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Background
Sweating is a natural phenomenon necessary for the regulation of an individual's body temperature. Hyperhidrosis, or excessive sweating, is a medical condition that is defined as sweating beyond what is necessary to maintain thermal regulation.
Hyperhidrosis is classified as primary or secondary, depending on its cause or origin. Primary hyperhidrosis, also known as essential or idiopathic hyperhidrosis, is caused by an over-active sympathetic nervous system. It can lead to intractable and profuse sweating in several locations of the body, including palms (hands), axillae (armpits), and planta (feet). Secondary hyperhidrosis is the result of an underlying condition, such as Parkinson's disease, hyperthyroidism, diabetes mellitus, hyperpituitarism, pyrexia, hypoglycemia, or menopause. Secondary hyperhidrosis usually affects the whole body.
Regardless of the type or cause of hyperhidrosis, severe palmar and plantar hyperhidrosis can disrupt professional and social life and may lead to emotional problems. In the case of secondary hyperhidrosis, treatment of the underlying condition should first be attempted. In patients with disabling primary hyperhidrosis, a variety of treatment methods have been used.
The simplest method to control or reduce profuse sweating is the application of topical agents, such as aluminum chloride or other extra-strength chemical anti-perspirants. Usually recommended as the first therapeutic measure, topical antiperspirants are effective in cases with light to moderate hyperhidrosis but have to be repeated regularly. Drysol (aluminum chloride hexahydrate) is a prescription topical anti-perspirant commonly prescribed for excessive sweating. Drysol is reported to work in 80 % of persons who use it for excessive sweating. Treatment is repeated nightly until sweating is under control. Thereafter, Drysol is applied once- or twice-weekly or as needed.
Persons with with hyperhidrosis should be instructed on the difference between an anti-perspirant and a deodorant (deodorants mask odors caused by sweat, but do not reduce sweating), and that they are using an anti-perspirant correctly (CKS, 2009; Hornberger et al, 2004). An absorbent dusting powder (talc) may also be helpful (CKS, 2009; Lowe et al, 2003).
A number of other conservative measures can be employed to manage hyperhidrosis (Lowe et al, 2003; CKS, 2009). Trigger factors, such as specific foods or hot environments, should be identified and avoided (CKS, 2009; Lowe et al, 2003). Soap substitutes (e.g., emollient washes) can be used in place of soap-based cleaners to reduce the chance of skin irritation.
Persons with hyperhidrosis should be advised to wear loose-fitting clothing. They should avoid clothes made of synthetic materials such as Lycra and nylon that trap moisture, and to avoid clothes that show up sweat marks readily. Persons with plantar hyperhidrosis should be advised to wear cotton or other moisture wicking socks, and change socks and use absorbent foot powder at least twice-daily. They may also use absorbent insoles. They should be advised to wear a different pair of shoes on alternate days, to allow them to dry fully. They should be advised to wear non-occlusive footwear (leather shoes), and avoid athletic shoes or boots, as these are likely to have an occlusive effect (CKS, 2009; Hornberger et al, 2004; IHS, 2008).
Generalized hyperhidrosis is usually secondary to an underlying illness or a side effect of a medication, and the first approach to providing relief from the excessive sweating is to investigate the cause (IHS, 2008). Underlying conditions should then be treated appropriately and relevant medications should be adjusted, if possible, to relieve the sweating symptoms. In the rare instance in which there is no underlying cause found for generalized hyperhidrosis, consideration must be given to treating the most involved areas as one would in focal hyperhidrosis.
Oral prescription medications may be prescribed for situational or episodic hyperhidrosis, including anti-cholinergics (e.g., Robinul, Ditropan), beta-blockers (e.g., atenolol, propanolol), and benzodiazapines (e.g., Valium, Ativan). Anti-cholinergic medications may be effective for alleviating hyperhidrosis (ATTRACT, 2002: Altman and Kihiczak, 2002; GP Notebook, 2003). Anti-cholinergics such as propantheline bromide, glycopyrrolate, oxybutynin, and benztropine are effective because the pre-glandular neurotransmitter for sweat secretion is acetylcholine (although the sympathetic nervous system innervates the eccrine sweat glands). Some anti-cholinergics are better tolerated than others. Nyamekye (2004) stated: "The most effective anticholinergic drug, glycopyrrolate (Robinul and Robinul Forte, Mikart, Inc., Pharmaceutical Manufacturers, Atlanta, GA) has mild side-effects and is generally well tolerated .... Topical glycopyrrolate has also been used in the treatment of localised secondary gustatory sweating." Guidance from the NHS Institute for Innovation and Improvement (CKS, 2009) state that systemic anticholinergics may have a role before surgery is considered (particularly if the symptoms of severe). In such circumstances, propantheline bromide is typically used (CKS, 2009; Hornberger et al, 2004). Guidelines from the International Hyperhydrosis Society (IHS, 2008) state that systemic medications are also indicated in the treatment of generalized hyperhidrosis if treatment of the underlying condition and medication adjustments fail to reduce sweating.
