DOI: 10.1111/j.1468-3083.2011.04173.

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REVIEW ARTICLE

Primary focal hyperhidrosis: current treatment options and a step-by-step approach

I. Hoorens,* K. Ongenae
Department of Dermatology, University Hospital, Ghent, Belgium *Correspondence: I. Hoorens. E-mail: isabelle.hoorens@ugent.be

Abstract
Primary focal hyperhidrosis is a common disorder for which treatment is often a therapeutic challenge. A systematic review of current literature on the various treatment modalities for primary focal hyperhidrosis was performed and a step-by-step approach for the different types of primary focal hyperhidrosis (axillary, palmar, plantar and craniofacial) was established. Non-surgical treatments (aluminium salts, local and systemic anticholinergics, botulinum toxin A (BTX-A) injections and iontophoresis) are adequately supported by the current literature. More invasive surgical procedures (suction curettage and sympathetic denervation) have also been extensively investigated, and can offer a more denitive solution for cases of hyperhidrosis that are unresponsive to non-surgical treatments. There is no consensus on specic techniques for sympathetic denervation, and this issue should be further examined by meta-analysis. There are numerous treatment options available to improve the quality of life (QOL) of the hyperhidrosis patient. In practice, however, the challenge for the dermatologist remains to evaluate the severity of hyperhidrosis to achieve the best therapeutic outcome, this can be done most effectively using the Hyperhidrosis Disease Severity Scale (HDSS). Received: 9 January 2011; Accepted: 15 June 2011

Conict of interest
The authors have no conicts of interest to declare.

Funding sources
The authors have no funding sources to declare.

Introduction
Hyperhidrosis (excessive sweating) can be local, regional or general. Generalized hyperhidrosis is characterized by sweating over the entire body with no apparent underlying aetiology. Possible causes can be neurological, infectious, endocrine or pharmacological in nature.1 Local or regional hyperhidrosis, including primary focal hyperhidrosis, is distinguished by sweating in the axillae, hands, feet, face or forehead, in addition to the crown or inguinal region. Exacerbating factors are heat, stress, olfactory and gustatory stimuli.2 Particularly, a neurological lesion called Freys syndrome gives rise to local hyperhidrosis.3,4 Primary focal hyperhidrosis is idiopathic and occurs in otherwise healthy people.1 Hyperhidrosis has a prevalence of 2.8% in the United States,5 while a prevalence of 1% was reported in a population of Israeli adolescents.6 Regardless of type, hyperhidrosis often has a major impact on the social, professional and daily activities of patients.7 The publication of a well-designed Cochrane protocol in 2009 entitled Interventions for localized excess sweating, by Rzany and Spinner supported the need for evidence-based guidelines for

treatment of hyperhidrosis.8 In addition, the need for standardization in the surgical treatment approach for hyperhidrosis was recently highlighted in an expert consensus report.9 The purpose of the present review is to give an update and a critical analysis on the effects of pharmaceutical, physical and surgical therapies in patients with hyperhidrosis and specically for the four most frequently affected body regions (axillar, plantar, palmar and craniofacial).

Methods
The PUBMED and Cochrane databases were searched using the following terms: hyperhidrosis, excessive sweating, local treatment, systemic treatment, aluminium salts, anticholinergics, iontophoresis, botulinum toxin A (BTX-A), surgery, sympathectomy, suction curettage and clinical outcomes. More than 300 English language abstracts were analysed; the end-points of interest were patient satisfaction, gravimetric results, adverse reactions, long-term effects and quality of life (QOL). A step-by-step approach was developed for the four most frequent forms of primary focal hyperhidrosis

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based on a critical analysis of the reviewed studies according to the Oxford Centre for Evidence-Based Medicine (OCEBM) Levels of Evidence Working Group, designated as the Oxford 2011 level of evidence10 (Table 1).

Results
Pathophysiology

There are four million sweat glands distributed over the human body. Eccrine sweat glands, associated with hyperhidrosis, are ubiquitous but are most densely located in the palms, soles, axillae and forehead. Apoeccrine sweat glands are mixed glands that have seven times higher output than eccrine sweat glands and were designated by several authors to be instrumental in the pathophysiology of hyperhidrosis.11,12 Eccrine sweat glands are innervated by cholinergic bres, while the apocrine sweat glands are innervated by adrenergic bres.11 There are no quantitative or qualitative histopathological changes in the eccrine sweat glands of hyperhidrosis patients. The nature of hyperhidrosis is primarily a complex dysfunction and overstimulation of the sympathetic nervous system13 due to a defect in the hypothalamus, leading to a lack of regulatory feedback of peripheral thermoreceptors.14 Recently, a role for nitric oxide (NO) in the pathophysiology of primary focal hyperhidrosis was proposed.15 Hyperhidrosis patients were found to have higher plasma values of NO when compared to healthy controls. NO synthase is found in eccrine sweat glands, where it may act as a neurotransmitter or induce local vasodilatation leading to excessive sweating.15 There is a familial history in 3050% of hyperhidrosis cases suggesting genetic involvement.2,16 One study highlights the specic role of chromosome 14 (Locus 14q11.2q13) in the development of primary focal hyperhidrosis.17 This genetic factor is autosomal dominant with variable penetrance.18 Importantly, excessive sweating does not occur during sleep indicating the role of emotional factors in the pathophysiology of this disease.19 However, hyperhidrosis is not generally considered an emotional disorder, but rather as a physiological disorder, noting the occasional onset of hyperhidrosis in childhood or infancy as further evidence.20
Diagnosis and clinical presentation

