17

FACIAL PLASTIC
SURGERY CLINICS
OF NORTH AMERICA
Facial Plast Surg Clin N Am 15 (2007) 17–30

Diagnosis, Impact, and Management

of Focal Hyperhidrosis: Treatment
Review Including Botulinum Toxin
Therapy
Joel L. Cohen, MDa,*, Goldie Cohen, MD
b
, Nowell Solish, MD
c
,
Christian A. Murray, MDc

- Definition of hyperhidrosis - Surgical procedures

- Epidemiology of focal hyperhidrosis Excision
- Symptoms of focal hyperhidrosis Curettage and liposuction
- Social implications Endoscopic thoracic sympathectomy
- Anatomy - Botulinum toxin therapy
- Physiology Axillary
- General evaluation and documentation Palmar
of severity Plantar
- Topical treatment Facial
Aluminum chloride Frey’s syndrome
Aldehydes - Botulinum toxin injection tips
Topical anesthetics Starch-iodine testing
Topical anticholinergics Anesthesia
- Iontophoresis therapy Injection
- Systemic agents - Summary
- Alternative treatments - References

Definition of hyperhidrosis what is necessary for thermoregulation, is the

Fluid excreted by eccrine glands in the skin is called
sweat. Sweat production is a normal physiologic
process allowing heat loss and thermoregulation.
Only when sweat production is excessive, beyond
term hyperhidrosis applied.
A standard definition of excessive sweating has
not been established. Normal quantities of sweat
have been defined in one study as less than
1 mL/m2/min [1]. Axillary hyperhidrosis has been

a
AboutSkin Dermatology and DermSurgery, 499 East Hampden Avenue, Suite 450, Englewood, CO 80113,
USA
b
Department of Pediatrics, Denver Children’s Hospital, University of Colorado, 499 East Hampden Avenue,
Suite 450, Englewood, CO 80113, USA
c
Division of Dermatology, University of Toronto, 76 Grenville Street, Room 841, Toronto, Ontario M5S 1B2,
Canada
* Corresponding author. AboutSkin Dermatology and DermSurgery, 499 East Hampden Avenue, Suite 450,
Englewood, CO 80113.
E-mail address: denverskindoc@yahoo.com (J.L. Cohen).

1064-7406/07/$ – see front matter ª 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.fsc.2006.10.002
facialplastic.theclinics.com
18 Cohen et al
classified as the production of more than 100 mg of
sweat in one axilla within 5 minutes, or more than
50 mg within 1 minute [2]. These attempts at stan-
dardization of a normal sweat rate in humans fail
to take into account the critical element of surface
area. Clearly, more surface area leads to more sweat
production; therefore, these definitions unfairly put
smaller people (and often women) below the
quantitative threshold of hyperhidrosis. At least
for the time being, one is forced to use the subjec-
tive and individualistic definition that estimates
how hyperhidrosis affects a patient’s quality of
life, that is, ‘‘excessive sweat production.’’ For practi-
cal purposes, any sweating that significantly inter-
feres with daily life (physically or psychologically
in either social or occupational realms) should be
viewed as abnormal.
Hyperhidrosis can be categorized as focal or gen-
eralized. Focal hyperhidrosis, also known as primary
hyperhidrosis, affects isolated areas such as the axil-
lae, palms, soles, face, or other specific sites. Some
forms of isolated hyperhidrosis have an underlying
cause, for example, post parotidectomy, and these
instances are characterized as secondary localized
hyperhidrosis. The term focal hyperhidrosis is used
when the etiology is unknown; therefore, it is often
referred to as primary or idiopathic hyperhidrosis.
Generalized hyperhidrosis, as the name implies,
usually affects the entire body surface area and can
often be attributed to one of a variety of causes (in-
cluding endocrine, infectious, menopause/physio-
logic, neurologic, oncologic, or adverse effects of
medications such as antidepressants). The mandate
of this article is to discuss the isolated type, focal
hyperhidrosis, in which no specific etiology is
pinpointed but emotional stimuli usually have
some minor role. A recent working group suggested
the diagnostic criteria in Box 1 based on a review of
the literature [3].
Epidemiology of focal hyperhidrosis
It has long been reported that approximately 1% of
the population sustains focal hyperhidrosis [4,5].
Box 1: Diagnostic criteria for primary focal
idiopathic hyperhidrosis
Focal, visible, excessive sweating of at least 6
months duration without secondary cause with
at least two of the following characteristics:
Bilateral and relatively symmetric sweating
Frequency of at least 1 episode per week
Impairment of daily activities
Age at onset less than 25 years
Positive family history
Cessation of sweating during sleep
This statistic is now recognized to be an underesti-
mation owing to the significant negative social im-
plication of hyperhidrosis, resulting in frank
underreporting. In addition, many people who
have this disorder are simply unaware that they
have a specific diagnosis that is a recognized medical
problem. A more recent large study reported a preva-
lence of 2.8% in a US based survey of 150,000
households (with a 64% response rate) [6]. Most
of those affected in this study indicated that they
did not discuss their problem with health care pro-
fessionals. The condition seems to affect males and
females at an equal rate, with the most common
prevalence among persons aged 25 to 64 years. No
studies have documented the natural progression
of disease with age, but the authors’ experience sug-
gests a decreasing severity in the fifth or sixth decade.
Individuals sustaining focal hyperhidrosis often go
to considerable lengths to hide their condition [7].
Symptoms of focal hyperhidrosis
In some patients with hyperhidrosis, sweat produc-
tion is so profound that it can exceed greater than
40 mL/m2/min, forty times the normal defined
rate [1]. Even when rates are not this extreme, focal
hyperhidrosis can be extremely disabling socially
and professionally [7] and can dramatically reduce
the quality of life [8–12].
Symptoms typically begin in adolescence or the
early twenties and affect one or more anatomic re-
gions, including the axillae, palms, soles, face, and
scalp [5]. The specific breakdown for the most com-
monly affected anatomic sites of involvement is as
follows: 51% axillae, 24% palmar, and 30% plantar
[6]. This report also indicated that 18% of those af-
fected have both axillary and palmar manifestations,
whereas 15% report both palmar and plantar in-
volvement [6]. Facial hyperhidrosis is less frequent,
affecting up to 10% of patients with focal hyperhi-
drosis [5]. With all types of focal hyperhidrosis,
emotional, thermal, and vasodilatory stimuli further
accentuate the baseline problem. The excessive
moisture can lead to maceration of the skin, which
can result in secondary skin infections or odor
(bromhidrosis). By the time of the latter teens or
early twenties, the social or occupational impair-
ment of the condition sometimes leads these indi-
viduals to present for treatment [13].
Social implications
Hyperhidrosis impairs daily functions, social inter-
actions, and work activities. Persons who seek
medical attention report a tremendous spectrum
of how their lives are affected. In one study, 32%
of individuals with axillary hyperhidrosis indicated
that their sweating was barely tolerable or

