ARTICLE "I
found Uriah reading a great fat book, with such demonstrative attention,
that his lank forefinger followed up every line as he read, and made clammy
tracks along the page (or so I fully believed) like a snail.
It was no fancy of mine about his hands, I observed; for he frequently
ground the palms against each other as if to squeeze them dry and warm,
besides often wiping them, in a stealthy way, on his pocket-handkerchief."
David Copperfield
Charles Dickens
Chapter XVI
Sweating is a function that is vital to our survival. Sweat serves as
the body's air conditioner by allowing water to evaporate thus protecting
the body from overheating. Humans have two different kinds of sweat glands:
one type is the exocrine sweat glands found all over the skin. These produce
an aqueous secretion rich in electrolytes and such glands are densely
grouped on the palms, soles and axillae. The body has approximately 2-3
million of these thermoregulatory glands that are controlled by the sympathetic
nervous system, which in turn innervates the glands via postsynaptic cholinergic
fibres. The other kind of sweat gland is the apocrine gland, which is
commonly localised in the axillary and genitoanal regions. The function
of these glands is regulated by hormonal processes. The secretion they
produce contains lipids, is slightly viscous and is rich in steroids and
other hormones that act as pheromones. Apocrine sweat glands have no thermoregulatory
effect.
Hyperhidrosis is defined as hyperfunction of the exocrine sweat glands.
A fundamental distinction is made between physiological, symptomatic and
idiopathic hyperhidrosis. Physiological hyperhidrosis includes the acclimatisation
process in tropical climates, gustatory sweating when certain spices or
foods are consumed and sweating due to physical exertion or obesity. In
diagnosing symptomatic hyperhidrosis, it should be determined whether
there are endocrinological causes (e.g. hyperthyroidism), an increased
release of catecholamines (e.g. phaeochromocytoma), neurological
dysfunctions (e.g. Ross syndrome [1], auriculotemporal syndrome,
Sudeck's syndrome, neuropathies) or naevoid malformations. The possibility
of idiopathic hyperhidrosis should not be considered until these causes
have been ruled out. Localised forms (e.g. axillary hyperhidrosis,
hyperhidrosis of the hands and feet, facial hyperhidrosis) are also to
be distinguished from generalised forms.
Patients who sweat excessively and pathologically are often subject
to enormous psychosocial pressure because of the restrictions this causes
in their personal and professional lives. Such people are often seen by
those around them as being negligent of their body care and the condition
itself encourages the development of other diseases such as bromhidrosis,
dermal mycoses, Gram-negative infections of the feet or plantar and palmar
warts. Furthermore, the complaints of many such patients are not often
taken seriously at first, because excessive sweating is not always recognised
as a disease. A patient in need of help is thus often confronted with
a long search for suitable therapy and must consult several physicians.
A hyperhidrotic area of skin can be made apparent by means of the Minor
test: a 2% iodine solution is applied to the affected area, followed by
starch in powder form once the solution has dried. The hyperhidrotic skin
then develops a blue-black coloration. There are various means of measuring
sweating objectively [2]. When gravimetry is used, blotting paper is pressed
onto the skin and the quantity of sweat absorbed is then determined using
an analytical balance. Measurements using hygrometry determine the evaporation
(in g/m2h) at defined points. Colorimetry is also used as a
semi-quantitative procedure similar to the Minor starch-iodine reaction;
with this method, colour changes that occur on specially coated paper
which is placed in contact with the sweat are analysed.
General measures to combat excessive sweating include wearing air-permeable
clothing made of natural fibres and frequent laundering of clothes and/or
changing shoes and clothing often. Substances such as coffee, alcohol
or hot spices can often increase sweating and should thus be avoided.
Specific therapeutic procedures for treating localised and generalised
forms of hyperhidrosis will be discussed below.
