Compared Evaluation of Botulinum Toxin A and a Cosmetic Antiperspirant in the Treatment of Focal Axillary Hyperhidrosis

doi:10.4236/jcdsa.2013.33029

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Journal of Cosmetics, Dermatological Sciences and Applications, 2013, 3, 190-196

http://dx.doi.org/10.4236/jcdsa.2013.33029 Published Online September 2013 (http://www.scirp.org/journal/jcdsa)

Compared Evaluation of Botulinum Toxin A and a

Cosmetic Antiperspirant in the Treatment of Focal

Axillary Hyperhidrosis

Meike Streker, Stefanie Lübberding, Martina Kerscher

Cosmetic Science, Department of Chemistry, University of Hamburg, Hamburg, Germany.

Email: [email protected]

Received March 27th, 2013; revised April 30th, 2013; accepted May 8th, 2013

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

ABSTRACT

Background: Primary focal hyperhidrosis can significantly reduce quality of life. Therefore a lot of treatment options in

a range of conservative, physical and surgical techniques are available. Objective: To assess the efficacy of an antiper-

spirant containing aluminum chloride compared to a Botulinumtoxin A treatment for patients with primary focal hyper-

hidrosis. Methods and material: In this randomized, single-center, half-side trail, a clinical score was done by patients

and physician to evaluate the severity of hyperhidrosis. Gravimetric tests were performed to gather the amount of sweat

per unit of time. Furthermore the efficacy was determined using a four point questionnaire. Skin irritation was assessed

by measuring pH value and transepidermal water loss. Results: A total of 22 patients were enrolled. Two weeks after

baseline the hyperhidrosis level was significantly reduced (BTX-A: −92.9%, AL: 66.7%). In addition both treatment

options induced a significant reduction of sweat production (BTX-A: −80.8%, AL: 68.8%). Please change in: Patients

evaluated good resp, very good efficacy for both treatment options at day 28. pH value and TEWL never left physio-

logical range. Conclusion: Both botulinum toxin A treatment and an antiperspirant containing aluminum chloride in the

evaluated galenic formulation are an effective and safe treatment option for axillary focal hyperhidrosis.

Keywords: Hyperhidrosis; Aluminum Chloride; Botulinum Toxin; Antiperspirant; Sweating

1. Background

Primary focal hyperhidrosis is a disorder of excessive

eccrine sweating that mainly affects the axillae, palmae

and plantae. At least 3% of the population is affected

persuadably with a high number of unreported cases due

to an associated social phobia [1,2]. According to a study

by Strutton et al., both axillary and palmar hyperhidrosis

have the earliest average age of onset between 13 and 19

years [3]. The mean peak differs between 18 and 54

years. A genetic disposition is assumed, due to a high

percentage of positive family history.

Hyperhidrosis can lead to frustration, embarrassment,

a low self-esteem and finally may rest in social with-

drawal [4]. Patients who are affected by axillary hyper-

hidrosis must change their clothing several times a day or

choose only dark clothing which sweat points are not as

visible. In addition skin maceration and secondary skin

diseases such as fungal infection are promoted and bac-

terial colonization particularly leads to an unpleasant

odor that also can significantly reduce quality of life [5].

The treatment options for primary focal hyperhidrosis

involve a range of conservative, physical and surgical

techniques. Iontophoresis causes a blockage of the sweat

duct in the stratum corneum by directing a mild electrical

current. However long-term maintenance therapy is re-

quired to keep patients without symptoms [6,7]. Anticho-

linergic agents have substantial side effects such as dry-

ness of mouth, constipation and blurring of vision [8,9].

Surgical therapeutic options like endoscopic sympathec-

tomy are effective but have a main limitation in a great

potential of side effect and in a high incidence of mild to

severe compensatory hyperhidrosis [10].

Due to the limitation of the mentioned therapeutic op-

tions, the treatment of primary focal hyperhidrosis with

aluminum chloride or botulinum toxin A is the most

popularly therapeutic option. Both efficacies are proven

in several studies and the basic mechanism of actions has

been established [11-16].

