Abstract
Background
Primary hyperhidrosis is a functionally and socially disabling condition resulting in social embarrassment and low quality of life. Thoracic sympathectomy is a definitive choice of treatment with favorable results. However, patients may face another embarrassing condition following surgery as compensatory hyperhidrosis which has no definitive treatment. The predictors of compensatory hyperhidrosis are controversial and remain unclear.
Patients and methods
A total of 74 patients underwent a videothoracoscopic sympathectomy for primary hyperhidrosis. We statistically analyzed our patients with correlations and uni-multivariate logistic regression models to outline the possible predictors of compensatory hyperhidrosis.
Results
A total of 45 (60.8%) patients had compensatory hyperhidrosis. The correlations showed that patients, with age greater than 21 years (P = 0.018), with body mass index (BMI) greater than 22 kg / m2 (P = 0.045), with isolated facial hyperhidrosis (P = 0.044), and with smoking status (P = 0.015), had significantly greater rates of compensatory hyperhidrosis. Similarly, the significant univariate predictors of compensatory hyperhidrosis were age > 21 (P = 0.020), BMI > 22 kg / m2 (P = 0.048), and the presence of smoking status (P = 0.015). Multivariate analysis revealed only smoking as a predictor within the threshold of significance (P = 0.078).
Conclusion
The clinical predictors of compensatory hyperhidrosis following a thoracic sympathectomy appear as older age, greater body mass index, and smoking.
Keywords: Primary hyperhidrosis, Sympathectomy, Compensatory hyperhidrosis
Introduction
Primary hyperhidrosis is a common disorder in thoracic surgery practice mostly affecting the palms of the hands, armpits, face, and plantar surfaces. Although it is benign in nature, primary hyperhidrosis may limit professional and physical activities, resulting in emotional and psychological distress, causing a low quality of life [1].
Thoracic sympathectomy is the permanent choice of treatment for hyperhidrosis; however, some complications, particularly compensatory hyperhidrosis (CH), may occur after surgery. Compensatory hyperhidrosis, which is defined as intense sweating of unaffected areas before surgery, is the most compromising complication obscuring the success of sympathectomy [2, 3]. Therefore, the predictors of compensatory hyperhidrosis are of particular significance for the avoidance of this undesirable effect.
Although some previous studies reported that factors such as age, body mass index, temperature, and family history can be used as the predictors for compensatory hyperhidrosis, the clinical predictors of this complication are still controversial [4, 5]. We conducted a study in patients who underwent a thoracic sympathectomy for hyperhidrosis, and analyzed our data to identify possible predictors for compensatory hyperhidrosis.
Patient and methods
A total of 85 patients, 39 (45.9%) male and 46 (54.1%) female with a mean age of 24.0 ± 8.0 (median = 21) (range, 12 to 44) underwent a thoracic sympathectomy with the diagnosis of primary hyperhidrosis. Among these, 74 patients with all available data of clinical features and surgical outcome, 32 (43.2%) male and 42 (56.8%) female with a mean age of 23.4 ± 7.7 (median = 21) (range, 12 to 44), were the main subjects of this study. Sixty-two (83.8%) cases had palmoplantar hyperhidrosis, whereas 6 (8.1%) patients each had isolated facial and axillary hyperhidrosis. A total of 20 (27%) patients were smokers with a mean pack year of 8.2 ± 5.7 (median = 7) (range, 1 to 21). The overall mean of BMI was 22.6 ± 3.6 kg / m2 (median = 22) (range, 17 to 36). A total of 33 (44.6%) patients had a family history. All patients were examined for possible thyroid pathology with function tests including T3, T4, and thyroid-stimulating hormone levels in addition to routine laboratory examination. Moreover, all patients were asked for a possible night sweating which is not typical for primary hyperhidrosis.
