Palmar Hyperhidrosis: Long-term Follow-up of Nine Children and Adolescents Treated with Botulinum Toxin Type A

Transcription

1 Pediatric Dermatology Vol. 26 No , 2009 Palmar Hyperhidrosis: Long-term Follow-up of Nine Children and Adolescents Treated with Botulinum Toxin Type A Lúcia H. Coutinho dos Santos, M.D., Ph.D., Ariadne Miranda Gomes, M.D., Susana Giraldi, M.D., Kerstin Taniguchi Abagge, M.D., Ph.D., and Leide Parolim Marinoni, M.D. Pediatric Department of the Federal University of Parana, Parana, Brazil Abstract: Primary palmar hyperhidrosis in children and adolescents may be severe enough to affect school and physical activities, causing emotional problems, stress in the patient s life, and a compromised quality of life. Nine patients with palmar hyperhidrosis underwent treatment with botulinum A. Before the session, and in the 1-, 3-, 6-, 9-, and 12-month postsession follow-ups, the patients were administered the Minor test, gravimetry, the Scales of Frequency and Severity, and the Questionnaire of Quality of Life. The mean age was 11 years, with seven girls and two boys. Each patient was administered at least one treatment of botulinum toxin in the palm of the hands ( U for palm), with the mean number of sessions 2.2 (range: 1 4). All sessions in the patients resulted in drying of the hands, with a mean duration of effect of 7 months. Botulinum toxin A controls excessive sweat in the palms of children and adolescents who have primary palmar hyperhidrosis, with an improvement in the quality of life. The therapy is safe and effective in this pediatric group and can be considered before surgical interventions. INTRODUCTION Excessive perspiration beyond physiological needs is called hyperhidrosis (HH) (1). Hyperhidrosis may be secondary to endocrinological causes (e.g., hyperthyroidism), increased release of catecholamines (e.g., phaeochromocytoma), and neurological dysfunctions (e.g., Ross syndrome, auriculotemporal syndrome, Sudeck s syndrome, neuropathies) (2,3). Primary focal hyperhidrosis has a poorly understood pathophysiology, but is believed to be associated with over-stimulation of an autonomic pathway, occurring symmetrically in the axillary, palms, or soles, or the craniofacial region (1). Sttrutton et al. (3) studied the prevalence of axillary hyperhidrosis in the United States and observed a prevalence of 2.8%; this was lower in the pediatric age group (0 5 yrs, 0.5% and 6 11 yrs, 0.7%), affecting girls and boys similarly, with approximately one-half (1.4%) of affected individuals projected to have axillary hyperhidrosis and one-sixth (0.5%) projected to have sweating that was intolerable or interfered with daily activities. The presence of positive family history varies from 48% to 65% (1,4,5); Ro et al (5) concluded that palmar hyperhidrosis is a hereditary disorder with variable Address correspondence to Lu cia H. Coutinho dos Santos, M.D., Ph.D., Rua Floriano Essenfelder, Curitiba, Parana, Brazil, or luciacoutinho@ufpr.br. DOI: /j x Ó 2009 The Authors. Journal compilation Ó 2009 Wiley Periodicals, Inc. 439

