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Research Letter |

Increasing the Field Effects of Similar Doses of Clostridium botulinum Type A Toxin–Hemagglutinin Complex in the Treatment of Compensatory Hyperhidrosis FREE

Doris Maria Hexsel, MD; Mariana Soirefmann, MD; Ticiana C. Rodrigues, MD; Débora Zechmeister do Prado, PHARM
Arch Dermatol. 2009;145(7):837-840. doi:10.1001/archdermatol.2009.128.
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Published online

Hyperhidrosis (HH) is characterized by excessive sweating, usually exceeding thermoregulatory needs.1 Medical and surgical treatments can be used, depending on the type, location, and severity of the HH. Thoracic sympathectomy is indicated for selected cases of severe palmar HH,2 but the procedure may result in troublesome compensatory HH (CHH).3

Injections of botulinum toxin type A can temporarily interrupt sweating, and this new therapeutic option has emerged as a treatment for many forms of focal HH, including CHH.3 Because the diameter of the field effects (FEs) resulting from the injection of botulinum toxin type A is about 2 cm, a number of injections are needed to treat different forms of HH.

Herein, we describe a series of 3 women with CHH of the trunk occurring after thoracic sympathectomy. All 3 patients were treated with 5 U of Clostridium botulinum type A toxin–hemagglutinin complex (hereinafter “Dysport”; Ipsen Limited, Slough, England) at different dilutions and injected at different depths.

Three vials of Dysport, 500 U, were diluted with 2 mL, 4 mL, and 6 mL of 0.9% isotonic sodium chloride (saline), resulting in 3 separate preparations of different drug concentrations. Three women with CHH received 5-U injections from each vial in 3 vertical points on their backs corresponding to 3 different depths (2 mm, 3 mm, and 4 mm). The injection sites were numbered 1 to 9. A tenth injection site on the right side of the lumbar region received 5 U of Dysport at the 6-mL dilution and at an injection depth of 4 mm, followed by 60 seconds of local massage. To ensure that the different concentrations were injected at the specific depths, the cut cap of the needle was used as a guide (Figure 1). Evaluation of the FEs using the Minor test were performed 7 and 30 days after the injections.

Place holder to copy figure label and caption
Figure 1.

Injection equipment and technique. A, The cut caps of the needles were used as a guide to control the 3 different injection depths (2, 3, and 4 mm). B, Injection technique and points of injections are pictured.

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Measurements of the vertical diameters (VDs) and horizontal diameters (HDs) of the FEs obtained by the Minor test were taken at 7 and 30 days after injections using Mirror imaging software, version 7.0.2 (Canfield Scientific Inc, Fairfield, New Jersey).

Field effects 1, 2, and 3 were located on the left side of the patients' backs; FEs 4, 5, and 6 on the midline; and FEs 7, 8, 9, and 10 on the right side. The mean (SD) HDs and VDs are shown in Figure 2 and listed in Table 1 and Table 2.

Place holder to copy figure label and caption
Figure 2.

Numbered field effects on 3 patients. Numbered field effects on 3 patients 7 (A) and 30 (B) days after Dysport injection. (Dysport is the proprietary name for Clostridium botulinum type A toxin–hemagglutinin complex used by the manufacturer, Ipsen Limited, Slough, England.) In all cases, injection sites 1, 2, and 3 are located in the first vertical column of the injection site grid (left side of the back); 4, 5, and 6 in the second vertical column (midline); and 7, 8, and 9 in the third vertical column (right side of the back). Injection site 10, not visible in the first patient at day 7, was treated in all cases with a 1-minute postinjection massage.

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Table Graphic Jump LocationTable 1. Horizontal Diameters of All Field Effects
Table Graphic Jump LocationTable 2. Vertical Diameters of All Field Effects

Table 3 lists the mean HDs and VDs of the FEs resulting from first and third vertical columns of injections in the injection grids on the patients’ backs, excluding those in the midlines. Table 4 lists the mean HDs and VDs of the FEs resulting from isovolumetric injections at the same concentration and depth with and without postinjection massage.

Table Graphic Jump LocationTable 3. Horizontal and Vertical Diameters of Selected Field Effectsa
Table Graphic Jump LocationTable 4. Horizontal and Vertical Diameters of Field Effects With and Without Postinjection Massagea

Small doses of Dysport significantly reduce the sweating around the injected points, visible by the Minor test. In the present study, smaller FEs were found in the midline, corresponding to the 0.04-mL concentration injected in 3 different depths and coincidentally the area of increased sweating. These findings suggest that the type of skin, location, and amount of previous sweating may play a more important role in the size of the Dysport FE than depth and concentration of the product. On the other hand, cases of more intense sweating might need higher doses to achieve similar FE. This could indicate a competitive mechanism of action of the toxin in the release of acetylcholine at the neuromuscular junction.

The shapes of the FEs were round or oval, and the HDs were larger than the VDs. The differences in the FE measurements also suggest that other factors might affect the FE.

Table 3 lists the results from left and right columns of the injection site grid. The mean HDs and VDs of the HAs were larger at 7 and 30 days, but the larger sizes were not related to progressively deeper injections. After 30 days, the field effects at the sites of 3- and 4-mm depth injections had larger mean HDs than sites of the 2-mm injections. By volume injected, the HDs and VDs of the FEs resulting from more diluted product (0.06 mL) were larger at 7 and 30 days, the 1 exception being the mean VD of FE 9 at 30 days. However, considering the interindividual variations, the differences according to the different dilutions can be considered clinically irrelevant.

