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Botulinum toxin therapy for palmar hyperhidrosis
THERAPY Botulinum toxin therapy for palmar hyperhidrosis W. B. Shelley, MD, PhD,a N. Y. Talanin, MD, PhD,b and E. D. Shelley, MDa Toledo, Ohio Background: Severe palmar hyperhidrosis is a chronic disease, resistant to conventional therapy. Botulinum toxin inhibits sweat production by blocking release of acetylcholine from presynaptic membranes. Objective: Our purpose was to evaluate the short- and long-term effectiveness of botulinum toxin therapy in treatment of palmar hyperhidrosis. Methods: Four patients with severe palmar hyperhidrosis were treated with subepidermal injections of botulinum toxin. Fifty injections, 2 mouse units each, were used in each palm. Regional nerve blocks of the median and ulnar nerves were performed before the procedure. Patients were observed for 12 months after treatment. Results: Botulinum toxin injections significantly reduced sweat production in the treated areas of the palms. Anhidrosis lasted for 12 months in one patient, 7 months in two patients, and 4 months in one patient. Mild weakness of the thumb lasting 3 weeks occurred in one patient. No other side effects were observed. Conclusion: Botulinum toxin provides an effective, safe, and long-lasting alternative therapeutic modality for treatment of severe palmar hyperhidrosis. Additional studies are needed for optimization of the technique. (J Am Acad Dermatol 1998;38:227-9.)
Palmar hyperhidrosis can cause serious social, psychologic, and occupational problems. Conservative treatment, whether systemic or topical, is not always effective in severe cases.1,2 Endoscopic transthoracic sympathectomy provides a permanent solution, but complications include pneumothorax and the sequelae of general anesthesia.1,3,4 Botulinum toxin therapy has been recently used as a successful treatment of localized hyperhidrosis.5 It irreversibly blocks release of acetylcholine from presynaptic membranes and helps a variety of conditions including blepharospasm, strabismus, focal dystonias, spasmodic dysphonia, and achalasia.6 Two studies described the effectiveness of local injections of botulinum toxin in 12 patients with palmar hyperhidrosis.7,8 In all of these patients excessive sweating was abolished 1 week after treatment and lasted up to 14 weeks. We describe our experience with botulinum toxin therapy in four patients with palmar hyperhidrosis. From the Division of Dermatologya and the Department of Medicine,b Medical College of Ohio. Reprint requests: W. B. Shelley, MD, Division of Dermatology, Department of Medicine, Medical College of Ohio, P.O. Box 10008, Toledo, OH 43699-0008. Copyright © 1998 by the American Academy of Dermatology, Inc. 0190-9622/98/$5.00 + 0 16/1/87478
Fig. 1. Palm shows 40 sites of botulinum toxin injections spaced 1.0 cm apart. The two oval areas indicate where first 10 test injections of botulinum toxin were given 3 weeks earlier with resultant anhidrosis (see Fig. 2).
227
Journal of the American Academy of Dermatology February 1998
228 Shelley, Talanin, and Shelley
A
B Fig. 2. Palmar sweating documented by "iodine-paper" test. A, Hyperhidrosis before treatment. B, Focal anhidrosis 1 week after 10 subepidermal injections of botulinum toxin in two bands on right palm.
PATIENTS AND METHODS Four female patients, 14 to 34 years of age, participated in this study after appropriate ethical approval was obtained. They all had palmar hyperhidrosis since childhood and were dissatisfied with conventional treatments. Hyperhidrotic areas on both palms were evaluated by the "iodine-paper" test before and after botulinum toxin treatment.9 Thirty minutes before each treatment ulnar and median nerve blocks were performed at wrist level with 1% lidocaine.10 Botulinum toxin type A (Botox, Allergan, Irvine, Calif.; 100 mouse units [MU]/5.0 ml of 0.9% sterile normal saline without a preservative) was injected into the palms. Initially, botulinum toxin was injected subepidermally on one palm into 10 different sites (2 MU/0.1 ml per site) on one palm. Three weeks later an additional 40 sites on the same palm were treated. Four weeks later the second palm was similarly treated with 50 injections. Subepidermal injections with a 30-gauge needle were spaced 1.0 cm apart (Fig. 1). Patients were then observed for 12 months with serial "iodine-paper" records. RESULTS
In each of the four patients hyperhidrosis
improved after 1 week, with anhidrotic areas at the sites of botulinum toxin injections (Fig. 2). Each injection produced an area of anhidrosis on the palm measuring about 1.2 cm in diameter. To treat one entire palmar surface, approximately 50 injections were required. All patients reported significant improvement and were pleased with the results. Follow-up visits showed that the reduction in sweat production could last as long as 12 months. In patient 4 subjective improvement started to decline 4 months after treatment, although the "iodine-paper" test still demonstrated decreased sweat production compared with baseline. In patients 1 and 3 the decrease in sweat production lasted for 7 months. Patient 2 still had cessation of sweating after 12 months. The only side effect we encountered was mild thumb weakness in patient 2. That disappeared within 3 weeks. Among other complaints expressed by the patients the most common was continuation of sweating in areas that had not been treated, such as the sides of the fingers and the outer aspect of the thenar eminence.