2 440 Pediatric Dermatology Vol. 26 No. 4 July August 2009 penetrance and no proof of sex-linked transmission. Hyperhidrosis causes a significant impact and stress in the patient s life, with limitations in work, school, and physical activities and emotional problems (3,6). Specific therapies used to reduce sweat production include antiperspirants, tap water iontophoresis, botulinum toxin type A, anticholinergic drugs, and sympathectomy (1,6 16). Botulinum toxin type A (BTA) is one of the seven immunologically distinct toxins (A G) from the grampositive bacillus Clostridium botulinum. The toxin inhibits the release of acetylcholine at the neuromuscular junction and affects the postganglionic sympathetic innervation of the eccrine sweat gland (17). Botulinum toxin type A is injected intradermally in the affected areas by multiple injections spaced cm apart. Analgesic therapies are used with intention of relieving the pain, from topical application of a local anesthetic, cryoanalgesia with dichlorotetrafluoroethane, to ulnar and median nerve blocks and intravenous anesthetic. Anhidrosis can be observed within 1 week and persists for 4 14 months, resulting in an improvement in the quality of life (18 22). We describe the use of BTA in nine children and adolescents with palmar hyperhidrosis. SUBJECTS AND METHODS Between June 2003 and August 2005, nine patients with a diagnosis of palmar hyperhidrosis were sent by the Discipline of Pediatric Dermatology to the Neuropediatric Center of the Clinics Hospital of the Federal University of Paraná (CENEP-HC-UFPR), and they underwent treatment with botulinum toxin A (BOTOX Ò, Allergan, Irvine, CA, USA). The patients age ranged from 78 to 187 months (mean: 134 m), with the medium age at the beginning of hyperhidrosis of 64 m (range: m); seven patients were girls and two boys (Table 1). Each patient was treated with at least one session of BTA, with a median dose of 5.0 U kg (±3.0 U kg) in the palm of the hands ( U palm); the average number of sessions was 2.2 (range: 1 4). Each procedure lasted about 2 hours, including the time for the anesthetic blockade and the application of BTA. Before the application and in the 1-, 3-, 6-, 9-, and 12-month post-session follow-ups, the patients were administered the minor starch iodine test (Figs. 1 and 2), gravimetry, and classified according to the Scale of Frequency (A B C D) and Scale of Severity ( ), in which 5 and D correspond to the profuse and constant sweating, respectively, adapted from the scale used for drooling (23) (Table 2). The Questionnaire of Quality of Life (), composed of 14 subjects TABLE 1. Age, sex, age at the beginning of the palmar hyperhidrosis, number of sessions of botulinum toxin and interval in months among the sessions Case Age (months) Sex Age at the beginning (months) No. sessions Mean interval F F F , F F F M M F Mean SD F, female; M, male; SD, standard deviation. Figure 1. Minor starch iodine test pre-botulinum toxin session. (Table 3), was administered to the patients in these evaluations. Each one of the subjects of the questionnaire has a score from 1 to 10. Of the 14 subjects, eight (subjects 1, 2, 3, 4, 5, 7, 8, and 14) are related to the functionality, in other words, how the hyperhidrosis interferes in the child s daily activities: e.g., writing, riding a bicycle, playing video games, etc. The six remaining questions refer to self-esteem, for instance, how difficult it is to hold another child s hand, if he feels happy, if he thinks he is the only person to have this problem, etc. Botulinum toxin was applied intradermally using an insulin needle and standard syringe for dilution (0.5 unit of BTA: 1 unit of the dilution), 1 U of BOTOX per injection, at approximately 0.2-mm depth and 0.1 U spaced 1 cm apart. For the procedure, the children were administered ulnar and median lidocaine nerve blocks.

3 Coutinho dos Santos et al: Botulinum Toxin in Children with Palmar Hyperhidrosis 441 TABLE 2. Palmar hyperhidrosis Questionnaire of Quality of Life ME: DATE: AGE: SEX: Please, mark with a in the space below, according to the degree of difficulty or ease that you find in accomplishing the following tasks. If the item is not appropriate, circle. 1. To write? 2. To handle school materials? 3. To use the mouse of the computer? 4. To hold the handlebar of the bicycle or skateboard? 5. With that frequency you blot the notebook? Never Always 6. With that frequency you need to dry the hands? Never Always 7. For you it is easy to play with other children? Very easy Very difficult 8. For you it is easy to play video game? Very easy Very difficult 9. For you it is easy to play an instrument? Very easy Very difficult 10. With that frequency you think that you are the only person in the world to have this problem? Never Always 11. For you it is easy to take in another child s hand or adolescent? Very easy Very difficult 12. Like you feel about your appearance? Very satisfied Very unsatisfied 13. You feel that you are Very happy Very unhappy 14. How important they are these questions for your quality of life? Little important Very important Adapted of Caregiver Questionaire (Schneider JW, Gurucharri LM, Gutierrez AL, and Gaeber-Spira DJ. Dev Med Child Neurol 2001;43: ) for Lu cia H. Coutinho dos Santos, Neuropediatric Center of Clinics Hospital of UFPR. TABLE 3. Rating scales for severity and frequency of hyperhidrosis Severity: 1 = Dry (never hyperhidrosis) 2 = Mild (palms moist) 3 = Moderate (palms wet) 4 = Severe (clothing soiled) 5 = Profuse (blurry [wet] notebooks) Frequency: A = Never B = Occasional hyperhidrosis (not every day) C = Frequent (every day) D = Constant hyperhidrosis RESULTS Of the nine patients, 22% (2 patients) were administered four sessions, 11.1% (1 patient) three sessions, 33% (3 patients) two sessions, and 33% (3 patients) one session. The study included patients who had up to 3 treatment sessions and follow-up ranging from 1 to 2.5 years (Table 4). The time of the session was related to obtaining of appropriate nerve block. From 20 sessions all resulted in drying of the hands. The side effects observed in our study were pain at the moment of application of botulinum toxin A and anesthetic blockade; this, however, did not make the procedure unfeasible. A patient reported difficulty in fine handling 3 days after the session that lasted 1 week, but without loss of muscular force. Bruises, paresthesias or any other signs or symptoms were not observed. No patient presented compensatory hyperhidrosis. The nine patients who underwent treatment of palmar hyperhidrosis with botulinum toxin A were divided into three groups according to the number of treatments that were administered. In the first group, three patients were subjected to three sessions (Table 5), in the second group, three patients were subjected to two sessions (Table 6), and in the third, three patients were subjected to one session (Table 7). Of the nine patients, two presented with plantar hyperhidrosis and one with plantar and axillary.