hyperhidrosis is made based on the criteria according to Hornberger et al. (Table 2). A strong history and clinical examination are sufcient for diagnosis, making additional tests unnecessary.7 The Minor iodine test can be used for localization of the zone of excessive sweating and for treatment evaluation.21 Secondary causes, for example neuropathies, can be diagnosed by performing the thermoregulatory sweat test.22 Gravimetry is a quantitative tool to measure sweating, most useful in clinical trials to objectively evaluate the outcome of treatment. The criteria for excessive sweating depend on location and gender. One study denes a sweat rate of 50100 mg 5 min per axilla as necessary for the diagnosis of axillary hyperhidrosis.23
Impact on the quality of life

Hyperhidrosis has a signicant impact on social, professional and daily activities. QOL can be assessed by the Hyperhidrosis Impact Questionnaire (HHIQ), Dermatology Life Quality Index (DLQI) and the Hyperhidrosis Disease Severity Scale (HDSS).24 The HDSS is a four part questionnaire that provides a quantitative measure of disease severity and the impact on daily life before and after treatment. Up to 55.2% of hyperhidrosis patients have an HDSS score of 42,5 (Table 3).
Conservative treatment Topical treatment Aluminium salts: Aluminium chloride hexahydrate blocks the epidermal duct of eccrine sweat glands, and
Table 2 Diagnostic criteria of primary focal hyperhidrosis (adapted from Hornberger et al.7)
The presence of focal, visible sweating for at least 6 months without any obvious cause, besides the presence of at least two of the following characteristics: Bilateral and relatively symmetrical Affects the daily activities of the patient A frequency of more than one time per week Less than 25 years old at the beginning of hyperhidrosis A positive family history Absence of night sweats

The patient with primary focal hyperhidrosis presents with complaints of excessive (most often bilateral) sweating of the axillae, hands, soles or face. The diagnosis of primary idiopathic focal

Table 3 Hyperhidrosis Disease Severity Scale (HDSS) (adapted from Solish et al.26)
How would you rate the severity of your hyperhidrosis?

Table 1 The Oxford 2011 levels of evidence10

Level 1: Systematic review of randomized trials or n-of-1 trials Level 2: Randomized trial or observational study with dramatic effect Level 3: Non-randomized controlled cohort follow-up study Level 4: Case-series, casecontrol studies or historically controlled studies Level 5: Mechanism-based reasoning

My sweating is never noticeable and never interferes with my daily activities: 1 My sweating is tolerable but sometimes interferes with my daily activities: 2 My sweating is barely tolerable and frequently interferes with my daily activities: 3 My sweating is intolerable and always interferes with my daily activities: 4 Score of 1: mild; Score of 2: moderate; Score of 34: severe.

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Table 4 Current surgical and non-surgical treatment options in a step-by-step approach for the four most frequent forms of primary focal hyperhidrosis (axillary, palmar, plantar, craniofacial hyperhidrosis)
Step 1 Axillary hyperhidrosis Topical aluminium chloride hexahydrate 1520% (to 35%) in ethyl alcohol (L2), salicylic acid gel (L3) or thermophobic foam (L3) Topical aluminium chloride hexahydrate 1520% (35%) in ethyl alcohol (L2), salicylic acid gel (L3) or thermophobic foam (L3) Topical aluminium chloride hexahydrate 1520% (35%) in ethyl alcohol (L2) or salicylic acid gel (L3) Topical aluminium chloride hexahydrate 1520% (35%) in ethyl alcohol (L2), Topical glycopyrrolate (2%) (L3) Step 2 BTX-A injections (L2) Step 3 Systemic anticholinergics (L2) Step 4 Suction curettage (L2) or excision of the sweat glands (L3) Step 5 Repeat suction curettage (L3) or sympathetic denervation (L2)

Palmar hyperhidrosis

Iontophoresis,1520 mA, 2030 min, TWI (L2), Anticholinergics (L2), BTX-A (L3), Dry-type (L3)

BTX-A injections (L2)

Systemic anticholinergics (L4)

Sympathetic denervation (L2)

Plantar hyperhidrosis

Iontophoresis, 1520 mA, 2030 min, TWI (L2), Anticholinergics (L2) Systemic anticholinergics (L4)

BTX-A injections (L4)

Systemic anticholinergics (L4) Sympathetic denervation (L2)

Craniofacial hyperhidrosis

BTX-A injections (L4)

BTX-A = botulinum toxin A; L = level of evidence; TWI = tap water iontophoresis.

induces atrophy and vacuolization at the level of the glandular secretory cells. Necrosis of the epidermal cells of the duct delineation is also induced25 (Fig. 1). The initial dose is a 1012% solution which can be increased to a 35% solution dissolved in ethyl alcohol or a 24% salicylic acid gel.26 The keratolytic properties of salicylic acid gel improve the absorption of aluminium chloride hexahydrate in the hyperkeratotic skin. In addition, salicylic acid has antiperspirant qualities and maintains a normal level of skin hydration unlike ethyl alcohol.27,28 A recent study described the use of 20% aluminium sesqui-chlorhydrate thermophobic foam. This vehicle allows a more practical use on the hairy skin leading to increased patient compliance. Thermophobic foam is also less irritating than alcohol solutions and produces similar efcacy.29 The main side effects of aluminium chloride hexahydrate are skin irritation accompanied by a burning or painful sensation.

