Hiperhidrosis

Giuseppe Sito
Editor
Hyperhidrosis
Clinician’s Guide to
Diagnosis and Treatment
123
Hyperhidrosis
Giuseppe Sito
Editor
Hyperhidrosis
Clinician’s Guide to Diagnosis
and Treatment
Editor
Giuseppe Sito
II University of Naples
Naples
Italy
ISBN 978-3-319-26921-4 ISBN 978-3-319-26923-8 (eBook)

DOI 10.1007/978-3-319-26923-8
Library of Congress Control Number: 2016931334
Springer Cham Heidelberg New York Dordrecht London

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To those I loved and to those who loved me
Contents
1 Anatomy and Physiology of Sweat Glands . . . . . . . . 1

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
2 Classification of Hyperhidrosis . . . . . . . . . . . . . . . . . . 7
2.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
2.2 Primary Hyperhidrosis . . . . . . . . . . . . . . . . . . . . . 8
2.3 Secondary Hyperhidrosis . . . . . . . . . . . . . . . . . . . 10
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
3 Diagnosis of Hyperhidrosis . . . . . . . . . . . . . . . . . . . . . 13
3.1 Patient Evaluation. . . . . . . . . . . . . . . . . . . . . . . . . 13
3.2 Identification of the Treatment Area . . . . . . . . . 15
3.3 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
4 Therapies of Hyperhidrosis Through
Topical Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
4.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
Topical Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
vii
viii Contents
5 Oral Medication in Hyperhidrosis. . . . . . . . . . . . . . . 23

5.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
5.2 Discussion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
5.3 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
6 Surgical Therapy for Hyperhidrosis . . . . . . . . . . . . . 27
6.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
Local Excision . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
Liposuction-Curettage . . . . . . . . . . . . . . . . . . . . 28
Sympathectomy . . . . . . . . . . . . . . . . . . . . . . . . . . 29
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
7 Iontophoresis in Hyperhidrosis . . . . . . . . . . . . . . . . . 35
7.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35
7.2 Iontophoresis in Hyperhidrosis . . . . . . . . . . . . . 36
7.3 Iontophoresis Treatment. . . . . . . . . . . . . . . . . . . 37
7.4 Adverse Events . . . . . . . . . . . . . . . . . . . . . . . . . . 38
7.5 Contraindications . . . . . . . . . . . . . . . . . . . . . . . . 38
7.6 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
8 The Role of Botulinum Toxin
in Hyperhidrosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
8.1 Botulinum Toxin . . . . . . . . . . . . . . . . . . . . . . . . . 42
8.2 Dilution and Dosage . . . . . . . . . . . . . . . . . . . . . . 43
8.3 BoNT Treatment of Axillary
Hyperhidrosis . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
8.4 BoNT Treatment of Palmar
and Plantar Hyperhidrosis . . . . . . . . . . . . . . . . . 45
8.5 Adverse Events . . . . . . . . . . . . . . . . . . . . . . . . . . 51
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60
Contents ix
9 Psychological and Psychiatric Management

of Patients with Hyperhidrosis. . . . . . . . . . . . . . . . . . 63
9.1 Neurophysiopathological Substrate . . . . . . . . . 64
9.2 Psychological and Psychiatric
Aspects of PH . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
9.3 Social Impact of PH . . . . . . . . . . . . . . . . . . . . . . 67
9.4 Measurement of PH in the Psychiatric
Context. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68
9.5 Psychiatric and Psychological Treatment . . . . . . . 69
9.6 Tip for Managing PH. . . . . . . . . . . . . . . . . . . . . . . 71
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71
Credits
We are indebted to “Foto Macro © 2015 – macromedica.it” for

the pictures of this book.
xi
Introduction
The primary function of the eccrine sweat glands is to assist in

the maintenance of body temperature in response to heat expo-
sure or exercise. Hyperhidrosis may be defined as sweating
beyond what is necessary to maintain thermal regulation. It may
be primary (idiopathic, essential) or secondary to a number of
diseases and prescribed drugs. Hyperhidrosis can be localized
or generalized. Regardless of the type or cause of the hyperhi-
drosis, it is frequently socially embarrassing and occupationally
disabling. Excess sweat on the hands may soil paper and art-
work and make it virtually impossible to play many musical
instruments. Careers in fields that require contact with paper,
metal, and electrical components become unrealizable. Axillary
and plantar hyperhidrosis may result in stains and damage to
clothing and shoes. Generalized hyperhidrosis leaves affected
individuals with wet clothing that may have to be changed a
number of times each day.
Physiologically, sweating is a function of the sympathetic
nervous system. A sweat control center located in the preoptic
area and anterior hypothalamus contains neurons that are sensi-
tive to changes in internal temperature and also cerebral cortical
xiii
xiv Introduction
events. Sweat glands are innervated by sympathetic postgangli-

onic fibers, but unlike ordinary sympathetic innervation, the
chemical mediator is acetylcholine. Sweating in response to
thermal stimuli is generally acceptable and rarely a cause for
complaint. Emotionally induced sweating tends to be localized
to the palms, soles, and sometimes the forehead. Axillary sweat-
ing may be the result of both emotional and thermal stimuli.
The causes for generalized hyperhidrosis include a number
of febrile illnesses, neoplastic and neurologic diseases, meta-
bolic disorders, and drugs. The causes and conditions associated
with localized hyperhidrosis include primary palmoplantar
hyperhidrosis, unilateral circumscribed hyperhidrosis, hyperhi-
drosis associated with intrathoracic neoplasms, olfactory hyper-
hidrosis, gustatory hyperhidrosis, spinal cord injuries, and
Frey’s syndrome. Although primary or essential hyperhidrosis is
the most common cause of palmoplantar hyperhidrosis, it may
also occur in some patients with Raynaud’s disease, rheumatoid
arthritis, erythromelalgia, nail patella syndrome, keratosis pal-
maris et plantaris with clinodactyly, atrioventricular fistula, and
cold injury. Whenever possible, the cause for hyperhidrosis
should be identified and, if possible, treated.
Primary or essential hyperhidrosis is a disorder that causes
hyperhidrosis of the hands, feet, and sometimes the axillae. It
is estimated that 0.6–1.0 % of the population suffers from this
problem. Primary hyperhidrosis may be inherited and in con-
trast to generalized hyperhidrosis usually has its time of onset
in adolescence, but may begin in childhood and even infancy. It
characteristically does not occur while sleeping. Primary
hyperhidrosis is made worse by heat and emotional stimuli;
however, it is important to note that although emotional stimuli
are necessary for primary hyperhidrosis to occur in affected
individuals, it is not a psychological disease but rather a physi-
ologic disorder. It seems that in patients with primary hyperhi-
drosis, the hypothalamic sweat centers are more sensitive to
emotional stimuli of cerebral origin than in ordinary people.
Introduction xv
A number of medical and surgical remedies are available for

the treatment of hyperhidrosis. In this monograph we will
analyze every aspect of hyperhidrosis from physiopathology,
classification and diagnosis to the available therapies and their
complication.
Naples, Italy Giuseppe Sito, MD

Chapter 1
Anatomy and Physiology
of Sweat Glands
Gabriella Brancaccio and Teresa Russo
Abstract To understand pathologic mechanisms at the

base of hyperhidrosis, a brief review of anatomy and physi-
ologic function of sweat glands is provided.
Eccrine sweat glands are simple coiled tubular glands with a

merocrine secretion (a cell is classified as merocrine if the secre-
tions of that cell are excreted via exocytosis from secretory cells
into an epithelial-walled duct or ducts and thence onto a bodily
surface or into the lumen). Their total number is between two and
four million, and in humans, they are found at virtually all skin
sites. However, they are most abundant on the palms, soles, fore-
head, axillae, and groins. There is no difference between male and
female, but in Afro-Americans, they are more numerous, proba-
bly more for environmental than genetic causes (Groscurth 2002).
Eccrine glands are composed of an intraepidermal spiral
duct, the “acrosyringium”; a dermal duct, comprising a straight
G. Brancaccio, MD () • T. Russo, MD

Dermatology Unit, Second University of Naples,
Via S. Pansini 5, 80131 Naples, Italy
e-mail: gabri.brancaccio@gmail.com
G. Sito (ed.), Hyperhidrosis: Clinician’s Guide to Diagnosis 1

and Treatment, DOI 10.1007/978-3-319-26923-8_1,
2 G. Brancaccio and T. Russo
Fig. 1.1 Eccrine sweat

gland: A epidermis, B dermis,
C ipodermis
and coiled portion; and a secretory tubule, coiled deep in the

dermis or hypodermis (Fig. 1.1).
The secretion of eccrine glands is a sterile, dilute electrolyte
solution with primary components of bicarbonate, potassium, and
sodium chloride (NaCl). There are other components secreted
such as glucose, pyruvate, lactate, cytokines, immunoglobulins,
antimicrobial peptides, and many others (Sato et al 1989a).
1 Anatomy and Physiology of Sweat Glands 3
Functions of sweat glands are:

• Thermoregulation: perspiration increases with increasing
body temperature so that a part of the heat produced by the
body is used in the evaporation of the water contained in the
sweat.
• Excretion of solutes: they have an excretory function similar
to that of the kidney but obviously of minor importance. So,
they participate to the regulation of the fluid.
• Contribution to the formation of the hydrolipidic film.
Physiologic secretion of sweat occurs as a result of many fac-
tors and is mediated by cholinergic innervation and its primary
neurotransmitter acetylcholine (Stashak et al 2014). Heat is a
prime stimulus to increased sweating, but other physiologic
stimuli, including emotional stress, are important as well. During
early development, there is a switch between adrenergic and
cholinergic innervation of sweat glands. Some responsiveness to
both cholinergic and adrenergic stimuli persists. Cholinergic
sweating involves a biphasic response, with initially hyperpolar-
ization and secondary depolarization mediated by the activation
of calcium and chloride ion conductance. Adrenergic secretion
involves monophasic depolarization and is dependent on cystic
fibrosis transmembrane conductance regulator-GCI. Cells from
patients with cystic fibrosis demonstrate no adrenergic secretion.
Vasoactive intestinal polypeptide may also play a role in stimu-
lating eccrine secretion (Vetrugno et al 2003).
A central sudomotor efferent pathway is suggested for hyper-
hidrosis with the following connections: (1) cerebral cortex to
hypothalamus, (2) hypothalamus to medulla, (3) fibers crossing
in the medulla oblongata and travelling to the lateral horn of the
spinal cord, (4) the lateral horn to sympathetic ganglia, and (5)
sympathetic ganglia to sweat glands as postganglionic C fibers.
Because the sympathetic fibers arising from the hypothalamus
cross mostly at the level of the pons, and most of this crossing
is completed in the medulla oblongata, lesions in the medulla
4 G. Brancaccio and T. Russo
Corpus
Cerebrum callosum
Thalamus
PO/AH; Preoptic area and Descending autonomic

anterior hypothalamus Mid- pathways (brainstem)
Hypophysis brain
Descending sweat fibers
Ascending impulses
Eccrine sweat gland Postganglionic
sympathetic axons Thoracolumbar intermedialateral
cell columns (spinal cord)
Epidermis
Ducts
Sudomotor Epidermis
neurons
Sympathetic ganglia
Pressure on thermo-
Preganglionic receptors under skin
sympathetic axons
Sensory afferents
(temperature)
Fig. 1.2 Anatomy of physiologic perspiration pathway
may cause altered sweating, such as the ipsilateral anhidrosis

seen in Horner’s syndrome (Fig. 1.2) (Sato et al 1989b; Lakraj
et al 2013).
References
Groscurth P. Anatomy of sweat glands. Curr Probl Dermatol. 2002;30:1–9.