intolerable, and frequently or always interfered
with their daily activities [6]. In this report, 35%
of persons with focal hyperhidrosis decreased the
amount of time they spent doing leisure activities,
and 22% decreased the amount of time they spent
working [6] as a result of their symptoms. Another
study documented that more than one half of
patients found that hyperhidrosis moderately or
severely affected their emotional state [11]. When
validated scales of quality of life are used to mea-
sure disease burden, the effects of hyperhidrosis
are comparable with those of severe psoriasis,
end-stage renal disease, rheumatoid arthritis, and
multiple sclerosis [8,9].
Many patients report humiliation owing to soak-
ing or staining of their clothes or perceived odors.
They spend considerable time each day wiping,
changing clothes, refreshing, and bathing. Most
are concerned about discrimination and social stig-
matization as a result of their problem. Many have
difficulty developing relationships, because greet-
ings and simple intimacies such as holding hands
or hugging become awkward. Those affected fre-
quently keep their arms tight to their side to hide
underarm staining and odor, or their palms against
their pants to wipe the moisture. Job security and
discrimination are a major concern as patients
fear a perception of nervousness, especially with fa-
cial hyperhidrosis. Staining or smudging papers
such as documents or homework is a frequent
complaint. Large expenses are incurred in buying
new clothes (often two of the same shirts to
change mid-day), antiperspirants, and cosmetics,
as well as on laundry bills. A great deal of time is
spent in coping with the problem, including shop-
ping, cleaning, attempts at drying, and physician
visits.
A significant number of persons who have hyper-
hidrosis do not realize they have a medical issue
and simply blame themselves. Furthermore, hyper-
hidrosis patients have been documented to have
poorer general coping abilities and more emotional
problems than general dermatologic patients and
normal controls [7,14]. Studies also indicate that
those who suffer most usually have had hyperhi-
drosis for a longer duration of time [7], indicating
that the ability to cope with the problem does not
improve.
Anatomy
Sweat glands are distributed throughout the skin.
Different anatomic areas have varying numbers of
the three types of sweat glands: eccrine, apocrine,
and apoeccrine. Apocrine glands are far less numer-
ous and are specifically localized to the urogenital
regions as well as the axillae. Apocrine glands
Botulinum Toxin Therapy for Focal Hyperhidrosis 19
produce a viscid secretion that can become mal-
odorous owing to bacterial breakdown [15,16].
Eccrine glands, which are the causative gland re-
sponsible for focal hyperhidrosis, are the most nu-
merous sweat glands, with 2 to 4 million glands
distributed over almost the entire body surface at
birth [1]. These eccrine glands normally function
in a thermoregulatory capacity but are also affected
by emotional and gustatory stimuli. Eccrine glands
typically do not reside on the mucosa, nail beds,
nipples, glans penis, clitoris, labia minora, or exter-
nal auditory canal. They are most numerous on the
palms and soles, forehead, axillae, and the cheeks
[17].
Eccrine glands are not spatially related to other
adnexal structures and derive embryologically
from the epidermis and not the folliculosebaceous
unit. They are composed of a secretory coil (in the
deep dermis and superficial fat), a duct (traverses
the dermis), and an intraepidermal pore (passes be-
tween keratinocytes and opens onto the surface of
the skin). Eccrine glands produce a thin secretion
that is hypotonic to plasma (B, Atkins). Surpris-
ingly, histologic studies in patients with focal hyper-
hidrosis have not shown an increase in the number
or size of eccrine glands [18]. On the contrary, it is
believed that hyperhidrosis is caused by neurogenic
overactivity of normal numbers of normal-sized ec-
crine sweat glands in the affected area. Part of this
neurogenic hyperactivity may be heritable, because
30% to 65% of patients have a positive family his-
tory of hyperhidrosis [5,18,19]. In one prospective
study of focal hyperhidrosis patients presenting
for treatment, 32 of 49 patients (65%) who pro-
vided information on relatives indicated that they
had a positive family history.
Physiology
Sweat gland function is mediated by the autonomic
nervous system, which is innervated by neurons
that secrete acetylcholine at the sympathetic nerve
endings. Innervation of sweat glands originates
from the hypothalamic preoptic sweat center and
travels down through the brainstem and medulla.
These nerve fibers synapse in the intermediolateral
cell nuclei of the spinal cord in the respective ana-
tomic areas [1,20].
In normal eccrine gland physiology, the volume
and rate of sweat production vary depending on
thermoregulatory requirements. In addition, emo-
tional and physical stresses are related to increased
rates of secretion. In individuals who have idio-
pathic focal hyperhidrosis, there appears to be
a raised basal level of sweat secretion [15]; however,
many of these patients also have an exaggerated
20 Cohen et al
response to increased temperature or emotional or
physical stimuli [15].
The etiology of hyperhidrosis is believed to stem
from a dysfunction of the central sympathetic ner-
vous system affecting the hypothalamic nuclei, pre-
frontal areas, or their cholinergic connections
downstream [8,21–24]. It is thought that this appar-
ent neurogenic overactivity may be due to hyperex-
itability of these reflex circuits involved in eccrine
secretion [21,24]. An electroencephalographic anal-
ysis of one subject with hyperhidrosis found an
abnormality in frontal cortical areas where hyper-
perfusion was demonstrated during sweating epi-
sodes [25]. An autonomic function study looking
specifically at palmar sweating reported hyperfunc-
tioning of the sympathetic nerves passing through
T2-3 ganglia [26].
Interestingly, patients with focal hyperhidrosis
have traditionally been believed to manifest no
other symptoms of autonomic dysfunction; how-
ever, studies have shown differences in cardiac
autonomic function in comparison with normal
controls, indicating that the neurogenic overactivity
believed to cause focal hyperhidrosis is, in some
individuals, potentially part of a more complex
spectrum of autonomic dysfunction [27,28].
General evaluation and documentation
of severity
The clinical history should evaluate the pattern of
disease by outlining the duration, frequency, trig-
gers, volume, distribution, nocturnal symptoms,
impact on daily life, and family history. A review
of systems helps to rule out a secondary cause and
document any contraindications to therapy, such
as pregnancy. A comprehensive review of all of the
conditions associated with hyperhidrosis is beyond
the scope of this article and has been well described
in other sources [15,29–31].
Generalized hyperhidrosis usually affects the en-
tire body surface area and has a variety of causes
(eg, endocrine, infectious, menopause/physiologic,
neurologic, and oncologic). When specifically eval-
uating a patient with likely focal hyperhidrosis, a
detailed history should be performed to identify
any possibility of secondary causes. Any suspicion
should be investigated by an appropriate work-up.
The physical examination will be guided by any
suggestion of secondary hyperhidrosis and attempts
to confirm the distribution of disease. Usually, lab-
oratory diagnostic tests are not necessary in clear cut
or characteristic cases of focal hyperhidrosis, espe-
cially if the patient presents with an adolescent on-
set, positive family history, and symmetric focal
involvement. Focal excessive sweating is usually
dramatic and is usually obvious, especially to
touch. Individuals with axillary hyperhidrosis gen-
erally produce four to five times more sweat than
individuals without hyperhidrosis [32].
The severity of hyperhidrosis is assessed by quan-
titative and qualitative methods. Each evaluation
should attempt to determine the volume of sweat
production, the distribution of hyperhidrosis, and
the affect on quality of life. Gravimetric testing
with filter paper measures the volume of sweat
over a fixed period of time. It is a helpful research
technique but impractical for routine clinical prac-
tice. The Minor starch-iodine test (reviewed herein)
is easy to perform and with its color change pro-
vides a rough qualitative assessment of the volume
of sweat production and the extent of distribution
[12,33]. The starch-iodine test is also helpful after
a treatment modality, because it can identify focal
areas of persistent sweating where small ‘‘touch-
ups’’ may be then focused.
Quality of life for patients affected by focal idio-
pathic hyperhidrosis may be measured with the
Medical Outcomes Trust Short Form 12 Health Sur-
vey (SF-12), Dermatology Life Quality Index
(DLQI), Hyperhidrosis Impact Questionnaire
(HHIQ) [11,12], Hyperhidrosis Disease Severity
Scale (HDSS) [6], and various measures of psychiat-
ric morbidity [34]. In clinical practice, formalized
assessment tests are not required. The DLQI is a val-
idated tool that certainly could be used clinically
because of its simplicity. The DLQI has been used
in a variety of dermatologic conditions and mea-
sures the degree of change in quality of life follow-
ing treatment [35].
Topical treatment
Topical products are the first line of therapy in treat-
ing focal hyperhidrosis. Most of these products are
composed of some type of antiperspirant.
Aluminum chloride
Aluminum chloride is the active ingredient in most
antiperspirant agents. Aluminum chloride, like
other metallic salts, exerts its anhidrotic effect by
obstructing the distal sweat ducts within the acro-
syringium by facilitating the formation of a precipi-
tate [36]. Most commercial antiperspirants contain
1% to 2% of aluminum chloride, but higher
concentration formulations are also available over
the counter. Prescription formulations contain
10% to 35% aluminum chloride hexahydrate in
absolute alcohol or salicylic acid gel. All of these
products should be applied daily to dry skin at
bedtime and washed off after 6 to 8 hours. Once
sweating has reduced to a tolerable level, the fre-
quency of application may be reduced to every 1
to 3 weeks. Burning, stinging, and irritation (often