Concomitant use of a local hydrocortisone 1% is suggested to relieve pain.30 A notable disadvantage of aluminium salt treatment is the short duration of the effect (within one week the condition reverts to the level of the untreated stage).31 Nevertheless, due to efcacy, low cost and convenience, topical treatment with aluminium salts should be the rst line treatment for all mild forms of primary focal hyperhidrosis. The vehicle can be adjusted depending on localization of the condition (Table 4). Topical anticholinergics: Topical anticholinergics are used mostly in the treatment of craniofacial hyperhidrosis. Two casereports describe successful topical treatment with 0.5% topical glycopyrrolate for craniofacial hyperhidrosis.32,33 A clinical trial of 25 patients conrmed these results, showing a signicant reduction in craniofacial sweating with 2% topical glycopyrronium solution applied to one side of the face compared to

AlCl

Figure 1 The eccrine sweat gland and the different targets for hyperhidrosis treatment. M = inhibition muscarinic receptors; ? = mechanism of iontophoresis unknown; x = inhibition of acetylcholine release; = mechanical destruction; AlCl = aluminium chloride.

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placebo on the other side. However, the effect lasted for only one to two days.34
Iontophoresis Tap water iontophoresis (TWI): While the mechanism of action of TWI is not yet entirely clear, it is an effective treatment in the inhibition of sweat secretion (Fig. 1). TWI treatment consists of 2030 min treatments, three to four times per week. Each palm or sole is placed in a small tray lled with tap water with a current of 1520 mA.26 Upon euhidrosis, maintenance treatment consisting of one session per week or even one session per month can be effective. Favourable results are attained in 81.2% of patients with palmoplantar hyperhidrosis after eight initial treatments. The main side effects are erythema, burning sensation and temporary vesicle formation on the palms and soles.35 Most iontophoretic systems use direct current (DC) although alternating current (AC) can also be used or even AC with DC offset (AC DC). Lesser side effects are associated with devices that use AC DC.36 TWI is a safe, cost-effective and efcient treatment for the motivated patient with palmar or plantar hyperhidrosis and should be considered when topical treatment fails (Table 4). Administration of anticholinergics through iontophoresis: Glycopyrronium or hexopyrronium bromide (0.1%) administration through iontophoresis has signicantly prolonged effectiveness compared to TWI.37 However, all 26 patients enrolled in this study experienced varying degrees of systemic effects (dry mouth, accommodation disturbances, abdominal pain and bladder dysfunction). Another study described the use of a 0.5% solution of poldine methosulphate with similar systemic side effects.38 A recent controlled clinical trial found a signicantly greater effect of iontophoresis with administration of a 0.05% glycopyrrolate solution compared to TWI in the treatment of palmoplantar hyperhidrosis with only one patient experiencing dry mouth and throat.39 If TWI fails, administration of low dose anticholinergic agents through iontophoresis may be considered. However, this treatment option is not recommended by the Canadian Hyperhidrosis Advisory Committee (Table 4). Administration of botulinum toxin A through iontophoresis: A recent study found efcacy in the treatment of palmar hyperhidrosis with the BTX-A, Dysport (n = 8). Patients were treated with 250 units of Dysport dissolved in 3 mL saline on one hand and TWI on the other hand. Hyperhidrosis was signicantly improved with Dysport iontophoresis treatment compared to TWI. In addition, there were no typical BTX-A side effects, such as loss of muscle strength, observed.40 Moreover, iontophoresis administration of BTX-A is preferable since injections are often painful. Another study (n = 8) found similar results with the application of 100 units of Botox dissolved in 2.7 mL saline to one hand. However, this study reported compensatory hyperhidrosis of the control palm treated with TWI.41 A case report describes similar positive results with BTX-A iontophoresis in two patients with needle phobia.42 The current role of BTX-A iontophoresis in treating hyperhidrosis is not entirely clear, but appears to be a promising technique.