Aluminum chloride in concentrations of 12.5% to 25%

reduces sweating by occluding the ducts of the eccrine

Compared Evaluation of Botulinum Toxin A and a Cosmetic Antiperspirant

in the Treatment of Focal Axillary Hyperhidrosis

191

sweat glands [11,13]. They diffuse into the sweat duct

and form complexes with mucopolysaccharides and

metal ions. Compared with the nocturnal activity of ec-

crine sweat glands antiperspirants including aluminum

chloride have to apply at night. In some cases the appli-

cation of aluminum chloride must be discontinued because

of skin irritations.

Intradermal injections of botulinum toxin A reversibly

block autonomic cholinergic nerve fibres. Acetylcholine

is no longer released and the sweat glands chemically

denervated [16]. Earlier studies have shown the efficacy

in reducing sweat production. In addition, since there is a

successful treatment of focal hyperhidrosis with botuli-

num toxin A in a few case reports, chemodenervation has

emerged as a safe and effective treatment in several

clinical trials [17-20]. Because of disappearing after 6

month, this treatment option is costly intensive.

The aim of the study was to compare a single treat-

ment of botulinum toxin A with topical treatments of an

antiperspirant, including aluminum chloride in a low dose

formation for patients with primary focal hyperhidrosis

using clinical scores and biophysical measurements.

2. Methods

2.1. Patients

This randomized, single-center half-side trail was con-

ducted between March and September 2011. It was ap-

proved by the local ethical committee of Hamburg, Ger-

many. Patients with primary focal hyperhidrosis on basis

of the history questionnaire according to Bechara and of

sweat production greater than 50 mg per minute were

included [21]. Moreover subjects who have not used an-

tiperspirant, iontophoresis in the last 6 month or had been

treated with botulinum toxin A in the last 12 month were

selected. Patients had to understand the requirements of

the study and sign an informed consent form. Skin dis-

eases such as atopic dermatitis or fungal infections in the

treatment area or known intolerability of aluminum salts

were represented exclusion criteria. In total we enrolled

22 female patients aged 32 to 60 years.

2.2. Study Design and Measurements

After enrollment, patients received therapy with 12.5%

aluminum chloride (Sweat-Off®, Sweat-off GmbH, Hü-

gelsheim, Germany) on one side and 50 U of onabotu-

linumtoxin A. on the contralateral side following a ran-

domization plan.

For the first two weeks the patients were asked to use

the topical antiperspirant every evening. After reduce of

the sweat production the patients have to apply the pre-

paration according to the sweating.

For each patient one vial of onabotulinumtoxin A

(BTX-A) was prepared according to the randomization

plan. One vial contained 100 U powders for solution

which was reconstituted with 4.0 ml sterile physiological

(0.9%) sodium chloride solution. After cleaning the

treating area local anesthetic was applied before injection.

All patients received 50 U of onabotulinumtoxin A into

10 to 15 intradermal injection points in an even distribu-

tion within the hyperhidrotic area which were previously

defined by Minor’s iodine-starch test.

The severity of hyperhidrosis was determined using a

clinical score by Wörle et al. [21]. This was performed

by investigator and patients themselves.

Gravimetric measurements were performed to evaluate

the amount of sweat per unit of time. After an acclima-

tion time of 30 min the amount of sweat was absorbed by

filter paper (Melitta, Minden, Germany) and subsequent-

ly weighed using an ultra-fine scale.

In addition a four point subject questionnaire was per-

formed to evaluate the efficacy; following the points: no

efficacy, minimal efficacy, good efficacy and very good

efficacy.

To evaluate the tolerability of the treatments, the pH

value was measured using a combination electrode with

the measurement and reference electrodes integrated in a

single probe with measurement of potential using elec-

trodes made of silver chloride or mercuric wire (Skin pH

Meter PH 900, Courage and Khazaka, Cologne, Ger-

many). In addition the transepidermal water loss (TEWL)

was measured by using a condenser-chamber method

(Aqua Flux Model AF200, London, UK) to evaluate the

effects of aluminum chloride and botulinum toxin A of

the skin barrier.

