Primary Focal Hyperhidrosis Current Treatment Options

REVIEW ARTICLE

Primary focal hyperhidrosis: current treatment optionsand a step-by-step approach

I. Hoorens,* K. Ongenae

Department of Dermatology, University Hospital, Ghent, Belgium

*Correspondence: I. Hoorens. E-mail: [email protected]

AbstractPrimary 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 definitive solution for cases of hyperhidrosis that are unresponsive to non-surgical

treatments. There is no consensus on specific 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

Conflict of interestThe authors have no conflicts of interest to declare.

Funding sourcesThe authors have no funding sources to declare.

IntroductionHyperhidrosis (excessive sweating) can be local, regional or

general. Generalized hyperhidrosis is characterized by sweating

over the entire body with no apparent underlying aetiology. Possi-

ble causes can be neurological, infectious, endocrine or pharmaco-

logical 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 Frey’s

syndrome gives rise to local hyperhidrosis.3,4 Primary focal hyper-

hidrosis 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 standardiza-

tion 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 specifically for the four most

frequently affected body regions (axillar, plantar, palmar and

craniofacial).

MethodsThe PUBMED and Cochrane databases were searched using the

following terms: hyperhidrosis, excessive sweating, local treatment,

systemic treatment, aluminium salts, anticholinergics, iontophore-

sis, 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 sat-

isfaction, 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

ª 2011 The Authors

JEADV 2012, 26, 1–8 Journal of the European Academy of Dermatology and Venereology ª 2011 European Academy of Dermatology and Venereology

DOI: 10.1111/j.1468-3083.2011.04173.x JEADV

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 des-

ignated by several authors to be instrumental in the pathophysiol-

ogy of hyperhidrosis.11,12 Eccrine sweat glands are innervated by

cholinergic fibres, while the apocrine sweat glands are innervated

by adrenergic fibres.11 There are no quantitative or qualitative his-

topathological changes in the eccrine sweat glands of hyperhidrosis

patients. The nature of hyperhidrosis is primarily a complex dys-

function 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 hyper-

hidrosis was proposed.15 Hyperhidrosis patients were found to

have higher plasma values of NO when compared to healthy con-

trols. 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 30–50% of

hyperhidrosis cases suggesting genetic involvement.2,16 One study

highlights the specific role of chromosome 14 (Locus 14q11.2-

q13) 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 indi-

cating 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

The patient with primary focal hyperhidrosis presents with com-

plaints of excessive (most often bilateral) sweating of the axillae,

hands, soles or face. The diagnosis of primary idiopathic focal

hyperhidrosis is made based on the criteria according to Hornber-

ger et al. (Table 2). A strong history and clinical examination are

sufficient for diagnosis, making additional tests unnecessary.7 The

Minor iodine test can be used for localization of the zone of exces-

sive sweating and for treatment evaluation.21 Secondary causes, for

example neuropathies, can be diagnosed by performing the ther-

moregulatory sweat test.22 Gravimetry is a quantitative tool to

measure sweating, most useful in clinical trials to objectively evalu-

ate the outcome of treatment. The criteria for excessive sweating

depend on location and gender. One study defines a sweat rate of

50–100 mg ⁄ 5 min per axilla as necessary for the diagnosis of axil-

lary hyperhidrosis.23

Impact on the quality of life

Hyperhidrosis has a significant 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 hexa-

hydrate blocks the epidermal duct of eccrine sweat glands, and

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, case–control studies or historically controlledstudies

Level 5: Mechanism-based reasoning

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 withoutany obvious cause, besides the presence of at least two of thefollowing 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

Table 3 Hyperhidrosis Disease Severity Scale (HDSS) (adapted

from Solish et al.26)

‘How would you rate the severity of your hyperhidrosis?’

• My sweating is never noticeable and never interferes with my dailyactivities: 1

• My sweating is tolerable but sometimes interferes with my dailyactivities: 2

• My sweating is barely tolerable and frequently interferes with mydaily activities: 3

• My sweating is intolerable and always interferes with my dailyactivities: 4

Score of 1: mild; Score of 2: moderate; Score of 3–4: severe.