Lakraj AA, Moghimi N, Jabbari B. Hyperhidrosis: anatomy, pathophysiol-
ogy and treatment with emphasis on the role of botulinum toxins. Toxins
(Basel). 2013;5(4):821–40.
Sato K, Kang WH, Saga K, Sato KT. Biology of sweat glands and their
disorders. I. Normal sweat gland function. J Am Acad Dermatol.
1989a;20:537–63.
1 Anatomy and Physiology of Sweat Glands 5
Sato K, Kang WH, Saga K, Sato KT. Biology of sweat glands and their
disorders. II. Disorders of sweat gland function. J Am Acad Dermatol.
1989b;20:713–26.
Stashak AB, Brewer JD. Management of hyperhidrosis. Clin Cosmet
Investig Dermatol. 2014;7:285–99.
Vetrugno R, Liguori R, Cortelli P, Montagna P. Sympathetic skin response:
basic mechanisms and clinical applications. Clin Auton Res. 2003;13(4):
256–70.
Chapter 2
Classification of Hyperhidrosis
Giuseppe Sito and Gabriella Brancaccio
Abstract Hyperhidrosis is broadly classified into two

categories: primary and secondary hyperhidrosis. In this
chapter, the author aims to provide an easy overview of this
disease with focus on differential diagnosis.
2.1 Introduction
Hyperhidrosis is the excessive production of sweat affecting 1–3 %

of the US population, with a sex ratio of 1, and is most prevalent
among those aged 25–64 years. It can have major psychosocial
repercussion for patient (Strutton et al, 2004). Sweat is secreted and
excreted by the eccrine sweat glands, which are innervated by cho-
linergic fibers, paradoxically, via the sympathetic system.
Hyperhidrosis is broadly classified into two categories: pri-
mary and secondary hyperhidrosis. Primary hyperhidrosis is by
G. Sito, MD ()
AITEB - Italian Association of Botulinum toxin
Therapy in Aesthetics, Via Alberto da Giussano, 18, Milan, Italy
e-mail: mail@giuseppesito.it
G. Brancaccio, MD
Dermatology Unit, Second University of Naples, Naples, Italy
8 G. Sito and G. Brancaccio
definition not associated with an underlying medical condition.

Therefore, the diagnosis requires that other causative patholo-
gies are ruled out. It is most often focal and generally causes
idiopathic, symmetrically bilateral excessive sweating of the
axillae, palms, soles, and craniofacial region.
Secondary hyperhidrosis may be attributed to a number of
other conditions, such as drugs, endocrine disturbances, obesity,
hypoglycemia, heart failure, certain malignancies, and central
nervous system abnormalities.
Hyperhidrosis can be further distinguished by anatomic distri-
bution of affected regions (focal or generalized) and by laterality
(unilateral or bilateral and symmetrical) (Moraites et al, 2014).
2.2 Primary Hyperhidrosis
Primary or essential hyperhidrosis is caused by a deregulation of

autonomic neural system. Primary hyperhidrosis is more often
focal. The dysfunction tends to occur in areas where there is a
higher concentration of eccrine glands such as the palms, soles,
and axillae. Less common sites are the scalp or face. Few cases
of a rare form of localized unilateral hyperhidrosis affecting
forearm or forehead are described in literature (Cohen et al
2007). A family history is often present (Table 2.1).
It is possible that primary hyperhidrosis is due to abnormal
central control of emotional sweating given that it affects the
same body areas as those affected in emotional sweating (hands,
feet, and axillae). Histologic evaluation of the affected areas dem-
onstrates normal-appearing eccrine sweat glands with a normal
number, size, and density of the glands. Because the quantity of
neurotransmitters is not altered, the most plausible theory is that
normal stimuli that usually increase sweating (stress, hot or cold,
hot beverages, etc.) cause hyperactivity of eccrine sweat glands.
This mechanism does not involve apocrine sweat glands (Moraites
et al, 2014; Solish et al, 2007).
2 Classification of Hyperhidrosis 9
Table 2.1 Primary and secondary hyperhidrosis: differential diagnosis

Primary
hyperhidrosis Secondary hyperhidrosis
Body region Axillae Generalized
Palms Focal (peripheral nervous
Soles dysfunction)
Face
Laterality Bilateral Most often unilateral or
asymmetrical
Familial history Present Absent
Onset <25 years >25 years
Timing Present during sleep
Associated None Neurological
symptoms Endocrinological and others
Until recently, there were few data available on the prevalence

of primary hyperhidrosis. A consumer survey of a nationally rep-
resentative sample of 150,000 households in the USA screened
for the presence of hyperhidrosis. The survey results showed that
the prevalence of hyperhidrosis in the USA is 2.8 % (7.8 million
Americans). Of those with hyperhidrosis, only 38 % consulted
their physician about their excessive sweating. The authors of the
survey report conclude that hyperhidrosis actually affects more
people than previously thought (Strutton et al, 2004).
Focal primary hyperhidrosis usually has an onset during
childhood or adolescence and peaks in the third and fourth
decade but can be seen in childhood and even infancy. In the US
consumer survey, the average age at onset was 25 years but
varied with location of hyperhidrosis. The highest prevalence
rates were seen between 25 and 65 years of age (3.5–4.5 %), and
the lowest less than 12 years of age (0.5–0.7 %) prevalence
(Strutton et al, 2004).
Prevalence of the types of primary hyperhidrosis based on
body location has been reported in several patient populations.
Most of the patients suffer from axillary hyperhidrosis, followed
by palmar, plantar, and craniofacial hyperhidrosis. According to
the US consumer survey, 51 % of hyperhidrosis patients have

axillary hyperhidrosis alone or in combination with hyperhidro-
sis in another location, 9.5 % have axillary hyperhidrosis alone,
25 % have palmar hyperhidrosis alone or in combination with
hyperhidrosis in another area, and only 1 % have palmar hyper-
hidrosis alone (Strutton et al, 2004).
2.3 Secondary Hyperhidrosis
Secondary generalized hyperhidrosis is excessive sweating that is

caused by a medical condition or medication. Underlying condi-
tions that may cause secondary hyperhidrosis can be physiologic,
such as pregnancy, menopause, fever, excessive heat, or patho-
logic, including malignancies, carcinoid syndrome, hyperthyroid-
ism, pheochromocytoma, tuberculosis, endocarditis, HIV, among
others. Drugs that are known to cause hyperhidrosis include
antidepressants, hypoglycemic agents, triptans, antipyretics, cho-
linergics, and many others. It is worth noting that it is also a clini-
cal feature of social anxiety disorder. Periphery nerve injury may
also cause secondary focal hyperhidrosis (Walling, 2011).
Clinical characteristics that help distinguish between primary
and secondary types of hyperhidrosis include onset of the disease,
characteristic of the sweating, and associated symptoms. Patient
with secondary hyperhidrosis are more likely to have onset older
than 25 years compared with patients with primary hyperhidrosis.
Although patients with primary hyperhidrosis are much more
likely to have sweating in typical distribution, those with second-
ary hyperhidrosis are significantly more likely to exhibit unilat-
eral or asymmetrical sweating, to be generalized rather than focal,
and to have symptoms during sleep (“night sweats”). Secondary
hyperhidrosis is less often associated with positive family history.
A middle-aged patient presenting with new-onset generalized or
asymmetrical sweating that also occurs while sleeping is highly
suspicious for secondary hyperhidrosis (Benson et al, 2013).
2 Classification of Hyperhidrosis 11
References
Benson RA, Palin R, Holt PJ, Loftus IM. Diagnosis and management of
hyperhidrosis. BMJ. 2013;347:f6800.
Cohen JL, Cohen G, Solish N, Murray CA. Diagnosis, impact, and manage-
ment of focal hyperhidrosis: treatment review including botulinum toxin
therapy. Facial Plast Surg Clin North Am. 2007 Feb;15(1):17–30, v–vi.
Moraites E, Vaughn OA, Hill S. Incidence and prevalence of hyperhidrosis.
Dermatol Clin. 2014 Oct;32(4):457–65.
Solish N, Bertucci V, Dansereau A, Hong HC, Lynde C, Lupin M, Smith
KC, Storwick G; Canadian Hyperhidrosis Advisory Committee. A com-
prehensive approach to the recognition, diagnosis, and severity-based
treatment of focal hyperhidrosis: recommendations of the Canadian
Hyperhidrosis Advisory Committee. Dermatol Surg. 2007 Aug;33(8):
908–23.
Strutton DR, Kowalski JW, Glaser DA, Stang PE. US prevalence of hyper-
hidrosis and impact on individuals with axillary hyperhidrosis: results
from a national survey. J Am Acad Dermatol. 2004 Aug;51(2):241–8.
Walling HW. Clinical differentiation of primary from secondary hyperhi-
drosis. J Am Acad Dermatol. 2011 Apr;64(4):690–5.
Chapter 3
Diagnosis of Hyperhidrosis
Gabriella Brancaccio and Giuseppe Sito
Abstract Before diagnosing primary focal hyperhidrosis,

several systemic diseases must be ruled out. Patient motiva-
tion to treatment and impairment of quality of life should
be deeply investigated. In this review, a brief overview of
the diagnostic algorithm is provided.
3.1 Patient Evaluation
Primary hyperhidrosis is a condition of great discomfort for

the patient. “Excessive sweating” is hard to define, but a level
that has an unacceptable impact on quality of life is a good
indication.
G. Brancaccio, MD ()
Via S. Pansini 5, Naples 80131, Italy
G. Sito, MD

14 G. Brancaccio and G. Sito
Table 3.1 Diagnostic features of primary hyperhidrosis

Diagnostic features of primary hyperhidrosis
Excessive sweating occurring in at least 1 of the following sites: axillae,
palms, soles, craniofacial region
At least 6 months’ duration
Without apparent secondary causes (e.g., medications, endocrine disease,
neurologic disease)
Including two or more of the following characteristics:
Bilateral and approximately symmetric
Age of onset less than 25 years
Frequency of episodes at least once per week
Positive family history
Cessation of excessive sweating on sleep
Impairment of daily activities
From Pariser and Ballard (2014)
The first step when evaluating a patient presenting with

hyperhidrosis is a detailed clinical history with a focus on fea-
tures of primary hyperhidrosis (Table 3.1). Usually the diagnos-
tic clues of primary focal hyperhidrosis are the exclusion of
secondary causes as medications, endocrine or neurologic dis-
eases, and the presence of excessive sweating occurring bilater-
ally in one or more of the following site: axillae, palms, soles,
or craniofacial region (Pariser and Ballard 2014). Many patients
have a positive familial history and complain of at least one
episode per week. Of course, motivation to the treatment is
essential, so a deep conversation on impairment of daily activi-
ties should be a step of medical examination. A useful scale to
quantify the impact of hyperhidrosis on the patient quality of
life is the Hyperhidrosis Disease Severity Scale (Table 3.2).
Indications that a patient has secondary hyperhidrosis include
generalized sweating, predominantly nighttime sweating (hema-
tological cancer or infection, such as brucellosis), use of drugs
with related side effects, history of illicit drug use, weight loss
(cancer), palpitation (thyrotoxicosis), or asthenia (Table 3.3).
Measure full blood count, renal and liver function, erythrocyte
sedimentation rate, thyroid function tests, and random glucose
to exclude other disease.
3 Diagnosis of Hyperhidrosis 15
Table 3.2 HDSS (from Weinberg et al 2014)

“How would you rate the severity of your Clinical
hyperhidrosis?” Patient response Score interpretation
My sweating is never noticeable and never 1 Mild
interferes with my daily activities
My sweating is tolerable but sometimes 2 Moderate
My sweating is barely tolerable and 3 Severe
frequently interferes with my daily
activities
My sweating is intolerable and always 4 Very severe
Table 3.3 Differential diagnosis of generalized excessive sweating

