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Original Articles: General Thoracic

Primary Palmoplantar Hyperhidrosis and Thoracoscopic Sympathectomy: A New Objective Assessment Method

Division of Thoracic and Foregut Surgery, Department of Surgery, University of Minnesota, Minneapolis, Minnesota

Accepted for publication October 8, 2008.

^_* Address correspondence to Dr Andrade, University of Minnesota, Department of Surgery, Division of Thoracic and Foregut Surgery, MMC 207, 420 Delaware St, SE, Minneapolis, MN 55455 (Email: andr0119{at}umn.edu).

Presented at the Forty-fourth Annual Meeting of The Society of Thoracic Surgeons, Fort Lauderdale, FL, Jan 28–30, 2008.

	Abstract

Top Abstract Introduction Material and Methods Results Comment Appendix 1 Appendix 2 Discussion Acknowledgments References

 
Background: This study was conducted to establish an objective approach to evaluate symptoms and sweat production in patients with primary palmoplantar hyperhidrosis (PPH) and assess their response to bilateral thoracoscopic sympathectomy (BTS).

Methods: We conducted two institutional review board-approved studies. We performed a one-time evaluation of healthy volunteers (controls) with three questionnaires (Hyperhidrosis Disease Severity Scale, Dermatology Life Quality Index, and Short Form-36) and measurement of transepidermal water loss (TEWL; g/m²/h). We evaluated PPH patients with these same tools before and 1 month after BTS and compared them with controls.

Results: We evaluated 35 controls (mean age, 23.0 ± 3.3 years) and 45 PPH patients (mean age, 26.5 ± 12.3 years); 18 PPH patients underwent BTS and the 1-month postoperative evaluation. Hyperhidrosis Disease Severity Scale and Dermatology Life Quality Index scores were higher in PPH patients than in controls (p < 0.0001), but normalized after BTS. Short Form-36 scale scores were lower in PPH patients than in controls (p < 0.05), but improved significantly after BTS. Compared with controls, preoperative TEWL values were significantly higher in PPH patients (palmar: 142.7 ± 43.6 PPH vs 115.8 ± 48.7 controls, p = 0.011; plantar: 87.5 ± 28.8 PPH vs 57.7 ± 24.7 controls, p < 0.0001). After BTS, palmar TEWL values were significantly lower (49.1 ± 29.8, p < 0.0001). Plantar TEWL did not change significantly (77.6 ± 46.6, p = 0.52).

Conclusions: PPH patients should be objectively evaluated with standardized quality of life measures and TEWL measurements before and after treatment. We believe that this objective practical approach provides a benchmark for clinical practice and research.

	Introduction

Top Abstract Introduction Material and Methods Results Comment Appendix 1 Appendix 2 Discussion Acknowledgments References

 
Primary palmoplantar hyperhidrosis (PPH) is a vexing condition that may significantly impact quality of life (QOL). Bilateral thoracoscopic sympathectomy (BTS) is a successful treatment for patients with severe PPH, which is defined as grade 3 or 4 on the Hyperhidrosis Disease Severity Scale (HDSS). After BTS, patient satisfaction [1–4] and QOL improve [1, 3, 5–8]. However, the lack of a uniform standardized objective evaluation of such patients challenges our ability to interpret published data.

An indirect (but quantitative) measure of sweating can be obtained by measuring transepidermal water loss (TEWL), the amount of water that evaporates from the skin surface during a period of time (g/m²/h). Previously, measuring TEWL was impractical and lacked population-based norms [9–11]. However, the recent development of the hand-held VapoMeter (Delfin Technologies Ltd, Kuopio, Finland) provides a practical method to quickly assess (within 10 seconds) TEWL [12–14]. Although TEWL has been used to study contact dermatitis and to evaluate the efficacy of cosmetics and antiperspirants [15, 16], it has not been routinely used to evaluate hyperhidrosis, and few data are available on TEWL in healthy individuals. To our knowledge, two studies have objectively measured sweating (TEWL) in patients with hyperhidrosis undergoing sympathectomy [17, 18].

The purpose of our study was (1) to establish a range of normal TEWL rates for comparison with PPH patients and (2) to establish an objective, standardized, practical approach to assess PPH patients and their response to BTS.