4 442 Pediatric Dermatology Vol. 26 No. 4 July August 2009 TABLE 4. Follow-up of the nine patients by severity and frequency scales, gravimetry, and Questionnaire of Quality of Life () Session Month of follow-up Severity scale mean Frequency scale mean Gravimetry mean functional self-esteem 1 Before Before Before TABLE 5. Improvement in % considering pre-treatment values of group I three sessions of BTA Session Month of follow-up Severity Frequency Patient 1 presented with palmoplantar and axillary hyperhidrosis and started treatment with BTA in these areas on November 28, In the follow-up, she did not complain of plantar and axillary hyperhidrosis for 3 years and 3 months later when again after treatment she had improvement of the plantar Gravimetry functional , Questionnaire of Quality of Life; BTA, botulinum toxin type A. TABLE 6. Improvement in % considering pre-treatment values of group II two sessions of BTA Session Month of follow-up Severity Frequency Gravimetry functional , Questionnaire of Quality of Life; BTA, botulinum toxin type A. self-esteem self-esteem and axillary hyperhidrosis. Patient 4 presented with palmoplantar hyperhidrosis and after treatment with BTA had improvement for a period of 15 months, when she needed a repeat treatment. In this group of patients, only one reported that a cousin also suffered from hyperhidrosis.

5 Coutinho dos Santos et al: Botulinum Toxin in Children with Palmar Hyperhidrosis 443 TABLE 7. Improvement in % considering pre-treatment values of group III one session of BTA Session Month of follow-up Severity Frequency Gravimetry functional self-esteem , Questionnaire of Quality of Life; BTA, botulinum toxin type A. Figure 2. Minor starch iodine test after botulinum toxin session. DISCUSSION Children and adolescents with palmar hyperhidrosis present with psycho-social stress, as they feel prejudiced in their activities of daily life, especially in those related to school. The main complaint of this group of patients was related to the inability to participate in school activities because of palmar hyperhidrosis and also the way others see them, causing low self esteem. No patient directed for evaluation gave up the treatment, getting full support from families, confirming the negative effect of hyperhidrosis in their lives. The few isolated reports of the use of botulinum toxin A in children and adolescents with hyperhidrosis motivated us to publish this series of cases (13). The advantages of botulinum toxin therapy are its effectiveness, fast action, ease of use, and the associated safety of the procedure. The disadvantages are its temporary effect and cost. The average of effect of BTA was 9 months, with three patients having accomplished this after just one session, with the results observed over more than 12 months. All of the patients had clinical improvements after the treatment with BTA. Some were free from symptoms for a longer period of time than others, suggesting different degrees of severity of the disorder. Patient 7 continues without hyperhidrosis after 3 years of only one BTA session. The need for a new session was determined by the observation that hyperhidrosis interfered in the activities of the individual s daily life. We observed that the severity and frequency scales and the Questionnaire of Quality of Life reflected this better than the gravimetry and Minor tests. We attributed this observation to the stress suffered by the patients at the time of consultation and to our observation that at the time of evaluation, there was an increase in sweat compared with moments before in the same consultation. The interference of emotional factors should be taken into account in the hyperhidrosis patients evaluations. Although the answer to the also varies depending on other existing situations in the individual s life, it was useful in this patient sample, especially with regard to the items related to functionality. The items related to self-esteem showed a larger impact in the beginning of the treatment, and a subsequent reduction that was related to additional sessions. The observation of smaller results in the subsequent sessions suggests caution in the indication for the procedure. Whether hyperhidrosis is in fact interfering in the activities of the child s daily life should be carefully evaluated, with the possibility of reserving treatment for another time, which might bring greater impact in his or her life because there was evidence of a diminished effect with subsequent treatments, similar to that described by Berweck et al (24) in the treatment of drooling. CONCLUSIONS The study demonstrated that the botulinum toxin type A controls excessive sweat in the palms of children and adolescents with primary palmar hyperhidrosis, with a duration of effect ranging from 3 to 16 months. The first session demonstrated better results than the subsequent ones. The sweat decrease resulted in an improved quality of life. Botulinum toxin therapy is effective and sustained in children and adolescents with palmar hyperhidrosis, and can be considered instead of more aggressive approaches such as surgical interventions in the pediatric population.