Infective: acute viral or bacterial infections; chronic infections, such as
tuberculosis, malaria, brucellosis
Drugs: alcohol, cocaine, heroin (including withdrawal), ciprofloxacin,
acyclovir, esomeprazole, sertraline, and other antidepressants
Endocrine: diabetes, hyperthyroidism, menopause, pregnancy, carcinoid
syndrome, hyperpituitarism, pheochromocytoma, acromegaly
Neurological disorders: stroke, spinal cord injuries, gustatory sweating
after parotidectomy, Parkinson’s disease
Other: lymphoma and other myeloproliferative disorders, congestive
heart failure, anxiety, obesity
From Benson et al. (2013)
3.2 Identification of the Treatment Area
A useful and simply tool to identify the extension of the

affected area is the Minor iodine-starch test (Cohen et al
2007). After the area to be studied is dried thoroughly, iodine
solution is painted over the affected area and a starch powder
such as cornstarch is applied. With the interaction of the sweat,
the area turns into a purple-black color (decolorized iodine
solutions do not perform the colorimetric change properly and
should not be used) (Figs. 3.1, 3.2, 3.3, and 3.4).
Fig. 3.1 Minor iodine-starch test of the hands. Painting with the iodine
solution
Fig. 3.2 Minor iodine-starch test. Pre-post
Minor iodine-starch test is also very helpful after treatment

(iontophoresis, oral agent, botulinum toxin) to evaluate the reduc-
tion of sweating obtained and the needing of a re-treatment.
For iodine-sensitive patients, Ponceau red tincture is a valid
alternative. When mixed with starch and in contact with sweat,
this tincture develops a pinkish color. For both techniques, the
3 Diagnosis of Hyperhidrosis 17
Fig. 3.3 Virtual grid on the affected area
Fig. 3.4 Minor iodine-starch test of the axilla
distribution and maximal perspiration sites must be photo-

graphically recorded for future comparison (de Almeida et
Montagner 2014).
Another useful method for research trials, but time-consuming
in daily practice, is gravimetric testing. Gravimetric assessment
identifies the amount of sweat produced during a given time.
The affected area is dried using absorbent tissue, and then a
previously weighed filter paper is applied and left in place for a
certain period of time. The volume of produced sweat during
this interval of time is quantified by measuring the weight of the
paper before and after contact. The evaluation period may range
from 1 to 15 min (Hund et al 2002).
3.3 Conclusion
Diagnosis of hyperhidrosis is essentially based on clinical his-

tory and medical examination of the patient. Minor iodine-
starch test is a helpful tool to identify the treatment area and to
follow up the post-therapy result. Gravimetric testing, although
the only method supporting quantitative evidence, is restricted
to research and trials.
References
therapy. Facial Plast Surg Clin North Am. 2007 Feb;15(1):17–30, v–vi.
de Almeida AR, Montagner S. Botulinum toxin for axillary hyperhidrosis.
Dermatol Clin. 2014;32(4):495–504.
Hund M, Kinkelin I, Naumann M, Hamm H. Definition of axillary hyperhi-
drosis by gravimetric assessment. Arch Dermatol. 2002;138(4):
539–41.
Pariser DM, Ballard A. Topical therapies in hyperhidrosis care. Dermatol
Clin. 2014;32(4):485–90.
Weinberg T, Solish N, Murray C. Botulinum neurotoxin treatment of pal-
mar and plantar hyperhidrosis. Dermatol Clin. 2014;32(4):505–15.
Chapter 4
Therapies of Hyperhidrosis Through
Topical Agents
Gabriella Brancaccio and Giuseppe Sito
Abstract Primary or essential hyperhidrosis is a disorder that

causes hyperhidrosis of the hands, feet, and sometimes the axil-
lae. A number of medical and surgical remedies are available
for the treatment of hyperhidrosis. A brief review on topical
agents (anticholinergics, astringents, fragrances, and antiper-
spirants) useful in the treatment of hyperhidrosis is provided.
4.1 Introduction
Primary or essential hyperhidrosis is a disorder that causes

hyperhidrosis of the hands, feet, and sometimes the axillae. It is
G. Sito, MD
AITEB - Italian Association of Botulinum Toxin Therapy in Aesthetics,
Via Alberto da Giussano, 18, Milan, Italy

estimated that 0.6–1.0 % of the population suffers from this

problem. Primary hyperhidrosis may be inherited and in con-
trast to generalized hyperhidrosis usually has its time of onset in
adolescence, but may begin in childhood and even infancy. It
characteristically does not occur while sleeping. Primary hyper-
hidrosis is made worse by heat and emotional stimuli; however,
it is important to note that although emotional stimuli are neces-
sary for primary hyperhidrosis to occur in affected individuals,
it is not a psychological disease but rather a physiologic disor-
der. It seems that in patients with primary hyperhidrosis, the
hypothalamic sweat centers are more sensitive to emotional
stimuli of cerebral origin than in ordinary people. The occa-
sional onset of primary hyperhidrosis in the neonatal period is
evidence that this is far more than an emotional disorder! A
number of medical and surgical remedies are available for the
treatment of hyperhidrosis.
Topical Agents
Topical therapy of hyperhidrosis is based on different drugs:

• Anticholinergics
• Astringents
• Fragrances
• Antiperspirants
Experienced anticholinergics are propantheline, scopol-
amine, glycopyrrolate bromide, and glycopyrronium. All of
these demonstrate clinical efficacy in various trials; however,
the topical concentration needed for sweat reduction is often
correlated to systemic adsorption and adverse effects.
Glycopyrrolate is an anticholinergic agent that is used off-
label systemically for the treatment of hyperhidrosis. Topical
glycopyrrolate may also be effective for focal hyperhidrosis. A
topical application of 0.5 or 1 % glycopyrrolate was studied in
16 patients with Frey syndrome (gustatory hyperhidrosis) and
4 Therapies of Hyperhidrosis Through Topical Agents 21
was effective and free of adverse effects. In another study of

25 patients with craniofacial hyperhidrosis, all the patients had
half their foreheads treated with 2 % glycopyrrolate and the
other half treated with placebo. This split-face study found that
96 % of the patients were satisfied with the effectiveness,
whereas 1 patient did not tolerate the regimen because of head-
ache. Improvement was transient, lasting 1–2 days for most
patients (Pariser and Ballard 2014). Topical glycopyrrolate may
also be considered as a treatment option for large areas of sweat-
ing with side effects being mydriasis and accommodation fail-
ure and urinary retention (Izadi et al. 2006).
Astringent substances are classified in two chemical groups:
acids and aldehydes. Between aldehydes there are formaldehyde
and glutaraldehyde. Formaldehyde causes allergic contact der-
matitis in 15–20 % of patients (Walling and Swick 2011).
Patients allergic to formaldehyde are not to glutaraldehyde; any-
way, this substance causes a white-brown coloration of the skin
and is not well tolerated. Tannic acid and trichloroacetic acid are
currently used at low concentration in numerous OTC products.
The mainstays of hyperhidrosis topical treatment are antiper-
spirants, especially aluminum salts (aluminum chloride and alu-
minum chlorohydrate). With regard to mechanism of action,
numerous studies have shown that the metal ions precipitate with
the lipids and mucopolysaccharides in the lumen of the ducts.
The complex metal-lipid that forms (gel-like) obstructs the ducts
of the sweat glands. Subsequently epithelial cells are damaged
and, flaking, contribute to the formation of an “occlusive cap.”
The sweat continues to be produced but does not reach the sur-
face and can thus be observed miliaria as a result of thermal
stress (Hölzle and Braun-Falco 1984). However, the normal
glandular function is restored with the epidermal renewal, and
for this reason, treatment one or two times per week is needed.
Long-term histologic studies of eccrine glands in patients on
chronic aluminum salt treatment have shown destruction of some
secretory cells, accounting for the clinical finding of reduced
severity of hyperhidrosis over time, as reflected by the need
for less-frequent treatments. Other metallic salts such as zirco-

nium, vanadium, and indium are thought to work by the same
mechanism. Some of these salts are more effective than alumi-
num salts, but aluminum salts have been used for more than
80 years and are inexpensive, easily available, and nontoxic, so
they remain the common active ingredient in most preparation.
Aluminum salts in the presence of water (sweat) degenerate
in hydrochloric acid that irritates the skin. Therefore, it is bet-
ter to apply the antiperspirants at night when the sweating is
very low (Stolman 1998).
References
Hölzle E, Braun-Falco O. Structural changes in axillary eccrine glands fol-

lowing long-term treatment with aluminium chloride hexahydrate solu-
tion. Br J Dermatol. 1984;110(4):399–403.
Izadi S, Choudhary A, Newman W. Mydriasis and accommodative failure
from exposure to topical glycopyrrolate used in hyperhidrosis.
J Neuroophthalmol. 2006;26(3):232–3.
Pariser DM, Ballard A. Topical therapies in hyperhidrosis care. Dermatol
Clin. 2014;32(4):485–90.
Stolman LP. Treatment of hyperhidrosis. Dermatol Clin. 1998;16(4):
863–9.
Walling HW, Swick BL. Treatment options for hyperhidrosis. Am J Clin
Dermatol. 2011;12:285–95.
Chapter 5
Oral Medication in Hyperhidrosis
Teresa Russo and Gabriella Brancaccio
Abstract A variety of treatments have been proposed to

control or decrease the sweating of idiopathic hyperhidro-
sis. Oral agents are most commonly used in clinical practice
and are somewhat effective at controlling the secretion, but
long-term usage and adverse side effects could make them
unsafe for patient.
5.1 Introduction
A variety of treatments have been proposed to control or

decrease the sweating of idiopathic hyperhidrosis. The medical
treatments currently available include topical therapy, systemic
therapy, iontophoresis, botulinum toxin injections, and surgery
therapy (thoracic sympathectomy).
T. Russo, MD () • G. Brancaccio, MD

e-mail: russo.teresa87@gmail.com

24 T. Russo and G. Brancaccio
Oral agents are most commonly used in clinical practice and

are somewhat effective at controlling the secretion, but long-term
usage and adverse side effects could make them unsafe for patient.
5.2 Discussion
The most commonly used medications for managing excessive

sweating are anticholinergics. These include medicines such as gly-
copyrrolate, oxybutynin, benztropine, propantheline, and others.
Anticholinergic agents work by competitive inhibition of
acetylcholine at muscarinic receptors (affinity for M3 receptors
in glandular issue).
Many medical professionals and hyperhidrosis patients expe-
rience great success with anticholinergic therapy. Anticholinergics
have not, however, been studied in controlled clinical trials
specifically for hyperhidrosis. Their use for hyperhidrosis is
thus “off-label.” Some anticholinergics, such as glycopyrrolate
and oxybutynin, have even been found to be safe in young chil-
dren. Two of the most commonly prescribed anticholinergic
medications are now available in liquid formulations, which is
important and helpful for children who suffer from
hyperhidrosis.
Optimum doses of these agents are still under study; however,
the following dosages are often clinically practiced: glycopyrro-
late 1–2 mg twice a day (Glaser 2014), oxybutynin 5–7.5 mg
twice a day (Try et al 2012), and methantheline bromide 50 mg
twice a day (Hund et al 2004). Side effects can be very disabling
and include dry mouth, blurring of vision, urinary hesitancy, diz-
ziness, tachycardia, and confusion. Contraindications include
myasthenia gravis, pyloric stenosis, narrow-angle glaucoma, and
paralytic ileus. Also, caution should be used in patients having
gastroesophageal reflux disease, glaucoma, bladder outflow
5 Oral Medication in Hyperhidrosis 25
obstruction, and cardiac insufficiency (Ghaleiha et al 2012).