	Material and Methods

Top Abstract Introduction Material and Methods Results Comment Appendix 1 Appendix 2 Discussion Acknowledgments References

 
Our study was approved by the Institutional Review Board. All participants provided informed consent.

Controls
We conducted a prospective study of healthy volunteers to obtain a range of normal palmar and plantar TEWL values for comparison with PPH patients. We only included individuals 18 to 30 years old, with normal body mass index (BMI; 18.5 to 24.9 kg/m²), who did not take medications (except birth control pills), who did not smoke, and who had an HDSS score of 1. We excluded patients who were pregnant or had a history of hyperhidrosis. Controls underwent a one-time evaluation with HDSS, Dermatology Life Quality Index (DLQI), Medical Outcomes Study Short-Form 36 Health Survey (SF-36), and TEWL.

PPH Patients
We reviewed the records of all consecutive PPH patients, including those with concomitant axillary hyperhidrosis, who were seen in our clinic from February 1, 2006, through December 31, 2007. All patients were evaluated with HDSS, DLQI, SF-36, and TEWL on their initial clinic visit. For those patients who underwent BTS, these measures were reassessed 1 month after BTS. After BTS, all PPH patients answered a nonstandardized questionnaire to assess the presence and severity of compensatory sweating (CS) ([Appendix 1). Patients with any of the following features were excluded: any comorbidities, pregnancy, obesity, current use of medications (except birth control pills); primary hyperhidrosis of the trunk, face, or scalp; secondary hyperhidrosis, previous sympathectomy; or previous treatment with botulinum toxin.

Questionnaires
We used 3 tools to evaluate symptoms and their impact on QOL:

HDSS
The HDSS is a validated disease-specific scale that provides a qualitative measure of the effect of patients' symptoms on their daily activities [19, 20]. The effect of symptoms on daily activities is graded in order of severity from 1 to 4: (1) sweating is never noticeable and never interferes with daily activities; (2) sweating is tolerable and sometimes interferes with daily activities; (3) sweating is barely tolerable and frequently interferes with daily activities; (4) sweating is intolerable and always interferes with daily activities.

DLQI
The DLQI (Appendix 2) is a practical, validated questionnaire for assessing QOL in patients with a variety of dermatologic conditions, including PPH [21]. The DLQI is a 10-question survey that is scored on a scale of 0 to 30, with higher scores reflecting greater impairment. The mean ± SD score for healthy volunteers is 0.5 ± 1.1.

SF-36
The SF-36 is a QOL measure that assesses eight health concepts: (1) limitations in physical activities, (2) limitations in social activities, (3) limitations in usual role activities because of physical health problems, (4) bodily pain, (5) general mental health, (6) limitations in usual role activities because of emotional problems, (7) vitality, and (8) general health perceptions. From these data, the Physical Component Summary (PCS) scale and Mental Component Summary (MCS) scale scores are calculated [22, 23].

TEWL Measurements
We used the VapoMeter for TEWL measurements. The VapoMeter is a hand-held, noninvasive, closed-chamber device that allows for precise measurement of TEWL in g/m²/h. The closed-chamber principle eliminates the influence of ambient airflows; this device is operational at evaporation rates of up to 300 g/m²/h.

The VapoMeter is calibrated gravimetrically against evaporation of three standardization samples at three evaporation rates (10, 50, and 170 g/m²/h). To calculate evaporation rates, the change of the mass (m) of the samples is plotted vs time (t). The data are fitted using the least squares method, and the slope of the regression line (k = m/t) is calculated. Because the area (A) of the sample is known, its evaporation rate (k/A) can be calculated. The manufacturer recommends the recalibration of the VapoMeter every other year.

The VapoMeter has been validated for clinical use and has a higher correlation coefficient with TEWL than gravimetry and open-chamber measurement devices, which are the established methods for assessing TEWL [12–14]. The intraindividual coefficient of variation for 10 palmar TEWL measurements with the VapoMeter in healthy volunteers is 10.1% [14].