Operative procedure
Patients were operated under general anesthesia which was maintained by double lumen endotracheal intubation after placing in a semi-Fowler’s sitting position with both arms abducted and lying laterally. We opened a camera port at the level of fifth intercostal space on the anterior axillary line and a manipulation port at the level of third intercostal space on the midaxillary line with laparoscopic bladeless optical trocars (Versaport, Covidien, USA). The lungs were collapsed by either the double lumen tube or CO2 insufflation. A total of 8 (10.8%) patients had pleural adhesions. The pleural adhesions were lysed with either ligasure (Covidien, Mansfield, MA) or hook cautery if present. Firstly, we identified the sympathetic chain along the costovertebral sulcus and opened the parietal pleura with the hook cautery. Thereafter, we dissected and lifted the chain upward with the hook cautery. We performed a T2 for facial, T3 for palmar and T4 for axillary sweating. Cases with palmoplantar hyperhidrosis with varying degrees of facial hyperhidrosis underwent a T2-T4 sympathectomy. We used endoclips (Acuclip, Covidien, USA) which we applied two clips at the upper and lower levels of the related thoracic sympathetic ganglions. We started from the right side and introduced a small caliber chest tube connected to suction at both sides, which were removed following reexpansion of the lungs.
Complications
We had complications in 6 (8.1%) patients, which resulted in longer hospitalization. Among these, two (2.7%) were prolonged air leak and another two (2.7%) were pneumothorax requiring drainage. A 13-year-old girl had intraoperative cardiac arrest and was discharged on postoperative day six. Another female patient had a chylothorax. She did well after catheter drainage and chylothorax diet.
Data collection and follow-up
The pre- and postoperative data were obtained on physical examinations, hospital stays, follow-ups, with questionnaire sent via e-mail and telephone calls. Most of the patients were discharged at postoperative day 1 following chest X-ray examination. The mean of overall postoperative hospital stay was 1.3 ± 1.3 (median = 1) (range, 0 to 8) days. Excluding the complicated cases, the mean of postoperative hospital stay was 1.0 ± 0.3 days (median = 1) (range, 0 to 3) days.
All patients were subjected to a questionnaire and asked to grade the affected site of the body part in three categories as dry, humid, or persistent. If present, the severity of CH was classified into four categories: absent, mild, embarrassing, and disabling which meant that patients needed changing their clothes during the day [6].
A total of 45 (60.8%) patients had compensatory hyperhidrosis. Among these patients, 4 (8.9%) had mild, 23 (51.1%) had embarrassing, and 18 (40%) had disabling compensatory hyperhidrosis. Two (2.7%) patients had gustatory sweating. All patients were subjected to a questionnaire of a visual analog scale (VAS) for the satisfaction level after surgery categorized; much better (9–10); better (6–8); worse (3–5); much worse (0–2). The satisfaction level was much better in 35 (47.3%), better in 34 (45.9%) patients and worse in 5 (6.8%) patients. None of the patients declared a much worse satisfaction level for this question. The quality of life (QOL) after surgery was also evaluated as excellent, favorable, poor, and very poor. QOL was excellent, favorable and poor in 34 (45.9%), 35 (47.3%), and 5 (6.8%) patients, respectively. The mean postoperative follow-up time was 12.6 ± 7.8 months (median = 15) (range, 1 to 27).
Statistical analysis
Categorical variables were analyzed with the chi-square and Fisher’s exact tests as appropriate in contingency tables, whereas Student’s t test is performed for the comparison of continuous variables. The logistic regression analysis along with a stepwise procedure was applied for univariate and multivariate analyses to confirm the impact of the clinical factors on compensatory hyperhidrosis. The age, body mass index (kg / m2), and the pack year of smoking were grouped regarding the median value. The operation date was classified as spring / summer and fall / winter to assess the effect of season on compensatory hyperhidrosis.
We analyzed age, gender, body mass index (kg / m2), smoking status, family history, the location of hyperhidrosis, the season of the operation, pleural adhesion, and postoperative complication as the possible predictors of compensatory hyperhidrosis. Data were expressed as mean ± standard deviation. A P value of less than 0.05 was considered as statistically significant. All statistical analyses were performed with the statistical package for social sciences (SPSS, version 23.0, Chicago, IL, USA).