Clonidine, given as 0.1 mg twice a day, is an antihypertensive
agent that by enhancing the function of alpha-adrenergic recep-
tors (α2-agonist) inhibits the sympathetic output. Side effects
include dry mouth, dizziness, constipation, sedation, and symp-
tomatic decrease in blood pressure.
Other oral medications besides anticholinergics that are suc-
cessful in treating patients with specific types of hyperhidrosis
are available. Beta-blockers (propranolol) and benzodiazepines
work by “blocking” the physical manifestations of anxiety.
These meds act on the central nervous system and are best for
patients who experience episodic or event-driven hyperhidrosis
(such as excessive sweating brought on by job interviews or
presentations). Side effects limit their long-term use. For
instance, benzodiazepines can be habit-forming, and many
patients cannot tolerate the sedative effects caused by both of
these drug therapies (Glaser 2014).
There have also been single-case or small samples of patients
with specific types of hyperhidrosis who responded to a variety
of other oral medications. Agents such as clonidine, indometha-
cin, gabapentin, and multiple others have shown effectiveness in
very specific cases of hyperhidrosis (Walling and Swick 2011).
5.3 Conclusion
Oral anticholinergic, beta-blockers, calcium channel blockers,

nonsteroidal anti-inflammatory drugs, and anxiolytics may be
useful for some patients and represent another therapeutic
chance for the clinician. However, considering the side effects
of a long-term therapy with oral drugs, we must remember that
they are indicated when other treatment and medication adjust-
ments fail to reduce sweating.
References
Ghaleiha A, Jahangard L, Sherafat Z, Ahmadpanah M, Brand S, Holsboer-

Trachsler E, Bajoghli H, Haghighi M. Oxybutynin reduces sweating in
depressed patients treated with sertraline: a double-blind, placebo-
controlled, clinical study. Neuropsychiatr Dis Treat. 2012;8:407–12.
Glaser DA. Oral medications. Dermatol Clin. 2014;32(4):527–32.
Hund M, Sinkgraven R, Rzany B. Randomized, placebo-controlled, double
blind clinical trial for the evaluation of the efficacy and safety of oral
methantheliniumbromide (vagantin) in the treatment of focal hyperhi-
drosis. J Ger Soc Dermatol. 2004;2:343–9.
Try C, Messikh R, Elkhyat A, Aubin F, Humbert RP. Use of oral oxybutynin
at 7.5 mg per day in primary hyperhidrosis. Rev Med Liege.
2012;67:520–6.
Walling HW, Swick BL. Treatment options for hyperhidrosis. Am J Clin
Dermatol. 2011;12:285–95.
Chapter 6
Surgical Therapy for Hyperhidrosis
Giuseppe Sito
Abstract Surgical procedures can provide long-lasting

relief from primary focal hyperhidrosis, in those cases
where topical agents have failed and the patient is not
compliant to botulinum toxin injections. In this chapter,
we encompass all the possible surgical therapies for hyper-
hidrosis from local excision to liposuction-curettage and
sympathectomy, with focus on efficacy and adverse events.
6.1 Introduction
Severe hyperhidrosis can cause extreme embarrassment that

may lead to social and professional isolation. There are now a
number of treatment options available for the control of hyper-
hidrosis. These differing therapies vary in their invasiveness,
efficacy, and side-effect profile. Although authors often seek to
highlight the benefits of one treatment over another, specific
therapies can now be tailored to a patient’s individual requirement,
G. Sito, MD
e-mail: mail@giuseppesito.it

28 G. Sito
to gain maximum symptomatic improvement with minimum

invasiveness and side effects. In this chapter, we will encompass
all the surgical strategy to take into account when other first-line
therapies (topical therapy and BTX injections) fail.
Local Excision
Local excision of eccrine glands has been a treatment option for

axillary hyperhidrosis for decades. The procedure, which is con-
ducted on an outpatient basis with local anesthesia, can be per-
formed either in combination with overlying skin excision (radical
skin excision) or without skin removal (skin sparing) (Hafner and
Beer 2002). Proponents of radical skin excision consider this
method to be more comprehensive because it involves removal of
dermally located eccrine glands in addition to those located in the
dermal-subcutaneous junction. Although effective in resolving
symptoms, this procedure often requires the placement of drains
and is associated with a number of complications and side effects,
including infection, seroma, hematoma, necrosis, and atrophic or
hypertrophic scarring. Since the introduction of glandular exci-
sion, advances in the local surgical treatment of axillary HH have
included the addition of liposuction and/or curettage, with the goal
of optimizing glandular disruption while minimizing surgical
complications and offensive scars (Bechara et al 2008).
Liposuction-Curettage
Unlike excision of axillary skin and eccrine glands, liposuction-

curettage is a minimally invasive and effective treatment for
hyperhidrosis that results in improved cosmetic outcomes and
less scarring. One retrospective trial performed in Germany
highlights the advantages and disadvantages of both surgical
procedures (Stashak and Brewer 2014).
6 Surgical Therapy for Hyperhidrosis 29
Liposuction-curettage is a less painful procedure with less com-

plication than local skin excision with subcutaneous curettage. A
number of complications were seen after the excision: protracted
healing time, wound infections, and bleeding (Wollina et al 2008).
Complications noted after liposuction-curettage are minor,
including mild hematoma and suture-associated irritation. Also
noteworthy for this procedure is a significantly shorter time to
return to work and surgical scars without atrophy, hypertrophy, or
hyperpigmentation. Therefore, considering the less serious compli-
cations (and lower associated costs), better cosmetic outcome, and
resolution of symptoms, liposuction-curettage provides a promis-
ing option for axillary hyperhidrosis (Glaser and Galperin 2014).
Sympathectomy
In the interests of developing a safer procedure with optimized

visualization of the sympathetic chain, Kux introduced a now
commonly performed operation called endoscopic thoracic
sympathectomy (ETS) in 1951. Initially recommended in the
treatment of peptic ulcer disease and other maladies, ETS has
since been applied successfully to the treatment of primary
hyperhidrosis, particularly of the palms and soles. Although
very effective in resolving symptoms of hyperhidrosis, a signifi-
cant concern with ETS is the development of compensatory
hyperhidrosis (CH), a postsympathectomy condition of exces-
sive sweating in a different anatomic region from the original
manifestation. Patients should be well informed about the irre-
versible nature of the surgery and the permanence of side effect.
Reported rates of CH after sympathectomy range from 30 to
90 % (Ibrahim et al 2013; Askari et al 2013); therefore, the
Society of Thoracic Surgeons consensus document recommends
excluding patients with widespread hyperhidrosis from surgery.
Severe CH is defined as CH troublesome enough that the patient
regrets undergoing ETS.
30 G. Sito
Sympathectomy is usually performed as a day-case procedure

under general anesthesia by a vascular surgeon. The sympathetic
chain is divided, or clipped, within the pleural cavity. Complications
during the operation are pleuritic chest pain, pneumothorax or
need for a chest drain, recurrent symptoms requiring reoperation,
and Horner’s syndrome (Moraites et al 2014; Vanni et al 2013).
In a retrospective cohort study of 210 patients with palmar,
axillary, and/or craniofacial hyperhidrosis, Bell et al. evaluated
the efficacy and incidence of adverse events with ETS as per-
formed by a single surgeon. Electrocautery ablation was used
on the sympathetic chain along its course over the second,
third, and fourth ribs to target the second, third, and fourth
thoracic ganglia; if identified intraoperatively, the accessory
nerve(s) of Kuntz was also ablated. The median age of patients
was 28 years, the youngest of whom was 11 years old. ETS for
palmar and craniofacial hyperhidrosis yielded better resolution
than for axillary hyperhidrosis, although all groups demon-
strated statistically significant improvement: 97 % improve-
ment in palmar, 93 % in craniofacial, and 71 % in axillary
hyperhidrosis (P < 0.001). Although 75 % of patients developed
CH, only 12 % considered it bothersome. The rates of severe
CH were greatest in those treated for axillary hyperhidrosis
(26 %) and craniofacial hyperhidrosis (44.5 %) and lowest in
those treated for palmar hyperhidrosis (8 %; P = 0.0003).
Furthermore, while rates of severe CH increased with patient
age, satisfaction with the results of ETS declined with age in a
similar manner (Bell 2014).
An alternative to sympathectomy, sympathotomy disrupts
axons postsynaptically after the T2 ganglion to avoid overzealous
neural injury that may result in the neuronal regeneration leading
to severe CH. In contrast with sympathectomy, sympathotomy
does not include ganglionectomy. While the incidence of severe
CH after sympathectomy is approximately 35 %, the rate of this
adverse event after sympathotomy is approximately only 1.3 %. In
a study of 155 patients (44 male, 111 female) with palmar-plantar
HH, Atkinson et al. evaluated the results from endoscopic thoracic
limited sympathotomy, where the ganglion cells in T1 and T2

were undisturbed. Immediately postoperatively, all 155 study
patients exhibited warm, dry palms, and after more than 3 months
postoperatively, 96.6 % demonstrated successful control of palmar
hydrosols, 69.2 % had diminished axillary sweating, and 39.8 %
had decreased plantar sweating. Long-term follow-up revealed
recurrence of palmar sweating in five patients, and severe CH was
noted in only two patients (1.3 %) (Atkinson et al 2011).
Although degree of sympathotomy/sympathectomy (total
number of levels disrupted) has not been conclusively correlated
with risk of CH, it appears that the absolute level has, with lower
chain disruption resulting in lower CH incidence.
Some studies suggest that limiting the levels obliterated dur-
ing ETS may result in lower risk of CH, while others refute this
claim. Lesèche et al. evaluated 134 patients with either isolated
palmar or axillary HH or a combination of the two to determine
the relationship between extent of sympathectomy and occur-
rence of CH. Although sympathectomies can range from level
T1 to T5, a recent prospective study revealed no significant dif-
ference in incidence and severity of CH with respect to degree
of sympathectomy. The authors concede that low statistical
power may have contributed to limitations of this study’s inter-
pretability (reviewed in Stashak and Brewer 2014).
Miller and Force presented the option of performing a tem-
porary sympathetic blockade before definitive sympathectomy
to predict those patients most likely to develop CH and therefore
be dissatisfied with the results of ETS. In their assessment of 18
patients suffering from combinations of palmar, axillary, and
plantar HH, the operators performed temporary blockades of
T2, T3, and accessory nerves with bupivacaine plus epineph-
rine. For a median of 4 days, all patients experienced relief of
HH and three of the 18 (12 %) developed CH. Only one of these
patients reported severe CH and decided not to proceed with
ETS. Interestingly, the two patients who endorsed mild CH
symptoms after temporary blockade were the same two partici-
pants who experienced mild CH after ETS. Nevertheless, all
32 G. Sito
patients who underwent ETS were satisfied with the results of

the procedure. The authors suggest that temporary sympathetic
blockade at the anticipated surgical levels be performed to help
predict likelihood of developing CH after ETS (reviewed in
Stashak and Brewer 2014).
Beyond the risk of CH following ETS, there is also concern
about cosmetic outcome and risk of chronic chest wall pain and
paresthesias. Although the thoracic wall approach with endos-
copy involves the creation of relatively small incisions, the desire
for a less invasive approach and interest in preventing intercostal
nerve injury have driven new procedural innovations. Investigators
in the People’s Republic of China have recently explored the pos-
sibility of using natural orifice access for thoracic sympathectomy
in the treatment of hyperhidrosis and have shown promising pre-
liminary results. A transumbilical approach for sympathectomy
may be associated with fewer postoperative complications, lower
risk of chest wall pain and paresthesias, and better cosmetic out-
comes (reviewed in Stashak and Brewer 2014).
References
Askari A, Kordzadeh A, Lee GH, Harvey M. Endoscopic thoracic sympa-

thectomy for primary hyperhidrosis: a 16-year follow up in a single UK
centre. Surgeon. 2013;11(3):130–3.
Atkinson JL, Fode-Thomas NC, Fealey RD, Eisenach JH, Goerss SJ.
Endoscopic transthoracic limited sympathotomy for palmar-plantar
hyperhidrosis: outcomes and complications during a 10-year period.
Mayo Clin Proc. 2011 Aug;86(8):721–9.
Bechara FG, Sand M, Hoffmann K, Boorboor P, Altmeyer P, Stuecker
M. Histological and clinical findings in different surgical strategies for
focal axillary hyperhidrosis. Dermatol Surg. 2008;34(8):1001–9; dis-
cussion 1009.
Bechara FG, Sand M, Altmeyer P. Characteristics of refractory sweating
areas following minimally invasive surgery for axillary hyperhidrosis.
Aesthetic Plast Surg. 2009;33(3):308–11.
Bell D, Jedynak J, Bell R. Predictors of outcome following endoscopic