Adverse effects of anti-cholinergics include mydriasis, blurry vision, dry mouth and eyes, difficulty with micturition, and constipation (CKS, 2009). Topical anti-cholinergic drugs, such as glycopyrronium bromide, may have markedly less adverse effects than systemic anti-cholinergic drugs (CKS, 2009). Anxiolytics, sedatives, or beta-blockers (e.g., propranolol) may be helpful when history indicates that symptoms are precipitated or exacerbated by stress (see Tyrer, 1998; Noyes, 1985; Fonte and Stevenson, 1985; GP Notebook, 2003; CKS, 2009; IHS, 2008). In addition, there is some evidence that other systemic medications, such as indomethacin and calcium channel blockers, may be beneficial in the treatment of palmoplantar hyperhidrosis (see Feder, 1995 Eedy and Corbett, 1978; Tkach, 1982; IHS, 2008).
Iontophoresis or electrophoresis can be tried if anti-perspirants are not effective. Iontophoresis appears to alleviate symptoms in approximately 85 % of patients with palmar or plantar hyperhidrosis and is safe and simple to perform (Smith, 2008). Iontophoresis causes blockage of sweat ducts by directing a mild electrical current through the skin (CKS, 2009). Iontophoresis has been used mainly to treat palmar and plantar hyperhidrosis, but can also be used to treat axillary hyperhidrosis with a special axillary electrode (Smith, 2008; CKS, 2009; Hornberger et al, 2004). Evidence for effectiveness is from small controlled trials and observational studies (CKS, 2009). However, some people seem to gain considerable symptom relief. The procedure has to be repeated regularly, initially in 20-min sessions several times a week, gradually stretching out the interval between treatments to 1 to 4 weeks (CKS, 2009; Hornberger et al, 2004). Most people report an improvement after 6 to 10 sessions (CKS, 2009; Hornberger et al, 2004). Treatments must be maintained indefinitely to control the symptoms. The results, however, vary: some many find the electric current uncomfortable and the treatments time consuming and not lasting long enough. The Drionic device (General Medical Co., Los Angeles, CA) is an iontophoretic device that can be purchased for home use.
Botulinum toxin type A (Botox) has been found to inhibit the release of acetylcholine not only at the neuromuscular junction, but also in post-ganglionic sympathetic fibers to sweat gland. It is indicated for the treatment of hyperhidrosis of the palms and axillae; intra-cutaneous injections of Botox have been shown to induce a temporary anhidrosis. Responses have been as long as 1 year, but in most cases the effect begins to weaken in 4 months. Naumann et al (2003) reported on a trial of botulinum toxin for persons (n = 320) with axillary hyperhidrosis; the mean duration between botulinum toxin treatments was 7 months, and 28 % of people required only 1 treatment over the 16-month duration of the trial. Although effective, the clinical usefulness of this treatment is limited by the need for multiple and repetitive relatively painful injections into sensitive palms and soles for palmoplantar hyperhidrosis. Application of a topical anesthetic prior to the injection of botulinum toxin may help alleviate some of the discomfort (Smith, 2008). The reports in clinical trials of increased palmar sweating in patients with axillary hyperhidrosis should also be noted; in the study by Naumann and colleagues, 5 % of patients treated with botulinum toxin reported an increase in non-axillary sweating (Naumann and Lowe, 2001). It has not been reported in clinical trials whether this subsided as the effects of treatment wore off. In patients with palmar hyperhidrosis, another consideration might be the long-term effects on muscle tone, as weakness has been reported in the small muscles of the hands with botulinum toxin treatment (Bandolier, 2002). In one study of botulinum toxin for palmar hyperhidrosis, 21 % of subjects reported weakness that lasted an average of 3 weeks (Solomon and Hayman, 2000).
Patients with severe, intractable palmar hyperhidrosis who fail topical therapies and iontophoresis, and who do not tolerate or get relief from botulinum toxin, can be treated effectively with endoscopic thoracic sympathectomy (ETS). The principle of sympathectomy is to interrupt the nerve tracks and nodes that transmit the signals to the sweat glands. This can basically be achieved for all locations in the body, but only the nerve nodes responsible for the sweat glands of the palms and the face are accessible without the need for a major surgical procedure. With the advent of minimally invasive endoscopic sympathectomy, open surgical sympathectomy or upper thoracic ganglionectomy at T2 to T4 has come into disfavor because of the magnitude of the procedure, the long periods of hospitalization and recovery, and the complication rate. Whether performed open or endoscopically, the most common side effect of surgery is compensatory hyperhidrosis characterized by an increase in sweating in other parts of the body. In a study of 158 patients who underwent endoscopic thoracic sympathectomy for palmar, axillary or facial hyperhidrosis, compensatory sweating occurred in 89 % of patients and was so severe in 35 % that they often had to change their clothes during the day (Licht and Pilegaard, 2004). A rare side effect is "gustatory sweating", a condition that leads to the sensation of sweating when eating. Another possible complication is Horner's syndrome resulting in a slightly smaller pupil and a slightly drooping eyelid on the affected side. This complication is estimated to occur in less than 1 % of patients, is usually temporary, but is sometimes permanent (CKS, 2009). Other complications include pneumothorax (1 to 5 %), brachial plexus injuries, post-operative neuralgia, and recurrent laryngeal nerve palsy (CKS, 2009). Side effects, especially compensatory hyperhidrosis in other parts of the body, may reduce long-term patient satisfaction with this procedure. The new technique of clipping the sympathetic nerve is generally viewed as the best option currently available because it is potentially reversible by removing the nerve clip in patients with severe and unmanageable compensatory sweating. Endoscopic thoracic sympathectomy can also be used for axillary hyperhidrosis, but the relapse rate is high. In a study of 382 patients with upper limb hyperhidrosis treated with endoscopic thoracic sympathectomy, patients with palmar hyperhidrosis had a relapse rate of 6.6 % and patients with axillary hyperhidrosis had a relapse rate of 65 % (Gossot et al, 2003). While endoscopic thoracic sympathectomy has also been used for facial hyperhidrosis, rates of compensatory and gustatory hyperhidrosis after the procedure appear to be very high (Licht et al, 2006). Lumbar sympathectomy, an open abdominal procedure, can cure isolated plantar hyperhidrosis; however, it is not usually employed because of the risk of sexual dysfunction.