Journal of the American Academy of Dermatology Volume 38, Number 2, Part 1
DISCUSSION
Our study confirmed the effectiveness of botulinum toxin type A in reducing palmar hyperhidrosis.7,8 Earlier studies had reported pain during injections as one of the main disadvantages of treatment.8 This is probably due to the abundance of sensory receptors in the palms because botulinum toxin injections into the axillary areas and the backs of the hands are relatively painless.11 Because the "free nerve-endings" responsible for pain sensation occur in the papillary dermis and epidermis, subcutaneous injections of botulinum toxin would be less painful.8,12 Nevertheless, to deliver botulinum toxin as close to the sweat glands as possible, we considered subepidermal injections more appropriate than subcutaneous, although they may be more painful. Nerve block provided sufficient anesthesia in our patients to make botulinum toxin injections significantly less painful. Neural blockade allowed us to inject botulinum toxin superficially into the fingertips, overcoming the potential hazard of injecting the toxin into an extensive capillary network.8 To avoid weakness of the small muscles of the hand, the only documented complication of botulinum toxin,7,8 we tried to inject the toxin as superficially as possible. Nevertheless, one of our patients reported thumb weakness after treatment. Presumably, this might be avoided by reducing the total dose of toxin, as recommended previously.8 Our study shows that the effect of botulinum toxin therapy on palmar hyperhidrosis can last as long as 12 months. Earlier studies reported therapeutic effects lasting at least 14 weeks, the length of the observation period.7,8 The treatment effects have persisted for 8 months in axillary hyperhidrosis and for up to 13 months in gustatory sweating.11,13 In healthy volunteers the anhidrotic effect of botulinum toxin injections lasted for 4 months in the palm and 11 months on the dorsum of the hands.13,14
Shelley, Talanin, and Shelley 229 We used botulinum toxin in 20 MU/ml concentration, delivering 2 MU per each injection site. This dose was similar to the one used in the treatment of gustatory sweating in Frey's syndrome (2.5 MU/ml), the only report on use of this preparation in sweating disorders available at the time we started our study.13 Our results show that superficial botulinum toxin injections are effective therapy for palmar hyperhidrosis. It is comparatively safe and gives long-lasting relief of sweating. REFERENCES 1. Claes G, Drott C. Hyperhidrosis. Lancet 1994;1:247-8. 2. Shelley WB, Shelley ED. Advanced dermatologic therapy. Philadelphia: WB Saunders; 1987. p. 260-6. 3. Quinn AC, Edwards RE, Newman PJ, Fawcett WJ. Complications of endoscopic sympathectomy. BMJ 1993;306: 1752. 4. Drott C, Gothberg G, Claes G. Endoscopic transthoracic sympathectomy: an efficient and safe method for the treatment of hyperhidrosis. J Am Acad Dermatol 1995;33:78-81. 5. Bushara KO, Park DM. Botulinum toxin and sweating. J Neurol Neurosurg Psychiatry 1994;57:1437-8. 6. Simpson LL. Botulinum toxin: a deadly poison sheds its negative image. Ann Int Med 1996;125:616-7. 7. Naumann M, Flachenecker P, Brocker EB, Toyka KV, Reiners K. Botulinum toxin for palmar hyperhidrosis. Lancet 1997;1:252. 8. Schnider P, Binder M, Auff E, Kittler H, Berger T, Wolff K. Double-blind trial of botulinum A toxin for the treatment of focal hyperhidrosis of the palms. Br J Dermatol 1997;136:548-52. 9. Champion RH. Disorders of sweat glands. In: Champion RH, Burton JL, Ebling FJG, editors. Textbook of dermatology; vol. 3. 5th ed. Oxford: Blackwell Scientific; 1992. p. 1745-62. 10. Colins VJ, Rovenstine EA. Fundamentals of nerve blocking. Philadelphia: Lea & Febiger; 1960. p. 253-8. 11. Bushara KO, Park DM, Jones JC, Schutta HS. Botulinum toxin: a possible new treatment for axillary hyperhidrosis. Clin Exp Dermatol 1996;21:276-8. 12. Weddell G, Palmer E, Pallie W. Nerve endings in mammalian skin. Biol Rev Camb Phil Soc 1955;30:159-93. 13. Drobik C, Laskawi R, Schwab S. Die therapie des Freysyndroms mit botulinumtoxin A. HNO 1995;43:644-8. 14. Schnider P, Binder M, Berger T, Auff E. Botulinum toxin injections in focal hyperhidrosis. Br J Dermatol 1996; 134:1160-1.