Dry-type iontophoretic device: The dry-type iontophoretic device uses patient sweat for conduction. The patient holds a cylinder during treatment. Effects similar to TWI have been described with the advantage of this method being that it can be administered while performing daily activities such as reading, watching TV or even jogging.43 One study conrms the effectiveness of dry-type iontophoresis for palmar hyperhidrosis using conductive pads applied to the patients palmar side of the lower forearm.44 This system induces an immediate reduction in sweat production conrmed by the Minor iodine test. Further studies should be performed directly comparing dry-type iontophoresis and TWI.
BTX-A The BTX-A binds to presynaptic cholinergic neuromuscular junction receptors and autonomic cholinergic neurons. Upon entering the cytosol, BTX-A breaks down polypeptides necessary for exocytosis of acetylcholine (Fig. 1) resulting in accid paralysis and autonomic dysfunction. Neural activity of eccrine sweat secretion is regulated by acetylcholine, and therefore, BTX-A injections decrease sweat secretion.45 Several randomized control trials (RCTs) have demonstrated the effectiveness of BTX-A in the treatment of axillary hyperhidrosis.4649 One study showed an 81.4% reduction in sweat production as measured by gravimetry after injection of 200 units Dysport. BTX-A, however, has a temporary effect ranging from 4 to 17 months.46 BTX-A injections for axillary hyperhidrosis results in a drastic improvement of the QOL (measured by the HHIQ).48 A major drawback of BTX-A treatment is the cost. Complications include headache, myalgia, itching and increased compensatory sweating of the face.46 Compensatory sweating is seen in 5% of the patients treated with BTX-A for axillary hyperhidrosis.49 BTX-A is also an option in the treatment of palmar hyperhidrosis. BTX-A affects acetylcholine secretion at the level of the neuromuscular junction, and thus could lead to adverse effects on hand motor function. However, there is no signicant difference in grip strength (measured by hydraulic dynamometer) between palms receiving BTX-A and palms receiving placebo.50,51 In contrast, thumb-index pinch strength decreased after injections of BTX-A, and 77% of the patients who received 100 units of BTX-A reported hand weakness.51 Three studies have shown BTX-A treatment to be effective and safe for plantar hyperhidrosis.5254 The role of BTX-A in the treatment of craniofacial hyperhidrosis55 is investigated and is an alternative to tackle the problem. Indeed the Canadian Hyperhidrosis Advisory Committee recommends BTX-A injections as a treatment option for axillary, palmar, plantar and craniofacial hyperhidrosis26 (Table 4). Pain during axillary injections can be reduced through cryotherapy (cold air systems, ice or gel packs)56 while a peripheral nerve block has been shown to be useful during palmar injections.57 A recent RCT found that BTX-A reconstituted with lidocaine signicantly reduces pain while providing similar efcacy on sweat reduction compared to BTX-A dissolved in a salt solution.58

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Systemic anticholinergics Systemic anticholinergics inhibit sweating by competitive blocking of muscarinic receptors near the eccrine sweat glands (Fig. 1). The use of anticholinergic drugs, however, is greatly limited due to well-known side effects. An RCT described efcacy of methanthelinium bromide (Vagantin) in a dose of 50 mg, twice daily for axillary hyperhidrosis with acceptable tolerance.59 A retrospective study reported effective treatment with glycopyrronium bromide (2 mg, two to three times daily over 4 years) for both generalized and local hyperhidrosis in 75% of patients. However, 79% of patients complained of dry mouth, causing a 50% dropout rate.60 Systemic anticholinergics are recommended by the Canadian Hyperhidrosis Advisory Committee only if other non-surgical treatments fail26 (Table 4). A case report described the use of Paroxetine (10 mg per day) as a successful treatment in palmoplantar hyperhidrosis. The most likely mechanisms of action are anticholinergic and anxiolytic effects.61 Indeed, the role of anxiety and stress as precipitating factors in the exacerbation of hyperhidrosis is reported in epidemiological studies.2 The possible contribution of psychotropic drugs in the treatment of primary focal hyperhidrosis should be further investigated. Surgical treatment Local surgery Excision of the sweat glands: A euhidrotic state can be induced by local surgical removal of sweat glands (Fig. 1). The rst reports of surgical excision of axillary sweat glands described high complication rates (less arm movement, unaesthetic scars, infection and haematomas).6264 A clinical trial in 2006 reported a 65% success rate by Shelleys procedure.65 A recent study reported that suction curettage was as successful as radical excision with Y-plasty and a skin conserving operation while achieving a lower complication rate.66 Suction curettage: Curettage and tumescent liposuction have been used separately and in combination in the treatment of axillary hyperhidrosis. A cannula is placed at the junction between the dermis and hypodermis where most sweat glands are located.67 The major advantage of tumescent liposuction is the absence of unaesthetic scar formation. The success rate varies; one study of 10 patients describes a relapse of 40%.68 Tumescent liposuction has been found to be particularly effective in the treatment of axillary bromhidrosis.69 Possible complications are bleeding, pain, haematoma, secondary infection, seroma and damage to the brachial plexus.6769 Jemec70 was the rst to describe the use of curettage in the treatment of axillary hyperhidrosis. This technique requires two 1.5 cm skin incisions in the armpit under either local or general anaesthesia. A curette is used to remove the entire subcutaneous tissue. A study of 161 patients found 36% of patients dissatised with the outcome, reporting signicant side effects such as haematomas, abscesses and severe necrosis with the need for skin grafting.71