thoracic sympathectomy. ANZ J Surg. 2014;84(1–2):68–72.
Glaser DA, Galperin TA. Local procedural approaches for axillary hyperhi-
drosis. Dermatol Clin. 2014;32(4):533–40.
Hafner J, Beer GM. Axillary sweat gland excision. Curr Probl Dermatol.
2002;30:57–63.
Ibrahim O, Kakar R, Bolotin D, Nodzenski M, Disphanurat W, Pace N,
Becker L, West DP, Poon E, Veledar E, Alam M. The comparative effec-
tiveness of suction-curettage and onabotulinumtoxin-A injections for
the treatment of primary focal axillary hyperhidrosis: a randomized con-
trol trial. J Am Acad Dermatol. 2013;69(1):88–95.
Moraites E, Vaughn OA, Hill S. Endoscopic thoracic sympathectomy.
Dermatol Clin. 2014;32(4):541–8.
Vanni C, Venuta F, Rendina EA. Two-stage unilateral versus one-stage
bilateral single-port sympathectomy for palmar and axillary hyperhidro-
sis. Interact Cardiovasc Thorac Surg. 2013;16(6):834–8.
Wollina U, Köstler E, Schönlebe J, Haroske G. Tumescent suction curettage
versus minimal skin resection with subcutaneous curettage of sweat
glands in axillary hyperhidrosis. Dermatol Surg. 2008;34(5):709–16.
Chapter 7
Iontophoresis in Hyperhidrosis
Teresa Russo and Gabriella Brancaccio
Abstract Hyperhidrosis continues to be undertreated in

our view, despite it considerably impairs quality of life of
patients. A well-known treatment option for hyperhidrosis
is iontophoresis that has been used to treat uncontrollable,
excessive sweating on the hands and feet since the 1940s.
7.1 Introduction
Hyperhidrosis continues to be undertreated in our view, despite

it considerably impairs quality of life of patients. A correct thera-
peutical approach requires several steps: (1) determine the physi-
ological cause of excess sweating; (2) establish the type of
hyperhidrosis and screen causes of secondary hyperhidrosis before
diagnosing essential hyperhidrosis; (3) evaluate the severity of the
T. Russo, MD () • G. Brancaccio, MD

e-mail: russo.teresa87@gmail.com

hyperhidrosis with a validated scale (HDSS score), minor’s starch-

iodine test, or gravimetric analysis; and (4) select one of the
currently available medical therapies, i.e., topical therapy (antiper-
spirants, iontophoresis, or botulinum toxin injection), systemic
therapy (oxybutynin), or surgery (thoracic sympathectomy).
A well-known treatment option for hyperhidrosis is ionto-
phoresis that has been used to treat uncontrollable, excessive
sweating on the hands and feet since the 1940s (Stolman 1987).
It is particularly useful for people who have tried topical anti-
perspirants without effects or have had skin irritation or contact
allergy using them. Moreover, patients who prefer to manage
their excessive sweating treatment at home may find iontopho-
resis a particularly attractive option.
7.2 Iontophoresis in Hyperhidrosis
Iontophoresis consists in the introduction of an ionized sub-

stance through the application of a direct current on intact skin.
Although the exact mechanism of action is unknown, this tech-
nique facilitates transdermal movement of solute ions by gen-
eration of an electrical potential gradient. Penetration of neutral
compounds is also facilitated. Tap water, anticholinergic agents
(glycopyrrolate), and botulinum toxin are candidates for use in
iontophoresis (Davarian et al. 2008). The latter are less often
used due to their large molecular size.
Tap water iontophoresis is the most frequently used and must
be performed initially every 2–3 days until therapeutic effect is
achieved. Once therapeutic effect is achieved for 2 weeks, treat-
ment can be done once every 2–3 weeks. Duration of effect is
only a few days with tap water and anticholinergic iontophore-
sis; however, iontophoresis with botulinum toxin may provide
relief for 3 months. The short-lived effect of current methods of
electrophoresis is the main negative aspect of this type of treat-
ment for patient (Reinaurer et al. 1993).
7 Iontophoresis in Hyperhidrosis 37
Tap water iontophoresis selectively targets areas with high

levels of electrolytes because of enhanced current flow. A local
electrochemical coagulation of proteins occurs in these areas and
subsequently disrupts eccrine gland function or causes inter-
rupted stimulus-secretion coupling that leads to a functional
disturbance of sweat secretion. Very limited published data on
successful treatment protocols is available. Recently, some
authors have evaluated the effectiveness of tap water iontophore-
sis, used on Monday, Wednesday, and Friday for 4 weeks, in 23
patients with palmar or plantar hyperhidrosis, and have con-
cluded that this therapy has been very effective to control focal
hyperhidrosis for their patients (Siah and Hampton 2013).
7.3 Iontophoresis Treatment
Iontophoresis treatment requires a specific medical device.

There are many specific machines designed to deliver this type
of treatment and some of them are for patient home use.
Iontophoresis treatment usually begins in the clinics under the
care and direction of a doctor or a nurse. In general, patients sit
with both hands or both feet, or one hand and one foot, immersed
in shallow trays filled with tap water for a short period of time
(20–40 min), while the device sends a small electrical current
through the water. The process is normally repeated three times
per week until the desired results are achieved. Once satisfactory
dryness has been reached, patients are switched to a maintenance
schedule, usually once per week. The patient at home using a
device purchased for this purpose could perform the mainte-
nance treatment (Pariser and Ballard 2014).
Sometimes, tap water in certain geographic locations may be
too soft in terms of mineral content, and for this reason, it may
induce an insufficient current flow during the treatment. This
situation can be corrected by adding 5 g of baking soda to each
water tray.
If a patient fails to respond to tap water iontophoresis alone,

it is possible to add to the water trays an anticholinergic
(as 2 mg tablets of glycopyrrolate) (Stolman 2008).
Patients who do not respond to iontophoresis may be candi-
dates for a combination therapy, such as iontophoresis com-
bined with topical antiperspirants.
7.4 Adverse Events
Tingling and itching were the most common side effects the
subjects experienced in the first 30 min of the electrical current
application.
Side effects of iontophoresis are rare but can include minor
pain, sign of skin irritation like burning, erythema, vesicles,
cracking, fissures, and blisters in the sites where the electrical
current was applied. In these instances, decreasing the fre-
quency of iontophoresis may be necessary.
7.5 Contraindications
Presence of metallic implants, such as cardiac pacemakers, arti-

ficial orthopedic joints, or bone implants and pregnancy are
contraindications for iontophoresis.
7.6 Conclusions
Iontophoresis has a long history of safe and effective use, and it

is a valid alternative when antiperspirants have been ineffective
or have resulted in a skin irritation; however, the short-lived
effect of this method often makes it undesirable for patients.
7 Iontophoresis in Hyperhidrosis 39
References
Davarian S, Kalantari KK, Rezasoltani A, Rahimi A. Effect and persistency

of botulinum toxin iontophoresis in the treatment of palmar hyperhidro-
sis. Australas J Dermatol. 2008;49:75–9.
Pariser DM, Ballard A. Iontophoresis for palmar and plantar hyperhidrosis.
Dermatol Clin. 2014;32:491–4.
Reinaurer S, Neusser A, Schauf G, Holzle E. Iontophoresis with alternating
current and direct current offset (AC/DC iontophoresis): a new approach
for the treatment of hyperhidrosis. Br J Dermatol. 1993;129:166–9.
Siah TW, Hampton PJ. The effectiveness of tap water iontophoresis for pal-
moplantar hyperhidrosis using a Monday, Wednesday, and Friday treat-
ment regime. Dermatol Online J. 2013;19:14.
Stolman LP. Treatment of excess sweating of the palms by iontophoresis.
Arch Dermatol. 1987;123:893–6.
Stolman LP. Hyperhidrosis: medical and surgical treatment. Eplasty.
2008;8:e22.
Chapter 8
The Role of Botulinum Toxin
in Hyperhidrosis
Giuseppe Sito and Gabriella Brancaccio
Abstract Botulinum toxin (BoNT) effect on sweating

was first described in 1993. From that moment, numerous
studies attested that BoNT local therapy for the axillary,
palmar, and plantar hyperhidrosis is an effective, easy,
and fast procedure. In this chapter, a review of the lit-
erature and description of procedures are provided with
particular attention to dilution, dosage, and injection
techniques.
G. Sito, MD
Second University of Naples, Naples, Italy

8.1 Botulinum Toxin
Botulinum toxin (BoNT) is a neurotoxic protein produced by

the bacterium Clostridium botulinum and related species. There
are seven different neurotoxins (labeled as types A, B, C [C1,
C2], D, E, F, and G), which are antigenically and serologically
distinct but structurally similar. They work by cleaving proteins
(SNARE) necessary for fusion of acetylcholine vesicles with the
presynaptic membrane thus inhibiting its release. Therefore, the
effect of BoNT is a temporary and reversible chemodenervation
with block of muscular contraction (useful for treatment of
spasms and dystonia and for improvement of wrinkles) and
reduction of sweating. Bushara and Park were the first to dem-
onstrate a nonmuscular use of BTX-A while treating patients
with hemifacial spasm in England in 1994, showing that botuli-
num toxin injections inhibit sweating and so are useful in treat-
ing hyperhidrosis (Bushara and Park 1994). BoNT injections are
less invasive than surgical procedures and provide longer-lasting
results than topical therapies.
The two serotypes of BoNTs used most commonly in the
clinical realm are toxins A and B, which cleave receptor proteins
SNAP-25 and synaptobrevin, respectively. Both have been
found to have similar efficacy for the treatment of axillary
hyperhidrosis. However, local injection of botulinum toxin type
A (BoNT-A) results in a more safe solution for primary hyper-
hidrosis, with a lower incidence of autonomic side effects and
pain at the injection site (Cohen et al 2007; D’Epiro et al. 2014).
The poor literature available on BoNT-B treatment in hyperhi-
drosis describes side effects related to distant spread of the
toxin, such as dry eyes and dry mouth (de Almeida and
Montagner 2014).
Four types of BoNTs are approved by the FDA for clinical
use in the USA, and everyone have a European equivalent:
onabotulinumtoxinA (A/Ona, Botox 100 U-Vistabel 50 U),
incobotulinumtoxinA (A/Inco, Xeomin 100 U-Bocouture 50
U), abobotulinumtoxinA (A/Abo, Dysport 375 U-Azzalure 125
8 The Role of Botulinum Toxin in Hyperhidrosis 43
U), and rimabotulinumtoxinB (B/Rima, Myobloc-Neurobloc).

The dose correlation between BoNT-A and BoNT-B varies
from 20 to 100 U of RimaB to 1 U of OnaA (de Almeida and
Montagner 2014). However, only onabotulinumtoxinA is indi-
cated for the treatment of hyperhidrosis, while the others are
still considered off-label. It is approved for the same indication
also in Europe.
The three formulations of BoNT-A and their role in hyperhi-
drosis have been compared in many studies (Stashak et al. 2014).
Many investigators did not find any statistically significant dif-
ference between the formulations in efficacy, onset of action,
and duration or side effects (Dressler 2010; Talarico-Filho et al.
2007; Campanati et al. 2014), while others found a faster onset
of action (Vergilis-Kalner 2011) but a greater area of diffusion
(Ko et al. 2014) for A/Abo, which could be responsible for more
side effects.
Despite the great efficacy of BoNTs, an accurate patient
screening is always important. Absolute contraindications for
injection with BoNT include skin infections and allergies to any
of the ingredients in BoNT formulation. Relative contraindica-
tions include illnesses resulting in muscle weakness, dysphagia,
or respiratory compromise (Lakraj et al. 2013). There are medi-
cations responsible for an increase of muscular weakness as
ciclosporin and aminoglycosides, and other drug that may inter-
act with BoNT are succinylcholine, pancuronium, gallamine
triethiodide, and D-penicillamine.
8.2 Dilution and Dosage
BoNT presented as 100 units of freeze dried powder in a glass

vial. There are strict guidelines for storage of botulinum toxin in
order to prevent denaturation and maintain maximum efficacy.
BoNT-A should be stored, before and after reconstitution, at
2–8 °C (refrigeration temperature). In unopened vials, it can be
stored till 18 months, while if diluted with saline, it should not