Consensus guidelines from the Society of Thoracic Surgeons (Cerfolio, et al., 2012) on surgical treatment of hyperhidrosis state that primary hyperhidrosis of the extremities, axillae or face is best treated by endoscopic thoracic sympathectomy (ETS). Interruption of the sympathetic chain can be achieved either by electrocautery or clipping. The highest success rates occur when interruption is performed at the top of rib level (R) 3 or the top of R4 for palmar-only hyperhidrosis. R4 may offer a lower incidence of compensatory hyperhidrosis but moister hands. For palmar and axillary, palmar, axillary and pedal and for axillary-only hyperhidrosis interruptions at R4 and R5 are recommended. The top of R3 is best for craniofacial hyperhidrosis.
Guidelines from the Canadian Hyperhidrosis Advisory Committee (Solish et al, 2007) state that local surgery (axillary) and endoscopic thoracic sympathectomy (palms and soles) should only be considered after failure of all other treatment options. For patients with severe axillary hyperhidrosis, the guidelines recommend as first-line therapy the use of topical aluminum chloride and botulinum toxin. If a patient fails to respond to topical or botulinum toxin therapy, the guidelines recommend use of both in combination. For patients who fail to respond to topical or botulinum toxin therapy, oral medications may be used alone or as an adjuvant therapy. Glycopyrrolate (1 to 2 mg) can be taken up to 3 times per day; other anticholinergics are also sometimes used. The guidelines state that endoscopic thoracic sympathectomy (ETS) should be the last resort in patients not responding to therapy: "Local surgery and ETS should only be considered in severe cases of hyperhidrosis in which the patient fails to respond to all other treatment options." The guidelines state that patients must be well informed and willing to accept both the surgical risks and the significant risk of compensatory sweating.
For patients with severe palmar hyperhidrosis, these guidelines indicate that topical aluminum chloride, botulinum toxin, and iontophoresis are all considered to be first-line therapy (Solish et al, 2007). Oral medications may be considered for patients who fail first-line therapy. The guidelines also note that iontophoresis with glycopyrrolate solution has been shown to increase efficacy of iontophoresis but can increase side effects. The guidelines indicate that endoscopic thoracic sympathectomy should be the last resort in patients not responding to therapy, and that patients must be well-informed and willing to accept both the surgical risks and the significant risk of compensatory hyperhidrosis." The guidelines provide a similar algorithm for management of severe plantar hyperhidrosis. The guidelines state that endoscopic thoracic sympathectomy "should only be considered in severe cases of hyperhidrosis in which the patient fails to respond to all other treatment options."
For patients with severe craniofacial hyperhidrosis, the guidelines indiate that topical aluminum chloride, botulinum toxin, and oral medications (glycopyrrholate) are considered first-line therapy (Solish et al, 2007). The guidelines state that the safety and effectiveness of endoscopic thoracic sympathectomy for craniofacial hyperhidrosis has not been extensively studied, and should be the last resort in patients with severe hyperhidrosis not responding to therapy. The guidelines note that patients must be well- informed and willing to accept the risks of endoscopic thoracic sympathectomy, including the success rate of surgery and the high risk of compensatory hyperhidrosis.
Regarding use of endoscopic thoracic sympathectomy in axillary hyperhidrosis, the guidelines (Solish et al, 2007) state that endoscopic thoracic sympathectomy is generally not recommended and should be considered the last treatment option only in patients with severe axillary hyperhidrosis. The guidelines identified 2 studies (Herbst et al, 1994; Zacherl et al, 1998) that examined the long-term outcomes after endoscopic thoracic sympathectomy and found that permanent side effects impaired patient satisfaction; compensatory sweating was seen in 67 % of patients, and individuals treated for axillary hyperhidrosis without palmar involvement were significantly less satisfied with endoscopic thoracic sympathectomy (33 % versus 67 %).