precipitating contact sensitization) are common
side effects (especially in the axillae) seen more
often with higher concentrations, usually limiting
the efficacy of this modality to mild cases of hyper-
hidrosis. For those patients who respond to antiper-
spirants, long-term use can sometimes result in
degeneration of the eccrine unit and resolution of
the localized hyperhidrosis [37].
Aldehydes
Topical aldehyde agents, such as formaldehyde and
glutaraldehyde, have also been employed in focal
hyperhidrosis. Their mechanism of action also
seems to involve blockage of the sweat duct through
denaturing the keratin at the top of eccrine pores
[38,39]. Because the obstruction created is localized
to the superficial stratum corneum, epidermal re-
generation reopens the lumen within a few days,
forcing frequent (usually daily) application. Signif-
icant topical side effects, especially with daily use,
have deterred the use of aldehydes in most treat-
ment protocols for hyperhidrosis. The most prob-
lematic aspect of formaldehyde treatment is
contact sensitization occurring in as many as 20%
of patients [40]. In addition, aldehydes are ex-
tremely irritating and can cause a yellow-brown
discoloration of the skin.
Topical anesthetics
Topical anesthetics have also been tried to reduce
sweat production in focal hyperhidrosis. These
agents potentially exert their effect by blockade of
peripheral nerves and, theoretically, also adjacent
sympathetic nerve fibers supplying eccrine glands
[40]. In one study using 5% lidocaine and 5% pri-
locaine, there was a measurable suppression of ec-
crine secretory activity [41]; however, in practice,
topical anesthetics are of little value in controlling
focal hyperhidrosis [40].
Topical anticholinergics
Topical anticholinergics have long been the intui-
tive option for treating focal hyperhidrosis, because
eccrine glands are innervated by sympathetic cho-
linergic fibers [42]; however, there are two principal
problems with their use in these disorders. First, cu-
taneous absorption is often insufficient. Second, us-
ing more volume of these products to overcome the
poor absorption (or simply to treat larger areas) fre-
quently causes systemic side effects of cholinergic
blockade [40]. Contact sensitization has also been
seen with the use of topical anticholinergics [43].
Despite these shortcomings, there have been re-
ports of efficacy in Frey’s syndrome [44], primary
craniofacial hyperhidrosis [45,46], and diabetic
gustatory sweating [47]. No large study has docu-
mented efficacy in the more common palmar,
Botulinum Toxin Therapy for Focal Hyperhidrosis 21
plantar, or axillary types of focal hyperhidrosis.
Similar to aldehydes and topical anesthetics, topical
anticholinergics are not frequently used in focal
hyperhidrosis treatment regimens.
Iontophoresis therapy
Iontophoresis involves the topical introduction of
ionized particles into the skin using direct current.
Tap water is most frequently used, but anticholiner-
gic agents are sometimes added and have been
reported to improve efficacy [48] The exact mecha-
nism of action of iontophoresis is not exactly clear,
but it is believed to work by a charged particle oc-
cluding the duct or by the electrical change disrupt-
ing eccrine gland secretion [49,50]. Although
reports of the efficacy of tap water iontophoresis
for hyperhidrosis date back to the late 1930s and
early 1940s, it did not become more recognized
as a practical approach in the treatment of hyperhi-
drosis until 1968 [50,51]. No large randomized tri-
als have been performed, but several smaller trials
suggest significant benefit [52,53]. Irritation is a sig-
nificant problem with this technique as well [50]. It
causes dry, peeling, and cracked skin at the treat-
ment site, especially in the axillae treatment site,
at least 4 days per week. One group has reported
that treatment with alternating current combined
with direct current was equally as effective as tradi-
tional tap water iontophoresis but dramatically al-
leviated the irritation and discomfort of the
procedure [52]. After topical aluminum chloride,
tap water iontophoresis is traditionally thought of
as the second line in treating palmar or plantar
hyperhidrosis, but it is frequently too irritating for
regular use in the axillae. Treatment is contraindi-
cated in patients who are pregnant or who have
a pacemaker or defibrillator.
Systemic agents
Oral anticholinergic agents are the most commonly
used systemic therapies in the treatment of all forms
of hyperhidrosis, including specifically focal hyper-
hidrosis [54,55]. These agents function as competi-
tive inhibitors of synaptic acetylcholine, leading to
blockade of neuroglandular signaling. The problem
is their lack of specificity, frequently causing normal
physiologic cholinergic processes to be blocked as
well. Even when used for focal hyperhidrosis, these
agents commonly cause intolerable side effects
including blurred vision, dry mouth, tachycardia,
urinary retention, and constipation. The efficacy
of these agents has not been well documented in
clinical studies [3].
In regard to other oral therapies, a few isolated
case reports have described some level of efficacy
22 Cohen et al
in treating hyperhidrosis with several other systemic
agents, including tranquilizers (diazepam), beta
blockers (propranolol), spasmolytics (belladonna),
non-steroidal anti-inflammatory agents (indometh-
acin), alpha-2-adrenergic agonists (clonidine,
phentolamine, phenoxybenzamine), and calcium
channel blockers (diltiazem) [54,56]. Gabapentin,
an anticonvulsant with an unknown mechanism
of action, was reported to be effective in a pediatric
spinal cord injury patient with isolated areas of hy-
perhidrosis [55]. Most of these reports have in-
volved patients with generalized rather than focal
hyperhidrosis. None of these agents have been
shown to be consistently effective for any form of
hyperhidrosis, and various side effects have been
frequently encountered. To date, the role of sys-
temic agents in the treatment of focal hyperhidrosis
has not been established.
Alternative treatments
Sparse case reports and various anecdotal claims
have described some degree of success in treating
hyperhidrosis with different alternative medicine
modalities. Biofeedback, hypnosis, and several
forms of relaxation techniques have been employed
in treating different forms of hyperhidrosis [57–
59]. Claims in the lay media have been made
regarding efficacy with various herbal remedies
including chamomile and St. John’s wort. The role
of these treatments in focal hyperhidrosis is difficult
to evaluate properly without well-documented clin-
ical trials.
Surgical procedures
Excision
Excision of the axillary vault has long been attemp-
ted to remove the hyperfunctional eccrine glands
from this area completely [60]. Since the initial re-
port in 1963 recommending elliptical excision, var-
ious excisional techniques have been described to
remove or disrupt the sweat production apparatus
within the axilla [61,62]. Success rates have ranged
from 50% to 90% [62]. Case reports have shown
that excisional surgery at any level within the skin
can be complicated by infection, bleeding, delayed
healing, flap necrosis, significant scarring, or scar
contracture [62]. Long-term cosmesis, scarring,
and range of motion issues remain the major prob-
lems with this type of invasive treatment. Recently,
combination surgical resection and carbon dioxide
laser vaporization was reported in one study to be
effective for axillary hyperhidrosis with few compli-
cations [63].
Curettage and liposuction
In an effort to decrease postoperative morbidity as-
sociated with excisional techniques, Jemec pro-
posed subcutaneous curettage of the axillary vault
[64]. Using a small incision, curettage is performed
in an attempt to destroy eccrine glandular tissue
from beneath the skin surface. The report by Jemec
describes a high level of efficacy, with 17 of 20 pa-
tients achieving satisfactory improvement. Since
the late 1980s, axillary liposuction has also been ad-
vocated in an attempt to destroy and remove the
glandular tissue, with acceptable efficacy and fewer
side effects than traditional surgical techniques
[65–67].
Some practitioners have used botulinum toxin A
to treat isolated residual or recurrent areas of axil-
lary hyperhidrosis following liposuction (personal
communication, Patrick Lillis, MD, 2003.).
Endoscopic thoracic sympathectomy
Sympathectomy can be performed nonsurgically
with the use of CT-guided injection of phenol or al-
cohol [68]. Surgical intervention can be done by
open incisions and the more popular endoscopic
techniques. In endoscopic thoracic sympathectomy,
the sympathetic ganglia are destroyed by excision,
ablation, or clipping. Endoscopic thoracic sympa-
thectomy has been most frequently used for focal
palmar hyperhidrosis, for which rates of success
have been as high as 98% [69]. A recent study docu-
mented a 78% overall mean patient satisfaction rate
[70]; however, many of these studies have had
short-term follow-up.
The main problem with sympathectomy for focal
hyperhidrosis is the high incidence of compensa-
tory hyperhidrosis in other regions, with one study
indicating occurrence in as many as 96% of cases
[70,71] The largest study on endoscopic thoracic
sympathectomy encompassed 2200 patients and
indicated that compensatory sweating could occur
in as many as 88% of patients treated for hyperhi-
drosis [72]. This compensatory sweating is often
mild but has been reported to be severe in as
many as 40% of patients treated with endoscopic
thoracic sympathectomy [73]. It typically begins 2
to 8 weeks after sympathectomy [70]. Because of
the significance of this side effect, up to one third
of patients are moderately dissatisfied with their
treatment [74]. Other surgical complications in en-
doscopic thoracic sympathectomy are much less
common than with traditional excisional tech-
niques. Potential complications include chest wall
paresthesia (up to 50%) [75], Horner’s syndrome
(<1%), pneumothorax (7%) [76], hemothorax
(<1%), and rare cardiac arrest or arrhythmias
[69,77].