ª 2011 The Authors


2 Hoorens and Ongenae

induces atrophy and vacuolization at the level of the glandular

secretory cells. Necrosis of the epidermal cells of the duct delinea-

tion is also induced25 (Fig. 1). The initial dose is a 10–12% solu-

tion which can be increased to a 35% solution dissolved in ethyl

alcohol or a 2–4% 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 efficacy.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

efficacy, low cost and convenience, topical treatment with alumin-

ium salts should be the first line treatment for all mild forms of

primary focal hyperhidrosis. The vehicle can be adjusted depend-

ing on localization of the condition (Table 4).

Topical anticholinergics: Topical anticholinergics are used

mostly in the treatment of craniofacial hyperhidrosis. Two case-

reports describe successful topical treatment with 0.5% topical

glycopyrrolate for craniofacial hyperhidrosis.32,33 A clinical trial

of 25 patients confirmed these results, showing a significant

reduction in craniofacial sweating with 2% topical glycopyrroni-

um solution applied to one side of the face compared to

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 Step 2 Step 3 Step 4 Step 5

Axillaryhyperhidrosis

Topical aluminiumchloridehexahydrate15–20% (to 35%)in ethyl alcohol (L2),salicylic acid gel(L3) or thermophobicfoam (L3)

BTX-A injections (L2) Systemicanticholinergics(L2)

Suction curettage(L2) or excisionof the sweatglands (L3)

Repeat suction curettage(L3) or sympatheticdenervation (L2)

Palmarhyperhidrosis

Topical aluminiumchloridehexahydrate15–20% (35%) inethyl alcohol (L2),salicylic acid gel(L3) or thermophobicfoam (L3)

Iontophoresis,15–20 mA,20–30 min, TWI (L2),Anticholinergics (L2),BTX-A (L3),Dry-type (L3)

BTX-Ainjections (L2)

Systemicanticholinergics(L4)

Sympatheticdenervation (L2)

Plantarhyperhidrosis

Topical aluminium chloridehexahydrate 15–20%(35%) in ethyl alcohol (L2)or salicylic acid gel (L3)

Iontophoresis, 15–20 mA,20–30 min, TWI (L2),Anticholinergics (L2)


Systemicanticholinergics(L4)

Craniofacialhyperhidrosis

Topical aluminium chloridehexahydrate 15–20%(35%) in ethyl alcohol (L2),Topical glycopyrrolate(2%) (L3)

Systemicanticholinergics (L4)


Sympatheticdenervation (L2)

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

AlCl

?

M

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.

ª 2011 The Authors


Primary focal hyperhidrosis 3

placebo on the other side. However, the effect lasted for only

one to two days.34

Iontophoresis Tap water iontophoresis (TWI): While the mecha-

nism of action of TWI is not yet entirely clear, it is an effective

treatment in the inhibition of sweat secretion (Fig. 1). TWI treat-

ment consists of 20–30 min treatments, three to four times per

week. Each palm or sole is placed in a small tray filled with tap

water with a current of 15–20 mA.26 Upon euhidrosis, mainte-

nance 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 sen-

sation 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 off-

set (AC ⁄ DC). Lesser side effects are associated with devices that

use AC ⁄ DC.36 TWI is a safe, cost-effective and efficient 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: Glyco-

pyrronium or hexopyrronium bromide (0.1%) administration

through iontophoresis has significantly 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 dys-

function). 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 significantly greater effect of

iontophoresis with administration of a 0.05% glycopyrrolate solu-

tion compared to TWI in the treatment of palmoplantar hyperhi-

drosis 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 treat-

ment option is not recommended by the Canadian Hyperhidrosis

Advisory Committee (Table 4).

Administration of botulinum toxin A through iontophoresis: A

recent study found efficacy in the treatment of palmar hyperhidro-

sis 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 significantly improved

with Dysport iontophoresis treatment compared to TWI. In addi-

tion, there were no typical BTX-A side effects, such as loss of mus-

cle 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 pho-

bia.42 The current role of BTX-A iontophoresis in treating hyperhi-

drosis 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 cyl-

inder 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 confirms the effective-

ness 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 confirmed 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 neuromus-

cular junction receptors and autonomic cholinergic neurons.