Palmar hyperhidrosis can cause serious social, psychologic, and occupational problems. Conservative treatment, whether systemic or topical, is not always effective in severe cases.1,2 Endoscopic transthoracic sympathectomy provides a permanent solution, but complications include pneumothorax and the sequelae of general anesthesia.1,3,4 Botulinum toxin therapy has been recently used as a successful treatment of localized hyperhidrosis.5 It irreversibly blocks release of acetylcholine from presynaptic membranes and helps a variety of conditions including blepharospasm, strabismus, focal dystonias, spasmodic dysphonia, and achalasia.6 Two studies described the effectiveness of local injections of botulinum toxin in 12 patients with palmar hyperhidrosis.7,8 In all of these patients excessive sweating was abolished 1 week after treatment and lasted up to 14 weeks. We describe our experience with botulinum toxin therapy in four patients with palmar hyperhidrosis. From the Division of Dermatologya and the Department of Medicine,b Medical College of Ohio. Reprint requests: W. B. Shelley, MD, Division of Dermatology, Department of Medicine, Medical College of Ohio, P.O. Box 10008, Toledo, OH 43699-0008. Copyright © 1998 by the American Academy of Dermatology, Inc. 0190-9622/98/$5.00 + 0 16/1/87478
Fig. 1. Palm shows 40 sites of botulinum toxin injections spaced 1.0 cm apart. The two oval areas indicate where first 10 test injections of botulinum toxin were given 3 weeks earlier with resultant anhidrosis (see Fig. 2).
227
Journal of the American Academy of Dermatology February 1998
228 Shelley, Talanin, and Shelley
A
B Fig. 2. Palmar sweating documented by "iodine-paper" test. A, Hyperhidrosis before treatment. B, Focal anhidrosis 1 week after 10 subepidermal injections of botulinum toxin in two bands on right palm.
PATIENTS AND METHODS Four female patients, 14 to 34 years of age, participated in this study after appropriate ethical approval was obtained. They all had palmar hyperhidrosis since childhood and were dissatisfied with conventional treatments. Hyperhidrotic areas on both palms were evaluated by the "iodine-paper" test before and after botulinum toxin treatment.9 Thirty minutes before each treatment ulnar and median nerve blocks were performed at wrist level with 1% lidocaine.10 Botulinum toxin type A (Botox, Allergan, Irvine, Calif.; 100 mouse units [MU]/5.0 ml of 0.9% sterile normal saline without a preservative) was injected into the palms. Initially, botulinum toxin was injected subepidermally on one palm into 10 different sites (2 MU/0.1 ml per site) on one palm. Three weeks later an additional 40 sites on the same palm were treated. Four weeks later the second palm was similarly treated with 50 injections. Subepidermal injections with a 30-gauge needle were spaced 1.0 cm apart (Fig. 1). Patients were then observed for 12 months with serial "iodine-paper" records. RESULTS
In each of the four patients hyperhidrosis
improved after 1 week, with anhidrotic areas at the sites of botulinum toxin injections (Fig. 2). Each injection produced an area of anhidrosis on the palm measuring about 1.2 cm in diameter. To treat one entire palmar surface, approximately 50 injections were required. All patients reported significant improvement and were pleased with the results. Follow-up visits showed that the reduction in sweat production could last as long as 12 months. In patient 4 subjective improvement started to decline 4 months after treatment, although the "iodine-paper" test still demonstrated decreased sweat production compared with baseline. In patients 1 and 3 the decrease in sweat production lasted for 7 months. Patient 2 still had cessation of sweating after 12 months. The only side effect we encountered was mild thumb weakness in patient 2. That disappeared within 3 weeks. Among other complaints expressed by the patients the most common was continuation of sweating in areas that had not been treated, such as the sides of the fingers and the outer aspect of the thenar eminence.