We obtained TEWL measurements at room temperature in a quiet, air-conditioned environment. Healthy volunteers and PPH patients were allowed to acclimate in scrubs for 20 to 30 minutes. We measured palmar (midpalm) and plantar (midsole) surfaces three times on each side, calculating an average value per site for each individual. Using the VapoMeter, we also recorded the ambient temperature and humidity.

All measurements were made in accordance to the guidelines dictated by the European Expert Group for Efficacy Measurements of Cosmetics and Other Topical Products (EEMCO), including an ambient temperature 20°C to 22° ± 1°C and relative humidity of less than 50% [16].

Bilateral Thoracoscopic Sympathectomy
We performed BTS under general anesthesia, with a single-lumen endotracheal tube. Patients are positioned supine. A 5-mm camera port is placed in the inframammary crease (fifth intercostal space in the anterior axillary line) and a second 5-mm port in the third intercostal space midaxillary line. After carbon dioxide insufflation (8 to 12 mm Hg), we skeletonized the sympathetic chain from the inferior border of the second rib to the superior border of the fourth rib and transected all branches. Next, we clipped the sympathetic chain immediately underneath the second rib and immediately above the fourth rib to ensure exclusion of the third ganglion. The chain was neither transected nor excised. We cauterized the pleura along the top of the third rib laterally, for 3 to 4 cm, to transect any potential accessory sympathetic chain branches.

In patients who also had axillary hyperhidrosis, we extended the dissection of the sympathetic chain from the inferior border of the second rib to the superior border of the fifth rib and clipped below the fourth ganglion (superior border of the fifth rib). At the conclusion of the procedure, the ports were removed while the lung was expanded with positive pressure to evacuate the pneumothorax. We do not place a pleural drain. We performed the procedure on both sides sequentially.

Statistical Analysis
To analyze data, we used SAS 9.1 software (SAS Institute, Cary, NC). Where appropriate, we report our results as mean ± SD. For between group comparisons, we used a two-sample t test for continuous variables and a ² test for categoric variables. To compare HDSS and DLQI results before and after BTS, we used a Wilcoxon matched-pairs signed-rank test. To compare SF-36 scores in PPH patients before and after BTS, we used a paired t test. Under all null hypotheses, we used a two-sided = 0.05.

	Results

Top Abstract Introduction Material and Methods Results Comment Appendix 1 Appendix 2 Discussion Acknowledgments References

 
We evaluated 35 controls (22 women and 13 men; mean age, 23.0 ± 3.3) and 45 PPH patients (28 women and 17 men; mean age, 26.5 ± 12.3; 40 PPH only and 5 PPH and axillary hyperhidrosis). During the study period, 18 PPH patients (7 women and 11 men; 13 PPH and 5 PPH and axillary hyperhidrosis) underwent BTS (13 at T3; 5 at T3 and T4) and completed the 1-month postoperative evaluation. We found no complications associated with BTS; all patients were discharged home on the same day of operation. The remainder of the PPH patients had not undergone BTS by the end of the study period due to delay or rejection from their medical insurance companies.

Questionnaire Scores
Controls vs PPH patients
The HDSS and DLQI scores were significantly higher in PPH patients than in controls (Table 1). All SF-36 scale scores, except for Vitality, were significantly lower in PPH patients than in controls (Table 2).

Compensatory sweating
CS occurred in 16 of 17 of patients (94.1%) who underwent BTS (1 patient did not fill out the CS questionnaire). All patients with CS rated their symptoms as less bothersome than their original PPH symptoms. CS was mild in 15 patients (93.8%) and moderate in 1 patient with a BTS at T3. Body areas affected by CS in order of frequency were trunk (58.8%), inner thigh (47.1%), popliteal fossa (47.1%), back (23.5%), lower legs (23.5%), groin (17.6%), abdomen (5.9%), and face (5.9%). We observed no significant difference in CS between patients undergoing BTS at T3 vs BTS at T3 and T4.

TEWL in controls vs PPH patients
Palmar and plantar TEWL was significantly higher in PPH patients than in controls (Table 6). Palmar TEWL was higher in female controls than in male controls (129.5 ± 48.2 vs 92.6 ± 41.5, p = 0.03). Mean ambient temperature and humidity were 22.3°C and 26.6% for the control group and 23.1°C and 40.8% for PPH patients (p = 0.0002).