Successful results of suction curettage, as evaluated by gravimetry, have been reported with a 12 month follow-up.72 These results were only signicant for patients with a high pre-operative sweat rate (25 mg min). A hypertrophic scar was reported in 1 out of 28 patients, which required skin grafting.72 Other side effects described were local bruising, skin erosion, bridle formation, seroma, local alopecia and dysesthesia.73 A recent study of 163 patients compared subcutaneous curettage with tumescent suction curettage. Patient satisfaction was 97% vs. 89.2% (subcutaneous curettage vs. tumescent suction curettage respectively). However, there were greater number of side effects and a prolonged hospital stay in patients undergoing subcutaneous curettage.74 Another study reported a 79% success rate with suction curettage, but in some cases there was a need for reoperation after 6 months due to persistent high sweat secretion75 which according to Bechara et al.76 was due to insufciently aggressive treatment. A comparative study using a aggressive cannula conrmed this theory but reported a higher complication rate. However, the authors considered the gain in sweat reduction (66.1% vs. 44.6%) to outweigh the complications.77 In cases where suction curettage is insufcient, reoperation with a more aggressive method can be an option. A study examining the safety and efcacy of repeating suction curettage reported that 89% of patients showed a signicant decrease in sweat secretion, with acceptable complications.78 In conclusion, suction curettage appears to be an effective and relatively safe treatment for axillary hyperhidrosis after attempting non-surgical treatments and before stepping up to sympathetic denervation (Table 4).
Sympathetic denervation There are three different techniques for the treatment of hyperhidrosis by sympathetic denervation. (Fig. 1). The rst method is sympathectomy or ganglionectomy (for example of the T2 ganglion) and is performed by a transection above and below the T2 ganglion or by resection or ablation of the actual ganglion. The second method is a sympathotomy or sympathicotomy which is performed by interrupting the rami interganglionares between the stellate ganglion and the T2 ganglion. Finally, a ramectomy results in the interruption of the rami communicantes.79,80 The terms sympathectomy, sympathotomy and ramectomy are often used interchangeably without a proper denition and therefore need clarication. Clipping is the analogue of sympathotomy but uses a clip to interrupt the sympathic chain instead of ablation or resection. Blocking is the analogue of sympathectomy by using a clip. The post-operative results of sympathectomy, sympathotomy and clipping or blocking are similar.81,82 The advantage of the clip is that it can be removed if excessive compensatory sweating occurs.83,84 Sympathetic denervation is the last step in treating severe palmar, craniofacial and axillary hyperhidrosis (Table 4). Studies in the treatment of plantar hyperhidrosis by lumbar sympathectomy have reported good results at follow-up.8587 The major

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complication described is sexual dysfunction87,88 and therefore, ne tuning of the technique is necessary to introduce it as a standard approach. The most common side effect of sympathetic denervation in the treatment of primary axillary, palmar and craniofacial hyperhidrosis is compensatory sweating, with incidence ranging from 14% to 90% for mild compensatory sweating and 1.2% to 30.9% for severe compensatory sweating.89 The large range in results may partly rely on a lack of objective methodology for dening compensatory sweating, as well as the wide variety of techniques of sympathetic denervation. Compensatory sweating was originally thought to be a mechanism of excessive sweating (in an anatomical region with an intact sympathetic nervous system) to maintain a constant rate of total sweat secretion.90 However, this theory was not conrmed by other studies, demonstrating that compensatory sweating represented a reex action by an altered feedback mechanism at the level of the hypothalamus which is dependent on the level at which sympathetic denervation occurs. Sympathectomy at the level of the T2 ganglion leads to decreased negative feedback to the hypothalamus. When performing a sympathectomy at a lower level, the negative feedback to the hypothalamus is less inhibited, leading to a decrease in compensatory sweating. Chou et al.91 have proposed the term reex sweating to replace compensatory sweating. Other side effects described in a review article by Dumont89 are gustatory sweating, cardiac effects, phantom sweating, lung function changes, dry hands and altered taste. Besides these side effects there are signicant risks of complications during and after surgery (arterial or venous vascular injury, pneumothorax, infection, Horner syndrome etc.).

factors such as the duration of effect, side effects, complications, cost, local level of availability of health care and patient wishes must be considered when deciding on treatment options. Since hyperhidrosis is not a life-threatening condition, but rather a condition which signicantly interferes with social, professional and daily activities, the patient must make an informed decision concerning the best management strategy. The precise pathogenesis of hyperhidrosis is not yet fully understood and as such current treatments are focused on symptoms instead of underlying cause. The use of BTX-A and anticholinergics through iontophoresis, and the new dry-type iontophoresis may offer new treatment possibilities. To nd a more causal therapeutic approach, clinical trials should examine the effect of psychotropic drugs on excessive sweating. In the case of more aggressive therapy, the level at which sympathetic denervation should be performed to insure optimal outcome and reduce compensatory sweating for the different types of hyperhidrosis remains unclear. Future studies should focus on the specic neurophysiological dysregulation of the autonomic nervous system, the role of specic neurotransmitters and the genetic basis of primary focal hyperhidrosis to support the development of more specic causal therapies.