be stored for longer than 8 h. Usually a 5 ml syringe with a
25-gauge needle is used to inject the desired volume of normal
preservative-free saline. It is important to not agitate the
solution.
BoNT dilution volumes for treatment of glabellar and crows
feet wrinkles are well established and internationally standard-
ized. On the contrary, dilutions reported in literature for hyper-
hidrosis treatment range from 1 to 10 ml of saline solution.
High, medium, or low volume may be used according to the
desired spreading effect.
Recently AITEB (Associazione Italiana Terapia Estetica
Botulino) officially suggested a high dilution volume for hyperhi-
drosis therapy: 2.5 ml for onabotulinum and incobotulinum toxins
and 1.25 ml for abobotulinum toxin. The conversion ratio between
onabotulinum or incobotulinum and abobotulinum (Vistabex,
Bocouture/Azzalure) suggested is 1:2.5; this means that the units
of the first two are considered 2.5 times more strength than abob-
otulinum units. However, the three formulations are different from
each other and cannot be directly compared.
Interestingly, some reports in literature suggest the addition
to the reconstituted solution of lidocaine thus to cause less pain
and discomfort for the patient (de Almeida and Montagner
2014).
The number of injections and the total dose depend on the
involved area extension. The treatment goal is to create conflu-
ent overlapping anhidrotic halos to achieve an optimal outcome.
According to literature, the mean dose (per axilla and per hands)
is 50 U for onabotulinum and incobotulinum and from 125 U for
abobotulinum (de Almeida and Montagner 2014; Weinberg
et al. 2014).
Noteworthy, we use 32- or 33-gauge needles to minimize
injection pain.
8.3 BoNT Treatment of Axillary Hyperhidrosis
Axillary hyperhidrosis (AH) is usually bilateral and phasic,

often precipitated by heat and stress. Treatment of the disorder
with BoNT-A has been deeply reviewed in literature (Naumann
et al. 2013; Stashak and Brewer 2014) and reaches a high level
of evidence (level A collectively), while BoNT-B has an insuf-
ficient level of evidence (level U) (Lakraj et al. 2013).
Minor test is always useful to identify the affected area (see
Chap. 4). It should be photographed and delimited, and a grid
(squares with side around 1 cm) may be designed (Figs. 8.1 and
8.2). In fact, every injection must be spaced 1–2 cm apart to
reach an overlapping effect. We use from 30- to 33-gauge needle
to minimize pain. The application of a 33 % lidocaine ointment
around 15 min before the treatment is also very useful to reduce
discomfort for the patient. Usually 10–20 intradermal injections
are sufficient to treat each axilla.
As the toxin effect is delayed (around 3 days), performing a
minor test at week 1 post-treatment will evidence the obtained
result. The effects of BoNT-A last for 4–9 months on average in
axillary use and are associated with a very high satisfaction rate
among patients.
8.4 BoNT Treatment of Palmar and Plantar

Hyperhidrosis
It is important to know that treatment of palms and soles for

primary focal hyperhidrosis is considered an off-label use of
BoNT. Moreover, while iontophoresis is avoided for axillary
hyperhidrosis, in palmar and plantar hyperhidrosis many guide-
lines place BoNT alongside iontophoresis (Benson et al. 2013).
Fig. 8.1 Axillary grid
“Sweaty palms” is a so disabling disturb that we prefer perform-

ing BoNT treatment, as improving in quality of life is almost
immediate. Its efficacy is well documented in literature
(Naumann et al. 2013; Weinberg et al. 2014).
The injection procedure is similar to the treatment of axilla.
Also in this case, a gird may be helpfully designed (Figs. 8.3
and 8.4). The major drawback in this case is the great sensitivity
Fig. 8.2 Axillary grid (graphical representation)
(and consequently pain) of these areas. There are different

techniques available to reduce injection pain (ice, skin cooling
devices, vibration analgesia, etc.), but we prefer to use needle-
free anesthesia (33 % lidocaine ointment) or nerve block in less
compliant patients.
Fig. 8.3 Palmar grid
The ulnar nerve block is carried out with elbow flexed at 30°,
injecting 3–5 ml of anesthetic in the subcutaneous tissue, below
the fascia, in the hollow between the medial condyle and the
olecranon. The needle is parallel to the nerve direction. For the
median nerve block, the brachial artery pulsation is palpated,
and 5–7 ml of local anesthetic are injected about two cm above
the antecubital fold. In this way, an “anesthetic barrier” is cre-
ated (Figs. 8.5, 8.6, 8.7, and 8.8).
For plantar injections, the posterior tibial nerve block is
needed and will lead to the almost complete analgesia of the
sole. With the patient in supine position and leg externally
rotated, the needle is positioned just behind the posterior tibial
artery and maintained perpendicular to the cutis till it matches
the bone. Then it is slightly retracted (2–3 mm) and 5 ml of local
anesthetic are injected (Figs. 8.9, 8.10, and 8.11). It is possible
to perform also the sural nerve block that anesthetizes the fifth
toe and the lateral side of the sole. It requires injection of 3–5 ml
of local anesthetic between the lateral malleolus and the
Achilles tendon.
Fig. 8.4 Palmar grid (graphical representation)
It is important to remind that nerve blocks do have several

disadvantages. They are very user dependent and nerve injury is
a significant risk. Moreover the patients spend a long time in the
office and there is a longer recovery time.
After 15 min, the anesthesia take effect and it is possible to
proceed with the injection that will be spaced 1–2 cm apart as in
the axilla (Figs. 8.12, 8.13, and 8.14).
Although BoNT injection is efficacious for both axillae and
palms, in some studies a greater effectiveness of the axillary treat-
ment compared to the palmar one has been shown. Moreover,
using the same dosage per cm2, the therapeutic response to
BoNT-A in patients suffering from palmar hyperhidrosis is shorter
than in patients suffering from axillary hyperhidrosis (D’Epiro
et al. 2014; Naumann and Lowe 2001; Campanati et al. 2014).
Lateral cutaneous nerve
Biceps Tendon
Brachial artery
Radial nerve
Lateral epicondyle
Median nerve of the humerus
Medial epicondyle
of the humerus Olecranus
Ulnar nerve
Fig. 8.5 Arm section
Recent studies confirmed that repetition of injection (with an inter-

val of at least 3 months to prevent the production of neutralizing
antibodies) might be a valid strategy to increase the duration of
efficacy (Lecouflet et al. 2014; Brehmer et al 2015).
Fig. 8.6 Nerve block
8.5 Adverse Events
The most common side effects from injection of BoNT are

bruising and discomfort during and immediately after treatment.
However, this common reaction is temporary and of short
duration. In a review by Lakraj et al., all the major side effects
were reported: skin irritation, pruritus, flu-like symptoms, dry
mouth, and compensatory sweating.
BoNT injection in the palm can lead to weakness of the
muscles of the hand and over time may lead to atrophy.
Weakness is quite common, more frequent with higher doses
of the agent, but usually of short duration (Weinberg et al.
2014).
Fig. 8.7 Anatomy

section (1) Ulnar
nerve (2) Median
nerve (3) Median
nerve (4) Brachial
artery (5) Deep
branch of the radial
nerve (6) Superficial
branch of the radial
nerve
Fig. 8.8 Arm nerves representation (1) Median nerve (2) Ppalmaris longus
muscle tendon (3) Radial artery (4) Flexor carpi radialis muscle tendon (5)
Ulnar artery (6) Ulnar nerve (7) Flexor pollicis longus tendon (8) Tendon
of the Flexor digitorum superficialis (of the V finger) or also flexor tendon
of the V finger
Superficial
Saphenous peroneal nerve
nerve
Deep
peroneal nerve
Medial malleolus
Lateral malleolus
Posterior
tibial tendon
Posterior tibial nerve
Posterior tibial
artery and vein
Sural nerve
Calcaneus
Fig. 8.9 Ankle section

Fig. 8.10 Nerve land marks

Fig. 8.11 Innervation representation

Fig. 8.12 Pretreatment

Fig. 8.13 After the first session

Fig. 8.14 After the second session

References
Brehmer F, Lockmann A, Grönemeyer LL, Kretschmer L, Schön MP,
Thoms KM. Repetitive injections of botulinum toxin A continuously
increase the duration of efficacy in primary axillary hyperhidrosis: a ret-
rospective analysis in 101 patients. J Dtsch Dermatol Ges.
2015;13(8):799–805.
Bushara KO, Park DM. Botulinum toxin and sweating. J Neurol Neurosurg
Psychiatry. 1994;57(11):1437–8.
Campanati A, Giuliodori K, Martina E, Giuliano A, Ganzetti G, Offidani
A. Onabotulinumtoxin type A (Botox(®)) versus Incobotulinumtoxin
type A (Xeomin(®)) in the treatment of focal idiopathic palmar hyper-
hidrosis: results of a comparative double-blind clinical trial. J Neural
Transm. 2014;121(1):21–6.
therapy. Facial Plast Surg Clin North Am. 2007;15(1):17–30, v–vi.
de Almeida AR, Montagner S. Botulinum toxin for axillary hyperhidrosis.
Dermatol Clin. 2014;32(4):495–504.
D’Epiro S, Macaluso L, Salvi M, Luci C, Mattozzi C, Marzocca F, Salvo V,
Scarnò M, Calvieri S, Richetta AG. Safety and prolonged efficacy of
Botulin Toxin A in primary hyperhidrosis. Clin Ter.
2014;165(6):e395–400.
Dressler D. Comparing Botox and Xeomin for axillar hyperhidrosis.
J Neural Transm. 2010;117(3):317–9.
Ko EJ, Mun SK, Oh IY, Kwon TR, Kim BJ, Kim MN. Comparison of effi-
cacy and diffusion of three formulations of botulinum toxin type A in
two patients with forehead hyperhidrosis. Clin Exp Dermatol.
2014;39(5):673–5.
Lakraj AA, Moghimi N, Jabbari B. Hyperhidrosis: anatomy, pathophysiol-
ogy and treatment with emphasis on the role of botulinum toxins. Toxins
(Basel). 2013;5(4):821–40.
Lecouflet M, Leux C, Fenot M, Célerier P, Maillard H. Duration of efficacy
increases with the repetition of botulinum toxin A injections in primary
palmar hyperhidrosis: a study of 28 patients. J Am Acad Dermatol.
2014;70(6):1083–7.
Naumann M, Lowe NJ. Botulinum toxin type A in treatment of bilateral
primary axillary hyperhidrosis: randomised, parallel group, double
blind, placebo controlled trial. BMJ. 2001;323(7313):596–9.
Naumann M, Dressler D, Hallett M, Jankovic J, Schiavo G, Segal KR,

Truong D. Evidence-based review and assessment of botulinum neuro-
toxin for the treatment of secretory disorders. Toxicon.
2013;67:141–52.
Skiveren J, Nordahl Larsen H, Kjaerby E, Larsen R. The influence of needle
size on pain perception in patients treated with botulinum toxin A injec-
tions for axillary hyperhidrosis. Acta Derm Venereol. 2011;91(1):72–4.
Talarico-Filho S, Mendonça DO Nascimento M, Sperandeo DE Macedo F,
Sanctis DE, Pecora C. A double-blind, randomized, comparative study
of two type A botulinum toxins in the treatment of primary axillary
hyperhidrosis. Dermatol Surg. 2007;33(1 Spec No):S44–50.
Vergilis-Kalner IJ. Same-patient prospective comparison of Botox versus
Dysport for the treatment of primary axillary hyperhidrosis and review
of literature. J Drugs Dermatol. 2011;10(9):1013–5.
Weinberg T, Solish N, Murray C. Botulinum neurotoxin treatment of palmar
and plantar hyperhidrosis. Dermatol Clin. 2014;32(4):505–15.
Chapter 9
Psychological and Psychiatric
Management of Patients
with Hyperhidrosis
Alberto Caputo
Abstract Nowadays, sweating in a sauna, hammam, or

spa commodity is usually seen as an appropriate or even
trendy way of promoting our personal well-being and social
interaction (Gross et al., PLoS One 9(3):e92412, 2014).
However, in everyday life, excessive sweating is associated
with lacking hygiene, poor grooming, or emotional dis-
comfort. Furthermore, hyperhidrosis is often classified as a
“high-impact social no-go” and can be accompanied by psy-
chological distress, social self-imposed withdrawal or isola-
tion, and significantly decreased quality of life (Kopelman
et al., J Vasc Surg 24(2):194–199, 1996; Weber et al.,
Br J Dermatol 152(2):342–345, 2005; Gross et al., PLoS
One 9(3):e92412, 2014). So far, cause and consequence of
sweating, stress, and psychopathological symptoms are still
unclear due to their reciprocal interaction.
A. Caputo
Skindeep Center, Milan, Italy
e-mail: acaputo@skindeep.it