The guidelines (Solish et al, 2007) reviewed the evidence for endoscopic thoracic sympathectomy in palmar hyperhidrosis. They found that published reports of endoscopic thoracic sympathectomy in palmar hyperhidrosis lack consistency in patient selection, surgical technique, and quantitative and qualitative measurement of hyperhidrosis and quality of life. The guideilnes noted that, although success rates range from 92 % to 100 %, there are significant complications associated with sympathectomy, including pneumothorax, gustatory sweating, rhinitis, and Horner’s syndrome. The guidelines note that patients are often satisfied with sympathectomy in palmar hyperhidrosis, yet compensatory sweating may at times be worse than the original condition being treated.
Other groups have made similar recommendations regarding the management of hyperhidrosis (see Lowe, 2003; Hornberger et al, 2004; CKS, 2009; IHS, 2008; BAD, 2009). The Multi-Specialty Working Group on the Recognition, Diagnosis, and Treatment of Primary Focal Hyperhidrosis (Hornberger et al, 2004) states that failure to respond or intolerance to other treatments may be an indication for referral to surgery for severe axillary or palmar hyperhidrosis. The guidelines state that data on the efficacy and safety of endoscopic thoracic sympathectomy for craniofacial hyperhidrosis are extremely limited, and that this option should be restricted to selected patients who are unable to tolerate other therapies and for whom the burden of hyperhidrosis is severe. The guidelines state that potential candidates for surgery should be evaluated by a surgeon and a dermatologist. The guidelines state that sympathectomy is not recommended as a treatment for plantar hyperhidrosis because of the risk of sexual dysfunction.
Guidelines from the International Hyperhidrosis Society (IHS, 2008) make similar recommendations about the management of focal hyperhidrosis. For primary palmar hyperhidrosis, the guidelines indicate endoscopic thoracic sympathectomy for persons who have failed conservative measures, including topical antiperspirants, iontophoresis, and botulinum toxin. The guidelines indicate that the clinician should educate the patient on the proper timing and technique for application of topical antiperspirants, and about methods of avoiding side effects. Similarly, for iontophoresis, the clinician should pay attention to proper technique and patient education and training. Treatment with systemic medications should be considered, including anti-cholinergics (propantheline, oxybutynin, glycopyrronium, benztropine), benzodiazepines (short course, as needed), clonidine, diltiazem, and others. A trial of botulinum toxin should include repeated attempts and appropriate adjustments in technique and area covered. Endoscopic thoracic sympathectomy should be considered for persons with no response. Surgical candidates should be carefully selected and educated who fully understand the risks and complications of surgery including compensatory sweating.
Guidelines from the International Hyperhydrosis Society (IHS, 2008) indicate local sweat gland excision, but not endoscopic thoracic sympathectomy, for axillary hyperhidrosis. These guidelines include no recommendation for the use of surgery for primary plantar hyperhidrosis. Endoscopic thoracic sympathectomy is indicated as a last-resort treatment for facial sweating, after a trial of conservative management, including avoidance of triggers, expectant use of systemic medications, botulinum toxin, and topical anti-perspirants. The guidelines note that the evidence that endoscopic thoracic sympathectomy is effective for this indication comes from a small series of patients and the surgery is not as effective for facial/cranial sweating as for palmar sweating.
Guidelines from the International Hyperhidrosis Society (IHS, 2008) recommend investigation of the cause as the first approach to treatment of generalized hyperhidrosis, since generalized hyperhidrosis is usually secondary to an underlying illness or a side effect of a medication. Underlying conditions should then be treated appropriately and relevant medications should be adjusted, if possible, to relieve the sweating symptoms. If symptoms persist during or after treatment of the primary condition and/or medication adjustments, systemic medications can be used to reduce sweating. In addition, the guidelines state that systemic medications may be useful if symptoms seem to be worse in anxiety-provoking situations (such as during public speaking). The guidelines state that, in the rare instance in which there is no underlying cause found for generalized hyperhidrosis, the most involved areas may be treated as one would in focal hyperhidrosis.
Available evidence suggests that botulinum toxin A and botulinum toxin B are comparably effective for treatment of hyperhidrosis. Dressler and colleagues (2002) reported on a self-controlled study comparing the effectiveness of Botox and botulinum toxin type B in persons with bilateral axillary hyperhidrosis. A total of 19 subjects with axillary hyperhidrosis received botulinum toxin type B in one axilla and Botox in the other axilla. These investigators reported that all subjects except 1 reported excellent improvement in hyperhidrosis in both axillae, and that none of the subjects had residual hyperhidrosis on clinical examination. The duration of effect was not statistically significantly different between Botox and botulinum toxin type B.
In a randomized controlled clinical trial, Baumann and Halem (2004) reported on the use of botulinum toxin B in the treatment of patients with palmar hyperhidrosis. A total of 20 subjects with hyperhidrosis were randomly assigned to injection with botulinum toxin type B (n = 15) or placebo (n = 5). These researchers reported a significant difference in treatment response (as determined by participant assessment) between the subjects injected with botulinum toxin B and placebo. The duration of cessation of palmar sweating ranged from 2.3 months to 4.9 months, with a mean duration of 3.8 months. The authors stated, however, that 18 of 20 participants reported dry mouth/throat, 60 % reported indigestion/heartburn, 60 % reported muscle weakness, and 50 % reported decreased grip strength. These investigators concluded that botulinum toxin B was safe and effective in treating bilateral palmar hyperhidrosis. However, the side effect profile was substantial.