Local antiperspirants
Antiperspirants are substances which regulate the function of the sweat
glands. In the past, a number of topically applied substances were used
to treat hyperhidrosis. Anticholinergic drugs, formaldehyde and tanning
agents proved to be unsuitable, however, due to their low efficacy and/or
undesireable side effects. For example, after long-term application of
formaldehyde, 15-20% of the patients developed hypersensitivity [3]. The
use of metal salts in treating axillary hyperhidrosis has brought about
satisfactory results. Aluminium chloride in particular has the ability
to temporarily close the pores of the sweat glands in the lower and middle
epidermis [4]. This occlusion lasts for several days until it is exfoliated
by the physiological regeneration of the skin. Aluminium chloride is applied
at night when the exocrine sweat glands are largely inactive, thereby
making it possible for the active ingredients to penetrate the skin. For
use in the axillae, concentrations of 10-15% have been shown to be effective;
higher concentrations of aluminium chloride (up to 30%) are needed for
the hands and feet. One example of a formulation recommended by us:
R: AlCl3.6H20 : 13.0%
Adulsion MH300 : 1.5%
Purified water to : 100.0%
The pharmaceutical formulation is of considerable importance to the
efficacy of the treatment. The substance is applied every night for one
week and then only once every 1-2 weeks as maintenance therapy. The success
rates in treating axillary hyperhidrosis are well over 90% [5]. Long-term
application results in atrophy of the sweat gland acini, which means that
the frequency of treatment can be reduced over time. Because of their
excellent efficacy, aluminium chloride salts are also found in many commercially
available antiperspirants (e.g. Marbert Man antiperspirant stick®).
Contact allergies have not been described to date. It is a disadvantage
that textiles can be affected by the substance, which means that expensive
nightclothes should not be worn during treatment. Furthermore, atopic
skin in particular can develop temporary irritations which can, however,
be managed well under dermatological care.
Tap water iontophoresis
Iontophoresis is a procedure used in physical therapy which involves
a complex process of ion transport through the skin using galvanic current.
It was first described by Bouman and Grunewald-Lentzer in 1952 as a physiotherapeutic
means of treating hyperhidrosis [6]. Levit was responsible for establishing
the method as a recognised procedure suitable for practical dermatology
in 1968 [7]. The mode of action has still not been conclusively explained,
but it is assumed that a reversible disruption of the ion channel occurs
in the secretory glomeri of the sweat glands [8]. The treatment entails
filling just enough lukewarm water into shallow plastic basins to cover
the hyperhidrotic areas of skin on hands or feet. Defects in the horny
layer of palms, soles and nail folds should be carefully covered with
Vaseline to prevent an unnecessary sensation of burning in the rhagades.
Stainless steel or aluminium electrodes with a protective plastic coating
are used to conduct electricity into the water. The source of the direct
current is a galvanotherapeutic device; in most cases, a current between
8 and 20 m A is sufficient. After the hands or feet have been submerged
in the water, the current is gradually increased as needed until tingling
is felt in the affected areas; the sensation should not be considered
unpleasant. Anodes are attributed greater efficacy than cathodes and consequently
the direction of the current should be switched regularly to achieve a
uniform therapeutic effect [9, 10]. A session lasts 10-20 min and in cases
in which palmoplantar hyperhidrosis is present, the hands and feet can
be treated simultaneously to save time. Treatment usually begins with
3-4 sessions per week [11]. The response rate in palmoplantar hyperhidrosis
is approximately 90%. An improvement of the symptoms is usually achieved
after 5-10 sessions and complete therapeutic success is reached after
10-15 sessions. 1-2 sessions per week are usually needed to maintain the
euhidrotic state [2]. Schempp et al. and Wollina et al.
have reported an additional positive side effect of this method. Patients
with concomitant dyshidrotic eczema of the hands or feet experience resolution
of the eczema and a significant relapse-free interval due to tap water
iontophoresis treatment [12, 13].
Documented adverse effects include temporary dermal irritation, subjective
hyperaesthesia and occasionally transient blisters [2, 14]. Long-term
studies have shown that tap water iontophoresis can be performed for many
years without any difficulty [11, 14]. The disadvantage of tap water iontophoresis,
which is a long-term treatment with an undetermined duration, has been
eliminated by the development and availability of equipment for home use
[2]. These devices cost between euros 400 and euros 1,000 and are often
covered by health insurance companies on an individual basis.
Iontophoresis with additional anticholinergic
drugs
By adding anticholinergic substances such as glycopyrronium bromide,
poldine metilsulfate or hexopyrronium bromide to the tap water, the effects
of iontophoresis therapy become apparent more quickly and last longer
[8, 15]. Anticholinergic medications are always applied at the anode.