	Comment

Top Abstract Introduction Material and Methods Results Comment Appendix 1 Appendix 2 Discussion Acknowledgments References

 
We conducted this study to provide a practical, standardized approach to the evaluation of patients with PPH and to better quantify their response to BTS. Our assessment of PPH patients included validated symptom scoring and an objective indirect measure of sweating (ie, TEWL).

Symptom Evaluation
Our results confirm the validity of the HDSS and DLQI in evaluating PPH patients [19, 20, 24]. These questionnaire scores discriminate healthy volunteers and PPH patients. Furthermore, they are an objective measure of treatment response because questionnaire scores from PPH patients normalize after BTS. These questionnaires can be readily incorporated into clinical practice because they (1) are easy to administer and can be completed quickly during an outpatient visit and (2) have an uncomplicated scoring system.

The SF-36 scores demonstrated lower than normal physical and mental health dimensions in PPH patients. Within a month of operation, all components of the SF-36 (except for Physical Fitness) significantly improved. The persistence of a small difference in the Physical Fitness scale and the new change in Bodily Pain scale seen 1 month after BTS are likely explained by the effects of recent operation. In a study of 188 patients undergoing BTS for hyperhidrosis, Schmidt and colleagues [25] reported similar findings and noticed a gradual improvement in scores over time.

The most striking improvement after BTS was on the MCS scale (a marker of mental health), which increased by nearly a full standard deviation. Our SF-36 results emphasize that PPH has a significant effect on health-related QOL and that QOL significantly improves after BTS.

Transepidermal Water Loss
Our results showed that TEWL measurements with the VapoMeter were sensitive enough to detect a significant difference in palmar and plantar TEWL between controls and PPH patients. Because the VapoMeter is a closed-chamber system, it has the distinct advantage (compared with open-chamber systems) of being less dependent on ambient conditions.

The mean palmar TEWL in healthy volunteers from our study was about 15% higher than the mean TEWL reported by Nuutinen and colleagues [14] in another study that evaluated TEWL in healthy volunteers using the VapoMeter. The discordance in TEWL may be due to differences in ambient conditions, sample sizes (10 vs 35 in our study), and populations (age range 20 to 51 years vs 18 to 30 years in our study).

We also demonstrated that palmar TEWL values decreased dramatically after BTS in our PPH patients, confirming that TEWL can be used as an objective quantitative measure of a treatment effect in such patients. Our results also confirm that BTS is not an ideal treatment for plantar hyperhidrosis [26] because we were not able to demonstrate a significant difference in plantar TEWL after BTS.

Potential limitations to objective TEWL measurements in PPH patients are the large interindividual variability in palmar TEWL and the episodic nature of PPH [16, 27, 28]. Nonetheless, in our present study, palmar TEWL values were still significantly higher in our PPH patients than in our controls, suggesting that these limitations are of minimal (if any) significance.

Another potential limitation of our study was the dissimilar environmental conditions between controls and PPH patients. Although ambient temperature was similar (the mean difference was less than 1°C), ambient humidity was 14% higher in our PPH patients. The relationship between ambient humidity and TEWL is nonlinear, since the diffusion coefficient of the outer layer of the skin is not constant. TEWL rises linearly between a relative humidity of 3% and 25% and reaches a plateau between 25% and 50%. A further increase in relative humidity beyond 50% leads to a decrease in TEWL [27]. Our normal volunteers had TEWL measurements at a mean of 26.6% relative humidity, and our PPH patients had TEWL measurements at a mean relative humidity of 40.6%; these measurements are within the range where changes in relative humidity have a minimal effect on TEWL. Therefore, we do not believe that this difference would have significantly affected our TEWL results. Furthermore, our measurements were obtained at relative humidities that are within the United States federal recommendations for public buildings (20% to 60%) [29] and the EEMCO recommendations for measuring TEWL (25% and 50%) [16].

The inclusion of patients with PPH in combination with axillary hyperhidrosis could raise concern for confounding. However, we did not identify any differences in questionnaire scores, TEWL, and CS when comparing patients with PPH only with patients with PPH and axillary hyperhidrosis. Furthermore, we noted that outcomes after BTS at T3 and BTS at T3 and T4 were not significantly different. We believe that for the purpose of this study—objective evaluation of PPH and BTS—the inclusion of these patients does not confound our results.

