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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.
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