Surgical vs non-surgical treatment options

Treatment of hyperhidrosis is not solely surgical. In fact, a variety of non-operative therapeutic options exist, which are typically reserved for mild to moderate forms of the condition. The majority of these consist of topical agents that are applied directly to the affected area. These include: aluminum chloride hexahydrate (AlCl₃·6H₂O), which blocks the lumen of eccrine glands, and anticholinergic agents, which function to decrease the local cholinergic impulse at the end organ of the eccrine gland^[3]. Typically, topical agents are used as first-line treatment due to their ease of application and relative economic viability. The main side effect is skin irritation^[11]. Oral agents in the form of anticholinergic muscarinic receptor competitive blockers are not as commonly used due to significant degree of side effects^[3].

Iontophoresis (the passage of a galvanic current through skin that is submerged in water) has been used as first-line therapy for more severe cases. The principal function of iontophoresis is that the passage of current tends to disrupt and block the eccrine ducts. Contraindications to treatment include pacemakers, pregnancy and implanted metal devices^[16,29]. Botulinum toxin intradermal injections can also be used in the treatment of hyperhidrosis. The toxin works to inhibit the release of the cholinergic neuro transmitter acetylcholine at the synaptic junction. Botulinum toxin therapy (similar to iontophoresis) can be used in the setting of failed topical therapy and is considered by many to be first-line treatment in the setting of craniofacial hyperhidrosis. Improved clinical outcomes occur within 2 weeks of treatment and will last on average 6–8 months^[3]. Contraindications to treatment include hypersensitivity to albumin and history of peripheral neuropathies or neuromuscular junction disorders^[15,30]. The main limiting factor for the usage of botulinum toxin injections is the fact that the effect is temporary, and the cost of treatment is substantial.

The Canadian Hyperhidrosis Advisory Committee recently used an evidence-based approach to outline a treatment of hyperhidrosis primarily based on the location and severity of the disorder. Essentially, for palmorplantar and axillary mild forms of the disease, first-line therapy should consist of topical aluminum chloride, with botulinum toxin and iontophoresis therapy as second-line options in refractory cases. The latter two options are reserved as first-line treatment options for severe cases, as well as craniofacial hyperhidrosis. According to the expert consensus panel, surgical intervention should be reserved for refractory cases that do not respond to any of the aforementioned treatment modalities^[11]. It is important to note, however, that surgery is the only therapeutic option that offers permanent benefit, which is likely why it is becoming more actively sought out as compared to botulinum toxin intradermal injections^[31].

Surgery in the treatment of hyperhidrosis is not a new phenomenon. However, with the emergence of minimally invasive thoracoscopy, surgery has emerged as a viable option in the treatment of particularly palmar and plantar hyperhidrosis. Thoracic sympathectomy has evolved with time from an invasive and technically demanding procedure to a simple minimally invasive, bilateral same-day operation^[1,26,27]. With this progression and increased accessibility, the role of surgery in the treatment of hyperhidrosis has significantly developed. Initially, sympathectomy was performed via an open posterior approach (using paramedian incision around the vertebrae followed by resection of the proximal 3 cm of rib), as well as a supraclavicular approach (via dissection of the scalene muscle insertion without breaching of the pleura). More refined and potentially less morbid techniques were later developed, including the anterior transthoracic approach using a thoracotomy incision and the transaxillary approach entering the second intercostal space for more direct visualization of the sympathetic trunk in the superior sulcus. The latter approach has generated widespread acceptance, and is likely the next most feasible option in the case of failed thoracoscopic sympathectomy^[26].

Surgical principles of thoracic sympathectomy

The first minimally invasive thoracic sympathectomy was performed in the 1950s by Kux, who described an endoscopic technique for the procedure^[32]. Thoracoscopic sympathectomy for palmar hyperhidrosis emerged as the most definitive treatment in the early 1990s, and since then, several facets of the procedure have been under contention^[33]. The procedure is performed with single or double-lumen endotracheal ventilation, with the patient in the supine position and in deep reverse Trendelenburg. This allows the non-ventilated lung to fall away from the superior sulcus. Bilateral sympathectomies can be performed during the same procedure, and patients may not require a chest tube following lung re-expansion. Insufflation of the hemithorax with carbon dioxide (not exceeding 10 mmHg in order to avoid tension pneumothorax) may be performed in order to increase the working space and improve visualization. Disruption of the sympathetic chain takes place on the anterior surface of the corresponding dorsal rib, with the level of thoracic chain disruption (T2, T3, T4, etc.) corresponding to the rib^[26]. An important technical principle to consider is the presence of a communicating sympathetic ramus that crosses the second rib (Kuntz nerve). It may be prudent to attempt to locate this communicating nerve, if present, since incomplete disruption may lead to failure of the procedure with persistent transmission of sympathetic stimuli down the thoracic sympathetic chain^[1,26]. However, it is unclear at the moment if there is any definitive benefit in disrupting the nerve of Kuntz, and some authors even doubt the existence of the nerve as an anatomical entity.