However, there can be systemic adverse effects such as dryness of the
mucous membranes of the mouth, nose and throat, accommodation difficulties,
urinary retention or abdominal pain, which are dependent on the application
period. Due to the adverse effects described, pure tap water iontophoresis
is to be given preference as an initial treatment measure. If it is not
successful, then treatment with added anticholinergic agents can be attempted.
Botulinum toxin
Botulinum toxin is a neurotoxin produced by Clostridium botulinum (a
Gram-positive, spore-producing, anaerobic bacterium). It irreversibly
inhibits the release of acetylcholine from the presynaptic nerve endings
near the neuromuscular junctions and exocrine sweat glands. The first
clinical application of botulinum toxin in humans was by Scott in 1980
in patients with strabismus [16]. It was used exclusively to treat muscular
diseases until 1994. Bushara et al. first reported on its potential
use in hyperhidrosis in 1996 [17]. Botulinum toxin A has been available
in Germany since 1993 in the form of two commercially available products:
Botox® and Dysport®. The quantity of toxin
is given in m U (mouse units), although the different biological activity
of the m U of both means that they cannot be directly compared (1 m U
Botox® corresponds to approx. 3-5 m U Dysport®)
[18].
Before treatment with botulinum toxin begins, the hyperhidrotic area
is visualised using the Minor starch-iodine test. The intracutaneous administration
takes place either by single injections to create wheals at the injection
site or by manipulating the needle under the skin to distribute the substance.
Approximately 50 m U of the substance Botox® or approx.
200 m U Dysport® are needed for the treatment of one axilla
[19, 20]. The euhidrotic condition then lasts for 3-7 months. Studies
with higher dosages (200 m U Botox® per axilla) have been
conducted which demonstrate that a longer period of efficacy (8-9 months)
can achieved [21]. Botulinum toxin has also been administered successfully
to the palms of the hands. In comparison with the axillae, total dosages
of approx. 100-165 m U Botox® per palm are needed [20,
22, 23]. Here, another injection is necessary after a maximum of 9-12
months [20]. No studies have been published yet about the use of botulinum
toxin on the soles. On treatment of muscular diseases with botulinum toxin,
it has been shown that 3-5% of the patients develop neutralising antibodies
against the toxin that lead to resistance [24]. Apparently short intervals
between repetitions and high total doses are predisposing factors. To
date, resistance of this sort has not been described during the treatment
of hyperhidrosis. The primary adverse effect is the painfulness of the
injection. In the hands administration is only possible when anaesthetics
are used, e.g. carpal block. Small haematoma can appear at the
injection site. In the palmar region, there is also the danger of a temporary
weakness of smaller muscles in the hand that can last for up to 8 weeks.
Contraindications include pregnancy, neuromuscular diseases (e.g.
myasthenia gravis), blood-clotting disorders and concomitant ingestion
of drugs which also affect neuromuscular transmission (e.g. aminoglycoside
or macrolide antibiotics). A significant problem with botulinum therapy
is the cost factor involved. One ampoule of Dysport® (500
m U) currently costs approx. euros 420, and an ampoule of Botox®
(100 m U) costs about euros 370. An ampoule is used for a single treatment
of both axillae and two ampoules for both hands.
Surgical procedures
Surgical extirpation of the sweat glands is an invasive treatment option
for axillary hyperhidrosis. To this end, complete excision of the entire
hypersecretory skin region can be performed using various techniques,
which have been reported to have relapse rates of 10-20% [25]. Scar formation
can occur due to the development of a large wound; this can be cosmetically
displeasing or even lead to functional impairment in extreme cases (Fig.
1).
Another option is curettage with a scraper [26] or liposuction [27];
this entails only small incisions and generally there are no complications
apart from haematoma, postoperative pain and paraesthesia. Liposuction
seems to be an especially safe and effective therapy of axillary hyperhidrosis
[28, 29]. However, long-term results with respect to recurrence have not
been documented to date.