Botulinum toxin therapy
Axillary
Botulinum toxin has been known to block postgan-
glionic sympathetic cholinergic fibers to sweat
glands since animal studies in 1951 [78]. The first
report of the use of botulinum toxin to produce
an anhydrous effect in humans dates back to
1994 [79] when patients treated for hemifacial
spasm demonstrated a resolution of sweat produc-
tion in the area of treatment. The same group re-
ported the efficacy of subcutaneous botulinum
toxin specifically for axillary hyperhidrosis 2 years
later [80]. Since these reports, many other studies
have followed with large well-controlled trials
clearly identifying intradermal injections of botuli-
num toxin as a safe, effective, and well-tolerated al-
ternative to traditional topical, systemic, or surgical
approaches in the treatment of axillary hyperhidro-
sis [2,81–85]. Currently, the only US Food and Drug
Administration (FDA) approved formulation of
botulinum toxin for hyperhidrosis is Botox, which
is only approved for axillary hyperhidrosis. It has
been most studied and is the basis of most of the
following discussion. Some results for botulinum
toxin B (Myobloc) [86,87] and botulinum toxin A
(Dysport) also suggest they are effective agents in
this disorder. The two formulations of botulinum
toxin A cannot be used interchangeably because
their bioequivalency is completely different.
There is no downtime from this outpatient axil-
lary injection procedure. Efficacy usually begins in
7 to 10 days and lasts 6 to 8 months, no significant
side effects have been encountered, and quality of
life has been shown to improve dramatically after
treatment [9–12,34]. In fact, two recent reports
have shown that treatment of axillary hyperhidrosis
with botulinum toxin A improves health-related
quality of life and limitations in daily activities
[88,89]. Pain associated with these intradermal in-
jections is usually minimal in the axillae. Some
practitioners use ice or a topical anesthetic to fur-
ther minimize discomfort.
Studies on botulinum toxin therapy specifically
for axillary hyperhidrosis involve different agents
(usually botulinum toxin A in Botox or Dysport for-
mulations, but also botulinum toxin B as Myo-
bloc), different doses (often ranging between 50
and 100 U of Botox per axilla), and different dilu-
tions (usually reconstituted with 2.5 to 5 mL of sa-
line per 100 U vial of Botox). One report using
high-dose botulinum toxin A (200 U of Botox)
in each axilla describes efficacy for as long as
29 months [90]; however, most studies suggest little
significant improvement with dosing greater than
50 U per axillae. In the phase III clinical study
Botulinum Toxin Therapy for Focal Hyperhidrosis 23
used for the FDA approval of Botox for axillary hy-
perhidrosis, 50 U, 75 U, and placebo were com-
pared [91]. The HDSS scale was the primary
endpoint of the 322-patient trial. Subjects had to
have an HDSS score of 3 or 4 to enroll, and re-
sponders were defined as having at least a two-grade
improvement in their HDSS score. There was a 75%
response rate in the treatment groups, and there
was no significant difference in efficacy or duration
of action with the higher botulinum toxin dosage
(each dosing was markedly better than placebo).
The median duration of response was about
7 months.
One study incorporated the use of hyaluronidase
with botulinum toxin A to facilitate spread and
lower the overall dose [92], but the authors have
not found this to be helpful in their practices. Inter-
estingly, a recent report demonstrated that botuli-
num toxin A intradermal injections could
ameliorate body odor in healthy volunteers [93].
Although individuals with focal hyperhidrosis
rarely report body odor as one of their principle
symptoms [18], it remains to be investigated
whether chemodenervation of axillary cholinergic
glands with botulinum toxin A has a significant in-
fluence on odor. A recent report on intradermal bot-
ulinum toxin A describing efficacy in treating the
moist and eroded axillary plaques of Hailey-Hailey
disease did demonstrate improvement in odor as
well [94].
Palmar
Treatment of the palms with botulinum toxin A for
focal hyperhidrosis has the same mechanism of ac-
tion as in the axillae, that is, chemodenervation of
the cholinergic nerve fibers that supply eccrine
glands. Although such treatment has been shown
to be successful, fewer studies exist for the use of
botulinum toxin A in palmar hyperhidrosis com-
pared with in the axillae. In 1996, Bushara and co-
workers reported a significant reduction and long
lasting improvement of spontaneous sweating in
the palm using botulinum toxin A [80]. This study
was followed by a placebo-controlled, double-blind
study of palmar hyperhidrosis, confirming the
efficacy of botulinum toxin A [95]. More recent
placebo-controlled studies have continued to
demonstrate a significant improvement in treated
patients [84,96–99]. Efficacy rates measured by
gravimetric analysis, starch-iodine testing, and
patient assessments of satisfaction have all been
observed to be close to 80% to 90% [84,96–99].
The duration of efficacy for palmar hyperhidrosis
frequently lasts an average of 6 months.
Techniques and dosages of botulinum toxin A
differ among studies for this indication as well.
24 Cohen et al
Dermal injections spaced approximately 1 cm apart
seem to give the best results. It appears to be more
efficacious to treat palm size (and to adjust the dose
and number of injection points based on the
surface area of involvement) rather than have a stan-
dard number of injection sites [97]. Few botulinum
toxin dose ranging studies have been done for pal-
mar hyperhidrosis. Saadia and coworkers demon-
strated a similar improvement with 50 U of Botox
when compared with 100 U per palm [97]; how-
ever, there was a trend toward greater patient satis-
faction in the higher dose group. Wollina and
Karamfilov [98] used even higher doses of Botox,
200 U per palm, and noted that this accounted
for a longer duration of anhidrosis. In the authors’
experience, a typical dose for an average sized male
hand is about 100 U, whereas a usually smaller
hand in a woman requires about 80 U.
Pain seems to be the most common complaint of
palmar botulinum toxin treatment [84]. Although
some patients do not require any anesthesia aside
from ice, nerve blocks (median and ulnar with or
without radial) [100] or a Bier block [101] allow
for increased tolerability of the procedure. Vibra-
tory massage devices placed at the anterior and pos-
terior wrist can also be helpful in some patients.
Transient weakness is a potential complication of
palmar botulinum toxin, and as many as two thirds
of patients have noticed a minor weakness of finger
grip [102]. This reduction in grip strength can likely
be attributed to injections placed too deeply, with
botulinum toxin diffusion to underlying muscles.
The reduced grip strength is temporary, and patients
have reported resolution in days to weeks [9,99].
Action potentials for hand musculature have been
shown to normalize by 37 weeks [9]. Other rare
side effects of palmar botulinum toxin therapy
have been reported, including systemic effects in
two patients. A patient treated with botulinum
toxin type B (Myobloc) reported temporary blurred
vision, dry throat, indigestion, and dysphagia [103].
Another patient treated for palmar hyperhidrosis
with botulinum toxin A (Dysport) demonstrated
diffuse asthenia, diplopia, ptosis, and a decrease
in lacrimation, salivary production, and sweating
[104].
Plantar
Few studies have been dedicated exclusively to plan-
tar hyperhidrosis. In 1998 Naumann demonstrated
efficacy of botulinum toxin A in the treatment of
one patient with focal plantar hyperhidrosis [6].
Other studies have subsequently demonstrated im-
provement [105–107] with dosages similar to those
used in palmar studies and with a similar duration
of about 6 months. Regional block anesthesia (pos-
terior tibial and sural nerve) is usually required.
From a practical and medicolegal standpoint, pa-
tients should remain in the office until the anesthe-
sia wears off (or leave by wheelchair with a driver),
because they will have some changes in their ability
to ambulate owing to the ankle block for up to
2 hours. Recently, a Bier block has been demon-
strated to be superior to regional block anesthesia
for plantar hyperhidrosis botulinum toxin therapy
[101].
Facial
Focal hyperhidrosis can also affect the face, most
frequently, the forehead [5]. Although there are
few published reports, botulinum toxin A has
been shown to be an effective treatment for facial
hyperhidrosis [10,108]. The main site of injection
is usually a band near the hairline. The effects
have been documented to last 5 or more months
in most patients [10].
Frey’s syndrome
Facial gustatory sweating after parotid surgery or
trauma is a common complication called Frey’s
Syndrome. It can occur after face-lift surgery as
well, with varying degrees of severity. Frey’s Syn-
drome, classified as a secondary form of localized
hyperhidrosis, is thought to be due to transection
of the postganglionic sympathetic nerve fibers
from the optic ganglion originally directed to the
parotid gland. Following the disruption, it is be-
lieved that there is an aberrant re-innervation of
the facial cholinergic sweat glands. Patients com-
plain of sweating over the lower face and jaw,
most commonly while eating. Treatment with intra-
dermal botulinum toxin A has been shown to have
excellent results for this localized hyperhidrosis
syndrome [109–111]. Relatively low doses are usu-
ally needed (often, 20 to 50 U of Botox). Surpris-
ingly, these results last up to 15 months [104].
Side effects are usually minimal, with an occasional
patient reporting transient weakness of the lip or
mouth musculature [112]. The facial flushing asso-
ciated with this gustatory sweating in Frey’s Syn-
drome has also been shown to improve with
botulinum toxin A therapy.
Botulinum toxin injection tips
Before initiating treatment, the physician should re-
view expectations, potential risks, and alternatives
to botulinum toxin with each patient. Botox has re-
cently been FDA approved for the treatment of axil-
lary hyperhidrosis in the United States and is also
approved for such use in England, Canada, and
New Zealand. Contraindications to the use of botu-
linum toxin (including neuromuscular disease,
pregnancy/lactation, or interacting medications),