In a review on the use of botulinum toxins for the treatment of patients with hyperhidrosis and gustatory sweating syndrome, Glaser (2006) stated that both diseases respond very well to botulinum toxin therapy.
Surgical removal of sweat glands has been shown to be only effective in the treatment of axillary hyperhidrosis, and may leave significant scarring. For a person suffering from primary hyperhidrosis, this approach is usually only a partial solution to the problem, especially since the most annoying areas usually are the hands. Guidelines from the Canadian Hyperhidrosis Advisory Committee (Solish et al, 2007) state that reduction of sweat glands, done on an outpatient basis with local anesthesia, is indicated in patients with axillary hyperhidrosis who do not respond to treatment with topical aluminum chloride, botulinum toxin, and oral medications (glycopyrrolate). The guidelines indicate that local surgery should only be considered in severe cases of hyperhidrosis in which the patient fails to respond to all other treatment options.
Poor results have been reported with the use of psychotherapy and hypnosis. Psychological problems are in most cases a consequence of hyperhidrosis, not the cause. Hence, psychiatric or psychopharmacologic therapy can not cure this disorder; at most it may help the patient to accept living with the problem.
Alternative medicine interventions, including homeopathy, massage, acupuncture and phytotherapeutic drugs, have not been proven effective.
In a pilot study, Goldman and Wollina (2008) examined the effectiveness of subdermal Nd-YAG laser for the treatment of axillary hyperhidrosis. A total of 17 patients (2 men and 15 women) with axillary hyperhidrosis were treated using a subdermal 1,064-nm Nd-YAG laser. Results were assessed by the patients as well as by the physician. The objective evaluation was realized by Minor's iodine starch test combined with planimetry. Histology was performed in axillary skin after the laser treatment. The subdermal laser-assisted axillary hyperhidrosis treatment using a 1,064-nm Nd-YAG laser resulted in significant clinical improvement. The authors concluded that the treatment of axillary hyperhidrosis using the 1,064-nm Nd-YAG laser has the advantage of a minor invasive procedure without leaving large scars and causing temporary impairment. The laser proved to be effective and safe. Moreover, they stated that although the laser treatment has shown promising results, further studies are needed for final conclusions.
Ultrasonic liposuction has been used as an alternative to tumescent liposuction for treatment of axillary hyperhidrosis. Commons and Lim (2009) reported their findings on treatment of axillary hyperhidrosis/bromidrosis by means of ultrasonography. A total of 13 patients (3 males, 10 females) with significant axillary hyperhidrosis and/or bromidrosis were recruited, treated with the VASER ultrasound, and followed for 6 months. Pre-operative assessment of the impact of hyperhidrosis and/or bromidrosis on lifestyle and the degree of sweat/odor were completed. Post-operative assessment of changes relative to lifestyle and degree of sweat/odor reduction and patient and surgeon satisfaction were completed. Eleven of 13 patients had significant reduction in sweat/odor and had no recurrence of significant symptoms at 6 months. Two patients had a reduction in sweat/odor but not to the degree desired by the patients. No significant complications were noted. A simple amplitude and time protocol was established that provides consistent and predictable therapy. The complete procedure takes less than 1 hour to treat 2 axillae using local anesthetic. The authors concluded that the VASER is safe and effective for treatment of axillary hyperhidrosis/bromidrosis. The method is minimally invasive with immediate return to basic activities and only temporary minor restriction of arm movement. At 6 months the treatment appears to be long-lasting, but further follow-up is needed for verification of permanence. This was a small study; its findings need to be validated by well-designed studies with more patients and long-term follow-up.
Letada et al (2012) noted that axillary hyperhidrosis (AH) is a rather common idiopathic disorder of the eccrine sweat glands, which can interfere with daily activities and cause significant social distress. In a pilot study, these researchers examined the effects of 1,064-nm laser hair reduction on sweat production in patients with focal AH. In this prospective, case-controlled, randomized, pilot study, 1 axilla from 6 different subjects with AH was treated with monthly laser hair reduction sessions using the 1,064 nm Nd:YAG laser at typical settings. The contralateral axilla acted as a control. Subjects were asked to subjectively classify improvement of axillary sweating using a Global Assessment Questionnaire (GAQ) weekly after each treatment. Qualitative evaluation of sweating was also performed using a modified starch iodine test monthly after each treatment. In addition, prior to the first treatment and at 1 month following the final treatment, a punch biopsy was performed on the treatment axilla to assess for histologic changes to the eccrine gland and surrounding structures. Statistically significant improvements in subjective ratings of sweating using the GAQ compared to baseline were observed. Objective improvements in sweating with modified starch iodine testing comparing treated versus non-treated axillae were also seen for at least 9 months in selected subjects. No significant differences in pre- and post-treatment biopsies were noted on routine histology. The authors concluded that laser hair reduction using the 1,064-nm Nd:YAG at laser hair removal settings provided subjective and objective improvements in patients with focal AH. The findings of this small pilot study need to be validated by well-designed studies.