64 A. Caputo
9.1 Neurophysiopathological Substrate
A sympathetic overactivity of the autonomic nervous system has

been postulated (Shih et al. 1983; Ramos et al. 2005) to be a
putative cause of primary hyperhidrosis (PH), but it remains
unclear if it is generalized or localized. Although objective
measurements of the absolute sweat secretion can be easily
performed (Gross et al. 2014), the impact of PH and its diagno-
sis highly depend on the individual perception of sweating and
hence the psychological distress of the patients. The emotional
component is just part of a vast vicious circle (Sonntag and
Ruzicka 2004): eccrine glands are innervated by postganglionic
cholinergic fibers and, in case of overactivity, they lead to a
subsequent increase of sweat secretion. Moreover, apocrine
glands respond to emotional stimuli and are activated via inner-
vation or via circulating catecholamines. Apoeccrine glands are
mixed type glands and show a greater responsiveness to cholin-
ergic and adrenergic stimuli than eccrine glands. They have a
very high overall sweat rate and may contribute strongly to axil-
lary sweating (Wilke et al. 2007; Gross et al. 2014).
Various studies indicate that PH is characterized by increased
sweating primarily in the palms, soles, and armpits or in the
craniofacial regions. Sometimes, more than one region can be
involved (Ramos et al. 2005; Bellet 2010).
Some authors (Lerer 1977; Adar et al. 1977; Allen et al.
1974) claim that excessive sweating extends to other body
regions concluding that the sweat gland responses of the hands
and feet in reaction to emotional stimuli were not different from
those of the rest of the body. They proposed that emotional
sweating is a generalized body response although the patients
with PH are more aware of it on the palms.
However, no biochemical substrate that might explain this sym-
pathetic overactivity is clear and verified, as there is no subsequent
increase in the concentration of circulating catecholamines
9 Psychological and Psychiatric Management of Patients 65
(Noppen et al. 1997; Ramos et al. 2005). Bovell et al. (2001) found
morphological changes, typical of overstimulation, in the absence
of structural sweat gland impairment. Moya et al. (2003) reported
abnormalities in the sympathetic ganglia consistent with neural
aging, a finding that leads to consider overstimulation to be the
intermediate mechanism of action of PH. While cerebral cortex
controls emotional sweating, hypothalamus provides control on
thermal sweating. Abnormal or exaggerated central response to
normal emotional stress is still questionable (Bellet 2010).
9.2 Psychological and Psychiatric

Aspects of PH
The clinical picture of a high degree of anxiety and sympathetic

overfunction has led PH to be considered a sign of mental dis-
order (Engels 1982; Lerer 1977; Telaranta 1998). Due to the
limited number of researches related to psychopathology and
their conflicting results (Hornberger et al. 2004), PH has been
neglected in psychiatric practice e in DSM-5 classification,
although it is recognized as a distressing and disabling symptom
(Norton et al. 2001).
As a clinical problem, PH is most likely to be encountered in
the context of social anxiety disorder, social phobia, or somati-
zation disorder (Davidson et al. 2002), where it may command
clinical attention when facing emotional stimuli (Adar et al.
1977; Drummond and Lance 1987). The problem is unlikely to
be seen as significant in other mental diseases.
Although one study found that patients with hyperhidrosis
have no psychopathology (Ruchinskas et al. 2002), PH seems
responsible for a higher prevalence of anxiety symptoms than
what is usually reported among the general population and in
patients with other chronic diseases (Bragança et al. 2014).
66 A. Caputo
Ramos et al. (2005) noted that although these patients may not
meet the diagnostic criteria for general anxiety disorder (GAD),
they do experience a debilitating effect in their lives.
Depressive symptoms have a low prevalence rate in PH
patients, and they are often associated with anxiety symptoms
(Bragança et al. 2014). Anxiety and depression are not associ-
ated with gender or age (Bragança et al. 2014).
Moreover, it is suggested that alexithymia (insufficiency in
identification and expression of the emotions) is an important
feature in psychodermatological diseases (Poot et al. 2007).
Alexithymic individuals are claimed to be insufficient in config-
uring mental representations of emotions. Ordinary somatosen-
sory warnings are magnified in these individuals, and the
physical symptoms resulting from emotional stimulation are
interpreted as an indicator of physical illness (Costa et al. 2006;
Richards et al. 2005). Failure of alexithymic individuals to regu-
late emotional stress may result in exacerbated responses in
autonomic and neuroendocrine systems resulting in a range of
somatic diseases. Ak et al. (2013) found that PH patients are
significantly less successful, compared to the control group, in
the identification and expression of their feelings.
Lerer (1977) found that patients with hyperhidrosis had
poorer coping abilities and more emotional problems compared
with both dermatologic controls with non-psychogenic prob-
lems and normal subjects.
No data exist to indicate rates of PH in psychiatric settings. In
a speculative prospective, some indications can be derived from
patients affected by social phobia (SP). According to Davidson
et al. (2002), in a sample of 375 subjects with SP, almost 25 %
report severe or extreme PH prior to treatment. Approximately
50 % had mild to moderate levels of sweating, leaving only one
quarter with no excessive sweating at all. In attempting to char-
acterize those with hyperhidrosis, there were no demographic
differences with respect to age, gender, or age at onset.
9.3 Social Impact of PH
The self-perceived chronic psychological distress in PH has a

pivotal social component. PH usually implies avoiding
handshakes, wearing dark clothes, changing shirts several times
a day or worrying about someone seeing the armpit stains
(Kopelman et al. 1996). However, only few studies on quality of
life during PH have been performed (Weber et al. 2005; Wolosker
et al. 2012). The lack of self-confidence, bodily discomfort, and
feelings like shame and fear as mediators of disturbed interper-
sonal relationships (Strutton et al. 2004) and social exclusion
(Eisenach et al. 2005) can cause even more psychosocial distress
and become a considerable risk factor for the development of
depression (Lee et al. 2012).
Gross et al. (2014) found that lack of social recognition as
one indicator of chronic stress as well as the amount of depres-
sive symptoms is significantly higher in the hyperhidrotics
compared to matched healthy controls. These results are compa-
rable to a study of Lee et al. (2012).
Interestingly, in the former study, axillary sweating had the
highest impact on increasing distress and depressive symptoms
scores, which may result in the higher impairment of axillary
hyperhidrotics reported also by Hamm et al. (2006).
Hyperhidrosis, and most notably axillary sweating, might
attract negative attention causing considerable disruptions of
social and professional life and leading to severe limitations of
the person’s quality of life (Weber et al. 2005). Additionally, as
already mentioned, emotional processes stimulate or maintain
the secretion of sweat resulting in a vicious circle of sweating
and social stress described by Sonntag and Ruzicka (2004).
Amir et al. (2000) found that women are more impaired by
PH than were men and speculate that this finding may relate to
the strong esthetic connotations associated with the problem.
68 A. Caputo
Lastly, the majority of PH patients report the onset of their

symptoms in childhood or puberty: these two early stages of life are
very sensitive for changes and disturbances of the developmental
processes of self-esteem and identity (Benson et al. 2013; Hamm
et al. 2006). Amir et al. (2000) found that subjects who develop the
condition earlier in life suffer more than those with PH of later
onset. Rather than becoming habituated to the problem, subjects
who deals with the condition for a longer time have a lower quality
of life than those who copes with PH for shorter periods.
9.4 Measurement of PH in the Psychiatric

Context
Two scales developed for use in psychiatric practice include

5-point assessments of sweating (Schieman et al. 2010).
The Brief Social Phobia Scale (BSPS) (Davidson et al. 1997)
rates sweating on a 0–4 scale, in which 0 = none, 1 = mild (infre-
quent or not distressing), 2 = moderate (frequent and/or some-
what distressing), 3 = severe (constant or clearly distressing),
and 4 = extreme (incapacitating or painfully distressing). With
the BSPS, the subject is asked to consider any situation that
involves contact with other people – even just thinking about
such a situation – and assess the symptoms experienced. Since
subjects may have a history of avoiding distressing situations, it
is important to assess patients’ views of how they would react if
they were to place themselves in stressful situations.
The self-rated Social Phobia Inventory (SPIN, Connor et al.
2001) also adopts a 5-point range to assess sweating. With the
SPIN, the patient is asked to self-rate the extent to which
“sweating in front of people causes me distress”.
A disease-specific quality of life measure in hyperhidrosis,
the Hyperhidrosis Quality of Life Index (HidroQOL) has been
developed and validated by Kamudoni et al. (2015). The
HidroQoL’s item scores can be summed to form sub- and overall
scale scores: Q1–Q6 as the daily life activities domain score,

items Q7–Q18 as the psychosocial impact domain score, and all
items as overall scale score. The individual items are assumed
to have equal weighting, supporting a simple arithmetic summa-
tion in the calculation of domain and overall score. A 3-point
range is adopted (very much; a little; no, not at all).
Questionnaires that rate quality of life in regard to sweating
include the Amir Hyperhidrosis Quality of Life Scale (Amir
et al. 2000), a 26-item scale related to the following domains:
function, social activity, intimacy, self-appraisals, attributions
made to others, and exacerbating conditions.
Based on a cognitive-behavioral model of hyperhidrosis, the
Sweating Cognitions Inventory (Wheaton et al. 2011) consists of a
pool of 28 items designed to assess patients’ beliefs about the
nature and consequences of sweating (e.g., “People are disgusted
by my sweat”). Respondents rate their agreement with each item on
a 5-point scale ranging from 0 (“very little”) to 4 (“very much”).
9.5 Psychiatric and Psychological Treatment
While PH often provides the impetus for seeking treatment, lit-

tle is known about how and what to treat or how effective such
therapy might be in psychiatric practice (Schieman et al. 2010).
Pharmacotherapy of PH in psychiatry is poorly researched:
recent analyses suggest some benefits for selective serotonin
reuptake inhibitors (SSRIs), GABAergic anticonvulsant, and
benzodiazepine drugs. Davidson et al. (2002) noted a significant
53 % reduction in sweating with SSRI treatment (fluoxetine) in
social phobia patients. With a GABAergic anticonvulsant drug
(gabapentin) or clonazepam, a 40 % benefit that is not statisti-
cally different from placebo is noted. All active treatments are
superior to placebo, but many patients are left with residual
sweating, and while they may be somewhat less distressed about
having the symptom, further improvement would be desirable.
70 A. Caputo
These findings need to be interpreted in the context that all 3

treatments are generally effective in the social phobia popula-
tion. But we cannot assume that all treatments are broad spec-
trum in their effects, and further adjunctive treatment of PH is
perhaps desirable (Schieman et al. 2010).
On the other hand, beta-blockers (like propranolol) and ben-
zodiazepines target the physical manifestations of anxiety. This
approach is suitable for patients who experience episodic or
event-driven PH (such as excessive sweating brought on by job
interviews or presentations). Side effects limit their long-term
use. For instance, benzodiazepines can be habit forming (on
long term), and many patients cannot tolerate the sedative
effects caused by both of these drug therapies. Furthermore,
psychiatrists should be very cautious when prescribing benzodi-
azepines in pediatric patients.
Sometimes a minor sedative drug, controlling the stress compo-
nent, seems enough to stop the sweating. But this measure induces
only a partial remission: some individuals may respond better to
medications like amitriptyline and hydroxyzine which have a com-
bined mild, prolonged, sedative, and anticholinergic effect.
In the author’s experience, the combination of amitriptyline
and perphenazine at low doses (10–24 and 2–4 mg) can be effi-
cacious in treating anxiety and sweating. Instead of using a
SSRI compound, a SNRI like venlafaxine or duloxetine is an
interesting alternative.
Only a limited response to psychotherapy is reported for
PH. With cognitive behavior therapy (CBT), a reduction of
25 % of sweating has been observed (Davidson et al. 2002) in
social phobia patients with hyperhidrosis. Psychologists can
also assist the patients in reducing social anxiety implementing
methods such as attention training and confrontational training
to control sweating.
Biofeedback of galvanic skin resistance (GSR) can improve
cutaneous problems that have an autonomic nervous system
component (Shenefelt 2003; Duller and Gentry 1980). Hypnosis