described elsewhere in this issue, obviously apply to
its use for this indication as well.
Starch-iodine testing
Starch-iodine testing is a quick and easy qualitative
measure to identify and localize the specific sites of
involvement. This test should be administered be-
fore any anesthesia. A brown-orange iodine solu-
tion is painted over the area of skin to be
evaluated and briefly allowed to dry. A starch (po-
tato or corn) is then sprinkled over the area. Sweat
causes a dark blue discoloration. The distribution
and sites of maximal perspiration may be recorded
with photographs for future comparison or simply
identified for treatment. The authors sometimes
have patients return 2 weeks after treatment to re-
peat the starch-iodine testing and augment any sig-
nificant residual areas of hyperhidrosis. For best
results, patients should discontinue antiperspirants
(or any other topical treatments) 5 days before
starch-iodine tests.
Anesthesia
The thin skin of the axillae is easily penetrated with
30-gauge needles, and generally no anesthesia is re-
quired. Pre- or postinjection ice packs can be help-
ful to minimize mild discomfort. One should
clearly delineate the results of the starch-iodine
test (using a marker or gentian violet) before apply-
ing the ice, because condensation on the bag will
cause false-positive areas of involvement. If a marker
is used, the needle should be placed adjacent to
(rather than directly into) the ink to avoid tattooing
of the skin. When treating the palms or soles, it has
been the authors’ experience that most patients will
require a regional nerve block to minimize discom-
fort, especially for their initial treatment with its as-
sociated heightened anxiety. Small (30-gauge)
Fig. 1. (A) Focal axillary hyperhidrosis starch-iodine test before treatment. (B) Two weeks after treatment with
50 U of Botox in this axilla.
Botulinum Toxin Therapy for Focal Hyperhidrosis 25
needles are used to infiltrate 2% plain lidocaine ad-
jacent to the ulnar, median, and radial nerves of the
wrist, as well as the sural and tibial nerves of the an-
kle. The authors usually wait 15 minutes for the re-
gional block to take effect before beginning
injections. Despite meticulous technique, some pa-
tients may complain of injection pain even after re-
gional blockade. In these cases, an assistant applies
a vibrating wand (Accuvibe) to the skinimmediately
adjacent to the each injection to overstimulate the-
oretically the sensatory stimuli and lessen the pain
(as described by the Gates theory). Care is taken
to stabilize the tissue before placement to avoid
spillage or inadvertent needle-stick during the
vibration process. Over time, some patients can
be converted over from a regional nerve block and
often tolerate simply ice packs alone.
Injection
Intradermal injections are placed within the hyper-
hidrotic regions and are spaced 1 to 1.5 cm apart.
Injections are spaced slightly more closely for the
palms and soles, and more widely for the face and
axillae. Injection into the axillae can be performed
in the superficial fat without adverse events or sig-
nificant reduction in efficacy. In contrast, palmar in-
jections below the dermis have a higher risk of hand
weakness and should be avoided. Furthermore, one
should consider using a lower dose in the hands if
grip strength or fine motor skill is critical to the in-
dividual’s work or lifestyle. Many injectors begin at
the central axillary vault and spiral outward to the
periphery of axillary hair, whereas others use
a grid [113] or random pattern. The total dose
and number of injections should depend on the ac-
tual surface area of involvement in the affected an-
atomic region (Figs. 1 and 2). Depending on the
surface area, approximately 10 to 20 intradermal
26 Cohen et al
Fig. 2. (A) Focal palmar hyperhidrosis starch-iodine test before treatment. (B) Almost 2 weeks after treatment
with 75 U of Botox in each palm.
injections in 0.1 to 0.2 mL aliquots totaling 50 to
100 U of Botox are used for each axilla. For acral
treatment, a typical injection pattern is shown in di-
agram (showing dots on the palm and sole), with
total doses ranging from 50 to 100 U per palm or
sole. The authors reconstitute with 4 mL of pre-
served saline for 100 U of Botox. The Botox vial
should be opened with a bottle opener after saline
reconstitution. This practice allows the syringes to
be filled without dulling each needle with the rub-
ber stopper. One 3-mL Lure lock syringe with a
30-gauge needle may be used for one or both
axillae, depending on the total dose required. For
the palms and soles, needles tend to dull more
quickly; therefore, the needle should be replaced
several times [114]. Alternatively, Becton and
Dickinson Ultrafine II 50-U insulin syringes that
hold 0.5 mL are employed. The thick skin of the
palms and soles provides for easy injection into
the dermis. The typical wheal to identify proper
depth placement is often absent; however, a zone
of visible blanching is indicative of proper depth.
The Botox has a tendency to backflow from the in-
jection tract once the needle is removed. To reduce
this problem, the needle should be inserted slowly
and without pressure on the plunger. Removing the
injector’s thumb from the plunger and waiting a sec-
ond after injection allows time for diffusion and
minimizes backflow onto the skin surface.
In the authors’ practices, treatment of the axillae
results in successful improvement in hyperhidrosis
in the vast majority of patients. The effects last ap-
proximately 6 to 9 months. Palmar and facial hy-
perhidrosis also respond well, with most patients
experiencing considerable benefit for 6 months.
Treatment of the soles is less predictable despite
uniform technique. When concern exists regarding
hand weakness, such as in professional musicians
or surgeons, treatments are initiated at a low dose
or begun with the nondominant hand and per-
formed on a staggered schedule. The future holds
excitement for some innovative delivery systems
of the toxin to minimize discomfort. One report de-
scribes using a dermojet to deliver botulinum toxin
A for the treatment of plantar hyperhidrosis with-
out the use of analgesia [115]. In addition, there
has been one report of using an iontophoresis
unit to deliver botulinum toxin A transcutaneously
via an electric current [116].
Summary
Focal hyperhidrosis is a common problem affecting
up to 2.8% of the population, with dramatic psy-
chosocial implications. Traditional therapies have
fallen short for most of these patients, further add-
ing to patients’ anxiety. Botulinum toxin is emerg-
ing as a novel treatment for focal hyperhidrosis
that is proving to be safe and effective. To date, there
have been no reported cases of compensatory hy-
perhidrosis or botulinum toxin antibody produc-
tion as a result of hyperhidrosis treatment [117]. A
therapeutic protocol for focal hyperhidrosis in-
cludes an individualized treatment plan for each
site of involvement. For patients affected in the
palms and soles, the most common treatments in-
clude topical treatment with aluminum chloride,
iontophoresis, botulinum toxin, systemic medica-
tions, and sympathectomy. For patients with axil-
lary or facial focal hyperhidrosis, botulinum toxin
becomes the second-line therapy. Botox A has
been shown repeatedly to be a safe and effective
treatment for focal hyperhidrosis.
References
[1] Sato K, Kang WH, Saga KT. Biology of sweat
glands and their disorders. I. Normal sweat
gland function. J Am Acad Dermatol 1989;20:
537–63.
[2] Heckmann M, Ceballos-Baumann AO,
Plewig G. Botulinum toxin A for axillary hyper-
hidrosis. N Engl J Med 2001;344:488–93.