Bechara et al (2012) evaluated the effect of diode laser epilation on the sweat rate of patients with AH. These investigators performed a randomized half-side controlled trial. A total of 21 patients were treated with 5 cycles of an 800-nm diode laser. Sweat rates were documented using gravimetry and a visual analog scale. Histologic examination was performed in all patients before and after treatment. A significant reduction in sweat rate was observed on the laser-treated (median of 89 mg/min, range of 42 to 208 mg/min versus 48 mg/min, range of 17 to 119 mg/min; p < 0.001) and the untreated contralateral (median of 78 mg/min, range of 25 to 220 mg/min versus median 65 mg/min, range of 24 to 399 mg/min; p = 0.04) sides, although no significant difference was found between the treated and untreated sides (p = 0.10). The authors concluded that although they observed a significant decrease in sweat rate on laser-treated sites, laser epilation was not able to reduce the sweat rate significantly more than on the untreated contralateral side. They stated that these results probably indicated a placebo effect rather than a direct therapeutic effect of laser epilation.
Glaser et al (2012) noted that duration of effect and effectiveness limit current options for treating AH. These investigators examined the effectiveness of a new microwave procedure for treatment of AH. Adults with primary AH were enrolled in a randomized, sham-controlled, blinded study. Subjects were required to have a Hyperhidrosis Disease Severity Scale (HDSS) score of 3 or 4 and baseline sweat production greater than 50 mg/5 min. Procedures were administered using a proprietary microwave energy device that isolates and heats target tissue. Responders were defined as subjects reporting a HDSS score of 1 or 2. Subjects were followed for 6 months (sham group) or 12 months (active group). Thirty days after treatment, the active group had a responder rate of 89 % (72/81), and the sham group had a responder rate of 54 % (21/39) (p < 0.001). Treatment effectiveness was stable from 3 months (74 %) to 12 months (69 %), when follow-up ended. Adverse events were generally mild, and all but 1 resolved over time. The authors concluded that the procedure demonstrated statistically significant, long-term effectiveness in sweat reduction. Moreover, they stated that as with any new procedure, findings from this first investigational device study identified optimization strategies for the future.
Hong et al (2012) stated that a third-generation microwave-based device has been developed to treat AH by selectively heating the interface between the skin and underlying fat where the sweat glands reside. A total of 31 adults with primary AH were enrolled. All subjects had 1 to 3 procedure sessions over a 6-month period to treat both axillae fully. Effectiveness was assessed using the HDSS, gravimetric weight of sweat, and the Dermatologic Life Quality Index (DLQI), a dermatology-specific quality-of-life scale. Subject safety was assessed at each visit. Subjects were followed for 12 months after all procedure sessions were complete. At the 12-month follow-up visit, 90.3 % had HDSS scores of 1 or 2, 90.3 % had at least a 50 % reduction in axillary sweat from baseline, and 85.2 % had a reduction of at least 5 points on the DLQI. All subjects experienced transient effects in the treatment area such as swelling, discomfort, and numbness. The most common adverse event (12 subjects) was the presence of altered sensation in the skin of the arm that resolved in all subjects. The authors concluded that the microwave-based device provided effective and durable treatment for AH. The findings of this small study need to be validated by well-designed studies.
An UpToDate review on “Primary focal hyperhidrosis” (Smith and Pariser, 2013) states that “Early studies suggest that microwave energy can be utilized to destroy eccrine glands and relieve hyperhidrosis in the axilla. In a randomized trial of 120 adults with primary axillary hyperhidrosis who were given 1 to 3 treatments with a microwave energy device (n = 81) or a sham device (n = 39), patients treated with the microwave device were more likely to notice a subjective reduction in the severity of axillary hyperhidrosis 30 days after treatment than patients in the sham treatment group (89 versus 54 %). The difference in favor of active treatment remained statistically significant for up to 6 months. In addition, more patients in the active group achieved at least a 50 or 75 % reduction in a gravimetric measurement of sweat production through 6 months after treatment. However, this difference was only statistically significant for patients who achieved greater than or equal to 75 % improvement at the 30 day time point (62 versus 39 %). The most common side effects of treatment were altered skin sensation (median duration 25 days, range of 4 to 225 days), discomfort, and other local reactions. Additional studies are necessary to determine the role of microwave energy devices in the treatment of hyperhidrosis”.
Percutaneous thoracic phenol sympathicolysis (PTPS) entails the introduction of small volumes of phenol into multiple sites on each side of the T2 to T4 sympathetic trunks and ganglia. This procedure is performed under local or general anesthesia guided by C-arm fluoroscopy. Percutaneous thoracic phenol sympathicolysis is not widely used in clinical practice nor frequently referenced in the literature. There is currently insufficient evidence to support the use of PTPS for the treatment of hyperhidrosis.