To date, no consensus has been established on how to perform a thoracic sympathectomy for PPH. Our findings, although with short-term follow-up, also provide further objective evidence that an interruption of the sympathetic chain at the level of T3 is adequate for PPH [30, 31].

In conclusion, we present a comprehensive and detailed description of TEWL measurement as a tool for the objective evaluation of patients with PPH. PPH patients should be objectively evaluated with standardized QOL measures and with TEWL measurements before and after BTS. We believe that this standardized objective and practical approach to patients with PPH will provide a benchmark for clinical practice and research.

	Appendix 1

Top Abstract Introduction Material and Methods Results Comment Appendix 1 Appendix 2 Discussion Acknowledgments References

 
Nonstandardized Questionnaire to Assess Compensatory Sweating After Bilateral Thoracoscopic Sympathectomy. (Reprinted with permission from Allergan Inc, © 2004.)

Please circle the appropriate response.

1. Before surgery, where was your excessive sweating located (please describe below and list in order of severity)? 2. How did your initial sweating problem respond to surgery? Completely disappeared Improved Unchanged Worsened 3. How do you feel now, compared to before your surgery to relieve excess sweating? Better The Same Worse 4. Do you notice increased sweating in any new areas of your body? Yes No 5. Where is this new sweating located? Scalp Face Neck Arm Pits Hands Trunk Groin Inner aspect of thighs Behind the knees Feet Other (specify): 6. How severe is this new sweating? Mild Moderate Severe 7. How much does this new sweating bother you compared to the sweating you had before your surgery? Less than The same More than 8. Do you notice new sweating with spicy food? Yes (specify location): No 9. Please circle if you have noticed any of the following symptoms after surgery. Excessively dry hands Slow heart rate Fast heart rate Cough Wheezing Pain (rate from 1 to 10; 1 = minimal; 10 = intolerable) 1 2 3 4 5 6 7 8 9 10 Other symptoms (please specify): 10. Please add any additional comments you have.

	Appendix 2

Top Abstract Introduction Material and Methods Results Comment Appendix 1 Appendix 2 Discussion Acknowledgments References

 
Dermatology Life Quality Index. (Reprinted from with permission from Department of Dermatology, Wales College of Medicine, © A Y Finlay, G K Khan April 1992 www.dermatology.org.uk.)

DERMATOLOGY LIFE QUALITY INDEX DLQI Hospital No: Date: Score: Name: Diagnosis: Address: The aim of this questionnaire is to measure how much your skin problem has affected your life OVER THE LAST WEEK. Please tick one box for each question.

1. Over the last week, how itchy, sore, painful or stinging has your skin been? Very much A lot A little Not at all 2. Over the last week, how embarrassed or self conscious have you been because of your skin? Very much A lot A little Not at all 3. Over the last week, how much has your skin interfered with you going shopping or looking after your home or garden? Very much A lot A little Not at all Not relevant 4. Over the last week, how much has your skin influenced the clothes you wear? Very much A lot A little Not at all Not relevant 5. Over the last week, how much has your skin affected any social or leisure activities? Very much A lot A little Not at all Not relevant 6. Over the last week, how much has your skin made it difficult for you to do any sport? Very much A lot A little Not at all Not relevant 7. Over the last week, has your skin prevented you from working or studying? Yes No Not relevant If "No," over the last week how much has your skin been a problem at work or studying? A lot A little Not at all 8. Over the last week, how much has your skin created problems with your partner or any of your close friends or relatives? Very much A lot A little Not at all Not relevant 9. Over the last week, how much has your skin caused any sexual difficulties? Very much A lot A little Not at all Not relevant 10. Over the last week, how much of a problem has the treatment for your skin been, for example by making your home messy, or by taking up time? Very much A lot A little Not at all Not relevant

	Discussion

Top Abstract Introduction Material and Methods Results Comment Appendix 1 Appendix 2 Discussion Acknowledgments References

 
DR SCOTT J. SWANSON (New York, NY): Thanks very much. How much does this device cost, and are there any disposable costs associated with it, because I assume they are not recoverable charges?