Journal of the American Academy of Dermatology Volume 38, Number 2, Part 1
DISCUSSION
Our study confirmed the effectiveness of botulinum toxin type A in reducing palmar hyperhidrosis.7,8 Earlier studies had reported pain during injections as one of the main disadvantages of treatment.8 This is probably due to the abundance of sensory receptors in the palms because botulinum toxin injections into the axillary areas and the backs of the hands are relatively painless.11 Because the "free nerve-endings" responsible for pain sensation occur in the papillary dermis and epidermis, subcutaneous injections of botulinum toxin would be less painful.8,12 Nevertheless, to deliver botulinum toxin as close to the sweat glands as possible, we considered subepidermal injections more appropriate than subcutaneous, although they may be more painful. Nerve block provided sufficient anesthesia in our patients to make botulinum toxin injections significantly less painful. Neural blockade allowed us to inject botulinum toxin superficially into the fingertips, overcoming the potential hazard of injecting the toxin into an extensive capillary network.8 To avoid weakness of the small muscles of the hand, the only documented complication of botulinum toxin,7,8 we tried to inject the toxin as superficially as possible. Nevertheless, one of our patients reported thumb weakness after treatment. Presumably, this might be avoided by reducing the total dose of toxin, as recommended previously.8 Our study shows that the effect of botulinum toxin therapy on palmar hyperhidrosis can last as long as 12 months. Earlier studies reported therapeutic effects lasting at least 14 weeks, the length of the observation period.7,8 The treatment effects have persisted for 8 months in axillary hyperhidrosis and for up to 13 months in gustatory sweating.11,13 In healthy volunteers the anhidrotic effect of botulinum toxin injections lasted for 4 months in the palm and 11 months on the dorsum of the hands.13,14
Shelley, Talanin, and Shelley 229 We used botulinum toxin in 20 MU/ml concentration, delivering 2 MU per each injection site. This dose was similar to the one used in the treatment of gustatory sweating in Frey's syndrome (2.5 MU/ml), the only report on use of this preparation in sweating disorders available at the time we started our study.13 Our results show that superficial botulinum toxin injections are effective therapy for palmar hyperhidrosis. It is comparatively safe and gives long-lasting relief of sweating. REFERENCES 1. Claes G, Drott C. Hyperhidrosis. Lancet 1994;1:247-8. 2. Shelley WB, Shelley ED. Advanced dermatologic therapy. Philadelphia: WB Saunders; 1987. p. 260-6. 3. Quinn AC, Edwards RE, Newman PJ, Fawcett WJ. Complications of endoscopic sympathectomy. BMJ 1993;306: 1752. 4. Drott C, Gothberg G, Claes G. Endoscopic transthoracic sympathectomy: an efficient and safe method for the treatment of hyperhidrosis. J Am Acad Dermatol 1995;33:78-81. 5. Bushara KO, Park DM. Botulinum toxin and sweating. J Neurol Neurosurg Psychiatry 1994;57:1437-8. 6. Simpson LL. Botulinum toxin: a deadly poison sheds its negative image. Ann Int Med 1996;125:616-7. 7. Naumann M, Flachenecker P, Brocker EB, Toyka KV, Reiners K. Botulinum toxin for palmar hyperhidrosis. Lancet 1997;1:252. 8. Schnider P, Binder M, Auff E, Kittler H, Berger T, Wolff K. Double-blind trial of botulinum A toxin for the treatment of focal hyperhidrosis of the palms. Br J Dermatol 1997;136:548-52. 9. Champion RH. Disorders of sweat glands. In: Champion RH, Burton JL, Ebling FJG, editors. Textbook of dermatology; vol. 3. 5th ed. Oxford: Blackwell Scientific; 1992. p. 1745-62. 10. Colins VJ, Rovenstine EA. Fundamentals of nerve blocking. Philadelphia: Lea & Febiger; 1960. p. 253-8. 11. Bushara KO, Park DM, Jones JC, Schutta HS. Botulinum toxin: a possible new treatment for axillary hyperhidrosis. Clin Exp Dermatol 1996;21:276-8. 12. Weddell G, Palmer E, Pallie W. Nerve endings in mammalian skin. Biol Rev Camb Phil Soc 1955;30:159-93. 13. Drobik C, Laskawi R, Schwab S. Die therapie des Freysyndroms mit botulinumtoxin A. HNO 1995;43:644-8. 14. Schnider P, Binder M, Berger T, Auff E. Botulinum toxin injections in focal hyperhidrosis. Br J Dermatol 1996; 134:1160-1.