6 444 Pediatric Dermatology Vol. 26 No. 4 July August 2009 ACKNOWLEDGMENTS The authors would like to thank Dr Isac Bruck and Dr Mitsuru Miyaki for helpful discussion on this article. REFERENCES 1. Adar R, Kurchin A, Zweig A et al. Palmar hyperhidrosis and its surgical treatment: a report of 100 cases. Ann Surg 1977;186: Togel B, Greve B, Raulin C. Current therapeutic strategies for hyperhidrosis: a review. Eur J Dermatol 2002;12: Strutton DR, Kowalski JW, Glaser DA et al. US prevalence of hyperhidrosis and impact on individuals with axilary hyperhidrosis: results from a national survey. J Am Acad Dermatol 2004;51: Ramos R, Moya J, Pe rez J et al. Hiperhidrosis primaria: estu dio prospectivo de 338 pacientes. Med Clin (Barc) 2003;121: Ro KM, Cantor RM, Lange KL et al. Palmar hyperhidrosis: evidence of genetic transmission. J Vasc Surg 2002;35: Milanez de Campos JR, Kauffman P, Werebe EC et al. Quality of life, before and after thoracic sympathectomy: report on 378 operated patients. Ann Thorac Surg 2003;76: Hornberger J, Grimes K, Naumann M et al. Recognition, diagnosis, and treatment of primary focal hyperhidrosis. J Am Acad Dermatol 2004;51: Thomas I, Brown J, Vafaie J et al. Palmoplantar hyperhidrosis: a therapeutic challenge. Am Fam Physician 2004;69: Karakoc Y, Aydemir EH, Kalkan T et al. Safe control of palmoplantar hiperhidrosis with direct electrical current. Int J Dermatol 2002;41: Eisenach JH, Atkinson JLD, Fealey RD. Hyperhidrosis: evolving therapies for a well-established phenomenon. Mayo Clin Proc 2005;80: Lin T-S, Huang L-C, Wang N-P et al. Endoscopic thoracic sympathetic block by clipping for palmar and axillary hyperhidrosis in children and adolescents. Pediatr Surg Int 2001;17: Licht PB, Pilegaard HK. Severity of compensatory sweating after thoracoscopic sympathectomy. Ann Thorac Surg 2004;78: Farrugia M-K, Nicholls EA. Intradermal botulinum A toxin injection for axillary hyperhidrosis. J Pediatr Surg 2005;40: Gordon N. The role of botulinus toxin type A in treatment with special reference to children. Brain Dev 1999; 21: Chutorian AM. Botulinum toxin therapy in children. Int Pediatr 2001;16: Wenzel R. Pharmacology of botulinum neurotoxin serotype A. Am J Health-Syst Pharm 2004;61(Suppl. 6):S5 S Jankovic J. Botulinum toxin in clinical practice. J Neurol Neurosurg Psychiatr 2004;75: Charles PD. Botulinum neurotoxin serotype A: a clinical update on non-cosmetic uses. Am J Health-Syst Pharm 2004;61(Suppl. 6):S11 S Cheng CM, Chen JS, Patel RP. Unlabeled uses of botulinum toxins: a review, part 2. Am J Health-Syst Pharm 2006;63:225 S Goldman A. Treatment of axillary an palmar hyperhidrosis with botulinum toxin. Aesthetic Plast Surg 2000;24: Naumann M, Lowe NJ. Botulinum toxin type A in treatment of bilateral primary axillary hyperhidrosis: randomized, parallel group, double blind, placebo controlled trial. BMJ 2001;323: Campanati A, Penna L, Guzzo T et al. Quality-of-life assessment in patients with hyperhidrosis before and after treatment with botulinum toxin: results of an open-label study. Clin Ther 2003;25: Crysdale WS, White A. Submandibular duct relocation for drooling: A 10-year experience with 194 patients. Otoryngol Head Neck Surg 1989; 101: In: Pal PK, Calne DB, Calne S, Tsui JKC. Botulinum toxin A as treatment for drooling saliva in PD. Neurology 2000;54: Berweck S, Schroeder AS, Lee S-H et al. Secondary nonresponse due to antibody formation in a child after three injections of botulinum toxin B into the salivary glands. Dev Med Child Neurol 2007;49:62 64.