All measurements were performed at baseline, at day

14, at day 28, at day 84 and at day 168 after first treat-

ment (Table 1). Statistical analyses were performed with

SPSS®. The data were analyzed using the Kolmogorov-

Smirnow test and the paired t-test. Values of p ≤ 0.05

were considered significant.

3. Results

Data from 22 patients (mean age MV 47.8 ± 5.7) where

was eligible. Baseline characteristics like age, weight and

bodymass-index were not associated with sweat produc-

tion.

Both injection with 50 U onabotulinumtoxin A and the

treatment with an antiperspirant containing aluminum

chloride induced a significant reduction of sweat secre-

tion (Figure 1). At visit 2, 14 days after treatment resp.

after starting treatment the hyperhidrosis level decreased

treatment −92.9%, after topical aluminum chloride

−66.7%. At visit 3, 28 days the reduction in both thera-

peutic options was significant (BTX-A −100%; AL

Compared Evaluation of Botulinum Toxin A and a Cosmetic Antiperspirant

in the Treatment of Focal Axillary Hyperhidrosis

192

Table 1. Study overview.

Baseline V1 0 1 - 13 V2 14 15 - 27V3 28 29 - 84V4 84 85 - 167V5 168

enrollment X - - - - - - - - -

injection - X - - - - - - - -

acclimazation of 30 min X X - X - X - X - X

apply of antiperspirant - X X - X - X - X -

gravimetric measurements X X - X - X - X - X

clinical score - X - X - X - X - X

pH-value - X - X - X - X - X

TEWL - X - X - X - X - X

Figure 1. Degree of hyperhidrosis compared to baseline (p < 0.05).

−73.3%; p ≤ 0.05). 6 months after injection the BTX-A

treated side was till significant reduced. Furthermore the

aluminum chloride treated side was also still decreased.

The mean rates of sweat production at baseline were

165 mg/5 min in the axillae assigned to the treatment

with botulinum toxin A and 184 mg/5 min in the axillae

assigned to the treatment with aluminum chloride. The

sweat production of both sides decreased significantly

over the whole study period (Figure 2). Two weeks after

initial treatment, the mean rates of sweat production were

31 mg/5 min in the axillae treated with botulinum toxin

A and 57 mg/5 min in the axillae treated with aluminum

chloride (BTX-A −80.8%; AL −68.8%; p < 0.05). 168

days after baseline the sweat production were 65 mg/5

min in the axillae treated with BTX-A and 57 mg/5 min

in the aluminum chloride treated side (BTX-A −60.4%;

AL −68.9%; p < 0.05).

Patients evaluated for both products 28 days after

baseline good efficacy resp. very good efficacy. 6 mon-

ths after baseline patients rated the BTX-A treated side

between minimal to good efficacy and the antiperspirant

treated side as minimal efficacy (Figure 3).

The evaluation of skin surface pH revealed a reduction

for both test products at all follow-up visits. During the

use of the antiperspirant the pH-value decreased for 13%.

After injection of BTX-A the pH-value decreased for 7%,

6 months after baseline (Figure 4). Both reductions were

not statistically significant.

Compared Evaluation of Botulinum Toxin A and a Cosmetic Antiperspirant

in the Treatment of Focal Axillary Hyperhidrosis

193

Figure 2. Gravimetric values compared to baseline (p < 0.05).

Figure 3. Improvement of hyperhidrosis; 0 = no efficacy; 1 = minimal efficacy; 2 = good efficacy; 3 = very good efficacy.

The TEWL values increased in the axillae assigned to

the treatment with BTX-A over the study period. The

mean increase in the TEWL value two weeks after base-

line with BTX-A was 46.7%, after starting treatment

with aluminum chloride it was 12.8%. 84 days after base-

line the increase in the BTX-A treated side was −32.7%.

The axillae assigned to the aluminum chloride treated

side increased by 12.3%. At the last follow-up visit, 168

days after baseline the values after treatment with BTX-

A were decreased by 28.9%. The TEWL values after

treatment with aluminum chloride increased by 53.1%

(Figure 5).