Table 4 lists the results of an FE 9 and 10 comparison. Injection at the tenth injection site was followed by 1 minute of local massage and ultimately resulted in FEs with smaller HDs and VDs.

Hsu and colleagues4 also observed that botulinum toxin type A injection diluted at higher volume resulted in greater FE and larger areas of effects on the forehead. However, a recent study5 showed no differences with different dilutions (100.0, 33.3, 20.0, or 10.0 U/mL) in the glabella.5 New studies with higher numbers of patients are needed to confirm these preliminary results and perhaps demonstrate changes in techniques to increase the FE of botulinum toxin type A and allow treatments with fewer injections.

ARTICLE INFORMATION

Correspondence: Dr Hexsel, Brazilian Center for Studies in Dermatology, 782 Dr Timoteo, Porto Alegre RS 90570040, Brazil (dohexsel@terra.com.br).

Author Contributions:Study concept and design: Hexsel and Soirefmann. Acquisition of data: Soirefmann. Analysis and interpretation of data: Hexsel, Rodrigues, and Zechmeister do Prado. Drafting of the manuscript: Hexsel, Soirefmann, Rodrigues, and Zechmeister do Prado. Critical revision of the manuscript for important intellectual content: Hexsel, Soirefmann, Rodrigues, and Zechmeister do Prado. Statistical analysis: Rodrigues. Administrative, technical, and material support: Hexsel. Study supervision: Hexsel.

Financial Disclosure: None reported.

Previous Presentation: This article was presented as an abstract to an exhibit poster at the 67th American Academy of Dermatology Meeting; March 6-10, 2009; San Francisco, California.

Efthymiou  CAThorpe  JA Compensatory hyperhidrosis: a consequence of truncal sympathectomy treated by video-assisted application of botulinum toxin and reoperation. Eur J Cardiothorac Surg 2008;33 (6) 1157- 1158
PubMed Link to Article
Rodríguez  PMFreixinet  JLHussein  M  et al.  Side effects, complications and outcome of thoracoscopic sympathectomy for palmar and axillary hyperhidrosis in 406 patients. Eur J Cardiothorac Surg 2008;34 (3) 514- 519
PubMed Link to Article
Naumann  MFlachenecker  PBröcker  EBToyka  KVReiners  K Botulinum toxin for palmar hyperhidrosis. Lancet 1997;349 (9047) 252
PubMed Link to Article
Hsu  TSJDover  JSArndt  KA Effect of volume and concentration on the diffusion of botulinum exotoxin A. Arch Dermatol 2004;140 (11) 1351- 1354
PubMed Link to Article
Carruthers  ACarruthers  JCohen  J Dilution volume of botulinum toxin type A for the treatment of glabellar rhythides: does it matter? Dermatol Surg 2007;33 (1 Spec No.) S97- S104
PubMed Link to Article

Figures

Place holder to copy figure label and caption
Figure 1.

Injection equipment and technique. A, The cut caps of the needles were used as a guide to control the 3 different injection depths (2, 3, and 4 mm). B, Injection technique and points of injections are pictured.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

Numbered field effects on 3 patients. Numbered field effects on 3 patients 7 (A) and 30 (B) days after Dysport injection. (Dysport is the proprietary name for Clostridium botulinum type A toxin–hemagglutinin complex used by the manufacturer, Ipsen Limited, Slough, England.) In all cases, injection sites 1, 2, and 3 are located in the first vertical column of the injection site grid (left side of the back); 4, 5, and 6 in the second vertical column (midline); and 7, 8, and 9 in the third vertical column (right side of the back). Injection site 10, not visible in the first patient at day 7, was treated in all cases with a 1-minute postinjection massage.

Graphic Jump Location

Tables

Table Graphic Jump LocationTable 1. Horizontal Diameters of All Field Effects
Table Graphic Jump LocationTable 2. Vertical Diameters of All Field Effects
Table Graphic Jump LocationTable 3. Horizontal and Vertical Diameters of Selected Field Effectsa
Table Graphic Jump LocationTable 4. Horizontal and Vertical Diameters of Field Effects With and Without Postinjection Massagea

References

Efthymiou  CAThorpe  JA Compensatory hyperhidrosis: a consequence of truncal sympathectomy treated by video-assisted application of botulinum toxin and reoperation. Eur J Cardiothorac Surg 2008;33 (6) 1157- 1158
PubMed Link to Article
Rodríguez  PMFreixinet  JLHussein  M  et al.  Side effects, complications and outcome of thoracoscopic sympathectomy for palmar and axillary hyperhidrosis in 406 patients. Eur J Cardiothorac Surg 2008;34 (3) 514- 519
PubMed Link to Article
Naumann  MFlachenecker  PBröcker  EBToyka  KVReiners  K Botulinum toxin for palmar hyperhidrosis. Lancet 1997;349 (9047) 252
PubMed Link to Article
Hsu  TSJDover  JSArndt  KA Effect of volume and concentration on the diffusion of botulinum exotoxin A. Arch Dermatol 2004;140 (11) 1351- 1354
PubMed Link to Article
Carruthers  ACarruthers  JCohen  J Dilution volume of botulinum toxin type A for the treatment of glabellar rhythides: does it matter? Dermatol Surg 2007;33 (1 Spec No.) S97- S104
PubMed Link to Article

Correspondence

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