may enhance the effects obtained by biofeedback. All these
techniques are beneficial in a small number of cases (Connolly
and de Berker 2003).
9.6 Tip for Managing PH
Teach the patients to keep a “sweat journal.” The knowledge of

various “trigger situations” is important in order to avoid them
or to ask the proper help in advance. A sweat journal can also
track the treatment progress.
References
Adar R, Kurchin A, Zweig A, et al. Palmar hyperhidrosis and its surgical

treatment. Ann Surg. 1977;186:34–41.
Ak M, Dinçer D, Haciomeroglu B et al. The evaluation of primary idio-
pathic focal hyperhidrosis patients in terms of alexithymia. J Health
Psychol. 2013;18(5):704–10. Epub 2012 Aug 29.
Allen J, Armstrong J, Croddie I. Sweat responses of a hyperhidrotic subject.
Br J Dermatol. 1974;90:277–81.
Amir M, Arish A, Weinstein Y, et al. Impairment in quality of life among
patients seeking surgery for hyperhidrosis (excessive sweating): pre-
liminary results. Isr J Psychiatry Relat Sci. 2000;37(1):25–31.
Bellet JS. Diagnosis and treatment of primary focal hyperhidrosis in chil-
dren and adolescents. Semin Cutan Med Surg. 2010;29(2):121–6.
Benson RA, Palin R, Holt PJE, et al. Diagnosis and management of hyper-
hidrosis. BMJ. 2013;347:f6800.
Bovell DL, Clunes M, Elder H, et al. Ultrastructure of the hyperhidrotic
eccrine sweat gland. Br J Dermatol. 2001;145:298–301.
Bragança GMG, Lima SO, Neto AFP, et al. Evaluation of anxiety and
depression prevalence in patients with primary severe hyperhidrosis. An
Bras Dermatol. 2014;89(2):230–5.
72 A. Caputo
Connolly M, de Berker D. Management of primary hyperhidrosis: a sum-

mary of the different treatment modalities. Am J Clin Dermatol.
2003;4(10):681–97.
Connor KM, Kobak KA, Churchill LE, et al. Mini-SPIN: a brief screening
assessment for generalized social anxiety disorder. Depress Anxiety.
2001;14(2):137–40.
Costa A, Peppe A, Carlesimo GA, et al. Alexithymia in Parkinson’s disease
is related to severity of depressive symptoms. European Journal of
Neurology. 2006;13:836–841.
Davidson JR, Miner CM, De Veaugh-Geiss J, et al. The Brief Social Phobia
Scale: a psychometric evaluation. Psychol Med. 1997;27(1):161–6.
Davidson JR, Foa EB, Connor KM, et al. Hyperhidrosis in social anxiety
disorder. Prog Neuropsychopharmacol Biol Psychiatry.
2002;26(7–8):1327–31.
Drummond PD, Lance JW. Facial flushing and sweating mediated by the
sympathetic nervous system. Brain. 1987;110(Pt 3):793–803.
Duller P, Gentry WD. Use of biofeedback in treating chronic hyperhidrosis:
a preliminary report. Br J Dermatol. 1980;103:143–6.
Eisenach JH, Atkinson JLD, Fealey RD. Hyperhidrosis: evolving therapies
for a well-established phenomenon. Mayo Clin Proc. 2005;80(5):
657–66.
Engels WD. Dermatologic disorders: psychosomatic illness review.
Psychosomatics. 1982;23:1209–19.
Gross KM, Schote AB, Schneider KK, et al. Elevated social stress levels
and depressive symptoms in primary hyperhidrosis. PLoS One.
2014;9(3):e92412.
Hamm H, Naumann MK, Kowalski JW, et al. Primary focal hyperhidrosis:
disease characteristics and functional impairment. Dermatology (Basel).
2006;212(4):343–53.
Hornberger J, Grimes K, Naumann M. Recognition, diagnosis, and treat-
ment of primary focal hyperhidrosis. J Am Acad Dermatol.
2004;51(2):274–86.
Kamudoni P, Mueller B, Salek MS. The development and validation of a
disease-specific quality of life measure in hyperhidrosis: the
Hyperhidrosis Quality of Life Index (HidroQOL©). Qual Life Res.
2015;24(4):1017–27.
Kopelman D, Hashmonai M, Ehrenreich M, Bahous H, Assalia A. Upper
dorsal thoracoscopic sympathectomy for palmar hyperhidrosis:
improved intermediate-term results. J Vasc Surg. 1996;24(2):194–9.
Lee HH, Kim DW, Kim C. Efficacy of glycopyrrolate in primary hyperhi-
drosis patients. Korean J Pain. 2012;25(1):28–32.
Lerer B. Hyperhidrosis: a review of its psychological aspects.

Psychosomatics. 1977;18:28–31.
Moya J, Ramos R, Prat J, et al. Cambios anatomopatológicos observados en
los ganglios simpáticos de pacientes intervenidos de hiperhidrosis palm-
araxilar. Estudio sobre 55 muestras. Arch Bronconeumol.
2003;39:115–7.
Noppen M, Sevens C, Gerlo E, et al. Plasma catecholamine concentrations
in essential hyperhidrosis and effects of thoracoscopic D2-D3 sympathi-
colysis. Eur J Clin Invest. 1997;27:202–5.
Norton PJ, Burns JA, Hope DA et al. Generalization of social anxiety to
sporting and athletic situations: gender, sports involvement and parental
pressure. Depress. Anxiety. 2001;12:193–203.
Poot F, Sampogna F, Onnis L. Basic knowledge in psychodermatology.
J Eur Acad Dermatol Venereol. 2007;21:227–34.
Ramos R, Moya J, Turón V, et al. Primary hyperhidrosis and anxiety: a
prospective preoperative survey of 158 patients. Arch Bronconeumol.
2005;41(2):88–92.
Richards HL, Fortune DG, Griffiths CE, et al. Alexithymia in patients with
psoriasis: Clinical correlates and psychometric properties of the Toronto
Alexithymia Scale-20. Journal of Psychosomatic Research. 2005;58:
89–96.
Ruchinskas RA, Narayan RK, Meagher RJ, et al. The relationship of psy-
chopathology and hyperhidrosis. Br J Dermatol. 2002;147(4):733–5.
Schieman C, Gelfand GJ, Grondin SC. Hyperhidrosis: Clinical Presentation,
Evaluation and Management. Expert Review of Dermatology. 2010;5(1)
Francis & Taylor Online.
Shenefelt PD. Biofeedback, cognitive-behavioral methods, and hypnosis in
dermatology: is it all in your mind? Dermatol Ther. 2003;16(2):114–22.
Shih CJ, Wu JJ, Lin MT. Autonomic dysfunction in palmar hyperhidrosis.
J Auton Nerv Syst. 1983;8(1):33–43.
Sonntag M, Ruzicka T. Hyperhidrosis-causes and current therapeutic strate-
gies. Z Allg Med. 2004;80(7):289–94.
Strutton DR, Kowalski JW, Glaser DA, et al. US prevalence of hyperhidro-
sis and impact on individuals with axillary hyperhidrosis: results from a
national survey. J Am Acad Dermatol. 2004;51(2):241–8.
Telaranta T. Treatment of social phobia by endoscopic thoracic sympathi-
cotomy. Eur J Surg. 1998;580:27–32.
Weber A, Heger S, Sinkgraven R, et al. Psychosocial aspects of patients
with focal hyperhidrosis. Marked reduction of social phobia, anxiety
and depression and increased quality of life after treatment with botuli-
num toxin A. Br J Dermatol. 2005;152(2):342–5.
74 A. Caputo
Wheaton MG, Braddock AE, Abramowitz JS. The sweating cognitions

inventory: a measure of cognitions in hyperhidrosis. J Psychopathol
Behav Assess. 2011;33:339–402.
Wilke K, Martin A, Terstegen L, Biel SS. A short history of sweat gland
biology. Int J Cosmet Sci. 2007;29(3):169–79.
Wolosker N, de Campos JRM, Kauffman P, et al. Evaluation of quality of
life over time among 453 patients with hyperhidrosis submitted to endo-
scopic thoracic sympathectomy. J Vasc Surg. 2012;55(1):154–6.

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Giuseppe Sito

ISBN 978-3-319-26921-4 ISBN 978-3-319-26923-8 (eBook)

Library of Congress Control Number: 2016931334

Springer Cham Heidelberg New York Dordrecht London

Printed on acid-free paper

Springer International Publishing AG Switzerland is part of Springer

1 Anatomy and Physiology of Sweat Glands . . . . . . . . 1

5 Oral Medication in Hyperhidrosis. . . . . . . . . . . . . . . 23

9 Psychological and Psychiatric Management

We are indebted to “Foto Macro © 2015 – macromedica.it” for

The primary function of the eccrine sweat glands is to assist in

events. Sweat glands are innervated by sympathetic postgangli-

A number of medical and surgical remedies are available for

Naples, Italy Giuseppe Sito, MD

Gabriella Brancaccio and Teresa Russo

Abstract To understand pathologic mechanisms at the

Eccrine sweat glands are simple coiled tubular glands with a

G. Brancaccio, MD () • T. Russo, MD

G. Sito (ed.), Hyperhidrosis: Clinician’s Guide to Diagnosis 1

Fig. 1.1 Eccrine sweat

and coiled portion; and a secretory tubule, coiled deep in the

Functions of sweat glands are:

PO/AH; Preoptic area and Descending autonomic

Fig. 1.2 Anatomy of physiologic perspiration pathway

may cause altered sweating, such as the ipsilateral anhidrosis

Groscurth P. Anatomy of sweat glands. Curr Probl Dermatol. 2002;30:1–9.

Giuseppe Sito and Gabriella Brancaccio

Abstract Hyperhidrosis is broadly classified into two

Hyperhidrosis is the excessive production of sweat affecting 1–3 %

definition not associated with an underlying medical condition.

2.2 Primary Hyperhidrosis

Primary or essential hyperhidrosis is caused by a deregulation of

Table 2.1 Primary and secondary hyperhidrosis: differential diagnosis

Until recently, there were few data available on the prevalence

the US consumer survey, 51 % of hyperhidrosis patients have

2.3 Secondary Hyperhidrosis

Secondary generalized hyperhidrosis is excessive sweating that is

Gabriella Brancaccio and Giuseppe Sito

Abstract Before diagnosing primary focal hyperhidrosis,

3.1 Patient Evaluation

Primary hyperhidrosis is a condition of great discomfort for

G. Sito (ed.), Hyperhidrosis: Clinician’s Guide to Diagnosis 13

Table 3.1 Diagnostic features of primary hyperhidrosis

The first step when evaluating a patient presenting with

Table 3.2 HDSS (from Weinberg et al 2014)

Table 3.3 Differential diagnosis of generalized excessive sweating

3.2 Identification of the Treatment Area

A useful and simply tool to identify the extension of the

Fig. 3.2 Minor iodine-starch test. Pre-post

Minor iodine-starch test is also very helpful after treatment

Fig. 3.3 Virtual grid on the affected area

Fig. 3.4 Minor iodine-starch test of the axilla

distribution and maximal perspiration sites must be photo-

Diagnosis of hyperhidrosis is essentially based on clinical his-

Gabriella Brancaccio and Giuseppe Sito

Abstract Primary or essential hyperhidrosis is a disorder that

Primary or essential hyperhidrosis is a disorder that causes

G. Sito (ed.), Hyperhidrosis: Clinician’s Guide to Diagnosis 19

estimated that 0.6–1.0 % of the population suffers from this