References
1 Sato K, Kang WH, Saga K, Sato KT. Biology of sweat glands and their disorders. II. Disorders of sweat gland function. J Am Acad Dermatol 1989; 1: 713726. 2 Lear W, Kessler E, Solish N, Glaser DA. An epidemiological study of hyperhidrosis. Dermatol Surg 2007; 33(1 Spec No.): S69S75. 3 Prattico F, Perfetti P. Images in clinical medicine. Freys syndrome. N Eng J Med 2006; 355: 66. 4 Burton MJ, Brochwicz-Lewinski M. Lucja Frey and the auriculotemporal nerve syndrome. J R Soc Med 1991; 84: 619620. 5 Strutton DR, Kowalski JW, Glaser DA, Stang PE. US prevalence of hyperhidrosis and impact on individuals with axillary hyperhidrosis: results from a national survey. J Am Acad Dermatol 2004; 51: 241248. 6 Adar R, Kurchin A, Zweig A, Mozes M. Palmar hyperhidrosis and its surgical treatment: a report of 100 cases. Ann Surg 1977; 186: 3441. 7 Hornberger J, Grimes K, Naumann M et al. Recognition, diagnosis, and treatment of primary focal hyperhidrosis. J Am Acad Dermatol 2004; 51: 274286. 8 Rzany BBR, Spinner D. Interventions for localised excessive sweating. Cochrane Database Syst Rev 2001; Issue 1. Art. No.: CD002953. DOI: 10.1002/14651858.CD002953. 9 Cerfolio RJ, De Campos JR, Bryant AS et al. The society of thoracic surgeons expert consensus for the surgical treatment of hyperhidrosis. Ann Thorac Surg 2011; 91: 16421648. 10 OCEBM. The Oxford 2011 levels of evidence. [WWW document] 2011. URL http://www.cebm.net/index.aspx?o=5653 (last accessed: 13 June 2011). 11 Sato K, Kang WH, Saga K, Sato KT. Biology of sweat glands and their disorders. I. Normal sweat gland function. J Am Acad Dermatol 1989; 20: 537563. 12 Bovell DL, Corbett AD, Holmes S, Macdonald A, Harker M. The absence of apoeccrine glands in the human axilla has disease pathogenetic implications, including axillary hyperhidrosis. Br J Dermatol 2007; 156: 12781286. 13 Bovell DL, Clunes MT, Elder HY, Milsom J, Jenkinson DM. Ultrastructure of the hyperhidrotic eccrine sweat gland. Br J Dermatol 2001; 145: 298301.

Discussion
Together, the literature on the severity and procentual risk of side effects associated with each treatment for hyperhidrosis suggests that disease severity (as measured by the HDSS) and affected body region must be considered when deciding on treatment. Table 4 summarizes the various effective surgical and non-surgical treatments for the four most frequent forms of primary focal hyperhidrosis. Table 1 reveals that no systematic reviews of RCTs (level 1) have been conducted to date. However, a protocol has been designed for such a review.8 There is a high level of evidence to support most therapeutic options in the step-by-step guidelines (level 2). Notably, the level of evidence for BTX-A injections depends on the treated region; with a high level of evidence for axillar and palmar hyperhidrosis, while a lower level of evidence (level 4) was found for craniofacial and plantar regions. Likewise, for systemic anticholinergics the level of evidence is high only for the axillar region (level 2), and low for all other locations (level 4). Finally, a higher level of evidence was found for aluminium hexahydrate formulation in ethyl alcohol (level 2) than the formulations in salicylic acid gel or thermophobic foam (level 3). The HDDS is useful in the assessment of severity of hyperhidrosis. However, in addition to the HDDS score and localization,

