry Med., 10(1) (1980) 59-67.
9. Lerer, Β. and Jacobowitz, J., Τreatment of essential hyperhidrosis by psychotherapy, Psychosomatics, 22(6) (1981) 536-8.
10. Malliani, A., Lombardi, F. and Pagani, M., Power spectrum analysis of heart rate variability: a tool to explore neural regulatory mechanisms, Br. Heart J., 71 (1994) 1-2.
11. Marquette‘s Electronics HRV Physician’s Guide (ME HRV PG) (2nd ed.), Milwaukee, 1992.
12. Neubauer, B. and Gundersen, J.G., Analysis of heart rate variations in patients with multiple sclerosis, J. Neurol., Neurosurg. Psychiatry, 41 (1978) 417-9.
13. Pagani, M., Lombardi, S., Guzzetti, S., et al., Power spectral analysis of heart rate and arterial pressure variabilities as a marker of sympatho-vagal interaction in man and conscious dog, Circ. Res., 59 (1986) 178-93.
14. Pomeranz, B., Macaulay, J., Caudill, M., et al., Assessment of autonomic function in humans by heart rate spectral analysis, Am. J. Physiol., 248 (1985) H151-3.
15. Sato, K., Kang, W., Saga, K. and Sato, K.T., Biology of sweat glands and their disorders: 2. Disorders of sweat gland function, J. Am. Acad. Dermatol., 20 (1989) 713-26.
16.Shih, C.J., Wu, J.J. and Lin, M.T., Autonomic dysfunction in palmar hyperhidrosis, J. Auton. Nerv. Syst., 8 (1983) 33-43.
17. Wallin, G. and Elam, M., Insights from intraneural recordings of sympathetic nerve traffic in humans, NIPS, 9 (1994) 203-7.
18. Wallin, G., Intraneural recordings of normal and abnormal sympathetic activity in man. In R. Bannister and C. Mathias (Eds.), Autonomic Failure, Oxford Medical Publications, London, 1992, pp. 359-77.
19. Wilcott, R., Adaptive value of arousal sweating and the epidermal mechanism related to skin potential and skin resistance, Psychophysiology, 2 (1966) 249-62.
20. Κερασίδης, Σ. και Μπιτζαράκη, Κ. Στοιχεία της προσωπικότητας των υπεριδρωτικών στις παλάμες [ Kerassidis, S. and Bitzaraki K., Personality traits of hyperhidrotics in palms], Ψυχιατρική, 8 (1997) 181-187.