[3] Hornberger J, Grimes K, Naumann M, et al. Rec-
ognition, diagnosis, and treatment of primary
focal hyperhydrosis. J Am Acad Dermatol
2004;51:274–86.
[4] Adar R, Kurchin A, Zweig A, et al. Palmar hyper-
hidrosis and its surgical treatment: a report of
100 cases. Ann Surg 1977;186:34–41.
[5] Stolman LP. Treatment of hyperhidrosis.
Dermatol Clin 1998;16:863–7.
[6] Strutton DR, Kowalski JW, Glaser DA, et al. US
prevalence of hyperhidrosis and impact on indi-
viduals with axillary hyperhidrosis: results from
a national survey. J Am Acad Dermatol 2004;51:
241–8.
[7] Amir M, Arish A, Weinstein Y, et al. Impairment
in quality of life among patients seeking surgery
for hyperhidrosis (excessive sweating): prelimi-
nary results. Isr J Psychiatry Relat Sci 2000;37:
25–31.
[8] Cina CS, Clase CM. The Illness Intrusiveness Rat-
ing Scale: a measure of severity in individuals
with hyperhidrosis. Qual Life Res 1999;8:693–8.
[9] Swartling C, Naver H, Lindberg M. Botulinum
A toxin improves life quality in severe primary
focal hyperhidrosis. Eur J Neurol 2001;8:
247–52.
[10] Tan SR, Solish N. Long-term efficacy and quality
of life in the treatment of focal hyperhidrosis
with botulinum toxin A. Dermatol Surg 2002;
28:495–9.
[11] Naumann M, Hamm H, Lowe N. Effect of bot-
ulinum toxin A on quality of life measures in
patients with excessive axillary sweating: a ran-
domized controlled trial. Br J Dermatol 2002;
147:1218–26.
[12] Campanati A, Penna L, Guzzo T, et al. A qual-
ity-of-life assessment in patients with hyperhi-
drosis before and after treatment with
botulinum toxin: results of an open-label study.
Clin Ther 2003;25(1):298–308.
[13] Hashmonai M, Kopelman D, Assalia A. The
treatment of primary palmar hyperhidrosis: a
review. Surg Today 2000;30:211–8.
[14] Lere B, Jacobowitz J, Wahaba A. Personality fea-
tures in essential hyperhidrosis. Int J Psychiatry
Med 1981;10:59–67.
[15] Atkins JL, Butler PEM. Hyperhidrosis: a review
of current management. Plast Reconstr Surg
2002;110:222–8.
[16] Naumann M, Hamm H, Kinkelin I, et al. Botu-
linum toxin type A in the treatment of focal, ax-
illary and palmar hyperhidrosis and other
hyperhidrotic conditions. Eur J Neurol 1999;6:
S111–5.
[17] Kreydon O, Scheidegger E. Anatomy of the sweat
glands, pharmacology of botulinum toxin, and
distinctive syndromes associated with hyperhi-
drosis. Clin Dermatol 2004;22:40–4.
[18] Sato K, Kang WT, Saga KT. Biology of sweat
glands and their disorders. II. Disorders of
sweat gland function. J Am Acad Dermatol
1989;20:713–26.
Botulinum Toxin Therapy for Focal Hyperhidrosis 27
[19] Ro KM, Cantor RM, Lange KL, et al. Palmar hy-
perhidrosis: evidence of genetic transmission.
J Vasc Surg 2002;35:382–6.
[20] Uno H. Sympathetic innervation of sweat glands
and piloerector muscle of macaques and human
beings. J Invest Dermatol 1977;69:112–7.
[21] Manca D, Valls-Sole J, Callejas MA. Excitability
recovery curve of the sympathetic skin response
in healthy volunteers and patients with palmer
hyperhidrosis. Clin Neurophysiol 2000;111:
1767–70.
[22] Freeman R, Waldorf HA, Dover JS. Autonomic
neurodermatology (part II): disorders of sweat-
ing and flushing. Semin Neurol 1992;12:
394–407.
[23] Glogau RG. Botulinum A neurotoxin for axil-
lary hyperhidrosis: no sweat Botox. Dermatol
Surg 1998;24:817–9.
[24] Iwase S, Ikelda T, Kitazawa H, et al. Altered re-
sponse in cutaneous sympathetic outflow to
mental and thermal stimuli in primary palmo-
plantar hyperhidrosis. J Auton Nerv Syst 1997;
64:65–73.
[25] Mamose T, Kunimoto M, Nishikawa J, et al.
N-isopropyl I-123 p-iodoamphetamine brain
scans with single photon emission computed
tomography: mental sweating and EEG abnor-
mality. Radiat Med 1986;4:46–50.
[26] Shih CJ, Wu JJ, Lin MT. Autonomic dysfunction
in palmar hyperhidrosis. J Auton Nerv Syst
1983;8:33–43.
[27] Birner P, Heinzl H, Schindl M, et al. Cardiac au-
tonomic function in patients suffering from pri-
mary focal hyperhidrosis. Eur Neurol 2000;44:
112–6.
[28] Kaya D, Karaca S, Barutcu I, et al. Heart rate var-
iability in patients with essential hyperhidrosis:
dynamic influence of sympathetic and para-
sympathetic maneuvers. Ann Noninvasive Elec-
trocardiol 2005;10(1):1–6.
[29] Kreyden OP, Boni R, Burg G. Hyperhidrosis and
botulinum toxin in dermatology. Curr Probl
Dermatol 2002;30:10–45.
[30] Kreyden OP. Rare forms of hyperhidrosis. Curr
Probl Dermatol 2002;30:178–87.
[31] Leung AKC, Chan PYH, Choi MCK. Hyperhi-
drosis. Int J Dermatol 1999;38:561–7.
[32] Hund M, Kinkelin I, Naumann M, et al.
Definition of axillary hyperhidrosis by gravi-
metric assessment. Arch Dermatol 2002;138:
539–41.
[33] Minor V. Ein neues Verfahren zu der klinischen
Unterschung der Schweibabsonderung. Dtsch Z
Nervenheilkd 1927;101:302–8.
[34] Weber A, Heger R, Sinkgraven M, et al. Psycho-
social aspects of patients with focal hyperhidro-
sis: marked reduction of social phobia, anxiety
and depression and increased quality of life
after treatment with botulinum toxin A. Br J
Dermatol 2005;114:343–5.
[35] Finlay AY, Khan GK. Dermatology Life Quality
Index (DLQI)—a simple practical measure for
28 Cohen et al
routine clinical use. Clin Exp Dermatol 1994;