Compared Evaluation of Botulinum Toxin A and a Cosmetic Antiperspirant

in the Treatment of Focal Axillary Hyperhidrosis

194

Figure 4. pH value compared to baseline.

Figure 5. Transepidermal water loss compared to baseline.

During the whole study period there were no major

adverse events. 6 patients recorded a mild to moderate

irritation in skin after die first to third applications of the

antiperspirant. There were no adverse events associated

with the treatment with botulinum toxin A.

4. Discussion

Hyperhidrosis is a common pathological condition which

can have a profound effect on patient’s behavior. Ex-

cessive sweating can inhibit social life and therefore de-

crease patient’s quality of life. Further, an excessive

sweating can induce skin maceration and causes second-

dary microbial infections. Treating primary focal hyper-

hidrosis with aluminum chloride often is the first treat-

ment therapy option in dermatology. Major limitations of

aluminum chloride are stinging sensations and burning

Compared Evaluation of Botulinum Toxin A and a Cosmetic Antiperspirant

in the Treatment of Focal Axillary Hyperhidrosis

195

after application. Moreover skin irritation can be a cumu-

lative side effect of long-term treatment.

Another effective treatment modality is the intrader-

mal injection of botulinum toxin A which has been stud-

ied in numerous clinical trials [15,17-20]. It has demon-

strated a sustained relief of symptoms with a good safety

profile in open-label studies of the treatment of axillary

hyperhidrosis. Naumann et al. demonstrated in a double-

blind, placebo-controlled trial a 93.8% response rate after

a single treatment with 50 U total onabotulinumtoxin A

and a safety profile that was comparable to that of pla-

cebo injections [19]. In addition Heckmann et al. showed

an efficacy of onabotulinumtoxin A in a placebo-con-

trolled trial [15].

Therefore we designed an inter-individual comparison

of onabotulinumtoxin A and a cosmetic antiperspirant

containing aluminum chloride in a panel of 22 female

patients suffering from hyperhidrosis as objected by gra-

vimetry.

Regarding skin physiology both treatments were well

tolerated. While TEWL decreased during both treatment

modalities (BTX-A: 5.9 to 5.54; AL: 5.97 to 5.17), skin

pH never left the physiological range.

Our study confirms and extends the results of previous

studies regarding the gravimetry, the rate of sweat pro-

duction and the tolerability [15-17,20-24].

Further to a previous study which compared botulinum

toxin A with a topical 20% aluminum chloride for the

treatment of focal axillary hyperhidrosis our data confirm

that both products provide efficacy treatment option al-

though our data are different concerning the tolerability

of the antiperspirant [25]. According to Flanagan et al.

the aluminum chloride treatment was well tolerated and

effective only in the minority of the patients. This might

be due to the lower dose of 12, 5% aluminum chloride.

However, while Flanagan et al. demonstrated a clean

superiority of onabotulinumtoxin A and a high risk for

skin irritation after treatment with aluminum chloride,

our data did not reveal any significant differences in ef-

ficacy and tolerability between both treatments. This

might be due to the special developed of non-alcoholic

galinic formation and the low aluminum chloride con-

centration of the Sweat-Off® lotion.

5. Conclusion

Treatments of axillary focal hyperhidrosis with BTX-A

or an antiperspirant containing aluminum chloride in the

evaluated galenic formulation and low dose concentra-

tion are effective and safe options. Both treatment mo-

dalities significantly reduced the degree of hyperhidrosis.

Patients rated both options as an effective treatment.

However, patients with sensitive skin treatments with on-

abotulinumtoxin A seem to have a better therapeutic in-

dex while topical treatment with aluminum chloride de-

monstrates a better economic impact.

REFERENCES

[1] F. G. Bechara, Current Treatment of Focal Hyperhidro-

sis,” Surgical Approaches Hautarzt, Vol. 60, No. 7, 2009,

pp. 538-545. doi:10.1007/s00105-009-1717-1

[2] F. G. Bechara, T. Gambichler, A. Bader, M. Sand, P.