Variation exists with regards to the method of disruption as well as the level of disruption. The latter two principles comprise the majority of the controversy regarding thoracic sympathectomy in the treatment of hyperhidrosis^[1,26,28,34].

It is important to establish definition in the case of such controversies. ‘Sympathectomy’ is defined as the removal/excision of the entire ganglion (ganglionectomy). This contrasts with ‘sympathotomy’, which is a mere disruption of the chain at the level of above the ganglion^[26]. The majority of sympathetic input to the palms is derived at the level of T2. Transection of the stellate ganglion (T1) is associated with higher rates of Horner’s syndrome. Moreover, it appears as though the higher the level of disruption, the greater is the risk of post-operative compensatory sweating (the most pertinent complication of thoracic sympathectomy)^[35]. Several studies have attempted to identify the appropriate level and extent of disruption that would lead to the optimal results while minimizing compensatory sweating. Chang et al. compared disruption at T2 vs T3 vs T4 and reported comparable rates of improvement of palmar hyperhidrosis but greater incidence of compensatory sweating in the higher levels (93, 92 and 80%, respectively). The severity of the compensatory sweating was significantly less in the T4 group, but gustatory sweating was greater in that group (11.4% in T4, 23.1% in T3 and 5.8% in T2).^[36] Moreover, it appears as though the extent of disruption (single vs multiple levels) may be a factor in compensatory sweating, with single-level disruption being associated with decreased rates of post-operative complications^[37,38].

Several methods of sympathetic chain disruption exist, each with varying benefits and risks. Resection of the sympathetic ganglion (ganglionectomy) more accurately defines a true sympathectomy^[26]. While more complete, this technique may potentiate increased rates of post-operative compensatory sweating^[35]. Transection of the chain is usually performed superior to the rib and is typically performed using thermo-ablative methods via cautery. The advantage to this approach is that it necessitates less dissection and is relatively simple to perform^[26]. Clipping over the sympathetic trunk can be performed over the level of the rib or both above and below the ganglion (corresponding to a functional ganglionectomy). Although it requires more pleural dissection in order to clearly delineate the sympathetic chain, the main advantage of clipping is its reversibility, particularly in the case of severe compensatory sweating. Reversal (which entails simple removal of the clips) is not perfect, with higher failure rates outside a 2-week post-operative time window secondary to permanent perineural damage^[39]. However, a few reports have shown acceptable results of up to 50% clinical reversibility when reversal is performed less than 6 months after the original sympathectomy^[40].

The Society of Thoracic Surgeons Expert Consensus for the Surgical Treatment of Hyperhidrosis established the importance of a standardized nomenclature with regard to details of the operative approach used to perform the sympathectomy. This nomenclature is to include both the level and method of interruption of the sympathetic trunk. With regards to the anatomical level of interruption, it was felt that a rib-oriented approach is perhaps more appropriate than using the thoracic spine as the point of reference. Accordingly, a disruption at a specific level refers to interruption of the sympathetic chain above the corresponding rib. This allows for more clarity and transferability from patient to patient and takes into consideration the probability of anatomical variation that can cloud the accuracy of reporting based on the thoracic spine^[28].

The panel also further outlined specific surgical guidelines based on disease site. For palmar hyperhidrosis, although having higher rates of compensatory sweating, the recommendation was to perform either a multi-level R3–R4 or single-level R4 interruptions. The latter is associated with lower rates of compensatory sweating, with the unfortunate potential for moister hands. In the case of palmoplantar hyperhidrosis, an R4–R5 disruption is recommended. The same holds true for patients who demonstrate axillary form of hyperhidrosis (even if combined with other sites of disease). In as much, craniofacial hyperhidrosis is to be treated with an R3 interruption, which has the dual effect of treating the condition, without the extra risk of Horner’s syndrome and compensatory sweating that are associated with the R2 disruption. With regards to the method of interruption, there appears to be no specific recommendation made – implying that all forms are adequate in ensuring that there is enough separation between the ends of the chain to prevent regrowth.^[28]