Wang et al (2001) noted that their previous study demonstrated that a high concentration of phenol (75 to 90 %) with minimal volume (0.02 ml) can elicit serious degeneration of ganglion cells of the stellate ganglia in cats. Another previous study demonstrated that approximately 84 to 90 % of the upper thoracic (T2 to T3) sympathetic trunks can be found under an endoscope on the ventral side of the T2 to T3 rib heads. In this report, these investigators presented a new mode of dorsal PTPS for the treatment of palmar hyperhidrosis or axillary bromidrosis (AB). A total of 50 patients with palmar hyperhidrosis or AB were injected with 75 % phenol into a total of 98 sides of the T2 to T3 or T3 to T4 sympathetic trunks and ganglia. The injected volume was 0.6 to 1.2 ml (average of 0.8 ml) for each side. The technique of dorsal percutaneous injection was performed under local anesthesia or local with intravenous general anesthesia and under the guidance of a C-arm fluoroscope. Forty patients (80 %) showed satisfactory results, including cessation of sweating. The success rates of PTPS were 83.7 % (41 of 49 patients) on the left side and 91.8 % (45 of 49 patients) on the right side. The skin temperature of the thumb increased by 5.3 to 5.4 degrees C approximately 1 hour after the phenol injection in patients with satisfactory results, whereas it increased by only 1.3 to 2.7 degrees C in patients who had unsatisfactory results. The authors concluded that PTPS may be a good alternative to endoscopic sympathectomy to treat palmar hyperhidrosis and AB.
Kao and colleagues (2004) stated that the difference between axillary osmidrosis (AO) and AB is the degree of odor and quantity of sweat, which is associated with selection of therapeutic modality theoretically. Upper thoracic sympathectomy has been used for both diseases but its effect needs to be further evaluated with more clinical data. These researchers collected 108 patients with AO or AB treated by upper thoracic sympathectomy from July 1995 to July 2002. Of these patients, 42 suffered AO alone, 17 had AB (AO with AH), and 49 had AO with palmar hyperhidrosis (PH). Ninety-two patients (183 sides) received anterior subaxillary transthoracic endoscopic sympathectomy and 17 patients (33 sides) PTPS. The levels of sympathectomy or sympathicolysis were T3 to T4 for AO and AB, and T2 to T4 for AO with PH. Mean follow-up period was 45.2 months (13 to 97 months). The satisfaction rates of patients were 52.4 %, 70.6 % and 61.2 % for AO, AB and AO with PH, respectively. The rates of patients with improvement and satisfaction were 78.6 %, 88.2 % and 85.7 % for AO, AB, and AO with PH, respectively. The authors concluded that these findings suggested that upper thoracic sympathectomy may be an acceptable treatment for AB or AO with PH rather than AO only.
An UpToDate review on “Primary focal hyperhidrosis” (Smith and Pariser, 2013) does not mention the use of percutaneous thoracic phenol sympathicolysis as a therapeutic option.
Duller and Gentry (1980) stated that preliminary findings attesting to the successful therapeutic use of biofeedback training in reducing symptoms of chronic hyperhidrosis have been reported; 11 of the 14 adult patients trained with biofeedback were able to demonstrate clinical improvement in their excessive sweating 6 weeks after termination of treatment. Relaxation was suggested as the active ingredient in the biofeedback treatment effect. These preliminary findings need to be validated by well-designed studies.
Lin et al (2000) noted that patients undergoing an unsuccessful sympathectomy experience dryness on one hand and excessive sweating on the other. This is embarrassing for the patients, and resolution of both a previous failed sympathectomy and recurrent hyperhidrosis is important. These investigators examined the effectiveness of repeat ETS for palmar and axillary hyperhidrosis. From September 1995 to January 1998, a total of 24 patients (11 men and 13 women; mean age of 28.2 years) underwent repeat ETS. The repeat ETS was performed with patients under general anesthesia using either a standard single-lumen endotracheal tube (12 patients) or a double-lumen endotracheal tube (12 patients). Ablation of T2 and T3 ganglia and any Kuntz fiber was performed in treating patients with palmar hyperhidrosis, and a similar procedure was performed on T3 and T4 ganglia for patients with axillary hyperhidrosis. The reasons for failure of the previous ETS were pleural adhesion (14/24), intact T2 ganglion (5/24), aberrant venous arch drainage to the superior vena cava (2/24), incomplete interruption of sympathetic nerve (2/24), and possible re-innervation (1/24). The mean operation time was 28 mins (range of 18 to 72 mins). In all, 23 patients had a satisfactory result, without recurrence of palmar or axillary hyperhidrosis. The mean follow-up time was 22 months (range of 5 to 30 months). The average hospital stay was 1.8 days. There was no surgical mortality. The authors concluded that repeat ETS is a safe and effective method for treating both an unsuccessful sympathectomy and recurrent palmar or axillary hyperhidrosis. Well-designed studies are needed to validate these preliminary findings.
In a case-study, Asik et al (2008) reported their experience with sympathetic radiofrequency (RF) neurolysis in a 35-year old male with right unilateral lumbar hyperhidrosis. Under scopy-guided localization of the lumbar spine sympathetic blockade with local anesthetics to L2 to L5 vertebral levels were performed as a diagnostic block. Lesion effectiveness was monitored by bilateral feet skin temperature measurement. Clinical effects produced by the first sympathetic ganglion block were sustained for 1 week and then RF neurolysis of lumbar sympathetic ganglion was performed to the same levels for a longer effect. The procedure was accomplished within 30 mins and the patient was discharged within 2 hrs after the procedure. Hyperhidrosis was relieved after the procedure and there were no post-sympathectomy neuralgia and sexual dysfunction. The patient obtained improvement of lumbar hyperhidrosis at his first month of follow-up and was satisfied with the outcome. The authors concluded that RF neurolysis of lumbar sympathetic ganglions is a safe and effective palliative procedure with minimal invasiveness for relieving excessive sweat secretion in patients with localized hyperhidrosis. The findings of this case-report need to be validated by well-designed studies.