19:210–6.
[36] Qualtrale RP, Coble DW, Stoner KL, et al. The
mechanism of antiperspirant action by alumi-
num salts. II. Histologic observations of human
eccrine sweat glands inhibited by aluminum
chlorohydrate. J Soc Cosmet Chem 1981;32:
107–36.
[37] Holzle E, Braun-Falco O. Structural alterations
of axillary eccrine glands in hyperhidrosis fol-
lowing long-term treatment with aluminum
chloride hexahydrate. Br J Dermatol 1984;110:
399–403.
[38] Gordon BI, Maibach HI. Eccrine anhidrosis due
to glutaraldehyde, formaldehyde and iontopho-
resis. J Invest Dermatol 1969;53:436–9.
[39] Sato K, Dobson RL. Mechanism of the antiper-
spirant effect of topical glutaraldehyde. Arch
Dermatol 1969;100:564–9.
[40] Holzle E. Topical pharmacologic treatment (in
hyperhidrosis and botulinum toxin in derma-
tology). Curr Probl Dermatol 2002;30:30–43.
[41] Juhlin L, Evers H, Broberg F. Inhibition of hy-
perhidrosis by application of a local anesthetic
composition. Acta Derm Venereol 1979;59:
556–9.
[42] MacMillan F, Reller H, Synder F. The antiperspi-
rant action of topically applied anticholiner-
gics. J Invest Dermatol 1964;43:363–77.
[43] Agren-Johnson S, Magnusson B. Sensitization
to propantheline bromide, trichlorocarbanilide
and propylene glycol in antiperspirant. Contact
Dermatitis 1976;2:79–80.
[44] Hays LL, Novack AJ, Worsham JC. The Frey syn-
drome: a simple, effective treatment. Otolaryng-
ol Head Neck Surg 1982;90:419–25.
[45] Seukeran DC, Higet AS. The use of topical gly-
copyrrolate in the treatment of hyperhidrosis.
Clin Exp Dermatol 1998;23:204–5.
[46] Luh J, Blackwell T. Craniofacial hyperhidrosis
successfully treated with topical glycopyrrolate.
South Med J 2002;95(7):756–8.
[47] Urman JD, Bobrove AM. Diabetic gustatory
sweating successfully treated with topical glyco-
pyrrolate: a report of a case and review of the
literature. Arch Intern Med 1999;159:877–8.
[48] Dolianitis C, Scarff CE, Kelly J, et al. Iontopho-
resis with glycopyrrolate for the treatment of
palmoplantar hyperhidrosis. Aust J Dermatol
2004;45(4):208–12.
[49] Sato K, Timm DE, Sato F, et al. Generation and
transit pathway of H1 is critical for inhibition
of palmar sweating by iontophoresis in water.
J Appl Physiol 1993;75:2258–64.
[50] Sloan JB, Soltani K. Iontophoresis is dermatol-
ogy. J Am Acad Dermatol 1986;15:671–84.
[51] Levit F. Simple device for the treatment of hy-
perhidrosis by iontophoresis. Arch Dermatol
1968;98:505–7.
[52] Reinauer S, Neusser A, Schauf G, et al. Ionto-
phoresis with alternation current and direct cur-
rent offset (AC/DC iontophoresis): a new
approach for the treatment of hyperhidrosis.
Br J Dermatol 1993;129:166–9.
[53] Karakoc Y, Aydemir EH, Kalkan MT, et al. Safe
control of palmoplantar hyperhidrosis with di-
rect electrical current. Int J Dermatol 2002;
41(9):602–5.
[54] Tkach JR. Indomethacin treatment of general-
ized hyperhidrosis. J Am Acad Dermatol 1982;
6:545.
[55] Adams BB, Vargus-Adams JN, Franz DN, et al.
Hyperhidrosis in pediatric spinal cord injury:
a case report and gabapentin therapy. J Am
Acad Dermatol 2002;46:444–6.
[56] Feder R. Clonidine treatment of excessive sweat-
ing. J Clin Psychiatry 1995;56:35.
[57] Bar LH, Kuypers BR. Behavior therapy in der-
matologic practice. Br J Dermatol 1973;88:591.
[58] Duller P, Gentry WD. Use of biofeedback in
treating chronic hyperhidrosis: a preliminary
report. Br J Dermatol 1980;103:143–6.
[59] Shenefelt PD. Hypnosis in dermatology. Arch
Dermatol 2000;136:393–9.
[60] Hurley HJ, Shelley WB. Simple surgical ap-
proach to the management of axillary hyperhi-
drosis. JAMA 1963;186:109.
[61] Wang HJ, Cheng TY, Chen TM. Surgical man-
agement of axillary bromhidrosis: a modified
Skoog procedure by an axillary bipedicle flap
approach. Plast Reconstr Surg 1996;98:524–9.
[62] Wu WH. Surgical treatment of axillary osmidro-
sis: an analysis of 343 cases. Plast Reconstr Surg
1994;94:288–94.
[63] Kim IH, Seo SL, Oh CH. Minimally invasive
surgery for axillary osmidrosis: combined oper-
ation with CO2 laser and subcutaneous tissue
remover. Dermatol Surg 1999;25:875–9.
[64] Jemec B. Abrasio axillae in hyperhidrosis. Scand
J Plast Reconstr Surg 1975;9:44.
[65] Tsai RY, Lin JY. Experience of tumescent liposuc-
tion in the treatment of osmidrosis. Dermatol
Surg 2001;27(5):446–8.
[66] Lillis PJ, Coleman WP. Liposuction for treat-
ment of axillary hyperhidrosis. Dermatol Clin
1990;8:479–82.
[67] Shenaq SM, Spira M. Treatment of bilateral ax-
illary hyperhidrosis by suction-assisted lipolysis
technique. Ann Plast Surg 1987;19:548–51.
[68] Dondelinger RF, Kurdziel JC. Percutaneous phe-
nol block of the upper thoracic sympathetic
chain with computed tomography guidance:
a new technique. Acta Radiol 1987;28:511–5.
[69] Kao MC, Chern SH, Cheng LC, et al. Minimally
invasive surgery: video endoscopic thoracic
sympathectomy for palmar hyperhidrosis. Ann
Acad Med Singapore 1996;25:673–8.
[70] Chiou TS. Chronological changes of postsym-
pathectomy compensatory hyperhidrosis and
recurrent sweating in patients with palmar
hyperhidrosis. J Neurosurg Spine 2005;2(2):
151–4.
[71] Ling TS, Fang HY. Thoracic endoscopic sympa-
thectomy in the treatment of palmar