Altmeyer and K. Hoffmann, “Assessment of Quality of

Life in Patients with Primary Axillary Hyperhidrosis

Before and After Suction-Curettage,” Journal of the

American Academy of Dermatology, Vol. 57, No. 2, 2007,

pp. 207-212. doi:10.1016/j.jaad.2007.01.035

[3] D. R. Strutton, J. W. Kowalski, D. A. Glaser and P. E.

Stang, “US Prevalence of Hyperhidrosis and Impact on

Individuals with Axillary Hyperhidrosis: Results from a

National Survey,” Journal of the American Academy of

Dermatology, Vol. 51, No. 2, 2004, pp. 241-248.

doi:10.1016/j.jaad.2003.12.040

[4] R. Ramos and J. Moya, “Primary Hyperhidrosis and An-

xiety: A Prospective Preoperative Survey of 158 Pati-

ents,” Archivos de Bronconeumología, Vol. 41, No. 2,

2005, pp. 88-92.

[5] M. Amir, A. Arish and Y. Weinstein, “Impairment in

Quality of Life among Patients Seeking Surgery for

Hyperhidrosis: Preliminary Results,” Israel Journal of

Psychiatry & Related Sciences, Vol. 37, No. 1, 2000, pp.

25-31.

[6] W. B. Shelley and H. J. Hurley Jr., “Studies on Topical

Antiperspirant Control of Axillary Hyperhidrosis,” Acta

Dermato-Venereologica, Vol. 55, No. 4, 1975, pp. 241-

260.

[7] H. Bouman, “The Treatment of Hyperhidrosis of Hands

and Feet with Constant Current,” American Journal of

Physical Medicine & Rehabilitation, Vol. 31, No. 3, 1952,

pp. 158-169.

[8] B. Przybilla, U. Schwab, E. Hölzle and J. Ring, “Contact

Sensitization to an Antiperspirant with the Active Ingre-

dient Propantheline Bromide,” Hautarzt, Vol. 34, No. 9,

1983, pp. 459-462.

[9] M. Hund, R. Sinkgraven and B. Rzany, “Randomized,

Placebo-Controlled, Double Blind Clinical Trial for the

Evaluation of the Efficacy and Safety of Oral Methanthe-

liniumbromide (Vagantin) in the Treatment of Focal

Hyperhidrosis,” Journal der Deutschen Dermatologis-

chen Gesellschaft, Vol. 2, No. 5, 2004, pp. 343-349.

doi:10.1046/j.1439-0353.2004.04765.x

[10] K. T. Moran and M. P. Brady, “Surgical Management of

Primary Hyperhidrosis,” British Journal of Surgery, Vol.

78, No. 3, 1991, pp. 279-283. doi:10.1002/bjs.1800780306

[11] E. Hölzle and O. Braun-Falco, “Structural Alteractions of

Axillary Eccrine Glands in Hyperhidrosis Following Long-

Term Treatment with Aluminium Chloride Hexahydrate,”

British Journal of Dermatology, Vol. 110, No. 4, 1984,

pp. 399-403. doi:10.1111/j.1365-2133.1984.tb04653.x

[12] E. Hölzle, “Topical Pharmacological Treatment,” Current

Compared Evaluation of Botulinum Toxin A and a Cosmetic Antiperspirant

in the Treatment of Focal Axillary Hyperhidrosis

196

Problems in Dermatology, Vol. 30, 2002, pp. 30-43.

doi:10.1159/000060693

[13] M. Streker, T. Reuther, S. Verst and M. Kerscher, “Axi-

llary Hyperhidrosis—Efficacy and Tolerability of an Alu-

minium Chloride Antiperspirant,” Hautarzt, Vol. 61, No.

2, 2010, pp. 139-144. doi:10.1007/s00105-009-1841-y

[14] L. Baumann, A. Slezinger, M. Halem, J. Vujevich, L. K.