Complications and side effects

At the time of surgery, certain considerations must be taken in order to avoid potentially dangerous and life-threatening complications. The greatest complication of thoracic sympathectomy is failure of the procedure. Overall, failure rates are low, ranging from 0.2–3.7% in the literature^[41]. Technical aspects are often the culprit, leading to failed thoracic sympathectomies. These include anatomical variations (Kuntz nerve, pleural adhesions and aberrant anatomy), nerve regeneration and incomplete disruption of the chain^[41]. The latter is likely the greatest cause of failed sympathectomies^[42]. Intraoperative pulse oxymetry can be used to monitor adequate disruption during clipping and transection. The instantaneous physiological response to sympathetic disruption is peripheral vasodilation, which can be depicted via change in the amplitude reading suggestive of increased peripheral circulation^[43]. Moreover, left-sided sympathetic chain stimulation (particularly the stellate ganglion) can trigger ventricular tachycardia, and in some cases disruption of the sympathetic chain can lead to significant bradycardia. The latter cardiac complication can be a long-term side effect requiring pacemaker insertion – essentially sympathectomy leads to a beta-blockade effect, decreasing sympathetic tone to the heart and, in turn, decreasing heart rate and blood pressure. In fact, thoracic sympathectomy can uncommonly be used in the treatment of prolonged QT syndrome that is refractory to medical treatment^[41,44].

The most significant and pertinent side effect pertaining to thoracic sympathectomy is the phenomenon of compensatory sweating, where the hyperhidrosis is essentially transferred from previously affected areas on the palms, feet and axillae to previously denervated areas^[26,28,41]. Essentially, the body is separated into an anhidrotic segment above the nipple line and increased consequential sweating below the nipple line. Both mild (14–90%) and severe (1.2–31%) forms of compensatory sweating exist. The latter is characterized as split-body syndrome, where a part of the body previously suffering from excessive sweating becomes dead to sympathetic input, while the hidrotic segment of the body becomes hyperactive^[41]. Conceptually, the number of functional eccrine sweat glands decreases by 40%, but the total amount of body sweating does not change – implying that residual sweat glands in previously unaffected parts compensate with increased sweat production. The exact mechanism by which this takes place is unclear but could potentially be the result of defective negative- feedback mechanisms that can no longer pass through the disrupted sympathetic chain. It is these severe forms of compensatory sweating that carry significant morbidity and functional detriment to patients, often leading to regret towards undergoing thoracic sympathectomy to treat their primary disorder^[41,45].

As mentioned previously, the rates and severity of compensatory hyperhidrosis have been linked to two main technical concepts relating to thoracic sympathectomy: (1) the level of chain disruption and (2) the extent of disruption (single vs multi-level)^[1,24,26,28]. A variety of evidence supports the notion that limiting the extent of resection decreases post-operative compensatory sweating. The level of selective disruption has also been associated with differential compensatory hyperhidrosis. T2 level disruption appears to have the highest rate of compensatory sweating, with lower levels having proportionately less. Accordingly, certain recommendations suggest sympathectomy at the T3–T4 level.^[41] This is in relative contradiction to the notion that T2 level disruption typically leads to optimal outcomes in treating primary palmoplantar hyperhidrosis^[28]. Treatment options for compensatory hyperhidrosis are limited, and the possibility of sympathectomy revision (mainly via removal of clips) exists, but to a limited extent^[39]. Overall, the effect of compensatory sweating in consequence to idiopathic hyperhidrosis treatment is relative and subjective – based on patient values, tolerance and the initial morbidity associated with the primary disease^[28].

Other less common side effects of thoracic sympathectomy include gustatory sweating, Horner’s syndrome and phantom sweating. Gustatory sweating describes post-prandial facial sweating. The mechanism is unclear, but rates of gustatory sweating are lower than those of compensatory sweating (0–38%). Phantom sweating, on the other hand, is a sensation experienced by patients post-operatively, where sweat appears to be ready to secrete out of sweat glands, without its actual occurrence. Rates of phantom sweating vary in the literature from 0–59%. Finally, Horner’s syndrome (with an incidence of 0.7–3%) is likely more of a concern in patients with craniofacial hyperhidrosis who may inadvertently receive an R2 interruption^[28,41].

The aforementioned complications can occur relatively early post-operatively but typically employ a gradual and insidious course of onset, often developing over months. As such, expert consensus is that patient follow-up should occur at 1 month, 6 months, 1 year and yearly thereafter for at least 5 years^[28]. Follow-up invokes on the surgeon a responsibility to adequately assess and address patient satisfaction and quality of life. As clearly outlined, more severe cases of hyperhidrosis tend to be more responsive and appreciative of surgical intervention^[26,28,41]. Patients with facial blushing/sweating appear to have the least satisfaction, with those with palmoplantar hyperhidrosis having the most. Essentially, the post-operative complications of compensatory sweating (with its significant prevalence) is better tolerated by patients who had more severe primary disease. A study conducted in 2007 comparing patients receiving thoracic sympathectomy to counterparts who were refused coverage by insurance companies (although having the same indications) demonstrated that overall quality of life of the surgical arm (with regards to social, professional and cosmetic outcomes) was greater than in those not undergoing surgery. This is in the face of the potential adverse consequences of compensatory hyperhidrosis^[46].