hyperhidrosis with emphasis on preoperative
management. Surg Neurol 1999;52:453–7.
[72] Lin TS, Wang NP, Huang LC. Pitfalls and com-
plication avoidance associated with transtho-
racic endoscopic sympathectomy for primary
hyperhidrosis (analysis of 2200 cases). Int
J Surg Invest 2001;2:377–85.
[73] Han PP, Gottfried ON, Kenny KJ, et al. Biportal
thoracic sympathectomy: surgical techniques
and clinical results for the treatment of hyperhi-
drosis. Neurosurgery 2002;50:306–11.
[74] Rex LO, Drott C, Claes G, et al. The Boras
experience of endoscopic sympathectomy for
the treatment of palmar, axillary, facial hyper-
hydrosis and facial blushing and palmar plan-
tar hyperhidrosis. Eur J Surg Suppl 1998;580:
23–6.
[75] Sihoe AD, Cheung CS, Lai HK, et al. Incidence
of chest wall paresthesia after needlescopic
video-assisted thoracic surgery for palmar
hyperhidrosis. Eur J Cardiothorac Surg 2005;
27(2):313–9.
[76] Duarte JB, Kux P. Improvements in video en-
doscopic sympathectomy for the treatment of
palmar, axillary, facial, and palmar plantar
hyperhidrosis. Eur J Surg Suppl 1998;580:
9–11.
[77] Dumont P, Denoyer A, Robin P. Long-term re-
sults of thoracoscopic sympathectomy of hyper-
hidrosis. Ann Thorac Surg 2004;78(5):1801–7.
[78] Ambache N. A further survey of the action of
clostridium botulinum toxin upon different
types of autonomic nerve fiber. J Physiol 1951;
113:1–17.
[79] Bushara KO, Park DM. Botulinum toxin and
sweating. J Neurol Neurosurg Psychiatry 1994;
57:1437–8.
[80] Bushara KO, Park DM, Jones JC. Botulinum
toxin: a possible new treatment for axillary
hyperhidrosis. Clin Exp Dermatol 1996;21:
276–8.
[81] Odderson IR. Axillary hyperhidrosis: treatment
with botulinum toxin A. Arch Phys Med Rehabil
1998;79:350–2.
[82] Schnider P, Binder M, Kittler H, et al. A ran-
domized, double-blind, placebo-controlled
trial of botulinum A toxin for severe axillary hy-
perhidrosis. Br J Dermatol 1999;140:677–80.
[83] Naumann MK, Lowe NJ. Botulinum toxin A in
treatment of bilateral primary axillary hyperhi-
drosis: a randomized, parallel group, double
blind, placebo controlled trial. BMJ 2001;323:
596–9.
[84] Lowe NJ, Yamaushi PS, Lask GP, et al. Efficacy
and safety of botulinum toxin type A in the
treatment of palmar hyperhidrosis: a double-
blind, randomized, placebo-controlled study.
Dermatol Surg 2002;28(9):822–7.
[85] Sinclair MT, Russell W, Toosey RW, et al. Pro-
spective double blind randomized controlled
trial of botulinum toxin A in axillary hyperhi-
drosis. Br J Surg 2001;88:80.
Botulinum Toxin Therapy for Focal Hyperhidrosis 29
[86] Baumann L, Halem M. Botulinum toxin B and
management of hyperhidrosis. Clin Dermatol
2004;22:60–5.
[87] Nelson L, Bachoo P, Holmes J. Botulinum toxin
type B: a new therapy for axillary hyperhidrosis.
Br J Plast Surg 2005;58:228–32.
[88] Glaser DA, Solish N, Naumann MK, et al.
[Poster abstract]. Botulinum toxin type A im-
proves occupational impairment associated
with primary axillary hyperhidrosis and results
in high levels of satisfaction with treatment.
Presented at the Summer Meeting of the Amer-
ican Academy of Dermatology. New York, July,
2004.
[89] Glaser DA, Kowalski JW, Weng Y, et al. [Poster
abstract]. Effect of repeated botulinum toxin
type A treatment on quality of life and function-
ing in patients with severe primary axillary hy-
perhidrosis: results from 2 years longitudinal
data. Presented at the Summer Meeting of the
American Academy of Dermatology. Chicago,
July, 2005.
[90] Wollina U, Karamfilov MD, Konrad H. High-
dose botulinum toxin type A therapy for
axillary hyperhidrosis markedly prolongs the
relapse-free interval. J Am Acad Dermatol
2002;29:533–8.
[91] Glaser A, et al. [Abstract 195]. Presented at the
American Academy of Dermatology 62nd
Annual Meeting. Washington, DC, February
2004.
[92] Goodman G. Diffusion and short-term efficacy
of botulinum toxin A after the addition of hyal-
uronidase and its possible application for the
treatment of axillary hyperhidrosis. Dermatol
Surg 2003;29:533–8.
[93] Heckman M, Teichman B, Pause BM, et al.
Amelioration of body odor after intracutaneous
axillary injection of botulinum toxin A. Arch
Dermatol 2003;139:57–9.
[94] Lapiere JC, Hirsh A, Gordon KB, et al. Botuli-
num toxin type A for the treatment of axillary
Hailey-Hailey disease. Dermatol Surg 2000;26:
371–4.
[95] Schnider P, Binder M, Berger T, et al. Botulinum
toxin injection in focal hyperhidrosis. Br J Der-
matol 1996;131:1151–65.
[96] Schnider P, Binder M, Berger T, et al. Double-
blind trial of botulinum A toxin in the treat-
ment of focal hyperhidrosis of the palms. Br
J Dermatol 1997;136:548–52.
[97] Saadia D, Voustianiouk A, Ang AK, et al. Botu-
linum toxin type A in primary palmar hyperhi-
drosis. Neurology 2001;57:2095–9.
[98] Wollina U, Karamfilov T. Botulinum toxin A for
palmar hyperhidrosis. J Eur Acad Dermatol
Venereol 2001;15(6):555–8.
[99] Solomon BA, Hayman R. Botulinum toxin A
therapy for palmar and digital hyperhidrosis.
J Am Acad Dermatol 2000;42(6):1026–9.
[100] De-Almeida AR, Kadunc BV, De Liveira EM. Im-
proving botulinum toxin therapy for palmar
30 Cohen et al
hyperhidrosis: wrist block and technical consid-
erations. Dermatol Surg 2001;27:34–6.
[101] Blaheta HJ, Vollert B, Zuder D, et al. Intrave-
nous regional anesthesia (Bier’s block) for bot-
ulinum toxin therapy of palmar hyperhidrosis
is safe and effective. Dermatol Surg 2002;
28(8):666–71.
[102] Swartlng C, Farnstand C, Abt G, et al. Side-ef-
fects of intradermal injections of botulinum A
toxin in the treatment of palmar hyperhidrosis:
a neurophysiological study. Eur J Neurol 2001;
8(5):451–6.
[103] Baumann LS, Halem ML. Systemic adverse
effects after botulinum toxin type B (myo-
bloc) injections for the treatment of palmar
hyperhidrosis. Arch Dermatol 2003;139(2):
226–7.
[104] Tugnoli V, et al. Botulism-like syndrome after
botulinum toxin type A injections for focal hy-
perhidrosis. Br J Dermatol 2002;147(4):808–9.
[105] Naumann M, et al. Focal hyperhidrosis: effec-
tive treatment with intracutaneous botulinum
toxin. Arch Dermatol 1998;134(3):301–4.
[106] Sevin S, Dogu O, Kaleagasi H. Botulinum toxin-
A therapy for palmar and plantar hyperhidrosis.
Acta Neurol Belg 2002;102(4):167–70.
[107] Vodoud-Seyedi J, Simonart T, Heenn N. Treat-
ment of plantar hyperhidrosis with dermojet in-
jections of botulinum toxin. Dermatology
2000;201(2):179.
[108] Kinkelin I, Hund M, Naumann M, et al. Effec-
tive treatment of frontal hyperhidrosis with bot-
ulinum toxin A. Br J Dermatol 2000;143(4):
824–7.
[109] Tugnoli V, et al. The role of gustatory flushing in
Frey’s syndrome and its treatment with botuli-
num toxin type A. Clin Auton Res 2002;12:
174–8.
[110] Naumann M, Zellner M, Tokya TV, et al. Treat-
ment of gustatory sweating with botulinum
toxin. Ann Neurol 1997;42:973–5.
[111] Laccourreye O, et al. Recurrent gustatory sweat-
ing (Frey syndrome) after intracutaneous injec-
tion of botulinum toxin type A: incidence,
management, and outcome. Arch Otolaryngol
Head Neck Surg 1999;125(3):283–6.
[112] Kyrmizakis DE, Pangalos A, Papadakis CE, et al.
J Oral Maxillofac Surg 2004;62:840–4.
[113] Lam DG, Choudhary S. Use of a grid to simplify
botulinum toxin injection for axillary hyperhi-
drosis. Plast Reconstr Surg 2003;112(6):1741–2.
[114] Becton-Dickinson, Franklin Lakes, New Jersey.
[115] Vadoud-Seyedi J. Int J Dermatol 2004;43:
969–71.
[116] Kavanaugh GM, Oh C, Shams K. Br J Dermatol
2004;151:1093–5.
[117] Krogstad A, Skymne A, Pegenius G, et al. No
compensatory sweating after botulinum toxin
treatment of palmar hyperhidrosis. Br J Derma-
tol 2005;152:329–33.