Another possible surgical procedure is sympathectomy. Here the sweat
glands in the hands are denervated by removal of the sympathetic nerve
trunk T2 to T3; for the feet, L3 ganglia
are removed. Surgical sympathectomy for axillary hyperhidrosis is considered
to be difficult since the ganglia T3 to T6 must
be destroyed for this procedure. The open operations that were previously
conducted very often led to complications such as Horner syndrome, pneumothorax,
haematothorax and infected wounds. These complications occur much less
frequently with newer minimally invasive operation techniques involving
endoscopic-electrocaustic obliteration of the sympathetic trunk and the
ganglia [30]. However, other adverse effects appear such as compensatory
sweating elsewhere on the body (37-75%) (Fig.2),
gustatory sweating (in approx. one-third of the patients) or subjective
phantom sweating (in approx. a quarter of the patients) [31].
In conclusion, it must be stated that due to the potential complications
and the invasiveness of the procedure, sympathectomies are only to be
performed in extreme cases after extensive discussions with the patient.
Surgical removal of the axillary sweat glands, especially liposuction
as a safe and effective technique, can be recommended only if the conservative
measures fail.
Other procedures and supportive measures
Herbal substances such as sage tea (at least 1 litre per day) or sage
tablets (e.g. Sweatosan®) can occasionally be helpful
in both localised and generalised forms of hyperhidrosis. In any case,
adjuvant measures can be recommended: psychosomatic therapeutic measures
such as autogenic training or relaxation exercises as taught by Jacobsen.
In severe cases of localised or in cases of generalised hyperhidrosis,
an additional trial of systemic anticholinergic drugs can be made. Since
exocrine sweat glands are stimulated via cholinergic sympathetic fibres,
the stimulation of these glands can be blocked by anticholinergic drugs.
Bornaprine hydrochloride (Sormodren®) in particular is
often administered; this medication is commonly prescribed for Parkinson's
disease and specifically licensed for the diagnosis of hyperhidrosis in
Germany. In 80% of the cases treated, symptoms improve greatly within
2 weeks; however, its use is accompanied by undesirable adverse effects
such as dry mouth, accommodation disorders, constipation, tachycardia
or sleep disorders and other such restricting conditions listed in the
patient information leaflet that cause the patients concern [32-35].
Another potential means of treating generalised hyperhidrosis is Stanger
baths. These are hydroelectric baths that administer low-voltage direct
current and are used for such conditions as rheumatic diseases or nerve
pain. Like tap water iontophoresis, Stanger baths have been used successfully
for some of our patients with generalised idiopathic hyperhidrosis [5].
CONCLUSION
Treating localised hyperhidrosis is no longer an unmanageable problem.
For axillary hyperhidrosis, local application of aluminium chloride
may be considered to be the method of choice. The procedure can be easily
performed, has few adverse effects, is inexpensive and leads to the desired
success in over 90% of patients. If the condition does not improve, another
alternative is botulinum toxin; its efficacy for 3 to 9 months is an advantage.
Surgical procedures should be considered only if the conservative methods
fail. Liposuction seems to be an especially safe and effective therapy
of axillary hyperhidrosis.
The method of choice in treating palmoplantar hyperhidrosis is
tap-water iontophoresis. This has few adverse effects, is successful in
approx. 90% of all cases and can be continued for several years without
any difficulties. Adding anticholinergic substances to the water produces
a more rapid therapeutic success that lasts longer as well. If iontophoresis
does not lead to the desired results, botulinum toxin can be an effective
and promising alternative, although it must be noted that we have observed
several non-responders. Considering the fact that palmar and plantar hyperhidrosis
often appear concurrently and botulinum toxin has not yet been demonstrated
to be effective on the soles, the substance only seems to solve half of
the problem. Numerous reports about botulinum toxin in the lay press have
led to patients pressurising their physicians to prescribe botulinum treatment.
In each individual case, the indication must be critically considered
and alternatives must be assessed in order to prevent the application
of a "lifestyle drug" [36]. Surgical treatment, i.e. sympathectomy,
does bring about long-term resolution of the problem, but should only
be considered in justified and extreme cases because of the highly invasive
character of the procedure.
The overall situation in patients with a generalised tendency to
excessive sweating differs from that of localised cases. The use of
systemic anticholinergic medication is often limited because of the marked
adverse effects. We urgently appeal to the research-based pharmaceutical
industry to look for innovative medications that can be well tolerated.
In conclusion it can be stated that, in spite of interesting and promising
new alternatives, especially botulinum toxin, the tried-and-true procedures
such as tap water iontophoresis and aluminium chloride salts still have
a firm place in the treatment of hyperhidrosis.
Article accepted on 6/2/02
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