Martin, L. Black and J. Bryde, “Pilot Study of the Safety

and Efficacy of Myobloc® (Botulinum Toxin Type B) for

Treatment of Axillary Hyperhidrosis,” International Jour-

nal of Dermatology, Vol. 44, No. 5, 2005, pp. 418-424.

doi:10.1111/j.1365-4632.2004.02531.x

[15] M. Heckmann, A. O. Ceballos-Baumann and G. Plewig,

“Botulinum Toxin A for Axillary Hyperhidrosis (Exces-

sive Sweating),” New England Journal of Medicine, Vol.

344, 2001, pp. 488-493.

doi:10.1056/NEJM200102153440704

[16] B. Sommer and G. Sattler, “Botulinum Toxin in der Aes-

thetischen Medizin Blackwell Wissenschafts-Verlag,”

Wien, Berlin, 2001.

[17] N. J. Lowe, D. A. Glaser, N. Eadie, S. Daggett, J. W. Ko-

walski and P. Y. Lai, “North American Botox in Primary

Axillary Hyperhidrosis Clinical Study Group. Botulinum

Toxin Type A in the Treatment of Primary Axillary Hy-

perhidrosis: A 52-Week Multicenter Double-Blind, Ran-

domized, Placebo-Controlled Study of Efficacy and Safe-

ty,” Journal of the American Academy of Dermatology,

Vol. 56, No. 4, 2007, pp. 604-611.

doi:10.1016/j.jaad.2007.01.009

[18] D. Dressler, “Comparing Botox® and Xeomin® for Axil-

lar Hyperhidrosis,” Journal of Neural Transmission, Vol.

117, No. 3, 2010, pp. 317-319.

doi:10.1007/s00702-010-0372-0

[19] M. Naumann and N. J. Lowe, “Botulinum Toxin Type A

in the Treatment of Bilateral Primary Axillary Hyperhi-

drosis: Randomised, Parallel Group, Double Blind, Place-

bo Controlled Trial,” BMJ, Vol. 323, No. 15, 2001, pp.

596-599. doi:10.1136/bmj.323.7313.596

[20] K. O. Bushara, D. M. Park, J. C. Jones and H. S. Schutta,

“Botulinum Toxin—A Possible New Treatment for Axil-

lary Hyperhidrosis,” Clinical and Experimental Dermato-

logy, Vol. 21, No. 4, 1996, pp. 276-278.

doi:10.1111/j.1365-2230.1996.tb00093.x

[21] B. Wörle, S. Rapprich and M. Heckmann, “Definition and

Treatment of Primary Hyperhidrosis,” Journal der Deu-

tschen Dermatologischen Gesellschaft, Vol. 5, No. 7,

2007, pp. 625-628.

doi:10.1111/j.1610-0387.2007.06409.x

[22] N. Skroza, N. Bernardini, G. La Torre, G. La Viola and C.

Potenza, “Correlation between Dermatology Life Quality

Index and Minor Test and Differences in Their Levels

over Time in Patients with Axillary Hyperhidrosis Trea-

ted with Botulinum Toxin Type A,” Acta Dermatove-

nerologica Croatica, Vol. 19, No. 1, 2011, pp. 16-20.

[23] M. Naumann, N. J. Lowe, C. J. Kumar, et al., “Botulinum

Toxin Type A Is a Safe and Effective Treatment for

Axillary Hyperhidrosis over 16 Months: A Prospective

Study,” Archives of Dermatology, Vol, 139, No. 6, 2003,

pp. 731-736. doi:10.1001/archderm.139.6.731

[24] M. Heckmann and G. Plewig, “Hyperhidrosis Study

Group. Low-Dose Efficacy of Botulinum Toxin A for

Axillary Hyperhidrosis: A Randomised, Side-by-Side,

Open-Label Study,” Archives of Dermatology, Vol. 141,

No. 10, 2001, pp. 1255-1259.

doi:10.1001/archderm.141.10.1255

[25] K. H. Flanagan, R. King and D. A. Glaser, “Botulinum

Toxin Type a Versus Topical 20% Aluminum Chloride

for the Treatment of Moderate to Severe Primary Focal

Axillary Hyperhidrosis,” Journal of Drugs in Dermatolo-

gy, Vol. 7, No. 3, 2008, pp. 221-227.