DR ANDRADE: It costs about $5,000 USD. One cannot bill for the measurements; there's no CPT [Current Procedural Terminology] code for it yet.

DR SWANSON: Are there any reusable charges?

DR ANDRADE: There are no reusable charges.

DR SWANSON: Is it disposable?

DR ANDRADE: No, you don't have to dispose of anything.

DR JOSE RIBAS M. DE CAMPOS (Sao Paulo, Brazil): Congratulations for your excellent paper and presentation and also excellent results. I have a comment for you. We are also working with this device. It is a very good one. It is also very important to transform a subjective complaint of the patient into an objective measure. And I will push you to study the results after 6 months of evaluation. In 6 months, maybe you will have in the operated patients, almost the same level of the control group. If it happens, the results will be very good for your paper. And we are also studying this subject using the same device to try to find data for the normal results for the populations without hyperhidrosis, and how could be the best way to measure that. Thanks and congratulations again for your presentation.

DR ANDRADE: Thank you. We plan to follow-up on these patients in about a year. In our patient population— college age people—long-term follow-up is difficult, since they move a lot. It is very, very hard to get them back. Hopefully we will be able to get a handful of these patients back at about 1 year. We are currently still recruiting healthy volunteers to establish a population-based norm of TEWL [transepidermal water loss] values.

DR SWANSON: And do you ever measure the trunk or thighs for compensatory hyperhidrosis?

DR ANDRADE: Yes. All I showed today were the palmar data. We measure our volunteers and the PPH patients at about 20 different sites. We plan to wait with our compensatory sweating data analysis until we have completed our volunteer study.

DR SWANSON: Do you have any data on that now?

DR ANDRADE: Not now.

DR DANIEL L. MILLER (Atlanta, GA): I applaud you for an excellent presentation and your new idea. As we are faced with treating these patients, the more objective data the better, especially in regards to insurance coverage. There are a significant number of patients who undergo this procedure who should never have it done.

My question is related to the age of your patients. Practicing in a large college town, did you look at any correlation in regards to alcohol ingestion the day or two before this analysis because I think it would really throw things off related to alcohol-induced volume changes?

The number one problem with this procedure is compensatory sweating. We have found multiple factors that increase the risk of compensatory hyperhidrosis, higher BMI [body mass index], older patients, multiple level procedure, and a history of presympathectomy truncal or groin sweating. I was wondering if you plan to look at compensatory hyperhidrosis risks in the future?

DR ANDRADE: I guess I never thought about asking them if they had something to drink the night before.

DR MILLER: I lived in Minnesota for 8 years, and there is a significant amount of alcohol ingestion during the winter months.

DR ANDRADE: All we can say is that these are healthy people. The inclusion criteria are a normal BMI, no smoking, and no over-the-counter medications except birth control pills. I did not make the effort of asking them to abstain from alcohol for a week.

DR MILLER: I think it would be very interesting if insurance companies would use this to determine if someone has failed primary treatment, such as Robinul (First Horizon Pharmaceutical Corp, Alpharetta, GA), Drysol (Person and Covery Inc, Glendale, CA), or Drionics (General Medical Co, Los Angeles, CA). They may ask in the future for this type of data to say that a patient failed conservative treatment before paying for their sympathectomy. Great job.

DR ANDRADE: Thank you.

DR RODRIGO CABEZAS (Alajuela, Costa Rica): I congratulate you on having some objective data, because when I practiced in Atlanta, my colleagues and I would operate on 1 or 2 patients per year. And now we are seeing a series of hundreds of patients, and I wonder how many of those patients really need to be operated on. So I congratulate you. And this reminds me of the first rib resections where there are pockets in the country where the rate of resection of the first rib is, like, crazy because of lack of preoperative objective evaluation. Thank you.

	Acknowledgments

Top Abstract Introduction Material and Methods Results Comment Appendix 1 Appendix 2 Discussion Acknowledgments References

 
This study was supported in part by a grant from Delfin Technologies Ltd, Kuopio, Finland. We thank Mary Knatterud, PhD, for her excellent editorial assistance.

	References

Top Abstract Introduction Material and Methods Results Comment Appendix 1 Appendix 2 Discussion Acknowledgments References

 

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