Sugimura et al (2009) evaluated (i) post-operative satisfaction and the occurrence of compensatory sweating after ETS clipping in a consecutive series of patients, and (ii) the reversibility of adverse effects by removing the surgical clips. Between June 1998 and March 2006, a total of 727 patients undergoing bilateral endoscopic thoracic sympathetic clipping for hyperhidrosis or facial blushing were prospectively followed for post-operative satisfaction and subjective compensatory sweating. The effect of removing the surgical clips was assessed in 34 patients who underwent a subsequent reversal procedure after ETS clipping. Satisfaction and compensatory sweating were assessed using a visual analog scale (VAS) ranging from 0 to 10, with 10 indicating the highest degree. Follow-up was complete in 666 patients (92 %). The median age was 26.9 years, and 383 (53 %) were men. The level of sympathetic clipping was T2 in 399 patients (55 %), T2 + T3 in 55 patients (8 %), and T3 + T4 in 273 patients (38 %). Median follow-up was 10.4 months (range of 0 to 83 months). Excellent satisfaction (8 to 10 on VAS) was seen at last follow-up in 288 (74 %) of the T2 group, 33 (62 %) of the T2 + T3 group, and 184 (85 %) of the T3 + T4 group. Post-operative satisfaction was significantly higher in the T3 + T4 group when compared with the T2 or T2 + T3 groups (p < 0.01). Severe compensatory sweating (8 to 10 on the VAS) was reported in 42 (13 %) of the T2 group, 11 (28 %) of the T2 + T3 group, and 17 (8 %) of the T3 + T4 group. Post-operative compensatory sweating was significantly lower in the T3 + T4 group when compared with the T2 or T2 + T3 groups (p < 0.05). Thirty-four patients have subsequently undergone removal of the surgical clips after ETS clipping. Follow-up was complete in 31 patients. The reasons for removal included severe compensatory sweating in 32 patients, anhydrosis of the upper limb in 4 patients, lack of improvement or recurrence of hyperhidrosis in 5 patients, and other adverse symptoms in 5 patients. The reversal procedure was done after a median time of 11.0 months (range of 1 to 57 months) after ETS clipping. The initial level of clipping was T2 in 21 patients, T2 + T3 in 7 patients, and T3 + T4 in 6 patients. There was a trend toward fewer subsequent reversal procedures in the T3 + T4 group when compared with the T2 or T2 + T3 groups (p = 0.06). Fifteen patients (48 %) reported a substantial decrease in their compensatory sweating (5 to 10 on the VAS) after reversal. Thirteen patients (42 %) reported that their initial hyperhidrosis or facial blushing has remained well controlled (8 to 10 on the VAS) after reversal. There was no significant relationship between the original level of clipping and the interval between ETS clipping and the subsequent reversal and reversibility of symptoms. The authors concluded that when compared with ETS clipping at the T2 or T2 + T3 levels, ETS clipping at the T3 + T4 level was associated with a higher satisfaction rate, a lower rate of severe compensatory sweating, and a trend toward fewer subsequent reversal procedures. Subjective reversibility of adverse effects after ETS clipping was seen in approximately 50 % of the patients who underwent endoscopic removal of surgical clips. Moreover, they stated that although yet to be supported by electrophysiologic studies, reversal of sympathetic clipping appeared to provide acceptable results and should be considered in selected patients.
Purtuloglu et al (2013) tested the primary hypothesis that RF therapy is independently associated with decreased palmar hyperhidrosis and compared results for patients receiving this treatment with patients who underwent surgical sympathectomy. These researchers included all the patients undergoing treatment for hyperhidrosis between March 2010 and April 2012. Patients who underwent either surgical sympathectomy or RF ablation for palmar hyperhidrosis were included and analyzed. The outcomes studied included complications, success of the procedure, patient satisfaction with their procedure and compensatory hyperhidrosis. There were 94 patients who met inclusion criteria, of whom 46 (49 %) had surgical sympathectomy and 48 (51 %) had RF ablation performed. Radiofrequency had a success rate of 75 % in treating hyperhidrosis, but this was found to be statistically lower than for surgical sympathectomy (95 %; p < 0.01). The groups were similar regarding patient satisfaction (p = 0.26) and compensatory hyperhidrosis (p = 0.78). The authors concluded that this was the first clinical study to evaluate the role of RF ablation and compare it with the surgical treatment option for palmar hyperhidrosis. They stated that RF ablation significantly decreased hyperhidrosis, but it had a lower success rate than surgical sympathectomy.
Furthermore, an UpToDate review on “Primary focal hyperhidrosis” (Smith and Pariser, 2014) does not mention the use of biofeedback, RF ablation, and radiotherapy as therapeutic options.
In summary, there is currently insufficient evidence in the peer-reviewed literature to support the use of biofeedback, RF ablation, and radiotherapy as management tools.
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