Results
Correlations
The mean ages of patients with and without CH showed a significant difference (P = 0.008) (Table 1). Similarly, the age groups were significantly different with respect to CH. Patients older than 21 years had a rate of CH as 75.8% (P = 0.018). The mean BMI of patients with and without CH presented significant difference (P = 0.019). Likewise, the rate of CH (74.2%) in patients with BMI greater than 22 kg / m2 was significantly greater (P = 0.045). All patients with isolated facial hyperhidrosis developed CH (P = 0.044). In addition, smokers had a greater rate of CH as 85% (P = 0.015). Other clinical features did not show significant relationship with compensatory hyperhidrosis.
Table 1.
Correlations of clinical features with compensatory hyperhidrosis
| Variable | Compensatory sweating (+) no (%) | Compensatory sweating (−) no (%) | P value |
|---|---|---|---|
| Age (years old) | 25.3 ± 8.4 | 20.4 ± 5.5 | 0.008 |
| Age | |||
| ≤ 21 | 20 (48.8) | 21 (51.2) | 0.018 |
| > 21 | 25 (75.8) | 8 (24.2) | |
| Gender | |||
| Male | 21 (65.6) | 11 (34.4) | 0.459 |
| Female | 24 (57.1) | 18 (42.9) | |
| BMI (Body mass index) | 23.4 ± 3.7 | 21.4 ± 3.0 | 0.019 |
| BMI (Body mass index) | |||
| ≤ 22 | 22 (51.2) | 21 (48.8) | 0.045 |
| > 22 | 23 (74.2) | 8 (25.8) | |
| Smoking status | |||
| Present | 17 (85) | 3 (15) | 0.015 |
| Absent | 28 (51.9) | 26 (48.1) | |
| Smoking status (pack year) | |||
| ≤ 7 | 10 (90.9) | 1 (9.1) | 0.566 |
| > 7 | 7 (77.8) | 2 (22.2) | |
| Family history | |||
| Present | 19 (57.6) | 14 (42.4) | 0.609 |
| Absent | 26 (63.4) | 15 (36.6) | |
| Location of hyperhidrosis | |||
| Palmoplantar | 36 (58.1) | 26 (41.9) | 0.751 |
| Facial/axillary | 8 (66.7) | 4 (33.3) | |
| Location of hyperhidrosis | |||
| Isolated facial | 6 (100) | – | 0.044 |
| Palmoplantar/axillary | 39 (57.4) | 29 (42.6) | |
| Location of hyperhidrosis | |||
| Plantar | 34 (59.6) | 23 (40.4) | 0.583 |
| Non-plantar | 10 (58.8) | 7 (41.2) | |
| Season of operation | |||
| Spring/summer | 30 (62.5) | 18 (37.5) | 0.686 |
| Fall/winter | 15 (57.7) | 11 (42.3) | |
| Pleural adhesion | |||
| Present | 4 (50) | 4 (50) | 0.704 |
| Absent | 41 (62.1) | 25 (37.9) | |
| Postoperative complication | |||
| Present | 5 (83.3) | 1 (16.7) | 0.394 |
| Absent | 40 (58.8) | 28 (41.2) | |
| Discharge time (days) | 1.4 ± 1.6 | 1.2 ± 0.9 | 0.662 |
Univariate and multivariate analysis
The significant univariate predictors of CH were age > 21 (P = 0.020), BMI > 22 kg / m2 (P = 0.048), and the presence of smoking status (P = 0.015) (Table 2). However, only the presence of smoking status showed a trend towards the significance in multivariate analysis (P = 0.078) (Table 3).
Table 2.