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37 Abell E, Morgan K. The treatment of idiopathic hyperhidrosis by glycopyrronium bromide and tap water iontophoresis. Br J Dermatol 1974; 91: 8791. 38 Hill BH. Poldine iontophoresis in the treatment of palmar and plantar hyperhidrosis. Australas J Dermatol 1976; 17: 9293. 39 Dolianitis C, Scarff CE, Kelly J, Sinclair R. Iontophoresis with glycopyrrolate for the treatment of palmoplantar hyperhidrosis. Australas J Dermatol 2004; 45: 208212. 40 Davarian S, Kalantari KK, Rezasoltani A, Rahimi A. Effect and persistency of botulinum toxin iontophoresis in the treatment of palmar hyperhidrosis. Australas J Dermatol 2008; 49: 7579. 41 Kavanagh GM, Shams K. Botulinum toxin type A by iontophoresis for primary palmar hyperhidrosis. J Am Acad Dermatol 2006; 5(Suppl): S115S117. 42 Kavanagh GM, Oh C, Shams K. BOTOX delivery by iontophoresis. Br J Dermatol 2004; 151: 10931095. 43 Na GY, Park BC, Lee WJ, Park DJ, Kim do W, Kim MN. Control of palmar hyperhidrosis with a new dry-type iontophoretic device. Dermatol Surg 2007; 33: 5761. 44 Shams K, Kavanagh GM. Immediate reduction in sweat secretion with electric current application in primary palmar hyperhidrosis. Arch Dermatol 2011; 147: 241242. 45 Simpson LL. Identication of the major steps in botulinum toxin action. Annu Rev Pharmacol Toxicol 2004; 44: 167193. 46 Heckmann M, Ceballos-Baumann AO, Plewig G. Botulinum toxin A for axillary hyperhidrosis (excessive sweating). N Engl J Med 2001; 344: 488493. 47 Lowe NJ, Glaser DA, Eadie N, Daggett S, Kowalski JW, Lai PY. Botulinum toxin type A in the treatment of primary axillary hyperhidrosis: a 52-week multicenter double-blind, randomized, placebocontrolled study of efcacy and safety. J Am Acad Dermatol 2007; 56: 604611. 48 Naumann MK, Hamm H, Lowe NJ. Effect of botulinum toxin type A on quality of life measures in patients with excessive axillary sweating: a randomized controlled trial. Br J Dermatol 2002; 147: 12181226. 49 Naumann M, Lowe NJ. Botulinum toxin type A in treatment of bilateral primary axillary hyperhidrosis: randomised, parallel group, double blind, placebo controlled trial. BMJ 2001; 323: 596599. 50 Lowe NJ, Yamauchi PS, Lask GP, Patnaik R, Iyer S. Efcacy and safety of botulinum toxin type a in the treatment of palmar hyperhidrosis: a double-blind, randomized, placebo-controlled study. Dermatol Surg 2002; 28: 822827. 51 Saadia D, Voustianiouk A, Wang AK, Kaufmann H. Botulinum toxin type A in primary palmar hyperhidrosis: randomized, single-blind, twodose study. Neurology 2001; 57: 20952099. 52 Campanati A, Bernardini ML, Gesuita R, Ofdani A. Plantar focal idiopathic hyperhidrosis and botulinum toxin: a pilot study. Eur J Dermatol 2007; 17: 5254. 53 Sevim S, Dogu O, Kaleagasi H. Botulinum toxin-A therapy for palmar and plantar hyperhidrosis. Acta Neurol Belg 2002; 102: 167170. 54 Vadoud-Seyedi J. Treatment of plantar hyperhidrosis with botulinum toxin type A. Int J Dermatol 2004; 43: 969971. 55 Boger A, Herath H, Rompel R, Ferbert A. Botulinum toxin for treatment of craniofacial hyperhidrosis. J Neurol 2000; 247: 857861. 56 Bechara FG, Sand M, Altmeyer P, Sand D, Hoffmann K. Skin cooling for botulinum toxin A injection in patients with focal axillary hyperhidrosis: a prospective, randomized, controlled study. Ann Plast Surg 2007; 58: 299302. 57 Hayton MJ, Stanley JK, Lowe NJ. A review of peripheral nerve blockade as local anaesthesia in the treatment of palmar hyperhidrosis. Br J Dermatol 2003; 149: 447451. 58 Vadoud-Seyedi J, Simonart T. Treatment of axillary hyperhidrosis with botulinum toxin type A reconstituted in lidocaine or in normal saline: a randomized, side-by-side, double-blind study. Br J Dermatol 2007; 156: 986989.

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59 Hund M, Sinkgraven R, Rzany B. [Randomized, placebo-controlled, double blind clinical trial for the evaluation of the efcacy and safety of oral methantheliniumbromide (Vagantin) in the treatment of focal hyperhidrosis]. J Dtsch Dermatol Ges 2004; 2: 343349. 60 Bajaj V, Langtry JA. Use of oral glycopyrronium bromide in hyperhidrosis. Br J Dermatol 2007; 157: 118121. 61 Praharaj SK, Arora M. Paroxetine useful for palmar-plantar hyperhidrosis. Ann Pharmacother 2006; 40: 18841886. 62 Hurley HJ, Shelley WB. A simple surgical approach to the management of axillary hyperidrosis. JAMA 1963; 186: 109112. 63 Skoog T, Thyresson N. Hyperhidrosis of the axillae. A method of surgical treatment. Acta Chir Scand 1962; 124: 531538. 64 Breach NM. Axillary hyperhidrosis: surgical cure with aesthetic scars. Ann R Coll Surg Engl 1979; 61: 295297. 65 Lawrence CM, Lonsdale Eccles AA. Selective sweat gland removal with minimal skin excision in the treatment of axillary hyperhidrosis: a retrospective clinical and histological review of 15 patients. Br J Dermatol 2006; 155: 115118. 66 Bechara FG, Sand M, Hoffmann K, Boorboor P, Altmeyer P, Stuecker M. Histological and clinical ndings in different surgical strategies for focal axillary hyperhidrosis. Dermatol Surg 2008; 34: 10011009; discussion 1009. 67 Swinehart JM. Treatment of axillary hyperhidrosis: combination of the starch-iodine test with the tumescent liposuction technique. Dermatol Surg 2000; 26: 392396. 68 Lee MR, Ryman WJ. Liposuction for axillary hyperhidrosis. Australas J Dermatol 2005; 46: 7679. 69 Ou LF, Yan RS, Chen IC, Tang YW. Treatment of axillary bromhidrosis with supercial liposuction. Plast Reconstr Surg 1998; 102: 14791485. 70 Jemec B. Abrasio axillae in hyperhidrosis. Scand J Plast Reconstr Surg 1975; 9: 4446. 71 Jemec B, Holm Hansen B. Follow-up of patients operated on for axillary hyperhidrosis by subcutaneous curettage. Scand J Plast Reconstr Surg 1978; 12: 6567. 72 Darabaneanu S, Darabaneanu HA, Niederberger U, Russo PA, Lischner S, Hauschild A. Long-term efcacy of subcutaneous sweat gland suction curettage for axillary hyperhidrosis: a prospective gravimetrically controlled study. Dermatol Surg 2008; 34: 11701177. 73 Bechara FG, Gambichler T, Bader A, Sand M, Altmeyer P, Hoffmann K. Assessment of quality of life in patients with primary axillary hyperhidrosis before and after suction-curettage. J Am Acad Dermatol 2007; 57: 207212. stler E, Scho nlebe J, Haroske G. Tumescent suction cur74 Wollina U, Ko ettage versus minimal skin resection with subcutaneous curettage of sweat glands in axillary hyperhidrosis. Dermatol Surg 2008; 34: 709716. 75 Boni R. Tumescent suction curettage in the treatment of axillary hyperhidrosis: experience in 63 patients. Dermatology 2006; 213: 215217. 76 Bechara FG, Tomi NS, Boorboor P, Sand M, Altmeyer P, Hoffmann K. Liposuction curettage for axillary hyperhidrosis: enhancing success rates and quantifying its efcacy. Dermatology 2007; 215: 268269.