Upon entering the cytosol, BTX-A breaks down polypeptides nec-

essary for exocytosis of acetylcholine (Fig. 1) resulting in flaccid

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.46–49 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 tem-

porary 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 treat-

ment 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 axil-

lary 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 sig-

nificant difference in grip strength (measured by hydraulic dyna-

mometer) 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.52–54 The role of BTX-A in the treat-

ment of craniofacial hyperhidrosis55 is investigated and is an alter-

native to tackle the problem. Indeed the Canadian Hyperhidrosis

Advisory Committee recommends BTX-A injections as a treat-

ment option for axillary, palmar, plantar and craniofacial hyperhi-

drosis26 (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 significantly reduces pain while providing similar efficacy

on sweat reduction compared to BTX-A dissolved in a salt

solution.58

ª 2011 The Authors



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 efficacy 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 hyperhi-

drosis in 75% of patients. However, 79% of patients complained

of dry mouth, causing a 50% dropout rate.60 Systemic anticholin-

ergics 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 fac-

tors in the exacerbation of hyperhidrosis is reported in epidemio-

logical 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 first reports of surgical excision of axillary sweat glands

described high complication rates (less arm movement, unaes-

thetic scars, infection and haematomas).62–64 A clinical trial in

2006 reported a 65% success rate by Shelley’s 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 axil-

lary 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 axil-

lary bromhidrosis.69 Possible complications are bleeding, pain,

haematoma, secondary infection, seroma and damage to the

brachial plexus.67–69

Jemec70 was the first 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 dissatisfied

with the outcome, reporting significant side effects such as

haematomas, abscesses and severe necrosis with the need for skin

grafting.71

Successful results of suction curettage, as evaluated by gravime-

try, have been reported with a 12 month follow-up.72 These results

were only significant 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, sero-

ma, local alopecia and dysesthesia.73

A recent study of 163 patients compared subcutaneous curet-

tage 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 insuffi-

ciently aggressive treatment. A comparative study using a aggres-

sive cannula confirmed 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 complica-

tions.77 In cases where suction curettage is insufficient, reopera-

tion with a more aggressive method can be an option. A study

examining the safety and efficacy of repeating suction curettage

reported that 89% of patients showed a significant 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 first method is sympathectomy or ganglionectomy

(for example of the T2 ganglion) and is performed by a transec-

tion 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 gan-

glion. 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

definition and therefore need clarification. Clipping is the ana-

logue 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 pal-

mar, craniofacial and axillary hyperhidrosis (Table 4). Studies

in the treatment of plantar hyperhidrosis by lumbar sympath-

ectomy have reported good results at follow-up.85–87 The major

ª 2011 The Authors



complication described is sexual dysfunction87,88 and therefore,

fine tuning of the technique is necessary to introduce it as a stan-

dard approach.

The most common side effect of sympathetic denervation in the

treatment of primary axillary, palmar and craniofacial hyperhidro-

sis 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 defining com-

pensatory 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 anatomi-

cal region with an intact sympathetic nervous system) to maintain

a constant rate of total sweat secretion.90 However, this theory was

not confirmed by other studies, demonstrating that compensatory

sweating represented a reflex action by an altered feedback mecha-

nism 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 ‘reflex sweating’ to replace com-

pensatory 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 significant risks of complications

during and after surgery (arterial or venous vascular injury, pneu-

mothorax, infection, Horner syndrome etc.).

DiscussionTogether, 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 for-

mulations in salicylic acid gel or thermophobic foam (level 3).

The HDDS is useful in the assessment of severity of hyperhidro-

sis. However, in addition to the HDDS score and localization,

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 con-

dition which significantly interferes with social, professional and

daily activities, the patient must make an informed decision con-

cerning the best management strategy. The precise pathogenesis of

hyperhidrosis is not yet fully understood and as such current treat-

ments 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 find 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 hyperhi-

drosis remains unclear. Future studies should focus on the specific

neurophysiological dysregulation of the autonomic nervous sys-

tem, the role of specific neurotransmitters and the genetic basis of

primary focal hyperhidrosis to support the development of more

specific causal therapies.

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