Univariate predictors of compensatory hyperhidrosis
| Variable | Relative risk | % 95 confidence | P value |
|---|---|---|---|
|
Age > 21 versus ≤ 21 |
3.281 | 1.202–8.959 | 0.020 |
|
Gender Male versus female |
1.432 | 0.553–3.708 | 0.460 |
|
BMI (Body mass index) > 22 versus ≤ 22 |
2.744 | 1.007–7.478 | 0.048 |
|
Smoking status Present versus absent |
5.262 | 1.380–20.064 | 0.015 |
|
Smoking status (pack year) ≤ 7 versus > 7 |
2.857 | 0.215–37.990 | 0.426 |
|
Family history Absent versus present |
1.277 | 0.500–3.264 | 0.609 |
|
Location of hyperhidrosis Facioaxillary versus palmoplantar |
2.167 | 0.534–8.792 | 0.279 |
|
Location of hyperhidrosis Facial versus palmoplantar/axillary |
3.718 | 0.412–33.560 | 0.242 |
|
Location of hyperhidrosis Plantar versus non-plantar |
1.035 | 0.344–3.113 | 0.951 |
|
Season of operation Spring/summer versus fall/winter |
1.222 | 0.462–3.234 | 0.686 |
|
Pleural adhesion Absent versus present |
1.640 | 0.376–7.150 | 0.510 |
|
Complication Present versus absent |
3.500 | 0.388–31.609 | 0.265 |
Table 3.
Multivariate predictors of compensatory hyperhidrosis
| Variable | Relative risk | % 95 confidence | P Value |
|---|---|---|---|
|
Age > 21 versus ≤ 21 |
1.809 | 0.581–5.635 | 0.307 |
|
BMI (Body mass index) > 22 versus ≤ 22 |
2.123 | 0.723–6.231 | 0.170 |
|
Smoking status Present versus absent |
3.663 | 0.864–15.528 | 0.078 |
Discussion
Primary hyperhidrosis is a sweating disorder, which results in mainly hygienic and social problems. The incidence is about 1% being more prevalent among teenagers and young adults. It is a chronic idiopathic condition which has also been defined as focal, visible, and excessive sweating of at least 6 months duration accompanied by two of the following characteristics: the bilateral and symmetric symptoms, the onset before age 25, the impairment of daily activities, at least one episode per week, the focal sweating that ceases during sleep or a family history [7]. The familial association for primary hyperhidrosis has been reported ranging from 13 to 57%, which was 44% in our study.
Although a number of non-surgical treatments with temporary relief are available for primary hyperhidrosis including medical treatment, botox injection, and iontophoresis, videothoracoscopic sympathectomy appears as the most promising treatment with its highly favorable and permanent results. However CH remains as a major issue following a sympathectomy with an incidence rate reported ranging from 3% to 98%, and without any definitive treatment [4]. Compensatory hyperhidrosis is actually the result of the thermoregulatory mechanism, which activates the sweat glands to compensate for the decreased sweating of the glands after sympathectomy. The total amount of body sweating shows no difference after sympathectomy [8]. Thus, it has been postulated that CH was a kind of redistribution of sweat from denervated areas to the areas still under the control of sympathetic system. Another hypothesis suggests the complication results from the reduced inhibitory feedback to the hypothalamus. Afferent signals regarding thermal information from different body parts to the hypothalamus result in efferent signals to the sweat glands. The interruption of the sympathetic ganglia blocks negative feedback signals and amplifies efferent amplitude, which induce excessive sweating on the entire body except in sympathetically denervated areas [9]. Sweating mainly affects the face, trunk, groin, and thigh as in our cases with a rate of 33 to 86%, and obscures the success of sympathectomy [2, 3].