77 Bechara FG, Sand M, Sand D, Altmeyer P, Hoffmann K. Suction-curettage as a surgical treatment of focal axillary hyperhidrosis: recommendation for an aggressive approach. Plast Reconstr Surg 2007; 119: 1390 1391. 78 Bechara FG, Sand M, Tomi NS, Altmeyer P, Hoffmann K. Repeat liposuction-curettage treatment of axillary hyperhidrosis is safe and effective. Br J Dermatol 2007; 157: 739743. 79 Weksler B, Luketich JD, Shende MR. Endoscopic thoracic sympathectomy: at what level should you perform surgery? Thorac Surg Clin 2008; 18: 183191. 80 Eisenach JH, Atkinson JL, Fealey RD. Hyperhidrosis: evolving therapies for a well-established phenomenon. Mayo Clin Proc 2005; 80: 657666. 81 Coelho Mde S, Silva RF, Mezzalira G et al. T3T4 endoscopic sympathetic blockade versus T3T4 video thoracoscopic sympathectomy in the treatment of axillary hyperhidrosis. Ann Thorac Surg 2009; 88: 1780 1785. 82 Inan K, Goksel OS, Uc ak A et al. Thoracic endoscopic surgery for hyperhidrosis: comparison of different techniques. Thorac Cardiovasc Surg 2008; 56: 210213. 83 Lin CC, Mo LR, Lee LS, Ng SM, Hwang MH. Thoracoscopic T2-sympathetic block by clipping a better and reversible operation for treatment of hyperhidrosis palmaris: experience with 326 cases. Eur J Surg Suppl 1998; 164: 1316. 84 Fibla JJ, Molins L, Mier JM, Vidal G. Effectiveness of sympathetic block by clipping in the treatment of hyperhidrosis and facial blushing. Interact Cardiovasc Thorac Surg 2009; 9: 970972. 85 Coelho M, Kondo W, Stunitz LC, Branco Filho AJ, Branco AW. Bilateral retroperitoneoscopic lumbar sympathectomy by unilateral access for plantar hyperhidrosis in women. J Laparoendosc Adv Surg Tech A 2010; 20: 16. 86 Rieger R, Pedevilla S. Retroperitoneoscopic lumbar sympathectomy for the treatment of plantar hyperhidrosis: technique and preliminary ndings. Surg Endosc 2007; 21: 129135. 87 Rieger R, Pedevilla S, Pochlauer S. Endoscopic lumbar sympathectomy for plantar hyperhidrosis. Br J Surg 2009; 96: 14221428. 88 Loureiro Mde P, de Campos JR, Kauffman P, Jatene FB, Weigmann S, Fontana A. Endoscopic lumbar sympathectomy for women: effect on compensatory sweat. Clinics (Sao Paulo) 2008; 63: 189196. 89 Dumont P. Side effects and complications of surgery for hyperhidrosis. Thorac Surg Clin 2008; 18: 193207. 90 Shoenfeld Y, Shapiro Y, Machtiger A, Magazanik A. Sweat studies in hyperhidrosis palmaris and plantaris. A survey of 60 patients before and after cervical sympathectomy. Dermatologica 1976; 152: 257262. 91 Chou SH, Kao EL, Lin CC, Chang YT, Huang MF. The importance of classication in sympathetic surgery and a proposed mechanism for compensatory hyperhidrosis: experience with 464 cases. Surg Endosc 2006; 20: 17491753.

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