Controversy exists regarding specific surgical technique and the thoracic level of sympathectomy to minimize the rate of CH with favorable outcomes. It was initially considered that fibers from T2 alone innervated eccrine sweat glands in the upper extremity and a limited T2 sympathectomy alone would be efficient. However, postganglionic nerves, called accessory nerves of Kuntz, were discovered to be emerging from T3 and T4 ganglions and entering the brachial plexus. This finding showed that denervation of T2 alone was not sufficient, and denervation of T2-T3 or T2-T4 was also necessary [10]. A recent study showed that R2/R3 sympathectomy has a significantly greater relative risk of CH comparing to R4/R5 sympathectomy [11]. However, patients undergoing unilateral T2 and contralateral T2-T3 sympathectomy developed bilateral CH at the same rate of 80% [12]. Similarly, a review of 87 articles concluded that limiting the level of sympathetic ablation did not decrease the incidence of CH [13]. On the other hand, we did not find any significant difference of CH with respect to the location of hyperhidrosis when we classified the subgroups as palmoplantar and facial-axillary hyperhidrosis. However, all of our six patients with facial hyperhidrosis who underwent a limited T2 sympathectomy developed CH in our study. Similarly, a recent study showed that the rates of CH are the least in patients with palmar hyperhidrosis (8%) and greater in patients with axillary (26%) and the highest in craniofacial (44%) hyperhidrosis [14].
Widespread hyperhidrosis, older age, the greater rates of body mass index (kg / m2), high ambient temperature and the family history have been reported as predictors for compensatory hyperhidrosis [4, 5, 11]. A previous series of 130 patients underwent videothoracoscopic sympathectomy reported that the season of the operation had an impact on compensatory sweating, and patients operated in winter and fall have lesser rates of compensatory sweating [15]. However, we could not find a significant seasonal difference in our study. Rodriquez et al. did not find age, family history, the type of hyperhidrosis, and the extent of sympathectomy as predictors of CH; however, female gender was a predisposing factor in their study [16]. Some authors also found the increased age to be a risk factor for CH [14, 17]. Different from other studies, we first analyzed our data with correlations in contingency tables. Thereafter, we performed a more powerful analysis with univariate and multivariate logistic regression model. We found older age, greater BMI (kg / m2) and smoking as clinical predictors of CH in univariate analysis, and only smoking showed a trend towards significance in multivariate analysis. Nicotinic acetylcholine receptors might have a role in this finding, which needs further studies [18]. In a recent paper, plantar sweating was also reported as the indicator of the lower risk of compensatory sweating after thoracic sympathectomy [19]. However, patients with or without plantar hyperhidrosis developed almost the same rates of CH in our study. On the other hand, our findings showed that the patients with facial hyperhidrosis, greater BMI rates (kg / m2) and older age developed CH at a higher rate following sympathectomy which was consistent with the findings of this recent study.
The experience on treatment of CH is very limited with small number of series and no definitive treatment is yet established. The medical treatment of CH includes topical agents such as aluminum chloride (Drysol), botulinum toxin A, and oral anticholinergics such as glycopyrrolate (Robinul), oxybutinine (Uropan), and also iontophoresis if available. The surgical treatment consists of removal of clips and T6-T9 sympathectomy. A study comparing the effect of these methods revealed that T6-T9 sympathectomy resulted in partial and transient diminishing of symptoms [20]. However, the most promising results were with regional abdomino-lumbar iontophoresis. The removal of clips did not have satisfactory results in this study. Likewise, it was shown that Wallerian degeneration of myelinated fibers and axonal loss occurred within 10 days after clipping of the sympathetic chain [21]. Thus, early removal of clips within 2 weeks was recommended for reversal of CH [22]. However, we removed the clips in our 6 patients within postoperative 1 to 27 months following an unfavorable medical treatment, and the patients did well with compensatory sweating without any reversal of improved palmar hyperhidrosis. Very recently, sympathetic nerve reconstruction was recommended with promising results as an alternative treatment for patients with severe CH that is unresponsive to conservative treatment [23].
In conclusion, compensatory hyperhydrosis is a common and sometimes a devastating complication following thoracic sympathectomy without any definitive treatment. Patients being operated for facial hyperhidrosis are under a great risk for compensatory hyperhidrosis. Older age, greater body mass index and smoking should be considered as the possible predictors of compensatory hyperhidrosis. Thus, the patients undergoing thoracic sympathectomy should be informed about this possible life-disrupting complication.
Compliance with ethical standards
Conflict of interest
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Our study has been performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. This is a retrospective study on a series of patients who underwent a thoracic sympathectomy for primary hyperhidrosis and “for this type of study formal consent is not required.
Footnotes
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